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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. Pathways Linking Socioeconomic Status and Postpartum Smoking Relapse

    PubMed Central

    Businelle, Michael S.; Kendzor, Darla E.; Reitzel, Lorraine R.; Vidrine, Jennifer Irvin; Castro, Yessenia; Mullen, Patricia Dolan; Velasquez, Mary M.; Cofta-Woerpel, Ludmila; Cinciripini, Paul M.; Greisinger, Anthony J.; Wetter, David W.

    2012-01-01

    Background Low socioeconomic status (SES) exacerbates the high rate of smoking relapse in women following childbirth. Purpose This study examined multiple models of potential mechanisms linking SES and postpartum smoking relapse among women who quit smoking due to pregnancy. Methods Participants were 251 women enrolled in a randomized clinical trial of a new postpartum smoking relapse prevention intervention. Four models of the prepartum mechanisms linking SES and postpartum smoking relapse were evaluated using a latent variable modeling approach. Results Each of the hypothesized models were a good fit for the data. As hypothesized, SES indirectly influenced postpartum smoking relapse through increased prepartum negative affect/stress, reduced sense of agency, and increased craving for cigarettes. However, the model that included craving as the sole final pathway between SES and relapse demonstrated superior fit when compared with all other models. Conclusions Findings have implications for future interventions that aim to reduce postpartum relapse. PMID:23086590

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

    PubMed Central

    Matthews, Karen A.; Gallo, Linda C.

    2011-01-01

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

  4. Pathways linking socioeconomic status to obesity through depression and lifestyle factors among young US adults

    PubMed Central

    Beydoun, May A.; Wang, Youfa

    2009-01-01

    Obesity and depression are two diseases of major public health importance. While both correlate with each other, potential pathways involving depression that would link socioeconomic status (SES) to lifestyle factors and obesity have not been systematically examined using nationally representative data. Using rich data on 2,217 US young adults aged 20–39 years from the 1999–2004 National Health and Nutrition Surveys (NHANES) and multivariate linear and logistic regression models, we examined associations between major depressive disorder (MDD), dietary intake, physical activity (PA), and measured body mass index (BMI) controlling for socio-demographic factors. Further, structural equations models (SEM) were fit to test pathway explaining SES disparities in BMI through MDD and lifestyle factors. Recent prevalence of MDD was lower among young US men than women (6.4% vs 9.2%) although their prevalence of obesity was similar (21.2% vs 22.7%). Among women, MDD was associated with higher BMI and inversely associated with PA, but not among men. MDD was specifically associated with increased risk of morbid obesity (BMI≥40) among women (OR: 2.88 (1.32, 6.30)). Using SEM, a main pathway linking SES to BMI among women was that linking SES → food insecurity → MDD → PA → BMI. A main pathway linking MDD to BMI in both genders was that going through PA rather than overall dietary quality. Gender and ethnic differences existed underlying how MDD, SES and lifestyle factors were associated with adiposity. Future prospective studies are needed to examine potential mechanisms using physiological markers of depression, lifestyle and obesity. PMID:19853306

  5. Biopsychosocial pathways linking subjective socioeconomic disadvantage to glycemic control in youths with type I diabetes.

    PubMed

    Zilioli, Samuele; Ellis, Deborah A; Carré, Justin M; Slatcher, Richard B

    2017-04-01

    Older adolescent and young adults (OAYA) with type 1 diabetes (T1D) living in contexts of socio-economic disadvantage (SED) suffer disproportionately from poor glycemic control and related health complications. Although SED may convey a variety of risks, it may exacerbate diabetes-related stress levels, which in turn may account for observed disparities in health outcomes. The primary goal of the present study was to investigate the relationship between subjective SED, diabetes-related perceived stress, and diurnal cortisol secretion in urban OAYA with T1D. A secondary goal was to determine if cortisol was related to measures of blood glucose (HbA1c and mean blood glucose). Analyses were conducted among OAYA ages 17-20 years (n=61) affected by T1D, who provided daily saliva samples for four days, measures of glycemic control (i.e., HbA1c and mean blood glucose assessed via Continuous Glucose Monitor), and completed psychosocial questionnaires. We found that subjective SED was associated with a flatter diurnal cortisol rhythm via diabetes-related stress. Flattened cortisol rhythm was, in turn, associated with higher levels of HbA1c, but not with mean blood glucose assessed via Continuous Glucose Monitor. These results represent some of the first empirical evidence on how distal social factors (i.e., subjective SED) and proximal psychological processes (diabetes-related perceived stress) are connected to condition-relevant biological mechanisms (i.e., elevated HbA1c), via broad biological pathways implicated in health (i.e., flatter cortisol slope).

  6. 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…

  7. Forecasting civil conflict along the shared socioeconomic pathways

    NASA Astrophysics Data System (ADS)

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

    2016-05-01

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

  8. Socioeconomic disparities and health: impacts and pathways.

    PubMed

    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.

  9. 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

  10. 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.

  11. Pathways between Socioeconomic Status and Modifiable Risk Factors Among African American Smokers

    PubMed Central

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

    2010-01-01

    Although socioeconomic status is a major contributing factor to health disparities, the mechanisms through which socioeconomic status influences health remain unclear. The purpose of the present study was to evaluate an a priori conceptual model of the pathways between socioeconomic status and modifiable health risk factors in a sample of 399 African Americans seeking smoking cessation treatment. A latent variable modeling approach was utilized to characterize the interrelationships among socioeconomic status, neighborhood disadvantage, social support, negative affect/perceived stress, and three specific modifiable risk factors (i.e., overweight/obesity, insufficient physical activity, at-risk drinking). Findings indicated that neighborhood disadvantage, social support, and negative affect/perceived stress function as pathways linking socioeconomic status and modifiable risk factors among African American smokers, and negative affect/perceived stress appears to play a key mediating role. Policy, community, and individual-level interventions may attenuate the impact of socioeconomic status on health by targeting intermediate psychosocial, environmental, and behavioral pathways. PMID:19757014

  12. Future air pollution in the Shared Socio-economic Pathways

    DOE PAGES

    Rao, Shilpa; Klimont, Zbigniew; Smith, Steven J.; ...

    2016-07-15

    Emissions of air pollutants such as sulfur and nitrogen oxides and particulates have significant health impacts as well as effects on natural and anthropogenic ecosystems. These same emissions also can change atmospheric chemistry and the planetary energy balance, thereby impacting global and regional climate. Long-term scenarios for air pollutant emissions are needed as inputs to global climate and chemistry models, and for analysis linking air pollutant impacts across sectors. In this paper we present methodology and results for air pollutant emissions in Shared Socioeconomic Pathways (SSP) scenarios. We first present a set of three air pollution narratives that describe high,more » central, and low pollution control ambitions over the 21st century. These narratives are then translated into quantitative guidance for use in integrated assessment models. We provide an overview of pollutant emission trajectories under the SSP scenarios. Pollutant emissions in these scenarios cover a wider range than the scenarios used in previous international climate model comparisons. Furthermore, the SSP scenarios provide the opportunity to access a more comprehensive range of future global and regional air quality outcomes.« less

  13. Future air pollution in the Shared Socio-economic Pathways

    SciTech Connect

    Rao, Shilpa; Klimont, Zbigniew; Smith, Steven J.; Van Dingenen, Rita; Dentener, Frank; Bouwman, Lex; Riahi, Keywan; Amann, Markus; Bodirsky, Benjamin Leon; van Vuuren, Detlef P.; Reis, Lara Aleluia; Calvin, Katherine; Drouet, Laurent; Fricko, Oliver; Fujimori, Shinichiro; Gernaat, David; Havlik, Petr; Harmsen, Mathijs; Hasegawa, Tomoko; Heyes, Chris; Hilaire, Jérôme; Luderer, Gunnar; Masui, Toshihiko; Stehfest, Elke; Strefler, Jessica; van der Sluis, Sietske; Tavoni, Massimo

    2016-07-15

    Emissions of air pollutants such as sulfur and nitrogen oxides and particulates have significant health impacts as well as effects on natural and anthropogenic ecosystems. These same emissions also can change atmospheric chemistry and the planetary energy balance, thereby impacting global and regional climate. Long-term scenarios for air pollutant emissions are needed as inputs to global climate and chemistry models, and for analysis linking air pollutant impacts across sectors. In this paper we present methodology and results for air pollutant emissions in Shared Socioeconomic Pathways (SSP) scenarios. We first present a set of three air pollution narratives that describe high, central, and low pollution control ambitions over the 21st century. These narratives are then translated into quantitative guidance for use in integrated assessment models. We provide an overview of pollutant emission trajectories under the SSP scenarios. Pollutant emissions in these scenarios cover a wider range than the scenarios used in previous international climate model comparisons. Furthermore, the SSP scenarios provide the opportunity to access a more comprehensive range of future global and regional air quality outcomes.

  14. Future Air Pollution in the Shared Socio-Economic Pathways

    SciTech Connect

    Rao, Shilpa; Klimont, Zbigniew; Smith, Steven J.; van Dingenen, Rita; Dentener, Frank; Bouwman, Lex; Riahi, Keywan; Amann, Markus; Bodirsky, Benjamin; Van Vuuren, Detlef; Reis, Lara; Calvin, Katherine V.; Drouet, Laurent; Fricko, Oliver; Fujimori, Shinichiro; Gernaat, David; Havlik, Petr; Harmsen, Mathijs; Hasegawa, Tomoko; Heyes, Chris; Hilaire, Jerome; Luderer, Gunnar; Masui, Toshihiko; Stehfest, Eike; Strefler, Jessica; van der Sluis, Sietske; Tavoni, Massimo

    2017-01-01

    Emissions of air pollutants such as sulfur and nitrogen oxides and particulates have significant health impacts as well as effects on natural and anthropogenic ecosystems. These same emissions also can change atmospheric chemistry and the planetary energy balance, thereby impacting global and regional climate. Long-term scenarios for air pollutant emissions are needed as inputs to global climate and chemistry models, and for analysis linking air pollutant impacts across sectors. In this paper we present methodology and results for air pollutant emissions in Shared Socioeconomic Pathways (SSP) scenarios. We first present a set of three air pollution narratives that describe high, central, and low pollution control ambitions over the 21st century. These narratives are then translated into quantitative guidance for use in integrated assessment models. We provide an overview of pollutant emission trajectories under the SSP scenarios. Pollutant emissions in these scenarios cover a wider range than the scenarios used in previous international climate model comparisons. The SSP scenarios provide the opportunity to access a more comprehensive range of future global and regional air quality outcomes.

  15. Stress and resource pathways connecting early socioeconomic adversity to young adults' physical health risk.

    PubMed

    Wickrama, Kandauda K A S; Lee, Tae Kyoung; O'Neal, Catherine Walker; Kwon, Josephine A

    2015-05-01

    Although research has established the impact of early stress, including stressful life contexts, and early resources, such as educational attainment, on various adolescent health outcomes, previous research has not adequately investigated "integrative models" incorporating both stress and resource mediational pathways to explain how early socioeconomic adversity impacts physical health outcomes, particularly in early life stages. Data on early childhood/adolescent stress and socioeconomic resources as well as biomarkers indicating physical health status in young adulthood were collected from 11,798 respondents (54 % female) over a 13-year period from youth participating in the National Study of Adolescent Health (Add Health). Physical health risk in young adulthood was measured using a composite index of nine regulatory biomarkers of cardiovascular and metabolic systems. Heterogeneity in stress and socioeconomic resource pathways was assessed using latent class analysis to identify clusters, or classes, of stress and socioeconomic resource trajectories. The influence of early socioeconomic adversity on young adults' physical health risk, as measured by biomarkers, was estimated, and the role of stress and socioeconomic resource trajectory classes as linking mechanisms was assessed. There was evidence for the influence of early socioeconomic adversity on young adults' physical health risk directly and indirectly through stress and socioeconomic resource trajectory classes over the early life course. These findings suggest that health models should be broadened to incorporate both stress and resource experiences simultaneously. Furthermore, these findings have prevention and intervention implications, including the importance of early socioeconomic adversity and key intervention points for "turning" the trajectories of at-risk youth.

  16. 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.…

  17. Data on fossil fuel availability for Shared Socioeconomic Pathways.

    PubMed

    Bauer, Nico; Hilaire, Jérôme; Brecha, Robert J; Edmonds, Jae; Jiang, Kejun; Kriegler, Elmar; Rogner, Hans-Holger; Sferra, Fabio

    2017-02-01

    The data files contain the assumptions and results for the construction of cumulative availability curves for coal, oil and gas for the five Shared Socioeconomic Pathways. The files include the maximum availability (also known as cumulative extraction cost curves) and the assumptions that are applied to construct the SSPs. The data is differentiated into twenty regions. The resulting cumulative availability curves are plotted and the aggregate data as well as cumulative availability curves are compared across SSPs. The methodology, the data sources and the assumptions are documented in a related article (N. Bauer, J. Hilaire, R.J. Brecha, J. Edmonds, K. Jiang, E. Kriegler, H.-H. Rogner, F. Sferra, 2016) [1] under DOI: http://dx.doi.org/10.1016/j.energy.2016.05.088.

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

    PubMed

    Tucker-Drob, Elliot M

    2013-06-01

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

  19. Pathways from Childhood Abuse and Other Adversities to Adult Health Risks: The Role of Adult Socioeconomic Conditions

    PubMed Central

    Maguire-Jack, Kathryn

    2015-01-01

    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

  20. 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.

  1. 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

  2. Water scarcity under various socio-economic pathways and its potential effects on food production in the Yellow River basin

    NASA Astrophysics Data System (ADS)

    Yin, Yuanyuan; Tang, Qiuhong; Liu, Xingcai; Zhang, Xuejun

    2017-02-01

    Increasing population and socio-economic development have put great pressure on water resources of the Yellow River (YR) basin. The anticipated climate and socio-economic changes may further increase water stress. Many studies have investigated the changes in renewable water resources under various climate change scenarios, but few have considered the joint pressure from both climate change and socio-economic development. In this study, we assess water scarcity under various socio-economic pathways with emphasis on the impact of water scarcity on food production. The water demands in the 21st century are estimated based on the newly developed shared socio-economic pathways (SSPs) and renewable water supply is estimated using the climate projections under the Representative Concentration Pathway (RCP) 8.5 scenario. The assessment predicts that the renewable water resources would decrease slightly then increase. The domestic and industrial water withdrawals are projected to increase in the next a few decades and then remain at the high level or decrease slightly during the 21st century. The increase in water withdrawals will put the middle and lower reaches in a condition of severe water scarcity beginning in the next a few decades. If 40 % of the renewable water resources were used to sustain ecosystems, a portion of irrigated land would have to be converted to rain-fed agriculture, which would lead to a 2-11 % reduction in food production. This study highlights the links between water, food and ecosystems in a changing environment and suggests that trade-offs should be considered when developing regional adaptation strategies.

  3. 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.

  4. Cascading events in linked ecological and socioeconomic systems

    USGS Publications Warehouse

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

    2007-01-01

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

  5. 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.

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

    PubMed

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

    2011-12-01

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

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

    SciTech Connect

    Absar, Syeda Mariya; Preston, Benjamin L.

    2015-05-25

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

  8. 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…

  9. 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…

  10. Certification Criteria for Linked Learning Pathways

    ERIC Educational Resources Information Center

    ConnectEd: The California Center for College and Career, 2010

    2010-01-01

    Pathways offer a promising strategy for transforming high schools and improving student outcomes. However, to achieve these desired results, pathways must be of high quality. To guide sites in planning and implementing such pathways, a design team of experts developed the criteria outlined in this document. Sites can choose to go through a…

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

    DOE PAGES

    Absar, Syeda Mariya; Preston, Benjamin L.

    2015-05-25

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

  12. The Pathways Between Socioeconomic Status and Adolescent Outcomes: A Systematic Review.

    PubMed

    Devenish, Bethany; Hooley, Merrilyn; Mellor, David

    2017-03-01

    Socioeconomic status (SES) is a significant risk factor for negative adolescent development outcomes. Identifying the pathways between SES and these outcomes may inform interventions for adolescents from this demographic. We conducted a systematic literature review of eight databases for studies investigating pathways between SES and adolescent psychosocial outcomes. A total of 59 articles met inclusion criteria. Significant risk factors identified include economic stress, chaos in the home, and violence in the community. These risk factors appear to be mediated through parent depression, conflict between parents, parenting practices, and adolescent resilience. Interventions focusing on the identified risk factors are recommended.

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

    PubMed Central

    2013-01-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2016-01-01

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

  16. 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.

  17. 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…

  18. 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

  19. PIKfyve Regulation of Endosome-Linked Pathways

    PubMed Central

    de Lartigue, Jane; Polson, Hannah; Feldman, Morri; Shokat, Kevan; Tooze, Sharon A; Urbé, Sylvie; Clague, Michael J

    2009-01-01

    The phosphoinositide 5-kinase (PIKfyve) is a critical enzyme for the synthesis of PtdIns(3,5)P2, that has been implicated in various trafficking events associated with the endocytic pathway. We have now directly compared the effects of siRNA-mediated knockdown of PIKfyve in HeLa cells with a specific pharmacological inhibitor of enzyme activity. Both approaches induce changes in the distribution of CI-M6PR and trans-Golgi network (TGN)-46 proteins, which cycles between endosomes and TGN, leading to their accumulation in dispersed punctae, whilst the TGN marker golgin-245 retains a perinuclear disposition. Trafficking of CD8-CI-M6PR (retromer-dependent) and CD8-Furin (retromer-independent) chimeras from the cell surface to the TGN is delayed following drug administration, as is the transport of the Shiga toxin B-subunit. siRNA knockdown of PIKfyve produced no defect in epidermal growth factor receptor (EGFR) degradation, unless combined with knockdown of its activator molecule Vac14, suggesting that a low threshold of PtdIns(3,5)P2 is necessary and sufficient for this pathway. Accordingly pharmacological inhibition of PIKfyve results in a profound block to the lysosomal degradation of activated epidermal growth factor (EGF) and Met receptors. Immunofluorescence revealed EGF receptors to be trapped in the interior of a swollen endosomal compartment. In cells starved of amino acids, PIKfyve inhibition leads to the accumulation of the lipidated form of GFP-LC3, a marker of autophagosomal structures, which can be visualized as fluorescent punctae. We suggest that PIKfyve inhibition may render the late endosome/lysosome compartment refractory to fusion with both autophagosomes and with EGFR-containing multivesicular bodies. PMID:19582903

  20. Adolescent depression linked to socioeconomic status? Molecular approaches for revealing premorbid risk factors.

    PubMed

    Uddin, Monica; Jansen, Stefan; Telzer, Eva H

    2017-03-01

    The means by which social environmental exposures influence risk of mental disorders is a persistent and still open question. A key candidate mechanism for the biologic mediation of environmental effects involves epigenetic factors, which regulate gene function without altering underlying DNA sequence. Recent work has shown that environmental exposures such as childhood abuse, family history of mental disorder, and low socioeconomic status (SES) associate with differential DNA methylation (5mC) - a relatively stable, but modifiable, epigenetic factor. However, the longitudinal relation among SES, 5mC, brain function, and risk of depression remains to be elucidated. Here, we briefly review literature relevant to these associations and discuss recent findings that, for the first time, prospectively demonstrate sequential links between low SES, changes in 5mC, changes in brain function, and risk of depression in a cohort of adolescents.

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

    PubMed

    You, Jihyun; Choo, Jina

    2016-03-09

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

  2. Eco-Health Linkages: evidence base and socio-economic considerations for linking ecosystem goods and services to human health

    EPA Science Inventory

    Ecosystem goods and services (EGS) are thought to play a role in protecting human health, but the empirical evidence directly linking EGS to human health outcomes is limited, and our ability to detect Eco-Health linkages is confounded by socio-economic factors. These limitations ...

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. Sensitivity of projected long-term CO2 emissions across the Shared Socioeconomic Pathways

    NASA Astrophysics Data System (ADS)

    Marangoni, G.; Tavoni, M.; Bosetti, V.; Borgonovo, E.; Capros, P.; Fricko, O.; Gernaat, D. E. H. J.; Guivarch, C.; Havlik, P.; Huppmann, D.; Johnson, N.; Karkatsoulis, P.; Keppo, I.; Krey, V.; Ó Broin, E.; Price, J.; van Vuuren, D. P.

    2017-01-01

    Scenarios showing future greenhouse gas emissions are needed to estimate climate impacts and the mitigation efforts required for climate stabilization. Recently, the Shared Socioeconomic Pathways (SSPs) have been introduced to describe alternative social, economic and technical narratives, spanning a wide range of plausible futures in terms of challenges to mitigation and adaptation. Thus far the key drivers of the uncertainty in emissions projections have not been robustly disentangled. Here we assess the sensitivities of future CO2 emissions to key drivers characterizing the SSPs. We use six state-of-the-art integrated assessment models with different structural characteristics, and study the impact of five families of parameters, related to population, income, energy efficiency, fossil fuel availability, and low-carbon energy technology development. A recently developed sensitivity analysis algorithm allows us to parsimoniously compute both the direct and interaction effects of each of these drivers on cumulative emissions. The study reveals that the SSP assumptions about energy intensity and economic growth are the most important determinants of future CO2 emissions from energy combustion, both with and without a climate policy. Interaction terms between parameters are shown to be important determinants of the total sensitivities.

  9. 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

  10. BID links ferroptosis to mitochondrial cell death pathways.

    PubMed

    Neitemeier, Sandra; Jelinek, Anja; Laino, Vincenzo; Hoffmann, Lena; Eisenbach, Ina; Eying, Roman; Ganjam, Goutham K; Dolga, Amalia M; Oppermann, Sina; Culmsee, Carsten

    2017-03-09

    Ferroptosis has been defined as an oxidative and iron-dependent pathway of regulated cell death that is distinct from caspase-dependent apoptosis and established pathways of death receptor-mediated regulated necrosis. While emerging evidence linked features of ferroptosis induced e.g. by erastin-mediated inhibition of the Xc(-) system or inhibition of glutathione peroxidase 4 (Gpx4) to an increasing number of oxidative cell death paradigms in cancer cells, neurons or kidney cells, the biochemical pathways of oxidative cell death remained largely unclear. In particular, the role of mitochondrial damage in paradigms of ferroptosis needs further investigation. In the present study, we find that erastin-induced ferroptosis in neuronal cells was accompanied by BID transactivation to mitochondria, loss of mitochondrial membrane potential, enhanced mitochondrial fragmentation and reduced ATP levels. These hallmarks of mitochondrial demise are also established features of oxytosis, a paradigm of cell death induced by Xc(-) inhibition by millimolar concentrations of glutamate. Bid knockout using CRISPR/Cas9 approaches preserved mitochondrial integrity and function, and mediated neuroprotective effects against both, ferroptosis and oxytosis. Furthermore, the BID-inhibitor BI-6c9 inhibited erastin-induced ferroptosis, and, in turn, the ferroptosis inhibitors ferrostatin-1 and liproxstatin-1 prevented mitochondrial dysfunction and cell death in the paradigm of oxytosis. These findings show that mitochondrial transactivation of BID links ferroptosis to mitochondrial damage as the final execution step in this paradigm of oxidative cell death.

  11. Television and the behaviour of adolescents: does socio-economic status moderate the link?

    PubMed

    Chowhan, James; Stewart, Jennifer M

    2007-10-01

    This paper examines the relationship between adolescent behaviour, television viewing and family socio-economic status (SES) using the Canadian National Longitudinal Survey of Children and Youth (NLSCY). The effect of television viewing on adolescents' behaviour, ranging from pro-social to aggressive, and whether this effect is moderated by family socio-economic status is investigated. An adolescent fixed effects model is used to estimate the effect of television viewing on behaviour. The results indicate that the effect of television viewing varies between males and females. Family SES has a role in the effect of television on adolescents' behaviour, although the results do not distinguish between the two proposed hypotheses.

  12. 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). ...

  13. 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.

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

    NASA Astrophysics Data System (ADS)

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

    2016-10-01

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

  15. Socioeconomic status and social support following illicit drug use: causal pathways or common liability?

    PubMed

    Bergen, Sarah E; Gardner, Charles O; Aggen, Steven H; Kendler, Kenneth S

    2008-06-01

    The negative social attributes associated with drug use and abuse/dependence may arise as a result of shared genetic or environmental factors rather than through causal pathways. To evaluate this possibility, structured interviews were conducted for 3969 male and female twins from the Mid-Atlantic Twin Registry and evaluations of their socioeconomic status (SES), social interactions, and use of drugs were obtained. Drug involvement was categorized as never used, tried, or met criteria for abuse or dependence. A co-twin control design was implemented using hierarchical linear modeling to assess whether twins who used drugs experienced lower SES and social support than non-using co-twins. Poorer social functioning in the drug-exposed twin is consistent with a causal relationship, while similar functioning in the drug exposed versus naive twins imply shared genetic or common environmental factors. Use of drugs was not significantly related to any SES measures. However, education and job status appear to share genetic influences with drug abuse/dependence. Lower income was not related to abuse/dependence of drugs. Negative interactions with friends and relatives share genetic factors with use of drugs, but the escalation from trying drugs to abusing them appears to generate discord between the abuser and friends and relatives in a causal fashion. These results indicate that presumptive causal influences of drug abuse/dependence on low SES may actually be mediated by shared genes. Drug use and social discord also appear to have shared genetic factors, but increased levels of drug involvement seem to causally influence social interactions.

  16. Building Links between Early Socioeconomic Status, Cognitive Ability, and Math and Science Achievement

    ERIC Educational Resources Information Center

    Blums, Angela; Belsky, Jay; Grimm, Kevin; Chen, Zhe

    2017-01-01

    The present study examined whether and how socioeconomic status (SES) predicts school achievement in science, technology, engineering, and math (STEM) using structural equation modeling and data from the National Institute of Child Health and Human Development Study of Child Care and Youth Development. The present inquiry addresses gaps in…

  17. 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);…

  18. 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

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

    PubMed

    Gianaros, Peter J; Wager, Tor D

    2015-08-01

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

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

    PubMed Central

    Gianaros, Peter J.; Wager, Tor D.

    2015-01-01

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

  1. Night-time lights: A global, long term look at links to socio-economic trends

    PubMed Central

    Zavala-Araiza, Daniel; Wagner, Gernot

    2017-01-01

    We use a parallelized spatial analytics platform to process the twenty-one year totality of the longest-running time series of night-time lights data—the Defense Meteorological Satellite Program (DMSP) dataset—surpassing the narrower scope of prior studies to assess changes in area lit of countries globally. Doing so allows a retrospective look at the global, long-term relationships between night-time lights and a series of socio-economic indicators. We find the strongest correlations with electricity consumption, CO2 emissions, and GDP, followed by population, CH4 emissions, N2O emissions, poverty (inverse) and F-gas emissions. Relating area lit to electricity consumption shows that while a basic linear model provides a good statistical fit, regional and temporal trends are found to have a significant impact. PMID:28346500

  2. Genetic link between family socioeconomic status and children's educational achievement estimated from genome-wide SNPs

    PubMed Central

    Krapohl, E; Plomin, R

    2016-01-01

    One of the best predictors of children's educational achievement is their family's socioeconomic status (SES), but the degree to which this association is genetically mediated remains unclear. For 3000 UK-representative unrelated children we found that genome-wide single-nucleotide polymorphisms could explain a third of the variance of scores on an age-16 UK national examination of educational achievement and half of the correlation between their scores and family SES. Moreover, genome-wide polygenic scores based on a previously published genome-wide association meta-analysis of total number of years in education accounted for ~3.0% variance in educational achievement and ~2.5% in family SES. This study provides the first molecular evidence for substantial genetic influence on differences in children's educational achievement and its association with family SES. PMID:25754083

  3. Urban-rural differences in the socioeconomic deprivation--sexual behavior link in Kenya.

    PubMed

    Dodoo, F Nii-Amoo; Zulu, Eliya M; Ezeh, Alex C

    2007-03-01

    We compare the impact of socioeconomic deprivation on risky sexual outcomes in rural and urban Kenya. Quantitative data are drawn from the Demographic & Health Surveys (DHS) and qualitative data from the Sexual Networking and Associated Reproductive and Social Health Concerns study. Using two separate indicators of deprivation we show that, although poverty is significantly associated with the examined sexual outcomes in all settings, the urban poor are significantly more likely than their rural counterparts to have an early sexual debut and a greater incidence of multiple sexual partnerships. The disadvantage of the urban poor is accentuated for married women; those in Nairobi's slums are at least three times as likely to have multiple sexual partners as their rural counterparts. The implications of these findings are discussed.

  4. Genetic link between family socioeconomic status and children's educational achievement estimated from genome-wide SNPs.

    PubMed

    Krapohl, E; Plomin, R

    2016-03-01

    One of the best predictors of children's educational achievement is their family's socioeconomic status (SES), but the degree to which this association is genetically mediated remains unclear. For 3000 UK-representative unrelated children we found that genome-wide single-nucleotide polymorphisms could explain a third of the variance of scores on an age-16 UK national examination of educational achievement and half of the correlation between their scores and family SES. Moreover, genome-wide polygenic scores based on a previously published genome-wide association meta-analysis of total number of years in education accounted for ~3.0% variance in educational achievement and ~2.5% in family SES. This study provides the first molecular evidence for substantial genetic influence on differences in children's educational achievement and its association with family SES.

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

    PubMed

    Ritchie, Stuart J; Bates, Timothy C

    2013-07-01

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

  6. Socio-economic factors related to moral reasoning in childhood and adolescence: the missing link between brain and behavior

    PubMed Central

    Caravita, Simona C. S.; Giardino, Simona; Lenzi, Leonardo; Salvaterra, Mariaelena; Antonietti, Alessandro

    2012-01-01

    Neuroscientific and psychological research on moral development has until now developed independently, referring to distinct theoretical models, contents, and methods. In particular, the influence of socio-economic and cultural factors on morality has been broadly investigated by psychologists but as yet has not been investigated by neuroscientists. The value of bridging these two areas both theoretically and methodologically has, however, been suggested. This study aims at providing a first connection between neuroscientific and psychological literature on morality by investigating whether socio-economic dimensions, i.e., living socio-geographic/economic area, immigrant status and socio-economic status (SES), affect moral reasoning as operationalized in moral domain theory (a seminal approach in psychological studies on morality) and in Greene et al. (2001) perspective (one of the main approaches in neuroethics research). Participants were 81 primary school (M = 8.98 years; SD = 0.39), 72 middle school (M = 12.14 years; SD = 0.61), and 73 high school (M = 15.10 years; SD = 0.38) students from rural and urban areas. Participants' immigrant status (native vs. immigrant) and family SES level were recorded. Moral reasoning was assessed by means of a series of personal and impersonal dilemmas based on Greene et al. (2001) neuroimaging experiment and a series of moral and socio-conventional rule dilemmas based on the moral domain theory. Living socio-geographic/economic area, immigrant status and SES mainly affected evaluations of moral and, to a higher extent, socio-conventional dilemmas, but had no impact on judgment of personal and impersonal dilemmas. Results are mainly discussed from the angle of possible theoretical links and suggestions emerging for studies on moral reasoning in the frameworks of neuroscience and psychology. PMID:23015787

  7. 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

  8. Socio-economic factors related to moral reasoning in childhood and adolescence: the missing link between brain and behavior.

    PubMed

    Caravita, Simona C S; Giardino, Simona; Lenzi, Leonardo; Salvaterra, Mariaelena; Antonietti, Alessandro

    2012-01-01

    Neuroscientific and psychological research on moral development has until now developed independently, referring to distinct theoretical models, contents, and methods. In particular, the influence of socio-economic and cultural factors on morality has been broadly investigated by psychologists but as yet has not been investigated by neuroscientists. The value of bridging these two areas both theoretically and methodologically has, however, been suggested. This study aims at providing a first connection between neuroscientific and psychological literature on morality by investigating whether socio-economic dimensions, i.e., living socio-geographic/economic area, immigrant status and socio-economic status (SES), affect moral reasoning as operationalized in moral domain theory (a seminal approach in psychological studies on morality) and in Greene et al. (2001) perspective (one of the main approaches in neuroethics research). Participants were 81 primary school (M = 8.98 years; SD = 0.39), 72 middle school (M = 12.14 years; SD = 0.61), and 73 high school (M = 15.10 years; SD = 0.38) students from rural and urban areas. Participants' immigrant status (native vs. immigrant) and family SES level were recorded. Moral reasoning was assessed by means of a series of personal and impersonal dilemmas based on Greene et al. (2001) neuroimaging experiment and a series of moral and socio-conventional rule dilemmas based on the moral domain theory. Living socio-geographic/economic area, immigrant status and SES mainly affected evaluations of moral and, to a higher extent, socio-conventional dilemmas, but had no impact on judgment of personal and impersonal dilemmas. Results are mainly discussed from the angle of possible theoretical links and suggestions emerging for studies on moral reasoning in the frameworks of neuroscience and psychology.

  9. An epigenetic mechanism links socioeconomic status to changes in depression-related brain function in high-risk adolescents

    PubMed Central

    Swartz, Johnna R.

    2016-01-01

    Identifying biological mechanisms through which the experience of adversity emerges as individual risk for mental illness is an important step towards developing strategies for personalized treatment and, ultimately, prevention. Preclinical studies have identified epigenetic modification of gene expression as one such mechanism. Recent clinical studies have suggested that epigenetic modification, particularly methylation of gene regulatory regions, also acts to shape human brain function associated with risk for mental illness. However, it is not yet clear if differential gene methylation as a function of adversity contributes to the emergence of individual risk for mental illness. Using prospective longitudinal epigenetic, neuroimaging, and behavioral data from 132 adolescents, we demonstrate that changes in gene methylation associated with lower socioeconomic status predict changes in risk-related brain function. Specifically, we find that lower socioeconomic status during adolescence is associated with an increase in methylation of the proximal promoter of the serotonin transporter gene, which predicts greater increases in threat-related amygdala reactivity. We subsequently demonstrate that greater increases in amygdala reactivity moderate the association between a positive family history for depression and the later manifestation of depressive symptoms. These initial results suggest a specific biological mechanism through which adversity contributes to altered brain function, which in turn moderates the emergence of general liability as individual risk for mental illness. If replicated, this prospective pathway may represent a novel target biomarker for intervention and prevention amongst high-risk individuals. PMID:27217150

  10. 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

  11. 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...

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

    PubMed

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

    1999-01-01

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

  13. 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.

  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. Pathways to a Four-Year Degree: Determinants of Degree Completion among Socioeconomically Disadvantaged Students.

    ERIC Educational Resources Information Center

    Cabrera, Alberto F.; Burkum, Kurt R.; La Nasa, Steven M.

    The High School Sophomore Cohort of 1980 followed nine different pathways to a 4-year college degree. These paths were formed by a combination of different levels of academic preparation secured in high school and the first type of postsecondary institution attended. The pathway most likely to lead to a 4-year degree is one defined by acquiring…

  16. 5-HTTLPR polymorphism is linked to neural mechanisms of selective attention in preschoolers from lower socioeconomic status backgrounds.

    PubMed

    Isbell, Elif; Stevens, Courtney; Hampton Wray, Amanda; Bell, Theodore; Neville, Helen J

    2016-12-01

    While a growing body of research has identified experiential factors associated with differences in selective attention, relatively little is known about the contribution of genetic factors to the skill of sustained selective attention, especially in early childhood. Here, we assessed the association between the serotonin transporter linked polymorphic region (5-HTTLPR) genotypes and the neural mechanisms of selective attention in young children from lower socioeconomic status (SES) backgrounds. Event-related potentials (ERPs) were recorded during a dichotic listening task from 121 children (76 females, aged 40-67 months), who were also genotyped for the short and long allele of 5-HTTLPR. The effect of selective attention was measured as the difference in ERP mean amplitudes elicited by identical probe stimuli embedded in stories when they were attended versus unattended. Compared to children homozygous for the long allele, children who carried at least one copy of the short allele showed larger effects of selective attention on neural processing. These findings link the short allele of the 5-HTTLPR to enhanced neural mechanisms of selective attention and lay the groundwork for future studies of gene-by-environment interactions in the context of key cognitive skills.

  17. 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

  18. Socio-economic inequalities in stage at diagnosis, and in time intervals on the lung cancer pathway from first symptom to treatment: systematic review and meta-analysis.

    PubMed

    Forrest, Lynne F; Sowden, Sarah; Rubin, Greg; White, Martin; Adams, Jean

    2017-05-01

    Cancer diagnosis at an early stage increases the chance of curative treatment and of survival. It has been suggested that delays on the pathway from first symptom to diagnosis and treatment may be socio-economically patterned, and contribute to socio-economic differences in receipt of treatment and in cancer survival. This review aimed to assess the published evidence for socio-economic inequalities in stage at diagnosis of lung cancer, and in the length of time spent on the lung cancer pathway. MEDLINE, EMBASE and CINAHL databases were searched to locate cohort studies of adults with a primary diagnosis of lung cancer, where the outcome was stage at diagnosis or the length of time spent within an interval on the care pathway, or a suitable proxy measure, analysed according to a measure of socio-economic position. Meta-analysis was undertaken when there were studies available with suitable data. Of the 461 records screened, 39 papers were included in the review (20 from the UK) and seven in a final meta-analysis for stage at diagnosis. There was no evidence of socio-economic inequalities in late stage at diagnosis in the most, compared with the least, deprived group (OR=1.04, 95% CI=0.92 to 1.19). No socio-economic inequalities in the patient interval or in time from diagnosis to treatment were found. Socio-economic inequalities in stage at diagnosis are thought to be an important explanatory factor for survival inequalities in cancer. However, socio-economic inequalities in stage at diagnosis were not found in a meta-analysis for lung cancer.

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

    NASA Astrophysics Data System (ADS)

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

    2013-07-01

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

  20. A global water scarcity assessment under shared socio-economic pathways - Part 2: Water availability and scarcity

    NASA Astrophysics Data System (ADS)

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

    2012-12-01

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

  1. Mediating pathways in the socio-economic gradient of child development

    PubMed Central

    Attanasio, Orazio; Grantham-McGregor, Sally

    2016-01-01

    Research has previously shown a gap of near 0.5 of a standard deviation (SD) in cognition and language development between the top and bottom household wealth quartile in children aged 6–42 months in a large representative sample of low- and middle-income families in Bogota, using the Bayley Scales of Infant and Toddler Development. The gaps in fine motor and socio-emotional development were about half that size. Developmental deficits increased with age. The current study explored the associations amongst child development, household socio-economic status (SES), and a set of potential mediating variables—parental characteristics, child biomedical factors, and the quality of the home environment—in this sample. We ran mediation tests to quantify the contribution of these variables to the SES gap, and explored the role of age as a moderator. Parental education, particularly maternal education, and the quality of the home environment mediated the SES gap in all outcomes examined. Height-for-age mediated a small amount of the deficit in language scales only. More educated mothers provided better home stimulation than less educated mothers and the home environment partly mediated the effect of maternal education. These results suggested that in interventions aimed at promoting child development, those focusing on the quality of the home environment should be effective. PMID:27885311

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

    PubMed

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

    2013-11-01

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

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

    ERIC Educational Resources Information Center

    Lundy-Wagner, Valerie

    2016-01-01

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

  4. 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…

  5. 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

  6. Building a Linked Learning Pathway: A Guide for Transforming High Schools for College and Career Success

    ERIC Educational Resources Information Center

    Atterbury, Rob

    2014-01-01

    This guide provides an overview of a more robust online guide and toolkit available through ConnectEd Studios. It supplies a glimpse of the sequence of steps involved in creating a new Linked Learning pathway. This publication can help coaches, district leadership, and pathway teams gain an understanding of the overall process of designing and…

  7. Cellular and molecular pathways linking inflammation and cancer.

    PubMed

    Porta, Chiara; Larghi, Paola; Rimoldi, Monica; Totaro, Maria Grazia; Allavena, Paola; Mantovani, Alberto; Sica, Antonio

    2009-01-01

    Several experimental and epidemiological evidence indicate that, irrespective of the trigger for the development (chronic infection/inflammation or genetic alteration), a "smouldering" inflammation is associated with the most of, if not all, tumours and supports their progression. Several evidence have highlighted that tumours promote a constant influx of myelomonocytic cells that express inflammatory mediators supporting pro-tumoral functions. Myelomonocytic cells are key orchestrators of cancer-related inflammation associated with proliferation and survival of malignant cells, subversion of adaptive immune response, angiogenesis, stroma remodelling and metastasis formation. Although the connection between inflammation and cancer is unequivocal the mechanistic basis of such association are largely unknown. Recent advances in the understanding of the cellular and molecular pathways involved in cancer-related inflammation as well as their potential relevance as diagnostic, prognostic and therapeutic targets are herein discussed.

  8. Common developmental pathways link tooth shape to regeneration

    PubMed Central

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

    2013-01-01

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

  9. 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

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

    PubMed Central

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

    2013-01-01

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

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

    ERIC Educational Resources Information Center

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

    2013-01-01

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

  12. 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…

  13. Pathways to Hazardous Drinking Among Racially and Socioeconomically Diverse Lesbian Women: Sexual Minority Stress, Rumination, Social Isolation, and Drinking to Cope.

    PubMed

    Lewis, Robin J; Mason, Tyler B; Winstead, Barbara A; Gaskins, Melissa; Irons, Lance B

    2016-01-01

    Lesbian women engage in more hazardous drinking than heterosexual women yet we know relatively little about what explains this disparity. In the present study, race, socioeconomic status, minority stress, general psychological processes and distress were examined as pathways to hazardous drinking among young (18-35 years) Black and non-Hispanic White lesbian women. We used the psychological mediation framework adaptation of minority stress theory and the reserve capacity model as theoretical underpinnings of the conceptual model in the current study. Self-identified lesbian participants (N= 867) completed a one-time online survey that assessed race, socioeconomic status, perceived sexual minority discrimination, proximal minority stress (concealment, internalized homophobia, lack of connection to lesbian community), rumination, social isolation, psychological distress, drinking to cope, and hazardous drinking. Cross-sectional results demonstrated that being Black was associated with hazardous drinking via sequential mediators of rumination, psychological distress, and drinking to cope. Socioeconomic status was associated with hazardous drinking via sequential mediators of sexual minority discrimination, proximal minority stress, rumination, social isolation, psychological distress, and drinking to cope. Understanding these pathways can aid researchers and clinicians studying and working with lesbians who are at risk for hazardous drinking.

  14. 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

  15. 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

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

    PubMed Central

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

    2016-01-01

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

  17. 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…

  18. 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

  19. 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

  20. The tor pathway regulates gene expression by linking nutrient sensing to histone acetylation.

    PubMed

    Rohde, John R; Cardenas, Maria E

    2003-01-01

    The Tor pathway mediates cell growth in response to nutrient availability, in part by inducing ribosomal protein (RP) gene expression via an unknown mechanism. Expression of RP genes coincides with recruitment of the Esa1 histone acetylase to RP gene promoters. We show that inhibition of Tor with rapamycin releases Esa1 from RP gene promoters and leads to histone H4 deacetylation without affecting promoter occupancy by Rap1 and Abf1. Genetic and biochemical evidence identifies Rpd3 as the major histone deacetylase responsible for reversing histone H4 acetylation at RP gene promoters in response to Tor inhibition by rapamycin or nutrient limitation. Our results illustrate that the Tor pathway links nutrient sensing with histone acetylation to control RP gene expression and cell growth.

  1. The Fanconi anemia pathway promotes replication-dependent DNA interstrand cross-link repair.

    PubMed

    Knipscheer, Puck; Räschle, Markus; Smogorzewska, Agata; Enoiu, Milica; Ho, The Vinh; Schärer, Orlando D; Elledge, Stephen J; Walter, Johannes C

    2009-12-18

    Fanconi anemia is a human cancer predisposition syndrome caused by mutations in 13 Fanc genes. The disorder is characterized by genomic instability and cellular hypersensitivity to chemicals that generate DNA interstrand cross-links (ICLs). A central event in the activation of the Fanconi anemia pathway is the mono-ubiquitylation of the FANCI-FANCD2 complex, but how this complex confers ICL resistance remains enigmatic. Using a cell-free system, we showed that FANCI-FANCD2 is required for replication-coupled ICL repair in S phase. Removal of FANCD2 from extracts inhibits both nucleolytic incisions near the ICL and translesion DNA synthesis past the lesion. Reversal of these defects requires ubiquitylated FANCI-FANCD2. Our results show that multiple steps of the essential S-phase ICL repair mechanism fail when the Fanconi anemia pathway is compromised.

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

    PubMed

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

    2009-12-04

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

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

    PubMed

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

    2014-04-01

    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.

  4. Linking Biosynthetic Gene Clusters to their Metabolites via Pathway-Targeted Molecular Networking

    PubMed Central

    Trautman, Eric P.; Crawford, Jason M.

    2016-01-01

    The connection of microbial biosynthetic gene clusters to the small molecule metabolites they encode is central to the discovery and characterization of new metabolic pathways with ecological and pharmacological potential. With increasing microbial genome sequence information being deposited into publicly available databases, it is clear that microbes have the coding capacity for many more biologically active small molecules than previously realized. Of increasing interest are the small molecules encoded by the human microbiome, as these metabolites likely mediate a variety of currently uncharacterized human-microbe interactions that influence health and disease. In this mini-review, we describe the ongoing biosynthetic, structural, and functional characterizations of the genotoxic colibactin pathway in gut bacteria as a thematic example of linking biosynthetic gene clusters to their metabolites. We also highlight other natural products that are produced through analogous biosynthetic logic and comment on some current disconnects between bioinformatics predictions and experimental structural characterizations. Lastly, we describe the use of pathway-targeted molecular networking as a tool to characterize secondary metabolic pathways within complex metabolomes and to aid in downstream metabolite structural elucidation efforts. PMID:26456470

  5. Genome-Scale Networks Link Neurodegenerative Disease Genes to α-Synuclein through Specific Molecular Pathways.

    PubMed

    Khurana, Vikram; Peng, Jian; Chung, Chee Yeun; Auluck, Pavan K; Fanning, Saranna; Tardiff, Daniel F; Bartels, Theresa; Koeva, Martina; Eichhorn, Stephen W; Benyamini, Hadar; Lou, Yali; Nutter-Upham, Andy; Baru, Valeriya; Freyzon, Yelena; Tuncbag, Nurcan; Costanzo, Michael; San Luis, Bryan-Joseph; Schöndorf, David C; Barrasa, M Inmaculada; Ehsani, Sepehr; Sanjana, Neville; Zhong, Quan; Gasser, Thomas; Bartel, David P; Vidal, Marc; Deleidi, Michela; Boone, Charles; Fraenkel, Ernest; Berger, Bonnie; Lindquist, Susan

    2017-02-22

    Numerous genes and molecular pathways are implicated in neurodegenerative proteinopathies, but their inter-relationships are poorly understood. We systematically mapped molecular pathways underlying the toxicity of alpha-synuclein (α-syn), a protein central to Parkinson's disease. Genome-wide screens in yeast identified 332 genes that impact α-syn toxicity. To "humanize" this molecular network, we developed a computational method, TransposeNet. This integrates a Steiner prize-collecting approach with homology assignment through sequence, structure, and interaction topology. TransposeNet linked α-syn to multiple parkinsonism genes and druggable targets through perturbed protein trafficking and ER quality control as well as mRNA metabolism and translation. A calcium signaling hub linked these processes to perturbed mitochondrial quality control and function, metal ion transport, transcriptional regulation, and signal transduction. Parkinsonism gene interaction profiles spatially opposed in the network (ATP13A2/PARK9 and VPS35/PARK17) were highly distinct, and network relationships for specific genes (LRRK2/PARK8, ATXN2, and EIF4G1/PARK18) were confirmed in patient induced pluripotent stem cell (iPSC)-derived neurons. This cross-species platform connected diverse neurodegenerative genes to proteinopathy through specific mechanisms and may facilitate patient stratification for targeted therapy.

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

    PubMed

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

    2011-10-01

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

  7. IKKbeta suppression of TSC1 function links the mTOR pathway with insulin resistance.

    PubMed

    Lee, Dung-Fang; Kuo, Hsu-Ping; Chen, Chun-Te; Wei, Yongkun; Chou, Chao-Kai; Hung, Jen-Yu; Yen, Chia-Jui; Hung, Mien-Chie

    2008-11-01

    The proinflammatory cytokine TNFalpha is one of the factors that links obesity-derived chronic inflammation with insulin resistance. Activation of mTOR signaling pathway has been found to suppress insulin sensitivity through serine phosphorylation and the inhibition of IRS1 by mTOR and its downstream effector, S6K1. It remains elusive that whether the mTOR pathway has a role in TNFalpha-mediated insulin resistance. In the present study, we demonstrated that TNFalpha-IKKbeta-mediated inactivation of TSC1 resulted in increasing phosphorylation of IRS1 serine 307 and serine 636/639, impaired insulin-induced glucose uptake, tyrosine phosphorylation of IRS1, and the association between IRS1 and PI3K p85. Furthermore, a higher expression of pIKKbeta (S181), pTSC1(S511), and pS6(S240/244) was found in livers obtained from both C57BL/6J mice on a high-fat diet and B6.V-Lepob/J mice. Collectively, dysregulation of the TSC1/ TSC2/mTOR signaling pathway by IKKbeta is a common molecular switch for both cancer pathogenesis and diet- and obesity-induced insulin resistance.

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

    PubMed Central

    2016-01-01

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

  9. Jagged1 is the pathological link between Wnt and Notch pathways in colorectal cancer

    PubMed Central

    Rodilla, Verónica; Villanueva, Alberto; Obrador-Hevia, Antonia; Robert-Moreno, Àlex; Fernández-Majada, Vanessa; Grilli, Andrea; López-Bigas, Nuria; Bellora, Nicolás; Albà, M. Mar; Torres, Ferran; Duñach, Mireia; Sanjuan, Xavier; Gonzalez, Sara; Gridley, Thomas; Capella, Gabriel; Bigas, Anna; Espinosa, Lluís

    2009-01-01

    Notch has been linked to β-catenin-dependent tumorigenesis; however, the mechanisms leading to Notch activation and the contribution of the Notch pathway to colorectal cancer is not yet understood. By microarray analysis, we have identified a group of genes downstream of Wnt/β-catenin (down-regulated when blocking Wnt/β-catenin) that are directly regulated by Notch (repressed by γ-secretase inhibitors and up-regulated by active Notch1 in the absence of β-catenin signaling). We demonstrate that Notch is downstream of Wnt in colorectal cancer cells through β-catenin-mediated transcriptional activation of the Notch-ligand Jagged1. Consistently, expression of activated Notch1 partially reverts the effects of blocking Wnt/β-catenin pathway in tumors implanted s.c. in nude mice. Crossing APCMin/+ with Jagged1+/Δ mice is sufficient to significantly reduce the size of the polyps arising in the APC mutant background indicating that Notch is an essential modulator of tumorigenesis induced by nuclear β-catenin. We show that this mechanism is operating in human tumors from Familial Adenomatous Polyposis patients. We conclude that Notch activation, accomplished by β-catenin-mediated up-regulation of Jagged1, is required for tumorigenesis in the intestine. The Notch-specific genetic signature is sufficient to block differentiation and promote vasculogenesis in tumors whereas proliferation depends on both pathways. PMID:19325125

  10. Jagged1 is the pathological link between Wnt and Notch pathways in colorectal cancer.

    PubMed

    Rodilla, Verónica; Villanueva, Alberto; Obrador-Hevia, Antonia; Robert-Moreno, Alex; Fernández-Majada, Vanessa; Grilli, Andrea; López-Bigas, Nuria; Bellora, Nicolás; Albà, M Mar; Torres, Ferran; Duñach, Mireia; Sanjuan, Xavier; Gonzalez, Sara; Gridley, Thomas; Capella, Gabriel; Bigas, Anna; Espinosa, Lluís

    2009-04-14

    Notch has been linked to beta-catenin-dependent tumorigenesis; however, the mechanisms leading to Notch activation and the contribution of the Notch pathway to colorectal cancer is not yet understood. By microarray analysis, we have identified a group of genes downstream of Wnt/beta-catenin (down-regulated when blocking Wnt/beta-catenin) that are directly regulated by Notch (repressed by gamma-secretase inhibitors and up-regulated by active Notch1 in the absence of beta-catenin signaling). We demonstrate that Notch is downstream of Wnt in colorectal cancer cells through beta-catenin-mediated transcriptional activation of the Notch-ligand Jagged1. Consistently, expression of activated Notch1 partially reverts the effects of blocking Wnt/beta-catenin pathway in tumors implanted s.c. in nude mice. Crossing APC(Min/+) with Jagged1(+/Delta) mice is sufficient to significantly reduce the size of the polyps arising in the APC mutant background indicating that Notch is an essential modulator of tumorigenesis induced by nuclear beta-catenin. We show that this mechanism is operating in human tumors from Familial Adenomatous Polyposis patients. We conclude that Notch activation, accomplished by beta-catenin-mediated up-regulation of Jagged1, is required for tumorigenesis in the intestine. The Notch-specific genetic signature is sufficient to block differentiation and promote vasculogenesis in tumors whereas proliferation depends on both pathways.

  11. Adults with X-linked agammaglobulinemia: impact of disease on daily lives, quality of life, educational and socioeconomic status, knowledge of inheritance, and reproductive attitudes.

    PubMed

    Winkelstein, Jerry A; Conley, Mary Ellen; James, Cynthia; Howard, Vanessa; Boyle, John

    2008-09-01

    Since many children with X-linked agammaglobulinemia (XLA) can now be expected to reach adulthood, knowledge of the status of adults with XLA would be of importance to the patients, their families, and the physicians caring for these patients. We performed the current study in adults with XLA to examine the impact of XLA on their daily lives and quality of life, their educational and socioeconomic status, their knowledge of the inheritance of their disorder, and their reproductive attitudes. Physicians who had entered adult patients with XLA in a national registry were asked to pass on a survey instrument to their patients. The patients then filled out the survey instrument and returned it directly to the investigators. Adults with XLA were hospitalized more frequently and missed more work and/or school than did the general United States population. However, their quality of life was comparable to that of the general United States population. They achieved a higher level of education and had a higher income than did the general United States population. Their knowledge of the inheritance of their disease was excellent. Sixty percent of them would not exercise any reproductive planning options as a result of their disease. The results of the current study suggest that although the disease impacts the daily lives of adults with XLA, they still become productive members of society and excel in many areas.

  12. Neurocognitive development in socioeconomic context: multiple mechanisms and implications for measuring socioeconomic status

    PubMed Central

    Ursache, Alexandra; Noble, Kimberly G.

    2015-01-01

    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 high 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

  13. 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.

  14. Impact of service redesign on the socioeconomic inequity in revascularisation rates for patients with acute myocardial infarction: a natural experiment and electronic record-linked cohort study

    PubMed Central

    Evans, Lloyd W; van Woerden, Hugo; Fone, David

    2016-01-01

    Aim To investigate the impact of service redesign in the provision of revascularisation procedures on the historical socioeconomic inequity in revascularisation rates for patients with acute myocardial infarction (AMI). Design Natural experiment and retrospective cohort study using linked data sets in the Secure Anonymised Information Linkage databank. Non-randomised intervention An increase in the capacity of revascularisation procedures and service redesign in the provision of revascularisation in late 2011 to early 2012. Setting South Wales cardiac network, Census 2011 population 1 359 051 aged 35 years and over. Participants 9128 participants admitted to an NHS hospital with a first AMI between 1 January 2010 and 30 June 2013, with 6-months follow-up. Main outcome measure Hazard ratios (HRs) for the time to revascularisation for deprivation quintiles, age, gender, comorbidities, rural–urban classification and revascularisation facilities of admitting hospital. Results In the preintervention period, there was a statistically significant decreased adjusted risk of revascularisation for participants in the most deprived quintile compared to the least deprived quintile (HR 0.80; 95% CI 0.69 to 0.92, p=0.002). In the postintervention period, the increase in revascularisation rates was statistically significant in all quintiles, and there was no longer any statistically significant difference in the adjusted revascularisation risk between the most and the least deprived quintile (HR 1.04; 95% CI 0.89 to 1.20, p<0.649). However, inequity persisted for those aged 75 years and over (HR 0.40; 95% CI 0.35 to 0.46, p<0.001) and women (HR 0.77; 95% CI 0.70 to 0.86, p<0.001). Conclusions Socioeconomic inequity of access to revascularisation was no longer apparent following redesign of revascularisation services in the south Wales cardiac network, although inequity persisted for women and those aged 75+ years. Increasing the capacity of revascularisation did not

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

    PubMed

    Beaulieu, Marc-Alexandre

    2013-03-01

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

  16. Molecular pathways linking non-shivering thermogenesis and obesity: focusing on brown adipose tissue development.

    PubMed

    Valente, Angelica; Jamurtas, Athanasios Z; Koutedakis, Yiannis; Flouris, Andreas D

    2015-02-01

    An increase in energy intake and/or a decrease in energy expenditure lead to fat storage, causing overweight and obesity phenotypes. The objective of this review was to analyse, for the first time using a systematic approach, all published evidence from the past 8 years regarding the molecular pathways linking non-shivering thermogenesis and obesity in mammals, focusing on mechanisms involved in brown adipose tissue development. Two major databases were scanned from 2006 to 2013 using 'brown adipose tissue' AND 'uncoupling protein-1' AND 'mammalian thermoregulation' AND 'obesity' as key words. A total of 61 articles were retrieved using the search criteria. The available research used knockout methodologies, various substances, molecules and agonist treatments, or different temperature and diet conditions, to assess the molecular pathways linking non-shivering thermogenesis and obesity. By integrating the results of the evaluated animal and human studies, our analysis identified specific molecules that enhance non-shivering thermogenesis and metabolism by: (i) stimulating 'brite' (brown-like) cell development in white adipose tissue; (ii) increasing uncoupling protein-1 expression in brite adipocytes; and (iii) augmenting brown and/or brite adipose tissue mass. The latter can be also increased through low temperature, hibernation and/or molecules involved in brown adipocyte differentiation. Cold stimuli and/or certain molecules activate uncoupling protein-1 in the existing brown adipocytes, thus increasing total energy expenditure by a magnitude proportional to the number of available brown adipocytes. Future research should address the interplay between body mass, brown adipose tissue mass, as well as the main molecules involved in brite cell development.

  17. Elevated C-Reactive Protein in Children from Risky Neighborhoods: Evidence for a Stress Pathway Linking Neighborhoods and Inflammation in Children

    PubMed Central

    Broyles, Stephanie T.; Staiano, Amanda E.; Drazba, Kathryn T.; Gupta, Alok K.; Sothern, Melinda; Katzmarzyk, Peter T.

    2012-01-01

    Background Childhood socioeconomic status is linked to adult cardiovascular disease and disease risk. One proposed pathway involves inflammation due to exposure to a stress-inducing neighborhood environment. Whether CRP, a marker of systemic inflammation, is associated with stressful neighborhood conditions among children is unknown. Methods and Results The sample included 385 children 5–18 years of age from 255 households and 101 census tracts. Multilevel logistic regression analyses compared children and adolescents with CRP levels >3 mg/L to those with levels ≤3 mg/L across neighborhood environments. Among children living in neighborhoods (census tracts) in the upper tertile of poverty or crime, 18.6% had elevated CRP levels, in contrast to 7.9% of children living in neighborhoods with lower levels of poverty and crime. Children from neighborhoods with the highest levels of either crime or poverty had 2.7 (95% CI: 1.2–6.2) times the odds of having elevated CRP levels when compared to children from other neighborhoods, independent of adiposity, demographic and behavioral differences. Conclusions Children living in neighborhoods with high levels of poverty or crime had elevated CRP levels compared to children from other neighborhoods. This result is consistent with a psychosocial pathway favoring early development of cardiovascular risk that involves chronic stress from exposure to socially- and physically-disordered neighborhoods characteristic of poverty. PMID:23049799

  18. Mast cells' involvement in inflammation pathways linked to depression: evidence in mastocytosis.

    PubMed

    Georgin-Lavialle, S; Moura, D S; Salvador, A; Chauvet-Gelinier, J-C; Launay, J-M; Damaj, G; Côté, F; Soucié, E; Chandesris, M-O; Barète, S; Grandpeix-Guyodo, C; Bachmeyer, C; Alyanakian, M-A; Aouba, A; Lortholary, O; Dubreuil, P; Teyssier, J-R; Trojak, B; Haffen, E; Vandel, P; Bonin, B; Hermine, O; Gaillard, R

    2016-11-01

    Converging sources of evidence point to a role for inflammation in the development of depression, fatigue and cognitive dysfunction. More precisely, the tryptophan (TRP) catabolism is thought to play a major role in inflammation-induced depression. Mastocytosis is a rare disease in which chronic symptoms, including depression, are related to mast cell accumulation and activation. Our objectives were to study the correlations between neuropsychiatric features and the TRP catabolism pathway in mastocytosis in order to demonstrate mast cells' potential involvement in inflammation-induced depression. Fifty-four patients with mastocytosis and a mean age of 50.1 years were enrolled in the study and compared healthy age-matched controls. Depression and stress were evaluated with the Beck Depression Inventory revised and the Perceived Stress Scale. All patients had measurements of TRP, serotonin (5-HT), kynurenine (KYN), indoleamine 2,3-dioxygenase 1 (IDO1) activity (ratio KYN/TRP), kynurenic acid (KA) and quinolinic acid (QA). Patients displayed significantly lower levels of TRP and 5-HT without hypoalbuminemia or malabsorption, higher IDO1 activity, and higher levels of KA and QA, with an imbalance towards the latter. High perceived stress and high depression scores were associated with low TRP and high IDO1 activity. In conclusion, TRP metabolism is altered in mastocytosis and correlates with perceived stress and depression, demonstrating mast cells' involvement in inflammation pathways linked to depression.

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

    PubMed Central

    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

  20. Spin-selective charge transport pathways through p-oligophenylene-linked donor-bridge-acceptor molecules.

    PubMed

    Scott, Amy M; Miura, Tomoaki; Ricks, Annie Butler; Dance, Zachary E X; Giacobbe, Emilie M; Colvin, Michael T; Wasielewski, Michael R

    2009-12-09

    A series of donor-bridge-acceptor (D-B-A) triads have been synthesized in which the donor, 3,5-dimethyl-4-(9-anthracenyl)julolidine (DMJ-An), and the acceptor, naphthalene-1,8:4,5-bis(dicarboximide) (NI), are linked by p-oligophenylene (Ph(n)) bridging units (n = 1-5). Photoexcitation of DMJ-An produces DMJ(+*)-An(-*) quantitatively, so that An(-*) acts as a high potential electron donor, which rapidly transfers an electron to NI yielding a long-lived spin-coherent radical ion pair (DMJ(+*)-An-Ph(n)-NI(-*)). The charge transfer properties of 1-5 have been studied using transient absorption spectroscopy, magnetic field effects (MFEs) on radical pair and triplet yields, and time-resolved electron paramagnetic resonance (TREPR) spectroscopy. The charge separation (CS) and recombination (CR) reactions exhibit exponential distance dependencies with damping coefficients of beta = 0.35 A(-1) and 0.34 A(-1), respectively. Based on these data, a change in mechanism from superexchange to hopping was not observed for either process in this system. However, the CR reaction is spin-selective and produces the singlet ground state and both (3*)An and (3*)NI. A kinetic analysis of the MFE data shows that superexchange dominates both pathways with beta = 0.48 A(-1) for the singlet CR pathway and beta = 0.35 A(-1) for the triplet CR pathway. MFEs and TREPR experiments were used to measure the spin-spin exchange interaction, 2J, which is directly related to the electronic coupling matrix element for CR, V(CR)(2). The magnitude of 2J also shows an exponential distance dependence with a damping coefficient alpha = 0.36 A(-1), which agrees with the beta values obtained from the distance dependence for triplet CR. These results were analyzed in terms of the bridge molecular orbitals that participate in the charge transport mechanism.

  1. Slm35 links mitochondrial stress response and longevity through TOR signaling pathway

    PubMed Central

    Jose, L. Aguilar-Lopez; Laboy, Raymond; Fabiola, Jaimes-Miranda; Garay, Erika; Alexander, DeLuna; Funes, Soledad

    2016-01-01

    In most eukaryotic cells mitochondria are essential organelles involved in a great variety of cellular functions. One of the physiological processes linked to mitochondria is aging, a gradual process of damage accumulation that eventually promotes cell death. Aging depends on a balance between mitochondrial biogenesis, function and degradation. It has been previously shown that Tor1, Sch9 and Ras2 are activated in response to nutrient availability and regulate cell growth and division. A deficiency in any of these genes promotes lifespan extension and cell protection during oxidative and heat shock stress. In this work we report that in Saccharomyces cerevisiae, the uncharacterized mitochondrial protein Slm35 is functionally linked with the TOR signaling pathway. A Δtor1Δslm35 strain shows a severe decrease in lifespan and is unable to contend with oxidative and heat shock stresses. Specifically, this mutant shows decreased catalase activity indicating a misregulation of ROS scavenging mechanisms. In this study we show that Slm35 is also relevant for mitochondrial network dynamics and mitophagy. The results presented here suggest that Slm35 plays an important role connecting mitochondrial function with cytosolic responses and cell adaptation to stress and aging. PMID:27922823

  2. Slm35 links mitochondrial stress response and longevity through TOR signaling pathway.

    PubMed

    Aguilar-Lopez, Jose L; Laboy, Raymond; Jaimes-Miranda, Fabiola; Garay, Erika; DeLuna, Alexander; Funes, Soledad

    2016-12-02

    In most eukaryotic cells mitochondria are essential organelles involved in a great variety of cellular functions. One of the physiological processes linked to mitochondria is aging, a gradual process of damage accumulation that eventually promotes cell death. Aging depends on a balance between mitochondrial biogenesis, function and degradation. It has been previously shown that Tor1, Sch9 and Ras2 are activated in response to nutrient availability and regulate cell growth and division. A deficiency in any of these genes promotes lifespan extension and cell protection during oxidative and heat shock stress. In this work we report that in Saccharomyces cerevisiae, the uncharacterized mitochondrial protein Slm35 is functionally linked with the TOR signaling pathway. A Δtor1Δslm35 strain shows a severe decrease in lifespan and is unable to contend with oxidative and heat shock stresses. Specifically, this mutant shows decreased catalase activity indicating a misregulation of ROS scavenging mechanisms. In this study we show that Slm35 is also relevant for mitochondrial network dynamics and mitophagy. The results presented here suggest that Slm35 plays an important role connecting mitochondrial function with cytosolic responses and cell adaptation to stress and aging.

  3. XPF-ERCC1 participates in the Fanconi anemia pathway of cross-link repair.

    PubMed

    Bhagwat, Nikhil; Olsen, Anna L; Wang, Anderson T; Hanada, Katsuhiro; Stuckert, Patricia; Kanaar, Roland; D'Andrea, Alan; Niedernhofer, Laura J; McHugh, Peter J

    2009-12-01

    Interstrand cross-links (ICLs) prevent DNA strand separation and, therefore, transcription and replication, making them extremely cytotoxic. The precise mechanism by which ICLs are removed from mammalian genomes largely remains elusive. Genetic evidence implicates ATR, the Fanconi anemia proteins, proteins required for homologous recombination, translesion synthesis, and at least two endonucleases, MUS81-EME1 and XPF-ERCC1. ICLs cause replication-dependent DNA double-strand breaks (DSBs), and MUS81-EME1 facilitates DSB formation. The subsequent repair of these DSBs occurs via homologous recombination after the ICL is unhooked by XPF-ERCC1. Here, we examined the effect of the loss of either nuclease on FANCD2 monoubiquitination to determine if the nucleolytic processing of ICLs is required for the activation of the Fanconi anemia pathway. FANCD2 was monoubiquitinated in Mus81(-/-), Ercc1(-/-), and XPF-deficient human, mouse, and hamster cells exposed to cross-linking agents. However, the monoubiquitinated form of FANCD2 persisted longer in XPF-ERCC1-deficient cells than in wild-type cells. Moreover, the levels of chromatin-bound FANCD2 were dramatically reduced and the number of ICL-induced FANCD2 foci significantly lower in XPF-ERCC1-deficient cells. These data demonstrate that the unhooking of an ICL by XPF-ERCC1 is necessary for the stable localization of FANCD2 to the chromatin and subsequent homologous recombination-mediated DSB repair.

  4. 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.

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

    PubMed Central

    Richardson, Lindsey; Small, Will; Kerr, Thomas

    2015-01-01

    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 and conducted semi-structured retrospective interviews and employed a thematic analysis that draws on concepts from life course theory to explore mechanisms and pathways linking drug use and labour market trajectories. 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 multi-dimensional supports to mitigate the initiation, accumulation and entrenchment of labour market and drug-related disadvantage. PMID:26358407

  6. Socioeconomic environment

    SciTech Connect

    1995-10-01

    This portion of the Energy vision 2020 draft report discusses the socioeconomic environment of the Tennessee Valley region. It describes the region and mentions geographical factors, current economy, the agricultural sector, and future trends in the economy of the region.

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

    PubMed Central

    2013-01-01

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

  8. The human core of the shared socioeconomic pathways: Population scenarios by age, sex and level of education for all countries to 2100.

    PubMed

    Kc, Samir; Lutz, Wolfgang

    2017-01-01

    This paper applies the methods of multi-dimensional mathematical demography to project national populations based on alternative assumptions on future, fertility, mortality, migration and educational transitions that correspond to the five shared socioeconomic pathways (SSP) storylines. In doing so it goes a significant step beyond past population scenarios in the IPCC context which considered only total population size. By differentiating the human population not only by age and sex-as is conventionally done in demographic projections-but also by different levels of educational attainment the most fundamental aspects of human development and social change are being explicitly addressed through modeling the changing composition of populations by these three important individual characteristics. The scenarios have been defined in a collaborative effort of the international Integrated Assessment Modeling community with the medium scenario following that of a major new effort by the Wittgenstein Centre for Demography and Global Human Capital (IIASA, OEAW, WU) involving over 550 experts from around the world. As a result, in terms of total world population size the trajectories resulting from the five SSPs stay very close to each other until around 2030 and by the middle of the century already a visible differentiation appears with the range between the highest (SSP3) and the lowest (SSP1) trajectories spanning 1.5 billion. The range opens up much more with the SSP3 reaching 12.6 billion in 2100 and SSP1 falling to 6.9 billion which is lower than today's world population.

  9. The link between the PDL1 costimulatory pathway and Th17 in fetomaternal tolerance.

    PubMed

    D'Addio, Francesca; Riella, Leonardo V; Mfarrej, Bechara G; Chabtini, Lola; Adams, La Tonya; Yeung, Melissa; Yagita, Hideo; Azuma, Miyuki; Sayegh, Mohamed H; Guleria, Indira

    2011-11-01

    Fetomaternal tolerance has been shown to depend both on regulatory T cells (Tregs) and negative signals from the PD1-PDL1 costimulatory pathway. More recently, IL-17-producing T cells (Th17) have been recognized as a barrier in inducing tolerance in transplantation. In this study, we investigate the mechanisms of PDL1-mediated regulation of fetomaternal tolerance using an alloantigen-specific CD4(+) TCR transgenic mouse model system (ABM-tg mouse). PDL1 blockade led to an increase in embryo resorption and a reduction in litter size. This was associated with a decrease in Tregs, leading to a lower Treg/effector T cell ratio. Moreover, PDL1 blockade inhibited Ag-specific alloreactive T cell apoptosis and induced apoptosis of Tregs and a shift toward higher frequency of Th17 cells, breaking fetomaternal tolerance. These Th17 cells arose predominantly from CD4(+)Foxp3(-) cells, rather than from conversion of Tregs. Locally in the placenta, similar decrease in regulatory and apoptotic markers was observed by real-time PCR. Neutralization of IL-17 abrogated the anti-PDL1 effect on fetal survival rate and restored Treg numbers. Finally, the adoptive transfer of Tregs was also able to improve fetal survival in the setting of PDL1 blockade. This is to our knowledge the first report using an alloantigen-specific model that establishes a link between PDL1, Th17 cells, and fetomaternal tolerance.

  10. 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…

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

    PubMed Central

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

    2015-01-01

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

  12. Effect of uraemia on endothelial cell damage is mediated by the integrin linked kinase pathway

    PubMed Central

    García-Jérez, Andrea; Luengo, Alicia; Carracedo, Julia; Ramírez-Chamond, Rafael; Rodriguez-Puyol, Diego; Rodriguez-Puyol, Manuel; Calleros, Laura

    2015-01-01

    Patients with chronic kidney disease (CKD) have a higher risk of developing cardiovascular diseases. Their vascular endothelium is dysfunctional, among other things, because it is permanently exposed to uraemic toxins, several of which, mostly protein-bound compounds such as indoxyl sulfate (IS) and p-cresyl sulphate, having poor clearance by conventional dialysis, induce endothelial toxicity. However, the molecular mechanism by which uraemic toxins regulate early stages of endothelial dysfunction remains unclear. Recent studies have demonstrated the important role of integrin-linked kinase (ILK) in the maintenance of endothelial integrity. In this study, we investigate the involvement of ILK in the mechanism underlying vascular endothelial damage that occurs in uraemia. First, we show that incubation of EA.hy926 cells with human uraemic serum from CKD patients upregulates ILK activity. This ILK activation also occurs when the cells are exposed to IS (25–100 μg ml−1), p-cresol (10–100 μg ml−1) or both combined, compared to human serum control. Next, we observed that high doses of both toxins together induce a slight decrease in cell proliferation and increase apoptosis and reactive oxygen species production. Interestingly, these toxic effects displayed a strong increase when the ILK protein is knocked down by small interfering RNA, even at low doses of uraemic toxins. Abrogation of AKT has demonstrated the ILK/AKT signalling pathway involved in these processes. This study has demonstrated the implication of ILK in the protection against endothelial cell damage induced by uraemic toxins, a molecular mechanism that could play a protective role in the early stages of endothelial dysfunction observed in uraemic patients. PMID:25398526

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

    SciTech Connect

    Ushijima, Hironori; Maeda, Masatomo

    2012-07-13

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

  14. 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

  15. The Contours of Inequality: The Links between Socio-Economic Status of Students and Other Variables at the University of Johannesburg

    ERIC Educational Resources Information Center

    van Zyl, André

    2016-01-01

    The low level of student success in South Africa is an intractable problem, with levels of success differing between the various groups that make up South African society. One of the major constraints influencing student success involves the socio-economic status (SES) of newly entering students. In the South African context, with its very high…

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

    ERIC Educational Resources Information Center

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

    2010-01-01

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

  17. 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

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

    PubMed Central

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

    2015-01-01

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

  19. Neisseria gonorrhoeae O-linked pilin glycosylation: functional analyses define both the biosynthetic pathway and glycan structure

    PubMed Central

    Aas, Finn Erik; Vik, Åshild; Vedde, John; Koomey, Michael; Egge-Jacobsen, Wolfgang

    2007-01-01

    Neisseria gonorrhoeae expresses an O-linked protein glycosylation pathway that targets PilE, the major pilin subunit protein of the Type IV pilus colonization factor. Efforts to define glycan structure and thus the functions of pilin glycosylation (Pgl) components at the molecular level have been hindered by the lack of sensitive methodologies. Here, we utilized a ‘top-down’ mass spectrometric approach to characterize glycan status using intact pilin protein from isogenic mutants. These structural data enabled us to directly infer the function of six components required for pilin glycosylation and to define the glycan repertoire of strain N400. Additionally, we found that the N. gonorrhoeae pilin glycan is O-acetylated, and identified an enzyme essential for this unique modification. We also identified the N. gonorrhoeae pilin oligosaccharyltransferase using bioinformatics and confirmed its role in pilin glycosylation by directed mutagenesis. Finally, we examined the effects of expressing the PglA glycosyltransferase from the Campylobacter jejuni N-linked glycosylation system that adds N-acetylgalactosamine onto undecaprenylpyrophosphate-linked bacillosamine. The results indicate that the C. jejuni and N. gonorrhoeae pathways can interact in the synthesis of O-linked di- and trisaccharides, and therefore provide the first experimental evidence that biosynthesis of the N. gonorrhoeae pilin glycan involves a lipid-linked oligosaccharide precursor. Together, these findings underpin more detailed studies of pilin glycosylation biology in both N. gonorrhoeae and N. meningitidis, and demonstrate how components of bacterial O- and N-linked pathways can be combined in novel glycoengineering strategies. PMID:17608667

  20. Emerging evidence of a link between the polycystins and the mTOR pathways.

    PubMed

    Boletta, Alessandra

    2009-10-28

    Autosomal dominant polycystic kidney disease (ADPKD) is a genetic disease characterized by the formation of renal cysts. This disease can be caused by mutations in two genes, PKD1 and PKD2, which encode polycystin-1 (PC-1) and -2 (PC-2), respectively.PC-1 is a large plasma membrane receptor involved in the regulation of several biological functions and signaling pathways, and PC-2 is a calcium channel of the TRP family. The two proteins associate in a complex to prevent cyst formation, but the precise mechanism(s) involved remain largely unknown.This review will focus on recent advances in our understanding of the functions of polycystins and their role in signal transduction.Increased activity of the mammalian target of rapamycin (mTOR) kinase has been observed in cysts found in ADPKD tissues. Rapamycin has been shown to have beneficial effects in rodent models of polycystic kidney disease, prompting the initiation of pilot clinical trials with human patients. Furthermore, a direct role for PC-1 in the regulation of cell growth (size) via mTOR has recently been demonstrated.Major advancements in the study of mTOR biology have highlighted that this kinase exists in association with two different complexes, mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). The mTORC1 complex regulates cell growth (size), proliferation, translation and autophagy, and mTORC2 regulates the actin cytoskeleton and apoptosis. Interestingly, mTORC2 has been shown to contain the kinase responsible for the phosphorylation of Akt at Serine 473. Previous studies have shown that PC-1 controls the PI 3-kinase/Akt cascade to regulate apoptosis and the actin cytoskeleton, suggesting that this receptor might regulate mTOR at several levels.This review aims to discuss three different, inter-related themes emerging from the literature: (i) studies performed in our and other laboratories collectively suggest that PC-1 might be able to differentially regulate the two mTOR complexes; (ii) several

  1. Cell signaling pathways in the adrenal cortex: Links to stem/progenitor biology and neoplasia.

    PubMed

    Penny, Morgan K; Finco, Isabella; Hammer, Gary D

    2017-04-15

    The adrenal cortex is a dynamic tissue responsible for the synthesis of steroid hormones, including mineralocorticoids, glucocorticoids, and androgens in humans. Advances have been made in understanding the role of adrenocortical stem/progenitor cell populations in cortex homeostasis and self-renewal. Recently, large molecular profiling studies of adrenocortical carcinoma (ACC) have given insights into proteins and signaling pathways involved in normal tissue homeostasis that become dysregulated in cancer. These data provide an impetus to examine the cellular pathways implicated in adrenocortical disease and study connections, or lack thereof, between adrenal homeostasis and tumorigenesis, with a particular focus on stem and progenitor cell pathways. In this review, we discuss evidence for stem/progenitor cells in the adrenal cortex, proteins and signaling pathways that may regulate these cells, and the role these proteins play in pathologic and neoplastic conditions. In turn, we also examine common perturbations in adrenocortical tumors (ACT) and how these proteins and pathways may be involved in adrenal homeostasis.

  2. IKK beta suppression of TSC1 links inflammation and tumor angiogenesis via the mTOR pathway.

    PubMed

    Lee, Dung-Fang; Kuo, Hsu-Ping; Chen, Chun-Te; Hsu, Jung-Mao; Chou, Chao-Kai; Wei, Yongkun; Sun, Hui-Lung; Li, Long-Yuan; Ping, Bo; Huang, Wei-Chien; He, Xianghuo; Hung, Jen-Yu; Lai, Chien-Chen; Ding, Qingqing; Su, Jen-Liang; Yang, Jer-Yen; Sahin, Aysegul A; Hortobagyi, Gabriel N; Tsai, Fuu-Jen; Tsai, Chang-Hai; Hung, Mien-Chie

    2007-08-10

    TNFalpha has recently emerged as a regulator linking inflammation to cancer pathogenesis, but the detailed cellular and molecular mechanisms underlying this link remain to be elucidated. The tuberous sclerosis 1 (TSC1)/TSC2 tumor suppressor complex serves as a repressor of the mTOR pathway, and disruption of TSC1/TSC2 complex function may contribute to tumorigenesis. Here we show that IKKbeta, a major downstream kinase in the TNFalpha signaling pathway, physically interacts with and phosphorylates TSC1 at Ser487 and Ser511, resulting in suppression of TSC1. The IKKbeta-mediated TSC1 suppression activates the mTOR pathway, enhances angiogenesis, and results in tumor development. We further find that expression of activated IKKbeta is associated with TSC1 Ser511 phosphorylation and VEGF production in multiple tumor types and correlates with poor clinical outcome of breast cancer patients. Our findings identify a pathway that is critical for inflammation-mediated tumor angiogenesis and may provide a target for clinical intervention in human cancer.

  3. 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…

  4. 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...

  5. 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

  6. The role of the TOR pathway in mediating the link between nutrition and longevity.

    PubMed

    Lushchak, Oleh; Strilbytska, Olha; Piskovatska, Veronika; Storey, Kenneth B; Koliada, Alexander; Vaiserman, Alexander

    2017-03-16

    The target of rapamycin (TOR) pathway integrates signals from extracellular and intracellular agents, such as growth factors, nutrients, mediators of energy balance, oxygen availability and other environmental cues. It allows the regulation of multiple cellular processes including protein and lipid synthesis, ribosome biogenesis, autophagy and metabolic processes. Being conserved across different phyla, TOR regulates longevity of various organisms in response to dietary conditions. In this review we described the main components of the TOR pathway and its upstream effectors and downstream processes in relation to aging. The potential contribution of the TOR pathway in lifespan-extending effects of varied dietary interventions, and the anti-aging drugs rapamycin and metformin direct or indirect regulation of TOR activity in yeasts, worms, flies and mammals are also discussed.

  7. Ozone and Trace Gas Trends in the UK and Links to Changing Air Mass Pathways

    NASA Astrophysics Data System (ADS)

    Fleming, Z.; Monks, P. S.; Reeves, C.; Bohnenstengel, S.

    2014-12-01

    Trace gas measurements from UK measurement sites on the North Sea coast and in central London reveal a complicated relationship between NO2, CO, hydrocarbons and ozone. Due to the location of the sites, they receive air masses from the UK, Europe, the North sea, Scandinavia and the Arctic and Atlantic Seas and any seasonality is hard to discern. The transport pathway of air masses that can change on an hourly timescale clearly influences the trace gas levels. Investigations into how the transport pathways have changed over the years, using the NAME dispersion model try to elucidate whether it is the 'where' (transport pathway) or the 'what' (trace gas emissions) that is leading to the ozone trends recorded over the past few years.

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

    SciTech Connect

    Gopal, P.K.; Ballou, C.E.

    1987-12-01

    The yeast Saccharomyces cerevisiae X2180 strain with the mnn1 mnn2 mnn9 mutations, all of which affect mannoprotein glycosylation, synthesizes N-linked oligosaccharides. Membrane fractions from the mnn1 mnn2 and mnn1 mnn2 mnn9 mutants are equally effective in catalyzing transfer from GDP-(/sup 3/H)mannose to add mannose in both ..cap alpha..1 ..-->.. 2 and ..cap alpha..1 ..-->.. 6 linkages to an oligosaccharide. Neither membrane preparation can utilize the homologous mnn1 mnn2 mnn9 oligosaccharide as an acceptor. Thus, addition of the ..cap alpha..1 ..-->.. 2-linked mannose side chain to the terminal ..cap alpha..1 ..-->.. 6-linked mannose in oligosaccharides of the mnn9 mutant inhibits the elongation reaction and may serve as an important structural control of mannoprotein glycosylation. The mnn9 mutation also increases the transit time for invertase secretion, meaning that this mutation could affect the processing machinery in the Golgi apparatus.

  9. 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…

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

    PubMed Central

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

    2015-01-01

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

  11. 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…

  12. Caenorhabditis elegans POLQ-1 and HEL-308 function in two distinct DNA interstrand cross-link repair pathways.

    PubMed

    Muzzini, Diego M; Plevani, Paolo; Boulton, Simon J; Cassata, Giuseppe; Marini, Federica

    2008-06-01

    DNA interstrand cross-links (ICLs) are highly cytotoxic DNA lesions hindering DNA replication and transcription. Whereas in bacteria and yeast the molecular mechanisms involved in ICL repair are genetically well dissected, the scenario in multicellular organisms remains unclear. Here, we report that the two new mus308 genes, polq-1 and hel-308 are involved in ICL repair in Caenorhabditis elegans. After treatment with ICL agents, a decrease in survival and an increase in checkpoint-induced cell-cycle arrest and apoptosis of germ cells is observed in mutants of both genes. Although sensitive to ICL agents and to a minor extent to IR, cytological and epistatic analyses suggest that polq-1 and hel-308 are involved in different DNA repair pathways. While hel-308 functions in a Fanconi anemia-dependent pathway, polq-1 has a role in a novel distinct and brc-1 (CeBRCA1)-dependent ICL repair process in metazoans.

  13. Metabolic analysis reveals changes in the mevalonate and juvenile hormone synthesis pathways linked to the mosquito reproductive physiology.

    PubMed

    Rivera-Perez, Crisalejandra; Nouzova, Marcela; Lamboglia, Ivanna; Noriega, Fernando G

    2014-08-01

    Juvenile hormone (JH) regulates reproductive maturation in insects; therefore interruption of JH biosynthesis has been considered as a strategy for the development of target-specific insecticides. The corpora allata (CA) from mosquitoes is highly specialized to supply variable levels of JH, which are linked to ovarian developmental stages and influenced by nutritional signals. However, very little is known about how changes in JH synthesis relate to reproductive physiology and how JH synthesis regulation is translated into changes in the CA machinery. With the advent of new methods that facilitate the analysis of transcripts, enzymes and metabolites in the minuscule CA, we were able to provide comprehensive descriptions of the mevalonic (MVA) and JH synthesis pathways by integrating information on changes in the basic components of those pathways. Our results revealed remarkable dynamic changes in JH synthesis and exposed part of a complex mechanism that regulates CA activity. Principal component (PC) analyses validated that both pathways (MVAP and JH-branch) are transcriptionally co-regulated as a single unit, and catalytic activities for the enzymes of the MVAP and JH-branch also changed in a coordinate fashion. Metabolite studies showed that global fluctuations in the intermediate pool sizes in the MVAP and JH-branch were often inversely related. PC analyses suggest that in female mosquitoes, there are at least 4 developmental switches that alter JH synthesis by modulating the flux at distinctive points in both pathways.

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

    PubMed

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

    2009-01-01

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

  15. Details for Manuscript Number SSM-D-04-00268R3 “Urban-Rural Differences in the Socioeconomic Deprivation—Sexual Behavior Link in Kenya”

    PubMed Central

    Zulu, Eliya M.; Ezeh, Alex C.

    2007-01-01

    We compare the impact of socioeconomic deprivation on risky sexual outcomes in rural and urban Kenya. Quantitative data are drawn from the Demographic & Health Surveys (DHS) and qualitative data from the Sexual Networking and Associated Reproductive and Social Health Concerns study. Using two separate indicators of deprivation we show that, although poverty is significantly associated with the examined sexual outcomes in all settings, the urban poor are significantly more likely than their rural counterparts to have an early sexual debut and a greater incidence of multiple sexual partnerships. The disadvantage of the urban poor is accentuated for married women; those in Nairobi’s slums are at least three times as likely to have multiple sexual partners as their rural counterparts. The implications of these findings are discussed. PMID:17113695

  16. 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

  17. Linking social change and developmental change: shifting pathways of human development.

    PubMed

    Greenfield, Patricia M

    2009-03-01

    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 low-technology environments to urban residence, formal schooling, commerce, and high-technology environments. The former ecology is summarized by the German term Gemeinschaft ("community") and the latter by the German term Gesellschaft ("society"; Tönnies, 1887/1957). A review of empirical research demonstrates that, through adaptive processes, movement of any ecological variable in a Gesellschaft direction shifts cultural values in an individualistic direction and developmental pathways toward more independent social behavior and more abstract cognition--to give a few examples of the myriad behaviors that respond to these sociodemographic changes. In contrast, the (much less frequent) movement of any ecological variable in a Gemeinschaft direction is predicted to move cultural values and developmental pathways in the opposite direction. In conclusion, sociocultural environments are not static either in the developed or the developing world and therefore must be treated dynamically in developmental research.

  18. 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

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

    PubMed

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

    2015-12-01

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

  20. The aspartate-family pathway of plants: linking production of essential amino acids with energy and stress regulation.

    PubMed

    Galili, Gad

    2011-02-01

    The Asp family pathway of plants is highly important from a nutritional standpoint because it leads to the synthesis of the four essential amino acids Lys, Thr, Met and Ile. These amino acids are not synthesized by human and its monogastric livestock and should be supplemented in their diets. Among the Asp-family amino acids, Lys is considered as the nutritionally most important essential amino acid because its level is most limiting in cereal grains, representing the largest source of plant foods and feeds worldwide. Metabolic engineering approaches led to significant increase in Lys level in seeds by enhancing its synthesis and reducing its catabolism. However, results from the model plant Arabidopsis showed that this approach may retard seed germination due to a major negative effect on the levels of a number of TCA cycle metabolites that associate with cellular energy. In the present review, we discuss the regulatory metabolic link of the Asp-family pathway with the TCA cycle and its biological significance upon exposure to stress conditions that cause energy deprivation. In addition, we also discuss how deep understanding of the regulatory metabolic link of the Asp-family pathway with energy and stress regulation can be used to improve Lys level in seeds of important crop species, minimizing the interference with the cellular energy status and plant-stress interaction. This review thus provides an example showing how deep understanding the inter-regulation of metabolism with plant stress physiology can lead to successful nutritional improvements with minimal negative effect on plant growth and response to stressful environments.

  1. Signaling pathways in mammalian preimplantation development: Linking cellular phenotypes to lineage decisions.

    PubMed

    Menchero, Sergio; Rayon, Teresa; Andreu, Maria Jose; Manzanares, Miguel

    2017-04-01

    The first stages of mammalian development, before implantation of the embryo in the maternal uterus, result in the establishment of three cell populations in the blastocyst: trophectoderm, epiblast, and primitive endoderm. These events involve only a small number of cells, and are initiated by morphological differences among them related to cell adhesion and polarity. Much attention has been paid to the master transcription factors that are critical for establishing and maintaining early lineage choices. Nevertheless, a large body of work also reveals that additional molecular mechanisms are involved. Here, we provide an updated view of the role of different signaling pathways in the first stages of mouse development, and how their cross-talk and interplay determine the initial lineage decisions occurring in the blastocyst. We will also discuss how these pathways are critical for translating cellular phenotypes, the product of the morphogenetic events occurring at these stages, into transcriptional responses and expression of lineage-specifying transcription factors. Developmental Dynamics 246:245-261, 2017. © 2016 Wiley Periodicals, Inc.

  2. An essential pathway links FLT3-ITD, HCK and CDK6 in acute myeloid leukemia

    PubMed Central

    Lopez, Sophie; Voisset, Edwige; Tisserand, Julie C.; Mosca, Cyndie; Prebet, Thomas; Santamaria, David; Dubreuil, Patrice; Sepulveda, Paulo De

    2016-01-01

    CDK4/CDK6 and RB proteins drive the progression through the G1 phase of the cell cycle. In acute myeloid leukemia (AML), the activity of the CDK/Cyclin D complex is increased. The mechanism involved is unknown, as are the respective roles played by CDK4 or CDK6 in this process. Here, we report that AML cells carrying FLT3-ITD mutations are dependent on CDK6 for cell proliferation while CDK4 is not essential. We showed that FLT3-ITD signaling is responsible for CDK6 overexpression, through a pathway involving the SRC-family kinase HCK. Accordingly, FLT3-ITD failed to transform primary hematopoietic progenitor cells from Cdk6−/− mice. Our results demonstrate that CDK6 is the primary target of CDK4/CDK6 inhibitors in FLT3-ITD positive AML. Furthermore, we delineate an essential protein kinase pathway -FLT3/HCK/CDK6- in the context of AML with FLT3-ITD mutations. PMID:27323399

  3. Multiple Causal Links Between Magnocellular-Dorsal Pathway Deficit and Developmental Dyslexia.

    PubMed

    Gori, Simone; Seitz, Aaron R; Ronconi, Luca; Franceschini, Sandro; Facoetti, Andrea

    2015-09-22

    Although impaired auditory-phonological processing is the most popular explanation of developmental dyslexia (DD), the literature shows that the combination of several causes rather than a single factor contributes to DD. Functioning of the visual magnocellular-dorsal (MD) pathway, which plays a key role in motion perception, is a much debated, but heavily suspected factor contributing to DD. Here, we employ a comprehensive approach that incorporates all the accepted methods required to test the relationship between the MD pathway dysfunction and DD. The results of 4 experiments show that (1) Motion perception is impaired in children with dyslexia in comparison both with age-match and with reading-level controls; (2) pre-reading visual motion perception-independently from auditory-phonological skill-predicts future reading development, and (3) targeted MD trainings-not involving any auditory-phonological stimulation-leads to improved reading skill in children and adults with DD. Our findings demonstrate, for the first time, a causal relationship between MD deficits and DD, virtually closing a 30-year long debate. Since MD dysfunction can be diagnosed much earlier than reading and language disorders, our findings pave the way for low resource-intensive, early prevention programs that could drastically reduce the incidence of DD.

  4. 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.

  5. 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

  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. The BMP signaling pathway at the Drosophila neuromuscular junction and its links to neurodegenerative diseases

    PubMed Central

    Bayat, Vafa; Jaiswal, Manish; Bellen, Hugo J.

    2011-01-01

    Summary The Drosophila neuromuscular junction (NMJ) has recently provided new insights into the roles of various proteins in neurodegenerative diseases including Amyotrophic Lateral Sclerosis (ALS), Spinal Muscular Atrophy (SMA), Multiple Sclerosis (MS) Hereditary Spastic Paraplegia (HSP), and Huntington’s Disease (HD). Several developmental signaling pathways including WNT, MAPK and BMP/TGF-β signaling play important roles in the formation and growth of the Drosophila NMJ. Studies of the fly homologues of genes that cause neurodegenerative disease at the NMJ have resulted in a better understanding of the roles of these proteins in vivo. These studies may shed light on the pathological mechanisms of these diseases, with implications for reduced BMP/TGF-β signaling in ALS, SMA and HD and increased signaling in HSP and MS. PMID:20832291

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

    PubMed

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

    2007-09-26

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

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

    PubMed

    Christian, Lisa M

    2012-01-01

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

  10. Developmental pathways linking externalizing symptoms, internalizing symptoms, and academic competence to adolescent substance use.

    PubMed

    Englund, Michelle M; Siebenbruner, Jessica

    2012-10-01

    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 longitudinal study of first-born children of low-income mothers. Using data from ages 7, 9, 12, and 16 years, a series of nested two-part (semi-continuous) path models from a developmental cascade modeling framework were compared. Controlling for gender, SES, mother's age at child's birth, and minority status, we found (a) within-domain rank-order stability across time, (b) significant cross-domain effects over time, (c) higher externalizing symptoms significantly predicted use of alcohol and marijuana as well as higher levels of use in adolescence, and (d) higher levels of academic competence significantly added to the prediction of use of alcohol.

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

    PubMed Central

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

    2016-01-01

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

  12. Emotional Awareness as a Pathway Linking Adult Attachment to Subsequent Depression

    PubMed Central

    Monti, Jennifer D.; Rudolph, Karen D.

    2014-01-01

    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 females caregivers (N = 417, M age = 37.83) completed questionnaires annually for three 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

  13. 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.

  14. Usp5 links suppression of p53 and FAS levels in melanoma to the BRAF pathway

    PubMed Central

    Potu, Harish; Peterson, Luke F.; Pal, Anupama; Verhaegen, Monique; Cao, Juxiang; Talpaz, Moshe; Donato, Nicholas J.

    2014-01-01

    Usp5 is a deubiquitinase (DUB) previously shown to regulate unanchored polyubiquitin (Ub) chains, p53 transcriptional activity and double-strand DNA repair. In BRAF mutant melanoma cells, Usp5 activity was suppressed by BRAF inhibitor (vemurafenib) in sensitive but not in acquired or intrinsically resistant cells. Usp5 knockdown overcame acquired vemurafenib resistance and sensitized BRAF and NRAS mutant melanoma cells to apoptosis initiated by MEK inhibitor, cytokines or DNA-damaging agents. Knockdown and overexpression studies demonstrated that Usp5 regulates p53 (and p73) levels and alters cell growth and cell cycle distribution associated with p21 induction. Usp5 also regulates the intrinsic apoptotic pathway by modulating p53-dependent FAS expression. A small molecule DUB inhibitor (EOAI3402143) phenocopied the FAS induction and apoptotic sensitization of Usp5 knockdown and fully blocked melanoma tumor growth in mice. Overall, our results demonstrate that BRAF activates Usp5 to suppress cell cycle checkpoint control and apoptosis by blocking p53 and FAS induction; all of which can be restored by small molecule-mediated Usp5 inhibition. These results suggest that Usp5 inhibition can provide an alternate approach in recovery of diminished p53 (or p73) function in melanoma and can add to the targeted therapies already used in the treatment of melanoma. PMID:24980819

  15. 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

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

    PubMed

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

    2016-04-01

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

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

    PubMed

    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

    2015-08-06

    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.

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

    PubMed

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

    2014-05-01

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

  19. 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.

  20. 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.

  1. Production of Extrachromosomal MicroDNAs Is Linked to Mismatch Repair Pathways and Transcriptional Activity.

    PubMed

    Dillon, Laura W; Kumar, Pankaj; Shibata, Yoshiyuki; Wang, Yuh-Hwa; Willcox, Smaranda; Griffith, Jack D; Pommier, Yves; Takeda, Shunichi; Dutta, Anindya

    2015-06-23

    MicroDNAs are <400-base extrachromosomal circles found in mammalian cells. Tens of thousands of microDNAs have been found in all tissue types, including sperm. MicroDNAs arise preferentially from areas with high gene density, GC content, and exon density from promoters with activating chromatin modifications and in sperm from the 5'-UTR of full-length LINE-1 elements, but are depleted from lamin-associated heterochromatin. Analysis of microDNAs from a set of human cancer cell lines revealed lineage-specific patterns of microDNA origins. A survey of microDNAs from chicken cells defective in various DNA repair proteins reveals that homologous recombination and non-homologous end joining repair pathways are not required for microDNA production. Deletion of the MSH3 DNA mismatch repair protein results in a significant decrease in microDNA abundance, specifically from non-CpG genomic regions. Thus, microDNAs arise as part of normal cellular physiology—either from DNA breaks associated with RNA metabolism or from replication slippage followed by mismatch repair.

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

    PubMed Central

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

    2014-01-01

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

  3. 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.

  4. 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.

  5. Linking prenatal maternal adversity to developmental outcomes in infants: the role of epigenetic pathways.

    PubMed

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

    2012-11-01

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

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

    PubMed Central

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

    2013-01-01

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

  7. 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

  8. The Global Food System as a Transport Pathway for Hazardous Chemicals: The Missing Link between Emissions and Exposure

    PubMed Central

    Ng, Carla A.; von Goetz, Natalie

    2016-01-01

    Background: Food is a major pathway for human exposure to hazardous chemicals. The modern food system is becoming increasingly complex and globalized, but models for food-borne exposure typically assume locally derived diets or use concentrations directly measured in foods without accounting for food origin. Such approaches may not reflect actual chemical intakes because concentrations depend on food origin, and representative analysis is seldom available. Processing, packaging, storage, and transportation also impart different chemicals to food and are not yet adequately addressed. Thus, the link between environmental emissions and realistic human exposure is effectively broken. Objectives: We discuss the need for a fully integrated treatment of the modern industrialized food system, and we propose strategies for using existing models and relevant supporting data sources to track chemicals during production, processing, packaging, storage, and transport. Discussion: Fate and bioaccumulation models describe how chemicals distribute in the environment and accumulate through local food webs. Human exposure models can use concentrations in food to determine body burdens based on individual or population characteristics. New models now include the impacts of processing and packaging but are far from comprehensive. We propose to close the gap between emissions and exposure by utilizing a wider variety of models and data sources, including global food trade data, processing, and packaging models. Conclusions: A comprehensive approach that takes into account the complexity of the modern global food system is essential to enable better prediction of human exposure to chemicals in food, sound risk assessments, and more focused risk abatement strategies. Citation: Ng CA, von Goetz N. 2017. The global food system as a transport pathway for hazardous chemicals: the missing link between emissions and exposure. Environ Health Perspect 125:1–7; http://dx.doi.org/10.1289/EHP

  9. Developing food allergy: a potential immunologic pathway linking skin barrier to gut

    PubMed Central

    Wang, Yui-Hsi

    2016-01-01

    Immunoglobulin E (IgE)-mediated food allergy is an adverse reaction to foods and is driven by uncontrolled type-2 immune responses. Current knowledge cannot explain why only some individuals among those with food allergy are prone to develop life-threatening anaphylaxis. It is increasingly evident that the immunologic mechanisms involved in developing IgE-mediated food allergy are far more complex than allergic sensitization. Clinical observations suggest that patients who develop severe allergic reactions to food are often sensitized through the skin in early infancy. Environmental insults trigger epidermal thymic stromal lymphopoietin and interleukin-33 (IL-33) production, which endows dendritic cells with the ability to induce CD4 +TH2 cell-mediated allergic inflammation. Intestinal IL-25 propagates the allergic immune response by enhancing collaborative interactions between resident type-2 innate lymphoid cells and CD4 +TH2 cells expanded by ingested antigens in the gastrointestinal tract. IL-4 signaling provided by CD4 +TH2 cells induces emigrated mast cell progenitors to become multi-functional IL-9-producing mucosal mast cells, which then expand greatly after repeated food ingestions. Inflammatory cytokine IL-33 promotes the function and maturation of IL-9-producing mucosal mast cells, which amplify intestinal mastocytosis, resulting in increased clinical reactivity to ingested food allergens. These findings provide the plausible view that the combinatorial signals from atopic status, dietary allergen ingestions, and inflammatory cues may govern the perpetuation of allergic reactions from the skin to the gut and promote susceptibility to life-threatening anaphylaxis. Future in-depth studies of the molecular and cellular factors composing these stepwise pathways may facilitate the discovery of biomarkers and therapeutic targets for diagnosing, preventing, and treating food allergy. PMID:27853507

  10. Carboxypeptidase Z (CPZ) links thyroid hormone and Wnt signaling pathways in growth plate chondrocytes.

    PubMed

    Wang, Lai; Shao, Yvonne Y; Ballock, R Tracy

    2009-02-01

    Carboxypeptidase Z (CPZ) removes carboxyl-terminal basic amino acid residues, particularly arginine residues, from proteins. CPZ contains a cysteine-rich domain (CRD) similar to the CRD found in the frizzled family of Wnt receptors. We have previously shown that thyroid hormone regulates terminal differentiation of growth plate chondrocytes through activation of Wnt-4 expression and Wnt/beta-catenin signaling. The Wnt-4 protein contains a C-terminal arginine residue and binds to CPZ through the CRD. The objective of this study was to determine whether CPZ modulates Wnt/beta-catenin signaling and terminal differentiation of growth plate chondrocytes. Our results show that CPZ and Wnt-4 mRNA are co-expressed throughout growth plate cartilage. In primary pellet cultures of rat growth plate chondrocytes, thyroid hormone increases both Wnt-4 and CPZ expression, as well as CPZ enzymatic activity. Knockdown of either Wnt-4 or CPZ mRNA levels using an RNA interference technique or blocking CPZ enzymatic activity with the carboxypeptidase inhibitor GEMSA reduces the thyroid hormone effect on both alkaline phosphatase activity and Col10a1 mRNA expression. Adenoviral overexpression of CPZ activates Wnt/beta-catenin signaling and promotes the terminal differentiation of growth plate cells. Overexpression of CPZ in growth plate chondrocytes also removes the C-terminal arginine residue from a synthetic peptide consisting of the carboxyl-terminal 16 amino acids of the Wnt-4 protein. Removal of the C-terminal arginine residue of Wnt-4 by site-directed mutagenesis enhances the positive effect of Wnt-4 on terminal differentiation. These data indicate that thyroid hormone may regulate terminal differentiation of growth plate chondrocytes in part by modulating Wnt signaling pathways through the induction of CPZ and subsequent CPZ-enhanced activation of Wnt-4.

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

    PubMed Central

    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

  12. Maternal education and child nutritional status in Bolivia: finding the links.

    PubMed

    Frost, Michelle Bellessa; Forste, Renata; Haas, David W

    2005-01-01

    This study models various pathways linking maternal education and child nutritional status in Bolivia, using a national sample of children. Pathways examined include socioeconomic status, health knowledge, modern attitudes towards health care, female autonomy, and reproductive behavior. The data come from the 1998 Bolivia Demographic and Health Survey. Logistic regression results suggest that socioeconomic factors are the most important pathways linking maternal education and child nutritional status, and that modern attitudes about health care also explain the impact of education. Health care knowledge accounts for less of the effect of maternal education on child nutritional status, with autonomy being the weakest pathway. Other pathways, such as reproductive behaviors, appear to influence nutritional status independent of maternal education. Overall, the pathways examined accounted for 60 percent of the effect of maternal education on child nutritional status.

  13. Gemcitabine diphosphate choline is a major metabolite linked to the Kennedy pathway in pancreatic cancer models in vivo

    PubMed Central

    Bapiro, T E; Frese, K K; Courtin, A; Bramhall, J L; Madhu, B; Cook, N; Neesse, A; Griffiths, J R; Tuveson, D A; Jodrell, D I; Richards, F M

    2014-01-01

    Background: The modest benefits of gemcitabine (dFdC) therapy in patients with pancreatic ductal adenocarcinoma (PDAC) are well documented, with drug delivery and metabolic lability cited as important contributing factors. We have used a mouse model of PDAC: KRASG12D; p53R172H; pdx-Cre (KPC) that recapitulates the human disease to study dFdC intra-tumoural metabolism. Methods: LC-MS/MS and NMR were used to measure drug and physiological analytes. Cytotoxicity was assessed by the Sulphorhodamine B assay. Results: In KPC tumour tissue, we identified a new, Kennedy pathway-linked dFdC metabolite (gemcitabine diphosphate choline (GdPC)) present at equimolar amounts to its precursor, the accepted active metabolite gemcitabine triphosphate (dFdCTP). Utilising additional subcutaneous PDAC tumour models, we demonstrated an inverse correlation between GdPC/dFdCTP ratios and cytidine triphosphate (CTP). In tumour homogenates in vitro, CTP inhibited GdPC formation from dFdCTP, indicating competition between CTP and dFdCTP for CTP:phosphocholine cytidylyltransferase (CCT). As the structure of GdPC precludes entry into cells, potential cytotoxicity was assessed by stimulating CCT activity using linoleate in KPC cells in vitro, leading to increased GdPC concentration and synergistic growth inhibition after dFdC addition. Conclusions: GdPC is an important element of the intra-tumoural dFdC metabolic pathway in vivo. PMID:24874484

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2016-01-19

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

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

    PubMed

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

    2013-09-01

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

  17. 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.

  18. A novel oncogene, ost, encodes a guanine nucleotide exchange factor that potentially links Rho and Rac signaling pathways.

    PubMed Central

    Horii, Y; Beeler, J F; Sakaguchi, K; Tachibana, M; Miki, T

    1994-01-01

    Transfection of NIH3T3 cells with an osteosarcoma expression cDNA library led to the appearance of foci of morphologically transformed cells which were found to harbor a novel oncogene, ost. The ost product was activated by truncation of the N-terminal domain of the ost proto-oncogene and was highly tumorigenic in nude mouse assays. The proto-ost cDNA, isolated subsequently, encodes a predicted protein of 100 kDa containing DH (Db1 homology) and PH (pleckstrin homology) domains. Ost is mainly phosphorylated on serine and localized in the cytoplasm. Purified Ost protein catalyzed guanine nucleotide exchange on RhoA and Cdc42 among the Rho and Ras family members tested, indicating that Ost can activate these small GTP-binding proteins. Ost did not detectably associate with RhoA or Cdc42, but interacted specifically with the GTP-bound form of Rac1, suggesting that Ost can function as an effector of Rac1. These results suggest that Ost is a critical regulatory component which links pathways that signal through Rac1, RhoA and Cdc42. Of the tissues examined, expression of ost was the highest in brain and could be localized to neurons and alpha-tanycytes, suggesting that Ost may participate in axonal transport in these specialized cells. Images PMID:7957046

  19. Pharmacological inhibition of nicotinamide phosphoribosyltransferase/visfatin enzymatic activity identifies a new inflammatory pathway linked to NAD.

    PubMed

    Busso, Nathalie; Karababa, Mahir; Nobile, Massimo; Rolaz, Aline; Van Gool, Frédéric; Galli, Mara; Leo, Oberdan; So, Alexander; De Smedt, Thibaut

    2008-05-21

    Nicotinamide phosphoribosyltransferase (NAMPT), also known as visfatin, is the rate-limiting enzyme in the salvage pathway of NAD biosynthesis from nicotinamide. Since its expression is upregulated during inflammation, NAMPT represents a novel clinical biomarker in acute lung injury, rheumatoid arthritis, and Crohn's disease. However, its role in disease progression remains unknown. We report here that NAMPT is a key player in inflammatory arthritis. Increased expression of NAMPT was confirmed in mice with collagen-induced arthritis, both in serum and in the arthritic paw. Importantly, a specific competitive inhibitor of NAMPT effectively reduced arthritis severity with comparable activity to etanercept, and decreased pro-inflammatory cytokine secretion in affected joints. Moreover, NAMPT inhibition reduced intracellular NAD concentration in inflammatory cells and circulating TNFalpha levels during endotoxemia in mice. In vitro pharmacological inhibition of NAMPT reduced the intracellular concentration of NAD and pro-inflammatory cytokine secretion by inflammatory cells. Thus, NAMPT links NAD metabolism to inflammatory cytokine secretion by leukocytes, and its inhibition might therefore have therapeutic efficacy in immune-mediated inflammatory disorders.

  20. 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

  1. 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

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

    PubMed

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

    2014-02-01

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

  3. 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

  4. The "LEARn" (latent early-life associated regulation) model: an epigenetic pathway linking metabolic and cognitive disorders.

    PubMed

    Lahiri, Debomoy K; Maloney, Bryan

    2012-01-01

    Diabetes, cardiovascular disease, hypertension, and other disorders have been unified within the metabolic syndrome. Recently, it has been proposed that Alzheimer's disease (AD) and other degenerative, age-related neurological disorders may also be etiologically linked to the metabolic syndrome in a metabolic-cognitive syndrome. We review current evidence in the field for this unification. In addition, we describe how the latent early-life associated regulation (LEARn) model provides specific mechanisms to predict genetic targets for both metabolic disorders, e.g., diabetes, and neurodegenerative disorders, e.g., AD. The LEARn model is based on environmental induction of latent epigenetic misregulation, which develops into disease upon suffering additional environmental insults. We review structural differences between gene sequences that are and are not susceptible to LEARn misregulation. In addition to suggesting research targets such as the IDE and SORCS1 genes, which are implicated in both AD and diabetes, LEARn suggests specific mechanisms for pre-disease remediation, based on nutritional adjustment of aberrant DNA methylation and oxidation. The possibility of a single metabolic-cognitive disorder opens up the possibility of unified preventative treatments that reduce monetary and social costs of disease. LEARn suggests specific, testable pathways within the large theory.

  5. Identification of Components of the Murine Histone Deacetylase 6 Complex: Link between Acetylation and Ubiquitination Signaling Pathways

    PubMed Central

    Seigneurin-Berny, Daphné; Verdel, André; Curtet, Sandrine; Lemercier, Claudie; Garin, Jérôme; Rousseaux, Sophie; Khochbin, Saadi

    2001-01-01

    The immunopurification of the endogenous cytoplasmic murine histone deacetylase 6 (mHDAC6), a member of the class II HDACs, from mouse testis cytosolic extracts allowed the identification of two associated proteins. Both were mammalian homologues of yeast proteins known to interact with each other and involved in the ubiquitin signaling pathway: p97/VCP/Cdc48p, a homologue of yeast Cdc48p, and phospholipase A2-activating protein, a homologue of yeast UFD3 (ubiquitin fusion degradation protein 3). Moreover, in the C-terminal region of mHDAC6, a conserved zinc finger-containing domain named ZnF-UBP, also present in several ubiquitin-specific proteases, was discovered and was shown to mediate the specific binding of ubiquitin by mHDAC6. By using a ubiquitin pull-down approach, nine major ubiquitin-binding proteins were identified in mouse testis cytosolic extracts, and mHDAC6 was found to be one of them. All of these findings strongly suggest that mHDAC6 could be involved in the control of protein ubiquitination. The investigation of biochemical properties of the mHDAC6 complex in vitro further supported this hypothesis and clearly established a link between protein acetylation and protein ubiquitination. PMID:11689694

  6. The Fanconi anemia/BRCA pathway is involved in DNA interstrand cross-link repair of adriamycin-resistant leukemia cells.

    PubMed

    Yao, Chenjiao; Du, Wei; Chen, Haibing; Xiao, Sheng; Huang, Lihua; Chen, Fangping

    2015-03-01

    The Fanconi anemia/BRCA (FA/BRCA) pathway plays a vital role in DNA damage repair induced by DNA cross-linking agents and is closely related to drug response in cancer treatment. Here we demonstrate that the FA/BRCA pathway contributes to acquired drug resistance in adriamycin (ADR)-resistant leukemia cell lines, and disruption of this pathway partially reverses the drug resistance. We observed that ADR-resistant cells have reduced DNA interstrand cross-links (ICL) compared with ADR-sensitive cells. Western blot studies demonstrated enhanced FA protein expression in ADR-resistant cells. Using siRNA to knock down FANCF in K562/R drug-resistant cells showed increases in sensitivity to ADR and ADR-induced DNA damage, and demonstrated a direct relationship between the FA/BRCA pathway and drug sensitivity. Overexpression of FANCF in K562 drug-sensitive cells partially reproduced the drug-resistant phenotype. These results show that the FA/BRCA pathway is involved in acquired ADR resistance of leukemia cells. The FA/BRCA pathway may be a new target to reverse ADR resistance in leukemia treatment.

  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. 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…

  9. 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…

  10. 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

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

    PubMed Central

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

    2016-01-01

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

  12. 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

  13. 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

    2016-01-05

    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.

  14. The tumor suppressor gene WWOX links the canonical and noncanonical NF-κB pathways in HTLV-I Tax-mediated tumorigenesis.

    PubMed

    Fu, Jing; Qu, Zhaoxia; Yan, Pengrong; Ishikawa, Chie; Aqeilan, Rami I; Rabson, Arnold B; Xiao, Gutian

    2011-02-03

    Both the canonical and noncanonical nuclear factor κB (NF-κB) pathways have been linked to tumorigenesis. However, it remains unknown whether and how the 2 signaling pathways cooperate during tumorigenesis. We report that inhibition of the noncanonical NF-κB pathway significantly delays tumorigenesis mediated by the viral oncoprotein Tax. One function of noncanonical NF-κB activation was to repress expression of the WWOX tumor suppressor gene. Notably, WWOX specifically inhibited Tax-induced activation of the canonical, but not the noncanonical NF-κB pathway. Mechanistic studies indicated that WWOX blocked Tax-induced inhibitors of κB kinaseα (IKKα) recruitment to RelA and subsequent RelA phosphorylation at S536. In contrast, WWOX Y33R, a mutant unable to block the IKKα recruitment and RelA phosphorylation, lost the ability to inhibit Tax-mediated tumorigenesis. These data provide one important mechanism by which Tax coordinates the 2 NF-κB pathways for tumorigenesis. These data also suggest a novel role of WWOX in NF-κB regulation and viral tumorigenesis.

  15. The tumor suppressor gene WWOX links the canonical and noncanonical NF-κB pathways in HTLV-I Tax-mediated tumorigenesis

    PubMed Central

    Fu, Jing; Qu, Zhaoxia; Yan, Pengrong; Ishikawa, Chie; Aqeilan, Rami I.; Rabson, Arnold B.

    2011-01-01

    Both the canonical and noncanonical nuclear factor κB (NF-κB) pathways have been linked to tumorigenesis. However, it remains unknown whether and how the 2 signaling pathways cooperate during tumorigenesis. We report that inhibition of the noncanonical NF-κB pathway significantly delays tumorigenesis mediated by the viral oncoprotein Tax. One function of noncanonical NF-κB activation was to repress expression of the WWOX tumor suppressor gene. Notably, WWOX specifically inhibited Tax-induced activation of the canonical, but not the noncanonical NF-κB pathway. Mechanistic studies indicated that WWOX blocked Tax-induced inhibitors of κB kinaseα (IKKα) recruitment to RelA and subsequent RelA phosphorylation at S536. In contrast, WWOX Y33R, a mutant unable to block the IKKα recruitment and RelA phosphorylation, lost the ability to inhibit Tax-mediated tumorigenesis. These data provide one important mechanism by which Tax coordinates the 2 NF-κB pathways for tumorigenesis. These data also suggest a novel role of WWOX in NF-κB regulation and viral tumorigenesis. PMID:21115974

  16. l-xylo-3-Hexulose Reductase Is the Missing Link in the Oxidoreductive Pathway for d-Galactose Catabolism in Filamentous Fungi*

    PubMed Central

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

    2012-01-01

    In addition to the well established Leloir pathway for the catabolism of d-galactose in fungi, the oxidoreductive pathway has been recently identified. In this oxidoreductive pathway, d-galactose is converted via a series of NADPH-dependent reductions and NAD+-dependent oxidations into d-fructose. The pathway intermediates include galactitol, l-xylo-3-hexulose, and d-sorbitol. This study identified the missing link in the pathway, the l-xylo-3-hexulose reductase that catalyzes the conversion of l-xylo-3-hexulose to d-sorbitol. In Trichoderma reesei (Hypocrea jecorina) and Aspergillus niger, we identified the genes lxr4 and xhrA, respectively, that encode the l-xylo-3-hexulose reductases. The deletion of these genes resulted in no growth on galactitol and in reduced growth on d-galactose. The LXR4 was heterologously expressed, and the purified protein showed high specificity for l-xylo-3-hexulose with a Km = 2.0 ± 0.5 mm and a Vmax = 5.5 ± 1.0 units/mg. We also confirmed that the product of the LXR4 reaction is d-sorbitol. PMID:22654107

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

    PubMed

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

    2012-04-01

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

  18. 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

    2016-05-03

    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.

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

    DOE PAGES

    Teeguarden, Justin G.; Tan, Yu -Mei; Edwards, Stephen W.; ...

    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

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

    SciTech Connect

    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.; Harding, Anna K.

    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. 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.

  1. 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.

  2. The FA/BRCA pathway is involved in melphalan-induced DNA interstrand cross-link repair and accounts for melphalan resistance in multiple myeloma cells

    PubMed Central

    Chen, Qing; Van der Sluis, Pieter C.; Boulware, David; Hazlehurst, Lori A.; Dalton, William S.

    2005-01-01

    Melphalan, a DNA cross-linker, is one of the most widely used and effective drugs in the treatment of multiple myeloma (MM). In this report, we demonstrate that enhanced interstrand cross-link (ICL) repair via the Fanconi anemia (FA)/BRCA pathway contributes to acquired drug resistance in melphalan-resistant myeloma cell lines, and disruption of this pathway reverses drug resistance. Using the alkaline comet assay (single-cell gel electrophoresis), we observed that melphalan-resistant cells have reduced ICL formation and enhanced ICL repair compared with melphalan-sensitive cells. Cell-cycle studies demonstrated that enhanced ICL repair released cells from melphalan-induced cell-cycle delay. Using siRNA to knock down FANCF in 8226/LR5 and U266/LR6 drug-resistant cells demonstrated a direct relationship between ICL repair capacity and drug sensitivity. Overexpression of FANCF in 8226/S and U266/S drug-sensitive cells partially reproduced the drug-resistant phenotype. These data show that enhanced DNA repair via the Fanconi anemia/BRCA pathway is involved in acquired melphalan resistance. Our findings provide for a new target to enhance response to DNA cross-linking agents in cancer treatment. (Blood. 2005;106:698-705) PMID:15802532

  3. 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

  4. Depression and the Link with Cardiovascular Disease

    PubMed Central

    Dhar, Arup K.; Barton, David A.

    2016-01-01

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

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

    SciTech Connect

    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.

    2016-05-03

    Driven by major scientific advances in analytical methods, biomonitoring, and computational exposure assessment, 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 computationally enabled “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. The AEP framework offers an intuitive approach to successful organization of exposure science 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 pathway and adverse outcome pathways, completing the source to outcome continuum and setting the stage for more efficient integration of exposure science and toxicity testing information. Together these frameworks form and inform a decision making framework with the flexibility for risk-based, hazard-based or exposure-based decisions.

  6. Biological marks of early-life socioeconomic experience is detected in the adult inflammatory transcriptome

    PubMed Central

    Castagné, Raphaële; Kelly-Irving, Michelle; Campanella, Gianluca; Guida, Florence; Krogh, Vittorio; Palli, Domenico; Panico, Salvatore; Sacerdote, Carlotta; Tumino, Rosario; Kleinjans, Jos; de Kok, Theo; Kyrtopoulos, Soterios A.; Lang, Thierry; Stringhini, Silvia; Vermeulen, Roel; Vineis, Paolo; Delpierre, Cyrille; Chadeau-Hyam, Marc

    2016-01-01

    Consistent evidence is accumulating to link lower socioeconomic position (SEP) and poorer health, and the inflammatory system stands out as a potential pathway through which socioeconomic environment is biologically embedded. Using bloodderived genome-wide transcriptional profiles from 268 Italian participants of the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, we evaluated the association between early life, young and later adulthood SEP and the expression of 845 genes involved in human inflammatory responses. These were examined individually and jointly using several inflammatory scores. Our results consistently show that participants whose father had a manual (as compared to nonmanual) occupation exhibit, later in life, a higher inflammatory score, hence indicating an overall increased level of expression for the selected inflammatory-related genes. Adopting a life course approach, these associations remained statistically significant upon adjustment for later-in-life socioeconomic experiences. Sensitivity analyses indicated that our findings were not affected by the way the inflammatory score was calculated, and were replicated in an independent study. Our study provides additional evidence that childhood SEP is associated with a sustainable upregulation of the inflammatory transcriptome, independently of subsequent socioeconomic experiences. Our results support the hypothesis that early social inequalities impacts adult physiology. PMID:27934951

  7. 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.

  8. Bullying perpetration and victimization as externalizing and internalizing pathways: A retrospective study linking parenting styles and self-esteem to depression, alcohol use, and alcohol-related problems

    PubMed Central

    Patock-Peckham, Julie A; Medina, Mia; Terrell, Nathan; Belton, Daniel; King, Kevin M

    2016-01-01

    Emerging research suggests significant positive associations between bullying and substance use behaviors. However, these studies typically focused either on the link between substance use and bullying perpetration or victimization, and few have conceptualized bullying perpetration and/or victimization as mediators. In this study, we simultaneously tested past bullying perpetration and victimization as mediational pathways from retrospective report of parenting styles and global self-esteem to current depressive symptoms, alcohol use and alcohol-related problems. Data were collected from a college sample of 419 drinkers. Mediation effects were conducted using a bias-corrected bootstrap technique in structural equation modeling. Two-path mediation analyses indicated that mother and father authoritativeness were protective against bully victimization and depression through higher self-esteem. Conversely, having a permissive or authoritarian mother was positively linked to bullying perpetration, which in turn was associated with increased alcohol use, and to a lesser degree, more alcohol-related problems. Mother authoritarianism was associated with alcohol-related problems through depressive symptoms. Three-path mediation analyses suggested a trend in which individuals with higher self-esteem were less likely to report alcohol-related problems through lower levels of bullying victimization and depression. Results suggested that bullying perpetration and victimization may respectively serve as externalizing and internalizing pathways through which parenting styles and self-esteem are linked to depression and alcohol-related outcomes. The present study identified multiple modifiable precursors of, and mediational pathways to, alcohol-related problems which could guide the development and implementation of prevention programs targeting problematic alcohol use. PMID:26757486

  9. Substrate recognition and catalysis by GH47 α-mannosidases involved in Asn-linked glycan maturation in the mammalian secretory pathway

    SciTech Connect

    Xiang, Yong; Karaveg, Khanita; Moremen, Kelley W.

    2016-11-17

    Asn-linked glycosylation of newly synthesized polypeptides occurs in the endoplasmic reticulum of eukaryotic cells. Glycan structures are trimmed and remodeled as they transit the secretory pathway, and processing intermediates play various roles as ligands for folding chaperones and signals for quality control and intracellular transport. Key steps for the generation of these trimmed intermediates are catalyzed by glycoside hydrolase family 47 (GH47) α-mannosidases that selectively cleave α1,2-linked mannose residues. Despite the sequence and structural similarities among the GH47 enzymes, the molecular basis for residue-specific cleavage remains obscure. The present studies reveal enzyme–substrate complex structures for two related GH47 α-mannosidases and provide insights into how these enzymes recognize the same substrates differently and catalyze the complementary glycan trimming reactions necessary for glycan maturation.

  10. 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.

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

    PubMed Central

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

    2015-01-01

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

  12. An integrative model links multiple inputs and signaling pathways to the onset of DNA synthesis in hepatocytes

    PubMed Central

    Huard, Jérémy; Mueller, Stephanie; Gilles, Ernst D; Klingmüller, Ursula; Klamt, Steffen

    2012-01-01

    During liver regeneration, quiescent hepatocytes re-enter the cell cycle to proliferate and compensate for lost tissue. Multiple signals including hepatocyte growth factor, epidermal growth factor, tumor necrosis factor α, interleukin-6, insulin and transforming growth factor β orchestrate these responses and are integrated during the G1 phase of the cell cycle. To investigate how these inputs influence DNA synthesis as a measure for proliferation, we established a large-scale integrated logical model connecting multiple signaling pathways and the cell cycle. We constructed our model based upon established literature knowledge, and successively improved and validated its structure using hepatocyte-specific literature as well as experimental DNA synthesis data. Model analyses showed that activation of the mitogen-activated protein kinase and phosphatidylinositol 3-kinase pathways was sufficient and necessary for triggering DNA synthesis. In addition, we identified key species in these pathways that mediate DNA replication. Our model predicted oncogenic mutations that were compared with the COSMIC database, and proposed intervention targets to block hepatocyte growth factor-induced DNA synthesis, which we validated experimentally. Our integrative approach demonstrates that, despite the complexity and size of the underlying interlaced network, logical modeling enables an integrative understanding of signaling-controlled proliferation at the cellular level, and thus can provide intervention strategies for distinct perturbation scenarios at various regulatory levels. PMID:22443451

  13. 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

    2016-01-04

    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.

  14. 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.

  15. 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

  16. D₂-dopaminergic receptor-linked pathways: critical regulators of CYP3A, CYP2C, and CYP2D.

    PubMed

    Daskalopoulos, Evangelos P; Lang, Matti A; Marselos, Marios; Malliou, Foteini; Konstandi, Maria

    2012-10-01

    Various hormonal and monoaminergic systems play determinant roles in the regulation of several cytochromes P450 (P450s) in the liver. Growth hormone (GH), prolactin, and insulin are involved in P450 regulation, and their release is under dopaminergic control. This study focused on the role of D₂-dopaminergic systems in the regulation of the major drug-metabolizing P450s, i.e., CYP3A, CYP2C, and CYP2D. Blockade of D₂-dopaminergic receptors with either sulpiride (SULP) or 4-(4-chlorophenyl)-1-(1H-indol-3-ylmethyl)piperidin-4-ol (L-741,626) markedly down-regulated CYP3A1/2, CYP2C11, and CYP2D1 expression in rat liver. This suppressive effect appeared to be mediated by the insulin/phosphatidylinositol 3-kinase/Akt/FOXO1 signaling pathway. Furthermore, inactivation of the GH/STAT5b signaling pathway appeared to play a role in D₂-dopaminergic receptor-mediated down-regulating effects on these P450s. SULP suppressed plasma GH levels, with subsequently reduced activation of STAT5b, which is the major GH pulse-activated transcription factor and has up-regulating effects on various P450s in hepatic tissue. Levels of prolactin, which exerts down-regulating control on P450s, were increased by SULP, which may contribute to SULP-mediated effects. Finally, it appears that SULP-induced inactivation of the cAMP/protein kinase A/cAMP-response element-binding protein signaling pathway, which is a critical regulator of pregnane X receptor and hepatocyte nuclear factor 1α, and inactivation of the c-Jun N-terminal kinase contribute to SULP-induced down-regulation of the aforementioned P450s. Taken together, the present data provide evidence that drugs acting as D₂-dopaminergic receptor antagonists might interfere with several major signaling pathways involved in the regulation of CYP3A, CYP2C, and CYP2D, which are critical enzymes in drug metabolism, thus affecting the effectiveness of the majority of prescribed drugs and the toxicity and carcinogenic potency of a plethora of

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

    PubMed

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

    2016-01-01

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

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

    PubMed

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

    2015-11-01

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

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

    PubMed 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

  20. 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.

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

    PubMed

    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.

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

    PubMed

    Hellweg, Christine E

    2015-11-28

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

  3. Towards a pathway definition of Parkinson's disease: a complex disorder with links to cancer, diabetes and inflammation.

    PubMed

    Moran, Linda B; Graeber, Manuel B

    2008-02-01

    We have previously established a first whole genome transcriptomic profile of sporadic Parkinson's disease (PD). After extensive brain tissue-based validation combined with cycles of iterative data analysis and by focusing on the most comparable cases of the cohort, we have refined our analysis and established a list of 892 highly dysregulated priority genes that are considered to form the core of the diseased Parkinsonian metabolic network. The substantia nigra pathways, now under scrutiny, contain more than 100 genes whose association with PD is known from the literature. Of those, more than 40 genes belong to the highly significantly dysregulated group identified in our dataset. Apart from the complete list of 892 priority genes, we present pathways revealing PD 'hub' as well as 'peripheral' network genes. The latter include Lewy body components or interact with known PD genes. Biological associations of PD with cancer, diabetes and inflammation are discussed and interactions of the priority genes with several drugs are provided. Our study illustrates the value of rigorous clinico-pathological correlation when analysing high-throughput data to make optimal use of the histopathological phenome, or morphonome which currently serves as the key diagnostic reference for most human diseases. The need for systematic human tissue banking, following the highest possible professional and ethical standard to enable sustainability, becomes evident.

  4. 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.

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

    SciTech Connect

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

    2015-04-01

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

  6. Housing and health inequalities: A synthesis of systematic reviews of interventions aimed at different pathways linking housing and health

    PubMed Central

    Gibson, Marcia; Petticrew, Mark; Bambra, Clare; Sowden, Amanda J.; Wright, Kath E.; Whitehead, Margaret

    2011-01-01

    Housing and neighbourhood conditions are widely acknowledged to be important social determinants of health, through three main pathways: (1) internal housing conditions, (2) area characteristics and (3) housing tenure. We conducted a systematic overview of systematic reviews of intervention studies to provide an overview of the evidence on the impact of housing and neighbourhood interventions on health and health inequalities. There is relatively strong evidence for interventions aimed at improving area characteristics and compelling evidence for warmth and energy efficiency interventions targeted at vulnerable individuals. However, the health impacts of area-level internal housing improvement interventions are as yet unclear. We found no reviews of interventions aimed at altering housing tenure. This remains an important area for further research and potentially new evidence syntheses. PMID:21159542

  7. Functional coupling analysis suggests link between the obesity gene FTO and the BDNF-NTRK2 signaling pathway

    PubMed Central

    2011-01-01

    Background The Fat mass and obesity gene (FTO) has been identified through genome wide association studies as an important genetic factor contributing to a higher body mass index (BMI). However, the molecular context in which this effect is mediated has yet to be determined. We investigated the potential molecular network for FTO by analyzing co-expression and protein-protein interaction databases, Coxpresdb and IntAct, as well as the functional coupling predicting multi-source database, FunCoup. Hypothalamic expression of FTO-linked genes defined with this bioinformatics approach was subsequently studied using quantitative real time-PCR in mouse feeding models known to affect FTO expression. Results We identified several candidate genes for functional coupling to FTO through database studies and selected nine for further study in animal models. We observed hypothalamic expression of Profilin 2 (Pfn2), cAMP-dependent protein kinase catalytic subunit beta (Prkacb), Brain derived neurotrophic factor (Bdnf), neurotrophic tyrosine kinase, receptor, type 2 (Ntrk2), Signal transducer and activator of transcription 3 (Stat3), and Btbd12 to be co-regulated in concert with Fto. Pfn2 and Prkacb have previously not been linked to feeding regulation. Conclusions Gene expression studies validate several candidates generated through database studies of possible FTO-interactors. We speculate about a wider functional role for FTO in the context of current and recent findings, such as in extracellular ligand-induced neuronal plasticity via NTRK2/BDNF, possibly via interaction with the transcription factor CCAAT/enhancer binding protein β (C/EBPβ). PMID:22087873

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

    PubMed Central

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

    2015-01-01

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

  9. Identification of Norway Spruce MYB-bHLH-WDR Transcription Factor Complex Members Linked to Regulation of the Flavonoid Pathway

    PubMed Central

    Nemesio-Gorriz, Miguel; Blair, Peter B.; Dalman, Kerstin; Hammerbacher, Almuth; Arnerup, Jenny; Stenlid, Jan; Mukhtar, Shahid M.; Elfstrand, Malin

    2017-01-01

    Transcription factors (TFs) forming MYB-bHLH-WDR complexes are known to regulate the biosynthesis of specialized metabolites in angiosperms through an intricate network. These specialized metabolites participate in a wide range of biological processes including plant growth, development, reproduction as well as in plant immunity. Studying the regulation of their biosynthesis is thus essential. While MYB (TFs) have been previously shown to control specialized metabolism (SM) in gymnosperms, the identity of their partners, in particular bHLH or WDR members, has not yet been revealed. To gain knowledge about MYB-bHLH-WDR transcription factor complexes in gymnosperms and their regulation of SW, we identified two bHLH homologs of AtTT8, six homologs of the MYB transcription factor AtTT2 and one WDR ortholog of AtTTG1 in Norway spruce. We investigated the expression levels of these genes in diverse tissues and upon treatments with various stimuli including methyl-salicylate, methyl-jasmonate, wounding or fungal inoculation. In addition, we also identified protein-protein interactions among different homologs of MYB, bHLH and WDR. Finally, we generated transgenic spruce cell lines overexpressing four of the Norway spruce AtTT2 homologs and observed differential regulation of genes in the flavonoid pathway and flavonoid contents. PMID:28337212

  10. 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.

  11. RpiR Homologues May Link Staphylococcus aureus RNAIII Synthesis and Pentose Phosphate Pathway Regulation ▿ †

    PubMed Central

    Zhu, Yefei; Nandakumar, Renu; Sadykov, Marat R.; Madayiputhiya, Nandakumar; Luong, Thanh T.; Gaupp, Rosmarie; Lee, Chia Y.; Somerville, Greg A.

    2011-01-01

    Staphylococcus aureus is a medically important pathogen that synthesizes a wide range of virulence determinants. The synthesis of many staphylococcal virulence determinants is regulated in part by stress-induced changes in the activity of the tricarboxylic acid (TCA) cycle. One metabolic change associated with TCA cycle stress is an increased concentration of ribose, leading us to hypothesize that a pentose phosphate pathway (PPP)-responsive regulator mediates some of the TCA cycle-dependent regulatory effects. Using bioinformatics, we identified three potential ribose-responsive regulators that belong to the RpiR family of transcriptional regulators. To determine whether these RpiR homologues affect PPP activity and virulence determinant synthesis, the rpiR homologues were inactivated, and the effects on PPP activity and virulence factor synthesis were assessed. Two of the three homologues (RpiRB and RpiRC) positively influence the transcription of the PPP genes rpiA and zwf, while the third homologue (RpiRA) is slightly antagonistic to the other homologues. In addition, inactivation of RpiRC altered the temporal transcription of RNAIII, the effector molecule of the agr quorum-sensing system. These data confirm the close linkage of central metabolism and virulence determinant synthesis, and they establish a metabolic override for quorum-sensing-dependent regulation of RNAIII transcription. PMID:21926234

  12. TRYCAT pathways link peripheral inflammation, nicotine, somatization and depression in the etiology and course of Parkinson's disease.

    PubMed

    Anderson, George; Maes, Michael

    2014-02-01

    Increased depression, somatization, gut inflammation and wider peripheral inflammation are all associated with the early stages of Parkinson's disease (PD). Classically such concurrent conditions have been viewed as "comorbidities", driven by high levels of stress in a still poorly understood and treated disorder. Here we review the data on how oxidative and nitrosative stress in association with immuno-inflammatory responses, drives alteration in tryptophan catabolites, including kynurenine, kynurenic acid and quinolinic acid that drive not only the 'comorbidities" of PD but also important processes in the etiology and course of PD per se. The induction of indoleamine 2,3-dioxygenase, leading to the driving of tryptophan into neuroregulatory tryptophan catabolite products and away from serotonin and melatonin production, has significant implications for understanding the role of nicotine, melatonin, and caffeine in regulating PD susceptibility. Tryptophan catabolite pathway activation will also regulate blood-brain barrier permeability, glia and mast cell reactivity as well as wider innate and adaptive immune cell responses, all relevant to the course of PD. As such, the "comorbidities" of PD such as depression, somatization and peripheral inflammatory disorders can all be conceptualized as being an intricate part of the biological underpinnings of both the etiology and course of PD. As a consequence, the data reviewed here has treatment implications; relevant to both the course of PD and in the management of L-DOPA induced dyskinesias.

  13. Identification of Norway Spruce MYB-bHLH-WDR Transcription Factor Complex Members Linked to Regulation of the Flavonoid Pathway.

    PubMed

    Nemesio-Gorriz, Miguel; Blair, Peter B; Dalman, Kerstin; Hammerbacher, Almuth; Arnerup, Jenny; Stenlid, Jan; Mukhtar, Shahid M; Elfstrand, Malin

    2017-01-01

    Transcription factors (TFs) forming MYB-bHLH-WDR complexes are known to regulate the biosynthesis of specialized metabolites in angiosperms through an intricate network. These specialized metabolites participate in a wide range of biological processes including plant growth, development, reproduction as well as in plant immunity. Studying the regulation of their biosynthesis is thus essential. While MYB (TFs) have been previously shown to control specialized metabolism (SM) in gymnosperms, the identity of their partners, in particular bHLH or WDR members, has not yet been revealed. To gain knowledge about MYB-bHLH-WDR transcription factor complexes in gymnosperms and their regulation of SW, we identified two bHLH homologs of AtTT8, six homologs of the MYB transcription factor AtTT2 and one WDR ortholog of AtTTG1 in Norway spruce. We investigated the expression levels of these genes in diverse tissues and upon treatments with various stimuli including methyl-salicylate, methyl-jasmonate, wounding or fungal inoculation. In addition, we also identified protein-protein interactions among different homologs of MYB, bHLH and WDR. Finally, we generated transgenic spruce cell lines overexpressing four of the Norway spruce AtTT2 homologs and observed differential regulation of genes in the flavonoid pathway and flavonoid contents.

  14. Mutual repression between steroid and xenobiotic receptor and NF-kappaB signaling pathways links xenobiotic metabolism and inflammation.

    PubMed

    Zhou, Changcheng; Tabb, Michelle M; Nelson, Edward L; Grün, Felix; Verma, Suman; Sadatrafiei, Asal; Lin, Min; Mallick, Shyamali; Forman, Barry M; Thummel, Kenneth E; Blumberg, Bruce

    2006-08-01

    While it has long been known that inflammation and infection reduce expression of hepatic cytochrome P450 (CYP) genes involved in xenobiotic metabolism and that exposure to xenobiotic chemicals can impair immune function, the molecular mechanisms underlying both of these phenomena have remained largely unknown. Here we show that activation of the nuclear steroid and xenobiotic receptor (SXR) by commonly used drugs in humans inhibits the activity of NF-kappaB, a key regulator of inflammation and the immune response. NF-kappaB target genes are upregulated and small bowel inflammation is significantly increased in mice lacking the SXR ortholog pregnane X receptor (PXR), thereby demonstrating a direct link between SXR and drug-mediated antagonism of NF-kappaB. Interestingly, NF-kappaB activation reciprocally inhibits SXR and its target genes whereas inhibition of NF-kappaB enhances SXR activity. This SXR/PXR-NF-kappaB axis provides a molecular explanation for the suppression of hepatic CYP mRNAs by inflammatory stimuli as well as the immunosuppressant effects of xenobiotics and SXR-responsive drugs. This mechanistic relationship has clinical consequences for individuals undergoing therapeutic exposure to the wide variety of drugs that are also SXR agonists.

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

    PubMed

    Lin, Mary Grace; Zhong, Qing

    2011-03-01

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

  16. A plastid envelope location of Arabidopsis ent-kaurene oxidase links the plastid and endoplasmic reticulum steps of the gibberellin biosynthesis pathway.

    PubMed

    Helliwell, C A; Sullivan, J A; Mould, R M; Gray, J C; Peacock, W J; Dennis, E S

    2001-10-01

    We have used fusions of gibberellin biosynthesis enzymes to green fluorescent protein (GFP) to determine the subcellular localization of the early steps of the pathway. Gibberellin biosynthesis from geranylgeranyl diphosphate is catalysed by enzymes of the terpene cyclase, cytochrome P450 mono-oxygenase and 2-oxoglutarate-dependent dioxygenase classes. We show that the N-terminal pre-sequences of the Arabidopsis thaliana terpene cyclases copalyl diphosphate synthase (AtCPS1) and ent-kaurene synthase (AtKS1) direct GFP to chloroplasts in transient assays following microprojectile bombardment of tobacco leaves. The AtKS1-GFP fusion is also imported by isolated pea chloroplasts. The N-terminal portion of the cytochrome P450 protein ent-kaurene oxidase (AtKO1) directs GFP to chloroplasts in tobacco leaf transient assays. Chloroplast import assays with 35S-labelled AtKO1 protein show that it is targeted to the outer face of the chloroplast envelope. The leader sequences of the two ent-kaurenoic acid oxidases (AtKAO1 and AtKAO2) from Arabidopsis direct GFP to the endoplasmic reticulum. These data suggest that the AtKO1 protein links the plastid- and endoplasmic reticulum-located steps of the gibberellin biosynthesis pathway by association with the outer envelope of the plastid.

  17. Weight of evidence evaluation of a network of adverse outcome pathways linking activation of the nicotinic acetylcholine receptor in honey bees to colony death.

    PubMed

    LaLone, Carlie A; Villeneuve, Daniel L; Wu-Smart, Judy; Milsk, Rebecca Y; Sappington, Keith; Garber, Kristina V; Housenger, Justin; Ankley, Gerald T

    2017-04-15

    Ongoing honey bee (Apis mellifera) colony losses are of significant international concern because of the essential role these insects play in pollinating crops. Both chemical and non-chemical stressors have been implicated as possible contributors to colony failure; however, the potential role(s) of commonly-used neonicotinoid insecticides has emerged as particularly concerning. Neonicotinoids act on the nicotinic acetylcholine receptors (nAChRs) in the central nervous system to eliminate pest insects. However, mounting evidence indicates that neonicotinoids also may adversely affect beneficial pollinators, such as the honey bee, via impairments on learning and memory, and ultimately foraging success. The specific mechanisms linking activation of the nAChR to adverse effects on learning and memory are uncertain. Additionally, clear connections between observed impacts on individual bees and colony level effects are lacking. The objective of this review was to develop adverse outcome pathways (AOPs) as a means to evaluate the biological plausibility and empirical evidence supporting (or refuting) the linkage between activation of the physiological target site, the nAChR, and colony level consequences. Potential for exposure was not a consideration in AOP development and therefore this effort should not be considered a risk assessment. Nonetheless, development of the AOPs described herein has led to the identification of research gaps which, for example, may be of high priority in understanding how perturbation of pathways involved in neurotransmission can adversely affect normal colony functions, causing colony instability and subsequent bee population failure. A putative AOP network was developed, laying the foundation for further insights as to the role of combined chemical and non-chemical stressors in impacting bee populations. Insights gained from the AOP network assembly, which more realistically represents multi-stressor impacts on honey bee colonies, are

  18. Signaling Pathways Linked to Serotonin-Induced Superoxide Anion Production: A Physiological Role for Mitochondria in Pulmonary Arteries

    PubMed Central

    Genet, Nafiisha; Billaud, Marie; Rossignol, Rodrigue; Dubois, Mathilde; Gillibert-Duplantier, Jennifer; Isakson, Brant E.; Marthan, Roger; Savineau, Jean-Pierre; Guibert, Christelle

    2017-01-01

    Serotonin (5-HT) is a potent vasoconstrictor agonist and contributes to several vascular diseases including systemic or pulmonary hypertension and atherosclerosis. Although superoxide anion (O2•_) is commonly associated to cellular damages due to O2•_ overproduction, we previously demonstrated that, in physiological conditions, O2•_ also participates to the 5-HT contraction in intrapulmonary arteries (IPA). Here, we focused on the signaling pathways leading to O2•_ production in response to 5-HT in rat IPA. Using electron paramagnetic resonance on rat IPA, we showed that 5-HT (100 μM)-induced O2•_ production was inhibited by ketanserin (1 μM—an inhibitor of the 5-HT2 receptor), absence of extracellular calcium, two blockers of voltage-independent calcium permeable channels (RHC80267 50 μM and LOE-908 10 μM) and a blocker of the mitochondrial complex I (rotenone—100 nM). Depletion of calcium from the sarcoplasmic reticulum or nicardipine (1 μM—an inhibitor of the L-type voltage-dependent calcium channel) had no effect on the 5-HT-induced O2•_ production. O2•_ levels were also increased by α-methyl-5-HT (10 μM—a 5-HT2 receptors agonist) whereas GR127935 (1 μM—an antagonist of the 5-HT1B/D receptor) and citalopram (1 μM—a 5-HT transporter inhibitor) had no effect on the 5-HT-induced O2•_ production. Peroxynitrites were increased in response to 5-HT (100 μM). In isolated pulmonary arterial smooth muscle cells loaded with rhod-2 or mitosox probes, we respectively showed that 5-HT increased both mitochondrial calcium and O2•_ levels, which were both abrogated in absence of extracellular calcium. Mitochondrial O2•_ levels were also abolished in the presence of rotenone (100 nM). In pulmonary arterial smooth muscle cells loaded with TMRM, we showed that 5-HT transiently depolarized the mitochondrial membrane whereas in the absence of extracellular calcium the mitochondrial membrane depolarisation was delayed and sustained in

  19. 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

  20. Signaling Pathways Linked to Serotonin-Induced Superoxide Anion Production: A Physiological Role for Mitochondria in Pulmonary Arteries.

    PubMed

    Genet, Nafiisha; Billaud, Marie; Rossignol, Rodrigue; Dubois, Mathilde; Gillibert-Duplantier, Jennifer; Isakson, Brant E; Marthan, Roger; Savineau, Jean-Pierre; Guibert, Christelle

    2017-01-01

    Serotonin (5-HT) is a potent vasoconstrictor agonist and contributes to several vascular diseases including systemic or pulmonary hypertension and atherosclerosis. Although superoxide anion ([Formula: see text]) is commonly associated to cellular damages due to [Formula: see text] overproduction, we previously demonstrated that, in physiological conditions, [Formula: see text] also participates to the 5-HT contraction in intrapulmonary arteries (IPA). Here, we focused on the signaling pathways leading to [Formula: see text] production in response to 5-HT in rat IPA. Using electron paramagnetic resonance on rat IPA, we showed that 5-HT (100 μM)-induced [Formula: see text] production was inhibited by ketanserin (1 μM-an inhibitor of the 5-HT2 receptor), absence of extracellular calcium, two blockers of voltage-independent calcium permeable channels (RHC80267 50 μM and LOE-908 10 μM) and a blocker of the mitochondrial complex I (rotenone-100 nM). Depletion of calcium from the sarcoplasmic reticulum or nicardipine (1 μM-an inhibitor of the L-type voltage-dependent calcium channel) had no effect on the 5-HT-induced [Formula: see text] production. [Formula: see text] levels were also increased by α-methyl-5-HT (10 μM-a 5-HT2 receptors agonist) whereas GR127935 (1 μM-an antagonist of the 5-HT1B/D receptor) and citalopram (1 μM-a 5-HT transporter inhibitor) had no effect on the 5-HT-induced [Formula: see text] production. Peroxynitrites were increased in response to 5-HT (100 μM). In isolated pulmonary arterial smooth muscle cells loaded with rhod-2 or mitosox probes, we respectively showed that 5-HT increased both mitochondrial calcium and [Formula: see text] levels, which were both abrogated in absence of extracellular calcium. Mitochondrial [Formula: see text] levels were also abolished in the presence of rotenone (100 nM). In pulmonary arterial smooth muscle cells loaded with TMRM, we showed that 5-HT transiently depolarized the mitochondrial membrane whereas

  1. Caffeine, cognition, and socioeconomic status.

    PubMed

    Kyle, Janet; Fox, Helen C; Whalley, Lawrence J

    2010-01-01

    There is interest in age-related cognitive decline and environmental risk factors for Alzheimer's disease (AD). This interest is focused on individual differences in exposure to agents that may harm or protect cognitive function. Caffeine is used as a short acting mental stimulant and may possess longer-term properties that protect against age-related decline and, possibly, AD. The current study aimed to: 1) examine current cognitive function in a narrow age range sample (n=351) without dementia (MMSE>25) who are, by reason of age, entering the period of increased risk of AD; and 2) link cognitive function to self-reported intake of caffeine and socioeconomic status (SES). Possible confounding by gender, childhood intelligence, education, and symptoms of anxiety and depression was introduced into the statistical model. There were significant differences between SES groups in caffeine intake (p< 0.05) and cognitive performance (p< 0.001). Higher quartiles of caffeine intake were associated with slower digit symbol speed (F =3.38, p< 0.02) but this finding was removed after allowing for SES. The results are discussed in terms of the withdrawal effects of caffeine during cognitive testing and strong links between SES and cognitive performance. No evidence in support of cognitive enhancing effects of caffeine was found.

  2. 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

    2016-05-05

    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.

  3. Vulnerability to depression: a moderated mediation model of the roles of child maltreatment, peer victimization, and serotonin transporter linked polymorphic region genetic variation among children from low socioeconomic status backgrounds.

    PubMed

    Banny, Adrienne M; Cicchetti, Dante; Rogosch, Fred A; Oshri, Assaf; Crick, Nicki R

    2013-08-01

    Child maltreatment, peer victimization, and a polymorphism of the serotonin transporter gene (5-HTTLPR) were examined as predictors of depressive symptomatology. Children (M age = 11.26, SD = 1.65), including 156 maltreated and 145 nonmaltreated children from comparable low socioeconomic backgrounds, provided DNA samples and self-reports of relational peer victimization, overt peer victimization, and depressive symptoms. Path analysis showed that relational and overt victimization mediated the association between child maltreatment and depressive symptoms. Bootstrapping procedures were used to test moderated mediation and demonstrated that genotype moderated the indirect effects of relational and overt victimization on child depressive symptoms, such that victimized children with the long/long variation were at an increased risk for depressive symptoms compared to victimized children carrying a short allele. Results highlight the utility of examining process models that incorporate biological and psychological factors contributing to the development of depressive symptomatology and provide direction toward understanding and promoting resilience among high-risk youth from a multiple levels of analysis approach.

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

    PubMed Central

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

    2013-01-01

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

  5. 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

    2016-09-02

    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.

  6. An essential role for the integrin-linked kinase-glycogen synthase kinase-3 beta pathway during dendrite initiation and growth.

    PubMed

    Naska, Sibel; Park, Katya J; Hannigan, Gregory E; Dedhar, Shoukat; Miller, Freda D; Kaplan, David R

    2006-12-20

    Multiple cues, including growth factors and circuit activity, signal to regulate the initiation and growth of mammalian dendrites. In this study, we have asked how these environmental cues regulate dendrite formation, and in particular, whether dendrite initiation and growth requires integrin-linked kinase (ILK) or its downstream effector, glycogen synthase kinase-3beta (GSK-3beta). In cultured sympathetic neurons, NGF and neuronal depolarization activated ILK and promoted dendrite initiation and growth, and inhibition of ILK (either pharmacologically, with a dominant-negative form of ILK, or by genetic knockdown) reduced depolarization-induced dendrite formation. In sympathetic neurons, ILK phosphorylated and inhibited GSK-3beta, and inhibition of GSK-3beta (either pharmacologically, with dominant-negative GSK-3beta, or by genetic knockdown) caused robust dendrite initiation. GSK-3beta inhibition also caused dendrite initiation in cultured cortical neurons and growth of hippocampal neurons in slice cultures. GSK-3beta functioned downstream of ILK to regulate dendrite formation, because inhibition of GSK-3beta promoted dendrite initiation even when ILK was simultaneously inhibited. Moreover, GSK-3beta promoted dendrite formation in sympathetic neurons by regulating the activity of a key dendrite formation effector, the MAP (microtubule-associated protein) kinase kinase (MEK)-extracellular signal-regulated protein kinase (ERK) pathway. Specifically, inhibition of GSK-3beta led to increased ERK phosphorylation, and inhibition of MEK completely blocked the effects of GSK-3beta inhibition on dendrite initiation and growth. Thus, the ILK-GSK-3beta pathway plays a key role in regulating dendrite formation in developing mammalian neurons.

  7. 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.

  8. TGFβ2 Induces the Formation of Cross-Linked Actin Networks (CLANs) in Human Trabecular Meshwork Cells Through the Smad and Non-Smad Dependent Pathways

    PubMed Central

    Montecchi-Palmer, Michela; Bermudez, Jaclyn Y.; Webber, Hannah C.; Patel, Gaurang C.; Clark, Abbot F.; Mao, Weiming

    2017-01-01

    Purpose Increased intraocular pressure results from increased aqueous humor (AH) outflow resistance at the trabecular meshwork (TM) due to pathologic changes including the formation of cross-linked actin networks (CLANs). Transforming growth factor β2 (TGFβ2) is elevated in the AH and TM of primary open angle glaucoma (POAG) patients and induces POAG-associated TM changes, including CLANs. We determined the role of individual TGFβ2 signaling pathways in CLAN formation. Methods Cultured nonglaucomatous human TM (NTM) cells were treated with control or TGFβ2, with or without the inhibitors of TGFβ receptor, Smad3, c-Jun N-terminal kinases (JNK), extracellular signal regulated kinase (ERK), P38, or Rho-associated protein kinase (ROCK). NTM cells were cotreated with TGFβ2 plus inhibitors for 10 days or pretreated with TGFβ2 for 10 days followed by 1-hour inhibitor treatment. NTM cells were immunostained with phalloidin-Alexa-488 and 4′,6-diamidino-2-phenylindole (DAPI). Data were analyzed using 1-way ANOVA and Dunnett's post hoc test. Results TGFβ2 significantly induced CLAN formation (n = 6 to 12, P < 0.05), which was completely inhibited by TGFβ receptor, Smad3, and ERK inhibitors, as well as completely or partially inhibited by JNK, P38, and ROCK inhibitors, depending on cell strains. One-hour exposure to ROCK inhibitor completely resolved formed CLANs (P < 0.05), whereas TGFβ receptor, Smad3 inhibitor, and ERK inhibitors resulted in partial or complete resolution. The JNK and P38 inhibitors showed partial or no resolution. Among these inhibitors, the ROCK inhibitor was the most disruptive to the actin stress fibers, whereas ERK inhibition showed the least disruption. Conclusions TGFβ2-induced CLANs in NTM cells were prevented and resolved using various pathway inhibitors. Apart from CLAN inhibition, some of these inhibitors also had different effects on actin stress fibers. PMID:28241317

  9. Ubiquitin-specific protease 8 links the PTEN-Akt-AIP4 pathway to the control of FLIPS stability and TRAIL sensitivity in glioblastoma multiforme.

    PubMed

    Panner, Amith; Crane, Courtney A; Weng, Changjiang; Feletti, Alberto; Fang, Shanna; Parsa, Andrew T; Pieper, Russell O

    2010-06-15

    The antiapoptotic protein FLIP(S) is a key suppressor of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis in human glioblastoma multiforme (GBM) cells. We previously reported that a novel phosphatase and tensin homologue (PTEN)-Akt-atrophin-interacting protein 4 (AIP4) pathway regulates FLIP(S) ubiquitination and stability, although the means by which PTEN and Akt were linked to AIP4 activity were unclear. Here, we report that a second regulator of ubiquitin metabolism, the ubiquitin-specific protease 8 (USP8), is a downstream target of Akt, and that USP8 links Akt to AIP4 and the regulation of FLIP(S) stability and TRAIL resistance. In human GBM xenografts, levels of USP8 correlated inversely with pAkt levels, and genetic or pharmacologic manipulation of Akt regulated USP8 levels in an inverse manner. Overexpression of wild-type USP8, but not catalytically inactive USP8, increased FLIP(S) ubiquitination, decreased FLIP(S) half-life, decreased FLIP(S) steady-state levels, and decreased TRAIL resistance, whereas short interfering RNA (siRNA)-mediated suppression of USP8 levels had the opposite effect. Because high levels of the USP8 deubiquitinase correlated with high levels of FLIP(S) ubiquitination, USP8 seemed to control FLIP(S) ubiquitination through an intermediate target. Consistent with this idea, overexpression of wild-type USP8 decreased the ubiquitination of the FLIP(S) E3 ubiquitin ligase AIP4, an event previously shown to increase AIP4-FLIP(S) interaction, whereas siRNA-mediated suppression of USP8 increased AIP4 ubiquitination. Furthermore, the suppression of FLIP(S) levels by USP8 overexpression was reversed by the introduction of siRNA targeting AIP4. These results show that USP8, a downstream target of Akt, regulates the ability of AIP4 to control FLIP(S) stability and TRAIL sensitivity.

  10. USP8 links the PTEN-Akt-AIP4 pathway to the control of FLIPS stability and TRAIL sensitivity in glioblastoma multiforme

    PubMed Central

    Panner, Amith; Crane, Courtney A.; Weng, Changjiang; Feletti, Alberto; Fang, Shanna; Parsa, Andrew T.; Pieper, Russell O.

    2010-01-01

    The anti-apoptotic protein FLIPS is a key suppressor of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) -induced apoptosis in human glioblastoma multiforme (GBM) cells. We previously reported that a novel phosphatase and tensin homolog (PTEN)-Akt-atrophin interacting protein 4 (AIP4) pathway regulates FLIPS ubiquitination and stability, although the means by which PTEN and Akt were linked to AIP4 activity were unclear. We here report that a second regulator of ubiquitin metabolism, the ubiquitin-specific protease (USP) 8, is a downstream target of Akt, and that USP8 links Akt to AIP4 and the regulation of FLIPS stability and TRAIL resistance. In human GBM xenografts, levels of USP8 correlated inversely with pAkt levels, and genetic or pharmacologic manipulation of Akt regulated USP8 levels in an inverse manner. Over-expression of WT USP8, but not catalytically inactive USP8, increased FLIPS ubiquitination, decreased FLIPS half-life, decreased FLIPS steady-state levels, and decreased TRAIL resistance, while siRNA-mediated suppression of USP8 levels had the opposite effects. Because high levels of the USP8 deubiquitinase correlated with high levels of FLIPS ubiquitination, USP8 appeared to control FLIPS ubiquitination through an intermediate target. Consistent with this idea, over-expression of WT USP8 decreased ubiquitination of the FLIPS E3 ubiquitin ligase AIP4, an event previously shown to increase AIP4-FLIPS interaction, while siRNA-mediated suppression of USP8 increased AIP4 ubiquitination. Furthermore, the suppression of FLIPS levels by USP8 over-expression was reversed by introduction of siRNA targeting AIP4. These results show that USP8, a downstream target of Akt, regulates the ability of AIP4 to control FLIPS stability and TRAIL sensitivity. PMID:20484045

  11. 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.

  12. 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

  13. Evidence of molecular links between PKR and mTOR signalling pathways in Abeta neurotoxicity: role of p53, Redd1 and TSC2.

    PubMed

    Morel, Milena; Couturier, Julien; Pontcharraud, Raymond; Gil, Roger; Fauconneau, Bernard; Paccalin, Marc; Page, Guylène

    2009-10-01

    The control of translation is disturbed in Alzheimer's disease (AD). This study analysed the crosslink between the up regulation of double-stranded RNA-dependent-protein kinase (PKR) and the down regulation of mammalian target of rapamycin (mTOR) signalling pathways via p53, the protein Regulated in the Development and DNA damage response 1 (Redd1) and the tuberous sclerosis complex (TSC2) factors in two beta-amyloid peptide (Abeta) neurotoxicity models. In SH-SY5Y cells, Abeta42 induced an increase of P(T451)-PKR and of the ratio p66/(p66+p53) in nuclei and a physical interaction between these proteins. Redd1 gene levels increased and P(T1462)-TSC2 decreased. These disturbances were earlier in rat primary neurons with nuclear co-localization of Redd1 and PKR. The PKR gene silencing in SH-SY5Y cells prevented these alterations. p53, Redd1 and TSC2 could represent the molecular links between PKR and mTOR in Abeta neurotoxicity. PKR could be a critical target in a therapeutic program of AD.

  14. A redox-active, compact molecule for cross-linking amyloidogenic peptides into nontoxic, off-pathway aggregates: In vitro and in vivo efficacy and molecular mechanisms

    SciTech Connect

    Derrick, Jeffrey S.; Kerr, Richard A.; Nam, Younwoo; Oh, Shin Bi; Lee, Hyuck Jin; Earnest, Kaylin G.; Suh, Nayoung; Peck, Kristy L.; Ozbil, Mehmet; Korshavn, Kyle J.; Ramamoorthy, Ayyalusamy; Prabhakar, Rajeev; Merino, Edward J.; Shearer, Jason; Lee, Joo -Yong; Ruotolo, Brandon T.; Lim, Mi Hee

    2015-11-17

    Chemical reagents targeting and controlling amyloidogenic peptides have received much attention for helping identify their roles in the pathogenesis of protein-misfolding disorders. In this paper, we report a novel strategy for redirecting amyloidogenic peptides into nontoxic, off-pathway aggregates, which utilizes redox properties of a small molecule (DMPD, N,N-dimethyl-p-phenylenediamine) to trigger covalent adduct formation with the peptide. In addition, for the first time, biochemical, biophysical, and molecular dynamics simulation studies have been performed to demonstrate a mechanistic understanding for such an interaction between a small molecule (DMPD) and amyloid-β (Aβ) and its subsequent anti-amyloidogenic activity, which, upon its transformation, generates ligand–peptide adducts via primary amine-dependent intramolecular cross-linking correlated with structural compaction. Furthermore, in vivo efficacy of DMPD toward amyloid pathology and cognitive impairment was evaluated employing 5xFAD mice of Alzheimer’s disease (AD). Such a small molecule (DMPD) is indicated to noticeably reduce the overall cerebral amyloid load of soluble Aβ forms and amyloid deposits as well as significantly improve cognitive defects in the AD mouse model. Altogether our in vitro and in vivo studies of DMPD toward Aβ with the first molecular-level mechanistic investigations present the feasibility of developing new, innovative approaches that employ redox-active compounds without the structural complexity as next-generation chemical tools for amyloid management.

  15. A redox-active, compact molecule for cross-linking amyloidogenic peptides into nontoxic, off-pathway aggregates: In vitro and in vivo efficacy and molecular mechanisms

    DOE PAGES

    Derrick, Jeffrey S.; Kerr, Richard A.; Nam, Younwoo; ...

    2015-11-17

    Chemical reagents targeting and controlling amyloidogenic peptides have received much attention for helping identify their roles in the pathogenesis of protein-misfolding disorders. In this paper, we report a novel strategy for redirecting amyloidogenic peptides into nontoxic, off-pathway aggregates, which utilizes redox properties of a small molecule (DMPD, N,N-dimethyl-p-phenylenediamine) to trigger covalent adduct formation with the peptide. In addition, for the first time, biochemical, biophysical, and molecular dynamics simulation studies have been performed to demonstrate a mechanistic understanding for such an interaction between a small molecule (DMPD) and amyloid-β (Aβ) and its subsequent anti-amyloidogenic activity, which, upon its transformation, generates ligand–peptidemore » adducts via primary amine-dependent intramolecular cross-linking correlated with structural compaction. Furthermore, in vivo efficacy of DMPD toward amyloid pathology and cognitive impairment was evaluated employing 5xFAD mice of Alzheimer’s disease (AD). Such a small molecule (DMPD) is indicated to noticeably reduce the overall cerebral amyloid load of soluble Aβ forms and amyloid deposits as well as significantly improve cognitive defects in the AD mouse model. Altogether our in vitro and in vivo studies of DMPD toward Aβ with the first molecular-level mechanistic investigations present the feasibility of developing new, innovative approaches that employ redox-active compounds without the structural complexity as next-generation chemical tools for amyloid management.« less

  16. Socioeconomic factors and racial disparities in kidney disease outcomes.

    PubMed

    Crews, Deidra C; Pfaff, Teresa; Powe, Neil R

    2013-09-01

    African Americans suffer disproportionately from advanced and progressive chronic kidney disease (CKD). Socioeconomic factors are believed to play an important role in this disparity, and likely influence African Americans' increased risk of CKD through multiple pathways. Low socioeconomic status (SES) may contribute to racial disparities in CKD because of the greater prevalence of poverty, for example, among African Americans as compared with whites. However, low SES has a stronger relation with CKD among African Americans than among whites, underscoring that the context and magnitude of socioeconomic influences on CKD outcomes varies between these populations. These socioeconomic influences may produce new or potentiate existing racial differences in biology. This review discusses what is known about the role of SES in explaining racial disparities in CKD, highlights several knowledge gaps in this area, and suggests future directions toward the elimination of disparities in CKD.

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

    PubMed

    Gianaros, Peter J; Hackman, Daniel A

    2013-09-01

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

  18. [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.

  19. 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…

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

    PubMed

    Saeed, Muhammad Tariq; Ahmad, Jamil; Kanwal, Shahzina; Holowatyj, Andreana N; Sheikh, Iftikhar A; Zafar Paracha, Rehan; Shafi, Aamir; Siddiqa, Amnah; Bibi, Zurah; Khan, Mukaram; Ali, Amjad

    2016-01-01

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

  1. Thiocolchicoside Exhibits Anticancer Effects through Downregulation of NF-κB Pathway and Its Regulated Gene Products Linked to Inflammation and Cancer

    PubMed Central

    Reuter, Simone; Prasad, Sahdeo; Phromnoi, Kanokkarn; Ravindran, Jayaraj; Sung, Bokyung; Yadav, Vivek R.; Kannappan, Ramaswamy; Chaturvedi, Madan M.; Aggarwal, Bharat B.

    2011-01-01

    The discovery of new uses for older, clinically approved drugs is one way to expedite drug development for cancer. Thiocolchicoside, a semisynthetic colchicoside from the plant Gloriosa superba, is a muscle relaxant and used to treat rheumatologic and orthopedic disorders because of its analgesic and anti-inflammatory mechanisms. Given that activation of the transcription factor NF-κB plays a major role in inflammation and tumorigenesis, we postulated that thiocolchicoside would inhibit NF-κB and exhibit anticancer effects through the modulation of NF-κB–regulated proteins. We show that thiocolchicoside inhibited proliferation of leukemia, myeloma, squamous cell carcinoma, breast, colon, and kidney cancer cells. Formation of tumor colonies was also suppressed by thiocolchicoside. The colchicoside induced apoptosis, as indicated by caspase-3 and poly(ADP-ribose) polymerase cleavage, and suppressed the expression of cell survival [e.g., Bcl-2, X-linked inhibitor of apoptosis (XIAP), MCL-1, bcl-xL, cIAP-1, cIAP-2, and cFLIP] proteins. Cell proliferation biomarkers such as c-MYC and phosphorylation of phosphoinositide 3-kinase and glycogen synthase kinase 3β were also blocked by thiocolchicoside. Because most cell survival and proliferation gene products are regulated by NF-κB, we studied the effect of thiocolchicoside on this transcription factor and found that thiocolchicoside inhibited NF-κB activation, degradation of inhibitory κBα (IκBα), IκBα ubiquitination, and phosphorylation, abolished the activation of IκBα kinase, and suppressed p65 nuclear translocation. This effect of thiocolchicoside on the NF-κB pathway led to inhibition of NF-κB reporter activity and cyclooxygenase-2 promoter activity. Our results indicate that thiocolchicoside exhibits anticancer activity through inhibition of NF-κB and NF-κB–regulated gene products, which provides novel insight into a half-century old drug. PMID:20978115

  2. Thiocolchicoside exhibits anticancer effects through downregulation of NF-κB pathway and its regulated gene products linked to inflammation and cancer.

    PubMed

    Reuter, Simone; Prasad, Sahdeo; Phromnoi, Kanokkarn; Ravindran, Jayaraj; Sung, Bokyung; Yadav, Vivek R; Kannappan, Ramaswamy; Chaturvedi, Madan M; Aggarwal, Bharat B

    2010-11-01

    The discovery of new uses for older, clinically approved drugs is one way to expedite drug development for cancer. Thiocolchicoside, a semisynthetic colchicoside from the plant Gloriosa superba, is a muscle relaxant and used to treat rheumatologic and orthopedic disorders because of its analgesic and anti-inflammatory mechanisms. Given that activation of the transcription factor NF-κB plays a major role in inflammation and tumorigenesis, we postulated that thiocolchicoside would inhibit NF-κB and exhibit anticancer effects through the modulation of NF-κB-regulated proteins. We show that thiocolchicoside inhibited proliferation of leukemia, myeloma, squamous cell carcinoma, breast, colon, and kidney cancer cells. Formation of tumor colonies was also suppressed by thiocolchicoside. The colchicoside induced apoptosis, as indicated by caspase-3 and poly(ADP-ribose) polymerase cleavage, and suppressed the expression of cell survival [e.g., Bcl-2, X-linked inhibitor of apoptosis (XIAP), MCL-1, bcl-xL, cIAP-1, cIAP-2, and cFLIP] proteins. Cell proliferation biomarkers such as c-MYC and phosphorylation of phosphoinositide 3-kinase and glycogen synthase kinase 3β were also blocked by thiocolchicoside. Because most cell survival and proliferation gene products are regulated by NF-κB, we studied the effect of thiocolchicoside on this transcription factor and found that thiocolchicoside inhibited NF-κB activation, degradation of inhibitory κBα (IκBα), IκBα ubiquitination, and phosphorylation, abolished the activation of IκBα kinase, and suppressed p65 nuclear translocation. This effect of thiocolchicoside on the NF-κB pathway led to inhibition of NF-κB reporter activity and cyclooxygenase-2 promoter activity. Our results indicate that thiocolchicoside exhibits anticancer activity through inhibition of NF-κB and NF-κB-regulated gene products, which provides novel insight into a half-century old drug.

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

    PubMed Central

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

    2016-01-01

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

  4. 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

  5. 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

  6. 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…

  7. 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…

  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. 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

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

    PubMed Central

    Carmena, Ana; Speicher, Stephan; Baylies, Mary

    2006-01-01

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

  11. 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.

  12. 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

  13. 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

  14. Psychological Pathways Linking Social Support to Health Outcomes: A Visit with the “Ghosts” of Research Past, Present, and Future

    PubMed Central

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

    2012-01-01

    Contemporary models postulate the importance of psychological mechanisms linking perceived and received social support to physical health outcomes. In this review, we examine studies that directly tested the potential psychological mechanisms responsible for links between social support and health-relevant physiological processes (1980s to 2010). Inconsistent with existing theoretical models, no evidence was found that psychological mechanisms such as depression, perceived stress, and other affective processes are directly responsible for links between support and health. We discuss the importance of considering statistical/design issues, emerging conceptual perspectives, and limitations of our existing models for future research aimed at elucidating the psychological mechanisms responsible for links between social support and physical health outcomes. PMID:22326104

  15. 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

  16. 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.

  17. 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…

  18. Two New Plant-Like Pathways Link Hemoglobin Degradation to Lipid Biogenesis in Falciparum Malaria: Novel Targets for Anti-Malarial Chemotherapy

    DTIC Science & Technology

    2005-03-01

    0.1 M sodium borate as a standard. (75:45:12:4.5) as mobile phase. The identity of the radioactive spots was determined by TLC analysis using...formation of both PtdEtn and PtdCho (Fig. IA), (253aa) indicating the presence of a functional CDP- ethano [amine pathway for PtdEtn synthesis and

  19. 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)…

  20. 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.

  1. 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.

  2. 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…

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

    PubMed

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

    2014-03-15

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

  4. Impact of reproductive health on socio-economic development: a case study of Nigeria.

    PubMed

    Adinma, J I B; Adinma, E D

    2011-03-01

    The link between reproductive health, sexual and reproductive right, and development was highlighted at the International Conference on Population and Development held in Egypt. Developmental disparities are related to socio-economic differences which have led to the identification of distinct socio-economic classifications of nations. Human development represents the socioeconomic standing of any nation, in addition to literacy status and life expectancy. Africa accounts for 25% of the world's landmass but remains the world's poorest continent. Nigeria, the most populous country in Africa, has policies and programmes geared towards the improvement of its socio-economic standing and overal development, with little positive result. Reproductive health is a panacea towards reversing the stalled socio-economic growth of Nigeria as evident from the linkage between reproductive health and development, highlighted in Millennium Development Goals 3, 4, 5 and 6. Fast tracking Nigeria's development requires implementation of reproductive health policies and programmes targeted on women and children.

  5. Expression/activation of α5β1 integrin is linked to the β-catenin signaling pathway to drive migration in glioma cells

    PubMed Central

    Renner, Guillaume; Noulet, Fanny; Mercier, Marie-Cécile; Choulier, Laurence; Etienne-Selloum, Nelly; Gies, Jean-Pierre; Lehmann, Maxime; Lelong-Rebel, Isabelle; Martin, Sophie; Dontenwill, Monique

    2016-01-01

    The Wnt/beta catenin pathway has been highlighted as an important player of brain tumors aggressiveness and resistance to therapies. Increasing knowledges of the regulation of beta-catenin transactivation point out its hub position in different pathophysiological outcomes in glioma such as survival and migration. Crosstalks between integrins and beta-catenin pathways have been suggested in several tumor tissues. As we demonstrated earlier that α5β1 integrin may be considered as a therapeutic target in high grade glioma through its contribution to glioma cell migration and resistance to chemotherapy, we addressed here the potential relationship between α5β1 integrin and beta-catenin activation in glioma cells. We demonstrated that overexpression and activation by fibronectin of α5β1 integrin allowed the transactivation of beta-catenin gene targets included in an EMT-like program that induced an increase in cell migration. Hampering of beta catenin activation and cell migration could be similarly achieved by a specific integrin antagonist. In addition we showed that α5β1 integrin/AKT axis is mainly involved in these processes. However, blockade of beta-catenin by XAV939 (tankyrase inhibitor leading to beta-catenin degradation) did not synergize with p53 activation aiming to cell apoptosis as was the case with integrin antagonists. We therefore propose a dual implication of α5β1 integrin/AKT axis in glioma cell resistance to therapies and migration each supported by different signaling pathways. Our data thus suggest that α5β1 integrin may be added to the growing list of beta-catenin modulators and provide new evidences to assign this integrin as a valuable target to fight high grade glioma. PMID:27613837

  6. 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

  7. 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

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

    2016-02-24

    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.

  8. 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

  9. 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

  10. A pathway in the yeast cell division cycle linking protein kinase C (Pkc1) to activation of Cdc28 at START.

    PubMed Central

    Marini, N J; Meldrum, E; Buehrer, B; Hubberstey, A V; Stone, D E; Traynor-Kaplan, A; Reed, S I

    1996-01-01

    In an effort to study further the mechanism of Cdc28 function and cell cycle commitment, we describe here a genetic approach to identify components of pathways downstream of the Cdc28 kinase at START by screening for mutations that decrease the effectiveness of signaling by Cdc28. The first locus to be characterized in detail using this approach was PKC1 which encodes a homolog of the Ca(2+)-dependent isozymes of the mammalian protein kinase C (PKC) superfamily (Levin et al., 1990). By several genetic criteria, we show a functional interaction between CDC28 and PKC1 with PKC1 apparently functioning with respect to bud emergence downstream of START. Consistent with this, activity of the MAP kinase homolog Mpk1 (a putative Pkc1 effector) is stimulated by activation of Cdc28. Furthermore, we demonstrate a cell cycle-dependent hydrolysis of phosphatidylcholine to diacylglycerol (a PKC activator) and choline phosphate at START. Diacylglycerol production is stimulated by Cdc28 in cycling cells and is closely associated with Cdc28 activation at START. These results imply that the activation of Pkc1, which is known to be necessary during bud morphogenesis, is mediated via the CDC28-dependent stimulation of PC-PLC activity in a novel cell cycle-regulated signaling pathway. Images PMID:8670805

  11. 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

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

    PubMed Central

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

    2015-01-01

    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

  13. 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

  14. 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.

  15. Oxidatively Generated Guanine(C8)-Thymine(N3) Intrastrand Cross-links in Double-stranded DNA Are Repaired by Base Excision Repair Pathways.

    PubMed

    Talhaoui, Ibtissam; Shafirovich, Vladimir; Liu, Zhi; Saint-Pierre, Christine; Akishev, Zhiger; Matkarimov, Bakhyt T; Gasparutto, Didier; Geacintov, Nicholas E; Saparbaev, Murat

    2015-06-05

    Oxidatively generated guanine radical cations in DNA can undergo various nucleophilic reactions including the formation of C8-guanine cross-links with adjacent or nearby N3-thymines in DNA in the presence of O2. The G*[C8-N3]T* lesions have been identified in the DNA of human cells exposed to oxidative stress, and are most likely genotoxic if not removed by cellular defense mechanisms. It has been shown that the G*[C8-N3]T* lesions are substrates of nucleotide excision repair in human cell extracts. Cleavage at the sites of the lesions was also observed but not further investigated (Ding et al. (2012) Nucleic Acids Res. 40, 2506-2517). Using a panel of eukaryotic and prokaryotic bifunctional DNA glycosylases/lyases (NEIL1, Nei, Fpg, Nth, and NTH1) and apurinic/apyrimidinic (AP) endonucleases (Apn1, APE1, and Nfo), the analysis of cleavage fragments by PAGE and MALDI-TOF/MS show that the G*[C8-N3]T* lesions in 17-mer duplexes are incised on either side of G*, that none of the recovered cleavage fragments contain G*, and that T* is converted to a normal T in the 3'-fragment cleavage products. The abilities of the DNA glycosylases to incise the DNA strand adjacent to G*, while this base is initially cross-linked with T*, is a surprising observation and an indication of the versatility of these base excision repair proteins.

  16. FM19G11: A new modulator of HIF that links mTOR activation with the DNA damage checkpoint pathways.

    PubMed

    Rodríguez-Jiménez, Francisco Javier; Moreno-Manzano, Victoria; Mateos-Gregorio, Pablo; Royo, Inmaculada; Erceg, Slaven; Murguia, José Ramón; Sánchez-Puelles, Jose María

    2010-07-15

    The network consisting of mTOR and p53 pathways is crucial to understanding a wide variety of physiological and pathological events, including cancer and aging. In addition, the HIF1alpha protein, a downstream target of mTOR, is a hallmark of different tumor types and was the desired strategy of many drug discovery efforts. Here we present the novel chemical entity FM19G11, a new modulator of HIF1alpha expression, which was used as a molecular tool to dissect and further characterize the cross-talk between these signaling cascades in human colon carcinoma cell lines. To our knowledge, FM19G11 is the first drug that triggers a DNA damage response (DDR) associated with G(1)/S-phase arrest in a p53-dependent manner, due to rapid hyper-activation of the growth signaling pathway through mTOR. Assessment of colonies demonstrated that FM19G11 decreases the clonogenicity of HT29, HCT116/p53(+/+) and HCT116/p53(-/-) cells. Moreover, FM19G11 causes significant lower colony growth in soft agar of p53-proficient human colon cancer cells. Consequently, p53 sensitizes human colon cancer cells to FM19G11 by significant reduction of their viability, lessening their colony formation capability and shrinking their anchorage-independent growth. Cell signaling studies served to assign a new mode of action to FM19G11, whose tumor-suppressant activity compromises the survival of functional p53 malignant cells.

  17. Streptococcus pyogenes M49 plasminogen/plasmin binding facilitates keratinocyte invasion via integrin-integrin-linked kinase (ILK) pathways and protects from macrophage killing.

    PubMed

    Siemens, Nikolai; Patenge, Nadja; Otto, Juliane; Fiedler, Tomas; Kreikemeyer, Bernd

    2011-06-17

    The entry into epithelial cells and the prevention of primary immune responses are a prerequisite for a successful colonization and subsequent infection of the human host by Streptococcus pyogenes (group A streptococci, GAS). Here, we demonstrate that interaction of GAS with plasminogen promotes an integrin-mediated internalization of the bacteria into keratinocytes, which is independent from the serine protease activity of potentially generated plasmin. α(1)β(1)- and α(5)β(1)-integrins were identified as the major keratinocyte receptors involved in this process. Inhibition of integrin-linked kinase (ILK) expression by siRNA silencing or blocking of PI3K and Akt with specific inhibitors, reduced the GAS M49-plasminogen/plasmin-mediated invasion of keratinocytes. In addition, blocking of actin polymerization significantly reduced GAS internalization into keratinocytes. Altogether, these results provide a first model of plasminogen-mediated GAS invasion into keratinocytes. Furthermore, we demonstrate that plasminogen binding protects the bacteria against macrophage killing.

  18. 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

  19. The nuclease hSNM1B/Apollo is linked to the Fanconi anemia pathway via its interaction with FANCP/SLX4.

    PubMed

    Salewsky, Bastian; Schmiester, Maren; Schindler, Detlev; Digweed, Martin; Demuth, Ilja

    2012-11-15

    The recessive genetic disorder Fanconi anemia (FA) is clinically characterized by congenital defects, bone marrow failure and an increased incidence of cancer. Cells derived from FA patients exhibit hypersensitivity to DNA interstrand crosslink (ICL)-inducing agents. We have earlier reported a similar cellular phenotype for human cells depleted of hSNM1B/Apollo (siRNA). In fact, hSNM1B/Apollo has a dual role in the DNA damage response and in generation and maintenance of telomeres, the latter function involving interaction with the shelterin protein TRF2. Here we find that ectopically expressed hSNM1B/Apollo co-immunoprecipitates with SLX4, a protein recently identified as a new FA protein, FANCP, and known to interact with several structure-specific nucleases. As shown by immunofluorescence analysis, FANCP/SLX4 depletion (siRNA) resulted in a significant reduction of hSNM1B/Apollo nuclear foci, supporting the functional relevance of this new protein interaction. Interestingly, as an additional consequence of FANCP/SLX4 depletion, we found a reduction of cellular TRF2, in line with its telomere-related function. Finally, analysis of human cells following double knockdown of hSNM1B/Apollo and FANCP/SLX4 indicated that they function epistatically. These findings further substantiate the role of hSNM1B/Apollo in a downstream step of the FA pathway during the repair of DNA ICLs.

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

    PubMed Central

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

    2015-01-01

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

  1. JWA is required for arsenic trioxide induced apoptosis in HeLa and MCF-7 cells via reactive oxygen species and mitochondria linked signal pathway

    SciTech Connect

    Zhou Jinhong; Ye Jian; Zhao Xiaojia; Li Aiping; Zhou Jianwei

    2008-07-01

    Arsenic trioxide, emerging as a standard therapy for refractory acute promyelocytic leukemia, induces apoptosis in a variety of malignant cell lines. JWA, a novel retinoic acid-inducible gene, is known to be involved in apoptosis induced by various agents, for example, 12-O-tetradecanoylphorbol 13-acetate, N-4-hydroxy-phenyl-retinamide and arsenic trioxide. However, the molecular mechanisms underlying how JWA gene is functionally involved in apoptosis remain largely unknown. Herein, our studies demonstrated that treatment of arsenic trioxide produced apoptosis in HeLa and MCF-7 cells in a dose-dependent manner and paralleled with increased JWA expression. JWA expression was dependent upon generation of intracellular reactive oxygen species induced by arsenic trioxide. Knockdown of JWA attenuated arsenic trioxide induced apoptosis, and was accompanied by significantly reduced activity of caspase-9, enhanced Bad phosphorylation and inhibited MEK1/2, ERK1/2 and JNK phosphorylations. Arsenic trioxide induced loss of mitochondrial transmembrane potential was JWA-dependent. These findings suggest that JWA may serve as a pro-apoptotic molecule to mediate arsenic trioxide triggered apoptosis via a reactive oxygen species and mitochondria-associated signal pathway.

  2. The link in Linking

    PubMed Central

    Caldwell, Jane C; Chiale, Pablo A; Gonzalez, Mario D; Baranchuk, Adrian

    2013-01-01

    We present 2 cases of the slow-fast form of AVNRT with initially narrow QRS complexes followed by sudden unexpected transition to persistently wide QRS complexes due to aberrant intraventricular conduction. Introduction of a properly timed extrastimulus in one case and critical oscillations in cycle length due to short-long coupling in the second case set the stage for the initial bundle branch block. However, persistence of the aberrancy pattern once the initial event abated was maintained by the "linking" phenomenon. Delayed, retrograde concealed activation from the contralateral bundle branch perpetuated the initial bundle branch block. PMID:23840106

  3. The link in Linking.

    PubMed

    Caldwell, Jane C; Chiale, Pablo A; Gonzalez, Mario D; Baranchuk, Adrian

    2013-05-01

    We present 2 cases of the slow-fast form of AVNRT with initially narrow QRS complexes followed by sudden unexpected transition to persistently wide QRS complexes due to aberrant intraventricular conduction. Introduction of a properly timed extrastimulus in one case and critical oscillations in cycle length due to short-long coupling in the second case set the stage for the initial bundle branch block. However, persistence of the aberrancy pattern once the initial event abated was maintained by the "linking" phenomenon. Delayed, retrograde concealed activation from the contralateral bundle branch perpetuated the initial bundle branch block.

  4. Adolescent Expectations of Early Death Predict Young Adult Socioeconomic Status

    PubMed Central

    Nguyen, Quynh C.; Hussey, Jon M.; Halpern, Carolyn T.; Villaveces, Andres; Marshall, Stephen W.; Siddiqi, Arjumand; Poole, Charles

    2013-01-01

    Among adolescents, expectations of early death have been linked to future risk behaviors. These expectations may also reduce personal investment in education and training, thereby lowering adult socioeconomic status attainment. The importance of socioeconomic status is highlighted by pervasive health inequities and dramatic differences in life expectancy among education and income groups. The objectives of this study were to investigate patterns of change in perceived chances of living to age 35 (Perceived Survival Expectations; PSE), predictors of PSE, and associations between PSE and future socioeconomic status attainment. We utilized the U.S. National Longitudinal Study of Adolescent Health (Add Health) initiated in 1994-95 among 20,745 adolescents in grades 7-12 with follow-up interviews in 1996 (Wave II), 2001-02 (Wave III) and 2008 (Wave IV; ages 24-32). At Wave I, 14% reported ≤ 50% chance of living to age 35 and older adolescents reported lower PSE than younger adolescents. At Wave III, PSE were similar across age. Changes in PSE from Wave I to III were moderate, with 89% of respondents reporting no change (56%), one level higher (22%) or one level lower (10%) in a 5-level PSE variable. Higher block group poverty rate, perceptions that the neighborhood is unsafe, and less time in the U.S. (among the foreign-born) were related to low PSE at Waves I and III. Low PSE at Waves I and III predicted lower education attainment and personal earnings at Wave IV in multinomial logistic regression models controlling for confounding factors such as previous family socioeconomic status, individual demographic characteristics, and depressive symptoms. Anticipation of an early death is prevalent among adolescents and predictive of lower future socioeconomic status. Low PSE reported early in life may be a marker for worse health trajectories. PMID:22405687

  5. Enhanced Lithium Ion Transport in Poly(ethylene glycol) Diacrylate-Supported Solvate Ionogel Electrolytes via Chemically Cross-linked Ethylene Oxide Pathways.

    PubMed

    D'Angelo, Anthony J; Panzer, Matthew J

    2017-02-02

    Lithium-ion solvate ionic liquids (SILs), consisting of complexed Li(+) cations and a weakly basic anion, represent an emergent class of nonvolatile liquid electrolytes suitable for lithium-based electrochemical energy storage. In this report, solid-state, flexible solvate ionogel electrolytes are synthesized via UV-initiated free radical polymerization/cross-linking of poly(ethylene glycol) diacrylate (PEGDA) in situ within the [Li(G4)][TFSI] electrolyte, which is formed by an equimolar mixture of lithium bis(trifluoromethylsulfonyl)imide (LiTFSI) and tetraglyme (G4). Ion diffusivity measurements reveal enhanced Li(+) diffusion in PEGDA-supported solvate ionogels, as compared to poly(methyl methacrylate)-supported gels that lack ethylene oxide chains. At 21 vol% PEGDA, a maximum Li(+) transport number of 0.58 and a room temperature ionic conductivity of 0.43 mS/cm have been achieved in a solvate ionogel electrolyte that exhibits an elastic modulus of 0.47 MPa. These results demonstrate the importance of polymer scaffold selection on solvate ionogel electrolyte performance for advanced lithium-based batteries.

  6. 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.

  7. Overexpression of integrin-linked kinase (ILK) promotes glioma cell invasion and migration and down-regulates E-cadherin via the NF-κB pathway.

    PubMed

    Liang, Feng; Zhang, Shuqin; Wang, Bing; Qiu, Jianwu; Wang, Yunjie

    2014-04-01

    Integrin-linked kinase (ILK) is a ubiquitously expressed serine/threonine protein kinase that has been implicated in cancer development, progression and metastasis. The aim of the present study was to characterize the role of ILK in glioma cell invasion and migration. We generated a recombinant eukaryotic expression vector containing the human ILK gene and transfected it into human glioma SHG-44 cells. Real-time PCR and western blot analysis were used to identify the stable transformants. The wound healing and Transwell invasion assays showed that ectopic overexpression of ILK in SHG-44 cells significantly promoted their migration and invasion capabilities in culture. This was accompanied by a decrease in expression of E-cadherin and an increase in expression of Snail and Slug. Moreover, the decrease in E-cadherin expression induced by ILK overexpression was greatly restored by the nuclear factor-κB (NF-κB) inhibitor BAY 11-7028 or small interfering RNA targeting NF-κB p65, indicating an involvement of NF-κB in ILK-induced down-regulation of E-cadherin. In conclusion, our data underscore a novel role for ILK in glioma invasion and metastasis processes, implicating potential for therapeutic interference.

  8. 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.

  9. The maize (Zea mays) desynaptic (dy) mutation defines a pathway for meiotic chromosome segregation, linking nuclear morphology, telomere distribution and synapsis.

    PubMed

    Murphy, Shaun P; Bass, Hank W

    2012-08-01

    Meiosis involves a dramatic reorganization of the genetic material, along with changes in the architecture of the nucleoplasm and cytoplasm. In the opisthokonts, nuclear envelope and meiotic chromosome behavior are coordinated by forces generated in the cytoplasm and transferred to the nucleus by the nuclear-envelope protein linkers SUN and KASH. During meiotic prophase I, the telomere bouquet arrangement has roles in interhomolog recognition, pairing, synapsis, interlock resolution and homologous chromosome recombination. The maize desynaptic (dy) mutant is defective in homologous chromosome synapsis, recombination, telomere-nuclear envelope interactions and chromosome segregation. A detailed three-dimensional cytological analysis of dy revealed telomere misplacement during the bouquet stage, synaptic irregularities, nuclear envelope distortion and chromosome bridges at anaphase I. Using linkage and B-A translocation mapping, we placed dy on the long arm of chromosome 3, genetic bin 3.06. SSR marker analysis narrowed the mapping interval to 9 cM. Candidate genes in this region include a PM3-type SUN domain protein, ZmSUN3. No obvious genetic lesions were found in the ZmSUN3 allele of dy, but a conspicuous splice variant, ZmSUN3-sv1, was observed in mRNA from dy. The variant message is predicted to result in the synthesis of a truncated ZmSUN3 protein lacking two C-terminal transmembrane domains. Other potential candidate genes relevant to the documented phenotypes were also considered. In summary, this study reveals that dy causes disruption of a central meiotic pathway connecting nuclear envelope integrity to telomere localization and synapsis during meiotic prophase.

  10. A Kinetic Signature for Parallel Pathways: Conformational Selection and Induced Fit. Links and Disconnects between Observed Relaxation Rates and Fractional Equilibrium Flux under Pseudo-First-Order Conditions.

    PubMed

    Galburt, Eric A; Rammohan, Jayan

    2016-12-20

    Molecular association plays a ubiquitous role in biochemistry and is often accompanied by conformational exchange in one or both binding partners. Traditionally, two limiting mechanisms are considered for the association of two molecules. In a conformational selection (CS) mechanism, a ligand preferentially binds to a subset of conformations in its binding partner. In contrast, an induced fit (IF) mechanism describes the ligand-dependent isomerization of the binding partner in which binding occurs prior to conformational exchange. Measurements of the ligand concentration dependence of observed rates of relaxation are commonly used to probe whether CS or IF is taking place. Here we consider a four-state thermodynamic cycle subject to detailed balance and demonstrate the existence of a relatively unexplored class of kinetic signatures where an initial decrease in the observed rate is followed by a subsequent increase under pseudo-first-order conditions. We elucidate regions of rate space necessary to generate a nonmonotonic observed rate and show that, under certain conditions, the position of the minimum of the observed rate correlates with a transition in equilibrium flux between CS and IF pathways. Furthermore, we demonstrate that monotonic trends in the observed rate can occur when both CS and IF mechanisms are taking place, suggesting that caution must be taken not to overinterpret monotonic trends as evidence of the absence of either CS or IF. Lastly, we conclude that a nonmonotonic kinetic signature is uniquely unambiguous in the sense that when this trend is observed, one may conclude that both CS and IF mechanistic paths are utilized.

  11. A Disulfide Bond-forming Machine Is Linked to the Sortase-mediated Pilus Assembly Pathway in the Gram-positive Bacterium Actinomyces oris*

    PubMed Central

    Reardon-Robinson, Melissa E.; Osipiuk, Jerzy; Chang, Chungyu; Wu, Chenggang; Jooya, Neda; Joachimiak, Andrzej; Das, Asis; Ton-That, Hung

    2015-01-01

    Export of cell surface pilins in Gram-positive bacteria likely occurs by the translocation of unfolded precursor polypeptides; however, how the unfolded pilins gain their native conformation is presently unknown. Here, we present physiological studies to demonstrate that the FimA pilin of Actinomyces oris contains two disulfide bonds. Alanine substitution of cysteine residues forming the C-terminal disulfide bridge abrogates pilus assembly, in turn eliminating biofilm formation and polymicrobial interaction. Transposon mutagenesis of A. oris yielded a mutant defective in adherence to Streptococcus oralis, and revealed the essential role of a vitamin K epoxide reductase (VKOR) gene in pilus assembly. Targeted deletion of vkor results in the same defects, which are rescued by ectopic expression of VKOR, but not a mutant containing an alanine substitution in its conserved CXXC motif. Depletion of mdbA, which encodes a membrane-bound thiol-disulfide oxidoreductase, abrogates pilus assembly and alters cell morphology. Remarkably, overexpression of MdbA or a counterpart from Corynebacterium diphtheriae, rescues the Δvkor mutant. By alkylation assays, we demonstrate that VKOR is required for MdbA reoxidation. Furthermore, crystallographic studies reveal that A. oris MdbA harbors a thioredoxin-like fold with the conserved CXXC active site. Consistently, each MdbA enzyme catalyzes proper disulfide bond formation within FimA in vitro that requires the catalytic CXXC motif. Because the majority of signal peptide-containing proteins encoded by A. oris possess multiple Cys residues, we propose that MdbA and VKOR constitute a major folding machine for the secretome of this organism. This oxidative protein folding pathway may be a common feature in Actinobacteria. PMID:26170452

  12. Potential pathways for regulation of NK and T cell responses: differential X-linked lymphoproliferative syndrome gene product SAP interactions with SLAM and 2B4.

    PubMed

    Sayós, J; Nguyen, K B; Wu, C; Stepp, S E; Howie, D; Schatzle, J D; Kumar, V; Biron, C A; Terhorst, C

    2000-12-01

    SAP, the gene that is altered or absent in the X-linked lymphoproliferative syndrome (XLP), encodes a small protein that comprises a single SH2 domain and binds to the cell-surface protein SLAM which is present on activated or memory T and B cells. Because defective NK cell activity also has been reported in XLP patients, we studied the SAP gene in NK cells. SAP was induced upon viral infection of SCID mice and shown to be expressed in NK cells by in vitro culturing in the presence of IL-2. Moreover, SAP was expressed in the NK cell lines YT and RNK 16. Because SLAM, the cell-surface protein with which SAP interacts, and 2B4, a membrane protein having sequence homologies with SLAM, also were found to be expressed on the surfaces of activated NK and T cell populations, they may access SAP functions in these populations. Whereas we found that 2B4 also binds SAP, 2B4-SAP interactions occurred only upon tyrosine phosphorylation of 2B4. By contrast, SLAM-SAP interactions were independent of phosphorylation of Y281 and Y327 on SLAM. As CD48, the ligand for 2B4, is expressed on the surface of Epstein-Barr virus (EBV)-infected B cells, it is likely that SAP regulates signal transduction through this pair of cell-surface molecules. These data support the hypothesis that XLP is a result of both defective NK and T lymphocyte responses to EBV. The altered responses may be due to aberrant control of the signaling cascades which are initiated by the SLAM-SLAM and 2B4-CD48 interactions.

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

    PubMed

    Hulleman, John D; Kelly, Jeffery W

    2015-02-01

    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.

  14. The Role of Socioeconomic Factors in Black–White Disparities in Preterm Birth

    PubMed Central

    Heck, Katherine; Egerter, Susan; Marchi, Kristen S.; Dominguez, Tyan Parker; Cubbin, Catherine; Fingar, Kathryn; Pearson, Jay A.; Curtis, Michael

    2015-01-01

    Objectives. We investigated the role of socioeconomic factors in Black–White disparities in preterm birth (PTB). Methods. We used the population-based California Maternal and Infant Health Assessment survey and birth certificate data on 10 400 US-born Black and White California residents who gave birth during 2003 to 2010 to examine rates and relative likelihoods of PTB among Black versus White women, with adjustment for multiple socioeconomic factors and covariables. Results. Greater socioeconomic advantage was generally associated with lower PTB rates among White but not Black women. There were no significant Black–White disparities within the most socioeconomically disadvantaged subgroups; Black–White disparities were seen only within more advantaged subgroups. Conclusions. Socioeconomic factors play an important but complex role in PTB disparities. The absence of Black–White disparities in PTB within certain socioeconomic subgroups, alongside substantial disparities within others, suggests that social factors moderate the disparity. Further research should explore social factors suggested by the literature—including life course socioeconomic experiences and racism-related stress, and the biological pathways through which they operate—as potential contributors to PTB among Black and White women with different levels of social advantage. PMID:25211759

  15. Socio-economic factors in obesity: a case of slim chance in a fat world?

    PubMed

    Ball, Kylie; Crawford, David

    2006-01-01

    The global obesity pandemic has been well-documented and widely discussed by the public, the media, health officials, the food industry and academic researchers. While the problem is widely recognised, the potential solutions are far less clear. There is only limited evidence to guide decisions as to how best to manage obesity in individuals and in populations. While widely viewed as a clinical and public health problem in developed countries, it is now clear that many developing countries also have to grapple with this problem or face the crippling healthcare costs resulting from obesity-related morbidity. There is also abundant evidence that obesity is socio-economically distributed. In developed countries persons of lower socio-economic position are more likely to be affected, while in developing countries, it is often those of higher socio-economic position who are overweight or obese. The aim of this paper is to briefly review the evidence that links socio-economic position and obesity, to discuss what is known about underlying mechanisms, and to consider the role of social, physical, policy and cultural environments in explaining the relationships between socio-economic position and obesity. We introduce the concept of 'resilience' as a potential theoretical construct to guide research efforts aimed at understanding how some socio-economically disadvantaged individuals manage to avoid obesity. We conclude by considering an agenda to guide future research and programs focused on understanding and reducing obesity among those of low socio-economic position.

  16. 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.

  17. Link direction for link prediction

    NASA Astrophysics Data System (ADS)

    Shang, Ke-ke; Small, Michael; Yan, Wei-sheng

    2017-03-01

    Almost all previous studies on link prediction have focused on using the properties of the network to predict the existence of links between pairs of nodes. Unfortunately, previous methods rarely consider the role of link direction for link prediction. In fact, many real-world complex networks are directed and ignoring the link direction will mean overlooking important information. In this study, we propose a phase-dynamic algorithm of the directed network nodes to analyse the role of link directions and demonstrate that the bi-directional links and the one-directional links have different roles in link prediction and network structure formation. From this, we propose new directional prediction methods and use six real networks to test our algorithms. In real networks, we find that compared to a pair of nodes which are connected by a one-directional link, a pair of nodes which are connected by a bi-directional link always have higher probabilities to connect to the common neighbours with only bi-directional links (or conversely by one-directional links). We suggest that, in the real networks, the bi-directional links will generally be more informative for link prediction and network structure formation. In addition, we propose a new directional randomized algorithm to demonstrate that the direction of the links plays a significant role in link prediction and network structure formation.

  18. The socio-economic distribution of health-related occupational stressors among wage-earners in a Post-Fordist labour market

    PubMed Central

    2010-01-01

    Unequal exposure to occupational stressors is a central pathway towards socio-economic health inequalities in working populations. This paper assesses the differential exposure of such stressors within the population of Flemish wage-earners. Our focus is on differences in gender, age, skill levels, occupational and social class positions. Method The analyses are based on the "Flemish Quality of Labour Monitor 2004" (Vlaamse Werkbaarheidsmonitor 2004), a cross-sectional representative sample (N = 11,099) of 16- to 65-year-old wage-earners, living in Flanders. The investigated health-related working conditions are: high quantitative, emotional and physical demands, frequent repetitive movements, atypical work schedules, frequent overtime work and schedule changes, low job autonomy, task variation and superior-support, high job insecurity and exposure to bullying. The distribution of the working conditions is assessed by means of standard logistic regression analyses. Also gender specific analyses are performed. Results At least two clusters of health-related occupational stressors can be identified. On the one hand, high physical demands, atypical schedules, low control over the work environment and high job insecurity are more common in manual, unskilled and subordinate workers. On the other hand, high quantitative and emotional demands, as well as schedule unpredictability are characteristic of higher skilled, professional and managerial employees. Conclusion Since little empirical information on the socio-economic distribution of various health-related occupational stressors is available for Flanders, our results are important for obtaining more insight into the pathways linking occupational health risks to socio-economic health inequalities in the Flemish wage-earning population.

  19. 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.…

  20. 75 FR 69009 - Acquisition Regulation: Socioeconomic Programs

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-11-10

    ... Parts 919, 922, 923, 924, 925, 926, and 952 RIN 1991-AB87 Acquisition Regulation: Socioeconomic Programs... D--Socioeconomic Programs to conform it to the FAR. Changes are to DEAR parts 919, 922, 923, 925... in the introductory text to remove the ``.'' and adding in its place ``--''. 6. Subpart 922.6...

  1. 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.

  2. Adult children's socioeconomic positions and their parents' mortality: a comparison of education, occupational class, and income.

    PubMed

    Torssander, Jenny

    2014-12-01

    Recent research has shown that the parents of well-educated children live longer than do other parents and that this association is only partly confounded by the parent's own socioeconomic position. However, the relationships between other aspects of children's socioeconomic position (e.g., occupational class and economic resources) and parental mortality have not been examined. Using the Swedish Multi-generation Register that connects parents to their children, this paper studies the associations of children's various socioeconomic resources (education, occupation, and income) and parents' mortality. The models are adjusted for a range of parental socioeconomic resources and include the resources of the parents' partners. In addition to all-cause mortality, five causes of death are analyzed separately (circulatory disease mortality, overall cancer, lung cancer, breast cancer, and prostate cancer). The results show net associations between all included indicators of children's socioeconomic position and parents' mortality risk, with the clearest association for education. Children's education is significantly associated with all of the examined causes of death except prostate cancer. Breast cancer mortality is negatively related to offspring's education but not the mothers' own education. To conclude, children's education seems to be a key factor compared with other dimensions of socioeconomic position in the offspring generation. This finding suggests that explanations linked to behavioral norms or knowledge are more plausible than those linked to access to material resources. However, it is possible that children's education - to a greater degree than class and income - captures unmeasured parental characteristics. The cause-specific analyses imply that future research should investigate whether offspring's socioeconomic position is linked to the likelihood of developing diseases and/or the chances of treating them. A broader family perspective in the description

  3. 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.

  4. 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

  5. Socioeconomic implications of donation distributions

    NASA Astrophysics Data System (ADS)

    Wu, Yajing; Guo, Jinzhong; Chen, Qinghua; Wang, Yougui

    2011-11-01

    Individual donation depends on personal wealth and individual willingness to donate. On the basis of a donation model proposed in our previous study, a simplified version of an individual donation model is derived by relaxing the restrictions of the maximum wealth in the economy. Thus, the whole distribution is determined by only two parameters. One of them relates to the exponent of the distribution of society wealth and the other refers to the donation amount of the kindest poorest person. The parameters reflect the degree of wealth inequality and the charitable enthusiasm of society, respectively. Using actual donation data, we develop a specific parameter estimation method combining linear regression and the Kolmogorov-Smirnov (KS) statistic to get the value of two socioeconomic indicators. Applications to Chinese individual donations in response to the 2004 Indian Ocean tsunami and the 2008 Wenchuan earthquake indicate a rising inequality in social wealth distribution in China. Also, more charitable enthusiasm is observed in the response to the 2008 Wenchuan earthquake.

  6. Cancer in socioeconomically disadvantaged populations.

    PubMed

    Pamies, R J; Woodard, L J

    1992-09-01

    This article presents a summary of the health status of the disadvantaged populations in the United States, with specific regard to the incidence, treatment, and mortality of cancer. It begins with an historical overview of health care for the poor in this country, and continues with an explanation of the risk factors prevalent, if not inherent, in the life-style associated with low socioeconomic status, such as poor diet, cigarette smoking, and ignorance of preventive health measures and screening techniques. It includes a discussion of the different types that are overrepresented in this population and of the barriers to preventive care and treatment that still exist. The most important of these is decreased access to continuous medical care because of a lack of health insurance and an overdependence on emergency room treatment for all health care. The final section reviews solutions that have been preferred by physicians, nurses, lawmakers, public health workers, and community advocates for the poor. The most important parts of the solution are patient education for preventive health care, disease warning signs, and screening techniques and an overhaul of the present system of providing health care to ensure equal access and treatment for all members of the society.

  7. Forging Links.

    ERIC Educational Resources Information Center

    Stewig, John Warren

    Blacksmiths and their craft have changed with the times, and as times change for teachers, they too should be forgers of links. Teacher-to-teacher links should extend beyond the faculty lounge to support systems and active groups of individuals concerned about each other. Another personal link can be made by developing a grade level, system-wide…

  8. 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…

  9. 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…

  10. 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…

  11. Adolescent Precursors of Pathways from School to Work

    PubMed Central

    Vuolo, Mike; Mortimer, Jeylan T.; Staff, Jeremy

    2013-01-01

    Longitudinal data from the Youth Development Study is used to examine: (1) how young people establish work with self-identified career potential and how these patterns are linked to educational attainments; and (2) how adolescent achievement orientations, experiences in school and work, and sociodemographic background distinguish youth who establish themselves in careers and those who flounder during this transition. Multilevel latent class models reveal four school-to-work pathways from ages 18 to 31: two groups that attain careers through postsecondary education (via Bachelor’s or Associates-Vocational degrees) and two groups that do not (distinguished by attempting college). Multinomial logistic regression models demonstrate that academic orientations, socioeconomic background, and steady paid work during high school help adolescents avoid subsequent floundering during the school-to-work transition. PMID:24791132

  12. 77 FR 12930 - Federal Acquisition Regulation: Socioeconomic Program Parity

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-03-02

    ... 9000-AL88 Federal Acquisition Regulation: Socioeconomic Program Parity AGENCY: Department of Defense... parity and that contracting officers may exercise discretion when determining whether an acquisition will... Socioeconomic Programs Comment: One respondent noted that socioeconomic parity could not be implemented...

  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. A life course perspective on socioeconomic inequalities in health: a critical review of conceptual frameworks.

    PubMed

    Corna, Laurie M

    2013-06-01

    Social scientists and public health researchers have long known that social position is related to health and that socioeconomic inequalities in health persist in later life. Increasingly, a life course perspective is adopted to understand the socioeconomic position (SEP)-health dynamic. This paper critically reviews the conceptual perspectives underlying empirical research seeking to better understand socioeconomic inequalities in health in the context of the life course. I comment on the contributions of this work, but also its limitations. In particular, I note the emphasis on understanding the mechanisms linking SEP to health, to the exclusion of research on the institutional and structural factors associated with socioeconomic inequalities over the life course. I also critique the relative absence of gender in this work, and how, by not linking individual experiences to the social policy contexts that shape resources and opportunities, the proximal, rather than the structural or institutional determinants of health are emphasized. I suggest that moving forward, a return to some of the key tenets of life course theory, including contributions from the comparative welfare states literature, may better inform life course analyses of socioeconomic inequalities in health. Specific suggestions for life scholarship are discussed.

  15. 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

  16. Poverty, Socioeconomic Change, Institutional Anomie, and Homicide.

    PubMed

    Kim, Sang-Weon; Pridemore, William Alex

    2005-12-01

    Objective. This study examined institutional anomie theory in the context of transitional Russia. Methods. We employed an index of negative socioeconomic change and measures of family, education, and polity to test the hypothesis that institutional strength conditions the effects of poverty and socioeconomic change on homicide rates. Results. As expected, the results of models estimated using negative binomial regression show direct positive effects of poverty and socioeconomic change and direct negative effects of family strength and polity on regional homicide rates. There was no support, however, for the hypothesis that stronger social institutions reduce the effects of poverty and socioeconomic change on violence. Conclusions. We interpret these results in the Russia-specific setting, concluding that Russia is a rich laboratory for examining the effects of social change on crime and that empirical research in other nations is important when assessing the generalizability of theories developed to explain crime and violence in the United States.

  17. 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

  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. 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

  20. How structurally stable are global socioeconomic systems?

    PubMed

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

    2014-11-06

    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.

  1. Hair cortisol levels, perceived stress and body mass index in women and children living in socioeconomically disadvantaged neighborhoods: the READI study.

    PubMed

    Olstad, Dana Lee; Ball, Kylie; Wright, Craig; Abbott, Gavin; Brown, Erin; Turner, Anne Isabella

    2016-01-01

    Disadvantaged communities provide adverse psychosocial exposures that have been linked to high levels of stress, and this may provide one explanatory pathway linking socioeconomic disadvantage to obesity. This study used hair cortisol analysis to quantify associations between stress and body mass index (BMI), and between hair cortisol and perceived psychological stress levels, in women and children living in socioeconomically disadvantaged neighborhoods. Participants were a volunteer sample of 70 women from the Resilience for Eating and Activity Despite Inequality study, including 30 maternal-child pairs. Women self-reported body weight, height and perceived psychological stress using the Perceived Stress Scale (PSS), and provided hair samples for themselves and their child. Children's body weight and height were measured. Following extraction, hair cortisol levels were measured using enzyme-linked immunosorbent assay. Multiple linear regression models examined associations between stress and BMI, and between hair cortisol and perceived stress levels in women and children. Women's hair cortisol levels were not associated with their BMI or PSS scores. Women's PSS scores were positively associated with their BMI (p = 0.015). Within maternal-child pairs, mothers and children's hair cortisol levels were strongly positively associated (p = 0.006). Maternal hair cortisol levels and PSS scores were unrelated to their child's zBMI. Children's hair cortisol levels were not associated with their zBMI or with their mother's PSS score. Findings suggest that cortisol-based and perceived psychological measures of stress may be distinct among women and children living in disadvantaged neighborhoods. Perceived psychological measures may be more important predictors of weight-related risk.

  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. 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

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

    1996-02-15

    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.

  4. Endoplasmic reticulum stress-mediated apoptosis of EBV-transformed B cells by cross-linking of CD70 is dependent upon generation of reactive oxygen species and activation of p38 MAPK and JNK pathway.

    PubMed

    Park, Ga Bin; Kim, Yeong Seok; Lee, Hyun-Kyung; Song, Hyunkeun; Cho, Dae-Ho; Lee, Wang Jae; Hur, Dae Young

    2010-12-15

    CD70 is expressed in normal activated immune cells as well as in several types of tumors. It has been established that anti-CD70 mAb induces complement-dependent death of CD70(+) tumor cells, but how anti-CD70 mAb affects the intrinsic signaling is poorly defined. In this report, we show that ligation of CD70 expressed on EBV-transformed B cells using anti-CD70 mAb induced production of reactive oxygen species (ROS) and subsequent apoptosis. We observed an early expression of endoplasmic reticulum (ER) stress response genes that preceded the release of apoptotic molecules from the mitochondria and the cleavage of caspases. CD70-induced apoptosis was inhibited by pretreatment with the ER stress inhibitor salubrinal, ROS quencher N-acetylcysteine, and Ca(2+) chelator BAPTA. We supposed that ROS generation might be the first event of CD70-induced apoptosis because N-acetylcysteine blocked increases of ROS and Ca(2+), but BAPTA did not block ROS generation. We also found that CD70 stimulation activated JNK and p38 MAPK. JNK inhibitor SP600125 and p38 inhibitor SB203580 effectively blocked upregulation of ER stress-related genes and cleavage of caspases. Inhibition of ROS generation completely blocked phosphorylation of JNK and p38 MAPK and induction of ER stress-related genes. Taken together, we concluded that cross-linking of CD70 on EBV-transformed B cells triggered ER stress-mediated apoptosis via ROS generation and JNK and p38 MAPK pathway activation. Our report reveals alternate mechanisms of direct apoptosis through CD70 signaling and provides data supporting CD70 as a viable target for an Ab-based therapy against EBV-related tumors.

  5. 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

  6. 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

  7. 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)

  8. Socioeconomic differentials in selected causes of death.

    PubMed Central

    Yeracaris, C A; Kim, J H

    1978-01-01

    The areal approach utilized in mortality analysis for cities in the past is argued to be fruitful for suburban mortality analysis as well. Through factor analysis of four Census Tract indicators, weighted scores were computed and socioeconomic groups were constructed for each central city and each suburban area for three selected metropolitan areas: Birmingham, AL, Buffalo, NY, and Indianapolis, IN. Mortality rates from Heart Diseases, Malignant Neoplasms, and All Other Causes of death were found to be inversely associated with socioeconomic status in both the central cities and the suburban communities of these selected metropolitan areas. Evidence points to increasing socioeconomic differentials between 1960 and 1970 especially for males for the central cities and for suburban rings in spite of reductions in mortality during this period. PMID:645980

  9. 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.

  10. Income inequality, parental socioeconomic status, and birth outcomes in Japan.

    PubMed

    Fujiwara, Takeo; Ito, Jun; Kawachi, Ichiro

    2013-05-15

    The purpose of this study was to investigate the impact of income inequality and parental socioeconomic status on several birth outcomes in Japan. Data were collected on birth outcomes and parental socioeconomic status by questionnaire from Japanese parents nationwide (n = 41,499) and then linked to Gini coefficients at the prefectural level in 2001. In multilevel analysis, z scores of birth weight for gestational age decreased by 0.018 (95% confidence interval (CI): -0.029, -0.006) per 1-standard-deviation (0.018-unit) increase in the Gini coefficient, while gestational age at delivery was not associated with the Gini coefficient. For dichotomous outcomes, mothers living in prefectures with middle and high Gini coefficients were 1.24 (95% CI: 1.05, 1.47) and 1.23 (95% CI: 1.02, 1.48) times more likely, respectively, to deliver a small-for-gestational-age infant than mothers living in more egalitarian prefectures (low Gini coefficients), although preterm births were not significantly associated with income distribution. Parental educational level, but not household income, was significantly associated with the z score of birth weight for gestational age and small-for-gestational-age status. Higher income inequality at the prefectural level and parental educational level, rather than household income, were associated with intrauterine growth but not with shorter gestational age at delivery.

  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. 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

  13. Integrating global socio-economic influences into a regional land use change model for China

    NASA Astrophysics Data System (ADS)

    Xu, Xia; Gao, Qiong; Peng, Changhui; Cui, Xuefeng; Liu, Yinghui; Jiang, Li

    2014-03-01

    With rapid economic development and urbanization, land use in China has experienced huge changes in recent years; and this will probably continue in the future. Land use problems in China are urgent and need further study. Rapid land-use change and economic development make China an ideal region for integrated land use change studies, particularly the examination of multiple factors and global-regional interactions in the context of global economic integration. This paper presents an integrated modeling approach to examine the impact of global socio-economic processes on land use changes at a regional scale. We develop an integrated model system by coupling a simple global socio-economic model (GLOBFOOD) and regional spatial allocation model (CLUE). The model system is illustrated with an application to land use in China. For a given climate change, population growth, and various socio-economic situations, a global socio-economic model simulates the impact of global market and economy on land use, and quantifies changes of different land use types. The land use spatial distribution model decides the type of land use most appropriate in each spatial grid by employing a weighted suitability index, derived from expert knowledge about the ecosystem state and site conditions. A series of model simulations will be conducted and analyzed to demonstrate the ability of the integrated model to link global socioeconomic factors with regional land use changes in China. The results allow an exploration of the future dynamics of land use and landscapes in China.

  14. Socio-economic risk factors for injuries in Swedish children and adolescents: a national study over 15 years.

    PubMed

    Nyberg, Cecilia; Schyllander, Jan; Stark Ekman, Diana; Janson, Staffan

    2012-01-01

    Few studies have assessed if Sweden's injury prevention work has been equally effective for children of different socio-economic backgrounds. The goal of this paper is to review the country's injury rates for children over time, stratified by socio-economic status (SES), to see if the effects are similar across SES levels. This study employs a retrospective case-control study design, using data from the hospitalisation records of 51,225 children, which were linked to family socio-economic data. Children and adolescents in families receiving social welfare benefits, and those living with single parents and mothers with less education had higher risks of injuries leading to hospitalisation. The population-based safety work over the past decades seems to have had only minor effects on reducing the impact of socio-economic based difference in injury risks to younger Swedes.

  15. Socioeconomic Status, Economic Problems, and Delinquency

    ERIC Educational Resources Information Center

    Agnew, Robert; Matthews, Shelley Keith; Bucher, Jacob; Welcher, Adria N.; Keyes, Corey

    2008-01-01

    Research indicates that the relationship between socioeconomic status (SES) and delinquency is not as strong as suggested by the leading crime theories. This article argues that such theories do not predict that SES in and of itself causes delinquency but rather that the economic problems associated with SES cause delinquency. Such problems…

  16. Socioeconomic Status, Parenting, and Child Development.

    ERIC Educational Resources Information Center

    Bornstein, Marc H., Ed.; Bradley, Robert H., Ed.

    Noting that there is near universal agreement that children from families with higher socioeconomic status (SES) have access to more of the resources needed to support their positive development than do lower SES children, this monograph examines the myriad questions remaining regarding relations among SES, parenting, and child development from a…

  17. Socioeconomic Status, Academic Achievement and Teacher Response.

    ERIC Educational Resources Information Center

    Shakiba-Nejad, Hadi; Yellin, David

    A recent study examined the socioeconomic status (SES), parent participation, teacher awareness, and academic achievement of 76 elementary school students. Results were obtained through interpretation of data and review of relevant literature. A strong positive correlation was found between a student's SES and academic achievement in school. Some…

  18. 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…

  19. 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…

  20. Socioeconomic Status, Subcultural Definitions, and Violent Delinquency.

    ERIC Educational Resources Information Center

    Heimer, Karen

    1997-01-01

    Analysis of national longitudinal survey data on 918 adolescent males and their parents shows that violent delinquency is a product of learning definitions favorable to violence; such learning is determined by association with aggressive peers, socioeconomic status, parenting practices, and prior violent delinquency. Emphasizes joint contributions…

  1. 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.…

  2. SOCIOECONOMIC VARIATIONS IN INDUCED ABORTION IN TURKEY.

    PubMed

    Ankara, Hasan Giray

    2017-01-01

    This study aimed to identify the levels of, and socioeconomic variations in, income-related inequality in induced abortion among Turkish women. The study included 15,480 ever-married women of reproductive age (15-49) from the 2003 and 2008 waves of the Turkish Demographic and Health Survey. The measured inequalities in abortion levels and their changes over time were decomposed into the percentage contributions of selected socioeconomic factors using ordinary least square analysis and concentration indices were calculated. The inequalities and their first difference (difference in inequalities between 2003 and 2008) were decomposed using the approaches of Wagstaff et al. (2003). Higher socioeconomic characteristics (such as higher levels of wealth and education and better neighbourhood) were found to be associated with higher rates of abortion. Inequality analyses indicated that although deprived women become more familiar with abortion over time, abortion was still more concentrated among affluent women in the 2008 survey. The decomposition analyses suggested that wealth, age, education and level of regional development were the most important contributors to income-related inequality in abortion. Therefore policies that (i) increase the level of wealth and education of deprived women, (ii) develop deprived regions of Turkey, (iii) improve knowledge about family planning and, especially (iv) enhance the accessibility of family planning services for deprived and/or rural women, may be beneficial for reducing socioeconomic variations in abortion in the country.

  3. Children--Socioeconomic Class and Equity

    ERIC Educational Resources Information Center

    Derman-Sparks, Louise

    2009-01-01

    This article discusses issues related to socioeconomic aspects of early childhood education work. It seeks to increase the visibility of equity issues and to encourage discussion of this important aspect of families' and children's lives. It offers some concrete suggestions for one's classroom and explores the author's own belief and attitudes…

  4. Socioeconomic Status and Cultural Influences on Language

    ERIC Educational Resources Information Center

    Hoff, E.; Tian, C.

    2005-01-01

    Two studies track connections from the distal variables of socioeconomic status (SES) and culture to properties of the interactions children experience and to the rate of children's language development. The first study is an investigation of the relations among family SES, properties of maternal child-directed speech, and child vocabulary growth…

  5. Socioeconomic Disparities Affect Prefrontal Function in Children

    ERIC Educational Resources Information Center

    Kishiyama, Mark M.; Boyce, W. Thomas; Jimenez, Amy M.; Perry, Lee M.; Knight, Robert T.

    2009-01-01

    Social inequalities have profound effects on the physical and mental health of children. Children from low socioeconomic status (SES) backgrounds perform below children from higher SES backgrounds on tests of intelligence and academic achievement, and recent findings indicate that low SES (LSES) children are impaired on behavioral measures of…

  6. 75 FR 33752 - Acquisition Regulation: Socioeconomic Programs

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-15

    ... Parts 919, 922, 923, 924, 925, 926, and 952 RIN 1991-AB87 Acquisition Regulation: Socioeconomic Programs... cause any significant expense for DOE or its contractors. Changes are proposed to DEAR parts 919, 922... remove the ``.'' and adding in its place ``--''. 6. Subpart 922.6 is removed and reserved. This...

  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. 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

  9. 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...

  10. 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

  11. 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…

  12. 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…

  13. 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.

  14. 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

  15. 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.

  16. 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.

  17. 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.

  18. Socioeconomic legacy yields an invasion debt.

    PubMed

    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

    2011-01-04

    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.

  19. 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

  20. 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.

  1. 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

  2. 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

  3. Systemic Inflammation in Midlife: Race, Socioeconomic Status, and Perceived Discrimination

    PubMed Central

    Stepanikova, Irena; Bateman, Lori Brand; Oates, Gabriela R.

    2017-01-01

    Introduction This study investigates social determinants of systemic inflammation, focusing on race, SES, and perceived discrimination. Methods Data on 884 white and 170 black participants were obtained from the Survey of Midlife in the U.S., a cross-sectional observational study combining survey measures, anthropometry, and biomarker assay. Data, collected in 2004–2009, were analyzed in 2016. Main outcome measures were fasting blood concentrations of C-reactive protein, interleukin 6, fibrinogen, and E-selectin. For each biomarker, series of multivariate linear regression models were estimated for the pooled sample and separately for blacks and whites. Full models included social determinants; psychological, lifestyle, and health factors; and demographic covariates. Results Bivariate analyses indicated higher concentrations of all inflammation markers among blacks compared with whites (p<0.001). In fully adjusted models using the pooled sample, racial differences persisted for interleukin 6 (p<0.001) and fibrinogen (p<0.01). For E-selectin and C-reactive protein, racial differences were explained after adjusting for covariates. Education was linked to lower fibrinogen concentration (p<0.05) in the fully adjusted model and C-reactive protein concentration (p<0.01) after adjusting for demographic factors and income. Lifetime perceived discrimination was related to higher concentrations of fibrinogen (p<0.05) in the fully adjusted model, and higher concentrations of E-selectin and interleukin 6 (p<0.05) after adjusting for socioeconomic status (SES) and demographic factors. Conclusions This study clarifies the contributions of race, SES, and perceived discrimination to inflammation. It suggests that inflammation-reducing interventions should focus on blacks and individuals facing socioeconomic disadvantages, especially low education. PMID:27989295

  4. Socioeconomic inequalities in breast cancer incidence and mortality in Europe—a systematic review and meta-analysis

    PubMed Central

    Andersson, Emelie; Ahlberg, Ida; Nilbert, Mef; Gerdtham, Ulf

    2016-01-01

    Background: Breast cancer is the leading cause of female cancer in Europe and is estimated to affect more than one in 10 women. Higher socioeconomic status has been linked to higher incidence but lower case fatality, while the impact on mortality is ambiguous. Methods: We performed a systematic literature review and meta-analysis on studies on association between socioeconomic status and breast cancer outcomes in Europe, with a focus on effects of confounding factors. Summary relative risks (SRRs) were calculated. Results: The systematic review included 25 articles of which 8 studied incidence, 10 case fatality and 8 mortality. The meta-analysis showed a significantly increased incidence (SRR 1.25, 1.17–1.32), a significantly decreased case fatality (SRR 0.72, 0.63–0.81) and a significantly increased mortality (SRR 1.16, 1.10–1.23) for women with higher socioeconomic status. The association for incidence became insignificant when reproductive factors were included. Case fatality remained significant after controlling for tumour characteristics, treatment factors, comorbidity and lifestyle factors. Mortality remained significant after controlling for reproductive factors. Conclusion: Women with higher socioeconomic status show significantly higher breast cancer incidence, which may be explained by reproductive factors, mammography screening, hormone replacement therapy and lifestyle factors. Lower case fatality for women with higher socioeconomic status may be partly explained by differences in tumour characteristics, treatment factors, comorbidity and lifestyle factors. Several factors linked to breast cancer risk and outcome, such as lower screening attendance for women with lower socioeconomic status, are suitable targets for policy intervention aimed at reducing socioeconomic-related inequalities in health outcomes. PMID:27221607

  5. Socioeconomic Status and Health Communication Inequalities in Japan: A Nationwide Cross-Sectional Survey

    PubMed Central

    Ishikawa, Yoshiki; Nishiuchi, Hiromu; Hayashi, Hana; Viswanath, Kasisomayajula

    2012-01-01

    Background Considerable evidence suggests that communication inequality is one potential mechanism linking social determinants, particularly socioeconomic status, and health inequalities. This study aimed to examine how dimensions of health communication outcomes (health information seeking, self-efficacy, exposure, and trust) are patterned by socioeconomic status in Japan. Methods Data of a nationally representative cross-sectional survey of 2,455 people aged 15–75 years in Japan were used for secondary analysis. Measures included socio-demographic characteristics, subjective health, recent health information seeking, self-efficacy in seeking health information, and exposure to and trust in health information from different media. Results A total of 1,311 participants completed the questionnaire, giving a response rate of 53.6%. Multivariate logistic regression revealed that education and household income, but not employment, were significantly associated with health information seeking and self-efficacy. Socioeconomic status was not associated with exposure to and trust in health information from mass media, but was significantly associated with health information from healthcare providers and the Internet. Conclusion Health communication outcomes were patterned by socioeconomic status in Japan thus demonstrating the prevalence of health communication inequalities. Providing customized exposure to and enhancing the quality of health information by considering social determinants may contribute to addressing social disparities in health in Japan. PMID:22808229

  6. Community Socioeconomic Disadvantage and the Survival of Infants With Congenital Heart Defects

    PubMed Central

    Nembhard, Wendy N.; Donohue, Pamela; Devine, Owen; Wang, Ying; Minkovitz, Cynthia S.; Burke, Thomas

    2014-01-01

    Objectives. We examined the association between survival of infants with severe congenital heart defects (CHDs) and community-level indicators of socioeconomic status. Methods. We identified infants born to residents of Arizona, New Jersey, New York, and Texas between 1999 and 2007 with selected CHDs from 4 population-based, statewide birth defect surveillance programs. We linked data to the 2000 US Census to obtain 11 census tract–level socioeconomic indicators. We estimated survival probabilities and hazard ratios adjusted for individual characteristics. Results. We observed differences in infant survival for 8 community socioeconomic indicators (P < .05). The greatest mortality risk was associated with residing in communities in the most disadvantaged deciles for poverty (adjusted hazard ratio [AHR] = 1.49; 95% confidence interval [CI]  = 1.11, 1.99), education (AHR = 1.51; 95% CI = 1.16, 1.96), and operator or laborer occupations (AHR = 1.54; 95% CI = 1.16, 1.96). Survival decreased with increasing numbers of indicators that were in the most disadvantaged decile. Community-level mortality risk persisted when we adjusted for individual-level characteristics. Conclusions. The increased mortality risk among infants with CHDs living in socioeconomically deprived communities might indicate barriers to quality and timely care at which public health interventions might be targeted. PMID:25211743

  7. Low-Income Students and the Socioeconomic Composition of Public High Schools

    PubMed Central

    Crosnoe, Robert

    2011-01-01

    Increasing constraints placed on race-based school diversification have shifted attention to socioeconomic desegregation. Although past research suggests that socioeconomic desegregation can produce heightened achievement, the “frog pond” perspective points to potential problems with socioeconomic desegregation in nonachievement domains. Such problems are important in their own right, and they may also chip away at the magnitude of potential achievement benefits. In this article, I report conducted propensity score analyses and robustness calculations on a sample of public high schools in the National Longitudinal Study of Adolescent Health. As the proportion of the student body with middle- or high-income parents increased, low-income students progressed less far in math and science. Moreover, as the proportion of the student body with middle- or high-income or college-educated parents increased, low-income students experienced more psychosocial problems. Such patterns were often more pronounced among African American and Latino students. These findings suggest curricular and social psychological mechanisms of oft-noted frog pond effects in schools and extend the frog pond framework beyond achievement itself to demographic statuses (e.g., race/ethnicity and SES) perceptually linked to achievement. In terms of policy, these findings indicate that socioeconomic desegregation plans should also attend to equity in course enrollments and the social integration of students more generally. PMID:21546987

  8. 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.

  9. Jubba Environmental and Socio-economic Studies (JESS). Volume 3. Socio-economic studies. Final report

    SciTech Connect

    Not Available

    1989-01-01

    The Government of the Somali Democratic Republic (GSDR), with the support of the international donor community, is prepared to launch a comprehensive program for the development of Jubba Valley. The keystone of the program is construction of a dam on the Jubba River near Baardheere. Planners have been looking toward construction of the dam, among other things, to increase agricultural output by fostering irrigation development. The objectives of the Socio-economic Baseline Study (SEBS) report are to: present a body of a new information on socio-economic life in Jubba Valley; assess the impact of development efforts on socio-economic life; recommend measures to enhance beneficial impacts and mitigate adverse ones; and propose a program to monitor the progress of those impacts and interventions.

  10. 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.

  11. Genome-wide identification of microRNAs and their targets in wild type and phyB mutant provides a key link between microRNAs and the phyB-mediated light signaling pathway in rice

    PubMed Central

    Sun, Wei; Xu, Xiao Hui; Wu, Xiu; Wang, Yong; Lu, Xingbo; Sun, Hongwei; Xie, Xianzhi

    2015-01-01

    Phytochrome B (phyB), a member of the phytochrome family in rice, plays important roles in regulating a range of developmental processes and stress responses. However, little information about the mechanisms involved in the phyB-mediated light signaling pathway has been reported in rice. MicroRNAs (miRNAs) also perform important roles in plant development and stress responses. Thus, it is intriguing to explore the role of miRNAs in the phyB-mediated light signaling pathway in rice. In this study, comparative high-throughput sequencing and degradome analysis were used to identify candidate miRNAs and their targets that participate in the phyB-mediated light signaling pathway. A total of 720 known miRNAs, 704 novel miRNAs and 1957 target genes were identified from the fourth leaves of wild-type (WT) and phyB mutant rice at the five-leaf stage. Among them, 135 miRNAs showed differential expression, suggesting that the expression of these miRNAs is directly or indirectly under the control of phyB. In addition, 32 out of the 135 differentially expressed miRNAs were found to slice 70 genes in the rice genome. Analysis of these target genes showed that members of various transcription factor families constituted the largest proportion, indicating miRNAs are probably involved in the phyB-mediated light signaling pathway mainly by regulating the expression of transcription factors. Our results provide new clues for functional characterization of miRNAs in the phyB-mediated light signaling pathway, which should be helpful in comprehensively uncovering the molecular mechanisms of phytochrome-mediated photomorphogenesis and stress responses in plants. PMID:26074936

  12. Library links on medical school home pages.

    PubMed

    Thomas, Sheila L

    2011-01-01

    The purpose of this study was to assess the websites of American Association of Medical Colleges (AAMC)-member medical schools for the presence of library links. Sixty-one percent (n = 92) of home pages of the 150 member schools of the AAMC contain library links. For the 58 home pages not offering such links, 50 provided a pathway of two or three clicks to a library link. The absence of library links on 39% of AAMC medical school home pages indicates that the designers of those pages did not consider the library to be a primary destination for their visitors.

  13. Family and Community Influences on Health and Socioeconomic Status: Sibling Correlations Over the Life Course.

    PubMed

    Mazumder, Bhashkar

    2011-09-06

    This paper presents new estimates of sibling correlations in health and socioeconomic outcomes over the life course in the U.S. Sibling correlations provide an omnibus measure of the importance of all family and community influences. I find that sibling correlations in a range of health and socioeconomic outcomes start quite high at birth and remain high over the life course. The sibling correlation in birth weight is estimated to be 0.5. Sibling correlations in test scores during childhood are as high as 0.6. Sibling correlations in adult men's wages are also around 0.5. Decompositions provide suggestive evidence on which pathways may account for the gradients in health and SES by family background. For example, sibling correlations in cognitive skills and non-cognitive skills during childhood are lower controlling for family income. Similarly, parent education levels can account for a sizable portion of the correlation in adult health status among brothers.

  14. Family and Community Influences on Health and Socioeconomic Status: Sibling Correlations Over the Life Course*

    PubMed Central

    Mazumder, Bhashkar

    2012-01-01

    This paper presents new estimates of sibling correlations in health and socioeconomic outcomes over the life course in the U.S. Sibling correlations provide an omnibus measure of the importance of all family and community influences. I find that sibling correlations in a range of health and socioeconomic outcomes start quite high at birth and remain high over the life course. The sibling correlation in birth weight is estimated to be 0.5. Sibling correlations in test scores during childhood are as high as 0.6. Sibling correlations in adult men’s wages are also around 0.5. Decompositions provide suggestive evidence on which pathways may account for the gradients in health and SES by family background. For example, sibling correlations in cognitive skills and non-cognitive skills during childhood are lower controlling for family income. Similarly, parent education levels can account for a sizable portion of the correlation in adult health status among brothers. PMID:23412989

  15. 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

  16. 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

    2016-01-04

    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.

  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. 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

  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. Designing a socio-economic assessment method for integrative biomedical research: the Osteoporotic Virtual Physiological Human project.

    PubMed

    Thiel, Rainer; Stroetmann, Karl A; Stroetmann, Veli N; Viceconti, Marco

    2009-01-01

    In integrative biomedical research, methods assessing the clinical or even socio-economic impact of more complex technologies such as Information and Communication Technology (ICT)-based tools for modelling and simulation of human physiology have rarely been applied. The EU funded Osteoporotic Virtual Physiological Human (VPHOP) research project, part of the Virtual Physiological Human (VPH) European initiative, will create a patient-specific hypermodel to predict the absolute risk of bone fracture much more accurately than predictions based on current clinical practice. The project has developed an innovative, multilevel generic methodological framework to assess the clinical and socio-economic impact of biocomputational models. The assessment framework consists of three components: a socio-economic cost benefit analysis, health economic analysis of care pathways, and disease cost simulation models. Through its holistic perspective, the method provides a tool to appraise the overall value of biocomputational models for society.

  1. Survival after acute lymphocytic leukaemia: effects of socioeconomic status and geographic region

    PubMed Central

    Schillinger, J.; Grosclaude, P.; Honjo, S.; Quinn, M.; Sloggett, A.; Coleman, M.

    1999-01-01

    National cancer registry data, linked to an areal measure of material deprivation, were used to explore possible socioeconomic and regional variation in the survival of children (0-14 years) diagnosed with acute lymphocytic leukaemia (ALL) in England and Wales from 1971 to 1990. Survival analysis and Poisson regression were used to estimate observed (crude) survival probabilities and the adjusted hazard of death. There was little evidence of a socioeconomic gradient in survival. Regional differences in survival were observed over time. These differences were most pronounced in the first six months after diagnosis, and may be attributable to differential access to centralised paediatric oncology services or treatment protocols, or to the artefact of variations in regional cancer registry practice. Similar analyses should be repeated for other, less treatable childhood cancers. The results of this study can be used to help identify ways of reducing regional variation in survival.

 PMID:10086933

  2. Communalism predicts prenatal affect, stress, and physiology better than ethnicity and socioeconomic status.

    PubMed

    Abdou, Cleopatra M; Dunkel Schetter, Christine; Campos, Belinda; Hilmert, Clayton J; Dominguez, Tyan Parker; Hobel, Calvin J; Glynn, Laura M; Sandman, Curt

    2010-07-01

    The authors examined the relevance of communalism, operationalized as a cultural orientation emphasizing interdependence, to maternal prenatal emotional health and physiology and distinguished its effects from those of ethnicity and childhood and adult socioeconomic status (SES). African American and European American women (N = 297) were recruited early in pregnancy and followed through 32 weeks gestation using interviews and medical chart review. Overall, African American women and women of lower socioeconomic backgrounds had higher levels of negative affect, stress, and blood pressure, but these ethnic and socioeconomic disparities were not observed among women higher in communalism. Hierarchical multivariate regression analyses showed that communalism was a more robust predictor of prenatal emotional health than ethnicity, childhood SES, and adult SES. Communalism also interacted with ethnicity and SES, resulting in lower blood pressure during pregnancy for African American women and women who experienced socioeconomic disadvantage over the life course. The effects of communalism on prenatal affect, stress, and physiology were not explained by depressive symptoms at study entry, perceived availability of social support, self-esteem, optimism, mastery, nor pregnancy-specific factors, including whether the pregnancy was planned, whether the pregnancy was desired after conception, or how frequently the woman felt happy to be pregnant. This suggests that a communal cultural orientation benefits maternal prenatal emotional health and physiology over and above its links to better understood personal and social resources in addition to economic resources. Implications of culture as a determinant of maternal prenatal health and well-being and an important lens for examining ethnic and socioeconomic inequalities in health are discussed.

  3. 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.

  4. Socioeconomic status and smoking: a review.

    PubMed

    Hiscock, Rosemary; Bauld, Linda; Amos, Amanda; Fidler, Jennifer A; Munafò, Marcus

    2012-02-01

    Smoking prevalence is higher among disadvantaged groups, and disadvantaged smokers may face higher exposure to tobacco's harms. Uptake may also be higher among those with low socioeconomic status (SES), and quit attempts are less likely to be successful. Studies have suggested that this may be the result of reduced social support for quitting, low motivation to quit, stronger addiction to tobacco, increased likelihood of not completing courses of pharmacotherapy or behavioral support sessions, psychological differences such as lack of self-efficacy, and tobacco industry marketing. Evidence of interventions that work among lower socioeconomic groups is sparse. Raising the price of tobacco products appears to be the tobacco control intervention with the most potential to reduce health inequalities from tobacco. Targeted cessation programs and mass media interventions can also contribute to reducing inequalities. To tackle the high prevalence of smoking among disadvantaged groups, a combination of tobacco control measures is required, and these should be delivered in conjunction with wider attempts to address inequalities in health.

  5. 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

  6. Early-life course socioeconomic factors and chronic kidney disease.

    PubMed

    Brophy, Patrick D; Shoham, David A; Charlton, Jennifer R; Carmody, J Bryan; Reidy, Kimberly J; Harshman, Lyndsay; Segar, Jeffrey; Askenazi, David

    2015-01-01

    Kidney failure or ESRD affects approximately 650,000 Americans, whereas the number with earlier stages of CKD is much higher. Although CKD and ESRD are usually associated with adulthood, it is likely that the initial stages of CKD begin early in life. Many of these pathways are associated with low birth weight and disadvantaged socioeconomic status (SES) in childhood, translating childhood risk into later-life CKD and kidney failure. Social factors are thought to be fundamental causes of disease. Although the relationship between adult SES and CKD has been well established, the role of early childhood SES for CKD risk remains obscure. This review provides a rationale for examining the association between early-life SES and CKD. By collecting data on early-life SES and CKD, the interaction with other periods in the life course could also be studied, allowing for examination of whether SES trajectories (eg, poverty followed by affluence) or cumulative burden (eg, poverty at multiple time points) are more relevant to lifetime CKD risk.

  7. Rich do not rise early: spatio-temporal patterns in the mobility networks of different socio-economic classes

    NASA Astrophysics Data System (ADS)

    Lotero, Laura; Hurtado, Rafael G.; Floría, Luis Mario; Gómez-Gardeñes, Jesús

    2016-10-01

    We analyse the urban mobility in the cities of Medellín and Manizales (Colombia). Each city is represented by six mobility networks, each one encoding the origin-destination trips performed by a subset of the population corresponding to a particular socio-economic status. The nodes of each network are the different urban locations whereas links account for the existence of a trip between two different areas of the city. We study the main structural properties of these mobility networks by focusing on their spatio-temporal patterns. Our goal is to relate these patterns with the partition into six socio-economic compartments of these two societies. Our results show that spatial and temporal patterns vary across these socio-economic groups. In particular, the two datasets show that as wealth increases the early-morning activity is delayed, the midday peak becomes smoother and the spatial distribution of trips becomes more localized.

  8. Rich do not rise early: spatio-temporal patterns in the mobility networks of different socio-economic classes.

    PubMed

    Lotero, Laura; Hurtado, Rafael G; Floría, Luis Mario; Gómez-Gardeñes, Jesús

    2016-10-01

    We analyse the urban mobility in the cities of Medellín and Manizales (Colombia). Each city is represented by six mobility networks, each one encoding the origin-destination trips performed by a subset of the population corresponding to a particular socio-economic status. The nodes of each network are the different urban locations whereas links account for the existence of a trip between two different areas of the city. We study the main structural properties of these mobility networks by focusing on their spatio-temporal patterns. Our goal is to relate these patterns with the partition into six socio-economic compartments of these two societies. Our results show that spatial and temporal patterns vary across these socio-economic groups. In particular, the two datasets show that as wealth increases the early-morning activity is delayed, the midday peak becomes smoother and the spatial distribution of trips becomes more localized.

  9. Rich do not rise early: spatio-temporal patterns in the mobility networks of different socio-economic classes

    PubMed Central

    Hurtado, Rafael G.; Floría, Luis Mario

    2016-01-01

    We analyse the urban mobility in the cities of Medellín and Manizales (Colombia). Each city is represented by six mobility networks, each one encoding the origin-destination trips performed by a subset of the population corresponding to a particular socio-economic status. The nodes of each network are the different urban locations whereas links account for the existence of a trip between two different areas of the city. We study the main structural properties of these mobility networks by focusing on their spatio-temporal patterns. Our goal is to relate these patterns with the partition into six socio-economic compartments of these two societies. Our results show that spatial and temporal patterns vary across these socio-economic groups. In particular, the two datasets show that as wealth increases the early-morning activity is delayed, the midday peak becomes smoother and the spatial distribution of trips becomes more localized. PMID:27853531

  10. 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)

  11. Examining the Links between Air Toxics Risk and Academic Performance in the Great Lakes Region Using the TRI

    EPA Pesticide Factsheets

    A study aimed at understanding the distribution of air pollution from industrial sources around U.S. public schools, whether racial and socioeconomic disparities in such distribution exist, and if these burdens are linked with student performance/health.

  12. 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.

  13. Socioeconomic stereotypes among undergraduate college students.

    PubMed

    Gilmore, Amanda K; Harris, Paul B

    2008-12-01

    Classism, i.e., socioeconomic stereotypes, prejudice, and discrimination that college students direct toward their peers, was examined. A sample of 53 undergraduate students (36 women and 17 men), ages 18 to 22 years (M = 19.0, SD = 1.2), were recruited from psychology courses. Utilizing a computer-administered questionnaire, participants were randomly assigned to rate a fictitious student whose family income was specified as among the lowest or highest at the college. Upper Income targets were rated as more sociable, judgmental, attractive, more likely to use alcohol and drugs, and more likely to belong to a fraternity or sorority. Lower Income targets were rated as more likable, agreeable, conscientious, intelligent, creative, and better able to maintain close friendships. Research directed toward the middle class could help fill a gap in the classism literature. Research on classism in higher education could clarify this potentially divisive issue among undergraduates.

  14. Marriage and Socioeconomic Change in Contemporary Indonesia

    PubMed Central

    Nobles, Jenna; Buttenheim, Alison

    2015-01-01

    This study investigates the relationship between economic trends and entry into marriage in a rapidly developing setting. We examine Indonesian marriage in the 1990’s, a decade of substantial economic growth followed by a sudden financial collapse in 1998. We use discrete-time hazard models to analyze information on 4,078 women and 4,496 men from the Indonesia Family Life Survey. While previous research has shown that marriages may be postponed after economic downturn, we find no evidence of such delays at the national level following the 1998 financial crisis. In contrast, we use regional wage rate data to show that entry into marriage is inversely related to economic growth throughout the decade for all women and for men from lower socioeconomic strata. PMID:26336321

  15. 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.

  16. Epidemiology and socioeconomic aspects of urolithiasis.

    PubMed

    Asper, R

    1984-01-01

    This epidemiologic study reveals that the occurrence of urolithiasis in the nineteenth century population in Europe is quite similar to that of the twentieth century in Asia. The analogy is demonstrated for age distribution, stone localization, male/female ratio, and stone composition. The distribution of urolithiasis in a low socioeconomic level population is defined by: highest frequency in childhood, more than 40% bladder stones, less than 20% female patients, less than 40% calcium-oxalate stones, and more than 30% uric acid/urate stones. Typical for a population with a high level these characteristics of urolithiasis are: highest frequency among adults, less than 10% bladder stones, more than 25% female patients, more than 60% calcium oxalate stones, and less than 20% uric acid/urate stones. In partially developed countries those values fall in between.

  17. Socioeconomic Distinction, Cultural Tastes, and Cigarette Smoking.

    PubMed

    Pampel, Fred C

    2006-03-01

    OBJECTIVES: The inverse relationship between socioeconomic status (SES) and smoking is typically seen in terms of the greater economic and social resources of advantaged groups, but it may also relate to cultural resources. This study aims to test theories of symbolic distinction by examining relationships between smoking and ostensibly unrelated cultural preferences. METHODS: Using the 1993 General Social Survey, ordinal logistic regression models, and a three-category dependent variable (never, former, and current smoker), the analysis estimates relationships of musical likes and dislikes with smoking while controlling for SES and social strain. RESULTS: Preferences for classical music are associated with lower smoking, while preferences for bluegrass, jazz, and heavy metal music are associated with higher smoking. CONCLUSIONS: The results suggest that SES groups may use smoking, like other cultural tastes, to distinguish their lifestyles from those of others.

  18. Socioeconomic Distinction, Cultural Tastes, and Cigarette Smoking*

    PubMed Central

    Pampel, Fred C.

    2011-01-01

    Objectives The inverse relationship between socioeconomic status (SES) and smoking is typically seen in terms of the greater economic and social resources of advantaged groups, but it may also relate to cultural resources. This study aims to test theories of symbolic distinction by examining relationships between smoking and ostensibly unrelated cultural preferences. Methods Using the 1993 General Social Survey, ordinal logistic regression models, and a three-category dependent variable (never, former, and current smoker), the analysis estimates relationships of musical likes and dislikes with smoking while controlling for SES and social strain. Results Preferences for classical music are associated with lower smoking, while preferences for bluegrass, jazz, and heavy metal music are associated with higher smoking. Conclusions The results suggest that SES groups may use smoking, like other cultural tastes, to distinguish their lifestyles from those of others. PMID:21874073

  19. TEP1, the yeast homolog of the human tumor suppressor gene PTEN/MMAC1/TEP1, is linked to the phosphatidylinositol pathway and plays a role in the developmental process of sporulation.

    PubMed

    Heymont, J; Berenfeld, L; Collins, J; Kaganovich, A; Maynes, B; Moulin, A; Ratskovskaya, I; Poon, P P; Johnston, G C; Kamenetsky, M; DeSilva, J; Sun, H; Petsko, G A; Engebrecht, J

    2000-11-07

    PTEN/MMAC1/TEP1 (PTEN, phosphatase deleted on chromosome ten; MMAC1, mutated in multiple advanced cancers; TEP1, tensin-like phosphatase) is a major human tumor suppressor gene whose suppressive activity operates on the phosphatidylinositol pathway. A single homologue of this gene, TEP1 (YNL128w), exists in the budding yeast Saccharomyces cerevisiae. Yeast strains deleted for TEP1 exhibit essentially no phenotype in haploids; however, diploids exhibit resistance to the phosphatidylinositol-3-phosphate kinase inhibitor wortmannin and to lithium ions. Although rates of cancer increase with age, neither tep1 haploids nor diploids have altered life spans. TEP1 RNA is present throughout the cell cycle, and levels are dramatically up-regulated during meiotic development. Although homozygous tep1 mutants initiate the meiotic program and form spores with wild-type kinetics, analysis of the spores produced in tep1 mutants indicates a specific defect in the trafficking or deposition of dityrosine, a major component of yeast spore walls, to the surface. Introduction of a common PTEN mutation found in human tumors into the analogous position in Tep1p produces a nonfunctional protein based on in vivo activity. These studies implicate Tep1p in a specific developmental trafficking or deposition event and suggest that Tep1p, like its mammalian counterpart, impinges on the phosphatidylinositol pathway.

  20. TEP1, the yeast homolog of the human tumor suppressor gene PTEN/MMAC1/TEP1, is linked to the phosphatidylinositol pathway and plays a role in the developmental process of sporulation

    PubMed Central

    Heymont, Jennifer; Berenfeld, Ludmilla; Collins, Jennifer; Kaganovich, Alexandra; Maynes, Bradford; Moulin, Aaron; Ratskovskaya, Irina; Poon, Pak P.; Johnston, Gerald C.; Kamenetsky, Margarita; DeSilva, John; Sun, Hong; Petsko, Gregory A.; Engebrecht, JoAnne

    2000-01-01

    PTEN/MMAC1/TEP1 (PTEN, phosphatase deleted on chromosome ten; MMAC1, mutated in multiple advanced cancers; TEP1, tensin-like phosphatase) is a major human tumor suppressor gene whose suppressive activity operates on the phosphatidylinositol pathway. A single homologue of this gene, TEP1 (YNL128w), exists in the budding yeast Saccharomyces cerevisiae. Yeast strains deleted for TEP1 exhibit essentially no phenotype in haploids; however, diploids exhibit resistance to the phosphatidylinositol-3-phosphate kinase inhibitor wortmannin and to lithium ions. Although rates of cancer increase with age, neither tep1 haploids nor diploids have altered life spans. TEP1 RNA is present throughout the cell cycle, and levels are dramatically up-regulated during meiotic development. Although homozygous tep1 mutants initiate the meiotic program and form spores with wild-type kinetics, analysis of the spores produced in tep1 mutants indicates a specific defect in the trafficking or deposition of dityrosine, a major component of yeast spore walls, to the surface. Introduction of a common PTEN mutation found in human tumors into the analogous position in Tep1p produces a nonfunctional protein based on in vivo activity. These studies implicate Tep1p in a specific developmental trafficking or deposition event and suggest that Tep1p, like its mammalian counterpart, impinges on the phosphatidylinositol pathway. PMID:11070083

  1. Dexter energy transfer pathways

    PubMed Central

    Skourtis, Spiros S.; Liu, Chaoren; Antoniou, Panayiotis; Virshup, Aaron M.; Beratan, David N.

    2016-01-01

    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

  2. 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.

  3. Are Worry and Rumination Specific Pathways Linking Neuroticism and Symptoms of Anxiety and Depression in Patients with Generalized Anxiety Disorder, Major Depressive Disorder and Mixed Anxiety-Depressive Disorder?

    PubMed

    Merino, Hipólito; Senra, Carmen; Ferreiro, Fátima

    2016-01-01

    This study examines the relationships between neuroticism (higher-order vulnerability factor), the cognitive styles of worry, brooding and reflection (second-order vulnerability factors) and symptoms of anxiety and depression in three groups of patients: patients with Generalized Anxiety Disorder (GAD), with Major Depressive Disorder (MDD) and with Mixed Anxiety-Depressive Disorder (MADD). One hundred and thirty four patients completed a battery of questionnaires including measures of neuroticism, worry, rumination (brooding and reflection), anxiety and depression. Multiple mediation analyses indicate that worry may act as a mediating mechanism linking neuroticism and anxiety symptoms in the three diagnostic groups, whereas brooding-rumination may play a mediating role between neuroticism and depressive symptoms in patients with MDD and MADD and, with less certainty, in patients with GAD. Overall, our findings suggest that neuroticism may increase the risk of anxious and depressive symptoms via specific links involving either worry or brooding, respectively, and that both worry and brooding may operate in the three groups examined, irrespectively of whether anxiety or depression are the main emotions or whether they coexist without any clear predominance; consequently, we hypothesize the existence of "specific transdiagnostic" mechanisms.

  4. 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

  5. Socioeconomic and Emotional Predictors of Decision Making for Timing Motherhood Among Iranian Women in 2013

    PubMed Central

    Kariman, Nourossadat; Simbar, Masoumeh; Ahmadi, Fazlollah; Vedadhir, Abou Ali

    2014-01-01

    Background: Decision making for timing motherhood is one of the vital aspects of reproductive health. Separating sexual relationship from having a child has led to a different and unprecedented lifestyle in human history. Objectives: The objective of this study was to determine the socioeconomic and emotional factors predicting decision making for timing motherhood among Iranian women using the statistical softwares of IBM SPSS 21 and LISREL 8.8. Patients and Methods: This cross-sectional study enrolled 820 primiparous women from different hospitals across the country using multistage random sampling method in 2013. The tools of the study were enrich marital satisfaction, socioeconomic status, perceived social support, hopefulness, and life regard index. The data was analyzed using SPSS 20 and LISREL 8.8. Results: The results revealed that among direct pathways, marital age (β = 0.62) was the most effective predictor of timing motherhood. The hopefulness had an inverse association with timing motherhood through inverse effect of marital satisfaction. Moreover, marital satisfaction (β = -0.09), perceived social support (β = -0.09), and life regard index (β = 0.01) had an inverse effect on timing motherhood. Marital satisfaction had a non-causal effect of 0.024. Conclusions: Marital age, and socioeconomic status had a direct association, and hopefulness and marital satisfaction had an indirect one with Iranian women’s decision for timing motherhood. Therefore, this is the responsibility of policy-makers and healthcare providers to advise women by providing appropriate interventions and facilities. PMID:24719733

  6. 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

    Noodleman, Louis; Han Du, Wen-Ge; Fee, James A; Götz, Andreas W; Walker, Ross C

    2014-07-07

    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.

  7. 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…

  8. Information and Socioeconomic Class in U.S. Constitutional Law.

    ERIC Educational Resources Information Center

    Braman, Sandra

    1989-01-01

    Examines Supreme Court decisions on information policy during the 1980s. Finds they support socioeconomic class divisions by: providing relatively few protections for media available to those of low socioeconomic status; directly limiting expenditures for court costs; deferring to labor law; and defining informational rights and responsibilities…

  9. 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…

  10. 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…

  11. 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…

  12. 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 maternal…

  13. Effective Intervention across Socioeconomic Classes for Improvement in Language Outcomes

    ERIC Educational Resources Information Center

    Kanwal, Afia; Shehzad, Wasima

    2017-01-01

    Students in higher education bring with them a difference of linguistic abilities that is often due to the difference in socioeconomic status and early schooling. The lack of linguistic capacity hampers academic pace and introduces discrepancies in performance of learners. This paper examines the persistence of socioeconomic differences being…

  14. Neighbourhood socioeconomic inequalities in incidence of acute myocardial infarction: a cohort study quantifying age- and gender-specific differences in relative and absolute terms

    PubMed Central

    2012-01-01

    Background Socioeconomic status has a profound effect on the risk of having a first acute myocardial infarction (AMI). Information on socioeconomic inequalities in AMI incidence across age- gender-groups is lacking. Our objective was to examine socioeconomic inequalities in the incidence of AMI considering both relative and absolute measures of risk differences, with a particular focus on age and gender. Methods We identified all patients with a first AMI from 1997 to 2007 through linked hospital discharge and death records covering the Dutch population. Relative risks (RR) of AMI incidence were estimated by mean equivalent household income at neighbourhood-level for strata of age and gender using Poisson regression models. Socioeconomic inequalities were also shown within the stratified age-gender groups by calculating the total number of events attributable to socioeconomic disadvantage. Results Between 1997 and 2007, 317,564 people had a first AMI. When comparing the most deprived socioeconomic quintile with the most affluent quintile, the overall RR for AMI was 1.34 (95 % confidence interval (CI): 1.32 – 1.36) in men and 1.44 (95 % CI: 1.42 – 1.47) in women. The socioeconomic gradient decreased with age. Relative socioeconomic inequalities were most apparent in men under 35 years and in women under 65 years. The largest number of events attributable to socioeconomic inequalities was found in men aged 45–74 years and in women aged 65–84 years. The total proportion of AMIs that was attributable to socioeconomic inequalities in the Dutch population of 1997 to 2007 was 14 % in men and 18 % in women. Conclusions Neighbourhood socioeconomic inequalities were observed in AMI incidence in the Netherlands, but the magnitude across age-gender groups depended on whether inequality was expressed in relative or absolute terms. Relative socioeconomic inequalities were high in young persons and women, where the absolute burden of AMI was low. Absolute

  15. 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.

  16. 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

    2014-10-06

    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.

  17. 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

  18. Socio-economic and climate change impacts on agriculture: an integrated assessment, 1990–2080

    PubMed Central

    Fischer, Günther; Shah, Mahendra; N. Tubiello, Francesco; van Velhuizen, Harrij

    2005-01-01

    A comprehensive assessment of the impacts of climate change on agro-ecosystems over this century is developed, up to 2080 and at a global level, albeit with significant regional detail. To this end an integrated ecological–economic modelling framework is employed, encompassing climate scenarios, agro-ecological zoning information, socio-economic drivers, as well as world food trade dynamics. Specifically, global simulations are performed using the FAO/IIASA agro-ecological zone model, in conjunction with IIASAs global food system model, using climate variables from five different general circulation models, under four different socio-economic scenarios from the intergovernmental panel on climate change. First, impacts of different scenarios of climate change on bio-physical soil and crop growth determinants of yield are evaluated on a 5′×5′ latitude/longitude global grid; second, the extent of potential agricultural land and related potential crop production is computed. The detailed bio-physical results are then fed into an economic analysis, to assess how climate impacts may interact with alternative development pathways, and key trends expected over this century for food demand and production, and trade, as well as key composite indices such as risk of hunger and malnutrition, are computed. This modelling approach connects the relevant bio-physical and socio-economic variables within a unified and coherent framework to produce a global assessment of food production and security under climate change. The results from the study suggest that critical impact asymmetries due to both climate and socio-economic structures may deepen current production and consumption gaps between developed and developing world; it is suggested that adaptation of agricultural techniques will be central to limit potential damages under climate change. PMID:16433094

  19. 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.

  20. The role of socioeconomic status in longitudinal trends of cholera in Matlab, Bangladesh, 1993-2007.

    PubMed

    Root, Elisabeth Dowling; Rodd, Joshua; Yunus, Mohammad; Emch, Michael

    2013-01-01

    There has been little evidence of a decline in the global burden of cholera in recent years as the number of cholera cases reported to WHO continues to rise. Cholera remains a global threat to public health and a key indicator of lack of socioeconomic development. Overall socioeconomic development is the ultimate solution for control of cholera as evidenced in developed countries. However, most research has focused on cross-county comparisons so that the role of individual- or small area-level socioeconomic status (SES) in cholera dynamics has not been carefully studied. Reported cases of cholera in Matlab, Bangladesh have fluctuated greatly over time and epidemic outbreaks of cholera continue, most recently with the introduction of a new serotype into the region. The wealth of longitudinal data on the population of Matlab provides a unique opportunity to explore the impact of socioeconomic status and other demographic characteristics on the long-term temporal dynamics of cholera in the region. In this population-based study we examine which factors impact the initial number of cholera cases in a bari at the beginning of the 0139 epidemic and the factors impacting the number of cases over time. Cholera data were derived from the ICDDR,B health records and linked to socioeconomic and geographic data collected as part of the Matlab Health and Demographic Surveillance System. Longitudinal zero-inflated Poisson (ZIP) multilevel regression models are used to examine the impact of environmental and socio-demographic factors on cholera counts across baris. Results indicate that baris with a high socioeconomic status had lower initial rates of cholera at the beginning of the 0139 epidemic (γ(01) = -0.147, p = 0.041) and a higher probability of reporting no cholera cases (α(01) = 0.156, p = 0.061). Populations in baris characterized by low SES are more likely to experience higher cholera morbidity at the beginning of an epidemic than populations in high

  1. 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

  2. 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.

  3. 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

  4. Heat Shock Protein HSP27 Secretion by Ovarian Cancer Cells Is Linked to Intracellular Expression Levels, Occurs Independently of the Endoplasmic Reticulum Pathway and HSP27's Phosphorylation Status, and Is Mediated by Exosome Liberation

    PubMed Central

    Klinkmann, Gerd; Diesing, Karoline; Koensgen, Dominique; Burchardt, Martin

    2017-01-01

    The heat shock protein HSP27 has been correlated in ovarian cancer (OC) patients with aggressiveness and chemoresistance and, therefore, represents a promising potential biomarker for OC diagnosis, prognosis, and treatment response. Notably, secretion of soluble HSP27 has been described by a few cell types and may take place as well in OC cells. Therefore, we studied HSP27 secretion mechanisms under diverse cellular conditions in an OC cell model system. Secretion of HSP27 was characterized after overexpression of HSP27 by transfected plasmids and after heat shock. Intra- and extracellular HSP27 amounts were assessed by Western blotting and ELISA. Protein secretion was blocked by brefeldin A and the impact of the HSP27 phosphorylation status was analyzed overexpressing HSP27 phosphomutants. The present study demonstrated that HSP27 secretion by OVCAR-3 and SK-OV-3 cells depends on intracellular HSP27 concentrations. Moreover, HSP27 secretion is independent of the endoplasmic reticulum secretory pathway and HSP27 phosphorylation. Notably, analysis of OC cell-born exosomes not only confirmed the concentration-dependent correlation of HSP27 expression and secretion but also demonstrated a concentration-dependent incorporation of HSP27 protein into exosomes. Thus, secreted HSP27 may become more important as an extracellular factor which controls the tumor microenvironment and might be a noninvasive biomarker. PMID:28325957

  5. Understanding socio-economic inequalities in food choice behaviour: can Maslow's pyramid help?

    PubMed

    van Lenthe, Frank J; Jansen, Tessa; Kamphuis, Carlijn B M

    2015-04-14

    Socio-economic groups differ in their material, living, working and social circumstances, which may result in different priorities about their daily-life needs, including the priority to make healthy food choices. Following Maslow's hierarchy of human needs, we hypothesised that socio-economic inequalities in healthy food choices can be explained by differences in the levels of need fulfilment. Postal survey data collected in 2011 (67·2 % response) from 2903 participants aged 20-75 years in the Dutch GLOBE (Gezondheid en Levens Omstandigheden Bevolking Eindhoven en omstreken) study were analysed. Maslow's hierarchy of human needs (measured with the Basic Need Satisfaction Inventory) was added to age- and sex-adjusted linear regression models that linked education and net household income levels to healthy food choices (measured by a FFQ). Most participants (38·6 %) were in the self-actualisation layer of the pyramid. This proportion was highest among the highest education group (47·6 %). Being in a higher level of the hierarchy was associated with a higher consumption of fruits and vegetables as well as more healthy than unhealthy bread, snack and dairy consumption. Educational inequalities in fruit and vegetable intake (B= -1·79, 95 % CI -2·31, -1·28 in the lowest education group) were most reduced after the hierarchy of needs score was included (B= -1·57, 95 % CI - ·09, -1·05). Inequalities in other healthy food choices hardly changed after the hierarchy of needs score was included. People who are satisfied with higher-level needs make healthier food choices. Studies aimed at understanding socio-economic inequalities in food choice behaviour need to take differences in the priority given to daily-life needs by different socio-economic groups into account, but Maslow's pyramid offers little help.

  6. The effect of socioeconomic deprivation on fracture incidence in the United Kingdom.

    PubMed

    Jones, Sarah; Johansen, Antony; Brennan, Julieann; Butler, John; Lyons, Ronan A

    2004-07-01

    Lifestyle factors such as diet and physical activity vary in different social and income groups, and are known to be important influences on the incidence of osteoporotic fractures. Financial and social pressures are a common concern for older people. We set out to study the effect of socioeconomic deprivation on the incidence of fracture in older people and to compare the findings with those for younger groups. The All Wales Injury Surveillance System (AWISS) is a computerized system that collects injury data from most A&E departments throughout Wales. In this population-based study of 1.8 million people living in the 445 electoral tracts covered by AWISS in south, west, and northeastern Wales, we identified all 60,106 residents who presented with a fracture in 1999 and 2000. We linked details of their fracture with published Townsend deprivation scores for the electoral tract in which they were living and calculated fracture rates by fifths of deprivation. We observed the expected pattern of increasing fracture incidence in older age groups. Fracture incidence was significantly higher in electoral wards with poorer Townsend scores, resulting from a marked effect of socioeconomic deprivation on fracture incidence among younger adults with a rate ratio of 1.64 (95% CI, 1.57 to 1.72). This effect diminished with age, and was not observed in older age groups. At ages 85 and over the rate ratio was 0.94 (95% CI, 0.87 to 1.01). Socioeconomic factors clearly play a part in the causation of fracture in younger adults. Lifestyle influences are important in older age groups, but socioeconomic deprivation does not appear to be a risk factor for the development of osteoporotic fractures in elderly people.

  7. A study of suicide and socioeconomic factors.

    PubMed

    Ying, Yung-Hsiang; Chang, Koyin

    2009-04-01

    The topic of suicide has long been an important socioeconomic issue studied in many countries. Suicides inject an atmosphere of unrest into society, and media attention furthers that social uneasiness. From the viewpoint of economics and management, suicide is a waste of human resource: it decreases the labor force in society and deteriorates human capital. This paper provides a series of analyses of suicide rate based on theoretical reasoning and empirical approaches. Aggregate data from G7 countries are obtained and stacked into panel data for analysis. Data are collected for different age groups. Even though suicide issues have been extensively discussed in the past, newly developed econometric tools are applied to her. Beyond previously recognized relationships between economic factors and suicide rates findings include that unemployment strikes men more than women in terms of psychological pressure: for middle age or older women, unemployment may even be positive for the entire family; and female labor force participation exerts pressure on male counterparts and increases its suicide rate. As a result, a low income family with an unemployed man and an employed woman is at high risk for adult male suicide.

  8. Socioeconomic status, race, and COPD health outcomes

    PubMed Central

    Eisner, Mark D.; Blanc, Paul D.; Omachi, Theodore A.; Yelin, Edward H.; Sidney, Stephen; Katz, Patricia P.; Ackerson, Lynn M.; Sanchez, Gabriela; Tolstykh, Irina; Iribarren, Carlos

    2010-01-01

    Background Although COPD is a common cause of death and disability, little is known about the effects of socioeconomic status (SES) and race-ethnicity on health outcomes. Methods We aimed to determine the independent impacts of SES and race-ethnicity on COPD severity status, functional limitations, and acute exacerbations of COPD among patients with access to health care. Data were used from the FLOW cohort study of 1,202 Kaiser Permanente Northern California Medical Care Plan members with COPD. Results Lower educational attainment and household income were consistently related to greater disease severity, poorer lung function, and greater physical functional limitations in cross-sectional analysis. Black race was associated with greater COPD severity, but these differences were no longer apparent after controlling for SES variables and other covariates (comorbidities, smoking, body mass index, and occupational exposures). Both lower education and income were independently related to a greater prospective risk of acute COPD exacerbation (HR 1.5; 95% CI 1.01 to 2.1; and HR 2.1; 95% CI 1.4 to 3.4, respectively). Conclusion Low SES is a risk factor for a broad array of adverse COPD health outcomes. Clinicians and disease management programs should consider SES as a key patient-level marker of risk for poor outcomes. PMID:19854747

  9. Microbial 'old friends', immunoregulation and socioeconomic status.

    PubMed

    Rook, G A W; Raison, C L; Lowry, C A

    2014-07-01

    The immune system evolved to require input from at least three sources that we collectively term the 'old friends': (i) the commensal microbiotas transmitted by mothers and other family members; (ii) organisms from the natural environment that modulate and diversify the commensal microbiotas; and (iii) the 'old' infections that could persist in small isolated hunter-gatherer groups as relatively harmless subclinical infections or carrier states. These categories of organism had to be tolerated and co-evolved roles in the development and regulation of the immune system. By contrast, the 'crowd infections' (such as childhood virus infections) evolved later, when urbanization led to large communities. They did not evolve immunoregulatory roles because they either killed the host or induced solid immunity, and could not persist in hunter-gatherer groups. Because the western lifestyle and medical practice deplete the 'old' infections (for example helminths), immunoregulatory disorders have increased, and the immune system has become more dependent upon microbiotas and the natural environment. However, urbanization maintains exposure to the crowd infections that lack immunoregulatory roles, while accelerating loss of exposure to the natural environment. This effect is most pronounced in individuals of low socioeconomic status (SES) who lack rural second homes and rural holidays. Interestingly, large epidemiological studies indicate that the health benefits of living close to green spaces are most pronounced for individuals of low SES. Here we discuss the immunoregulatory role of the natural environment, and how this may interact with, and modulate, the proinflammatory effects of psychosocial stressors in low SES individuals.

  10. A novel approach to measuring residential socioeconomic ...

    EPA Pesticide Factsheets

    Individual-level characteristics, including socioeconomic status, have been associated with poor metabolic and cardiovascular health; however, residential area-level characteristics may also independently contribute to health status. In the current study, we used a novel application of hierarchical clustering to aggregate 444 US Census block groups in Durham, Orange, and Wake Counties, NC, USA into six homogenous clusters of similar characteristics based on 12 demographic factors. We assigned 2254 cardiac catheterization patients to these clusters based on residence at first catheterization. After controlling for individual age, sex, smoking status, and race, there were elevated odds of patients being obese (OR = 1.92, 95% CI = 1.39, 2.67), and having diabetes (OR = 2.19, 95% CI = 1.57, 3.04) and hypertension (OR = 2.05, 95% CI = 1.38, 3.11) in a cluster that was urban, impoverished, and unemployed, compared to a cluster that was urban with a low percentage of people that were impoverished or unemployed. Our findings demonstrate the feasibility of applying hierarchical clustering to an assessment of area-level characteristics and that living in impoverished, urban residential clusters may have an adverse impact on health. This abstract does not necessarily reflect U.S. EPA policy. This is an abstract of a presentation to be presented at the International Society for Environmental Epidemiology (ISEE) 2016 Conference. Reactions to this presentation will guid

  11. [Socioeconomic impacts of an emerging disease].

    PubMed

    Grisotti, Márcia; de Avila-Pires, Fernando Dias

    2011-02-01

    In 1955 a population explosion of the slug Sarasinula linguaeformis (Semper, 1885) damaged crop plantations in the municipalities of Nova Itaberaba and Planalto Alegre, western of Santa Catarina State, Brazil. In this article we analyze the socioeconomic impacts caused by the emergence of this plague, which raised the suspicion, eventually confirmed, of the occurrence of human cases of abdominal angyostrongiliasis. The data were collected through the observation of a serological study during the period of August 2000 to August 2001 by a research team from the Catholic University of Rio Grande do Sul (PUCRS) together with field technicians from the Empresa de Pesquisa Agropecuária e Extensão Rural de Santa Catarina S.A. (Epagri-SC), and with the members of 50 local families. In order to analyze these impacts, we elaborated several analytical categories as economic losses; preventive measures, habit change and social prejudice, that emerged from the narratives of the residents interviewed. It became evident the need for sociological analyses of epidemiological problems, in addition to strictly medico-sanitary considerations.

  12. 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

  13. 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…

  14. Lower respiratory illness in infants and low socioeconomic status.

    PubMed Central

    Margolis, P A; Greenberg, R A; Keyes, L L; LaVange, L M; Chapman, R S; Denny, F W; Bauman, K E; Boat, B W

    1992-01-01

    OBJECTIVES. Infants from families of low socioeconomic status are said to suffer higher rates of lower respiratory illness, but this assertion has not been carefully examined. METHODS. We studied the frequency and determinants of lower respiratory illness in infants of different socioeconomic status (n = 393) by analyzing data from a community-based cohort study of respiratory illness during the first year of life in central North Carolina. RESULTS. The incidence of lower respiratory illness was 1.41 in the low socioeconomic group, 1.26 in the middle group, and 0.67 in the high group. The prevalence of persistent respiratory symptoms was 39% in infants in the low socioeconomic group, 24% in infants in the middle group, and 14% in infants in the high group. The odds of persistent respiratory symptoms in infants of low and middle socioeconomic status were reduced after controlling for environmental risk factors for lower respiratory illness. Enrollment in day care was associated with an increased risk of persistent symptoms among infants of high but not low socioeconomic status. CONCLUSIONS. Infants of low socioeconomic status are at increased risk of persistent respiratory symptoms. This risk can be partly attributed to environmental exposures, most of which could be changed. PMID:1636832

  15. Socioeconomic Disparities in Telephone-Based Treatment of Tobacco Dependence

    PubMed Central

    Varghese, Merilyn; Stitzer, Maxine; Landes, Reid; Brackman, S. Laney; Munn, Tiffany

    2014-01-01

    Objectives. We examined socioeconomic disparities in tobacco dependence treatment outcomes from a free, proactive telephone counseling quitline. Methods. We delivered cognitive–behavioral treatment and nicotine patches to 6626 smokers and examined socioeconomic differences in demographic, clinical, environmental, and treatment use factors. We used logistic regressions and generalized estimating equations (GEE) to model abstinence and account for socioeconomic differences in the models. Results. The odds of achieving long-term abstinence differed by socioeconomic status (SES). In the GEE model, the odds of abstinence for the highest SES participants were 1.75 times those of the lowest SES participants. Logistic regression models revealed no treatment outcome disparity at the end of treatment, but significant disparities 3 and 6 months after treatment. Conclusions. Although quitlines often increase access to treatment for some lower SES smokers, significant socioeconomic disparities in treatment outcomes raise questions about whether current approaches are contributing to tobacco-related socioeconomic health disparities. Strategies to improve treatment outcomes for lower SES smokers might include novel methods to address multiple factors associated with socioeconomic disparities. PMID:24922165

  16. Topological knots and links in proteins

    PubMed Central

    Dabrowski-Tumanski, Pawel; Sulkowska, Joanna I.

    2017-01-01

    Twenty years after their discovery, knots in proteins are now quite well understood. They are believed to be functionally advantageous and provide extra stability to protein chains. In this work, we go one step further and search for links—entangled structures, more complex than knots, which consist of several components. We derive conditions that proteins need to meet to be able to form links. We search through the entire Protein Data Bank and identify several sequentially nonhomologous chains that form a Hopf link and a Solomon link. We relate topological properties of these proteins to their function and stability and show that the link topology is characteristic of eukaryotes only. We also explain how the presence of links affects the folding pathways of proteins. Finally, we define necessary conditions to form Borromean rings in proteins and show that no structure in the Protein Data Bank forms a link of this type. PMID:28280100

  17. 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.