We develop and test a theoretical framework delineating the dual affective and motivational experiences arising from perceptions of being envied in the workplace. We theorize that being envied can be ...pleasantly or unpleasantly experienced with opposite downstream effects on motivation and job performance. We test our model in two field studies using a sample of government employees (Study 1) and a sample of employees in the financial industry (Study 2). Our results indicate that being envied can elicit unpleasant mood and anxiety that influence work engagement and job performance in negative ways. In addition, we found that positive emotional experiences from being envied bolster work engagement and performance through positive mood but not pride. Implications of our findings are discussed.
Progress toward understanding Zika virus (ZIKV) pathogenesis is hindered by lack of immunocompetent small animal models, in part because ZIKV fails to effectively antagonize Stat2-dependent ...interferon (IFN) responses in mice. To address this limitation, we first passaged an African ZIKV strain (ZIKV-Dak-41525) through Rag1−/− mice to obtain a mouse-adapted virus (ZIKV-Dak-MA) that was more virulent than ZIKV-Dak-41525 in mice treated with an anti-Ifnar1 antibody. A G18R substitution in NS4B was the genetic basis for the increased replication, and resulted in decreased IFN-β production, diminished IFN-stimulated gene expression, and the greater brain infection observed with ZIKV-Dak-MA. To generate a fully immunocompetent mouse model of ZIKV infection, human STAT2 was introduced into the mouse Stat2 locus (hSTAT2 KI). Subcutaneous inoculation of pregnant hSTAT2 KI mice with ZIKV-Dak-MA resulted in spread to the placenta and fetal brain. An immunocompetent mouse model of ZIKV infection may prove valuable for evaluating countermeasures to limit disease.
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•A mouse-adapted ZIKV (Dak-MA) with enhanced brain and NSC infectivity was generated•NS4B G18R mutation enhances pathogenicity of African and American ZIKV strains•Immunocompetent human STAT2 knockin mice generated that are susceptible to ZIKV NS4B G18R•ZIKV-Dak-MA spreads to the placenta and fetus in immunocompetent hSTAT2 knockin mice
An immunocompetent mouse model of ZIKV infection is needed. Gorman et al. generated ZIKV-Dak-MA, a strain with a mutation in NS4B that causes greater disease in mice than the parental virus. Human STAT2 knockin mice were generated and challenged with ZIKV-Dak-MA to establish a fully immunocompetent ZIKV mouse model.
Moderate to heavy alcohol consumption is associated with an increased risk of breast cancer. The etiologic role of genetic variation in genes involved in ethanol metabolism has not been established, ...with little information available among women of African ancestry.
Our analysis from the African American Breast Cancer Epidemiology and Risk (AMBER) Consortium included 2889 U.S. Black women who were current drinkers at the time of breast cancer diagnosis (N cases = 715) and had available genetic data for four ethanol metabolism genomic regions (ADH, ALDH, CYP2E1, and ALDH2). We used generalized estimating equations to calculate genetic effects, gene* alcohol consumption (≥ 7drinks/week vs. < 7/week) interactions, and joint main plus interaction effects of up to 23,247 variants in ethanol metabolism genomic regions on odds of breast cancer.
Among current drinkers, 21% of cases and 14% of controls reported consuming ≥ 7 drinks per week. We identified statistically significant genetic effects for rs79865122-C in CYP2E1 with odds of ER- breast cancer and odds of triple negative breast cancer, as well as a significant joint effect with odds of ER- breast cancer (≥ 7drinks per week OR = 3.92, < 7 drinks per week OR = 0.24, p
= 3.74 × 10
). In addition, there was a statistically significant interaction of rs3858704-A in ALDH2 with consumption of ≥ 7 drinks/week on odds of triple negative breast cancer (≥ 7drinks per week OR = 4.41, < 7 drinks per week OR = 0.57, p
= 8.97 × 10
).
There is a paucity of information on the impact of genetic variation in alcohol metabolism genes on odds of breast cancer among Black women. Our analysis of variants in four genomic regions harboring ethanol metabolism genes in a large consortium of U.S. Black women identified significant associations between rs79865122-C in CYP2E1 and odds of ER- and triple negative breast cancer. Replication of these findings is warranted.
Carbon nanotubes are commercially-important products of nanotechnology; however, their low density and small size makes carbon nanotube respiratory exposures likely during their production or ...processing. We have previously shown mitotic spindle aberrations in cultured primary and immortalized human airway epithelial cells exposed to single-walled carbon nanotubes (SWCNT). In this study, we examined whether multi-walled carbon nanotubes (MWCNT) cause mitotic spindle damage in cultured cells at doses equivalent to 34 years of exposure at the NIOSH Recommended Exposure Limit (REL). MWCNT induced a dose responsive increase in disrupted centrosomes, abnormal mitotic spindles and aneuploid chromosome number 24 hours after exposure to 0.024, 0.24, 2.4 and 24 μg/cm² MWCNT. Monopolar mitotic spindles comprised 95% of disrupted mitoses. Three-dimensional reconstructions of 0.1 μm optical sections showed carbon nanotubes integrated with microtubules, DNA and within the centrosome structure. Cell cycle analysis demonstrated a greater number of cells in S-phase and fewer cells in the G2 phase in MWCNT-treated compared to diluent control, indicating a G1/S block in the cell cycle. The monopolar phenotype of the disrupted mitotic spindles and the G1/S block in the cell cycle is in sharp contrast to the multi-polar spindle and G2 block in the cell cycle previously observed following exposure to SWCNT. One month following exposure to MWCNT there was a dramatic increase in both size and number of colonies compared to diluent control cultures, indicating a potential to pass the genetic damage to daughter cells. Our results demonstrate significant disruption of the mitotic spindle by MWCNT at occupationally relevant exposure levels.
US Hispanic/Latino individuals are diverse in genetic ancestry, culture, and environmental exposures. Here, we characterized and controlled for this diversity in genome-wide association studies ...(GWASs) for the Hispanic Community Health Study/Study of Latinos (HCHS/SOL). We simultaneously estimated population-structure principal components (PCs) robust to familial relatedness and pairwise kinship coefficients (KCs) robust to population structure, admixture, and Hardy-Weinberg departures. The PCs revealed substantial genetic differentiation within and among six self-identified background groups (Cuban, Dominican, Puerto Rican, Mexican, and Central and South American). To control for variation among groups, we developed a multi-dimensional clustering method to define a “genetic-analysis group” variable that retains many properties of self-identified background while achieving substantially greater genetic homogeneity within groups and including participants with non-specific self-identification. In GWASs of 22 biomedical traits, we used a linear mixed model (LMM) including pairwise empirical KCs to account for familial relatedness, PCs for ancestry, and genetic-analysis groups for additional group-associated effects. Including the genetic-analysis group as a covariate accounted for significant trait variation in 8 of 22 traits, even after we fit 20 PCs. Additionally, genetic-analysis groups had significant heterogeneity of residual variance for 20 of 22 traits, and modeling this heteroscedasticity within the LMM reduced genomic inflation for 19 traits. Furthermore, fitting an LMM that utilized a genetic-analysis group rather than a self-identified background group achieved higher power to detect previously reported associations. We expect that the methods applied here will be useful in other studies with multiple ethnic groups, admixture, and relatedness.
The structure-based design and optimization of a novel series of selective PERK inhibitors are described resulting in the identification of 44 as a potent, highly selective, and orally active tool ...compound suitable for PERK pathway biology exploration both in vitro and in vivo.
Genetics of Obesity in Diverse Populations Young, Kristin L.; Graff, Mariaelisa; Fernandez-Rhodes, Lindsay ...
Current diabetes reports,
12/2018, Letnik:
18, Številka:
12
Journal Article
Recenzirano
Odprti dostop
Purpose of Review
The prevalence of obesity continues to rise, fueling a global public health crisis characterized by dramatic increases in type 2 diabetes, cardiovascular disease, and many cancers. ...In the USA, several minority populations, who bear much of the obesity burden (47% in African Americans and Hispanic/Latinos, compared to 38% in European descent groups), are particularly at risk of downstream chronic disease. Compounding these disparities, most genome-wide association studies (GWAS)—including those of obesity—have largely been conducted in populations of European or East Asian ancestry. In fact, analysis of the GWAS Catalog found that while the proportion of participants of non-European or non-Asian descent had risen from 4% in 2009 to 19% in 2016, African-ancestry participants are still just 3% of GWAS, Hispanic/Latinos are < 0.5%, and other ancestries are < 0.3% or not represented at all. This review summarizes recent developments in obesity genomics in US minority populations, with the goal of reducing obesity health disparities and improving public health programs and access to precision medicine.
Recent Findings
GWAS of populations with the highest burden of obesity are essential to narrow candidate variants for functional follow-up, to identify additional ancestry-specific variants that contribute to individual genetic susceptibility, and to advance both public health and precision medicine approaches to obesity.
Summary
Given the global public health burden posed by obesity and downstream chronic conditions which disproportionately affect non-European populations, GWAS of obesity-related traits in diverse populations is essential to (1) locate causal variants in GWAS-identified regions through fine mapping, (2) identify variants which influence obesity across ancestries through generalization, and (3) discover novel ancestry-specific variants which may be low frequency in European populations but common in other groups. Recent efforts to expand obesity genomic studies to understudied and underserved populations, including AAAGC, PAGE, and HISLA, are working to reduce obesity health disparities, improve public health, and bring the promise of precision medicine to all.
Background: Dietary intake of antioxidants such as vitamins C and E protect against oxidative stress, and may also be associated with altered DNA methylation patterns.
Methods: We meta-analysed ...epigenome-wide association study (EWAS) results from 11,866 participants across eight population-based cohorts to evaluate the association between self-reported dietary and supplemental intake of vitamins C and E with DNA methylation. EWAS were adjusted for age, sex, BMI, caloric intake, blood cell type proportion, smoking status, alcohol consumption, and technical covariates. Significant results of the meta-analysis were subsequently evaluated in gene set enrichment analysis (GSEA) and expression quantitative trait methylation (eQTM) analysis.
Results: In meta-analysis, methylation at 4,656 CpG sites was significantly associated with vitamin C intake at FDR ≤ 0.05. The most significant CpG sites associated with vitamin C (at FDR ≤ 0.01) were enriched for pathways associated with systems development and cell signalling in GSEA, and were associated with downstream expression of genes enriched in the immune response in eQTM analysis. Furthermore, methylation at 160 CpG sites was significantly associated with vitamin E intake at FDR ≤ 0.05, but GSEA and eQTM analysis of the top most significant CpG sites associated with vitamin E did not identify significant enrichment of any biological pathways investigated.
Conclusions: We identified significant associations of many CpG sites with vitamin C and E intake, and our results suggest that vitamin C intake may be associated with systems development and the immune response.
Climate change is increasing the severity and extent of extreme droughts events, posing a critical threat to freshwater ecosystems, particularly with increasing human demands for diminishing water ...supplies. Despite the importance of drought as a significant driver of ecological and evolutionary dynamics, current understanding of drought consequences for freshwater biodiversity is very limited. We describe key barriers that hinder integrative drought research and monitoring across riverscapes. The primary constraint limiting understanding of ecological drought is an existing monitoring framework focused on human water consumption and flood risk in mainstem rivers. This approach is misaligned with escalating needs for research and data collection that illuminate exposure, sensitivity, and adaptive capacity (i.e., vulnerability) of biota to drought across entire riverscapes. We present a hierarchical framework for integrated ecological drought monitoring and research that addresses drought vulnerability across riverscapes and describe how this approach can directly inform natural-resource management.
Research on team leadership has primarily focused on leadership processes targeted within teams, in support of team objectives. Yet, teams are open systems that interact with other teams to achieve ...proximal as well as distal goals. This review clarifies that defining ‘what’ constitutes functionally effective leadership in interteam contexts requires greater precision with regard to where (within teams, across teams) and why (team goals, system goals) leadership processes are enacted, as well as greater consideration of when and among whom leadership processes arise. We begin by synthesizing findings from empirical studies published over the past 30 years that shed light on questions of what, where, why, when, and who related to interteam leadership and end by providing three overarching recommendations for how research should proceed in order to provide a more comprehensive picture of leadership in interteam contexts.
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