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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. Adolescent Smoking and Tertiary Education: Opposing Pathways linking Socioeconomic Background to Alcohol Consumption

    PubMed Central

    Green, Michael J; Leyland, Alastair H; Sweeting, Helen; Benzeval, Michaela

    2016-01-01

    Background and aims If socioeconomic 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 UK Participants Were from the 1958 National Child Development Study (NCDS58; N=15,672), 1970 British birth cohort study (BCS70; N=12,735), and the West of Scotland Twenty-07 1970s cohort (T07; N=1,515). Measurements Participants self-reported daily smoking and weekly drinking in adolescence (age 16) and heavy drinking (>14/21 units in past week) in early adulthood (ages 22-26). Parental occupational class (manual vs. non-manual) indicated socioeconomic 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 and university) despite socioeconomic background being associated in opposite directions with these

  3. 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…

  4. 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

  5. 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.

  6. Socioeconomic Disparities and Health: Impacts and Pathways

    PubMed Central

    Kondo, Naoki

    2012-01-01

    Growing socioeconomic disparity is a global concern, as it could affect population health. The author and colleagues have investigated the health impacts of socioeconomic disparities as well as the pathways that underlie those disparities. Our meta-analysis found that a large population has risks of mortality and poor self-rated health that are attributable to income inequality. The study results also suggested the existence of threshold effects (ie, a threshold of income inequality over which the adverse impacts on health increase), period effects (ie, the potential for larger impacts in later years, specifically after the 1990s), and lag effects between income inequality and health outcomes. Our other studies using Japanese national representative survey data and a large-scale cohort study of Japanese older adults (AGES cohort) support the relative deprivation hypothesis, namely, that invidious social comparisons arising from relative deprivation in an unequal society adversely affect health. A study with a natural experiment design found that the socioeconomic gradient in self-rated health might actually have become shallower after the 1997–98 economic crisis in Japan, due to smaller health improvements among middle-class white-collar workers and middle/upper-income workers. In conclusion, income inequality might have adverse impacts on individual health, and psychosocial stress due to relative deprivation may partially explain those impacts. Any study of the effects of macroeconomic fluctuations on health disparities should also consider multiple potential pathways, including expanding income inequality, changes in the labor market, and erosion of social capital. Further studies are needed to attain a better understanding of the social determinants of health in a rapidly changing society. PMID:22156290

  7. Scenarios Based on Shared Socioeconomic Pathway Assumptions

    NASA Astrophysics Data System (ADS)

    Edmonds, J.

    2013-12-01

    A set of new scenarios is being developed by the international scientific community as part of a larger program that was articulated in Moss, et al. (2009), published in Nature. A long series of meetings including climate researchers drawn from the climate modeling, impacts, adaptation and vulnerability (IAV) and integrated assessment modeling (IAM) communities have led to the development of a set of five Shared Socioeconomic Pathways (SSPs), which define the state of human and natural societies at a macro scale over the course of the 21st century without regard to climate mitigation or change. SSPs were designed to explore a range of possible futures consistent with greater or lesser challenges to mitigation and challenges to adaptation. They include a narrative storyline and a set of quantified measures--e.g. demographic and economic profiles--that define the high-level state of society as it evolves over the 21st century under the assumption of no significant climate feedback. SSPs can be used to develop quantitative scenarios of human Earth systems using IAMs. IAMs produce information about greenhouse gas emissions, energy systems, the economy, agriculture and land use. Each set of SSPs will have a different human Earth system realization for each IAM. Five groups from the IAM community have begun to explore the implications of SSP assumptions for emissions, energy, economy, agriculture and land use. We report the quantitative results of initial experiments from those groups. A major goal of the Moss, et al. strategy was to enable the use of CMIP5 climate model ensemble products for IAV research. CMIP5 climate scenarios used four Representative Concentration Pathway (RCP) scenarios, defined in terms of radiative forcing in the year 2100: 2.6, 4.5, 6.0, and 8.5 Wm-2. There is no reason to believe that the SSPs will generate year 2100 levels of radiative forcing that correspond to the four RCP levels, though it is important that at least one SSP produce a

  8. Parenting, Race, and Socioeconomic Status: Links to School Readiness

    ERIC Educational Resources Information Center

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

    2012-01-01

    This study examined the link between socioeconomic status (SES) and school readiness, testing whether parenting (maternal sensitivity and negative behavior/intrusiveness) and financial stress mediated this association and if race moderated these paths. Participants included 164 mother-child dyads from African American and European American…

  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. Beyond Social Address: Linking Socioeconomic Status to Family Functioning.

    ERIC Educational Resources Information Center

    Luster, Tom

    The present study attempts to move beyond the social address research design to investigate the process by which socioeconomic status (SES) exerts its influence on parenting practices. Of particular interest were maternal practices related to cognitive outcomes in children. The conceptual model of the study was based on the reliable finding that…

  13. Multiple Pathways Linking Racism to Health Outcomes

    PubMed Central

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

    2012-01-01

    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. PMID:22518195

  14. 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. PMID:26059537

  15. 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

  16. 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

  17. 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.

  18. 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.

  19. Socioeconomic risk moderates the link between household chaos and maternal executive function.

    PubMed

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

    2012-06-01

    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

  20. Cascading events in linked ecological and socioeconomic systems

    USGS Publications Warehouse

    Peters, D.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. 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

  2. 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.

  3. Socio-Economic Background, Senior Secondary Mathematics, and Post-Secondary Pathways

    ERIC Educational Resources Information Center

    Yeoh, Eng; Leigh-Lancaster, David

    2010-01-01

    The relationship between socio-economic background and completion of senior secondary mathematics study leading to various post-schooling pathways has been an area of keen interest to researchers, school systems and policy makers for some time. This paper briefly considers some aspects of this relationship using recent Victorian data relating to…

  4. 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…

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

    DOE PAGESBeta

    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

  6. 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…

  7. Linking multiple pathogenic pathways in Alzheimer's disease.

    PubMed

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

    2016-06-22

    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

  8. 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

  9. 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

  10. A hybrid framework for assessing socioeconomic drought: Linking climate variability, local resilience, and demand

    NASA Astrophysics Data System (ADS)

    Mehran, Ali; Mazdiyasni, Omid; AghaKouchak, Amir

    2015-08-01

    Socioeconomic drought broadly refers to conditions whereby the water supply cannot satisfy the demand. Most previous studies describe droughts based on large-scale meteorological/hydrologic conditions, ignoring the demand and local resilience to cope with climate variability. Reservoirs provide resilience against climatic extremes and play a key role in water supply and demand management. Here we outline a unique multivariate approach as a measure of socioeconomic drought, termed Multivariate Standardized Reliability and Resilience Index (MSRRI). The model combines information on the inflow and reservoir storage relative to the demand. MSRRI combines (I) a "top-down" approach that focuses on processes/phenomena that cannot be simply controlled or altered by decision makers, such as climate change and variability, and (II) a "bottom-up" methodology that represents the local resilience and societal capacity to respond or adapt to droughts. MSRRI is based on a nonparametric multivariate distribution function that links inflow-demand reliability indicator to water storage resilience indicator. These indicators are used to assess socioeconomic drought during the Australian Millennium drought (1998-2010) and the 2011-2014 California drought. The results show that MSRRI is superior to univariate indices because it captures both early onset and persistence of water stress over time. The suggested framework can be applied to both individual reservoirs and a group of reservoirs in a region, and it is consistent with the currently available standardized drought indicators. MSRRI provides complementary information on socioeconomic drought development and recovery based on reservoir storage and demand that cannot be achieved from the commonly used drought indicators.

  11. 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

  12. A global water scarcity assessment under Shared Socio-economic Pathways - Part 1: Water use

    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 novel global water scarcity assessment for the 21st century is presented in a two-part paper. In this first paper, water use scenarios are presented for the latest global hydrological models. The scenarios are compatible with the socio-economic scenarios of the Shared Socio-economic Pathways (SSPs), which are a part of the latest set of scenarios on global change developed by the integrated assessment, the IAV (climate change impact, adaptation, and vulnerability assessment), and the climate modeling community. The SSPs depict five global situations based on substantially different socio-economic conditions during the 21st century. Water use scenarios were developed to reflect not only quantitative socio-economic factors, such as population and electricity production, but also key qualitative concepts such as the degree of technological change and overall environmental consciousness. Each scenario consists of five factors: irrigated area, crop intensity, irrigation efficiency, and withdrawal-based potential industrial and municipal water demands. The first three factors are used to estimate the potential irrigation water demand. All factors were developed using simple models based on a literature review and analysis of historical records. The factors are grid-based at a spatial resolution of 0.5° × 0.5° and cover the whole 21st century in five-year intervals. Each factor shows wide variation among the different global situations depicted: the irrigated area in 2085 varies between 2.7 × 106 and 4.5 × 106 km2, withdrawal-based potential industrial water demand between 246 and 1714 km3 yr-1, and municipal water between 573 and 1280 km3 yr-1. The water use scenarios can be used for global water scarcity assessments that identify the regions vulnerable to water scarcity and analyze the timing and magnitude of scarcity conditions.

  13. 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.

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

    ERIC Educational Resources Information Center

    Tucker-Drob, Elliot M.

    2013-01-01

    Children whose parents are more highly educated 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.…

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

    PubMed Central

    You, Jihyun; Choo, Jina

    2016-01-01

    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. PMID:27005654

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

    PubMed

    You, Jihyun; Choo, Jina

    2016-01-01

    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. PMID:27005654

  17. A global water scarcity assessment under shared socio-economic pathways - Part 1: Water use

    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.

    2012-12-01

    A novel global water scarcity assessment for the 21st century is presented in a two-part paper. In this first paper, water use scenarios are presented for the latest global hydrological models. The scenarios are compatible with the socio-economic scenarios of the Shared Socio-economic Pathways (SSPs), which are a part of the latest set of scenarios on global change developed by the integrated assessment, IAV (climate change impact, adaptation, and vulnerability assessment), and climate modeling community. The SSPs depict five global situations based on substantially different socio-economic conditions during the 21st century. Water use scenarios were developed to reflect the key concepts underpinning each situation. Each scenario consists of five factors: irrigation area, crop intensity, irrigation efficiency, industrial water withdrawal, and municipal water withdrawal. The first three factors are used to estimate agricultural water withdrawal. All factors were developed using simple models based on a literature review and analysis of historical records. The factors are grid-based at a spatial resolution of 0.5° × 0.5° and cover the whole 21st century at 5-yr intervals. Each factor displays a wide variation among the different global situations depicted: the irrigation area in 2085 varies between 270 and 450 km2, industrial water between 246 and 1714 km3 yr-1, and domestic water withdrawal between 573 and 1280 km3 yr-1. The water use scenarios can be used for global water scarcity assessments by identifying the regions vulnerable to water scarcity and analyzing the timing and magnitude of scarcity conditions.

  18. 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.

  19. Causal pathways linking Farm to School to childhood obesity prevention.

    PubMed

    Joshi, Anupama; Ratcliffe, Michelle M

    2012-08-01

    Farm to School programs are rapidly gaining attention as a potential strategy for preventing childhood obesity; however, the causal linkages between Farm to School activities and health outcomes are not well documented. To capitalize on the increased interest in and momentum for Farm to School, researchers and practitioners need to move from developing and implementing evidence informed programs and policies to ones that are evidence-based. The purpose of this article is to outline a framework for facilitating an evidence base for Farm to School programs and policies through a systematic and coordinated approach. Employing the concepts of causal pathways, the authors introduce a proposed framework for organizing and systematically testing out multiple hypotheses (or potential causal links) for how, why, and under what conditions Farm to School Inputs and Activities may result in what Outputs, Effects, and Impacts. Using the causal pathways framework may help develop and test competing hypotheses, identify multicausality, strength, and interactions of causes, and discern the difference between catalysts and causes. In this article, we introduce causal pathways, present menus of potential independent and dependent variables from which to create and test causal pathways linking Farm to School interventions and their role in preventing childhood obesity, discuss their applicability to Farm to School research and practice, and outline proposed next steps for developing a coordinated research framework for Farm to School programs. PMID:22867068

  20. 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.

  1. Mevalonate Pathway Blockade, Mitochondrial Dysfunction and Autophagy: A Possible Link

    PubMed Central

    Tricarico, Paola Maura; Crovella, Sergio; Celsi, Fulvio

    2015-01-01

    The mevalonate pathway, crucial for cholesterol synthesis, plays a key role in multiple cellular processes. Deregulation of this pathway is also correlated with diminished protein prenylation, an important post-translational modification necessary to localize certain proteins, such as small GTPases, to membranes. Mevalonate pathway blockade has been linked to mitochondrial dysfunction: especially involving lower mitochondrial membrane potential and increased release of pro-apoptotic factors in cytosol. Furthermore a severe reduction of protein prenylation has also been associated with defective autophagy, possibly causing inflammasome activation and subsequent cell death. So, it is tempting to hypothesize a mechanism in which defective autophagy fails to remove damaged mitochondria, resulting in increased cell death. This mechanism could play a significant role in Mevalonate Kinase Deficiency, an autoinflammatory disease characterized by a defect in Mevalonate Kinase, a key enzyme of the mevalonate pathway. Patients carrying mutations in the MVK gene, encoding this enzyme, show increased inflammation and lower protein prenylation levels. This review aims at analysing the correlation between mevalonate pathway defects, mitochondrial dysfunction and defective autophagy, as well as inflammation, using Mevalonate Kinase Deficiency as a model to clarify the current pathogenetic hypothesis as the basis of the disease. PMID:26184189

  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. Pathways of Substance Users Linking (Or Not) With Treatment

    PubMed Central

    Redko, Cristina; Rapp, Richard C.; Carlson, Robert G.

    2007-01-01

    This qualitative paper describes different pathways substance users experience as they decide whether to link to treatment or not after being assessed in a centralized intake unit in a Midwestern city. The narratives of 16 participants who did not link with treatment were compared with the narratives of 20 participants who did. Narratives from both groups described similar themes that were experienced differently. Nonlinkers were characterized by pretreatment abstinence, a negative experience with previous treatment, little previous engagement in a treatment career, and meaningful social support coming from AA. Linkers were more likely to continue using drugs before treatment entry, yet they described more readiness for treatment and were more engaged in a treatment career. The treatment careers approach provides a broader framework for understanding linkage versus nonlinkage to treatment. PMID:18167518

  6. Hepatic Inflammation and Fibrosis: Functional Links and Key Pathways

    PubMed Central

    Seki, Ekihiro; Schwabe, Robert F.

    2014-01-01

    Inflammation is one of the most characteristic features of chronic liver disease of viral, alcoholic, fatty and autoimmune origin. Inflammation is typically present in all disease stages, and associated with the development of fibrosis, cirrhosis and hepatocellular carcinoma. In the past decade, numerous studies have contributed to improved understanding of the links between hepatic inflammation and fibrosis. Here, we review mechanisms that link inflammation with the development of liver fibrosis, focusing on the role of inflammatory mediators in hepatic stellate cell (HSC) activation and HSC survival during fibrogenesis and fibrosis regression. We will summarize the contributions of different inflammatory cells, including hepatic macrophages, T- and B-lymphocytes, NK cells and platelets, as well as key effectors such as cytokines, chemokines, and damage-associated molecular patterns. Furthermore, we will discuss the relevance of inflammatory signaling pathways for clinical liver disease and for the development of anti-fibrogenic strategies. PMID:25066777

  7. 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. PMID:25633946

  8. 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

  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. 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.

  11. 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);…

  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. PMID:25997776

  13. 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. PMID:25302554

  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. 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

  16. 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

  17. 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

  18. 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...

  19. 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

  20. Framework for Developing a System of Linked Learning Pathways

    ERIC Educational Resources Information Center

    Stearns, Roman

    2010-01-01

    This Framework is intended for use by school districts and their community partners as they plan and adopt systems of quality pathways. The Critical Elements that make up the Framework are intended to deepen and clarify the district's thinking about how to build the infrastructure that supports the design, implementation, and sustainability of a…

  1. 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

  2. Pathways to the Future: Linking Environmental Scanning to Strategic Management.

    ERIC Educational Resources Information Center

    Mecca, Thomas V.; Morrison, James L.

    1988-01-01

    Describes an ED QUEST (Quick Environmental Scanning Technique) workshop demonstrating the links between an environmental scanning/forecasting process and formulation of institutional strategy. Explains ED QUEST's use in identifying and analyzing critical trends and events, and identifying the nature of the organization; developing alternative…

  3. Linking pathways in the developing and aging brain with neurodegeneration.

    PubMed

    Kovacs, G G; Adle-Biassette, H; Milenkovic, I; Cipriani, S; van Scheppingen, J; Aronica, E

    2014-06-01

    The molecular and cellular mechanisms, which coordinate the critical stages of brain development to reach a normal structural organization with appropriate networks, are progressively being elucidated. Experimental and clinical studies provide evidence of the occurrence of developmental alterations induced by genetic or environmental factors leading to the formation of aberrant networks associated with learning disabilities. Moreover, evidence is accumulating that suggests that also late-onset neurological disorders, even Alzheimer's disease, might be considered disorders of aberrant neural development with pathological changes that are set up at early stages of development before the appearance of the symptoms. Thus, evaluating proteins and pathways that are important in age-related neurodegeneration in the developing brain together with the characterization of mechanisms important during brain development with relevance to brain aging are of crucial importance. In the present review we focus on (1) aspects of neurogenesis with relevance to aging; (2) neurodegenerative disease (NDD)-associated proteins/pathways in the developing brain; and (3) further pathways of the developing or neurodegenerating brains that show commonalities. Elucidation of complex pathogenetic routes characterizing the earliest stage of the detrimental processes that result in pathological aging represents an essential first step toward a therapeutic intervention which is able to reverse these pathological processes and prevent the onset of the disease. Based on the shared features between pathways, we conclude that prevention of NDDs of the elderly might begin during the fetal and childhood life by providing the mothers and their children a healthy environment for the fetal and childhood development. PMID:24699227

  4. 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

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

    PubMed Central

    Bachman, Jerald G.; Patrick, Jeremy Staff; O’Malley, 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 (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 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 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. PMID:23316768

  6. 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

  7. The inflammasome: Pathways linking psychological stress, depression, and systemic illnesses

    PubMed Central

    Iwata, Masaaki; Ota, Kristie T.; Duman, Ronald S.

    2015-01-01

    Stress is a common occurrence in everyday life and repeated or traumatic stress can be a precipitating factor for illnesses of the central nervous system, as well as peripheral organ systems. For example, severe or long-term psychological stress can not only induce depression, a leading illness worldwide, but can also cause psychosomatic diseases such as asthma and rheumatoid arthritis. Related key questions include how psychological stress influences both brain and peripheral systems, and what detection mechanisms underlie these effects? A clue is provided by the discovery of the pathways underlying the responses to host “danger” substances that cause systemic diseases, but can also contribute to depression. The inflammasome is a protein complex that can detect diverse danger signals and produce the accompanying immune-inflammatory reactions. Interestingly, the inflammasome can detect not only pathogen-associated molecules, but also cell damage-associated molecules such as ATP. Here, we propose a new inflammasome hypothesis of depression and related comorbid systemic illnesses. According to this hypothesis, the inflammasome is a central mediator by which psychological and physical stressors can contribute to the development of depression, and as well as a bridge to systemic diseases. This hypothesis includes an explanation for how psychological stress can influence systemic diseases, and conversely how systemic diseases can lead to psychiatric illnesses. The evidence suggests that the inflammasome may be a new target for the development of treatments for depression, as well as psychosomatic and somatopsycho diseases. PMID:23261775

  8. 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

  9. 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

  10. How socioeconomic inequalities impact pathways of care for coronary artery disease among elderly patients: study protocol for a qualitative longitudinal study

    PubMed Central

    Schröder, Sara L; Fink, Astrid; Schumann, Nadine; Moor, Irene; Plehn, Alexander; Richter, Matthias

    2015-01-01

    Introduction Several studies have identified that socioeconomic inequalities in coronary artery disease (CAD) morbidity and mortality lead to a disadvantage in patients with low socioeconomic status (SES). International studies have shown that socioeconomic inequalities also exist in terms of access, utilisation and quality of cardiac care. The aim of this qualitative study is to provide information on the impact of socioeconomic inequalities on the pathway of care for CAD, and to establish which factors lead to socioeconomic inequality of care to form and expand existing scientific theories. Methods and analysis A longitudinal qualitative study with 48 patients with CAD, aged 60–80 years, is being conducted. Patients have been recruited consecutively at the University Hospital in Halle/Saale, Germany, and will be followed for a period of 6 months. Patients are interviewed two times face-to-face using semistructured interviews. Data are transcribed and analysed based on grounded theory. Ethics and dissemination Only participants who have been informed and who have signed a declaration of consent have been included in the study. The study complies rigorously with data protection legislation. Approval of the Ethical Review Committee at the Martin-Luther University Halle-Wittenberg, Germany was obtained. The results of the study will be presented at several congresses, and will be published in high-quality peer-reviewed international journals. Trial registration number This study has been registered with the German Clinical Trials Register and assigned DRKS00007839. PMID:26553827

  11. Functional analysis of the Campylobacter jejuni N-linked protein glycosylation pathway.

    PubMed

    Linton, Dennis; Dorrell, Nick; Hitchen, Paul G; Amber, Saba; Karlyshev, Andrey V; Morris, Howard R; Dell, Anne; Valvano, Miguel A; Aebi, Markus; Wren, Brendan W

    2005-03-01

    We describe in this report the characterization of the recently discovered N-linked glycosylation locus of the human bacterial pathogen Campylobacter jejuni, the first such system found in a species from the domain Bacteria. We exploited the ability of this locus to function in Escherichia coli to demonstrate through mutational and structural analyses that variant glycan structures can be transferred onto protein indicating the relaxed specificity of the putative oligosaccharyltransferase PglB. Structural data derived from these variant glycans allowed us to infer the role of five individual glycosyltransferases in the biosynthesis of the N-linked heptasaccharide. Furthermore, we show that C. jejuni- and E. coli-derived pathways can interact in the biosynthesis of N-linked glycoproteins. In particular, the E. coli encoded WecA protein, a UDP-GlcNAc: undecaprenylphosphate GlcNAc-1-phosphate transferase involved in glycolipid biosynthesis, provides for an alternative N-linked heptasaccharide biosynthetic pathway bypassing the requirement for the C. jejuni-derived glycosyltransferase PglC. This is the first experimental evidence that biosynthesis of the N-linked glycan occurs on a lipid-linked precursor prior to transfer onto protein. These findings provide a framework for understanding the process of N-linked protein glycosylation in Bacteria and for devising strategies to exploit this system for glycoengineering. PMID:15752194

  12. 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'…

  13. Linking the VPS35 and EIF4G1 pathways in Parkinson's disease.

    PubMed

    Ross, Owen A; Cook, Casey; Petrucelli, Leonard

    2015-01-01

    Elucidating the underlying pathogenic pathways in Parkinson's disease will be critical for targeted drug development. In this issue of Neuron, Dhungel et al. (2015) utilize a yeast model to establish a link between VPS35 and EIF4G1 in α-synuclein-related neurodegeneration. PMID:25569341

  14. A CASE STUDY OF DESERTIFICATION LINKING BIOPHYSICAL AND SOCIOECONOMIC ASPECTS OF WATER USE IN THE SMALL MEXICAN VILLAGE OF AMAPOLA

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Desertification is a major global environmental problem of human societies in drylands and Mexico is one of the most severely affected countries in the Americas. An assessment of how hydrological, ecological, meteorological and socioeconomic processes simultaneously affect, and are affected by, lan...

  15. 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…

  16. Polyisoprenol specificity in the Campylobacter jejuni N-linked glycosylation pathway.

    PubMed

    Chen, Mark M; Weerapana, Eranthie; Ciepichal, Ewa; Stupak, Jacek; Reid, Christopher W; Swiezewska, Ewa; Imperiali, Barbara

    2007-12-18

    Campylobacter jejuni contains a general N-linked glycosylation pathway in which a heptasaccharide is sequentially assembled onto a polyisoprenyl diphosphate carrier and subsequently transferred to the asparagine side chain of an acceptor protein. The enzymes in the pathway function at a membrane interface and have in common amphiphilic membrane-bound polyisoprenyl-linked substrates. Herein, we examine the potential role of the polyisoprene component of the substrates by investigating the relative substrate efficiencies of polyisoprene-modified analogues in individual steps of the pathway. Chemically defined substrates for PglC, PglJ, and PglB are prepared via semisynthetic approaches. The substrates included polyisoprenols of varying length, double bond geometry, and degree of saturation for probing the role of the hydrophobic polyisoprene in substrate specificity. Kinetic analysis reveals that all three enzymes exhibit distinct preferences for the polyisoprenyl carrier whereby cis-double bond geometry and alpha-unsaturation of the native substrate are important features, while the precise polyisoprene length may be less critical. These findings suggest that the polyisoprenyl carrier plays a specific role in the function of these enzymes beyond a purely physical role as a membrane anchor. These studies underscore the potential of the C. jejuni N-linked glycosylation pathway as a system for investigating the biochemical and biophysical roles of polyisoprenyl carriers common to prokaryotic and eukaryotic glycosylation. PMID:18034500

  17. Parallel Driving and Modulatory Pathways Link the Prefrontal Cortex and Thalamus

    PubMed Central

    Zikopoulos, Basilis; Barbas, Helen

    2007-01-01

    Pathways linking the thalamus and cortex mediate our daily shifts from states of attention to quiet rest, or sleep, yet little is known about their architecture in high-order neural systems associated with cognition, emotion and action. We provide novel evidence for neurochemical and synaptic specificity of two complementary circuits linking one such system, the prefrontal cortex with the ventral anterior thalamic nucleus in primates. One circuit originated from the neurochemical group of parvalbumin-positive thalamic neurons and projected focally through large terminals to the middle cortical layers, resembling ‘drivers’ in sensory pathways. Parvalbumin thalamic neurons, in turn, were innervated by small ‘modulatory’ type cortical terminals, forming asymmetric (presumed excitatory) synapses at thalamic sites enriched with the specialized metabotropic glutamate receptors. A second circuit had a complementary organization: it originated from the neurochemical group of calbindin-positive thalamic neurons and terminated through small ‘modulatory’ terminals over long distances in the superficial prefrontal layers. Calbindin thalamic neurons, in turn, were innervated by prefrontal axons through small and large terminals that formed asymmetric synapses preferentially at sites with ionotropic glutamate receptors, consistent with a driving pathway. The largely parallel thalamo-cortical pathways terminated among distinct and laminar-specific neurochemical classes of inhibitory neurons that differ markedly in inhibitory control. The balance of activation of these parallel circuits that link a high-order association cortex with the thalamus may allow shifts to different states of consciousness, in processes that are disrupted in psychiatric diseases. PMID:17786219

  18. SignaLink 2 – a signaling pathway resource with multi-layered regulatory networks

    PubMed Central

    2013-01-01

    Background Signaling networks in eukaryotes are made up of upstream and downstream subnetworks. The upstream subnetwork contains the intertwined network of signaling pathways, while the downstream regulatory part contains transcription factors and their binding sites on the DNA as well as microRNAs and their mRNA targets. Currently, most signaling and regulatory databases contain only a subsection of this network, making comprehensive analyses highly time-consuming and dependent on specific data handling expertise. The need for detailed mapping of signaling systems is also supported by the fact that several drug development failures were caused by undiscovered cross-talk or regulatory effects of drug targets. We previously created a uniformly curated signaling pathway resource, SignaLink, to facilitate the analysis of pathway cross-talks. Here, we present SignaLink 2, which significantly extends the coverage and applications of its predecessor. Description We developed a novel concept to integrate and utilize different subsections (i.e., layers) of the signaling network. The multi-layered (onion-like) database structure is made up of signaling pathways, their pathway regulators (e.g., scaffold and endocytotic proteins) and modifier enzymes (e.g., phosphatases, ubiquitin ligases), as well as transcriptional and post-transcriptional regulators of all of these components. The user-friendly website allows the interactive exploration of how each signaling protein is regulated. The customizable download page enables the analysis of any user-specified part of the signaling network. Compared to other signaling resources, distinctive features of SignaLink 2 are the following: 1) it involves experimental data not only from humans but from two invertebrate model organisms, C. elegans and D. melanogaster; 2) combines manual curation with large-scale datasets; 3) provides confidence scores for each interaction; 4) operates a customizable download page with multiple file formats

  19. Linking socioeconomic classes and land cover data in Lima, Peru: Assessment through the application of remote sensing and GIS

    NASA Astrophysics Data System (ADS)

    Avelar, Silvania; Zah, Rainer; Tavares-Corrêa, Carlos

    2009-02-01

    The spatial differentiation of socioeconomic classes in a city can deliver insight into the nexus of urban development and the environment. The purpose of this paper is to identify poor and rich regions in large cities according to the predominant physical characteristics of the regions. Meaningful spatial information from urban systems can be derived using remote sensing and GIS tools, especially in large difficult-to-manage cities where the dynamics of development results in rapid changes to urban patterns. We use here very high resolution imagery data for the identification of homogeneous socioeconomic zones in a city. We formulate the categorization task as a GIS analysis of an image classified with conventional techniques. Experiments are conducted using a QuickBird image of a study area in Lima, Peru. We provide accuracy assessment of results compared to ground truth data. Results show an approximated allocation of socioeconomic zones within Lima. The methodology described could also be applied to other urban centers, particularly large cities of Latin America, which have characteristics similar to those of the study area.

  20. Two alanine aminotranferases link mitochondrial glycolate oxidation to the major photorespiratory pathway in Arabidopsis and rice.

    PubMed

    Niessen, Markus; Krause, Katrin; Horst, Ina; Staebler, Norma; Klaus, Stephanie; Gaertner, Stefanie; Kebeish, Rashad; Araujo, Wagner L; Fernie, Alisdair R; Peterhansel, Christoph

    2012-04-01

    The major photorespiratory pathway in higher plants is distributed over chloroplasts, mitochondria, and peroxisomes. In this pathway, glycolate oxidation takes place in peroxisomes. It was previously suggested that a mitochondrial glycolate dehydrogenase (GlcDH) that was conserved from green algae lacking leaf-type peroxisomes contributes to photorespiration in Arabidopsis thaliana. Here, the identification of two Arabidopsis mitochondrial alanine:glyoxylate aminotransferases (ALAATs) that link glycolate oxidation to glycine formation are described. By this reaction, the mitochondrial side pathway produces glycine from glyoxylate that can be used in the glycine decarboxylase (GCD) reaction of the major pathway. RNA interference (RNAi) suppression of mitochondrial ALAAT did not result in major changes in metabolite pools under standard conditions or enhanced photorespiratroy flux, respectively. However, RNAi lines showed reduced photorespiratory CO(2) release and a lower CO(2) compensation point. Mitochondria isolated from RNAi lines are incapable of converting glycolate to CO(2), whereas simultaneous overexpression of GlcDH and ALAATs in transiently transformed tobacco leaves enhances glycolate conversion. Furthermore, analyses of rice mitochondria suggest that the side pathway for glycolate oxidation and glycine formation is conserved in monocotyledoneous plants. It is concluded that the photorespiratory pathway from green algae has been functionally conserved in higher plants. PMID:22268146

  1. 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. PMID:26986982

  2. Biochemical evidence for an alternate pathway in N-linked glycoprotein biosynthesis

    PubMed Central

    Larkin, Angelyn; Chang, Michelle M.; Whitworth, Garrett E.; Imperiali, Barbara

    2013-01-01

    Asparagine-linked glycosylation is a complex protein modification conserved among all three domains of life. Herein we report the in vitro analysis of N-linked glycosylation from the methanogenic archaeon Methanococcus voltae. Using a suite of synthetic and semisynthetic substrates, we show that AglK initiates N-linked glycosylation in M. voltae through the formation of α-linked dolichyl monophosphate N-acetylglucosamine (Dol-P-GlcNAc), which contrasts with the polyprenyl-diphosphate intermediates that feature in both eukaryotes and bacteria. Intriguingly, AglK exhibits high sequence homology to dolichyl-phosphate β-glucosyltransferases, including Alg5 in eukaryotes, suggesting a common evolutionary origin. The combined action of the first two enzymes, AglK and AglC, afforded an α-linked Dol-P-glycan that serves as a competent substrate for the archaeal oligosaccharyl transferase AglB. These studies provide the first biochemical evidence revealing that despite the apparent similarity of the overall pathways, there are actually two general strategies to achieve N-linked glycoproteins across the domains of life. PMID:23624439

  3. Intergenerational Pathways Linking Childhood Sexual Abuse to HIV Risk Among Women

    PubMed Central

    Cavanaugh, Courtenay E.; Classen, Catherine C.

    2009-01-01

    Childhood sexual abuse is prevalent among women and it has been linked to a number of problems affecting women's health and functioning including women's parenting practices. Another body of literature has linked specific maternal parenting practices to daughters’ HIV risk, including mother-daughter sex communication, monitoring/knowledge about daughters’ activities, mother-daughter relationship quality, attitudes towards sex, and modeling of sexual values. This paper reviews and links these two bodies of literature to indicate how maternal histories of childhood sexual abuse may compromise mothers’ parenting practices, which may in turn impact daughters’ HIV risk. We also build upon Malow and colleagues’ model (2006) of the associations between childhood sexual abuse and HIV risk to present a model indicating potential intergenerational pathways between childhood sexual abuse and HIV risk among women. The literature supporting this model and gaps in the literature are described. PMID:19333846

  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. Calcium/calmodulin-dependent protein kinase II links ER stress with Fas and mitochondrial apoptosis pathways

    PubMed Central

    Timmins, Jenelle M.; Ozcan, Lale; Seimon, Tracie A.; Li, Gang; Malagelada, Cristina; Backs, Johannes; Backs, Thea; Bassel-Duby, Rhonda; Olson, Eric N.; Anderson, Mark E.; Tabas, Ira

    2009-01-01

    ER stress–induced apoptosis is implicated in various pathological conditions, but the mechanisms linking ER stress–mediated signaling to downstream apoptotic pathways remain unclear. Using human and mouse cell culture and in vivo mouse models of ER stress–induced apoptosis, we have shown that cytosolic calcium resulting from ER stress induces expression of the Fas death receptor through a pathway involving calcium/calmodulin-dependent protein kinase IIγ (CaMKIIγ) and JNK. Remarkably, CaMKIIγ was also responsible for processes involved in mitochondrial-dependent apoptosis, including release of mitochondrial cytochrome c and loss of mitochondrial membrane potential. CaMKII-dependent apoptosis was also observed in a number of cultured human and mouse cells relevant to ER stress–induced pathology, including cultured macrophages, endothelial cells, and neuronal cells subjected to proapoptotic ER stress. Moreover, WT mice subjected to systemic ER stress showed evidence of macrophage mitochondrial dysfunction and apoptosis, renal epithelial cell apoptosis, and renal dysfunction, and these effects were markedly reduced in CaMKIIγ-deficient mice. These data support an integrated model in which CaMKII serves as a unifying link between ER stress and the Fas and mitochondrial apoptotic pathways. Our study also revealed what we believe to be a novel proapoptotic function for CaMKII, namely, promotion of mitochondrial calcium uptake. These findings raise the possibility that CaMKII inhibitors could be useful in preventing apoptosis in pathological settings involving ER stress–induced apoptosis. PMID:19741297

  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. Hydrodynamics selects the pathway for displacive transformations in DNA-linked colloidal crystallites

    PubMed Central

    Jenkins, Ian C.; Casey, Marie T.; McGinley, James T.; Crocker, John C.; Sinno, Talid

    2014-01-01

    The degree to which DNA-linked particle crystals, particularly those composed of micrometer-scale colloids, are able to dynamically evolve or whether they are kinetically arrested after formation remains poorly understood. Here, we study a recently observed displacive transformation in colloidal binary superlattice crystals, whereby a body-centered cubic to face-centered cubic transformation is found to proceed spontaneously under some annealing conditions. Using a comprehensive suite of computer simulation tools, we develop a framework for analyzing the many displacive transformation pathways corresponding to distinct, but energetically degenerate, random hexagonal close-packed end states. Due to the short-ranged, spherically symmetric nature of the particle interactions the pathways are all barrierless, suggesting that all end states should be equally likely. Instead, we find that hydrodynamic correlations between particles result in anisotropic mobility along the various possible displacive pathways, strongly selecting for pathways that lead to the fcc-CuAu-I configuration, explaining recent experimental observations. This finding may provide clues for discovering new approaches for controlling structure in this emerging class of materials. PMID:24639545

  9. 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…

  10. Linking MLL and the HGF-MET signaling pathway in liver cancer.

    PubMed

    Marquardt, Jens U; Thorgeirsson, Snorri S

    2013-07-01

    Mixed-lineage leukemia (MLL; also known as myeloid/lymphoid), the human homolog of trithorax in Drosophila, is a transcriptional coactivator that plays an essential role during early development and hematopoiesis. Furthermore, MLL is critically involved in the epigenetic regulation of cell cycle, senescence, DNA damage, and stem cell self-renewal. Chromosomal aberrations of MLL in acute leukemias are well documented, but the role of this gene in solid malignancies remains unclear. In this issue of the JCI, Takeda et al. describe a novel epigenetic link between MLL and the HGF-MET signaling pathway conferring invasive and metastatic properties to hepatocellular carcinoma cells. PMID:23934122

  11. Wnt Signaling Translocates Lys48-Linked Polyubiquitinated Proteins to the Lysosomal Pathway.

    PubMed

    Kim, Hyunjoon; Vick, Philipp; Hedtke, Joshua; Ploper, Diego; De Robertis, Edward M

    2015-05-26

    Cellular proteins are degraded in either proteasomes or lysosomes depending on the types of ubiquitin chains that covalently modify them. It is not known whether the choice between these two pathways is physiologically regulated. The Lys48-polyubiquitin chain is the major signal directing proteins for degradation in proteasomes. Here, we report the unexpected finding that canonical Wnt signaling translocates some K48-linked polyubiquitinated proteins to the endolysosomal pathway. Proteasomal target proteins, such as b-catenin, Smad1, and Smad4, were targeted into endolysosomes in a process dependent on GSK3 activity. Relocalization was also dependent on Axin1 and the multivesicular body (MVB) proteins HRS/Vps27 and Vps4. The Wnt-induced accumulation of K48-linked polyubiquitinated proteins in endolysosomal organelles was accompanied by a transient decrease in cellular levels of free mono-ubiquitin, which may contribute to Wnt-regulated stabilization of proteins (Wnt/ STOP). We conclude that Wnt redirects Lys48-polyubiquitinated proteins that are normally degraded in proteasomes to endolysosomes. PMID:26004177

  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 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. PMID:25785227

  15. The organization and dynamics of corticostriatal pathways link the medial orbitofrontal cortex to future behavioral responses.

    PubMed

    Verstynen, Timothy D

    2014-11-15

    Accurately making a decision in the face of incongruent options increases the efficiency of making similar congruency decisions in the future. Contextual factors like reward can modulate this adaptive process, suggesting that networks associated with monitoring previous success and failure outcomes might contribute to this form of behavioral updating. To evaluate this possibility, a group of healthy adults (n = 30) were tested with functional MRI (fMRI) while they performed a color-word Stroop task. In a conflict-related region of the medial orbitofrontal cortex (mOFC), stronger BOLD responses predicted faster response times (RTs) on the next trial. More importantly, the degree of behavioral adaptation of RTs was correlated with the magnitude of mOFC-RT associations on the previous trial, but only after accounting for network-level interactions with prefrontal and striatal regions. This suggests that congruency sequencing effects may rely on interactions between distributed corticostriatal circuits. This possibility was evaluated by measuring the convergence of white matter projections from frontal areas into the striatum with diffusion-weighted imaging. In these pathways, greater convergence of corticostriatal projections correlated with stronger functional mOFC-RT associations that, in turn, provided an indirect pathway linking anatomical structure to behavior. Thus distributed corticostriatal processing may mediate the orbitofrontal cortex's influence on behavioral updating, even in the absence of explicit rewards. PMID:25143543

  16. 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

  17. 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. PMID:26358407

  18. The aryl hydrocarbon receptor links integrin signaling to the TGF-β pathway.

    PubMed

    Silginer, M; Burghardt, I; Gramatzki, D; Bunse, L; Leske, H; Rushing, E J; Hao, N; Platten, M; Weller, M; Roth, P

    2016-06-23

    Glioblastoma is the most common and aggressive form of intrinsic brain tumor. Transforming growth factor (TGF)-β represents a central mediator of the malignant phenotype of these tumors by promoting invasiveness and angiogenesis, maintaining tumor cell stemness and inducing profound immunosuppression. Integrins, which are highly expressed in glioma cells, interact with the TGF-β pathway. Furthermore, a link has been described between activity of the transcription factor aryl hydrocarbon receptor (AhR) and TGF-β expression. Here we demonstrate that integrin inhibition, using αv, β3 or β5 neutralizing antibodies, RNA interference-mediated integrin gene silencing or pharmacological inhibition by the cyclic RGD peptide EMD 121974 (cilengitide) or the non-peptidic molecule GLPG0187, inhibits AhR activity. These effects are independent of cell detachment or cell density. While AhR mRNA expression was not affected by integrin inhibition, AhR total and nuclear protein levels were reduced, suggesting that integrin inhibition-mediated regulation of AhR may occur at a post-transcriptional level. AhR-null astrocytes, AhR-null hepatocytes or glioblastoma cells with a transiently silenced AhR gene showed reduced sensitivity to integrin inhibition-mediated alterations in TGF-β signaling, indicating that AhR mediates integrin control of the TGF-β pathway. Accordingly, there was a significant correlation of αv integrin levels with nuclear AhR and pSmad2 levels as determined by immunohistochemistry in human glioblastoma in vivo. In summary, this study identifies a signaling network comprising integrins, AhR and TGF-β and validates integrin inhibition as a promising strategy not only to inhibit angiogenesis, but also to block AhR- and TGF-β-controlled features of malignancy in human glioblastoma. PMID:26500056

  19. Echistatin prevents posterior capsule opacification in diabetic rabbit model via integrin linked kinase signaling pathway

    PubMed Central

    Lin, Fengbin; Chen, Yingying; Liang, Hao; Tan, Shaojian

    2015-01-01

    Purpose: To investigate the effect of disintegrin echistatin on integrin linked kinase (ILK) and subsequent PI3-K/Akt and ERK1/2 signaling pathways in the posterior capsule opacification (PCO) model of diabetic rabbit. Methods: 56 rabbits were injected alloxan to model diabetic. Then they accepted lens extraction surgery and randomly and intraoperatively injected distilled water (control group; n = 28) or 10.0 mg·L-1 echistatin (echistatin-treated group; n = 28) into the anterior chamber. Each group was subdivided into ten days group (n = 14) and six weeks group (n = 14) respectively. The PCO severity was evaluated with a slit lamp microscope and light microscope for 10 days and 6 weeks postoperatively. The levels of ILK in the posterior capsule were determined by Q-PCR, Western blotting and Immunohistochemistry. Akt and ERK1/2 phosphorylation were analyzed by Western blotting. Results: 10 days and 6 weeks after surgery, the grades of PCO in the echistatin-treated group were lower than the control group. The lens epithelial cells (LECs) in the posterior capsule of echistatin-treated eyes had decreased degrees of proliferation and migration than the control group. And no significant side effects appeared after treated with echistatin. Echistatin could significantly reduce the expression of ILK in terms of both mRNA and protein levels. The phosphorylation levels of Akt and ERK1/2 were decreased in the echistatin-treated group compared with the control group. Conclusions: Echistatin could inhibit postoperative PCO occurrence and development in diabetic rabbit eyes, which may be related to down-regulation the expression of ILK and inhibition the PI3-K/Akt and ERK1/2 pathways. PMID:26823745

  20. 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

  1. The Vac14-interaction Network Is Linked to Regulators of the Endolysosomal and Autophagic Pathway*

    PubMed Central

    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

    2014-01-01

    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. PMID:24578385

  2. 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.

  3. 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.

  4. 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

  5. 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.

  6. 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

  7. 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…

  8. [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

  9. 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

  10. Meta gene set enrichment analyses link miR-137-regulated pathways with schizophrenia risk

    PubMed Central

    Wright, Carrie; Calhoun, Vince D.; Ehrlich, Stefan; Wang, Lei; Turner, Jessica A.; Bizzozero, Nora I. Perrone-

    2015-01-01

    Background: A single nucleotide polymorphism (SNP) within MIR137, the host gene for miR-137, has been identified repeatedly as a risk factor for schizophrenia. Previous genetic pathway analyses suggest that potential targets of this microRNA (miRNA) are also highly enriched in schizophrenia-relevant biological pathways, including those involved in nervous system development and function. Methods: In this study, we evaluated the schizophrenia risk of miR-137 target genes within these pathways. Gene set enrichment analysis of pathway-specific miR-137 targets was performed using the stage 1 (21,856 subjects) schizophrenia genome wide association study data from the Psychiatric Genomics Consortium and a small independent replication cohort (244 subjects) from the Mind Clinical Imaging Consortium and Northwestern University. Results: Gene sets of potential miR-137 targets were enriched with variants associated with schizophrenia risk, including target sets involved in axonal guidance signaling, Ephrin receptor signaling, long-term potentiation, PKA signaling, and Sertoli cell junction signaling. The schizophrenia-risk association of SNPs in PKA signaling targets was replicated in the second independent cohort. Conclusions: These results suggest that these biological pathways may be involved in the mechanisms by which this MIR137 variant enhances schizophrenia risk. SNPs in targets and the miRNA host gene may collectively lead to dysregulation of target expression and aberrant functioning of such implicated pathways. Pathway-guided gene set enrichment analyses should be useful in evaluating the impact of other miRNAs and target genes in different diseases. PMID:25941532

  11. 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...

  12. 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

  13. 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…

  14. 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…

  15. Neurodegenerative and Inflammatory Pathway Components Linked to TNF-α/TNFR1 Signaling in the Glaucomatous Human Retina

    PubMed Central

    Yang, Xiangjun; Luo, Cheng; Cai, Jian; Powell, David W.; Yu, Dahai; Kuehn, Markus H.

    2011-01-01

    Purpose. This study aimed to determine retinal proteomic alterations in human glaucoma, with particular focus on links to TNF-α/TNFR1 signaling. Methods. Human retinal protein samples were obtained from 20 donors with (n = 10) or without (n = 10) glaucoma. Alterations in protein expression were individually analyzed by quantitative LC-MS/MS. Quantitative Western blot analysis with cleavage or phosphorylation site-specific antibodies was used for data validation, and cellular localization of selected proteins was determined by immunohistochemical analysis of the retina in an additional group of glaucomatous human donor eyes (n = 38) and nonglaucomatous controls (n = 30). Results. Upregulated retinal proteins in human glaucoma included a number of downstream adaptor/interacting proteins and protein kinases involved in TNF-α/TNFR1 signaling. Bioinformatic analysis of the high-throughput data established extended networks of diverse functional interactions with death-promoting and survival-promoting pathways and mediation of immune response. Upregulated pathways included death receptor-mediated caspase cascade, mitochondrial dysfunction, endoplasmic reticulum stress, calpains leading to apoptotic cell death, NF-κB and JAK/STAT pathways, and inflammasome-assembly mediating inflammation. Interestingly, retinal expression pattern of a regulator molecule, TNFAIP3, exhibited prominent variability between individual samples, and methylation of cytosine nucleotides in the TNFAIP3 promoter was found to be correlated with this variability among glaucomatous donors. Conclusions. Findings of this study reveal a number of proteins upregulated in the glaucomatous human retina that exhibit many links to TNF-α/TNFR1 signaling. By highlighting various signaling molecules and regulators involved in cell death and immune response pathways and by correlating proteomic findings with epigenetic alterations, these findings provide a framework motivating further research. PMID:21917936

  16. Microbial pathways in colonic sulfur metabolism and links with health and disease

    PubMed Central

    Carbonero, Franck; Benefiel, Ann C.; Alizadeh-Ghamsari, Amir H.; Gaskins, H. Rex

    2012-01-01

    Sulfur is both crucial to life and a potential threat to health. While colonic sulfur metabolism mediated by eukaryotic cells is relatively well studied, much less is known about sulfur metabolism within gastrointestinal microbes. Sulfated compounds in the colon are either of inorganic (e.g., sulfates, sulfites) or organic (e.g., dietary amino acids and host mucins) origin. The most extensively studied of the microbes involved in colonic sulfur metabolism are the sulfate-reducing bacteria (SRB), which are common colonic inhabitants. Many other microbial pathways are likely to shape colonic sulfur metabolism as well as the composition and availability of sulfated compounds, and these interactions need to be examined in more detail. Hydrogen sulfide is the sulfur derivative that has attracted the most attention in the context of colonic health, and the extent to which it is detrimental or beneficial remains in debate. Several lines of evidence point to SRB or exogenous hydrogen sulfide as potential players in the etiology of intestinal disorders, inflammatory bowel diseases (IBDs) and colorectal cancer in particular. Generation of hydrogen sulfide via pathways other than dissimilatory sulfate reduction may be as, or more, important than those involving the SRB. We suggest here that a novel axis of research is to assess the effects of hydrogen sulfide in shaping colonic microbiome structure. Clearly, in-depth characterization of the microbial pathways involved in colonic sulfur metabolism is necessary for a better understanding of its contribution to colonic disorders and development of therapeutic strategies. PMID:23226130

  17. 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…

  18. Insulin/glucose induces natriuretic peptide clearance receptor in human adipocytes: a metabolic link with the cardiac natriuretic pathway.

    PubMed

    Bordicchia, M; Ceresiani, M; Pavani, M; Minardi, D; Polito, M; Wabitsch, M; Cannone, V; Burnett, J C; Dessì-Fulgheri, P; Sarzani, R

    2016-07-01

    Cardiac natriuretic peptides (NP) are involved in cardiorenal regulation and in lipolysis. The NP activity is largely dependent on the ratio between the signaling receptor NPRA and the clearance receptor NPRC. Lipolysis increases when NPRC is reduced by starving or very-low-calorie diet. On the contrary, insulin is an antilipolytic hormone that increases sodium retention, suggesting a possible functional link with NP. We examined the insulin-mediated regulation of NP receptors in differentiated human adipocytes and tested the association of NP receptor expression in visceral adipose tissue (VAT) with metabolic profiles of patients undergoing renal surgery. Differentiated human adipocytes from VAT and Simpson-Golabi-Behmel Syndrome (SGBS) adipocyte cell line were treated with insulin in the presence of high-glucose or low-glucose media to study NP receptors and insulin/glucose-regulated pathways. Fasting blood samples and VAT samples were taken from patients on the day of renal surgery. We observed a potent insulin-mediated and glucose-dependent upregulation of NPRC, through the phosphatidylinositol 3-kinase pathway, associated with lower lipolysis in differentiated adipocytes. No effect was observed on NPRA. Low-glucose medium, used to simulate in vivo starving conditions, hampered the insulin effect on NPRC through modulation of insulin/glucose-regulated pathways, allowing atrial natriuretic peptide to induce lipolysis and thermogenic genes. An expression ratio in favor of NPRC in adipose tissue was associated with higher fasting insulinemia, HOMA-IR, and atherogenic lipid levels. Insulin/glucose-dependent NPRC induction in adipocytes might be a key factor linking hyperinsulinemia, metabolic syndrome, and higher blood pressure by reducing NP effects on adipocytes. PMID:27101299

  19. Mfn2 deficiency links age-related sarcopenia and impaired autophagy to activation of an adaptive mitophagy pathway.

    PubMed

    Sebastián, David; Sorianello, Eleonora; Segalés, Jessica; Irazoki, Andrea; Ruiz-Bonilla, Vanessa; Sala, David; Planet, Evarist; Berenguer-Llergo, Antoni; Muñoz, Juan Pablo; Sánchez-Feutrie, Manuela; Plana, Natàlia; Hernández-Álvarez, María Isabel; Serrano, Antonio L; Palacín, Manuel; Zorzano, Antonio

    2016-08-01

    Mitochondrial dysfunction and accumulation of damaged mitochondria are considered major contributors to aging. However, the molecular mechanisms responsible for these mitochondrial alterations remain unknown. Here, we demonstrate that mitofusin 2 (Mfn2) plays a key role in the control of muscle mitochondrial damage. We show that aging is characterized by a progressive reduction in Mfn2 in mouse skeletal muscle and that skeletal muscle Mfn2 ablation in mice generates a gene signature linked to aging. Furthermore, analysis of muscle Mfn2-deficient mice revealed that aging-induced Mfn2 decrease underlies the age-related alterations in metabolic homeostasis and sarcopenia. Mfn2 deficiency reduced autophagy and impaired mitochondrial quality, which contributed to an exacerbated age-related mitochondrial dysfunction. Interestingly, aging-induced Mfn2 deficiency triggers a ROS-dependent adaptive signaling pathway through induction of HIF1α transcription factor and BNIP3. This pathway compensates for the loss of mitochondrial autophagy and minimizes mitochondrial damage. Our findings reveal that Mfn2 repression in muscle during aging is a determinant for the inhibition of mitophagy and accumulation of damaged mitochondria and triggers the induction of a mitochondrial quality control pathway. PMID:27334614

  20. 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

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

    PubMed

    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

  2. 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

  3. A functional link between the co-translational protein translocation pathway and the UPR

    PubMed Central

    Plumb, Rachel; Zhang, Zai-Rong; Appathurai, Suhila; Mariappan, Malaiyalam

    2015-01-01

    Upon endoplasmic reticulum (ER) stress, the transmembrane endoribonuclease Ire1α performs mRNA cleavage reactions to increase the ER folding capacity. It is unclear how the low abundant Ire1α efficiently finds and cleaves the majority of mRNAs at the ER membrane. Here, we reveal that Ire1α forms a complex with the Sec61 translocon to cleave its mRNA substrates. We show that Ire1α's key substrate, XBP1u mRNA, is recruited to the Ire1α-Sec61 translocon complex through its nascent chain, which contains a pseudo-transmembrane domain to utilize the signal recognition particle (SRP)-mediated pathway. Depletion of SRP, the SRP receptor or the Sec61 translocon in cells leads to reduced Ire1α-mediated splicing of XBP1u mRNA. Furthermore, mutations in Ire1α that disrupt the Ire1α-Sec61 complex causes reduced Ire1α-mediated cleavage of ER-targeted mRNAs. Thus, our data suggest that the Unfolded Protein Response is coupled with the co-translational protein translocation pathway to maintain protein homeostasis in the ER during stress conditions. DOI: http://dx.doi.org/10.7554/eLife.07426.001 PMID:25993558

  4. 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

  5. Developmental pathways linking childhood and adolescent internalizing, externalizing, academic competence, and adolescent depression.

    PubMed

    Weeks, Murray; Ploubidis, George B; Cairney, John; Wild, T Cameron; Naicker, Kiyuri; Colman, Ian

    2016-08-01

    This study examined longitudinal pathways through three domains of adaptation from ages 4-5 to 14-15 (internalizing problems, externalizing problems, and academic competence) towards depressive symptoms at age 16-17. Participants were 6425 Canadian children followed bi-annually as part of the National Longitudinal Study of Children and Youth. Within-domain (i.e., stability) effects were moderate in strength. We found longitudinal cross-domain effects across one time point (i.e., one-lag cascades) between internalizing and externalizing in early childhood (positive associations), and between academic competence and externalizing in later childhood and adolescence (negative associations). We also found cascade effects over multiple time points (i.e., multi-lag cascades); lower academic competence at age 4-5 and greater internalizing at age 6-7 predicted greater age 12-13 externalizing, and greater age 6-7 externalizing predicted greater age 16-17 depression. Important pathways towards adolescent depression include a stability path through childhood and adolescent internalizing, as well as a number of potential paths involving all domains of adaptation, highlighting the multifactorial nature of adolescent depression. PMID:27288965

  6. 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

  7. A genome wide association study links glutamate receptor pathway to sporadic Creutzfeldt-Jakob disease risk.

    PubMed

    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

    2014-01-01

    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

  8. Wallerian degeneration: an emerging axon death pathway linking injury and disease.

    PubMed

    Conforti, Laura; Gilley, Jonathan; Coleman, Michael P

    2014-06-01

    Axon degeneration is a prominent early feature of most neurodegenerative disorders and can also be induced directly by nerve injury in a process known as Wallerian degeneration. The discovery of genetic mutations that delay Wallerian degeneration has provided insight into mechanisms underlying axon degeneration in disease. Rapid Wallerian degeneration requires the pro-degenerative molecules SARM1 and PHR1. Nicotinamide mononucleotide adenylyltransferase 2 (NMNAT2) is essential for axon growth and survival. Its loss from injured axons may activate Wallerian degeneration, whereas NMNAT overexpression rescues axons from degeneration. Here, we discuss the roles of these and other proposed regulators of Wallerian degeneration, new opportunities for understanding disease mechanisms and intriguing links between Wallerian degeneration, innate immunity, synaptic growth and cell death. PMID:24840802

  9. Emotional awareness as a pathway linking adult attachment to subsequent depression.

    PubMed

    Monti, Jennifer D; Rudolph, Karen D

    2014-07-01

    Although research links insecure adult attachment with depression, the emotional processes accounting for this association over time remain relatively unexplored. To address this gap, this study investigated whether deficits in emotional awareness serve as one explanatory process. Adult female caregivers (N = 417, Mage = 37.83) completed questionnaires annually for 3 years. As anticipated, attachment avoidance exerted an indirect effect on depression via emotional awareness. Attachment anxiety directly predicted subsequent depression, but the indirect effect through emotional awareness was nonsignificant. These results suggest that an avoidant attachment style interferes with the effective processing of emotions, thereby placing women at risk for depression. This research implicates emotional awareness as a potential target for interventions aimed at reducing depressive symptoms in mothers with avoidant attachment styles. PMID:25019541

  10. Membrane-To-Nucleus Signaling Links Insulin-Like Growth Factor-1- and Stem Cell Factor-Activated Pathways

    PubMed Central

    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

  11. Developing Measures of Pathways that May Link Macro Social/Structural Changes with HIV Epidemiology.

    PubMed

    Pouget, Enrique R; Sandoval, Milagros; Nikolopoulos, Georgios K; Mateu-Gelabert, Pedro; Rossi, Diana; Smyrnov, Pavlo; Jones, Yolanda; Friedman, Samuel R

    2016-08-01

    Macro-social/structural events ("big events") such as wars, disasters, and large-scale changes in policies can affect HIV transmission by making risk behaviors more or less likely or by changing risk contexts. The purpose of this study was to develop new measures to investigate hypothesized pathways between macro-social changes and HIV transmission. We developed novel scales and indexes focused on topics including norms about sex and drug injecting under different conditions, involvement with social groups, helping others, and experiencing denial of dignity. We collected data from 300 people who inject drugs in New York City during 2012-2013. Most investigational measures showed evidence of validity (Pearson correlations with criterion variables range = 0.12-0.71) and reliability (Cronbach's alpha range = 0.62-0.91). Research is needed in different contexts to evaluate whether these measures can be used to better understand HIV outbreaks and help improve social/structural HIV prevention intervention programs. PMID:26796384

  12. 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

  13. Octopamine Neuromodulation Regulates Gr32a-Linked Aggression and Courtship Pathways in Drosophila Males

    PubMed Central

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

    2014-01-01

    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-FruM 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. PMID:24852170

  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). PMID:24478219

  15. 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

  16. 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

  17. 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

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

    PubMed Central

    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

    2014-01-01

    Whole genome sequencing (WGS) studies are uncovering disease-associated variants in both rare and non-rare 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 to 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. PMID:24478219

  19. MRNA and miRNA expression patterns associated to pathways linked to metal mixture health effects.

    PubMed

    Martínez-Pacheco, M; Hidalgo-Miranda, A; Romero-Córdoba, S; Valverde, M; Rojas, E

    2014-01-10

    Metals are a threat to human health by increasing disease risk. Experimental data have linked altered miRNA expression with exposure to some metals. MiRNAs comprise a large family of non-coding single-stranded molecules that primarily function to negatively regulate gene expression post-transcriptionally. Although several human populations are exposed to low concentrations of As, Cd and Pb as a mixture, most toxicology research focuses on the individual effects that these metals exert. Thus, this study aims to evaluate global miRNA and mRNA expression changes induced by a metal mixture containing NaAsO2, CdCl2, Pb(C2H3O2)2·3H2O and to predict possible metal-associated disease development under these conditions. Our results show that this metal mixture results in a miRNA expression profile that may be responsible for the mRNA expression changes observed under experimental conditions in which coding proteins are involved in cellular processes, including cell death, growth and proliferation related to the metal-associated inflammatory response and cancer. PMID:24080485

  20. 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

  1. Longitudinal pathways linking child maltreatment, emotion regulation, peer relations, and psychopathology

    PubMed Central

    Kim, Jungmeen; Cicchetti, Dante

    2012-01-01

    Background The aim of this study was to investigate longitudinal relations among child maltreatment, emotion regulation, peer acceptance and rejection, and psychopathology. Methods Data were collected on 215 maltreated and 206 nonmaltreated children (ages 6–12 years) from low-income families. Children were evaluated by camp counselors on emotion regulation and internalizing and externalizing symptomatology and were nominated by peers for peer acceptance and rejection. Results Structural equation modeling analyses revealed that experiencing neglect, physical and/or sexual abuse, multiple maltreatment subtypes, and earlier onset of maltreatment were related to emotion dysregulation. Lower emotion regulation (Time 1) was associated with higher externalizing symptomatology (Time 1) that contributed to later peer rejection (Time 2), which in turn was related to higher externalizing symptomatology (Time 2). Conversely, higher emotion regulation was predictive of higher peer acceptance over time, which was related to lower internalizing symptomatology controlling for initial levels of symptomatology. Conclusions The findings emphasize the important role of emotion regulation as a risk or a protective mechanism in the link between earlier child maltreatment and later psychopathology through its influences on peer relations. PMID:20050965

  2. 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

  3. 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

  4. FMNL2/FMNL3 formins are linked with oncogenic pathways and predict melanoma outcome

    PubMed Central

    Heuser, Vanina D; Koskivuo, Ilkka; Koivisto, Mari; Carpén, Olli

    2016-01-01

    Abstract While most early (stage I‐II) melanomas are cured by surgery, recurrence is not uncommon. Prognostication by current clinicopathological parameters does not provide sufficient means for identifying patients who are at risk of developing metastases and in need of adjuvant therapy. Actin‐regulating formins may account for invasive properties of cancer cells, including melanoma. Here, we studied formin‐like protein 2 and 3 (FMNL2 and FMNL3) in melanoma by analysing their role in the invasive properties of melanoma cells and by evaluating whether FMNL2 expression is associated with melanoma outcome. Immunohistochemical characterization of FMNL2 in a cohort of 175 primary cutaneous stage I‐II melanomas indicated that high FMNL2 reactivity correlates with poor outcome as evaluated by recurrence free survival (p < 0.0001) or disease specific survival (p < 0.0001). In multivariate analysis, Breslow's thickness (p < 0.05) and FMNL2 expression (p < 0.001) remained as independent prognostic factors. Cellular studies revealed that FMNL2 is a component of filopodia in many melanoma cell lines. Inhibition of either FMNL2 or the closely related FMNL3 affected the maintenance of melanoma cell morphology and reduced migration. Finally, inhibition of the BRAF, PI3K and MAPK oncogenic pathways markedly reduced expression of both FMNL2 and FMNL3 in melanoma cells. The results suggest a major role for FMNL2/FMNL3 formins in melanoma biology and raise the possibility that the novel targeted melanoma drugs may interfere with the cellular properties regulated by these formins.

  5. 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

  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. 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

  8. G protein-linked signaling pathways in bipolar and major depressive disorders.

    PubMed

    Tomita, Hiroaki; Ziegler, Mary E; Kim, Helen B; Evans, Simon J; Choudary, Prabhakara V; Li, Jun Z; Meng, Fan; Dai, Manhong; Myers, Richard M; Neal, Charles R; Speed, Terry P; Barchas, Jack D; Schatzberg, Alan F; Watson, Stanley J; Akil, Huda; Jones, Edward G; Bunney, William E; Vawter, Marquis P

    2013-01-01

    The G-protein linked signaling system (GPLS) comprises a large number of G-proteins, G protein-coupled receptors (GPCRs), GPCR ligands, and downstream effector molecules. G-proteins interact with both GPCRs and downstream effectors such as cyclic adenosine monophosphate (cAMP), phosphatidylinositols, and ion channels. The GPLS is implicated in the pathophysiology and pharmacology of both major depressive disorder (MDD) and bipolar disorder (BPD). This study evaluated whether GPLS is altered at the transcript level. The gene expression in the dorsolateral prefrontal (DLPFC) and anterior cingulate (ACC) were compared from MDD, BPD, and control subjects using Affymetrix Gene Chips and real time quantitative PCR. High quality brain tissue was used in the study to control for confounding effects of agonal events, tissue pH, RNA integrity, gender, and age. GPLS signaling transcripts were altered especially in the ACC of BPD and MDD subjects. Transcript levels of molecules which repress cAMP activity were increased in BPD and decreased in MDD. Two orphan GPCRs, GPRC5B and GPR37, showed significantly decreased expression levels in MDD, and significantly increased expression levels in BPD. Our results suggest opposite changes in BPD and MDD in the GPLS, "activated" cAMP signaling activity in BPD and "blunted" cAMP signaling activity in MDD. GPRC5B and GPR37 both appear to have behavioral effects, and are also candidate genes for neurodegenerative disorders. In the context of the opposite changes observed in BPD and MDD, these GPCRs warrant further study of their brain effects. PMID:24391664

  9. 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

  10. Nocistatin inhibits 5-hydroxytryptamine release in the mouse neocortex via presynaptic Gi/o protein linked pathways

    PubMed Central

    Fantin, M; Fischetti, C; Trapella, C; Morari, M

    2007-01-01

    Background and purpose: Nocistatin (NST) is a neuropeptide generated from cleavage of the nociceptin/orphanin FQ (N/OFQ) precursor. Evidence has been presented that NST acts as a functional antagonist of N/OFQ, although NST receptor and transduction pathways have not yet been identified. We previously showed that N/OFQ inhibited [3H]5-hydroxytryptamine ([3H]5-HT) release from mouse cortical synaptosomes via activation of NOP receptors. We now investigate whether NST regulates [3H]5-HT release in the same preparation. Experimental approach: Mouse and rat cerebrocortical synaptosomes in superfusion, preloaded with [3H]5-HT and stimulated with 1 min pulses of 10 mM KCl, were used. Key results: Bovine NST (b-NST) inhibited the K+-induced [3H]5-HT release, displaying similar efficacy but lower potency than N/OFQ. b-NST action underwent concentration-dependent and time-dependent desensitization, and was not prevented either by the NOP receptor antagonist [Nphe1 Arg14,Lys15]N/OFQ(1-13)-NH2 (UFP-101) or by the non-selective opioid receptor antagonist, naloxone. Contrary to N/OFQ, b-NST reduced [3H]5-HT release from synaptosomes obtained from NOP receptor knockout mice. However, both N/OFQ and NST were ineffective in synaptosomes pre-treated with the Gi/o protein inhibitor, Pertussis toxin. NST-N/OFQ interactions were also investigated. Co-application of maximal concentrations of both peptides did not result in additive effects, whereas pre-application of maximal b-NST concentrations partially attenuated N/OFQ inhibition. Conclusions and implications: We conclude that b-NST inhibits [3H]5-HT release via activation of Gi/o protein linked pathways, not involving classical opioid receptors and the NOP receptor. The present data strengthen the view that b-NST is, per se, a biologically active peptide endowed with agonist activity. PMID:17618307

  11. 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. PMID:24067295

  12. 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

  13. Involvement of net and Hif1alpha in distinct yet intricately linked hypoxia-induced signaling pathways.

    PubMed

    Serchov, Tsvetan; Dubois-Pot-Schneider, Helene; Charlot, Celine; Rösl, Frank; Wasylyk, Bohdan

    2010-07-01

    The present study compares negative Ets transcription factor (Net) and hypoxia-inducible factor 1alpha (HIF1alpha) regulation by hypoxia. Their protein stabilities are differently regulated by hypoxia, defining three periods in the kinetics: normoxia (high Net levels and low HIF1alpha levels), early hypoxia (high levels of Net and HIF1alpha), and late hypoxia (degradation of Net and HIF1alpha). Modulators of prolyl hydroxylase domain protein (PHD) activity induce a mobility shift of Net, similar to HIF1alpha, suggesting that post-translational modifications of both factors depend on PHD activity. The three PHDs have different roles in the regulation of Net protein levels; PHD1 and PHD3 are involved in the stabilization of Net, whereas PHD2 controls its degradation in late hypoxia. Net physically interacts with PHD2 in hypoxia, whereas PHD1 and PHD3 bind to Net in normoxia and hypoxia. Under the same conditions, PHD2 and PHD3 regulate both HIF1alpha stabilization in early hypoxia and its degradation at late hypoxia, whereas PHD1 is involved in HIF1alpha degradation in late hypoxia. We describe interconnections between the regulation of both Net and HIF1alpha at the protein level. Evidence is provided for a direct physical interaction between Net and HIF1alpha and indirect transcriptional regulation loops that involve the PHDs. Taken together our results indicate that Net and HIF1alpha are components of distinct signaling pathways that are intricately linked. PMID:20427288

  14. 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

  15. 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

  16. 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

  17. A Diet-Sensitive BAF60a-Mediated Pathway Links Hepatic Bile Acid Metabolism to Cholesterol Absorption and Atherosclerosis.

    PubMed

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

    2015-11-24

    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

  18. 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. PMID:25413497

  19. 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

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

    PubMed

    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

  1. Linking Electronic Health Records to Better Understand Breast Cancer Patient Pathways Within and Between Two Health Systems

    PubMed Central

    Thompson, Caroline A.; Kurian, Allison W.; Luft, Harold S.

    2015-01-01

    Introduction: In a fragmented health care system, research can be challenging when one seeks to follow cancer patients as they seek care which can continue for months or years and may reflect many physician and patient decisions. Claims data track patients, but lack clinical detail. Linking routine electronic health record (EHR) data with clinical registry data allows one to gain a more complete picture of the patient journey through a cancer care episode. However, valid analytical approaches to examining care trajectories must be longitudinal and account for the dynamic nature of what is “seen” in the EHR. Methods: The Oncoshare database combines clinical detail from the California Cancer Registry and EHR data from two large health care organizations in the same catchment area—a multisite community practice and an academic medical center—for all women treated in either organization for breast cancer from 2000 to 2012. We classified EHR encounters data according to typical periods of the cancer care episode (screening, diagnosis, treatment) and posttreatment surveillance, as well as by facility used to better characterize patterns of care for patients seen at both organizations. Findings: We identified a “treated” cohort consisting of women receiving interventions for their initial cancer diagnosis, and classified their encounters over time across multiple dimensions (type of care, provider of care, and timing of care with respect to their cancer diagnosis). Forty-three percent of the patients were treated at the academic center only, 42 percent at the community center only, and 16 percent of the patients obtained care at both health care organizations. Compared to women seen at only one organization, the last group had similar-length initial care episodes, but more frequently had multiple episodes and longer observation periods. Discussion: Linking EHR data from neighboring systems can enhance our information on care trajectories, but careful

  2. B cell receptor cross-linking triggers a caspase-8-dependent apoptotic pathway that is independent of the death effector domain of Fas-associated death domain protein.

    PubMed

    Besnault, L; Schrantz, N; Auffredou, M T; Leca, G; Bourgeade, M F; Vazquez, A

    2001-07-15

    We have previously reported that B cell receptors, depending on the degree to which they are cross-linked, can promote apoptosis in various human B cell types. In this study, we show that B cell receptors can trigger two apoptotic pathways according to cross-linking and that these pathways control mitochondrial activation in human Burkitt's lymphoma cells. Whereas soluble anti-mu Ab triggers caspase-independent mitochondrial activation, cross-linked anti-mu Ab induces an apoptotic response associated with a caspase-dependent loss of mitochondrial transmembrane potential. This B cell receptor-mediated caspase-dependent mitochondrial activation is associated with caspase-8 activation. We show here that caspase-8 inhibitors strongly decrease cross-linking-dependent B cell receptor-mediated apoptosis in Burkitt's lymphoma BL41 cells. These inhibitors act upstream from the mitochondria as they prevented the loss of mitochondrial membrane potential observed in B cell receptor-treated BL41 cells. Caspase-8 activation in these cells was also evident from the detection of cleaved fragments of caspase-8 and the cleavage of specific substrates, including Bid. Our data show that cross-linked B cell receptors induced an apoptotic pathway involving sequential caspase-8 activation, loss of mitochondrial membrane potential, and the activation of caspase-9 and caspase-3. Cells expressing a dominant negative mutant of Fas-associated death domain protein were sensitive to cross-linked B cell receptor-induced caspase-8 activation and apoptosis; therefore, this caspase-8 activation was independent of the death effector domain of Fas-associated death domain protein. PMID:11441077

  3. The mammalian target of rapamycin signaling pathway regulates myocyte enhancer factor-2C phosphorylation levels through integrin-linked kinase in goat skeletal muscle satellite cells.

    PubMed

    Wu, Haiqing; Ren, Yu; Pan, Wei; Dong, Zhenguo; Cang, Ming; Liu, Dongjun

    2015-11-01

    Mammalian target of rapamycin (mTOR) signaling pathway plays a key role in muscle development and is involved in multiple intracellular signaling pathways. Myocyte enhancer factor-2 (MEF2) regulates muscle cell proliferation and differentiation. However, how the mTOR signaling pathway regulates MEF2 activity remains unclear. We isolated goat skeletal muscle satellite cells (gSSCs) as model cells to explore mTOR signaling pathway regulation of MEF2C. We inhibited mTOR activity in gSSCs with PP242 and found that MEF2C phosphorylation was decreased and that muscle creatine kinase (MCK) expression was suppressed. Subsequently, we detected integrin-linked kinase (ILK) using MEF2C coimmunoprecipitation; ILK and MEF2C were colocalized in the gSSCs. We found that inhibiting mTOR activity increased ILK phosphorylation levels and that inhibiting ILK activity with Cpd 22 and knocking down ILK with small interfering RNA increased MEF2C phosphorylation and MCK expression. In the presence of Cpd 22, mTOR activity inhibition did not affect MEF2C phosphorylation. Moreover, ILK dephosphorylated MEF2C in vitro. These results suggest that the mTOR signaling pathway regulates MEF2C positively and regulates ILK negatively and that ILK regulates MEF2C negatively. It appears that the mTOR signaling pathway regulates MEF2C through ILK, further regulating the expression of muscle-related genes in gSSCs. PMID:26041412

  4. 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

  5. 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

  6. 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

  7. 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

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

    PubMed

    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; Waters, Katrina M; Harper, Stacey L; Williams, David E

    2016-05-01

    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. 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. PMID:26759916

  9. The noa gene is functionally linked to the activation of the Toll/Imd signaling pathways in Bactrocera dorsalis (Hendel).

    PubMed

    Dong, Xiaolong; Li, Qiujia; Zhang, Hongyu

    2016-02-01

    The noa gene is an essential gene encoding a very long chain fatty acid elongase. In this study, we cloned the noa gene of Bactrocera dorsalis, which encodes a protein sharing 84.50% identity to the NOA in Drosophila melanogaster. The expression profiles indicated that the transcriptional level of noa was high at the egg stage and in the testis tissue. The results showed that noa expression was up-regulated after Listeria monocytogenes, Staphylococcus aureus and Escherichia coli infection. Silencing of noa would influence the expression of immune related genes, including MyD88 and defensin in the Toll pathway and relish and diptericin in the Imd pathway. Moreover, infection with L. monocytogenes and S. aureus after feeding ds-noa, the expression of MyD88 and defensin down-regulated significantly in ds-noa group compared with in ds-egfp group, indicating that noa interference influenced the activation of the Toll pathway. Meanwhile, infection with L. monocytogenes and E. coli, which activated the Imd pathway, do not cause increase of the mRNA levels of relish and diptericin in ds-noa group as severely as in ds-egfp treatment, indicating that the Imd pathway was also repressed after silences of noa. PMID:26404497

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

    DOE PAGESBeta

    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

  11. Genome-wide genetic screen identified the link between dG9a and epidermal growth factor receptor signaling pathway in vivo.

    PubMed

    Shimaji, Kouhei; Konishi, Takahiro; Yoshida, Hideki; Kimura, Hiroshi; Yamaguchi, Masamitsu

    2016-08-01

    G9a is one of the histone H3 Lys 9 (H3K9) specific methyltransferases first identified in mammals. Drosophila G9a (dG9a) has been reported to induce H3K9 dimethylation in vivo, and the target genes of dG9a were identified during embryonic and larval stages. Although dG9a is important for a variety of developmental processes, the link between dG9a and signaling pathways are not addressed yet. Here, by genome-wide genetic screen, taking advantage of the rough eye phenotype of flies that over-express dG9a in eye discs, we identified 16 genes that enhanced the rough eye phenotype induced by dG9a over-expression. These 16 genes included Star, anterior open, bereft and F-box and leucine-rich repeat protein 6 which are components of epidermal growth factor receptor (EGFR) signaling pathway. When dG9a over-expression was combined with mutation of Star, differentiation of R7 photoreceptors in eye imaginal discs as well as cone cells and pigment cells in pupal retinae was severely inhibited. Furthermore, the dG9a over-expression reduced the activated ERK signals in eye discs. These data demonstrate a strong genetic link between dG9a and the EGFR signaling pathway. PMID:27343629

  12. 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

  13. Biochemical characterization of the O-linked glycosylation pathway in Neisseria gonorrhoeae responsible for biosynthesis of protein glycans containing N,N'-diacetylbacillosamine.

    PubMed

    Hartley, Meredith D; Morrison, Michael J; Aas, Finn Erik; Børud, Bente; Koomey, Michael; Imperiali, Barbara

    2011-06-01

    The O-linked protein glycosylation pathway in Neisseria gonorrhoeae is responsible for the synthesis of a complex oligosaccharide on undecaprenyl diphosphate and subsequent en bloc transfer of the glycan to serine residues of select periplasmic proteins. Protein glycosylation (pgl) genes have been annotated on the basis of bioinformatics and top-down mass spectrometry analysis of protein modifications in pgl-null strains [Aas, F. E., et al. (2007) Mol. Microbiol. 65, 607-624; Vik, A., et al. (2009) Proc. Natl. Acad. Sci. U.S.A. 106, 4447-4452], but relatively little biochemical analysis has been performed to date. In this report, we present the expression, purification, and functional characterization of seven Pgl enzymes. Specifically, the enzymes studied are responsible for synthesis of an uncommon uridine diphosphate (UDP)-sugar (PglD, PglC, and PglB-acetyltransferase domain), glycan assembly (PglB-phospho-glycosyltransferase domain, PglA, PglE, and PglH), and final oligosaccharide transfer (PglO). UDP-2,4-diacetamido-2,4,6-trideoxy-α-d-hexose (DATDH), which is the first sugar in glycan biosynthesis, was produced enzymatically, and the stereochemistry was assigned as uridine diphosphate N'-diacetylbacillosamine (UDP-diNAcBac) by nuclear magnetic resonance characterization. In addition, the substrate specificities of the phospho-glycosyltransferase, glycosyltransferases, and oligosaccharyltransferase (OTase) were analyzed in vitro, and in most cases, these enzymes exhibited strong preferences for the native substrates relative to closely related glycans. In particular, PglO, the O-linked OTase, and PglB(Cj), the N-linked OTase from Campylobacter jejuni, preferred the native N. gonorrhoeae and C. jejuni substrates, respectively. This study represents the first comprehensive biochemical characterization of this important O-linked glycosylation pathway and provides the basis for further investigations of these enzymes as antibacterial targets. PMID:21542610

  14. Formation pathways for lysine-arginine cross-links derived from hexoses and pentoses by Maillard processes: unraveling the structure of a pentosidine precursor.

    PubMed

    Biemel, K M; Reihl, O; Conrad, J; Lederer, M O

    2001-06-29

    Covalently cross-linked proteins are among the major modifications caused by the advanced Maillard reaction. So far, the chemical nature of these aggregates and their formation pathways are largely unknown. Synthesis and unequivocal structural characterization are reported for the lysine-arginine cross-links N(6)-(2-([(4S)-4-ammonio-5-oxido-5-oxopentyl]amino)-5-[(2S,3R)-2,3,4- trihydroxybutyl]-3,5-dihydro-4H-imidazol-4-ylidene)-l-lysinate (DOGDIC 12), N(6)-(2-([(4S)-4-ammonio-5-oxido-5-oxopentyl]amino)-5-[(2S)-2,3-dihydroxypropyl]-3,5-dihydro-4H-imidazol-4-ylidene)-l-lysinate (DOPDIC 13), and 6-((6S)-2-([(4S)-4-ammonio-5-oxido-5-oxopentyl] amino)-6-hydroxy-5,6,7,7a-tetrahydro-4H-imidazo[4,5-b] pyridin-4-yl)-l-norleucinate (pentosinane 10). For these compounds, as well as for glucosepane 9 and pentosidine 11, the formation pathways could be established by starting from native carbohydrates, Amadori products, and 3-deoxyosones, respectively. Pentosinane 10 was unequivocally proven to be an important precursor of pentosidine 11, which is a well established fluorescent indicator for advanced glycation processes in vivo. The Amadori products are shown to be the pivots in the formation of the various cross-links 9-13. The bicyclic structures 9-11 are directly derived from aminoketoses, whereas 12 and 13 stem from reaction with the 3-deoxyosones. All products 9-13 were identified and quantified from incubations of bovine serum albumin with the respective 3-deoxyosone or carbohydrate. From these results it seems fully justified to expect both glucosepane 9 and DOGDIC 12 to constitute important in vivo cross-links. PMID:11279247

  15. Socioeconomic Disparities and Influenza Hospitalizations, Tennessee, USA

    PubMed Central

    Sloan, Chantel; Chandrasekhar, Rameela; Mitchel, Edward; Schaffner, William

    2015-01-01

    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

  16. 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

  17. 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

  18. 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…

  19. 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…

  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. 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.

  2. 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

  3. 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

  4. Adaptor protein Ste50p links the Ste11p MEKK to the HOG pathway through plasma membrane association

    PubMed Central

    Wu, Cunle; Jansen, Gregor; Zhang, Jianchun; Thomas, David Y.; Whiteway, Malcolm

    2006-01-01

    In a variety of yeast cellular pathways, the Ste50p protein regulates the kinase function of the mitogen extracellular signal-regulated kinase kinase (MEKK) Ste11p. Both Ste11p and Ste50p contain sterile α motif (SAM) domains; these are interchangeable, and can be replaced by other protein-interacting modules. Furthermore, the function of the Ras association (RA)-like domain of Ste50p can be mimicked by a plasma membrane recruiting signal, and direct plasma membrane targeting of Ste11p bypasses the requirement of Ste50p for Ste11p function. Thus the regulatory role of Ste50p requires both the N-terminal SAM domain to bind Ste11p and the C-terminal RA-like domain to direct kinase localization. We have identified Opy2p, an integral membrane protein that can interact with Ste50p, as a new component in the Sho1p–Ste11p/Ste50p signaling branch of the high-osmolarity glycerol (HOG) pathway. We propose that Opy2p can serve as a membrane anchor for the Ste50p/Ste11p module in the activation of the HOG pathway. PMID:16543225

  5. UBL1 of Fusarium verticillioides links the N-end rule pathway to extracellular sensing and plant pathogenesis.

    PubMed

    Ridenour, John B; Smith, Jonathon E; Hirsch, Robert L; Horevaj, Peter; Kim, Hun; Sharma, Sandeep; Bluhm, Burton H

    2014-07-01

    Fusarium verticillioides produces fumonisin mycotoxins during colonization of maize. Currently, molecular mechanisms underlying responsiveness of F.verticillioides to extracellular cues during pathogenesis are poorly understood. In this study, insertional mutants were created and screened to identify genes involved in responses to extracellular starch. In one mutant, the restriction enzyme-mediated integration cassette disrupted a gene (UBL1) encoding a UBR-Box/RING domain E3 ubiquitin ligase involved in the N-end rule pathway. Disruption of UBL1 in F.verticillioides (Δubl1) influenced conidiation, hyphal morphology, pigmentation and amylolysis. Disruption of UBL1 also impaired kernel colonization, but the ratio of fumonisin B1 per unit growth was not significantly reduced. The inability of a Δubl1 mutant to recognize an N-end rule degron confirmed involvement of UBL1 in the N-end rule pathway. Additionally, Ubl1 physically interacted with two G protein α subunits of F.verticillioides, thus implicating UBL1 in G protein-mediated sensing of the external environment. Furthermore, deletion of the UBL1 orthologue in F.graminearum reduced virulence on wheat and maize, thus indicating that UBL1 has a broader role in virulence among Fusarium species. This study provides the first linkage between the N-end rule pathway and fungal pathogenesis, and illustrates a new mechanism through which fungi respond to the external environment. PMID:24237664

  6. A Direct Link between Abscisic Acid Sensing and the Chromatin-Remodeling ATPase BRAHMA via Core ABA Signaling Pathway Components.

    PubMed

    Peirats-Llobet, Marta; Han, Soon-Ki; Gonzalez-Guzman, Miguel; Jeong, Cheol Woong; Rodriguez, Lesia; Belda-Palazon, Borja; Wagner, Doris; Rodriguez, Pedro L

    2016-01-01

    Optimal response to drought is critical for plant survival and will affect biodiversity and crop performance during climate change. Mitotically heritable epigenetic or dynamic chromatin state changes have been implicated in the plant response to the drought stress hormone abscisic acid (ABA). The Arabidopsis SWI/SNF chromatin-remodeling ATPase BRAHMA (BRM) modulates response to ABA by preventing premature activation of stress response pathways during germination. We show that core ABA signaling pathway components physically interact with BRM and post-translationally modify BRM by phosphorylation/dephosphorylation. Genetic evidence suggests that BRM acts downstream of SnRK2.2/2.3 kinases, and biochemical studies identified phosphorylation sites in the C-terminal region of BRM at SnRK2 target sites that are evolutionarily conserved. Finally, the phosphomimetic BRM(S1760D S1762D) mutant displays ABA hypersensitivity. Prior studies showed that BRM resides at target loci in the ABA pathway in the presence and absence of the stimulus, but is only active in the absence of ABA. Our data suggest that SnRK2-dependent phosphorylation of BRM leads to its inhibition, and PP2CA-mediated dephosphorylation of BRM restores the ability of BRM to repress ABA response. These findings point to the presence of a rapid phosphorylation-based switch to control BRM activity; this property could be potentially harnessed to improve drought tolerance in plants. PMID:26499068

  7. 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. PMID:26995658

  8. 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

  9. 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

  10. 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

  11. 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

  12. 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

  13. Starvation-Dependent Regulation of Golgi Quality Control Links the TOR Signaling and Vacuolar Protein Sorting Pathways.

    PubMed

    Dobzinski, Niv; Chuartzman, Silvia G; Kama, Rachel; Schuldiner, Maya; Gerst, Jeffrey E

    2015-09-22

    Upon amino acid (AA) starvation and TOR inactivation, plasma-membrane-localized permeases rapidly undergo ubiquitination and internalization via the vacuolar protein sorting/multivesicular body (VPS-MVB) pathway and are degraded in the yeast vacuole. We now show that specific Golgi proteins are also directed to the vacuole under these conditions as part of a Golgi quality-control (GQC) process. The degradation of GQC substrates is dependent upon ubiquitination by the defective-for-SREBP-cleavage (DSC) complex, which was identified via genetic screening and includes the Tul1 E3 ligase. Using a model GQC substrate, GFP-tagged Yif1, we show that vacuolar targeting necessitates upregulation of the VPS pathway via proteasome-mediated degradation of the initial endosomal sorting complex required for transport, ESCRT-0, but not downstream ESCRT components. Thus, early cellular responses to starvation include the targeting of specific Golgi proteins for degradation, a phenomenon reminiscent of the inactivation of BTN1, the yeast Batten disease gene ortholog. PMID:26344761

  14. Intestinal myofibroblast-specific Tpl2-Cox-2-PGE2 pathway links innate sensing to epithelial homeostasis.

    PubMed

    Roulis, Manolis; Nikolaou, Christoforos; Kotsaki, Elena; Kaffe, Eleanna; Karagianni, Niki; Koliaraki, Vasiliki; Salpea, Klelia; Ragoussis, Jiannis; Aidinis, Vassilis; Martini, Eva; Becker, Christoph; Herschman, Harvey R; Vetrano, Stefania; Danese, Silvio; Kollias, George

    2014-10-28

    Tumor progression locus-2 (Tpl2) kinase is a major inflammatory mediator in immune cell types recently found to be genetically associated with inflammatory bowel diseases (IBDs). Here we show that Tpl2 may exert a dominant homeostatic rather than inflammatory function in the intestine mediated specifically by subepithelial intestinal myofibroblasts (IMFs). Mice with complete or IMF-specific Tpl2 ablation are highly susceptible to epithelial injury-induced colitis showing impaired compensatory proliferation in crypts and extensive ulcerations without significant changes in inflammatory responses. Following epithelial injury, IMFs sense innate or inflammatory signals and activate, via Tpl2, the cyclooxygenase-2 (Cox-2)-prostaglandin E2 (PGE2) pathway, which we show here to be essential for the epithelial homeostatic response. Exogenous PGE2 administration rescues mice with complete or IMF-specific Tpl2 ablation from defects in crypt function and susceptibility to colitis. We also show that Tpl2 expression is decreased in IMFs isolated from the inflamed ileum of IBD patients indicating that Tpl2 function in IMFs may be highly relevant to human disease. The IMF-mediated mechanism we propose also involves the IBD-associated genes IL1R1, MAPK1, and the PGE2 receptor-encoding PTGER4. Our results establish a previously unidentified myofibroblast-specific innate pathway that regulates intestinal homeostasis and may underlie IBD susceptibility in humans. PMID:25316791

  15. Modeling the air-soil transport pathway of perfluorooctanoic acid in the mid-Ohio Valley using linked air dispersion and vadose zone models

    NASA Astrophysics Data System (ADS)

    Shin, Hyeong-Moo; Ryan, P. Barry; Vieira, Verónica M.; Bartell, Scott M.

    2012-05-01

    As part of an extensive modeling effort on the air-soil-groundwater transport pathway of perfluorooctanoic acid (PFOA), this study was designed to compare the performance of different air dispersion modeling systems (AERMOD vs. ISCST3), and different approaches to handling incomplete meteorological data using a data set with substantial soil measurements and a well characterized point source for air emissions. Two of the most commonly used EPA air dispersion models, AERMOD and ISCST3, were linked with the EPA vadose zone model PRZM-3. Predicted deposition rates from the air dispersion model were used as input values for the vadose zone model to estimate soil concentrations of PFOA at different depths. We applied 34 years of meteorological data including hourly surface measurements from Parkersburg Airport and 5 years of onsite wind direction and speed to the air dispersion models. We compared offsite measured soil concentrations to predictions made for the corresponding sampling depths, focusing on soil rather than air measurements because the offsite soil samples were less likely to be influenced by short-term variability in emission rates and meteorological conditions. PFOA concentrations in surface soil (0-30 cm depth) were under-predicted and those in subsurface soil (>30 cm depth) were over-predicted compared to observed concentrations by both linked air and vadose zone model. Overall, the simulated values from the linked modeling system were positively correlated with those observed in surface soil (Spearman's rho, Rsp = 0.59-0.70) and subsurface soil (Rsp = 0.46-0.48). This approach provides a useful modeling scheme for similar exposure and risk analyses where the air-soil-groundwater transport is a primary contamination pathway.

  16. 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.

  17. SubtiWiki-a database for the model organism Bacillus subtilis that links pathway, interaction and expression information.

    PubMed

    Michna, Raphael H; Commichau, Fabian M; Tödter, Dominik; Zschiedrich, Christopher P; Stülke, Jörg

    2014-01-01

    Genome annotation and access to information from large-scale experimental approaches at the genome level are essential to improve our understanding of living cells and organisms. This is even more the case for model organisms that are the basis to study pathogens and technologically important species. We have generated SubtiWiki, a database for the Gram-positive model bacterium Bacillus subtilis (http://subtiwiki.uni-goettingen.de/). In addition to the established companion modules of SubtiWiki, SubtiPathways and SubtInteract, we have now created SubtiExpress, a third module, to visualize genome scale transcription data that are of unprecedented quality and density. Today, SubtiWiki is one of the most complete collections of knowledge on a living organism in one single resource. PMID:24178028

  18. SubtiWiki–a database for the model organism Bacillus subtilis that links pathway, interaction and expression information

    PubMed Central

    Michna, Raphael H.; Commichau, Fabian M.; Tödter, Dominik; Zschiedrich, Christopher P.; Stülke, Jörg

    2014-01-01

    Genome annotation and access to information from large-scale experimental approaches at the genome level are essential to improve our understanding of living cells and organisms. This is even more the case for model organisms that are the basis to study pathogens and technologically important species. We have generated SubtiWiki, a database for the Gram-positive model bacterium Bacillus subtilis (http://subtiwiki.uni-goettingen.de/). In addition to the established companion modules of SubtiWiki, SubtiPathways and SubtInteract, we have now created SubtiExpress, a third module, to visualize genome scale transcription data that are of unprecedented quality and density. Today, SubtiWiki is one of the most complete collections of knowledge on a living organism in one single resource. PMID:24178028

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

    PubMed

    Tucker-Drob, Elliot M; Harden, K Paige

    2012-02-01

    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 on early achievement is by facilitating the processes by which children select, evoke, and attend to learning experiences that are consistent with genetically influenced individual differences in their motivation to learn. We examined this hypothesis in a nationally representative sample of approximately 650 pairs of four-year old identical and fraternal twins who were administered a measure of math achievement, and rated by their parents on a broad set of items assessing learning motivation. Results indicated a genetic link between learning motivation and math achievement that varied positively with family socioeconomic status: Genetic differences in learning motivation contributed to math achievement more strongly in more advantaged homes. Once this effect of learning motivation was controlled for, gene-by-socioeconomic status interaction on math achievement was reduced from previously significant levels, to nonsignificant levels. PMID:22611326

  20. 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

  1. Sleep as a Mediator in the Pathway Linking Environmental Factors to Hypertension: A Review of the Literature

    PubMed Central

    Akinseye, Oluwaseun A.; Williams, Stephen K.; Seixas, Azizi; Pandi-Perumal, Seithikurippu R.; Vallon, Julian; Zizi, Ferdinand; Jean-Louis, Girardin

    2015-01-01

    Environmental factors, such as noise exposure and air pollution, are associated with hypertension. These environmental factors also affect sleep quality. Given the growing evidence linking sleep quality with hypertension, the purpose of this review is to investigate the role of sleep as a key mediator in the association between hypertension and environmental factors. Through this narrative review of the extant literature, we highlight that poor sleep quality mediates the relationship between environmental factors and hypertension. The conceptual model proposed in this review offers opportunities to address healthcare disparities in hypertension among African Americans by highlighting the disparate impact that the predictors (environmental factors) and mediator (sleep) have on the African-American community. Understanding the impact of these factors is crucial since the main outcome variable (hypertension) severely burdens the African-American community. PMID:25821594

  2. 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

  3. Stat3 activation links a C/EBPδ to myostatin pathway to stimulate loss of muscle mass.

    PubMed

    Zhang, Liping; Pan, Jenny; Dong, Yanjun; Tweardy, David J; Dong, Yanlan; Garibotto, Giacomo; Mitch, William E

    2013-09-01

    Catabolic conditions like chronic kidney disease (CKD) cause loss of muscle mass by unclear mechanisms. In muscle biopsies from CKD patients, we found activated Stat3 (p-Stat3) and hypothesized that p-Stat3 initiates muscle wasting. We created mice with muscle-specific knockout (KO) that prevents activation of Stat3. In these mice, losses of body and muscle weights were suppressed in models with CKD or acute diabetes. A small-molecule that inhibits Stat3 activation produced similar responses, suggesting a potential for translation strategies. Using CCAAT/enhancer-binding protein δ (C/EBPδ) KO mice and C2C12 myotubes with knockdown of C/EBPδ or myostatin, we determined that p-Stat3 initiates muscle wasting via C/EBPδ, stimulating myostatin, a negative muscle growth regulator. C/EBPδ KO also improved survival of CKD mice. We verified that p-Stat3, C/EBPδ, and myostatin were increased in muscles of CKD patients. The pathway from p-Stat3 to C/EBPδ to myostatin and muscle wasting could identify therapeutic targets that prevent muscle wasting. PMID:24011072

  4. Cross-talk between signaling pathways: the link between plant secondary metabolite production and wounding stress response.

    PubMed

    Jacobo-Velázquez, Daniel A; González-Agüero, Mauricio; Cisneros-Zevallos, Luis

    2015-01-01

    Plants subjected to wounding stress produce secondary metabolites. Several of these metabolites prevent chronic diseases and can be used as colorants, flavors, and as antimicrobials. This wound-induced production of plant secondary metabolites is mediated by signaling-molecules such as reactive oxygen species (ROS), ethylene (ET) and jasmonic acid (JA). However, their specific role and interactions that modulate the wound-respond in plants is not fully understood. In the present study, a subtractive cDNA library was generated, to better understand the global response of plants to wounding stress. Carrot (Daucus carota) was used as a model system for this study. A total of 335 unique expressed sequence tags (ESTs) sequences were obtained. ESTs sequences with a putative identity showed involvement in stress-signaling pathways as well as on the primary and secondary metabolism. Inhibitors of ROS biosynthesis, ET action, and JA biosynthesis alone and in combination were applied to wounded-carrots in order to determine, based on relative gene expression data, the regulatory role of ET, JA, and ROS on the wound-response in plants. Our results demonstrate that ROS play a key role as signaling-molecules for the wound-induced activation of the primary and secondary metabolism whereas ET and JA are essential to modulate ROS levels. PMID:25712739

  5. 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

  6. 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

  7. Cocktail of Four Active Components Derived from Sheng Mai San Inhibits Hydrogen Peroxide-Induced PC12 Cell Apoptosis Linked with the Caspase-3/ROCK1/MLC Pathway.

    PubMed

    Shen, Kai; Wang, Yan; Zhang, Yuanyuan; Zhou, Huana; Song, Yunfei; Cao, Zhengyu; Kou, Junping; Yu, Boyang

    2015-12-01

    SMXZF, a combination of four active components including ginsenoside Rb1, ginsenoside Rg1, schizandrin, and DT-13 (6:9:5:4) that is derived from Sheng Mai San, has previously been shown to exhibit a neuroprotective effect against focal ischemia/reperfusion injury. Due to the key role of oxidative stress-induced neuronal apoptosis in the pathogenesis of stroke, we examined the effect of SMXZF in oxidative stress responses and related signaling pathways in differentiated pheochromocytoma (PC12) cells. Our results showed that incubation with 100 μM hydrogen peroxide (H2O2) for 12 hr could reduce cell viability and superoxide dismutase (SOD) activity with an increase of intracellular reactive oxygen species (ROS) and malondialdehyde (MDA). In contrast, SMXZF alleviated oxidative stress by reducing the over-production of ROS and MDA in parallel to concentration dependently increasing SOD activity. In addition, SMXZF significantly attenuated H2O2-induced caspase-3 cleavage, Rho-associated coiled-coil-containing protein kinase-1 (ROCK1) activation, and myosin light-chain (MLC) phosphorylation. Inhibiting either caspase-3 or ROCK1 mimicked the effect. Consequently, our results suggest that SMXZF inhibits H2O2-induced neuronal apoptosis linked with the caspase-3/ROCK1/MLC pathway, which has also been confirmed to be a positive feedback loop in oxidative stress-injured PC12 cells. These findings support the pharmacological potential of SMXZF for neurodegenerative diseases and stroke. PMID:26058543

  8. 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

  9. PRO40 Is a Scaffold Protein of the Cell Wall Integrity Pathway, Linking the MAP Kinase Module to the Upstream Activator Protein Kinase C

    PubMed Central

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

    2014-01-01

    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. PMID:25188365

  10. 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

  11. Socioeconomic Status, Schooling, and the Developmental Trajectories of Adolescents

    ERIC Educational Resources Information Center

    Crosnoe, Robert; Huston, Aletha C.

    2007-01-01

    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…

  12. 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

  13. Apoptosis-linked gene-2 (ALG-2)/Sec31 interactions regulate endoplasmic reticulum (ER)-to-Golgi transport: a potential effector pathway for luminal calcium.

    PubMed

    Helm, Jared R; Bentley, Marvin; Thorsen, Kevin D; Wang, Ting; Foltz, Lauren; Oorschot, Viola; Klumperman, Judith; Hay, Jesse C

    2014-08-22

    Luminal calcium released from secretory organelles has been suggested to play a regulatory role in vesicle transport at several steps in the secretory pathway; however, its functional roles and effector pathways have not been elucidated. Here we demonstrate for the first time that specific luminal calcium depletion leads to a significant decrease in endoplasmic reticulum (ER)-to-Golgi transport rates in intact cells. Ultrastructural analysis revealed that luminal calcium depletion is accompanied by increased accumulation of intermediate compartment proteins in COPII buds and clusters of unfused COPII vesicles at ER exit sites. Furthermore, we present several lines of evidence suggesting that luminal calcium affected transport at least in part through calcium-dependent interactions between apoptosis-linked gene-2 (ALG-2) and the Sec31A proline-rich region: 1) targeted disruption of ALG-2/Sec31A interactions caused severe defects in ER-to-Golgi transport in intact cells; 2) effects of luminal calcium and ALG-2/Sec31A interactions on transport mutually required each other; and 3) Sec31A function in transport required luminal calcium. Morphological phenotypes of disrupted ALG-2/Sec31A interactions were characterized. We found that ALG-2/Sec31A interactions were not required for the localization of Sec31A to ER exit sites per se but appeared to acutely regulate the stability and trafficking of the cargo receptor p24 and the distribution of the vesicle tether protein p115. These results represent the first outline of a mechanism that connects luminal calcium to specific protein interactions regulating vesicle trafficking machinery. PMID:25006245

  14. ZEB1 Links p63 and p73 in a Novel Neuronal Survival Pathway Rapidly Induced in Response to Cortical Ischemia

    PubMed Central

    Bui, Thai; Sequeira, Judith; Wen, Tong Chun; Sola, Augusto; Higashi, Yujiro; Kondoh, Hisato; Genetta, Tom

    2009-01-01

    Background Acute hypoxic/ischemic insults to the forebrain, often resulting in significant cellular loss of the cortical parenchyma, are a major cause of debilitating injury in the industrialized world. A clearer understanding of the pro-death/pro-survival signaling pathways and their downstream targets is critical to the development of therapeutic interventions to mitigate permanent neurological damage. Methodology/Principal Findings We demonstrate here that the transcriptional repressor ZEB1, thought to be involved in regulating the timing and spatial boundaries of basic-Helix-Loop-Helix transactivator-mediated neurogenic determination/differentiation programs, functions to link a pro-survival transcriptional cascade rapidly induced in cortical neurons in response to experimentally induced ischemia. Employing histological, tissue culture, and molecular biological read-outs, we show that this novel pro-survival response, initiated through the rapid induction of p63, is mediated ultimately by the transcriptional repression of a pro-apoptotic isoform of p73 by ZEB1. We show further that this phylogenetically conserved pathway is induced as well in the human cortex subjected to episodes of clinically relevant stroke. Conclusions/Significance The data presented here provide the first evidence that ZEB1 induction is part of a protective response by neurons to ischemia. The stroke-induced increase in ZEB1 mRNA and protein levels in cortical neurons is both developmentally and phylogenetically conserved and may therefore be part of a fundamental cellular response to this insult. Beyond the context of stroke, the finding that ZEB1 is regulated by a member of the p53 family has implications for cell survival in other tissue and cellular environments subjected to ischemia, such as the myocardium and, in particular, tumor masses. PMID:19194497

  15. Subjective socioeconomic status and health: relationships reconsidered.

    PubMed

    Nobles, Jenna; Weintraub, Miranda Ritterman; Adler, Nancy E

    2013-04-01

    Subjective status, an individual's perception of her socioeconomic standing, is a robust predictor of physical health in many societies. To date, competing interpretations of this correlation remain unresolved. Using longitudinal data on 8430 older adults from the 2000 and 2007 waves of the Indonesia Family Life Survey, we test these oft-cited links. As in other settings, perceived status is a robust predictor of self-rated health, and also of physical functioning and nurse-assessed general health. These relationships persist in the presence of controls for unobserved traits, such as difficult-to-measure aspects of family background and persistent aspects of personality. However, we find evidence that these links likely represent bi-directional effects. Declines in health that accompany aging are robust predictors of declines in perceived socioeconomic status, net of observed changes to the economic profile of respondents. The results thus underscore the social value afforded good health status. PMID:23453318

  16. The 16p11.2 deletion mouse model of autism exhibits altered cortical progenitor proliferation and brain cytoarchitecture linked to the ERK MAPK pathway.

    PubMed

    Pucilowska, Joanna; Vithayathil, Joseph; Tavares, Emmanuel J; Kelly, Caitlin; Karlo, J Colleen; Landreth, Gary E

    2015-02-18

    Autism spectrum disorders are complex, highly heritable neurodevelopmental disorders affecting ∼1 in 100 children. Copy number variations of human chromosomal region 16p11.2 are genetically linked to 1% of autism-related disorders. This interval contains the MAPK3 gene, which encodes the MAP kinase, ERK1. Mutations in upstream elements regulating the ERK pathway are genetically linked to autism and other disorders of cognition including the neuro-cardio-facial cutaneous syndromes and copy number variations. We report that a murine model of human 16p11.2 deletion exhibits a reduction in brain size and perturbations in cortical cytoarchitecture. We observed enhanced progenitor proliferation and premature cell cycle exit, which are a consequence of altered levels of downstream ERK effectors cyclin D1 and p27(Kip1) during mid-neurogenesis. The increased progenitor proliferation and cell cycle withdrawal resulted in premature depletion of progenitor pools, altering the number and frequency of neurons ultimately populating cortical lamina. Specifically, we found a reduced number of upper layer pyramidal neurons and an increase in layer VI corticothalamic projection neurons, reflecting the altered cortical progenitor proliferation dynamics in these mice. Importantly, we observed a paradoxical increase in ERK signaling in mid-neurogenesis in the 16p11.2del mice, which is coincident with the development of aberrant cortical cytoarchitecture. The 16p11.2del mice exhibit anxiety-like behaviors and impaired memory. Our findings provide evidence of ERK dysregulation, developmental abnormalities in neurogenesis, and behavioral impairment associated with the 16p11.2 chromosomal deletion. PMID:25698753

  17. 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

  18. 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

  19. Genetic ablation of N-linked glycosylation reveals two key folding pathways for R345W fibulin-3, a secreted protein associated with retinal degeneration

    PubMed Central

    Hulleman, John D.; Kelly, Jeffery W.

    2015-01-01

    An R345W mutation in the N-glycoprotein, fibulin-3 (F3), results in inefficient F3 folding/secretion and higher intracellular F3 levels. Inheritance of this mutation causes the retinal dystrophy malattia leventinese. N-Linked glycosylation is a common cotranslational protein modification that can regulate protein folding efficiency and energetics. Therefore, we explored how N-glycosylation alters the protein homeostasis or proteostasis of wild-type (WT) and R345W F3 in ARPE-19 cells. Enzymatic and lectin binding assays confirmed that WT and R345W F3 are both primarily N-glycosylated at Asn249. Tunicamycin treatment selectively reduced R345W F3 secretion by 87% (vs. WT F3). Genetic elimination of F3 N-glycosylation (via an N249Q mutation) caused R345W F3 to aggregate intracellularly and adopt an altered secreted conformation. The endoplasmic reticulum (ER) chaperones GRP78 (glucose-regulated protein 78) and GRP94 (glucose-regulated protein 94), and the ER lectins calnexin and calreticulin were identified as F3 binding partners by immunoprecipitation. Significantly more N249Q and N249Q/R345W F3 interacted with GRP94, while substantially less N249Q and N249Q/R345W interacted with the ER lectins than their N-glycosylated counterparts. Inhibition of GRP94 ATPase activity reduced only N249Q/R345W F3 secretion (by 62%), demonstrating this variant’s unique reliance on GRP94 for secretion. These observations suggest that R345W F3, but not WT F3, requires N-glycosylation to acquire a stable, native-like structure.—Hulleman, J. D., Kelly, J. W. Genetic ablation of N-linked glycosylation reveals two key folding pathways for R345W fibulin-3, a secreted protein associated with retinal degeneration. PMID:25389134

  20. Bisphenol A promotes X-linked inhibitor of apoptosis protein-dependent angiogenesis via G protein-coupled estrogen receptor pathway.

    PubMed

    Liu, Jian; Jin, Xin; Zhao, Nana; Ye, Xiaolei; Ying, Chenjiang

    2015-11-01

    Bisphenol A (BPA), one of the high-volume chemicals worldwide, has a core structure resembling that of natural estradiol. Recent evidence has demonstrated that exposure to BPA has a relationship with the risk of cancer. The objective of our study is to investigate the mechanisms underlying the pro-angiogenic effects of BPA. We demonstrated that BPA markedly induces endothelial cell proliferation, migration and tube formation by activating endothelial nitric oxide synthase. BPA-induced nitric oxide generation appeared to be associated with the X-linked inhibitor of apoptosis protein (XIAP), which competes with endothelial nitric oxide synthase for caveolin-1. BPA was shown to exert its pro-angiogenic effect by upregulating XIAP expression via G protein-coupled estrogen receptor (ER) activation but not via ERα or ERβ. Our data suggest that 100 nM BPA promote angiogenesis in a G protein-coupled ER-dependent genomic pathway, and provide a novel insight into the potential role of XIAP in mediating the pro-angiogenic effects of BPA in endothelial cells. PMID:25663485

  1. Different exercise modalities have distinct effects on the integrin-linked kinase (ILK) and Ca2+ signaling pathways in the male rat bone

    PubMed Central

    Sontam, Dharani M; Firth, Elwyn C; Tsai, Peter; Vickers, Mark H; O’Sullivan, Justin M

    2015-01-01

    Mechanical loading is essential to maintain optimal skeletal health. Despite the fact that early-life exercise has positive, long-lasting effects on the musculo-skeletal system, the response of the musculo-skeletal system to spontaneous low-impact exercise has been poorly studied. Previously, we identified subtle morphological changes in the femoral diaphysis of exercised animals compared to nonexercised controls. We hypothesized that significant changes in gene expression of cells should precede significant measurable phenotypic changes in the tissues of which they are part. Here, we employed RNA-Seq to analyse the transcriptome of the cortical bone from the femoral mid-diaphysis of prepubertal male Sprague-Dawley rats that were assigned to control (CON); bipedal stance (BPS); or wheel exercise (WEX) groups for 15 days. We identified 808 and 324 differentially expressed transcripts in the BPS and WEX animals respectively. While a number of transcripts change their levels in an exercise-specific manner, we identified 191 transcripts that were differentially expressed in both BPS and WEX. Importantly, we observed that the exercise mode had diametrically opposite effects on transcripts for multiple genes within the integrin-linked kinase (ILK) and Ca2+ signaling pathways such that they were up-regulated in BPS and down-regulated in WEX. The findings are important for our understanding of possible ways in which different exercise regimens might affect bone when normal activities apply mechanical stimuli during postnatal growth and development. PMID:26471755

  2. 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

  3. 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

  4. 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

  5. The missing link in the fungal D-galacturonate pathway: identification of the L-threo-3-deoxy-hexulosonate aldolase.

    PubMed

    Hilditch, Satu; Berghäll, Suvi; Kalkkinen, Nisse; Penttilä, Merja; Richard, Peter

    2007-09-01

    The fungal path for the catabolism of D-galacturonate is only partially known. It is however distinctly different to the well-known bacterial path. The known elements of the fungal path are D-galacturonate reductase converting D-galacturonate to L-galactonate and L-galactonate dehydratase converting L-galactonate to L-threo-3-deoxy-hexulosonate (2-keto-3-deoxy-L-galactonate). Here we describe the missing link in this pathway, an aldolase converting L-threo-3-deoxy-hexulosonate to pyruvate and L-glyceraldehyde. Fungal enzymes converting L-glyceraldehyde to glycerol have been described previously. The L-threo-3-deoxy-hexulosonate aldolase activity was induced in the mold Hypocrea jecorina (Trichoderma reesei) during growth on D-galacturonate. The enzyme was purified from this mold and a partial amino acid sequence obtained. This sequence was then used to identify the corresponding gene from the H. jecorina genome. The deletion of the gene resulted in a strain unable to grow on d-galacturonate and accumulating L-threo-3-deoxy-hexulosonate. The open reading frame was cloned from cDNA and functionally expressed in the yeast Saccharomyces cerevisiae. A histidine-tagged protein was expressed, purified, and characterized. The enzyme catalyzed reaction was reversible. With L-threo-3-deoxy-hexulosonate as substrate the K(m) was 3.5 mM and with pyruvate and L-glyceraldehyde the K(m) were 0.5 and 1.2 mM, respectively. PMID:17609199

  6. Fiber tractography of the axonal pathways linking the basal ganglia and cerebellum in Parkinson disease: implications for targeting in deep brain stimulation

    PubMed Central

    Sweet, Jennifer A.; Walter, Benjamin L.; Gunalan, Kabilar; Chaturvedi, Ashutosh; Mcintyre, Cameron C.; Miller, Jonathan P.

    2015-01-01

    Object Stimulation of white matter pathways near targeted structures may contribute to therapeutic effects of deep brain stimulation (DBS) for patients with Parkinson disease (PD). Two tracts linking the basal ganglia and cerebellum have been described in primates: the subthalamopontocerebellar tract (SPCT) and the dentatothalamic tract (DTT). The authors used fiber tractography to evaluate white matter tracts that connect the cerebellum to the region of the basal ganglia in patients with PD who were candidates for DBS. Methods Fourteen patients with advanced PD underwent 3-T MRI, including 30-directional diffusion-weighted imaging sequences. Diffusion tensor tractography was performed using 2 regions of interest: ipsilateral subthalamic and red nuclei, and contralateral cerebellar hemisphere. Nine patients underwent subthalamic DBS, and the course of each tract was observed relative to the location of the most effective stimulation contact and the volume of tissue activated. Results In all patients 2 distinct tracts were identified that corresponded closely to the described anatomical features of the SPCT and DTT, respectively. The mean overall distance from the active contact to the DTT was 2.18 ± 0.35 mm, and the mean proportional distance relative to the volume of tissue activated was 1.35 ± 0.48. There was a nonsignificant trend toward better postoperative tremor control in patients with electrodes closer to the DTT. Conclusions The SPCT and the DTT may be related to the expression of symptoms in PD, and this may have implications for DBS targeting. The use of tractography to identify the DTT might assist with DBS targeting in the future. PMID:24484226

  7. Ether link cleavage is the major pathway of iodothyronine metabolism in the phagocytosing human leukocyte and also occurs in vivo in the rat.

    PubMed

    Burger, A G; Engler, D; Buergi, U; Weissel, M; Steiger, G; Ingbar, S H; Rosin, R E; Babior, B M

    1983-04-01

    These studies were performed to test the hypothesis that ether link cleavage (ELC) is an important pathway for the metabolism of thyroxine (T(4)) in the phagocytosing human leukocyte. When tyrosyl ring-labeled [(125)I]T(4)([Tyr(125)I]T(4)) was incubated with phagocytosing leukocytes, 50% of the degraded label was converted into [(125)I]3,5-diiodotyrosine ([(125)I]DIT). Of the remaining [Tyr(125)I]T(4) that was degraded, two-thirds was recovered as [(125)I]-nonextractable iodine ([(125)I]NEI), and one-third as [(125)I]iodide. The production of [(125)I]DIT was not observed when phenolic ring-labeled [(125)I]T(4) ([Phen(125)I]T(4)) was used, although [(125)I]NEI and [(125)I]iodide were produced. None of these iodinated compounds were formed in leukocytes that were not carrying out phagocytosis. The fraction of T(4) degraded by ELC was decreased by the addition of unlabeled T(4) and by preheating the leukocytes, findings which suggested that the process was enzymic in nature. ELC was enhanced by the catalase inhibitor aminotriazole, and was inhibited by the peroxidase inhibitor propylthiouracil, suggesting that the enzyme is a peroxidase and that hydrogen peroxide (H(2)O(2)) is a necessary cofactor in the reaction. To test this hypothesis, studies were performed in several inherited leukocytic disorders. ELC was not observed in the leukocytes of patients with chronic granulomatous disease, in which the respiratory burst that accompanies phagocytosis is absent. ELC was normal in the leukocytes of two subjects homozygous for Swiss-type acatalasemia, and aminotriazole enhanced ELC in these cells to an extent not significantly different from that observed in normal cells. ELC was normal in the leukocytes of a patient with myeloperoxidase deficiency, but could be induced by the incubation of [Tyr(125)I]T(4) with H(2)O(2) and horseradish peroxidase in the absence of leukocytes. The in vivo occurrence of ELC in the rat was confirmed by demonstrating the appearance of [(125)I

  8. 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...

  9. Socio-economic predictors of performance in the Undergraduate Medicine and Health Sciences Admission Test (UMAT)

    PubMed Central

    2013-01-01

    . Significant state-based differences largely reflected substantial socio-demographic differences across Australian states and territories. Conclusions Better performance by Australian candidates in the UMAT is linked to an increase in socio-economic advantage and reduced disadvantage.This observation provides a firm foundation for selection processes at medical schools in Australia that have incorporated affirmative action pathways to quarantine places for students from areas of socio-economic disadvantage. PMID:24286571

  10. 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…

  11. Is there a socioeconomic gradient in the prevalence of gestational diabetes mellitus?

    PubMed

    Cullinan, J; Gillespie, P; Owens, L; Avalos, G; Dunne, F P

    2012-05-01

    Previous studies have shown an association between Type 2 diabetes and lower socioeconomic status. This link is less clear in those with gestational diabetes mellitus (GDM). We test for a socioeconomic gradient in the prevalence of GDM by analysing data on 9,842 pregnant women who were offered testing for GDM in the Atlantic Diabetes in Pregnancy universal screening programme. A bivariate probit model relating GDM prevalence to socioeconomic status was estimated, controlling for variation in screening uptake rates across socioeconomic groups. The estimated increased prevalence of GDM is 8.6% [95% CI 2.7%-12.0%] for women in the lowest socioeconomic group when compared to the highest, suggesting a strong socioeconomic gradient in the prevalence of GDM. This gradient is found to be driven by differences in personal, clinical and lifestyle factors across socioeconomic groups. PMID:22838104

  12. [Socioeconomic variables and fertility].

    PubMed

    Arguello, O

    1980-08-01

    While making comparative analyses of data collected by the World Fertility Survey regarding Latin America, a group of investigators of CELADE (Centro Latinoamericano de Demografia) realized that the selection of economic variables for the study of fertility had serious limitations. Such limitations did not allow the elaboration of a theory which took into account the complicated process of fertility, in all its socioeconomic, cultural, and psychological manifestations. Thus, this paper intends to lay the theoretical basis for the selection of all relevant variables, distinguishing, for example, the average fertility of women according to area of residence, place of early socialization, migrant status, social status, occupation of husband, level of instruction, occupation, and all changes in occupational activities of women in fertile age. PMID:12336394

  13. Socioeconomic and Other Social Stressors and Biomarkers of Cardiometabolic Risk in Youth: A Systematic Review of Less Studied Risk Factors

    PubMed Central

    Slopen, Natalie; Goodman, Elizabeth; Koenen, Karestan C.; Kubzansky, Laura D.

    2013-01-01

    Background Socioeconomic disadvantage and other social stressors in childhood have been linked with cardiometabolic diseases in adulthood; however the mechanisms underlying these observed associations and the timing of their emergence are unclear. The aim of this review was to evaluate research that examined relationships between socioeconomic disadvantage and other social stressors in relation to less-studied cardiometabolic risk factors among youth, including carbohydrate metabolism-related factors, lipids, and central adiposity. Methods We searched PubMed and ISI Web of Science to identify relevant publications between 2001 and 2013.Studies were selected based on 4 criteria: (1) the study examined an association between at least one social or economic stressor and one relevant outcome prior to age 21; (2) the sample originated from a high-income country; (3) the sample was not selected based on a health condition; and (4) a central aim was to evaluate the effect of the social or economic stressor on at least one relevant outcome. Abstracts were screened and relevant publications were obtained and evaluated for inclusion criteria. We abstracted data from selected articles, summarized them by exposures and outcomes, and assigned an evidence grade. Results Our search identified 37 publications from 31 studies. Socioeconomic disadvantage was consistently associated with greater central adiposity. Research to date does not provide clear evidence of an association between childhood stressors and lipids or carbohydrate metabolism-related factors. Conclusions This review demonstrates a paucity of research on the relationship of socioeconomic disadvantage and other social stressors to lipid and carbohydrate metabolism-related factors in youth. Accordingly, it is not possible to form strong conclusions, particularly with regard to stressors other than socioeconomic disadvantage. Findings are used to inform priorities for future research. An improved understanding of these

  14. Modulation of the Akt Pathway Reveals a Novel Link with PERK/eIF2α, which Is Relevant during Hypoxia

    PubMed Central

    Sánchez, Manuel Alejandro; Urrutia, Carolina; Grande, Alicia; Risso, Guillermo; Srebrow, Anabella; Alfaro, Jennifer; Colman-Lerner, Alejandro

    2013-01-01

    The unfolded protein response (UPR) and the Akt signaling pathway share several regulatory functions and have the capacity to determine cell outcome under specific conditions. However, both pathways have largely been studied independently. Here, we asked whether the Akt pathway regulates the UPR. To this end, we used a series of chemical compounds that modulate PI3K/Akt pathway and monitored the activity of the three UPR branches: PERK, IRE1 and ATF6. The antiproliferative and antiviral drug Akt-IV strongly and persistently activated all three branches of the UPR. We present evidence that activation of PERK/eIF2α requires Akt and that PERK is a direct Akt target. Chemical activation of this novel Akt/PERK pathway by Akt-IV leads to cell death, which was largely dependent on the presence of PERK and IRE1. Finally, we show that hypoxia-induced activation of eIF2α requires Akt, providing a physiologically relevant condition for the interaction between Akt and the PERK branch of the UPR. These data suggest the UPR and the Akt pathway signal to one another as a means of controlling cell fate. PMID:23922774

  15. 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…

  16. 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…

  17. 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…

  18. 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

  19. Alternative Toxicity Testing: Analyses on Skin Sensitization, ToxCast Phases I and II, and Carcinogenicity Provide Indications on How to Model Mechanisms Linked to Adverse Outcome Pathways.

    PubMed

    Benigni, Romualdo; Battistelli, Chiara Laura; Bossa, Cecilia; Giuliani, Alessandro; Tcheremenskaia, Olga

    2015-01-01

    This article studies alternative toxicological approaches, with new (skin sensitization, ToxCast) and previous (carcinogenicity) analyses. Quantitative modeling of rate-limiting steps in skin sensitization and carcinogenicity predicts the majority of toxicants. Similarly, successful (Quantitative) Structure-Activity Relationships models exploit the quantification of only one, or few rate-limiting steps. High-throughput assays within ToxCast point to promising associations with endocrine disruption, whereas markers for pathways intermediate events have limited correlation with most endpoints. Since the pathways may be very different (often not simple linear chains of events), quantitative analysis is necessary to identify the type of mechanism and build the appropriate model. PMID:26398111

  20. 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.

  1. 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…

  2. Transcriptional and posttranscriptional inhibition of HMGCR and PC biosynthesis by geraniol in 2 Hep-G2 cell proliferation linked pathways.

    PubMed

    Crespo, Rosana; Montero Villegas, Sandra; Abba, Martín C; de Bravo, Margarita G; Polo, Mónica P

    2013-06-01

    Geraniol, present in the essential oils of many aromatic plants, has in vitro and in vivo antitumor activity against several cell lines. We investigated the effects of geraniol on lipid metabolic pathways involved in Hep-G2 cell proliferation and found that geraniol inhibits the mevalonate pathway, phosphatidylcholine biosynthesis, cell growth, and cell cycle progression (with an arrest occurring at the G0/G1 interphase) and increases apoptosis. The expression of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR), the rate-limiting step in cholesterol synthesis, was inhibited at the transcriptional and posttranscriptional levels, as assessed by real-time RT-PCR, Western blots, and [(14)C]HMG-CoA-conversion radioactivity assays. That geraniol decreased cholesterogenesis but increased the incorporation of [(14)C]acetate into other nonsaponifiable metabolites indicated the existence of a second control point between squalene and cholesterol involved in redirecting the flow of cholesterol-derived carbon toward other metabolites of the mevalonate pathway. That exogenous mevalonate failed to restore growth in geraniol-inhibited cells suggests that, in addition to the inhibition of HMGCR, other dose-dependent actions exist through which geraniol can impact the mevalonate pathway and consequently inhibit cell proliferation. These results suggest that geraniol, a nontoxic compound found in many fruits and herbs, exhibits notable potential as a natural agent for combatting cancer and (or) cardiovascular diseases. PMID:23668785

  3. 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

  4. 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

  5. Is there a signal transduction pathway that links events at the plasma membrane to the phosphorylation state of the mitochondrial pyruvate dehydrogenase complex?

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Monoclonal antibodies against the E1a subunit were used to quantify the mitochondrial pyruvate dehydrogenase complex (mtPDC) by enzyme-linked immunosorbent assay (ELISA). Recombinant Arabidopsis thaliana pyruvate dehydrogenase (E1) was used to calibrate the ELISA. Antibodies against a synthetic ph...

  6. 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

  7. High-to-Low CO2 Acclimation Reveals Plasticity of the Photorespiratory Pathway and Indicates Regulatory Links to Cellular Metabolism of Arabidopsis

    PubMed Central

    Frankenbach, Silja; Dreissen, Anne; Hocken, Nadine; Fernie, Alisdair R.; Walter, Achim; Bauwe, Hermann

    2012-01-01

    Background Photorespiratory carbon metabolism was long considered as an essentially closed and nonregulated pathway with little interaction to other metabolic routes except nitrogen metabolism and respiration. Most mutants of this pathway cannot survive in ambient air and require CO2-enriched air for normal growth. Several studies indicate that this CO2 requirement is very different for individual mutants, suggesting a higher plasticity and more interaction of photorespiratory metabolism as generally thought. To understand this better, we examined a variety of high- and low-level parameters at 1% CO2 and their alteration during acclimation of wild-type plants and selected photorespiratory mutants to ambient air. Methodology and Principal Findings The wild type and four photorespiratory mutants of Arabidopsis thaliana (Arabidopsis) were grown to a defined stadium at 1% CO2 and then transferred to normal air (0.038% CO2). All other conditions remained unchanged. This approach allowed unbiased side-by-side monitoring of acclimation processes on several levels. For all lines, diel (24 h) leaf growth, photosynthetic gas exchange, and PSII fluorescence were monitored. Metabolite profiling was performed for the wild type and two mutants. During acclimation, considerable variation between the individual genotypes was detected in many of the examined parameters, which correlated with the position of the impaired reaction in the photorespiratory pathway. Conclusions Photorespiratory carbon metabolism does not operate as a fully closed pathway. Acclimation from high to low CO2 was typically steady and consistent for a number of features over several days, but we also found unexpected short-term events, such as an intermittent very massive rise of glycine levels after transition of one particular mutant to ambient air. We conclude that photorespiration is possibly exposed to redox regulation beyond known substrate-level effects. Additionally, our data support the view that 2

  8. Modeling the Association between Lifecourse Socioeconomic Disadvantage and Systemic Inflammation in Healthy Adults: The Role of Self-Control

    PubMed Central

    Hostinar, Camelia E.; Ross, Kharah M.; Chen, Edith; Miller, Gregory E.

    2015-01-01

    Objective We sought to identify pathways connecting lifecourse socioeconomic status (SES) with chronic, low-grade inflammation, focusing on the explanatory roles of self-control, abdominal adiposity, and health practices. Methods Participants were 360 adults aged 15 - 55 who were free of chronic medical conditions. They were roughly equally divided between low and high current SES, with each group further divided between low and high early-life SES. Structural Equation Modeling (SEM) was used to identify direct and indirect pathways linking early-life and current SES with low-grade, chronic inflammation in adulthood, as manifest by serum interleukin-6 and C-reactive protein. Low SES was hypothesized to relate to inflammation by reducing self-control, which in turn was hypothesized to facilitate lifestyle factors that potentiate inflammation (smoking, alcohol use, sedentary behavior, and weight gain). Results Analyses revealed that self-control was pivotal in linking both early-life and current SES to inflammation. Low early-life SES was related to a harsher family climate, and in turn lower adult self-control, over and above the effects of current SES. Controlling for early-life SES, low current SES was associated with perceived stress, and in turn diminished self-control. Results showed that lower self-control primarily operated through higher abdominal adiposity to associate with greater inflammation. Conclusions The findings suggest a mechanistic scenario wherein low SES in early-life or adulthood depletes self-control and in turn fosters adiposity and inflammation. These pathways should be studied longitudinally to elucidate and potentially ameliorate socioeconomic disparities in health. PMID:25110854

  9. 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

  10. 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

  11. 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

  12. Longitudinal predictors of adult socioeconomic attainment: the roles of socioeconomic status, academic competence, and mental health.

    PubMed

    Slominski, Lisa; Sameroff, Arnold; Rosenblum, Katherine; Kasser, Tim

    2011-02-01

    Educational attainment and occupational status are key markers of success in adulthood. We expand upon previous research that focused primarily on the contributions of academic competence and family socioeconomic status (SES) by investigating the role of mental health in predicting adult SES. In a longitudinal study spanning 30 years, we used structural equation modeling to examine how parental mental health in early childhood and family SES, offspring academic competence, and offspring mental health in adolescence relate to occupational and educational attainment at age 30. Results were that adolescent academic competence predicted adult educational attainment, and that educational attainment then predicted occupational attainment. The pathways between academic competence and occupational attainment, family SES and educational attainment, and family SES and occupational attainment were not significant. In contrast, adolescent mental health not only predicted educational attainment, but was also directly related to adult occupational attainment. Finally, early maternal mental health was associated with offspring's adult socioeconomic attainment through its relations with adolescent academic competence and mental health. These results highlight the importance of mental health to adult socioeconomic attainment. PMID:21262057

  13. A New Role for Corporations: Linking Technology to Socioeconomic Development.

    ERIC Educational Resources Information Center

    Norris, William C.

    1984-01-01

    Describes a program through which one company, Control Data, has attempted to address unmet social needs in the areas of unemployment, especially for disadvantaged youth and the handicapped; more responsive education and training; revitalization of poverty-stricken areas; a more viable small business sector; and lower cost, more efficient public…

  14. 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

  15. 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

  16. 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

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

    PubMed

    Wang, Zi; Ma, Bianyin; Li, Hui; Xiao, Xiaojuan; 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

  18. RNA-Seq Links the Transcription Factors AINTEGUMENTA and AINTEGUMENTA-LIKE6 to Cell Wall Remodeling and Plant Defense Pathways.

    PubMed

    Krizek, Beth A; Bequette, Carlton J; Xu, Kaimei; Blakley, Ivory C; Fu, Zheng Qing; Stratmann, Johannes W; Loraine, Ann E

    2016-07-01

    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

  19. 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

  20. 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

  1. 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

  2. Socioeconomic status and the Rorschach.

    PubMed

    Frank, G

    1994-02-01

    People from lower socioeconomic status are making increasing use of mental health facilities. Surveys have indicated that the Rorschach is still one of the more frequently used instruments by psychologists in such facilities, but research has also shown that clinicians tend to misinterpret Rorschachs of people from the lower socioeconomic group as reflecting greater psychopathology than the same Rorschachs identified as being given by people from the middle class. Research has also shown that growing up in conditions of poverty significantly affects how people perform on tests of abstract thinking, tests of intelligence, and tests of academic achievement; the question was raised as to whether this extends to the Rorschach. The lack of sufficient research on the effect of socioeconomic status on responsiveness to the Rorschach precluded that question being answered. The kind of research still needed was discussed. PMID:8153241

  3. 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

  4. 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

  5. Targeting Smad4 links microRNA-146a to the TGF-beta pathway during retinoid acid induction in acute promyelocytic leukemia cell line.

    PubMed

    Zhong, Hua; Wang, Hai-rong; Yang, Shuang; Zhong, Ji-hua; Wang, Ting; Wang, Chun; Chen, Fang-yuan

    2010-07-01

    The expression pattern of microRNAs (miRNAs) and their potential target genes were investigated in acute promyelocytic leukemia (APL) cell line NB4 cells during all-trans-retinoid acid (ATRA) treatment by using a miRNA microarrays platform and real-time quantitative PCR (RTQ-PCR). MiR-146a as one of the miRNAs down-regulated by ATRA during APL differentiation was identified. Direct interaction between miR146a and its predictive target gene Smad4 were confirmed by Luciferase assay. Down-regulation of miR-146a and upregulation of Smad4 at protein levels were demonstrated. These data suggested that miR-146a might influence proliferation of APL cells through TGF-beta1/Smad signal transduction pathway during ATRA induction. PMID:20577838

  6. 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…

  7. 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…

  8. 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

  9. 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)

  10. 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…

  11. The jasmonic acid signaling pathway is linked to auxin homeostasis through the modulation of YUCCA8 and YUCCA9 gene expression.

    PubMed

    Hentrich, Mathias; Böttcher, Christine; Düchting, Petra; Cheng, Youfa; Zhao, Yunde; Berkowitz, Oliver; Masle, Josette; Medina, Joaquín; Pollmann, Stephan

    2013-05-01

    Interactions between phytohormones play important roles in the regulation of plant growth and development, but knowledge of the networks controlling hormonal relationships, such as between oxylipins and auxins, is just emerging. Here, we report the transcriptional regulation of two Arabidopsis YUCCA genes, YUC8 and YUC9, by oxylipins. Similar to previously characterized YUCCA family members, we show that both YUC8 and YUC9 are involved in auxin biosynthesis, as demonstrated by the increased auxin contents and auxin-dependent phenotypes displayed by gain-of-function mutants as well as the significantly decreased indole-3-acetic acid (IAA) levels in yuc8 and yuc8/9 knockout lines. Gene expression data obtained by qPCR analysis and microscopic examination of promoter-reporter lines reveal an oxylipin-mediated regulation of YUC9 expression that is dependent on the COI1 signal transduction pathway. In support of these findings, the roots of the analyzed yuc knockout mutants displayed a reduced response to methyl jasmonate (MeJA). The similar response of the yuc8 and yuc9 mutants to MeJA in cotyledons and hypocotyls suggests functional overlap of YUC8 and YUC9 in aerial tissues, while their function in roots shows some specificity, probably in part related to different spatio-temporal expression patterns of the two genes. These results provide evidence for an intimate functional relationship between oxylipin signaling and auxin homeostasis. PMID:23425284

  12. 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

  13. 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

  14. 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. PMID:18032807

  15. Ion Mobility-Mass Spectrometry Analysis of Cross-Linked Intact Multiprotein Complexes: Enhanced Gas-Phase Stabilities and Altered Dissociation Pathways.

    PubMed

    Samulak, Billy M; Niu, Shuai; Andrews, Philip C; Ruotolo, Brandon T

    2016-05-17

    Analysis of protein complexes by ion mobility-mass spectrometry is a valuable method for the rapid assessment of complex composition, binding stoichiometries, and structures. However, capturing labile, unknown protein assemblies directly from cells remains a challenge for the technology. Furthermore, ion mobility-mass spectrometry measurements of complexes, subcomplexes, and subunits are necessary to build complete models of intact assemblies, and such data can be difficult to acquire in a comprehensive fashion. Here, we present the use of novel mass spectrometry cleavable cross-linkers and tags to stabilize intact protein complexes for ion mobility-mass spectrometry. Our data reveal that tags and linkers bearing permanent charges are superior stabilizers relative to neutral cross-linkers, especially in the context of retaining compact forms of the assembly under a wide array of activating conditions. In addition, when cross-linked protein complexes are collisionally activated in the gas phase, a larger proportion of the product ions produced are often more compact and reflect native protein subcomplexes when compared with unmodified complexes activated in the same fashion, greatly enabling applications in structural biology. PMID:27078797

  16. Impact on offspring methylation patterns of maternal gestational diabetes mellitus and intrauterine growth restraint suggest common genes and pathways linked to subsequent type 2 diabetes risk.

    PubMed

    Quilter, Claire R; Cooper, Wendy N; Cliffe, Kerry M; Skinner, Benjamin M; Prentice, Philippa M; Nelson, LaTasha; Bauer, Julien; Ong, Ken K; Constância, Miguel; Lowe, William L; Affara, Nabeel A; Dunger, David B

    2014-11-01

    Size at birth, postnatal weight gain, and adult risk for type 2 diabetes may reflect environmental exposures during developmental plasticity and may be mediated by epigenetics. Both low birth weight (BW), as a marker of fetal growth restraint, and high birth weight (BW), especially after gestational diabetes mellitus (GDM), have been linked to increased risk of adult type 2 diabetes. We assessed DNA methylation patterns using a bead chip in cord blood samples from infants of mothers with GDM (group 1) and infants with prenatal growth restraint indicated by rapid postnatal catch-up growth (group 2), compared with infants with normal postnatal growth (group 3). Seventy-five CpG loci were differentially methylated in groups 1 and 2 compared with the controls (group 3), representing 72 genes, many relevant to growth and diabetes. In replication studies using similar methodology, many of these differentially methylated regions were associated with levels of maternal glucose exposure below that defined by GDM [the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study] or were identified as changes observed after randomized periconceptional nutritional supplementation in a Gambian cohort characterized by maternal deprivation. These studies provide support for the concept that similar epigenetic modifications may underpin different prenatal exposures and potentially increase long-term risk for diseases such as type 2 diabetes. PMID:25145626

  17. 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

  18. The Levels of the Lectin Pathway Serine Protease MASP-1 and Its Complex Formation with C1 Inhibitor Are Linked to the Severity of Hereditary Angioedema.

    PubMed

    Hansen, Cecilie Bo; Csuka, Dorottya; Munthe-Fog, Lea; Varga, Lilian; Farkas, Henriette; Hansen, Karin Møller; Koch, Claus; Skjødt, Karsten; Garred, Peter; Skjoedt, Mikkel-Ole

    2015-10-15

    C1 inhibitor (C1-INH) is known to form complexes with the lectin complement pathway serine proteases MASP-1 and MASP-2. Deficiency of C1-INH is associated with hereditary angioedema (HAE), an autosomal inherited disease characterized by swelling attacks caused by elevated levels of bradykinin. MASP-1 was shown to cleave high m.w. kininogen into bradykinin; therefore, we hypothesized that MASP-1 levels and the quantity of MASP-1/C1-INH complexes might be associated with different paraclinical and clinical outcomes of HAE. We measured MASP-1 serum concentrations and endogenous MASP-1/C1-INH complex levels in 128 HAE patients and 100 controls. Relatively high levels of pre-existing MASP-1/C1-INH complexes were observed in normal serum, and we found that both the serum levels of MASP-1 and the complex formation between MASP-1 and C1-INH were significantly reduced in HAE patients compared with matched controls (p < 0.0001). The level of MASP-1 and MASP-1/C1-INH complexes in HE patients correlated with the level of C1-INH (p = 0.0009 and p = 0.0047, respectively), the level of C4 (p = 0.0084 and p < 0.0001, respectively), and the number of attacks in the year of blood sampling (p = 0.0075 and p = 0.0058, respectively). In conclusion, we show that MASP-1/C1-INH complexes circulate in normal human blood. The levels of MASP-1 and MASP-1/C1-INH complexes are reduced in HAE patients compared with controls. Both MASP-1 and MASP-1/C1-INH complexes are related to the degree of complement C4 consumption, as well as the severity of disease. These results suggest that MASP-1 may exert a previously unrecognized role in the pathophysiology of HAE. PMID:26371246

  19. Radiation-induced mitotic cell death and glioblastoma radioresistance: a new regulating pathway controlled by integrin-linked kinase, hypoxia-inducible factor 1 alpha and survivin in U87 cells.

    PubMed

    Lanvin, Olivia; Monferran, Sylvie; Delmas, Caroline; Couderc, Bettina; Toulas, Christine; Cohen-Jonathan-Moyal, Elizabeth

    2013-09-01

    We have previously shown that integrin-linked kinase (ILK) regulates U87 glioblastoma cell radioresistance by modulating the main radiation-induced cell death mechanism in solid tumours, the mitotic cell death. To decipher the biological pathways involved in these mechanisms, we constructed a U87 glioblastoma cell model expressing an inducible shRNA directed against ILK (U87shILK). We then demonstrated that silencing ILK enhanced radiation-induced centrosome overduplication, leading to radiation-induced mitotic cell death. In this model, ionising radiations induce hypoxia-inducible factor 1 alpha (HIF-1α) stabilisation which is inhibited by silencing ILK. Moreover, silencing HIF-1α in U87 cells reduced the surviving fraction after 2 Gy irradiation by increasing cell sensitivity to radiation-induced mitotic cell death and centrosome amplification. Because it is known that HIF-1α controls survivin expression, we then looked at the ILK silencing effect on survivin expression. We show that survivin expression is decreased in U87shILK cells. Furthermore, treating U87 cells with the specific survivin suppressor YM155 significantly increased the percentage of giant multinucleated cells, centrosomal overduplication and thus U87 cell radiosensitivity. In consequence, we decipher here a new pathway of glioma radioresistance via the regulation of radiation-induced centrosome duplication and therefore mitotic cell death by ILK, HIF-1α and survivin. This work identifies new targets in glioblastoma with the intention of radiosensitising these highly radioresistant tumours. PMID:23747271

  20. 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

  1. Acute stress evokes selective mobilization of T cells that differ in chemokine receptor expression: a potential pathway linking immunologic reactivity to cardiovascular disease.

    PubMed

    Bosch, Jos A; Berntson, Gary G; Cacioppo, John T; Dhabhar, Firdaus S; Marucha, Phillip T

    2003-08-01

    T lymphocytes and monocytes/macrophages are the most abundant cells found in the atherosclerotic plaque. These cells can migrate towards the activated endothelium through the local release of chemotactic cytokines, or chemokines. Given the important role of leukocyte migration in atherosclerosis and the role of stress in mediating leukocyte trafficking, the present study examined the effects of an acute stressor on the redistribution of T cells (CD3+) and monocytes that express the chemokine receptors CCR5, CCR6, CXCR1, CXCR2, CXCR3, and CXCR4. Forty-four undergraduate students underwent a public speaking task. The acute stressor induced sympathetic cardiac activation, parasympathetic cardiac withdrawal, lymphocytosis, and monocytosis (all p<.001). Although the total number of T lymphocytes did not change, there was a selective increase in the number of circulating T cells expressing CXCR2, CXCR3, and CCR5. The ligands of these receptors are chemokines known to be secreted by activated endothelial cells. Analyses of individual differences in stress-induced responses demonstrated a positive relationship between sympathetic cardiac reactivity and mobilization of the various T cell subsets (.35link between stress, reactivity, and cardiovascular disease. PMID:12831827

  2. Progranulin deficiency induces overactivation of WNT5A expression via TNF-α/NF-κB pathway in peripheral cells from frontotemporal dementia-linked granulin mutation carriers

    PubMed Central

    Alquézar, Carolina; de la Encarnación, Ana; Moreno, Fermín; de Munain, Adolfo López; Martín-Requero, Ángeles

    2016-01-01

    mutations lead to haploinsufficiency of the protein. Conclusion Our results revealed an important role of NF-κB signalling in PGRN-associated FTLD-TDP and confirm that PGRN can bind to TNF-α receptors regulating the expression of WNT5A, suggesting novel targets for treatment of FTLD-TDP linked to GRN mutations. PMID:26624524

  3. 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

  4. Sleep disparity, race/ethnicity, and socioeconomic position.

    PubMed

    Grandner, Michael A; Williams, Natasha J; Knutson, Kristen L; Roberts, Dorothy; Jean-Louis, Girardin

    2016-02-01

    Sleep represents a set of biological functions necessary for the maintenance of life. Performing these functions, though, requires that an individual engage in behaviors, which are affected by social and environmental factors. Race/ethnicity and socioeconomic position represent categories of factors that likely play a role in the experience of sleep in the community. Previous studies have suggested that racial/ethnic minorities and the socioeconomically disadvantaged may be more likely to experience sleep patterns that are associated with adverse health outcomes. It is possible that disparities in sleep represent a pathway by which larger disparities in health emerge. This review (1) contextualizes the concept of race/ethnicity in biomedical research, (2) summarizes previous studies that describe patterns of sleep attainment across race/ethnicity groups, (3) discusses several pathways by which race/ethnicity may be associated with sleep, (4) introduces the potential role of socioeconomic position in the patterning of sleep, and (5) proposes future research directions to address this issue. PMID:26431755

  5. 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

  6. Neurophysiology and itch pathways.

    PubMed

    Schmelz, Martin

    2015-01-01

    As we all can easily differentiate the sensations of itch and pain, the most straightforward neurophysiologic concept would consist of two specific pathways that independently encode itch and pain. Indeed, a neuronal pathway for histamine-induced itch in the peripheral and central nervous system has been described in animals and humans, and recently several non-histaminergic pathways for itch have been discovered in rodents that support a dichotomous concept differentiated into a pain and an itch pathway, with both pathways being composed of different "flavors." Numerous markers and mediators have been found that are linked to itch processing pathways. Thus, the delineation of neuronal pathways for itch from pain pathways seemingly proves that all sensory aspects of itch are based on an itch-specific neuronal pathway. However, such a concept is incomplete as itch can also be induced by the activation of the pain pathway in particular when the stimulus is applied in a highly localized spatial pattern. These opposite views reflect the old dispute between specificity and pattern theories of itch. Rather than only being of theoretic interest, this conceptual problem has key implication for the strategy to treat chronic itch as key therapeutic targets would be either itch-specific pathways or unspecific nociceptive pathways. PMID:25861773

  7. Body height and socioeconomic status of females at different life stages.

    PubMed

    Wronka, Iwona

    2013-07-01

    Adult height reflects long-term nutritional status and exposure to infectious diseases, both of which are influenced by socioeconomic factors. Very little research has been done on these inequalities from a longitudinal perspective. This paper explores the links between body height at different life stages and socioeconomic characteristics. Data were obtained from 1008 Polish schoolgirls aged 16-18 years for whom earlier data on height were available. The height of each subject was measured. Socioeconomic status and age at menarche were assessed based on information received from the surveyed girls. Girls' heights in early life were ascertained from medical records. All girls were measured by trained school nurses at 7, 9 and 14 years of age. Socioeconomic status was found to be related to body height, but not to the rate of height gain during childhood and adolescence. Girls of a higher socioeconomic status were taller than girls of a lower socioeconomic status. On dividing the research material into homogeneous groups by maturity status, the same relationship was observed. No significant relationships were found between socioeconomic status and rate of height gain between ages 7 and 16, 17, 18 years. The findings suggest that socioeconomic variation in height is the result of living conditions during the first years of life. PMID:22989556

  8. 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

  9. 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

  10. 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

  11. 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

  12. 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

    Yong, Chun-Yan; Chen, Shu; Chen, Heng; Chu, Xiao; Zhang, Chao; Tan, Cheng; Ye, Lan; Li, Jiang-Shan

    2016-06-01

    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

  13. INTERSECTINg Pathways in Cell Biology

    PubMed Central

    O'Bryan, John P.

    2010-01-01

    The endocytic pathway is involved in activation and inhibition of cellular signaling. Thus, defining the regulatory mechanisms that link endocytosis and cellular signaling is of interest. An emerging link between these processes is a family of proteins called intersectins (ITSNs). These multi-domain proteins serve as scaffolds in the assembly of endocytic vesicles, and also regulate components of various signaling pathways, including kinases, GTPases, and ubiquitin ligases. This review will summarize research on the role of ITSNs in regulating both endocytic and signal transduction pathways, discuss the link of ITSNs with human disease, and highlight future directions in the study of ITSNs. PMID:21156937

  14. The Association Between Socioeconomic Disadvantage and Attention Deficit/Hyperactivity Disorder (ADHD): A Systematic Review.

    PubMed

    Russell, Abigail Emma; Ford, Tamsin; Williams, Rebecca; Russell, Ginny

    2016-06-01

    This systematic review examines associations between parental socioeconomic disadvantage and childhood attention deficit/hyperactivity disorder (ADHD). Socioeconomic status (SES) was measured by parental income, education, occupation and marital status. Results were mixed by measure of SES with no one aspect being differentially related to ADHD. 42 studies were included in the review, of which 35 found a significant univariate association between socioeconomic disadvantage and ADHD. Meta-analyses of dimensions of SES and their association with ADHD indicate that children in families of low SES are on average 1.85-2.21 more likely to have ADHD than their peers in high SES families. In spite of substantial between-study heterogeneity, there is evidence for an association between socioeconomic disadvantage and risk of ADHD measured in different ways. This is likely mediated by factors linked to low SES such as parental mental health and maternal smoking during pregnancy. PMID:26266467

  15. Neural correlates of socioeconomic status in the developing human brain.

    PubMed

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

    2012-07-01

    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 language, memory, social-emotional processing, and cognitive control exhibit relatively large differences across SES. Here we investigated whether volumetric differences could be observed across SES in several neural regions that support these skills. In a sample of 60 socioeconomically diverse children, highly significant SES differences in regional brain volume were observed in the hippocampus and the amygdala. In addition, SES × age interactions were observed in the left superior temporal gyrus and left inferior frontal gyrus, suggesting increasing SES differences with age in these regions. These results were not explained by differences in gender, race or IQ. Likely mechanisms include differences in the home linguistic environment and exposure to stress, which may serve as targets for intervention at a time of high neural plasticity. PMID:22709401

  16. Socioeconomic status and stress in Mexican-American women: a multi-method perspective.

    PubMed

    Gallo, Linda C; Shivpuri, Smriti; Gonzalez, Patricia; Fortmann, Addie L; de los Monteros, Karla Espinosa; Roesch, Scott C; Talavera, Gregory A; Matthews, Karen A

    2013-08-01

    Stress is a hypothesized pathway in socioeconomic status (SES)-physical health associations, but the available empirical data are inconsistent. In part, this may reflect discrepancies in the approach to measuring stress across studies, and differences in the nature of SES-stress associations across demographic groups. We examined associations of SES (education, income) with general and domain-specific chronic stressors, stressful life events, perceived stress, and stressful daily experiences in 318 Mexican-American women (40-65 years old). Women with higher SES reported lower perceived stress and fewer low-control experiences in everyday life (ps < .05), but greater chronic stress (education only, p < .05). Domain-specific analyses showed negative associations of income with chronic housing and financial stress (ps < .05), but positive associations of SES with chronic work and caregiving stress (all ps < .05 except for income and caregiving stress, p < .10). Sensitivity analyses showed that most SES-stress associations were consistent across acculturation levels. Future research should adopt a multi-dimensional assessment approach to better understand links among SES, stress, and physical health, and should consider the sociodemographic context in conceptualizing the role of stress in SES-related health inequalities. PMID:22644814

  17. Socioeconomic status, negative affect, and modifiable cancer risk factors in African-American smokers.

    PubMed

    Kendzor, Darla E; Cofta-Woerpel, Ludmila M; Mazas, Carlos A; Li, Yisheng; Vidrine, Jennifer Irvin; Reitzel, Lorraine R; Costello, Tracy J; Businelle, Michael S; Ahluwalia, Jasjit S; Cinciripini, Paul M; Wetter, David W

    2008-10-01

    The purpose of the present study was to describe the prevalence, patterns, and predictors of cooccurring modifiable cancer risk factors among African-Americans seeking smoking cessation treatment and to evaluate previously hypothesized models of the relationship between socioeconomic status (SES) and health behavior. Overweight/obesity, at-risk alcohol consumption, and insufficient physical activity were measured in 399 African-American smokers. Analyses indicated that 92.8% of participants had at least one cancer risk factor in addition to smoking. Univariate ordinal logistic regression analyses revealed that female gender, unemployment, lower positive affect, and greater negative affect were associated with having a greater number of cancer risk factors. Multivariate analyses yielded similar findings. A structural equation modeling approach indicated that stress/negative affect may function as one pathway linking SES and modifiable cancer risk factors among African-American smokers and that gender has a direct effect on modifiable cancer risk factors. Thus, risk patterns identified within each gender group may guide the development of multiple risk factor interventions for African-American smokers. Stress and negative affect may be an important treatment target within behavioral interventions for African-American smokers of low SES. PMID:18842995

  18. 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

  19. 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…

  20. Family Expressiveness: Sex and Socioeconomic Class Differences.

    ERIC Educational Resources Information Center

    Ingoldsby, Bron B.; McKim, Suzanne

    Communication, particularly in the form of self-disclosure or emotional expressiveness is important to happy, healthy relationships. Differences in emotional expressiveness between sexes, between socioeconomic groups, and within each of these groups were examined in 48 males and 44 females from high and low socioeconomic (SES) groups. Subjects…

  1. 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.…

  2. Control of 6-(D-threo-1',2'-dihydroxypropyl) pterin (dictyopterin) synthesis during aggregation of Dictyostelium discoideum. Involvement of the G-protein-linked signalling pathway in the regulation of GTP cyclohydrolase I activity.

    PubMed Central

    Gütlich, M; Witter, K; Bourdais, J; Veron, M; Rödl, W; Ziegler, I

    1996-01-01

    6-(D-threo-1',2'-Dihydroxypropylpterin (dictyopterin) has been identified in extracts of growing Dictyostelium dicoideum cells [Klein, Thiery and Tatischeff (1990) Eur. J. Biochem. 187, 665-669]. We demonstrate that it originates from GTP by de novo biosynthesis and that the first committed step is catalysed by GTP cyclohydrolase I, yielding dihydroneopterin triphosphate [neopterin is 6-(D-erythro-1',2',3'-trihydroxypropyl) pterin]. The GTP cyclohydrolase I activity is found in the cytosolic fraction and in a membrane-associated form. The level of a 0.9 kb mRNA coding for GTP cyclohydrolase I decreases to about 10% of its initial value within 2 h after Dictyostelium cells start development induced by starvation. In the cytosolic fraction, the specific activities of GTP cyclohydrolase I, as well as the concentrations of (6R/S)-5,6,7,8-tetrahydrodictyopterin (H4dictyopterin), follow this decline of the mRNA level. In the particulate fraction, however, the specific activities of GTP cyclohydrolase I and, in consequence, H4dictyopterin synthesis, transiently increase and reach a maximum after 4-5 h of development. The time-course of H4dictyopterin concentrations in the starvation medium closely correlates with its production in the membrane fraction. The activity of membrane-associated GTP cyclohydrolase I can be increased by pre-incubation of the cell lysate with guanosine 5'-[gamma-thio]triphosphate and Mg2+. This GTP analogue does not serve as a substrate and has no direct effect on the enzyme activity, indicating that a G-protein-linked signalling pathway is involved in the regulation of GTP cyclohydrolase I activity and thus in H4dictyopterin production during early development of D. discoideum. PMID:8660315

  3. 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.

  4. Behavioral pathways explaining oral health disparity in children.

    PubMed

    Gao, X-L; Hsu, C-Y S; Xu, Y C; Loh, T; Koh, D; Hwarng, H B

    2010-09-01

    Policymakers' understanding of and ability to reduce health disparities are pivotal for health promotion worldwide. This study aimed to verify the behavioral pathways leading to oral health disparities. Oral examinations were conducted for 1782 randomly selected preschoolers (3-6 yrs), and 1576 (88.4%) participants were followed up after 12 months. Parents were surveyed on their knowledge (K), attitude (A), and practices (P) regarding their children's oral health homecare (infant feeding, diet, and oral hygiene) and dental attendance. Structural equation modeling substantiated the links between specific KAs and corresponding practices, while generic KA did not affect practices. KAP pathways partly explained the ethnic and socio-economic disparities in oral health. Deprivation had a direct effect (not mediated by KA) on dental attendance, but not on oral health homecare. Ethnicity directly influenced oral health homecare practices, but not dental attendance. These behavioral pathways, furthering our understanding of health disparity, may have practical implications for health promotion and policy-making. PMID:20554887

  5. Case Study: The Perception of Online Tutorials--Habitually Absent Students with Familial or Socioeconomic Circumstances

    ERIC Educational Resources Information Center

    Hudson, Glyniss A.

    2013-01-01

    This case study explored the perception of online tutorials by habitually absent students with familial or socioeconomic circumstances. Researched literature confirmed a link between absenteeism, and academic achievement. Research Questions were designed to determine (a) student perception of online tutorials, and (b) motivation to achieve…

  6. 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…

  7. 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…

  8. Socioeconomic Differences in Elementary Students ICT Beliefs and Out-of-School Experiences

    ERIC Educational Resources Information Center

    Vekiri, Ioanna

    2010-01-01

    The purpose of the study was to explore possible links between student socioeconomic status (SES), beliefs about information and communication technologies (ICTs), and out-of-school learning resources. Grades 5 and 6 students (N = 345) who were enrolled in one private and six public elementary schools in Greece, located in areas with different…

  9. 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…

  10. 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

  11. 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. PMID:23544858

  12. Race/Ethnicity, Gender, and Monitoring Socioeconomic Gradients in Health: A Comparison of Area-Based Socioeconomic Measures—The Public Health Disparities Geocoding Project

    PubMed Central

    Krieger, Nancy; Chen, Jarvis T.; Waterman, Pamela D.; Rehkopf, David H.; Subramanian, S. V.

    2003-01-01

    Use of multilevel frameworks and area-based socioeconomic measures (ABSMs) for public health monitoring can potentially overcome the absence of socioeconomic data in most US public health surveillance systems. To assess whether ABSMs can meaningfully be used for diverse race/ethnicity–gender groups, we geocoded and linked public health surveillance data from Massachusetts and Rhode Island to 1990 block group, tract, and zip code ABSMs. Outcomes comprised death, birth, cancer incidence, tuberculosis, sexually transmitted infections, childhood lead poisoning, and nonfatal weapons-related injuries. Among White, Black, and Hispanic women and men, measures of economic deprivation (e.g., percentage below poverty) were most sensitive to expected socioeconomic gradients in health, with the most consistent results and maximal geocoding linkage evident for tract-level analyses. PMID:14534218

  13. 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.

  14. 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)

  15. 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.

  16. 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

  17. 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

  18. 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

  19. INTEGRATING ECOLOGY, HUMAN HEALTH AND SOCIOECONOMICS

    EPA Science Inventory

    This research involves collaboration with other ORD Labs and Centers, as well as external collaborators, to foster integration of assessment approaches used to evaluate human health and ecological risks and to demonstrate integrated environmental socioeconomic approaches. Part...

  20. Socioeconomic indicators that matter for population health.

    PubMed

    Lantz, Paula M; Pritchard, Andrew

    2010-07-01

    Increasing research and policy attention is being given to how the socioeconomic environment influences health. This article discusses potential indicators or metrics regarding the socioeconomic environment that could play a role in an incentive-based system for population health. Given the state of the research regarding the influence of socioeconomic contextual variables on health outcomes, the state of data and metrics for these variables at the local level, and the potential for program and policy intervention, we recommend a set of metrics related to the socioeconomic composition of a community (including poverty, unemployment, and public assistance rates); educational attainment and achievement; racial segregation; and social-capital indicators such as density of voluntary organizations and voter turnout. These indicators reflect the evidence that population health gains depend on improvements in many of the fundamental social determinants of health, including meaningful employment, income security, educational opportunities, and engaged, active communities. PMID:20550832

  1. 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

  2. Family Allowances and Fertility: Socioeconomic Differences

    PubMed Central

    SCHELLEKENS, JONA

    2009-01-01

    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. PMID:19771939

  3. How structurally stable are global socioeconomic systems?

    PubMed Central

    Saavedra, Serguei; Rohr, Rudolf P.; Gilarranz, Luis J.; Bascompte, Jordi

    2014-01-01

    The stability analysis of socioeconomic systems has been centred on answering whether small perturbations when a system is in a given quantitative state will push the system permanently to a different quantitative state. However, typically the quantitative state of socioeconomic systems is subject to constant change. Therefore, a key stability question that has been under-investigated is how strongly the conditions of a system itself can change before the system moves to a qualitatively different behaviour, i.e. how structurally stable the systems is. Here, we introduce a framework to investigate the structural stability of socioeconomic systems formed by a network of interactions among agents competing for resources. We measure the structural stability of the system as the range of conditions in the distribution and availability of resources compatible with the qualitative behaviour in which all the constituent agents can be self-sustained across time. To illustrate our framework, we study an empirical representation of the global socioeconomic system formed by countries sharing and competing for multinational companies used as proxy for resources. We demonstrate that the structural stability of the system is inversely associated with the level of competition and the level of heterogeneity in the distribution of resources. Importantly, we show that the qualitative behaviour of the observed global socioeconomic system is highly sensitive to changes in the distribution of resources. We believe that this work provides a methodological basis to develop sustainable strategies for socioeconomic systems subject to constantly changing conditions. PMID:25165600

  4. UniPathway: a resource for the exploration and annotation of metabolic pathways.

    PubMed

    Morgat, Anne; Coissac, Eric; Coudert, Elisabeth; Axelsen, Kristian B; Keller, Guillaume; Bairoch, Amos; Bridge, Alan; Bougueleret, Lydie; Xenarios, Ioannis; Viari, Alain

    2012-01-01

    UniPathway (http://www.unipathway.org) is a fully manually curated resource for the representation and annotation of metabolic pathways. UniPathway provides explicit representations of enzyme-catalyzed and spontaneous chemical reactions, as well as a hierarchical representation of metabolic pathways. This hierarchy uses linear subpathways as the basic building block for the assembly of larger and more complex pathways, including species-specific pathway variants. All of the pathway data in UniPathway has been extensively cross-linked to existing pathway resources such as KEGG and MetaCyc, as well as sequence resources such as the UniProt KnowledgeBase (UniProtKB), for which UniPathway provides a controlled vocabulary for pathway annotation. We introduce here the basic concepts underlying the UniPathway resource, with the aim of allowing users to fully exploit the information provided by UniPathway. PMID:22102589

  5. UniPathway: a resource for the exploration and annotation of metabolic pathways

    PubMed Central

    Morgat, Anne; Coissac, Eric; Coudert, Elisabeth; Axelsen, Kristian B.; Keller, Guillaume; Bairoch, Amos; Bridge, Alan; Bougueleret, Lydie; Xenarios, Ioannis; Viari, Alain

    2012-01-01

    UniPathway (http://www.unipathway.org) is a fully manually curated resource for the representation and annotation of metabolic pathways. UniPathway provides explicit representations of enzyme-catalyzed and spontaneous chemical reactions, as well as a hierarchical representation of metabolic pathways. This hierarchy uses linear subpathways as the basic building block for the assembly of larger and more complex pathways, including species-specific pathway variants. All of the pathway data in UniPathway has been extensively cross-linked to existing pathway resources such as KEGG and MetaCyc, as well as sequence resources such as the UniProt KnowledgeBase (UniProtKB), for which UniPathway provides a controlled vocabulary for pathway annotation. We introduce here the basic concepts underlying the UniPathway resource, with the aim of allowing users to fully exploit the information provided by UniPathway. PMID:22102589

  6. Linked Systems.

    ERIC Educational Resources Information Center

    Association of Research Libraries, Washington, DC.

    Three papers are compiled here for research library directors: (1) "Background: Open Systems Interconnection," in which David F. Bishop provides fundamental background information to explain the concept of the emerging technology of linked systems and open systems interconnection--i.e., an agreed upon standard set of conventions or rules that,…

  7. 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

  8. 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

  9. PATHWAYS - ELECTRON TUNNELING PATHWAYS IN PROTEINS

    NASA Technical Reports Server (NTRS)

    Beratan, D. N.

    1994-01-01

    The key to understanding the mechanisms of many important biological processes such as photosynthesis and respiration is a better understanding of the electron transfer processes which take place between metal atoms (and other groups) fixed within large protein molecules. Research is currently focused on the rate of electron transfer and the factors that influence it, such as protein composition and the distance between metal atoms. Current models explain the swift transfer of electrons over considerable distances by postulating bridge-mediated tunneling, or physical tunneling pathways, made up of interacting bonds in the medium around and between donor and acceptor sites. The program PATHWAYS is designed to predict the route along which electrons travel in the transfer processes. The basic strategy of PATHWAYS is to begin by recording each possible path element on a connectivity list, including in each entry which two atoms are connected and what contribution the connection would make to the overall rate if it were included in a pathway. The list begins with the bonded molecular structure (including the backbone sequence and side chain connectivity), and then adds probable hydrogen bond links and through-space contacts. Once this list is completed, the program runs a tree search from the donor to the acceptor site to find the dominant pathways. The speed and efficiency of the computer search offers an improvement over manual techniques. PATHWAYS is written in FORTRAN 77 for execution on DEC VAX series computers running VMS. The program inputs data from four data sets and one structure file. The software was written to input BIOGRAF (old format) structure files based on x-ray crystal structures and outputs ASCII files listing the best pathways and BIOGRAF vector files containing the paths. Relatively minor changes could be made in the input format statements for compatibility with other graphics software. The executable and source code are included with the

  10. 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

  11. Early Life Socioeconomic Circumstance and Late Life Brain Hyperintensities – A Population Based Cohort Study

    PubMed Central

    Murray, Alison D.; McNeil, Christopher J.; Salarirad, Sima; Whalley, Lawrence J.; Staff, Roger T.

    2014-01-01

    Context There have been many reports confirming the association between lower childhood socioeconomic circumstance and cardiovascular disease but evidence for links with cerebrovascular disease is contradictory. Hyperintensities on brain magnetic resonance imaging are associated with vascular risk factors, cognitive decline, dementia and death. However, the relationship between childhood socioeconomic circumstance and these lesions is unclear. Objective To test the hypothesis that childhood socioeconomic circumstance is associated with late life hyperintensity burden and that neither adult socioeconomic circumstance nor change in socioeconomic circumstance during life influence this effect. Design Cohort study Setting Community Participants 227 community dwelling members of the 1936 Aberdeen Birth Cohort aged 68 years, who were free from dementia. Main Outcome Measures Relationship between early life socioeconomic circumstance (paternal occupation) and abundance of late life brain hyperintensities. Results We find significant negative correlations between childhood socioeconomic circumstance and white matter hyperintensities (ρ = −0.18, P<0.01), and periventricular hyperintensities (ρ = −0.15, P<0.05), between educational attainment and white matter hyperintensities (ρ = −0.15, P<0.05) and periventricular hyperintensities (ρ = −0.17, P<0.05), and between childhood intelligence and periventricular hyperintensities (ρ = −0.14, P<0.05). The relationship is strongest for childhood socioeconomic circumstance and regional white matter hyperintensities, where there is a step change in increased burden from paternal occupation grades equivalent to a shift from “white collar” to “blue collar” paternal occupation. Significant correlations were also found between hypertension and hyperintensity burden in all brain regions (ρ = 0.15–0.24, P<0.05). In models that include hypertension, the magnitude of the effect of childhood

  12. Socioeconomics drive urban plant diversity

    PubMed Central

    Hope, Diane; Gries, Corinna; Zhu, Weixing; Fagan, William F.; Redman, Charles L.; Grimm, Nancy B.; Nelson, Amy L.; Martin, Chris; Kinzig, Ann

    2003-01-01

    Spatial variation in plant diversity has been attributed to heterogeneity in resource availability for many ecosystems. However, urbanization has resulted in entire landscapes that are now occupied by plant communities wholly created by humans, in which diversity may reflect social, economic, and cultural influences in addition to those recognized by traditional ecological theory. Here we use data from a probability-based survey to explore the variation in plant diversity across a large metropolitan area using spatial statistical analyses that incorporate biotic, abiotic, and human variables. Our prediction for the city was that land use, along with distance from urban center, would replace the dominantly geomorphic controls on spatial variation in plant diversity in the surrounding undeveloped Sonoran desert. However, in addition to elevation and current and former land use, family income and housing age best explained the observed variation in plant diversity across the city. We conclude that a functional relationship, which we term the “luxury effect,” may link human resource abundance (wealth) and plant diversity in urban ecosystems. This connection may be influenced by education, institutional control, and culture, and merits further study. PMID:12847293

  13. Pathways to chromothripsis

    PubMed Central

    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

  14. 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

  15. Ethnic and socioeconomic disparities in dermatology.

    PubMed

    Jackson, Chantal; Maibach, Howard

    2016-06-01

    Ethnic and socioeconomic disparities exist within healthcare. Specifically, minority group members experience more deleterious health outcomes than do majority group members. In this paper, we explore the factors that influence such variety, with a focus on the field of dermatology, in an attempt to understand the ways to improve minority group results. We also highlight how the prevalence of mental health issues within minority group and low socioeconomic status individuals can differentially influence dermatological disease states, such as the relationship between depression and psoriasis. PMID:26418077

  16. Explaining socio-economic status differences in walking for transport: An ecological analysis of individual, social and environmental factors

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The identification of potential mechanisms of influence (mediators) of socio-economic status (SES) on walking for transport is important, because the likely opposing forces of influence may obscure pathways for intervention across different SES groups. This study examined individual, and perceived s...

  17. 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

  18. WikiPathways: capturing the full diversity of pathway knowledge.

    PubMed

    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

  19. Dream recall frequency by socioeconomic status of Chinese students.

    PubMed

    Schredl, Michael

    2007-10-01

    Whereas the effect of sex and age on dream recall have been studied widely, socioeconomic status has rarely been investigated. However, two studies reported that higher socioeconomic status was related to greater frequency of dream recall. In the present sample of 612 Chinese students from three different schools, one elite (high socioeconomic status), one rural (low socioeconomic status) and one intermediate, analysis of variance indicated no significant association between frequency of dream recall and socioeconomic status. Researchers could investigate whether "dream socialization," e.g., encouragement of a child to remember his dreams, depends on socioeconomic background, whether these processes are mediated by culture. PMID:18065085

  20. 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…

  1. Teaching Technology in Low Socioeconomic Areas

    ERIC Educational Resources Information Center

    Thomas, Dianne

    2007-01-01

    For all students to become successful, productive citizens in the future, it is apparent that they must be well educated in technology. Those students who come from lower socioeconomic backgrounds have further to go in attaining that education because they often do not have the capabilities at home to practice technology nor do they have the…

  2. 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.…

  3. 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…

  4. 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…

  5. Socioeconomic Determinants of Early Retirement in Canada.

    ERIC Educational Resources Information Center

    McDonald, P. Lynn; Wanner, Richard A.

    1984-01-01

    This study attempts to determine the main socioeconomic factors influencing the decision to retire before age 65 among Canadian men and women. The study concludes that early retirees tend to be single men and married women employed by others who are better educated and whose nonearned income is higher than those who retire at a later age.…

  6. 75 FR 69009 - Acquisition Regulation: Socioeconomic Programs

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-11-10

    ...The Department of Energy (DOE) is amending the Department of Energy Acquisition Regulation (DEAR) Socioeconomic Programs to make changes to conform to the Federal Acquisition Regulation (FAR), remove out-of-date coverage, and update references. Today's rule does not alter substantive rights or obligations under current...

  7. 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…

  8. Socioeconomic Status and MMPI-2 Interpretation.

    ERIC Educational Resources Information Center

    Long, Kathleen A.; And Others

    1994-01-01

    Examined differences in Minnesota Multiphasic Personality Inventory-2 (MMPI-2) scores between persons of differing educational levels and family income in the MMPI-2 normative sample to determine if MMPI-2 scores are differentially accurate in predicting relevant extra-test characteristics of persons of differing socioeconomic levels. MMPI-2…

  9. 48 CFR 873.107 - Socioeconomic programs.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Socioeconomic programs. 873.107 Section 873.107 Federal Acquisition Regulations System DEPARTMENT OF VETERANS AFFAIRS... Small Business Administration (the 8(a) Program). The procedures of FAR 19.8 shall be followed where...

  10. 48 CFR 873.107 - Socioeconomic programs.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 48 Federal Acquisition Regulations System 5 2011-10-01 2011-10-01 false Socioeconomic programs. 873.107 Section 873.107 Federal Acquisition Regulations System DEPARTMENT OF VETERANS AFFAIRS... Small Business Administration (the 8(a) Program). The procedures of FAR 19.8 shall be followed where...

  11. Socioeconomic Achievements of Former College Students.

    ERIC Educational Resources Information Center

    Smart, John C.; Pasacarella, Ernest T.

    1986-01-01

    A causal model is proposed and estimated to assess the relative influence of precollege attributes, institutional characteristics, and academic, social, and career-related collegiate experiences on the socioeconomic achievement of 2,118 former college students over a nine-year period. (Author/MLW)

  12. Transatlantic link

    NASA Astrophysics Data System (ADS)

    (left) European Geophysical Society (EGS) President Rolf Meissner at AGU Headquarters with (center) Executive Director Fred Spilhaus and (right) Foreign Secretary Juan Roederer. Meissner attended the meeting of AGU's Committee on International Participation (CIP) on February 26, 1988. At that meeting, specific ways of fostering close links between AGU and EGS were discussed.A few weeks later, Roederer and AGU staff, working with EGS Secretary-General Arne Richter at the EGS meeting in Bologna, Italy, March 21-25, planned details of the establishment of an AGU office in Europe. The Copernicus Gesellschaft, a new entity located on the premises of the Max Planck Institute for Aeronomy in Lindau, Federal Republic of Germany, will provide the administrative staff and handle logistics.

  13. Young Girls' Arithmetic and Spatial Skills: The Distal and Proximal Roles of Family Socioeconomics and Home Learning Experiences

    ERIC Educational Resources Information Center

    Dearing, Eric; Casey, Beth M.; Ganley, Colleen M.; Tillinger, Miriam; Laski, Elida; Montecillo, Christine

    2012-01-01

    The present study addressed girls' (N=127) early numerical and spatial reasoning skills, within the context of a critical environment in which these cognitive skills develop, namely their homes. Specifically, proximal links between distal family socioeconomic conditions and first-grade girls' arithmetic and spatial skills were examined (mean…

  14. Gene Network Analysis of Glucose Linked Signaling Pathways and Their Role in Human Hepatocellular Carcinoma Cell Growth and Survival in HuH7 and HepG2 Cell Lines

    PubMed Central

    Berger, Emmanuelle; Vega, Nathalie; Weiss-Gayet, Michèle; Géloën, Alain

    2015-01-01

    Cancer progression may be affected by metabolism. In this study, we aimed to analyze the effect of glucose on the proliferation and/or survival of human hepatocellular carcinoma (HCC) cells. Human gene datasets regulated by glucose were compared to gene datasets either dysregulated in HCC or regulated by other signaling pathways. Significant numbers of common genes suggested putative involvement in transcriptional regulations by glucose. Real-time proliferation assays using high (4.5 g/L) versus low (1 g/L) glucose on two human HCC cell lines and specific inhibitors of selected pathways were used for experimental validations. High glucose promoted HuH7 cell proliferation but not that of HepG2 cell line. Gene network analyses suggest that gene transcription by glucose could be mediated at 92% through ChREBP in HepG2 cells, compared to 40% in either other human cells or rodent healthy liver, with alteration of LKB1 (serine/threonine kinase 11) and NOX (NADPH oxidases) signaling pathways and loss of transcriptional regulation of PPARGC1A (peroxisome-proliferator activated receptors gamma coactivator 1) target genes by high glucose. Both PPARA and PPARGC1A regulate transcription of genes commonly regulated by glycolysis, by the antidiabetic agent metformin and by NOX, suggesting their major interplay in the control of HCC progression. PMID:26380295

  15. 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

  16. A local coastal adaptation pathway

    NASA Astrophysics Data System (ADS)

    Barnett, J.; Graham, S.; Mortreux, C.; Fincher, R.; Waters, E.; Hurlimann, A.

    2014-12-01

    Local governments are not adapting to sea-level rise because it is difficult to build consensus on the need for change and the best way to implement it. In theory, adaptation pathways can resolve this impasse. Adaptation pathways are a sequence of linked strategies that are triggered by a change in environmental conditions, and in which initial decisions can have low regrets and preserve options for future generations. We report on a project that sought to empirically test the relevance and feasibility of a local pathway for adapting to sea-level rise. We find that triggers of change that have social impacts are salient to local people, and developing a local adaptation pathway helps build consensus among diverse constituencies. Our results show that adaptation pathways are feasible at the local scale, offering a low-risk, low-cost way to begin the long process of adaptation to sea-level rise.

  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. 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…

  19. 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

  20. 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.

  1. 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

  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. Socioeconomic legacy yields an invasion debt

    PubMed Central

    Essl, Franz; Dullinger, Stefan; Rabitsch, Wolfgang; Hulme, Philip E.; Hülber, Karl; Jarošík, Vojtěch; Kleinbauer, Ingrid; Krausmann, Fridolin; Kühn, Ingolf; Nentwig, Wolfgang; Vilà, Montserrat; Genovesi, Piero; Gherardi, Francesca; Desprez-Loustau, Marie-Laure; Roques, Alain; Pyšek, Petr

    2011-01-01

    Globalization and economic growth are widely recognized as important drivers of biological invasions. Consequently, there is an increasing need for governments to address the role of international trade in their strategies to prevent species introductions. However, many of the most problematic alien species are not recent arrivals but were introduced several decades ago. Hence, current patterns of alien-species richness may better reflect historical rather than contemporary human activities, a phenomenon which might be called “invasion debt.” Here, we show that across 10 taxonomic groups (vascular plants, bryophytes, fungi, birds, mammals, reptiles, amphibians, fish, terrestrial insects, and aquatic invertebrates) in 28 European countries, current numbers of alien species established in the wild are indeed more closely related to indicators of socioeconomic activity from the year 1900 than to those from 2000, although the majority of species introductions occurred during the second half of the 20th century. The strength of the historical signal varies among taxonomic groups, with those possessing good capabilities for dispersal (birds, insects) more strongly associated with recent socioeconomic drivers. Nevertheless, our results suggest a considerable historical legacy for the majority of the taxa analyzed. The consequences of the current high levels of socioeconomic activity on the extent of biological invasions will thus probably not be completely realized until several decades into the future. PMID:21173227

  4. Socioeconomic Factors and Asthma Control in Children

    PubMed Central

    Cope, Shannon F.; Ungar, Wendy J.; Glazier, Richard H.

    2016-01-01

    Summary Objectives The objective of this study was to evaluate the association between socioeconomic factors and asthma control in children, as defined by the Canadian Pediatric Asthma Consensus Guidelines. Patients and Methods Cross-sectional data from a completed study of 879 asthmatic children between the ages of 1 and 18 residing in the Greater Toronto Area were used. The database included data on demographics, health status, asthma control, and health-related quality of life. Stepwise forward modeling multiple regression was used to investigate the impact of socioeconomic status on asthma control, based on six control parameters from the 2003 Canadian Pediatric Asthma Consensus Guidelines. Results Only 11% of patients met the requirements for acceptable control, while 20% had intermediate control, and 69% had unacceptable asthma control. Children from families in lower income adequacy levels had poorer control. Conclusions Disparities in asthma control between children from families of different socio-economic strata persist, even with adjustment for utilization of primary care services and use of controller medications. PMID:18615669

  5. Strongyloidiasis: A Disease of Socioeconomic Disadvantage.

    PubMed

    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

  6. 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. PMID:23906118

  7. 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

  8. Spatial ascariasis risk estimation using socioeconomic variables.

    PubMed

    Valencia, Luis Iván Ortiz; Fortes, Bruno de Paula Menezes Drumond; Medronho, Roberto de Andrade

    2005-12-01

    Frequently, disease incidence is mapped as area data, for example, census tracts, districts or states. Spatial disease incidence can be highly heterogeneous inside these areas. Ascariasis is a highly prevalent disease, which is associated with poor sanitation and hygiene. Geostatistics was applied to model spatial distribution of Ascariasis risk and socioeconomic risk events in a poor community in Rio de Janeiro, Brazil. Data were gathered from a coproparasitologic and a domiciliary survey in 1550 children aged 1-9. Ascariasis risk and socioeconomic risk events were spatially estimated using Indicator Kriging. Cokriging models with a Linear Model of Coregionalization incorporating one socioeconomic variable were implemented. If a housewife attended school for less than four years, the non-use of a home water filter, a household density greater than one, and a household income lower than one Brazilian minimum wage increased the risk of Ascariasis. Cokriging improved spatial estimation of Ascariasis risk areas when compared to Indicator Kriging and detected more Ascariasis very-high risk areas than the GIS Overlay method. PMID:16506435

  9. Socioeconomic status and obesity in Abia State, South East Nigeria

    PubMed Central

    Chukwuonye, Innocent Ijezie; Chuku, Abali; Okpechi, Ikechi Gareth; Onyeonoro, Ugochukwu Uchenna; Madukwe, Okechukwu Ojoemelam; Okafor, Godwin Oguejiofor Chukwuebuka; Ogah, Okechukwu Samuel

    2013-01-01

    Background and objectives Obesity is a major risk factor for cardiovascular disease in developed and emerging economies. There is a paucity of data from Nigeria on the association between socioeconomic status and obesity. The aim of this study is to highlight that association in Abia State, South East Nigeria. Material and methods This was a cross-sectional survey in South East Nigeria. Participating subjects were recruited from the three senatorial zones of Abia state. A total of 2,487 adults took part in the study. The subjects were classified based on their monthly income and level of educational attainment (determinants of obesity). Monthly income was classified into three groups: low, middle, and upper income, while educational level was classified into four groups: no formal education, primary, secondary, and tertiary education. Body mass index of subjects was determined and used for defining obesity. Data on blood pressure and other anthropometric measurements were also collected using a questionnaire, modified from the World Health Organization STEPwise Approach to Chronic Disease Risk Factor Surveillance. Results Overall, the prevalence of obesity in low, middle, and upper income groups was 12.2%, 16%, and 20%, respectively. The overall prevalence of obesity in individuals with no formal education, primary, secondary, and tertiary education was 6.3%, 14.9%, 10.5%, and 17.7%, respectively. Educational status was found to be significantly associated with obesity in women, but not in men, or in the combined group. However, level of income was observed to be significantly associated with obesity in men, women, and in the combined group. Conclusion Sociodemographic and socioeconomic factors are important determinants of obesity in our study population, and therefore may be indirectly linked to the prevalence and the outcomes of cardiovascular disease in Nigeria. PMID:24204167

  10. 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. PMID:27382185

  11. 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

  12. The Reactome pathway knowledgebase.

    PubMed

    Croft, David; Mundo, Antonio Fabregat; Haw, Robin; Milacic, Marija; Weiser, Joel; Wu, Guanming; Caudy, Michael; Garapati, Phani; Gillespie, Marc; Kamdar, Maulik R; Jassal, Bijay; Jupe, Steven; Matthews, Lisa; May, Bruce; Palatnik, Stanislav; Rothfels, Karen; Shamovsky, Veronica; Song, Heeyeon; Williams, Mark; Birney, Ewan; Hermjakob, Henning; Stein, Lincoln; D'Eustachio, Peter

    2014-01-01

    Reactome (http://www.reactome.org) is a manually curated open-source open-data resource of human pathways and reactions. The current version 46 describes 7088 human proteins (34% of the predicted human proteome), participating in 6744 reactions based on data extracted from 15 107 research publications with PubMed links. The Reactome Web site and analysis tool set have been completely redesigned to increase speed, flexibility and user friendliness. The data model has been extended to support annotation of disease processes due to infectious agents and to mutation. PMID:24243840

  13. 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

  14. 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

  15. Sex-linked dominant

    MedlinePlus

    Inheritance - sex-linked dominant; Genetics - sex-linked dominant; X-linked dominant; Y-linked dominant ... one of the sex chromosomes, which are the X and Y chromosomes. Dominant inheritance occurs when an ...

  16. Sex-linked recessive

    MedlinePlus

    Inheritance - sex-linked recessive; Genetics - sex-linked recessive; X-linked recessive ... X-linked recessive diseases usually occur in males. Males have only one X chromosome. A single recessive ...

  17. Sex-linked dominant

    MedlinePlus

    Inheritance - sex-linked dominant; Genetics - sex-linked dominant; X-linked dominant; Y-linked dominant ... type of chromosome that is affected (autosomal or sex chromosome). It also depends on whether the trait ...

  18. Rates of breastfeeding and exposure to socio-economic adversity amongst children with intellectual disability.

    PubMed

    Gore, Nick; Emerson, Eric; Brady, Serena

    2015-04-01

    Children with intellectual disability are at increased risk of experiencing poor health relative to their typically developing peers. Previous research indicates that exposure to socio-economic disadvantage contributes towards this disparity but that additional factors (including parenting practices) may be involved in mediating/moderating pathways. This study examined duration of breastfeeding amongst children with and without intellectual disability by a secondary analysis of data from the UK Millennium Cohort Study. Children with intellectual disability were significantly less likely to have been ever breastfed; breastfed exclusively or at all at 3 months or breastfed at all at 6 months relative to children without intellectual disability. None of these differences remained significant when other psycho-social risk factors for reduced breastfeeding were controlled for. The study adds to both the sparse literature on breastfeeding practices amongst families of children with intellectual disability and research demonstrating relationships between socio-economic disadvantage and wellbeing for children with intellectual disability. PMID:25613368

  19. 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

  20. 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

  1. 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

  2. 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

  3. 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

  4. Hydrogen peroxide inhibits transforming growth factor-β1-induced cell cycle arrest by promoting Smad3 linker phosphorylation through activation of Akt-ERK1/2-linked signaling pathway

    SciTech Connect

    Choi, Jiyeon; Park, Seong Ji; Jo, Eun Ji; Lee, Hui-Young; Hong, Suntaek; Kim, Seong-Jin; Kim, Byung-Chul

    2013-06-14

    Highlights: •H{sub 2}O{sub 2} inhibits TGF-β1-induced cell cycle arrest. •H{sub 2}O{sub 2} induces Smad3 linker phosphorylation through Akt-ERK1/2 pathway. •H{sub 2}O{sub 2}-mediated suppression of TGF-β signal requires Smad3 linker phosphorylation. •This is a first report about interplay between H{sub 2}O{sub 2} and growth inhibition pathway. -- Abstract: Hydrogen peroxide (H{sub 2}O{sub 2}) functions as a second messenger in growth factor receptor-mediated intracellular signaling cascade and is tumorigenic by virtue of its ability to promote cell proliferation; however, the mechanisms underlying the growth stimulatory action of H{sub 2}O{sub 2} are less understood. Here we report an important mechanism for antagonistic effects of H{sub 2}O{sub 2} on growth inhibitory response to transforming growth factor-β1 (TGF-β1). In Mv1Lu and HepG2 cells, pretreatment of H{sub 2}O{sub 2} (0.05–0.2 mM) completely blocked TGF-β1-mediated induction of p15{sup INK4B} expression and increase of its promoter activity. Interestingly, H{sub 2}O{sub 2} selectively suppressed the transcriptional activation potential of Smad3, not Smad2, in the absence of effects on TGF-β1-induced phosphorylation of the COOH-tail SSXS motif of Smad3 and its nuclear translocation. Mechanism studies showed that H{sub 2}O{sub 2} increases the phosphorylation of Smad3 at the middle linker region in a concentration- and time-dependent manner and this effect is mediated by activation of extracellular signal-activated kinase 1/2 through Akt. Furthermore, expression of a mutant Smad3 in which linker phosphorylation sites were ablated significantly abrogated the inhibitory effects of H{sub 2}O{sub 2} on TGF-β1-induced increase of p15{sup INK4B}-Luc reporter activity and blockade of cell cycle progression from G1 to S phase. These findings for the first time define H{sub 2}O{sub 2} as a signaling molecule that modulate Smad3 linker phosphorylation and its transcriptional activity, thus providing

  5. 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

  6. PathwayMatrix: visualizing binary relationships between proteins in biological pathways

    PubMed Central

    2015-01-01

    Background Molecular activation pathways are inherently complex, and understanding relations across many biochemical reactions and reaction types is difficult. Visualizing and analyzing a pathway is a challenge due to the network size and the diversity of relations between proteins and molecules. Results In this paper, we introduce PathwayMatrix, a visualization tool that presents the binary relations between proteins in the pathway via the use of an interactive adjacency matrix. We provide filtering, lensing, clustering, and brushing and linking capabilities in order to present relevant details about proteins within a pathway. Conclusions We evaluated PathwayMatrix by conducting a series of in-depth interviews with domain experts who provided positive feedback, leading us to believe that our visualization technique could be helpful for the larger community of researchers utilizing pathway visualizations. PathwayMatrix is freely available at https://github.com/CreativeCodingLab/PathwayMatrix. PMID:26361499

  7. 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

  8. 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 Central

    Iafrati, J; Orejarena, M J; Lassalle, O; Bouamrane, L; Chavis, P

    2014-01-01

    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. PMID:23752244

  9. Linking Chemical Electron–Proton Transfer to Proton Pumping in Cytochrome c Oxidase: Broken-Symmetry DFT Exploration of Intermediates along the Catalytic Reaction Pathway of the Iron–Copper Dinuclear Complex

    PubMed Central

    2015-01-01

    After a summary of the problem of coupling electron and proton transfer to proton pumping in cytochrome c oxidase, we present the results of our earlier and recent density functional theory calculations for the dinuclear Fe-a3–CuB reaction center in this enzyme. A specific catalytic reaction wheel diagram is constructed from the calculations, based on the structures and relative energies of the intermediate states of the reaction cycle. A larger family of tautomers/protonation states is generated compared to our earlier work, and a new lowest-energy pathway is proposed. The entire reaction cycle is calculated for the new smaller model (about 185–190 atoms), and two selected arcs of the wheel are chosen for calculations using a larger model (about 205 atoms). We compare the structural and redox energetics and protonation calculations with available experimental data. The reaction cycle map that we have built is positioned for further improvement and testing against experiment. PMID:24960612

  10. Socioeconomic differences in alcohol-attributable mortality compared with all-cause mortality: a systematic review and meta-analysis

    PubMed Central

    Probst, Charlotte; Roerecke, Michael; Behrendt, Silke; Rehm, Jürgen

    2014-01-01

    Background: Factors underlying socioeconomic inequalities in mortality are not well understood. This study contributes to our understanding of potential pathways to result in socioeconomic inequalities, by examining alcohol consumption as one potential explanation via comparing socioeconomic inequalities in alcohol-attributable mortality and all-cause mortality. Methods: Web of Science, MEDLINE, PsycINFO and ETOH were searched systematically from their inception to second week of February 2013 for articles reporting alcohol-attributable mortality by socioeconomic status, operationalized by using information on education, occupation, employment status or income. The sex-specific ratios of relative risks (RRRs) of alcohol-attributable mortality to all-cause mortality were pooled for different operationalizations of socioeconomic status using inverse-variance weighted random effects models. These RRRs were then combined to a single estimate. Results: We identified 15 unique papers suitable for a meta-analysis; capturing about 133 million people, 3 741 334 deaths from all causes and 167 652 alcohol-attributable deaths. The overall RRRs amounted to RRR = 1.78 (95% confidence interval (CI) 1.43 to 2.22) and RRR = 1.66 (95% CI 1.20 to 2.31), for women and men, respectively. In other words: lower socioeconomic status leads to 1.5–2-fold higher mortality for alcohol-attributable causes compared with all causes. Conclusions: Alcohol was identified as a factor underlying higher mortality risks in more disadvantaged populations. All alcohol-attributable mortality is in principle avoidable, and future alcohol policies must take into consideration any differential effect on socioeconomic groups. PMID:24618188

  11. "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…

  12. 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

  13. 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.

  14. 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

  15. Integrating natural and socio-economic science in coastal management

    NASA Astrophysics Data System (ADS)

    Turner, R. Kerry

    2000-07-01

    The future more sustainable management of coastal resources is an important policy goal for all governments of countries with coastlines. Coastal areas are under intense environmental change pressure with extensive feedback effects between the natural systems and the human systems. It could be argued that there is just one jointly determined and coevolving system that needs to be studied and managed. Understanding the interactions between the coastal zone and environmental change cannot be achieved by observational studies alone. Modelling of key environmental and socio-economic processes is a vital tool, required to buttress coastal management institutions and practice. Three overlapping procedural stages can be identified in the coastal resource assessment process. The scoping and auditing stage, implemented via a 'pressure-state-impact-response' framework, details, among other thing, problems, system boundaries and value conflicts. The framework is itself based on a conceptual model, which lays stress on functional value diversity and the links between ecosystem processes, functions and outputs of goods and services which are deemed 'valuable' by society. The two subsequent stages are integrated modelling, combining natural and social science methodologies, and evaluation of management options and related gains and losses. An overview of a research project, which utilised the pressure-state-impacts-response (P-S-I-R) framework and supporting concepts and methods, is presented in the last section of the paper, together with some generic 'lessons' for interdisciplinary research.

  16. Socioeconomic status and indicators of asthma in children.

    PubMed

    Ernst, P; Demissie, K; Joseph, L; Locher, U; Becklake, M R

    1995-08-01

    Differential access and utilization of medical care by the poor and rich may contribute to differences in asthma prevalence. We therefore studied the relationship of socioeconomic status (SES) to various indicators of asthma in the Canadian context of universal access to medical care. Information on respiratory symptoms, demographics, and home exposures of 1,111 primary school children was collected by questionnaire. Parental occupation was used to establish SES. Exercise-induced bronchospasm (EIB) after a 6-min free-running test was our measure of airways responsiveness and was available for 989 children. As compared with children from the most advantaged homes, children from the least advantaged homes were more likely to present EIB (OR: 2.26, 95% CI: 1.12 to 4.58) and to report night cough (OR: 2.30, 95% CI: 1.04 to 5.06) and cough with mucus (OR: 3.15, 95% CI: 1.06 to 9.33), while there was no significant excess of the report of wheeze or diagnosed asthma. Among factors potentially linked to SES, the presence of a cat at home (OR: 1.63, 95% CI: 1.02 to 2.61) and lower respiratory infection before 2 yr of age were associated with an excess of EIB (OR: 1.71, 95% CI: 1.16 to 2.52). Our results suggest that unidentified environmental factors contribute to the excess asthma morbidity in poor children. PMID:7633709

  17. 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

  18. Socioeconomic resources in medicine: review of the literature.

    PubMed Central

    Austin, T

    1984-01-01

    In this era of intense competition in medicine, it is essential for health sciences librarians to keep abreast of the new and varied socioeconomic influences in the medical environment. A list of socioeconomic resources is provided to help meet this objective. A citation analysis of the Socioeconomic Bibliographic Information (SIB) database was used as a selection criterion. An annotated list of ninety journals, newspapers, and newsletters is included, which provides title of publication, publisher, cost, index information, and special characteristics. In addition, publishers and associations that provide socioeconomic information are listed, and an annotated list of standard statistical resource books is given. PMID:6378285

  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. Interactions between Sex, Socioeconomic Level, and Children's Cognitive Performance.

    PubMed

    Alves, Ana-Filipa; Martins, Ana; Almeida, Leandro S

    2016-04-01

    This study assesses the interactions between sex, socioeconomic level, and children's cognitive performance. Cognitive performance was measured for a sample of 453 Portuguese children, aged between 4 and 10 years, with 218 boys and 235 girls; verbal and nonverbal cognitive ability and intelligence quotient were measured by the Cognitive Skills Scale for Children. Multivariate analysis of variance assessed the effects of sex and family's socioeconomic level on intelligence quotient. A statistically significant interaction between sex and socioeconomic level was observed for nonverbal intelligence quotient, total intelligence quotient, and two subtests. Socioeconomic level had more influence than sex on most of the cognitive tests. PMID:27154374

  1. Effects of the UV-filter 2-ethyl-hexyl-4-trimethoxycinnamate (EHMC) on expression of genes involved in hormonal pathways in fathead minnows (Pimephales promelas) and link to vitellogenin induction and histology.

    PubMed

    Christen, Verena; Zucchi, Sara; Fent, Karl

    2011-04-01

    UV-filters are increasingly used in cosmetics and in the protection of materials against UV-irradiation, and ultimately they reach aquatic systems. The lipophilic UV-filter 2-ethyl-hexyl-4-trimethoxycinnamate (EHMC) belongs to one of the most frequently used UV-filters and accumulates in aquatic animals. Despite its ubiquitous presence in water and biota, very little is known about its potential hormonal effects on aquatic organisms. In our study, we evaluated the effects of measured water concentration of 5.4, 37.5, 244.5 and 394 μg/L EHMC on the expression of genes involved in hormonal pathways in the liver, testis and brain of male and female fathead minnows (Pimephales promelas). We compare the transcription profile with the plasma vitellogenin (VTG) content, secondary sex characteristics, and gonad histology. Transcripts of the androgen receptor (ar) were significantly down-regulated in the liver of females at 37.5, 244.5 μg/L and 394 μg/L EHMC. Additionally, the 3β-hydroxysteroid dehydrogenase (3β-HSD) transcript was significantly decreased in the liver of males at 37.5, 244.5 and 394 μg/L EHMC, and at 244.5 and 394 μg/L EHMC in females. The expressional changes were tissue-specific in most cases, being most significant in the liver. Vitellogenin plasma concentration was significantly increased at 244.5 μg/L EHMC in males. EHMC induced significant histological changes in testes and ovaries at 394 μg/L. Testes displayed a decrease in spermatocytes, and ovaries a decrease in previtellogenic oocytes. The induction of VTG plasma concentration and the histological changes in gonads suggest an estrogenic and/or antiandrogenic activity of EHMC. On the other hand, the gene expression profile shows an antiestrogenic (e.g.: down-regulation of esr1) activity of EHMC. In conclusion, our data demonstrate that EHMC displays low but multiple hormonal activities in fish. PMID:21356179

  2. Long-term depression and suicidal ideation outcomes subsequent to emancipation from foster care: pathways to psychiatric risk in the Métis population.

    PubMed

    Kaspar, Violet

    2014-02-28

    Major depressive episode (MDE) and suicidal ideation (SI) associated with history of foster care placement (HxFCP), and mediating effects of psychosocial and socioeconomic factors through which placement may confer psychiatric risks in the years subsequent to emancipation were examined in a national sample of 7534 Métis. More than one third of emancipated respondents reported past year MDE, a prevalence rate nearly 50% higher than the rate of MDE among Métis respondents without a history of placement in foster care. The 25% lifetime prevalence rate of SI in the emancipated group was more than twice the rate observed in the non-fostered group. Direct effects of HxFCP on post placement MDE and SI were significant in multivariate logistic regression analyses, even when effects of childhood predispositional risk factors were controlled statistically. Emancipated individuals were unduly affected by psychosocial and socioeconomic disadvantages signifying pathways that linked foster care placement history and psychiatric status. Main mediators of the effects demonstrated using effect decomposition procedures were self-esteem, income, and community adversity. The findings warrant consideration of foster care history in clarifying the complex etiologies of suicidal ideation and major depressive episode in the Métis population and risk factors ensuing in the intervening years as integral to the process linking placement to long-term psychiatric outcomes. PMID:24373554

  3. Socioeconomic deprivation, perceived neighborhood factors, and cortisol responses to induced stress among healthy adults

    PubMed Central

    Barrington, Wendy E.; Stafford, Mai; Hamer, Mark; Beresford, Shirley A.A.; Koepsell, Thomas; Steptoe, Andrew

    2014-01-01

    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 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

  4. 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

  5. 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. PMID:27288969

  6. 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.

  7. 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

  8. 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

  9. 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

  10. 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

  11. 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.

  12. Socioeconomic disparities in intimate partner violence against Native American women: a cross-sectional study

    PubMed Central

    Malcoe, Lorraine Halinka; Duran, Bonnie M; Montgomery, Juliann M

    2004-01-01

    exceptionally high rates of lifetime and past-year IPV. Additionally, within this low-income sample, there was strong evidence of socioeconomic variability in IPV. Further research should determine prevalence of IPV against Native American women from diverse tribes and regions, and examine pathways through which socioeconomic disadvantage may increase their IPV risk. PMID:15157273

  13. Ancient Human Bone Microstructure in Medieval England: Comparisons between Two Socio-Economic Groups.

    PubMed

    Miszkiewicz, Justyna J; Mahoney, Patrick

    2016-01-01

    Understanding the links between bone microstructure and human lifestyle is critical for clinical and anthropological research into skeletal growth and adaptation. The present study is the first to report correspondence between socio-economic status and variation in bone microstructure in ancient humans. Products of femoral cortical remodeling were assessed using histological methods in a large human medieval sample (N = 450) which represented two distinct socio-economic groups. Osteonal parameters were recorded in posterior midshaft femoral sections from adult males (N = 233) and females (N = 217). Using univariate and multivariate statistics, intact, fragmentary, and osteon population densities, Haversian canal area and diameter, and osteon area were compared between the two groups, accounting for sex, age, and estimated femoral robusticity. The size of osteons and their Haversian canals, as well as osteon density, varied significantly between the socio-economic groups, although minor inconsistencies were observed in females. Variation in microstructure was consistent with historical textual evidence that describes differences in mechanical loading and nutrition between the two groups. Results demonstrate that aspects of ancient human lifestyle can be inferred from bone microstructure. PMID:26480030

  14. Socio-economic status and socio-emotional health of orphans in South Africa.

    PubMed

    Pappin, Michele; Marais, Lochner; Sharp, Carla; Lenka, Molefi; Cloete, Jan; Skinner, Donald; Serekoane, Motsaathebe

    2015-02-01

    This paper investigates the relationship between socio-economic status and emotional well-being of orphans in Mangaung, South Africa. Five hundred orphans aged 7-11 years participated in the cross-sectional study between 2009 and 2012. Data was collected by trained fieldworkers, who conducted face-to-face interviews and questionnaires with the orphans, their teachers and caregivers, and the heads of the households where the orphans resided. The caregivers, children and teachers all completed the Strengths and Difficulties Questionnaire in order to measure the orphans' mental health, while heads of household provided information about socio-economic indicators. STATA version 12 was used to perform multivariate data analyses to identify socio-economic factors associated with the mental health of orphans. Food security, access to medical services and a male caregiver were factors associated with better emotional well-being of orphans, whereas other variables such as household asset index and monthly household expenditure were not linked with the orphans' mental health. Two of the three variables (food security and access to medical services) associated with better emotional well-being of orphans are also government interventions to assist orphans. Further research is needed to determine whether other government programs also impact the emotional well-being of orphans. PMID:24968757

  15. 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

  16. 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

  17. Socioeconomic and occupational risk factors for venous thromboembolism in Sweden: a nationwide epidemiological study.

    PubMed

    Zöller, Bengt; Li, Xinjun; Sundquist, Jan; Sundquist, Kristina

    2012-05-01

    Our aims were to investigate possible associations between hospitalisation for venous thromboembolism (VTE) and socioeconomic and occupational factors. A nationwide database was constructed by linking Swedish census data to the Hospital Discharge Register (1990-2007). Hospital diagnoses of VTE were based on the International Classification of Diseases. Standardised incidence ratios were calculated for different socioeconomic and occupational groups. A total of 43063 individuals aged >20 years were hospitalised for VTE. Individuals with >12 years of education were at lower risk for VTE. Blue-collar workers, farmers, and non-employed individuals had higher risks for VTE, and white collar workers and professionals lower risks. In males and/or females, risks for VTE were increased for assistant nurses; farmers; miners and quarry workers; mechanics, iron and metalware workers; wood workers; food manufacture workers; packers; loaders and warehouse workers; public safety and protection workers; cooks and stewards; home helpers; building caretakers; and cleaners. Decreased risks were observed for technical, chemical, physical, and biological workers; physicians; dentists; nurses; other health and medical workers; teachers, religious, juridical, and other social science-related workers; artistic workers; clerical workers; sale agents; and fishermen, whalers and sealers. High educational level and several occupations requiring high levels of education were protective against VTE, while the risks for VTE were increased for farmers, blue-collar workers and non-employed individuals. The mechanisms are unknown but it might involve persistent psychosocial stress related to low socioeconomic and occupational status. PMID:21868069

  18. SOCIOECONOMIC STATUS AND LEARNING PROFICIENCY IN YOUNG CHILDREN.

    ERIC Educational Resources Information Center

    ROHWER, WILLIAM D., JR.; AND OTHERS

    THIS STUDY WAS INITIATED TO DETERMINE WHY CHILDREN OF LOWER SOCIOECONOMIC STATUS, WHO DO INFERIOR WORK ON SCHOOL-RELATED LEARNING TASKS WHEN COMPARED TO UPPER SOCIOECONOMIC STATUS CHILDREN, LEARN AS EFFICIENTLY AS UPPER LEVEL CHILDREN ON PAIRED-ASSOCIATE TASKS. THE SAMPLE CONSISTED OF 120 LOWER STATUS CHILDREN AND 120 UPPER STATUS CHILDREN,…

  19. 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...

  20. 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…

  1. 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…

  2. 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…

  3. Demographic and Socioeconomic Aspects of Aging in the United States.

    ERIC Educational Resources Information Center

    Siegel, Jacob S.; Davidson, Maria

    1984-01-01

    This report (a substantial revision of a report issued in May, 1976 and reprinted in January, 1978) brings together and analyzes data on selected topics related to the demographic and socioeconomic aspects of aging, and the demographic and socioeconomic characteristics of the older population in the United States. The data come from the 1980…

  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. 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…

  6. 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. PMID:16433094

  7. 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

  8. 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

  9. 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…

  10. 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.

  11. 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

  12. 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

  13. Integrating Mechanisms for Insulin Resistance: Common Threads and Missing Links

    PubMed Central

    Samuel, Varman T.; Shulman, Gerald I.

    2012-01-01

    Insulin resistance is a complex metabolic disorder that defies a single etiological pathway. Accumulation of ectopic lipid metabolites, activation of the unfolded protein response (UPR) pathway and innate immune pathways have all been implicated in the pathogenesis of insulin resistance. However, these pathways are also closely linked to changes in fatty acid uptake, lipogenesis, and energy expenditure that can impact ectopic lipid deposition. Ultimately, accumulation of specific lipid metabolites (diacylglycerols and/or ceramides) in liver and skeletal muscle, may be a common pathway leading to impaired insulin signaling and insulin resistance. PMID:22385956

  14. 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

  15. 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

  16. Linking data sets: the case of Indonesia's Intercensal Population Surveys.

    PubMed

    Khoo, S; Suharto, S; Tom, J A; Supraptilah, B

    1980-01-01

    The authors describe the method used to merge two phases of the 1976 Indonesian Intercensal Population Surveys and to link them with community-level statistics collected separately by the Central Bureau of Statistics and the National Family Planning Coordinating Board. The use of the merged data set in examining the relative influence of individual characteristics, household socioeconomic status, community-level factors, and availability of family planning services on individual family planning behavior is evaluated PMID:12311723

  17. 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

  18. Student Movement: Pathways, Fields and Links to Work

    ERIC Educational Resources Information Center

    Fredman, Nick

    2013-01-01

    There is a lack of coherence between education, training and work in Australia indicated by low proportions of VET graduates who work in occupations related to their qualification and mismatches between qualifications, skills and work. This paper discusses how student flows through tertiary education can further illustrate this lack of coherence.…

  19. Country Roads Take Me...?: An Ethnographic Case Study of College Pathways among Rural, First-Generation Students

    ERIC Educational Resources Information Center

    Beasley, Sarah Elizabeth

    2011-01-01

    The purpose of this study was to examine college pathways or college access and success of rural, first-generation students. Most research on college pathways for low- and moderate-income students focuses on those students as a whole or on urban low-socioeconomic status (SES) students. (Caution is in order when generalizing the experiences of…

  20. Linking | Smokefree.gov

    Cancer.gov

    Links to individual pages within the Smokefree.gov Web site are permissible, provided attribution is made to Smokefree.gov and any descriptive notes accurately reflect the content of the linked page(s).

  1. 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

  2. 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. PMID:26189011

  3. Cross-sectional study on the effects of socioeconomic factors on lead exposure in children by gender in Serpong, Indonesia.

    PubMed

    Iriani, Dewi U; Matsukawa, Takehisa; Tadjudin, Muhammad K; Itoh, Hiroaki; Yokoyama, Kazuhito

    2012-11-01

    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

  4. Socioeconomic status and allied health use

    PubMed Central

    Yau, Ivan; Kendall, Claire

    2016-01-01

    Abstract Objective To identify whether socioeconomic status is associated with allied health use among patients in a large academic family health team (FHT). Design Data were collected through a retrospective chart review using an electronic medical record system. Setting A large academic FHT in Ottawa, Ont. Participants Patients with at least 1 in-person clinician encounter between January 1, 2012, and December 31, 2013. Main outcome measures Descriptive statistics were used to compare patients who accessed allied health services with those who did not. We conducted logistic regression analyses to determine whether income quintile was independently associated with allied health use after adjusting for other patient characteristics. Results The inclusion criteria identified 2938 unique patients, of whom 949 (32.3%) saw an allied health provider (AHP) during the study period. While patients in the fourth income quintile had the greatest AHP use per person (41.2% of patients had at least 1 AHP visit), those in the lowest income quintile had the greatest mean number of AHPs seen (mean [SD] = 1.48 [0.80]). After adjustment, the odds of seeing an AHP were significantly increased with older age (odds ratio [OR] = 1.02, 95% CI 1.01 to 1.02) and female sex (OR = 1.81, 95% CI 1.48 to 2.22). Compared with patients in the highest income quintile, patients in the lowest (OR = 1.33, 95% CI 1.02 to 1.72) and fourth (OR = 1.88, 95% CI 1.33 to 2.66) income quintiles had significantly higher odds of seeing AHPs. Conclusion Within an academic FHT, lower-income patients were more likely to use allied health services, suggesting equitable allocation of resources. We encourage other FHTs to similarly assess their allied health resource allocation as an important outcome for investments in Ontario FHTs.

  5. Using Socioeconomic Data to Calibrate Loss Estimates

    NASA Astrophysics Data System (ADS)

    Holliday, J. R.; Rundle, J. B.

    2013-12-01

    One of the loftier goals in seismic hazard analysis is the creation of an end-to-end earthquake prediction system: a "rupture to rafters" work flow that takes a prediction of fault rupture, propagates it with a ground shaking model, and outputs a damage or loss profile at a given location. So far, the initial prediction of an earthquake rupture (either as a point source or a fault system) has proven to be the most difficult and least solved step in this chain. However, this may soon change. The Collaboratory for the Study of Earthquake Predictability (CSEP) has amassed a suite of earthquake source models for assorted testing regions worldwide. These models are capable of providing rate-based forecasts for earthquake (point) sources over a range of time horizons. Furthermore, these rate forecasts can be easily refined into probabilistic source forecasts. While it's still difficult to fully assess the "goodness" of each of these models, progress is being made: new evaluation procedures are being devised and earthquake statistics continue to accumulate. The scientific community appears to be heading towards a better understanding of rupture predictability. Ground shaking mechanics are better understood, and many different sophisticated models exists. While these models tend to be computationally expensive and often regionally specific, they do a good job at matching empirical data. It is perhaps time to start addressing the third step in the seismic hazard prediction system. We present a model for rapid economic loss estimation using ground motion (PGA or PGV) and socioeconomic measures as its input. We show that the model can be calibrated on a global scale and applied worldwide. We also suggest how the model can be improved and generalized to non-seismic natural disasters such as hurricane and severe wind storms.

  6. Commercial Web Site Links.

    ERIC Educational Resources Information Center

    Thelwall, Mike

    2001-01-01

    Discusses business use of the Web and related search engine design issues as well as research on general and academic links before reporting on a survey of the links published by a collection of business Web sites. Results indicate around 66% of Web sites do carry external links, most of which are targeted at a specific purpose, but about 17%…

  7. 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),...

  8. Gardening's Socioeconomic Impacts: Community Gardening in an Urban Setting.

    ERIC Educational Resources Information Center

    Patel, Ishwarbhai C.

    1991-01-01

    Discusses a survey of 178 gardeners from Newark, New Jersey, and describes Extension's role in improving the life quality and socioeconomic well-being of individuals, families, and neighborhoods through community gardening in an urban environment. (Author)

  9. School Socioeconomic Composition and Adolescent Sexual Initiation in Malawi.

    PubMed

    Kim, Jinho

    2015-09-01

    Numerous studies have documented the determinants of sexual behavior among adolescents in less-developed countries, yet 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 2011-13, 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 initiation of sexual activity, independent of other important features of schools and individual-level characteristics. This study also finds that the association between school socioeconomic composition and sexual activity is statistically significant among male adolescents but not female adolescents, suggesting that schools' socioeconomic contexts may be more relevant to male adolescents' initiation of sexual activity. PMID:26347090

  10. Effects of parental socio-economic conditions on facial attractiveness.

    PubMed

    Huber, Susanne; Fieder, Martin

    2014-01-01

    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. PMID:25548886

  11. No socioeconomic inequalities in ovarian cancer survival within two randomised clinical trials

    PubMed Central

    Abdel-Rahman, M E; Butler, J; Sydes, M R; Parmar, M K B; Gordon, E; Harper, P; Williams, C; Crook, A; Sandercock, J; Swart, A M; Rachet, B; Coleman, M P

    2014-01-01

    Background: Ovarian cancer is the leading cause of death among cancers of the female genital tract, with poor outcomes despite chemotherapy. There was a persistent socioeconomic gradient in 1-year survival in England and Wales for more than 3 decades (1971–2001). Inequalities in 5-year survival persisted for more than 20 years but have been smaller for women diagnosed around 2000. We explored one possible explanation. Methods: We analysed data on 1406 women diagnosed with ovarian cancer during 1991–1998 and recruited to one of two randomised clinical trials. In the second International Collaborative Ovarian Neoplasm (ICON2) trial, women diagnosed between 1991 and 1996 were randomised to receive either the three-drug combination cyclophosphamide, doxorubicin and cisplatin (CAP) or single-agent carboplatin given at optimal dose. In the ICON3 trial, women diagnosed during 1995–1998 were randomised to receive either the same treatments as ICON2, or paclitaxel plus carboplatin. Relative survival at 1, 5 and 10 years was estimated for women in five categories of socioeconomic deprivation. The excess hazard of death over and above background mortality was estimated by fitting multivariable regression models with Poisson error structure and a dedicated link function in a generalised linear model framework, adjusting for the duration of follow-up and the confounding effects of age, Federation of Gynecology and Obstetrics (FIGO) stage and calendar period. Results: Unlike women with ovarian cancer in the general population, no statistically significant socioeconomic gradient was seen for women with ovarian cancer treated in the two randomised controlled trials. The deprivation gap in 1-year relative survival in the general population was statistically significant at −6.7% (95% CI (−8.1, −5.3)), compared with −3.6% (95% CI (−10.4, +3.2)) in the trial population. Conclusions: Although ovarian cancer survival is significantly lower among poor women than rich

  12. Oral Narrative Skills: Explaining the Language-Emergent Literacy Link by Race/Ethnicity and SES

    ERIC Educational Resources Information Center

    Gardner-Neblett, Nicole; Iruka, Iheoma U.

    2015-01-01

    Although children's early language skills have been found to predict literacy outcomes, little is known about the role of preschool oral narrative skills in the pathway between language and emergent literacy or how these associations differ by race/ethnicity and socioeconomic status. The current study uses the Early Childhood Longitudinal Study to…

  13. Sleep in adolescents of different socioeconomic status: a systematic review

    PubMed Central

    Felden, Érico Pereira Gomes; Leite, Carina Raffs; Rebelatto, Cleber Fernando; Andrade, Rubian Diego; Beltrame, Thais Silva

    2015-01-01

    Objective: To analyze the sleep characteristics in adolescents from different socioeconomic levels. Data source: Original studies found in the MEDLINE/PubMed and SciELO databases without language and period restrictions that analyzed associations between sleep variables and socioeconomic indicators. The initial search resulted in 99 articles. After reading the titles and abstracts and following inclusion and exclusion criteria, 12 articles with outcomes that included associations between sleep variables (disorders, duration, quality) and socioeconomic status (ethnicity, family income, and social status) were analyzed. Data synthesis: The studies associating sleep with socioeconomic variables are recent, published mainly after the year 2000. Half of the selected studies were performed with young Americans, and only one with Brazilian adolescents. Regarding ethnic differences, the studies do not have uniform conclusions. The main associations found were between sleep variables and family income or parental educational level, showing a trend among poor, low social status adolescents to manifest low duration, poor quality of sleeping patterns. Conclusions: The study found an association between socioeconomic indicators and quality of sleep in adolescents. Low socioeconomic status reflects a worse subjective perception of sleep quality, shorter duration, and greater daytime sleepiness. Considering the influence of sleep on physical and cognitive development and on the learning capacity of young individuals, the literature on the subject is scarce. There is a need for further research on sleep in different realities of the Brazilian population. PMID:26298657

  14. Molecular genetic contributions to socioeconomic status and intelligence.

    PubMed

    Marioni, Riccardo E; Davies, Gail; Hayward, Caroline; Liewald, Dave; Kerr, Shona M; Campbell, Archie; Luciano, Michelle; Smith, Blair H; Padmanabhan, Sandosh; Hocking, Lynne J; Hastie, Nicholas D; Wright, Alan F; Porteous, David J; Visscher, Peter M; Deary, Ian J

    2014-05-01

    Education, socioeconomic status, and intelligence are commonly used as predictors of health outcomes, social environment, and mortality. Education and socioeconomic status are typically viewed as environmental variables although both correlate with intelligence, which has a substantial genetic basis. Using data from 6815 unrelated subjects from the Generation Scotland study, we examined the genetic contributions to these variables and their genetic correlations. Subjects underwent genome-wide testing for common single nucleotide polymorphisms (SNPs). DNA-derived heritability estimates and genetic correlations were calculated using the 'Genome-wide Complex Trait Analyses' (GCTA) procedures. 21% of the variation in education, 18% of the variation in socioeconomic status, and 29% of the variation in general cognitive ability was explained by variation in common SNPs (SEs ~ 5%). The SNP-based genetic correlations of education and socioeconomic status with general intelligence were 0.95 (SE 0.13) and 0.26 (0.16), respectively. There are genetic contributions to intelligence and education with near-complete overlap between common additive SNP effects on these traits (genetic correlation ~ 1). Genetic influences on socioeconomic status are also associated with the genetic foundations of intelligence. The results are also compatible with substantial environmental contributions to socioeconomic status. PMID:24944428

  15. Socioeconomic implications of AIDS in developing countries.

    PubMed

    Armstrong, J

    1991-12-01

    The author succinctly presents the socioeconomic impact of AIDs in developing countries in terms of demographic effects; economic impact; and the impact on the formal sector, agriculture, human capital, health, food and nutrition, and women and children. The answer to what can be done is directed to policymakers. First, prevention, which has been urged by WHO, is necessary even in areas sexual behavior. Knowledge is not enough. The use of condoms and treatment of sexually transmitted diseases helps; i.e., Thailand's well established and highly visible program. Blood screening is needed as well as the use of protective medical garments (gloves) and clean syringes. The 2nd approach is to concentrate on designing measures to ameliorate the consequences of the HIV infection. Such strategies may involve providing school fees for orphans, introducing and providing labor saving technology, and disseminating prevention messages. The effort should involve cooperative effort between government, nongovernmental and community organizations. Governments must acknowledge the seriousness of the problem and take action. The donor community is faced with the challenge to identify areas of comparative expertise and coordinate approaches. Without such undertakings, the decline in economic and social progress in developing countries and human tragedy will ensue. WHO estimates that in 1991 9 million adults and 1 million children are HIV infected worldwide, of which 80% are in developing countries. Prior focus on the human toll and the strain on national health care systems obfuscates the present threat to economic and social systems. AIDs victims are young and economically productive adults. AIDs has been difficult to model because of the immunological effect, the long incubation period, and the sexual mode of transmission. The epidemic has spread the quickest in sub Saharan Africa, which accounts for 66% of infection world wide. It is expected that by 2000 increase in AIDs cases in

  16. The creation of reasonable projections toward sustainable development considering the climate and socioeconomic changes in the Pacific Islands

    NASA Astrophysics Data System (ADS)

    Watanabe, S.; Iida, A.; Nakatani, J.; Noda, K.; Take, M.; Nakamura, S.

    2015-12-01

    The impacts of climate and socioeconomic change in the future are important factors to consider when discussing the issues of sustainable development in the Pacific Islands, since their impacts here are relatively large compared to those in other regions due to the severe limitation of internal resources and the external dependency of the life essentials. The tourism industry is the key driving force behind the economic growth in island region and it is promoted by the environmental attractions. This study constructs scenarios that foresees the effects of these changes and assesses the subsequent impact on both the local community and the tourism industry. In this study, the scenarios have been developed based on the representative concentration pathways (RCPs) and the shared socioeconomic pathways (SSPs). The progress of climate change was expected to affect the attraction of tourists as well as resources availability and food production. The difference of SSPs was expected to affect the quality of life in the local society and the quantity and/or the quality of tourism. A downscale and bias-correction using a local dataset was applied to assess the impacts of climate change, and the relationships between GDP, population, and estimated land availability in the current situation were applied to assess the impact of socioeconomic change. As case studies, the scenarios were constructed to assess the impacts in the Republic of Palau and Ishigaki Island, Japan. Both are typical islands where tourism is the main industry. The situation of environmental resources, local society, and tourism under changing climate and socioeconomic conditions was assessed using these scenarios. The creation of reasonable projections under appropriate scenarios can contribute to sustainable development not only in these islands but also in most Pacific Islands.

  17. Functional and ultrastructural neuroanatomy of interactive intratectal/tectonigral mesencephalic opioid inhibitory links and nigrotectal GABAergic pathways: involvement of GABAA and mu1-opioid receptors in the modulation of panic-like reactions elicited by electrical stimulation of the dorsal midbrain.

    PubMed

    Ribeiro, S J; Ciscato, J G; de Oliveira, R; de Oliveira, R C; D'Angelo-Dias, R; Carvalho, A D; Felippotti, T T; Rebouças, E C C; Castellan-Baldan, L; Hoffmann, A; Corrêa, S A L; Moreira, J E; Coimbra, N C

    2005-12-01

    In the present study, the functional neuroanatomy of nigrotectal-tectonigral pathways as well as the effects of central administration of opioid antagonists on aversive stimuli-induced responses elicited by electrical stimulation of the midbrain tectum were determined. Central microinjections of naloxonazine, a selective mu(1)-opiod receptor antagonist, in the mesencephalic tectum (MT) caused a significant increase in the escape thresholds elicited by local electrical stimulation. Furthermore, either naltrexone or naloxonazine microinjected in the substantia nigra, pars reticulata (SNpr), caused a significant increase in the defensive thresholds elicited by electrical stimulation of the continuum comprised by dorsolateral aspects of the periaqueductal gray matter (dlPAG) and deep layers of the superior colliculus (dlSC), as compared with controls. These findings suggest an opioid modulation of GABAergic inhibitory inputs controlling the defensive behavior elicited by MT stimulation, in cranial aspects. In fact, iontophoretic microinjections of the neurotracer biodextran into the SNpr, a mesencephalic structure rich in GABA-containing neurons, show outputs to neural substrate of the dlSC/dlPAG involved with the generation and organization of fear- and panic-like reactions. Neurochemical lesion of the nigrotectal pathways increased the sensitivity of the MT to electrical (at alertness, freezing and escape thresholds) and chemical (blockade of GABA(A) receptors) stimulation, suggesting a tonic modulatory effect of the nigrotectal GABAergic outputs on the neural networks of the MT involved with the organization of the defensive behavior and panic-like reactions. Labeled neurons of the midbrain tectum send inputs with varicosities to ipsi and contralateral dlSC/dlPAG and ipsilateral substantia nigra, pars reticulata and compacta, in which the anterograde and retrograde tracing from a single injection indicates that the substantia nigra has reciprocal connections with

  18. Adverse outcome pathway (AOP) development I: Strategies and principles

    EPA Science Inventory

    An adverse outcome pathway (AOP) is a conceptual framework that organizes existing knowledge concerning biologically plausible, and empirically-supported, links between molecular-level perturbation of a biological system and an adverse outcome at a level of biological organizatio...

  19. Understanding the Positive Role of Neighborhood Socioeconomic Advantage in Achievement: The Contribution of the Home, Child Care and School Environments

    PubMed Central

    Dupéré, Véronique; Leventhal, Tama; Crosnoe, Robert; Dion, Éric

    2011-01-01

    The goal of this study was to examine the mechanisms underlying associations between neighborhood socioeconomic advantage and children’s achievement trajectories between 54 months and 15 years old. Results of hierarchical linear growth models based on a diverse sample of 1,364 children indicate that neighborhood socioeconomic advantage was non-linearly associated with youths’ initial vocabulary and reading scores, such that the presence of educated, affluent professionals in the neighborhood had a favorable association with children’s achievement among those in less advantaged neighborhoods until it leveled off at moderate levels of advantage. A similar tendency was observed for math achievement. The quality of the home and child care environments as well as school advantage partially explained these associations. The findings suggest that multiple environments need to be considered simultaneously for understanding neighborhood-achievement links. PMID:20822235

  20. Movin' on Up: Socioeconomic Mobility and the Risk of Delivering a Small-for-Gestational Age Infant.

    PubMed

    Slaughter-Acey, Jaime C; Holzman, Claudia; Calloway, Danuelle; Tian, Yan

    2016-03-01

    Objective Poor fetal growth is associated with increased rates of adverse health outcomes in children and adults. The social determinants of poor fetal growth are not well understood. Using multiple socioeconomic indicators measured at the individual level, this study examined changes in maternal socioeconomic position (SEP) from childhood to adulthood (socioeconomic mobility) in relation to poor fetal growth in offspring. Methods Data were from the Pregnancy Outcomes and Community Health Study (September 1998-June 2004) that enrolled women in mid-pregnancy from 52 clinics in five Michigan communities (2463 women: 1824 non-Hispanic White, 639 non-Hispanic Black). Fetal growth was defined by birthweight-for-gestational age percentiles; infants with birthweight-for-gestational age <10th percentile were referred to as small-for-gestational age (SGA). In logistic regression models, mothers whose SEP changed from childhood to adulthood were compared to two reference groups, the socioeconomic group they left and the group they joined. Results Approximately, 8.2 % of women (non-Hispanic White: 6.3 %, non-Hispanic Black: 13.9 %) delivered an SGA infant. Upward mobility was associated with decreased risk of delivering an SGA infant. Overall, the SGA adjusted-odds ratio was 0.34 [95 % confidence interval (CI) 0.17-0.69] for women who moved from lower to middle/upper versus static lower class, and 0.44 (CI 0.28-1.04) for women who moved from middle to upper versus static middle class. There were no significant differences in SGA risk when women were compared to the SEP group they joined. Conclusions Our findings support a link between mother's socioeconomic mobility and SGA offspring. Policies that allow for the redistribution or reinvestment of resources may reduce disparities in rates of SGA births. PMID:26541591

  1. Disentangling Adolescent Pathways of Sexual Risk Taking

    ERIC Educational Resources Information Center

    Brookmeyer, Kathryn A.; Henrich, Christopher C.

    2009-01-01

    Using data from the National Longitudinal Survey of Youth, the authors aimed to describe the pathways of risk within sexual risk taking, alcohol use, and delinquency, and then identify how the trajectory of sexual risk is linked to alcohol use and delinquency. Risk trajectories were measured with adolescents aged 15-24 years (N = 1,778). Using…

  2. Adverse outcome pathway (AOP) development and evaluation

    EPA Science Inventory

    The Adverse Outcome Pathway provides a construct for assembling mechanistic information at different levels of biological organization in a form designed to support regulatory decision making. In particular, it frames the link between molecular and cellular events that can be mea...

  3. Socioeconomic Inequalities in Unintended Pregnancy and Abortion Decision

    PubMed Central

    Font-Ribera, Laia; Salvador, Joaquín; Borrell, Carme

    2007-01-01

    Pregnancy planning allows women to better control their life trajectory and contributes to the future child’s health and development. Many studies that have analyzed socioeconomic inequalities in unintended pregnancy only took into account those pregnancies ending in births. Few of them that analyzed unintended pregnancy, including both induced abortion and births, and its socioeconomic determinants, concluded that unintended pregnancy is more frequent in young, poor, or unmarried women. These inequalities have been poorly studied in Europe, especially in the southern European context. The aim of the present study is to describe socioeconomic inequalities in unintended pregnancy and in abortion decision in Barcelona, Spain. The major findings are that unintended pregnancies accounted for 41% of total pregnancy and of these, 60% ended in abortion. From all pregnancies, the proportion of induced abortion reached 25.6%. Compared to women with university studies, those with primary education uncompleted had more unintended pregnancies (OR = 7.22). When facing an unintended pregnancy, women of lower socioeconomic position are more likely to choose induced abortion, although this is not the case among young or single women. This study reveals deep socioeconomic inequalities in unintended pregnancies and abortion decision in Barcelona, Spain, where the birth rate is very low and the abortion rate is rising. Women in low socioeconomic positions have many more unintended pregnancies than better educated women. Except for young or single women, the lower the socioeconomic position, the higher the proportion of women who choose an induced abortion when facing an unintended pregnancy. PMID:18038210

  4. Socioeconomic differences in the burden of disease in Sweden.

    PubMed Central

    Ljung, Rickard; Peterson, Stefan; Hallqvist, Johan; Heimerson, Inger; Diderichsen, Finn

    2005-01-01

    OBJECTIVE: We sought to analyse how much of the total burden of disease in Sweden, measured in disability-adjusted life years (DALYs), is a result of inequalities in health between socioeconomic groups. We also sought to determine how this unequal burden is distributed across different disease groups and socioeconomic groups. METHODS: Our analysis used data from the Swedish Burden of Disease Study. We studied all Swedish men and women in three age groups (15-44, 45-64, 65-84) and five major socioeconomic groups. The 18 disease and injury groups that contributed to 65% of the total burden of disease were analysed using attributable fractions and the slope index of inequality and the relative index of inequality. FINDINGS: About 30% of the burden of disease among women and 37% of the burden among men is a differential burden resulting from socioeconomic inequalities in health. A large part of this unequally distributed burden falls on unskilled manual workers. The largest contributors to inequalities in health for women are ischaemic heart disease, depression and neurosis, and stroke. For men, the largest contributors are ischaemic heart disease, alcohol addiction and self-inflicted injuries. CONCLUSION: This is the first study to use socioeconomic differences, measured by socioeconomic position, to assess the burden of disease using DALYs. We found that in Sweden one-third of the burden of the diseases we studied is unequally distributed. Studies of socioeconomic inequalities in the burden of disease that take both mortality and morbidity into account can help policy-makers understand the magnitude of inequalities in health for different disease groups. PMID:15744401

  5. Linking to the Future

    NASA Astrophysics Data System (ADS)

    Moore, John W.

    1999-09-01

    my copy of JCE in the mail each month, and I expect you do too. I can glance at the cover to get an overview of an issue's content, and I usually am enticed inside by intriguing cover art. I can scan the table of contents to find articles I want to read, or I can just browse through the issue to see what looks interesting. Usually the editors have juxtaposed related articles so that I often find a small treasure trove. The printed Journal is quite portable and can be read in a car or airplane. It will last a long time, and until the paper deteriorates, I will never have a problem reading back issues. I have almost every issue from the first day I subscribed and have even added some older ones from collections of retired colleagues who no longer had shelf space for them. I certainly would not want to give up my printed copies, and I want to keep getting them. I find that JCE Online provides a different kind of resource that is equally valuable. It contains more information, and information that is more appropriate in electronic form. It links related ideas into a much more complex web of information than is possible in print. And it opens pathways to lots of information that is not part of JCE but resides elsewhere. Using this issue as an example, let's take a tour of what JCE Online can do.

    • Point your Web browser to http://jchemed.chem.wisc.edu
    • Click on Journal and then on Current Issue (unless September 1999 is no longer the current issue, in which case you will find it in Past Issues).
    • In the table of contents, find the article "UV Catalysis, Cyanotype Photography, and Sunscreens". Click on the title.
    • When the abstract appears, click on Full Text (PDF) to see the article, just as it appears on page 1199 in this issue.
    • When you are prompted, enter the name and subscriber number from your address label.
    • At the end of the article you will find that supplementary materials are available (including a procedure for testing

    • Socioeconomic Status, Daily Affective and Social Experiences, and Inflammation during Adolescence

      PubMed Central

      Chiang, Jessica J.; Bower, Julienne E.; Almeida, David M.; Irwin, Michael R.; Seeman, Teresa E.; Fuligni, Andrew J.

      2015-01-01

      Objective To assess the relation between socioeconomic status (SES) and inflammation during adolescence and determine whether daily affective and social experiences across a 15-day period mediate this relation. Methods Adolescents (n = 316) completed daily diary reports of positive affect, negative affect, and negative social interactions for 15 days and provided whole blood spot samples for the assessment of C-reactive protein (CRP). Parents provided information on SES, including the highest level of education they and their spouses completed and household income. Results Lower parent education was associated with higher levels of adolescent CRP, controlling for age, gender, ethnicity, and body mass index (β = −.12; p = .031). Mean daily positive affect, negative affect, and negative social interactions were examined as potential mediators of this association. In these models, parent education was no longer associated with adolescent CRP (β = −.09; p = .12), and only positive affect was related to CRP (β = −.12; p = .025). Bootstrapping confirmed the mediating role of positive affect (indirect effect = −.015, 95% CI = [−.038, −.002]). Conclusions Adolescents with less educated parents tended to have higher levels of CRP, which may be explained by their lower levels of positive affect. Findings suggest that a lack of positive affect may be a pathway by which SES confers early risk for poor health in adulthood. It is possible that adolescents who display positive affect during daily life in circumstances of relatively adverse socioeconomic circumstances may have better health outcomes related to lower inflammatory factors. PMID:25829237

    • Evaluation of the Interactionist Model of Socioeconomic Status and Problem Behavior: A Developmental Cascade across Generations

      PubMed Central

      Martin, Monica J.; Conger, Rand D.; Schofield, Thomas J.; Dogan, Shannon J.; Widaman, Keith F.; Donnellan, M. Brent; Neppl, Tricia K.

      2010-01-01

      The current multigenerational study evaluates the utility of the Interactionist Model of Socioeconomic Influence on human development (IMSI) in explaining problem behaviors across generations. The IMSI proposes that the association between socioeconomic status (SES) and human development involves a dynamic interplay that includes both social causation (SES influences human development) and social selection (individual characteristics affect SES). As part of the developmental cascade proposed by the IMSI, the findings from this investigation showed that G1 adolescent problem behavior predicted later G1 SES, family stress, and parental emotional investments, as well as the next generation of children's problem behavior. These results are consistent with a social selection view. Consistent with the social causation perspective, we found a significant relation between G1 SES and family stress, and in turn, family stress predicted G2 problem behavior. Finally, G1 adult SES predicted both material and emotional investments in the G2 child. In turn, emotional investments predicted G2 problem behavior, as did material investments. Some of the predicted pathways varied by G1 parent gender. The results are consistent with the view that processes of both social selection and social causation account for the association between SES and human development. PMID:20576188

    • Effects of Socioeconomic Status on Nutrition in Asia and Future Nutrition Policy Studies.

      PubMed

      Murayama, Nobuko

      2015-01-01

      Evidence of health disparities has been reported around the world. One of the intermediate factors between socioeconomic status (SES) and health is nutrition. Many studies reported socioeconomically disadvantaged people had more risk of obesity and lifestyle-related diseases than others in western society. Micronutrient intake affected by SES, but little evidence indicates that SES affects either energy intake or the macronutrient composition of the diet in western countries. In contrast, there is not enough evidence of a consistent relationship between SES and nutrition in Asian countries at present. The present status of nutrition disparities in Asia is considered to vary by economic level of the country. For developing countries in Asia, India and Vietnam, SES associates with BMI positively in women. For relatively developed countries in Asia, Korea and Japan, SES associates with BMI negatively in women. Low SES groups consume more carbohydrate, and less protein and fat, so not only micronutrient but also macronutrient intake is affected by SES both in developing and in developed Asian countries. There are some studies on the pathway from SES to diet/nutrition. The association between low SES and obesity may be mediated, in part, by the low cost of energy-dense foods, concern about food price and dietary knowledge. Nutrition policy research is required to reduce nutrition disparities in Asia. We need a collaborative study of the impact of potential political options on diet and on health with other academic fields. PMID:26598891

    • The prospective association of socioeconomic status with C-reactive protein levels in the CARDIA study.

      PubMed

      Deverts, Denise Janicki; Cohen, Sheldon; Kalra, Preety; Matthews, Karen A

      2012-10-01

      Better health is a well-documented benefit of having a higher socioeconomic status (SES). Inflammation may be one pathway through which SES influences health. Using 2658 participants in the Coronary Artery Risk Development in Young Adults (CARDIA) Study, we examine whether two measures of SES assessed at baseline (mean age, 32 ± 4 years)-years of education and household income-predict change in C-reactive protein (CRP) concentrations over the course of 13 years. We also examine whether four health-related behaviors-smoking, fruit and vegetable consumption, physical activity, and alcohol consumption-mediate the prospective association of SES with CRP. Both higher education and household income predicted smaller increases in CRP over the 13 years of follow-up independent of age, sex, race, CARDIA center, body mass, medical diagnoses, medications, and hormone use (among women). Associations did not differ by race or sex. When examined in separate analyses, smoking and fruit and vegetable intake each accounted for a significant proportion of the respective effects of education and household income on CRP change, and physical activity a significant proportion of the effect of household income. These findings suggest that poor health behaviors among persons of lower socioeconomic status can have long-term effects on inflammation. PMID:22884413

    • Hypercholesterolemia links hematopoiesis with atherosclerosis.

      PubMed

      Soehnlein, Oliver; Swirski, Filip K

      2013-03-01

      Atherosclerosis is characterized by the progressive accumulation of lipids and leukocytes in the arterial wall. Leukocytes such as macrophages accumulate oxidized lipoproteins in the growing atheromata and give rise to foam cells, which can then contribute to the necrotic core of lesions. Lipids and leukocytes also interact in other important ways. In experimental models, systemic hypercholesterolemia is associated with severe neutrophilia and monocytosis. Recent evidence indicates that cholesterol-sensing pathways control the proliferation of hematopoietic stem-cell progenitors. Here we review some of the studies that are forging this particular link between metabolism and inflammation, and propose several strategies that could target this axis for the treatment of cardiovascular disease. PMID:23228326

    • Relationship between Statin Utilization and Socioeconomic Deprivation in Hungary

      PubMed Central

      Boruzs, Klára; Juhász, Attila; Nagy, Csilla; Ádány, Róza; Bíró, Klára

      2016-01-01

      The risk of premature mortality caused by cardiovascular diseases (CVDs) is approximately three times higher in the Central Eastern European region than in high income European countries, which suggests a lack and/or ineffectiveness of preventive interventions against CVDs. The aim of the present study was to provide data on the relationship between premature CVD mortality, statin utilization as a preventive medication and socioeconomic deprivation at the district level in Hungary. As a conceptually new approach, the prescription of statins, the prescription redemption and the ratio between redemption and prescription rates were also investigated. The number of prescriptions for statins and the number of redeemed statin prescriptions were obtained from the National Health Insurance Fund Administration of Hungary for each primary healthcare practice for the entire year of 2012. The data were aggregated at the district level. To define the frequency of prescription and of redemption, the denominator was the number of the 40+-year-old population adjusted by the rates of 60+-year-old population of the district. The standardized mortality rates, frequency of statin prescriptions, redeemed statin prescriptions, and ratios for compliance in relation to the national average were mapped using the “disease mapping” option, and their association with deprivation (tertile of deprivation index as a district-based categorical covariate) was defined using the risk analysis capabilities within the Rapid Inquiry Facility. The risk analysis showed a significant positive association between deprivation and the relative risk of premature cardiovascular mortality, and a reverse J-shaped association between the relative frequency of statin prescriptions and deprivation. Districts with the highest deprivation showed a low relative frequency of statin prescriptions; however, significantly higher primary compliance (redemption) was observed in districts with the highest deprivation

    • Neighborhood Socioeconomic Disadvantage and 30 Day Rehospitalizations: An Analysis of Medicare Data

      PubMed Central

      Kind, Amy JH; Jencks, Steve; Brock, Jane; Yu, Menggang; Bartels, Christie; Ehlenbach, William; Greenberg, Caprice; Smith, Maureen

      2014-01-01

      Background Measures of socioeconomic disadvantage may enable improved targeting of programs to prevent rehospitalizations, but obtaining such information directly from patients can be difficult. Measures of US neighborhood socioeconomic disadvantage are more readily available, although rarely employed clinically. Objective To evaluate the association between neighborhood socioeconomic disadvantage at the census block-group level, as measured by Singh’s validated Area Deprivation Index (ADI), and 30-day rehospitalization. Design Retrospective cohort study Setting United States Patients Random 5% national sample of fee-for-service Medicare patients discharged with congestive heart failure, pneumonia or myocardial infarction, 2004–2009 (N = 255,744) Measurements 30-day rehospitalizations. Medicare data were linked to 2000 Census data to construct an ADI for each patient’s census block-group, which were then sorted into percentiles by increasing ADI. Relationships between neighborhood ADI grouping and rehospitalization were evaluated using multivariate logistic regression models, controlling for patient sociodemographics, comorbidities/severity, and index hospital characteristics. Results The 30-day rehospitalization rate did not vary significantly across the least disadvantaged 85% of neighborhoods, which had an average rehospitalization rate=21%. However, within the most disadvantaged 15% of neighborhoods, rehospitalization rates rose from 22% to 27% with worsening ADI. This relationship persisted after full adjustment, with the most disadvantaged neighborhoods having a rehospitalization risk (adjusted risk ratio = 1.09, confidence interval 1.05–1.12) similar to that of chronic pulmonary disease (1.06, 1.04–1.08) and greater than that of diabetes (0.95, 0.94–0.97). Limitations No direct markers of care quality, access Conclusions Residence within a disadvantaged US neighborhood is a rehospitalization predictor of magnitude similar to chronic pulmonary

    • The Great 2008 Chinese ice storm, its socioeconomic-ecological impact, and sustainability lessons learned

      SciTech Connect

      Zhou, Dr. Benzhi; Gu, Lianhong; Ding, Yihui; Wu, Zhongmin; Shao, Lan; An, Yanfei; Cao, Yonghui; Duan, Aiguo; Kong, Weijian; Li, Changzhu; Li, Zhengcai; Sun, Honggang; Wang, Shengkun; Wang, Xiaoming; Wang, Xu; Yang, Xiaosheng; Yu, Mukui; Zeng, Bingshan

      2011-01-01

      . Extreme events often expose vulnerabilities of socioeconomic infrastructures and point to directions of much-needed policy change. Integrated impact assessment of such events can lead to finding of sustainability principles. Southern and central China has for decades been undergoing a breakneck pace of socioeconomic development. In early 2008, a massive ice storm struck this region, immobilizing millions of people. The storm was a consequence of sustained convergence between tropical maritime and continental polar air masses, caused by an anomalously stable atmospheric general circulation pattern in both low and high latitudes. Successive waves of freezing rain occurred during a month period, coating southern and central China with a layer of ice 50 to 160mm in thickness. We conducted an integrated impact assessment of this event to determine whether and how the context of socioeconomic and human-disturbed natural systems may affect the transition of natural events into human disasters. We found: 1) without contingency plans, advanced technologies dependent on interrelated energy supplies can create worse problems during extreme events, 2) the weakest link in disaster response lies between science and decision making, 3) biodiversity is a form of long-term insurance for sustainable forestry against extreme events, 4) sustainable extraction of non-timber goods and services is essential to risk planning for extreme events in forest resources use, 5) extreme events can cause food shortage directly by destroying crops and indirectly by disrupting food distribution channels, 6) concentrated economic development increases societal vulnerability to extreme events, and 7) formalized institutional mechanisms are needed to ensure that unexpected opportunities to learn lessons from weather disasters are not lost in distracting circumstances.

    • Relationship between diet quality and cognition depends on socioeconomic position in healthy older adults.

      PubMed

      Parrott, Matthew D; Shatenstein, Bryna; Ferland, Guylaine; Payette, Hélène; Morais, José A; Belleville, Sylvie; Kergoat, Marie-Jeanne; Gaudreau, Pierrette; Greenwood, Carol E

      2013-11-01

      Both diet quality and socioeconomic position (SEP) have been linked to age-related cognitive changes, but there is little understanding of how the socioeconomic context of dietary intake may shape its cognitive impact. We examined whether equal adherence to "prudent" and "Western" dietary patterns, identified by principal components analysis, was associated with global cognitive function [Modified Mini-Mental State Examination (3MS)] in independently living older adults with different SEPs (aged 68-84 y; n = 1099). The interaction of dietary pattern adherence with household income, educational attainment, occupational prestige, and a composite indicator of SEP combining all 3 was examined in multiple-adjusted mixed models over 3 y of follow-up in participants of the NuAge study (Quebec Longitudinal Study on Nutrition and Successful Aging). Adherence to the prudent pattern (vegetables, fruits, fish, poultry, and lower-fat dairy products) was related to higher 3MS scores at recruitment only in the upper categories of income [parameter estimate (B): 0.56; 95% CI: 0.11, 1.01], education (B: 0.44; 95% CI: 0.080, 0.80), or composite SEP (B: 0.37; 95% CI: 0.045, 0.70). High prudent pattern adherence was associated with less cognitive decline only in those with low composite SEP (B: 0.25; 95% CI: 0.0094, 0.50). Conversely, adherence to the Western pattern (meats, potatoes, processed foods, and higher-fat dairy products) was associated with more cognitive decline (B: -0.23; 95% CI: -0.43, -0.032) only in those with low educational attainment. In summary, among individuals with equivalent diet quality, the magnitude and characteristics of the diet-cognition relationship depended on their socioeconomic circumstances. These results suggest that interventions promoting retention of cognitive function through improved diet quality would provide maximum benefit to those with relatively low SEP. PMID:23986363

    • Socioeconomic Status and Internalizing Symptoms in Chilean Children: Does Reserve Capacity Matter?

      PubMed Central

      Martinez, Suzanna M; Castillo, Marcela; Lozoff, Betsy; Gahagan, Sheila

      2016-01-01

      Informed by the reserve capacity model, we examined pathways between socioeconomic status (SES) and internalizing symptoms (IS) in 1119 Chilean 10-year-olds. Mediators included parental disciplinary style and reserve capacity resources (RCR), namely home environment, parent-child engagement, and self-esteem, and conduct problems. Using structural equation modeling, the model was stratified by gender. For boys, the SES-IS relationship was mediated by the home environment and parental disciplinary style. For girls, the SES-IS relationship was mediated by the home environment, parent-child engagement, self-esteem, and conduct problems. Findings suggest different RCR may protect against IS in a sample of Chilean children. PMID:27123471

    • Variation in incidence of breast, lung and cervical cancer and malignant melanoma of skin by socioeconomic group in England

      PubMed Central

      Shack, Lorraine; Jordan, Catrina; Thomson, Catherine S; Mak, Vivian; Møller, Henrik

      2008-01-01

      Background Cancer incidence varies by socioeconomic group and these variations have been linked with environmental and lifestyle factors, differences in access to health care and health seeking behaviour. Socioeconomic variations in cancer incidence by region and age are less clearly understood but they are crucial for targeting prevention measures and health care commissioning. Methods Data were obtained from all eight English cancer registries for patients diagnosed between 1998 and 2003, for all invasive cases of female breast cancer (ICD-10 code C50), lung cancer (ICD-10 codes C33-C34), cervical cancer (ICD-10 code C53), and malignant melanoma of the skin (ICD-10 code C43). Socioeconomic status was assigned to each patient based on their postcode of residence at diagnosis, using the income domain of the Index of Multiple Deprivation 2004. We analysed the socioeconomic variations in the incidence of breast, lung and cervical cancer and malignant melanoma of the skin for England, and regionally and by age. Results Incidence was highest for the most deprived patients for lung cancer and cervical cancer, whilst the opposite was observed for malignant melanoma and breast cancer. The difference in incidence between the most and the least deprived groups was higher for lung cancer patients aged under 65 at diagnosis than those over 65 at diagnosis, which may indicate a cohort effect. There were regional differences in the socioeconomic gradients with the gap being widest for lung and cervical cancer in the North (North East, North West and Yorkshire and Humberside) and for malignant melanoma in the East and South West. There were only modest variations in breast cancer incidence by region. If the incidence of lung and cervical cancer were decreased to that of the least deprived group it would prevent 36% of lung cancer cases in men, 38% of lung cancer cases in women and 28% of cervical cancer cases. Incidence of breast cancer and melanoma was highest in the least

    • Modelling of INTER-Linkages Between LAND Cover Pattern and Socio-Economic Factors in the Idemili River Basin of South Eastern Nigeria

      NASA Astrophysics Data System (ADS)

      Maduekwe, N. I.; Adesina, F. A.

      2014-12-01

      This study explores the inter-relationships between socio-economic factors and land cover pattern in the Idemili River Basin of South Eastern Nigeria. It is based on the concept of coupled human environment systems and focuses on the modelling of community scale relationships between critical land cover parameter and socio-demographic, economic and cultural factors in the basin. The modelling was implemented with pixel level NDVI indicators of vegetation cover density developed from NigeriaSat image with 32m resolution linked to eight indicators of socio-economic factors developed from a household survey of the basin. NDVI and socio-economic data were matched for 25 sampled localities in the basin and their relationships modelled with correlation, regression and Principal Component Analysis statistics. NDVI based image analysis showed a high level of human impact on vegetation. The Model output shows that bivariate relationships between vegetation cover dynamics and socio-demographic variables were the most significant, with R Square values > 0.60 for linear and non linear models. Vegetation cover density has high inverse correlations with population, urbanization levels and number of households in localities. Population/urbanization status of localities was also the most significant Principal Component or underlying dimension linked to spatial dynamics of vegetation cover in the basin accounting for 50% of factor variations. Relationships between vegetation cover densities and economic factors (occupational and household energy patterns) and socio-cultural factors (environmental knowledge, values and governance) were weaker and less significant. The study captured the linkages between landcover- represented by vegetation cover- and socio-economic parameters. It demonstrates that socio-economic factors are major drivers of change in the basin. Key Words: Socio-economic factors, Vegetation Cover, NDVI, Socio-ecological Systems, State Variables, South Eastern Nigeria

    • Socioeconomic Factors and Vulnerability to Outbreaks of Leptospirosis in Nicaragua

      PubMed Central

      Bacallao, Jorge; Schneider, Maria Cristina; Najera, Patricia; Aldighieri, Sylvain; Soto, Aida; Marquiño, Wilmer; Sáenz, Carlos; Jiménez, Eduardo; Moreno, Gilberto; Chávez, Octavio; Galan, Deise I.; Espinal, Marcos A.

      2014-01-01

      Leptospirosis is an epidemic-prone zoonotic disease that occurs worldwide, with more than 500,000 human cases reported annually. It is influenced by environmental and socioeconomic factors that affect the occurrence of outbreaks and the incidence of the disease. Critical areas and potential drivers for leptospirosis outbreaks have been identified in Nicaragua, where several conditions converge and create an appropriate scenario for the development of leptospirosis. The objectives of this study were to explore possible socioeconomic variables related to leptospirosis critical areas and to construct and validate a vulnerability index based on municipal socioeconomic indicators. Municipalities with lower socioeconomic status (greater unsatisfied basic needs for quality of the household and for sanitary services, and higher extreme poverty and illiteracy rates) were identified with the highest leptospirosis rates. The municipalities with highest local vulnerability index should be the priority for intervention. A distinction between risk given by environmental factors and vulnerability to risk given by socioeconomic conditions was shown as important, which also applies to the “causes of outbreaks” and “causes of cases”. PMID:25153463

    • Environmental resources of selected areas of Hawaii: Socioeconomics

      SciTech Connect

      Saulsbury, J.W.; Sorensen, B.M.; Reed, R.M.; Schexnayder, S.M.

      1995-03-01

      This report has been prepared to make available and archive the background information on socioeconomic resources collected during the preparation of the environmental impact statement (EIS) for Phases 3--4 of the Hawaii Geothermal Project (HGP) as defined by the state of Hawaii in its April 1989 proposal to Congress. The USDOE published a notice withdrawing its Notice of Intent to prepare the HGP EIS. Since the state of Hawaii is no longer pursuing or planning to pursue the HGP, DOE considers the project to be terminated. This document provides background information on socioeconomic resources in Hawaii County, with particular emphasis on the Puna District. Information is being made available for use by others in conducting future socioeconomic impact assessments in this area. this report describes existing socioeconomic resources in the areas studied and does not represent an assessment of environmental impacts. The socioeconomic resources described are primarily those that would be affected by employment and population growth associated with any future large-scale development. These resource categories are population, housing, land use, economic structure, infrastructure and public services, local government revenues and expenditures, and tourism and recreation.

    • Socioeconomic thresholds that affect use of customary fisheries management tools.

      PubMed

      Cinner, Joshua E; Sutton, Stephen G; Bond, Trevor G

      2007-12-01

      Customary forms of resource management, such as taboos, have received considerable attention as a potential basis for conservation initiatives in the Indo-Pacific. Yet little is known about how socioeconomic factors influence the ability of communities to use customary management practices and whether socioeconomic transformations within communities will weaken conservation initiatives with a customary foundation. We used a comparative approach to examine how socioeconomic factors may influence whether communities use customary fisheries management in Papua New Guinea. We examined levels of material wealth (modernization), dependence on marine resources, population, and distance to market in 15 coastal communities. We compared these socioeconomic conditions in 5 communities that used a customary method of closing their fishing ground with 10 communities that did not use this type of management. There were apparent threshold levels of dependence on marine resources, modernization, distance to markets (<16.5 km), and population (>600 people) beyond which communities did not use customary fisheries closures. Nevertheless, economic inequality, rather than mean modernization levels seemed to influence the use of closures. Our results suggest that customary management institutions are not resilient to factors such as population growth and economic modernization. If customary management is to be used as a basis for modern conservation initiatives, cross-scale institutional arrangements such as networks and bridging organizations may be required to help filter the impacts of socioeconomic transformations. PMID:18173484

  1. Simulation Models for Socioeconomic Inequalities in Health: A Systematic Review

    PubMed Central

    Speybroeck, Niko; Van Malderen, Carine; Harper, Sam; Müller, Birgit; Devleesschauwer, Brecht

    2013-01-01

    Background: The emergence and evolution of socioeconomic inequalities in health involves multiple factors interacting with each other at different levels. Simulation models are suitable for studying such complex and dynamic systems and have the ability to test the impact of policy interventions in silico. Objective: To explore how simulation models were used in the field of socioeconomic inequalities in health. Methods: An electronic search of studies assessing socioeconomic inequalities in health using a simulation model was conducted. Characteristics of the simulation models were extracted and distinct simulation approaches were identified. As an illustration, a simple agent-based model of the emergence of socioeconomic differences in alcohol abuse was developed. Results: We found 61 studies published between 1989 and 2013. Ten different simulation approaches were identified. The agent-based model illustration showed that multilevel, reciprocal and indirect effects of social determinants on health can be modeled flexibly. Discussion and Conclusions: Based on the review, we discuss the utility of using simulation models for studying health inequalities, and refer to good modeling practices for developing such models. The review and the simulation model example suggest that the use of simulation models may enhance the understanding and debate about existing and new socioeconomic inequalities of health frameworks. PMID:24192788

  2. SOCIOECONOMIC CHANGE AND HOMICIDE IN A TRANSITIONAL SOCIETY

    PubMed Central

    Pridemore, William Alex; Kim, Sang-Weon

    2008-01-01

    Durkheim argued that rapid social change would produce anomic conditions which, in turn, would lead to increases in criminal and deviant behavior. Russia provides a unique opportunity to test this theory given the large-scale fundamental socioeconomic changes occurring in the nation. Russian homicide rates more than doubled in the years following the dissolution of the Soviet Union and are now among the highest in the world. The pace and effects of the socioeconomic transition vary widely throughout Russia, however, as do rates of and changes in violent crime. In this study, we took advantage of the unique natural experiment of the collapse of the Soviet Union to examine the association between socioeconomic change and homicide. We measured the negative effects of socioeconomic change by creating an index of changes in population size, unemployment, privatization, and foreign investment. Using data from Russian regions (n = 78) and controlling for other structural covariates, regression results indicated that regions that more strongly experienced the negative effects of socioeconomic change were regions where homicide rates increased the most between 1991 and 2000. Further analysis of the individual components of this index revealed that regions with greater increases in (1) unemployment experienced greater increases in homicide rates and (2) privatization experienced smaller increases in homicide rates. PMID:19043617

  3. Environmental Resources of Selected Areas of Hawaii: Socioeconomics (DRAFT)

    SciTech Connect

    Saulsbury, J.W.; Sorensen, B.M.; Schexnayder, S.M.

    1994-06-01

    This report has been prepared to make available and archive the background information on socioeconomic resources collected during the preparation of the Environmental Impact Statement (EIS) for Phases 3 and 4 of the Hawaii Geothermal Project (HGP) as defined by the state of Hawaii in its April 1989 proposal to Congress. The U.S. Department of Energy (DOE) published a notice in the Federal Register on May 17, 1994 (Fed. Regis. 5925638), withdrawing its Notice of Intent (Fed Regis. 57:5433), of February 14, 1992, to prepare the HGPEIS. Since the state of Hawaii is no longer pursuing or planning to pursue the HGP, DOE considers the project to be terminated. This document provides background information on socioeconomic resources in Hawaii County, with particular emphasis on the Puna District (Fig. 1). Information is being made available for use by others in conducting future socioeconomic impact assessments in this area. This report describes existing socioeconomic resources in the areas studied (i.e., the affected environment) and does not represent an assessment of environmental impacts. The socioeconomic resources described are primarily those that would be affected by employment and population growth associated with any future large-scale development. These resource categories are (1) population, (2) housing, (3) land use, (4) economic structure (primarily employment and income), (5) infrastructure and public services (education, ground transportation, police and fire protection, water, wastewater, solid waste disposal, electricity, and emergency planning), (6) local government revenues and expenditures, and (7) tourism and recreation.

  4. Access to primary care for socioeconomically disadvantaged older people in rural areas: a realist review

    PubMed Central

    Ford, John A; Wong, Geoff; Jones, Andy P; Steel, Nick

    2016-01-01

    Objective The aim of this review is to identify and understand the contexts that effect access to high-quality primary care for socioeconomically disadvantaged older people in rural areas. Design A realist review. Data sources MEDLINE and EMBASE electronic databases and grey literature (from inception to December 2014). Eligibility criteria for selecting studies Broad inclusion criteria were used to allow articles which were not specific, but might be relevant to the population of interest to be considered. Studies meeting the inclusion criteria were assessed for rigour and relevance and coded for concepts relating to context, mechanism or outcome. Analysis An overarching patient pathway was generated and used as the basis to explore contexts, causal mechanisms and outcomes. Results 162 articles were included. Most were from the USA or the UK, cross-sectional in design and presented subgroup data by age, rurality or deprivation. From these studies, a patient pathway was generated which included 7 steps (problem identified, decision to seek help, actively seek help, obtain appointment, get to appointment, primary care interaction and outcome). Important contexts were stoicism, education status, expectations of ageing, financial resources, understanding the healthcare system, access to suitable transport, capacity within practice, the booking system and experience of healthcare. Prominent causal mechanisms were health literacy, perceived convenience, patient empowerment and responsiveness of the practice. Conclusions Socioeconomically disadvantaged older people in rural areas face personal, community and healthcare barriers that limit their access to primary care. Initiatives should be targeted at local contextual factors to help individuals recognise problems, feel welcome, navigate the healthcare system, book appointments easily, access appropriate transport and have sufficient time with professional staff to improve their experience of healthcare; all of which

  5. Traffic, Air Pollution, Minority and Socio-Economic Status: Addressing Inequities in Exposure and Risk

    PubMed Central

    Pratt, Gregory C.; Vadali, Monika L.; Kvale, Dorian L.; Ellickson, Kristie M.

    2015-01-01

    Higher levels of nearby traffic increase exposure to air pollution and adversely affect health outcomes. Populations with lower socio-economic status (SES) are particularly vulnerable to stressors like air pollution. We investigated cumulative exposures and risks from traffic and from MNRiskS-modeled air pollution in multiple source categories across demographic groups. Exposures and risks, especially from on-road sources, were higher than the mean for minorities and low SES populations and lower than the mean for white and high SES populations. Owning multiple vehicles and driving alone were linked to lower household exposures and risks. Those not owning a vehicle and walking or using transit had higher household exposures and risks. These results confirm for our study location that populations on the lower end of the socio-economic spectrum and minorities are disproportionately exposed to traffic and air pollution and at higher risk for adverse health outcomes. A major source of disparities appears to be the transportation infrastructure. Those outside the urban core had lower risks but drove more, while those living nearer the urban core tended to drive less but had higher exposures and risks from on-road sources. We suggest policy considerations for addressing these inequities. PMID:25996888

  6. Impact of Hispanic Ethnic Concentration and Socioeconomic Status on Obesity Prevalence in Texas Countie

    PubMed Central

    Salinas, Jennifer J.; Rocha, Elizabeth; Abdelbary, Bassent E.; Gay, Jennifer; Sexton, Ken

    2012-01-01

    The purpose of this study is to determine whether Hispanic ethnic concentration is associated with a higher prevalence of obesity and, if this relationship exists, whether it is affected by the socioeconomic environment. The study uses the Texas Behavioral Risk Factor Surveillance System (BRFSS) linked to 2000 census data to access the relationship between prevalence of obesity, Hispanic ethnic concentration, poverty and level of education at a county-level. The findings suggest that the association of Hispanic ethnic concentration and obesity varies by socioeconomic environment. Although little influence was observed for % poverty, the relationship between Hispanic ethnic concentration and obesity differed by county-level educational attainment. High proportion of residents with a bachelor’s degree is associated with a low prevalence of obesity; counties with both high % Hispanic and high % with Bachelor’s degrees had the lowest prevalence of obesity. Our results suggest that promoting and improving education, perhaps including training on healthful living, may serve as an effective means of curbing current obesity trends and associated health problems in Hispanic and possibly other ethnic communities. PMID:22690191

  7. Impact of Rurality, Broiler Operations, and Community Socioeconomic Factors on the Risk of Campylobacteriosis in Maryland

    PubMed Central

    Zappe Pasturel, Barbara; Cruz-Cano, Raul; Rosenberg Goldstein, Rachel E.; Palmer, Amanda; Blythe, David; Ryan, Patricia; Hogan, Brenna; Jung, Carrianne; Joseph, Sam W.; Wang, Min Qi; Ting Lee, Mei-Ling; Puett, Robin

    2013-01-01

    Objectives. We evaluated the combined impact of community-level environmental and socioeconomic factors on the risk of campylobacteriosis. Methods. We obtained Campylobacter case data (2002–2010; n = 3694) from the Maryland Foodborne Diseases Active Surveillance Network. We obtained community-level socioeconomic and environmental data from the 2000 US Census and the 2007 US Census of Agriculture. We linked data by zip code. We derived incidence rate ratios by Poisson regressions. We mapped a subset of zip code–level characteristics. Results. In zip codes that were 100% rural, incidence rate ratios (IRRs) of campylobacteriosis were 6 times (IRR = 6.18; 95% confidence interval [CI] = 3.19, 11.97) greater than those in urban zip codes. In zip codes with broiler chicken operations, incidence rates were 1.45 times greater than those in zip codes without broilers (IRR = 1.45; 95% CI = 1.34, 1.58). We also observed higher rates in zip codes whose populations were predominantly White and had high median incomes. Conclusions. The community and environment in which one lives may significantly influence the risk of campylobacteriosis. PMID:24134343

  8. Measuring socioeconomic status/position in studies of racial/ethnic disparities: maternal and infant health.

    PubMed Central

    Braveman, P.; Cubbin, C.; Marchi, K.; Egerter, S.; Chavez, G.

    2001-01-01

    OBJECTIVE: Theoretical and empiric considerations raise concerns about how socioeconomic status/position (abbreviated here as SES) is often measured in health research. The authors aimed to guide the use of two common socioeconomic indicators, education and income, in studies of racial/ethnic disparities in low birthweight, delayed prenatal care, unintended pregnancy, and breastfeeding intention. METHODS: Data from a statewide postpartum survey in California (N = 10,055) were linked to birth certificates. Overall and by race/ethnicity, the authors examined: (a) correlations among several measures of education and income; (b) associations between each SES measure and health indicator; and (c) racial/ethnic disparities in the health indicators "adjusting" for different SES measures. RESULTS: Education-income correlations were moderate and varied by race/ethnicity. Racial/ethnic associations with the health indicators varied by SES measure, how SES was specified, and by health indicator. CONCLUSIONS: Conclusions about the role of race/ethnicity could vary with how SES is measured. Education is not an acceptable proxy for income in studies of ethnically diverse populations of childbearing women. SES measures generally should be outcome- and population-specific, and chosen on explicit conceptual grounds; researchers should test multiple theoretically appropriate measures and consider how conclusions might vary with how SES is measured. Researchers should recognize the difficulty of measuring SES and interpret findings accordingly. PMID:12042609

  9. Community socioeconomic context and its influence on intermediary determinants of child health: evidence from Colombia.

    PubMed

    Osorio, Ana María; Bolancé, Catalina; Madise, Nyovani

    2015-01-01

    Intermediary determinants are the most immediate mechanisms through which socioeconomic position shapes health inequities. This study examines the effect of community socioeconomic context on different indicators representing intermediary determinants of child health. In the context of Colombia, a developing country with a clear economic expansion, but one of the most unequal countries in the world, two categories of intermediary determinants, namely behavioural and psychosocial factors and the health system, are analysed. Using data from the 2010 Colombian Demographic and Health Survey (DHS), the results suggest that whilst the community context can exert a greater influence on factors linked directly to health, in the case of psychosocial factors and parent's behaviours, the family context can be more important. In addition, the results from multilevel analysis indicate that a significant percentage of the variability in the overall index of intermediary determinants of child health is explained by the community context, even after controlling for individual, family and community characteristics. These findings underline the importance of distinguishing between community and family intervention programmes in order to reduce place-based health inequities in Colombia. PMID:24555557

  10. Neighbourhood socioeconomic status and cardiovascular risk factors: a multilevel analysis of nine cities in the Czech Republic and Germany

    PubMed Central

    Dragano, Nico; Bobak, Martin; Wege, Natalia; Peasey, Anne; Verde, Pablo E; Kubinova, Ruzena; Weyers, Simone; Moebus, Susanne; Möhlenkamp, Stefan; Stang, Andreas; Erbel, Raimund; Jöckel, Karl-Heinz; Siegrist, Johannes; Pikhart, Hynek

    2007-01-01

    . Conclusion In this comparative study, the effects of neighbourhood deprivation varied by country and risk factor; the strongest and most consistent effects were found for smoking. Results indicate that area level SES is associated with health related lifestyles, which might be a possible pathway linking social status and cardiovascular disease. Individual-level education had a considerable influence on the association between neighbourhood characteristics and risk factors. PMID:17888149

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

    PubMed

    Said, Sarmad; Hernandez, German T

    2015-01-01

    Kidney disease disproportionately affects racial and ethnic minority populations, the poor, and the socially disadvantaged. The excess risk of kidney disease among minority and disadvantaged populations can only be partially explained by an excess of diabetes, hypertension, and poor access to preventive care. Disparities in the environmental exposure to nephrotoxicants have been documented in minority and disadvantaged populations and may explain some of the excess risk of kidney disease. High-level environmental and occupational exposure to lead, cadmium, and mercury are known to cause specific nephropathies. However, there is growing evidence that low-level exposures to heavy metals may contribute to the development of CKD and its progression. In this article, we summarize the excess risk of environmental exposures among minority and disadvantaged populations. We also review the epidemiologic and clinical data linking low-level environmental exposure to lead, cadmium, and mercury to CKD and its progression. Finally, we briefly describe Mesoamerican nephropathy, an epidemic of CKD affecting young men in Central America, which may have occupational and environmental exposures contributing to its development. PMID:25573511

  12. Synthesising Topological Links

    PubMed Central

    Baas, Nils A.; Seeman, Nadrian C.; Stacey, Andrew

    2014-01-01

    We discuss the chemical synthesis of topological links, in particular higher order links which have the Brunnian property (namely that removal of any one component unlinks the entire system). Furthermore, we suggest how to obtain both two dimensional and three dimensional objects (surfaces and solids, respectively) which also have this Brunnian property. PMID:25678732

  13. Socioeconomic differentials and availability of domestic water in South Africa

    NASA Astrophysics Data System (ADS)

    Dungumaro, Esther W.

    The past few decades has seen massive efforts to increasing provision of domestic water. However, water is still unavailable to many people most of them located in sub-Saharan Africa, South Asia and East Asia. Furthermore, availability of water varies greatly both spatially and temporary. While other people pay so dearly for domestic water others have an easy access to adequate clean water and sanitation. Accessibility and affordability of domestic water and sanitation is determined by a great variety of factors including socioeconomic status of households. The main objective of the paper is to inform on factors which need to be taken into account when coming up with projects to provide domestic water. It is more critical when the issue of water pricing comes into the equation. Water pricing has many facets, including equity, willingness to pay and affordability. In this premise, it is deemed important to understand the socioeconomic characteristics of the people before deciding on the amount of money they will have to pay for water consumption. It is argued that understanding people’s socioeconomic situation will greatly help to ensure that principles of sustainability and equity in water allocation and pricing are achieved. To do so, the paper utilized 2002 South Africa General Household Survey (GHS), to analyze socioeconomic variables and availability of domestic water. Analysis was mainly descriptive. However, logistic regression analysis was also utilized to determine the likelihood of living in a household that obtain water from a safe source. The study found that there is a strong relationship between availability of domestic water and socioeconomic conditions. Economic status, household size and to a lesser extent gender of head of household were found to be strong predictors of living in a household which obtained water from a safe source. The paper recommends that needs and priorities for interventions in water provision should take into account

  14. Charting Pathways to Completion for Low-Income Community College Students. CCRC Working Paper No. 34

    ERIC Educational Resources Information Center

    Jenkins, Davis; Weiss, Madeline Joy

    2011-01-01

    This study uses administrative data from Washington State to chart the educational pathways of first-time community college students over seven years, with a focus on young, socioeconomically disadvantaged students. Of particular interest are the rates at which students enter a course of study (by passing multiple college-level courses within a…

  15. Do Educational Pathways Contribute to Equity in Tertiary Education in Australia?

    ERIC Educational Resources Information Center

    Wheelahan, Leesa

    2009-01-01

    A key assumption of equity policies in Australia, as in many countries, is that pathways from lower-status, vocationally oriented "second" tiers of tertiary education to "first" tier higher education are able to act as an equity mechanism. This is because students from low socio-economic backgrounds are over-represented in former and…

  16. To Cross-Link or Not to Cross-Link? Cross-Linking Associated Foreign Body Response of Collagen-Based Devices

    PubMed Central

    Delgado, Luis M.; Bayon, Yves; Pandit, Abhay

    2015-01-01

    Collagen-based devices, in various physical conformations, are extensively used for tissue engineering and regenerative medicine applications. Given that the natural cross-linking pathway of collagen does not occur in vitro, chemical, physical, and biological cross-linking methods have been assessed over the years to control mechanical stability, degradation rate, and immunogenicity of the device upon implantation. Although in vitro data demonstrate that mechanical properties and degradation rate can be accurately controlled as a function of the cross-linking method utilized, preclinical and clinical data indicate that cross-linking methods employed may have adverse effects on host response, especially when potent cross-linking methods are employed. Experimental data suggest that more suitable cross-linking methods should be developed to achieve a balance between stability and functional remodeling. PMID:25517923

  17. Young adolescents' wellbeing and health-risk behaviours: gender and socio-economic differences.

    PubMed

    Bergman, M M; Scott, J

    2001-04-01

    In this paper we use the 1994-1997 Youth Surveys of the British Household Panel Study to examine the wellbeing of young adolescents. We conceptualize wellbeing as a multi-dimensional construct and we develop and test models of gender and age differences. Using confirmatory factor analysis, we find clear gender differences in self-esteem, self-efficacy, unhappiness and worries. We confirm that wellbeing and some health-risk behaviours (fighting and smoking) are linked. We test models that examine how family structure, father's occupation, tenure, and household income, affect adolescent wellbeing. While socio-economic factors affect health-risk behaviours and also adolescents' reported worries, they have little impact on other aspects of youth wellbeing. The implications of these findings are discussed. PMID:11437479

  18. Area-Level Socioeconomic Factors Are Associated With Noncompletion of Pediatric Preventive Services.

    PubMed

    Jones, Margaret N; Brown, Courtney M; Widener, Michael J; Sucharew, Heidi J; Beck, Andrew F

    2016-07-01

    We examined 4872 infants born consecutively, 2011-2012, and seen at 3 primary care centers to determine whether area-based socioeconomic measures were associated with noncompletion of common preventive services within the first 15 months. Addresses were geocoded and linked to census tract poverty, adult educational attainment, and household vehicle ownership rates. The quartile of patients in the highest poverty (adjusted odds ratio [aOR] 1.25; 95% confidence interval [CI] 1.01-1.54) and lowest vehicle ownership tracts (aOR 1.32; 95% CI 1.07-1.63) had significantly increased odds of service noncompletion. There were significant spatial clusters of low completion in Cincinnati's urban core. These findings have implications for preventive service delivery. PMID:26883436

  19. "When the skies fight": HIV, violence and pathways of precarity in South Africa.

    PubMed

    Mills, Elizabeth

    2016-05-01

    Based on multi-sited ethnographic fieldwork in South Africa, this article explores the skies that fight, the proverbial lightning strikes that bring HIV into women's lives and bodies. Departing from earlier studies on ARV programmes in and beyond South Africa, and broadening out to explore the chronic struggle for life in a context of entrenched socio-economic inequality, this article presents findings on women's embodiment of and strategic resistance to structural and interpersonal violence. These linked forms of violence are discussed in light of the concept of precarity. Across two sections, the findings trace the pathways through which precarity entered women's lives, drawing on verbal, visual and written accounts collected through participant observation, participatory photography and film, and journey mapping. In doing so, the ethnography articulates the intersection of structural and interpersonal violence in women's lives. It also reveals the extent to which women exert a 'constrained agency', on the one hand, to resist structural violence and reconfigure their political relationship with the state through health activism; and, on the other hand, to shift the gender dynamics that fuel interpersonal violence through a careful navigation of intimacy and independence. PMID:27578342

  20. [Migration and socioeconomic changes in the community of Zoogocho, Oaxaca].

    PubMed

    Ramos Pioquinto, D

    1991-01-01

    "This study of migration and the socioeconomic dynamics of the community of Zoogocho in the state of Oaxaca [Mexico] is an example of what happens in rural areas when Indian-campesinos establish contacts with foreign parts. The penetration of alien socioeconomic and cultural values alters both family and communal structures to such an extent that available resources prove insufficient in competing with the colliding external society. This leads to increasingly more complex movements of the population, the manifestations, causes and consequences of which vary through time not only in the places of origin but also in destinations." (SUMMARY IN ENG) PMID:12317735