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Diabetes is a contributor to morbidity across the globe and is often associated with obesity, metabolic syndrome and other inflammatory diseases associated with aging. In addition to genetic and lifestyle factors, environmental factors such as metals and persistent organic pollutants may increase the severity or lower the threshold of these conditions. In cell culture, methylmercury is toxic to adipocytes and may impact adipokine secretions. In this study, we determined the effects of different concentrations of theaflavin digallate on methylmercury exposed 3T3-L1 adipocytes in cell culture. Secretions of resistin, adiponectin and lipid peroxidation product, 4-hydroxynonenal (4-HNE) were monitored using ELISA assays. Cell morphology of methylmercury and theaflavin-3,3′-digallate treated adipocytes was assessed using Lipid (Oil Red O) staining. Exposure to methylmercury increased the levels of resistin and adiponectin as well as 4-HNE when compared to the control cells. Methylmercury treated cells resulted in smaller number of adipocytes and clumped lipid droplets. These results suggest that methylmercury induces reactive oxygen species leading to development of an inflammatory response. Theaflavin-3,3′-digallate reduced the impact of methylmercury by maintaining the adipocytes morphology and secretion patterns of adiponectin, resistin and 4-hydroxynonenal. With this experimental model system other anti-inflammatory and signaling agents could be tested at the biochemical level before eventually leading to studies in animal models.

Leukaemia progressively invades bone marrow (BM), outcompeting healthy haematopoiesis by mechanisms that are not fully understood. Combining cell number measurements with a short-timescale dual pulse labelling method, we simultaneously determine the proliferation dynamics of primitive haematopoietic compartments and acute myeloid leukaemia (AML). We observe an unchanging proportion of AML cells entering S phase per hour throughout disease progression, with substantial BM egress at high levels of infiltration. For healthy haematopoiesis, we find haematopoietic stem cells (HSCs) make a significant contribution to cell production, but we phenotypically identify a quiescent subpopulation with enhanced engraftment ability. During AML progression, we observe that multipotent progenitors maintain a constant proportion entering S phase per hour, despite a dramatic decrease in the overall population size. Primitive populations are lost from BM with kinetics that are consistent with ousting irrespective of cell cycle state, with the exception of the quiescent HSC subpopulation, which is more resistant to elimination. How leukaemia cells invade the bone marrow by outcompeting haematopoietic cells is still unclear. Here, the authors used detailed cell number measurements in conjunction with a dual pulse labelling method to determine proliferation rates and followed the in vivo dynamics of AML disease progression.

We used data collected from a field survey of 334 supervisor–subordinate dyads to test a model of the antecedents of abusive supervision. Path analytic tests of moderated mediation provided support for our prediction that supervisors' depression mediates the relationship between supervisors' procedural justice and subordinates' perceptions of their supervisors' abusiveness and that the mediation framework is stronger when subordinates are higher in negative affectivity. We discuss the study's implications for theory, research, and practice.

In the presence of antigen and costimulation, T cells undergo a characteristic response of expansion, cessation and contraction. Previous studies have revealed that population-level reproducibility is a consequence of multiple clones exhibiting considerable disparity in burst size, highlighting the requirement for single-cell information in understanding T-cell fate regulation. Here we show that individual T-cell clones resulting from controlled stimulation in vitro are strongly lineage imprinted with highly correlated expansion fates. Progeny from clonal families cease dividing in the same or adjacent generations, with inter-clonal variation producing burst-size diversity. The effects of costimulatory signals on individual clones sum together with stochastic independence; therefore, the net effect across multiple clones produces consistent, but heterogeneous population responses. These data demonstrate that substantial clonal heterogeneity arises through differences in experience of clonal progenitors, either through stochastic antigen interaction or by differences in initial receptor sensitivities. Why do populations of highly similar T cells have heterogeneous division destinies in response to antigenic stimulus? Here the authors develop a multiplex-dye assay and a mathematical framework to test clonal heterogeneity and show distinction in division destiny is a result of inter-clonal variability as lineage imprinting ensures clones share similar proliferation fates.

The bed nucleus of the stria terminalis (BNST) is a brain region important for regulating anxiety-related behavior in both humans and rodents. Here we used a chemogenetic strategy to investigate how engagement of G protein-coupled receptor (GPCR) signaling cascades in genetically defined GABAergic BNST neurons modulates anxiety-related behavior and downstream circuit function. We saw that stimulation of vesicular γ-aminobutyric acid (GABA) transporter (VGAT)-expressing BNST neurons using hM3Dq, but neither hM4Di nor rM3Ds designer receptors exclusively activated by a designer drug (DREADD), promotes anxiety-like behavior. Further, we identified that activation of hM3Dq receptors in BNST VGAT neurons can induce a long-term depression-like state of glutamatergic synaptic transmission, indicating DREADD-induced changes in synaptic plasticity. Further, we used DREADD-assisted metabolic mapping to profile brain-wide network activity following activation of Gq -mediated signaling in BNST VGAT neurons and saw increased activity within ventral midbrain structures, including the ventral tegmental area and hindbrain structures such as the locus coeruleus and parabrachial nucleus. These results highlight that Gq -mediated signaling in BNST VGAT neurons can drive downstream network activity that correlates with anxiety-like behavior and points to the importance of identifying endogenous GPCRs within genetically defined cell populations. We next used a microfluidics approach to profile the receptorome of single BNST VGAT neurons. This approach yielded multiple Gq -coupled receptors that are associated with anxiety-like behavior and several potential novel candidates for regulation of anxiety-like behavior. From this, we identified that stimulation of the Gq -coupled receptor 5-HT2C R in the BNST is sufficient to elevate anxiety-like behavior in an acoustic startle task. Together, these results provide a novel profile of receptors within genetically defined BNST VGAT neurons that may serve as therapeutic targets for regulating anxiety states and provide a blueprint for examining how G-protein-mediated signaling in a genetically defined cell type can be used to assess behavior and brain-wide circuit function.

Despite the identification of Aβ plaques and NFTs as biomarkers for Alzheimer’s disease (AD) pathology, therapeutic interventions remain elusive, with neither an absolute prophylactic nor a curative medication available to impede the progression of AD presently available. Current approaches focus on symptomatic treatments to maintain AD patients’ mental stability and behavioral symptoms by decreasing neuronal degeneration; however, the complexity of AD pathology requires a wide range of therapeutic approaches for both preventive and curative treatments. In this regard, this review summarizes the role of receptors as a potential target for treating AD and focuses on the path of major receptors which are responsible for AD progression. This review gives an overall idea centering on major receptors, their agonist and antagonist and future prospects of viral mimicry in AD pathology. This article aims to provide researchers and developers a comprehensive idea about the different receptors involved in AD pathogenesis that may lead to finding a new therapeutic strategy to treat AD.

Feeding habits of ringed (Phoca hispida), bearded (Erignathus barbatus), spotted (Phoca largha) and ribbon (Phoca fasciata) seals and walrus (Odobenus rosmarus) were studied using stomach contents and stable carbon and nitrogen isotopes. Bearded seals fed benthically, primarily crustaceans and mollusks. Both zooplankton and fish were significant prey for ringed seals, while fish was principal spotted seal prey. Few gastric contents were available from ribbon seals. δ^sup 15^N was positively correlated with age in ribbon seals and δ^sup 13^C was positively correlated with age in ringed and ribbon seals. δ^sup 15^N was highest in spotted seals, in agreement with their fish-dominated diet. δ^sup 15^N was not different between Alaskan-harvested ringed and bearded seals, while δ^sup 15^N was lowest in ribbon seals and walrus. Carbon-13 was most enriched in bearded seals and walrus reflecting benthic ecosystem use. Canadian ringed seals were depleted in ^sup 13^C compared to Alaskan pinnipeds, likely because of Beaufort Sea versus Chukchi and Bering seas influence.[PUBLICATION ABSTRACT]

Resume fraud is pervasive and has detrimental consequences, but researchers lack a way to study it. We develop and validate a measure for empirically investigating resume misrepresentations purposely designed to mislead recruiters. In study 1, an initial set of items designed to measure three theorized resume fraud dimensions (fabrication, embellishment, omission) are rated for content validity. In study 2, job seekers complete the measure and its factor structure is evaluated. In study 3, another sample of job seekers is surveyed to verify the measure’s factor structure and to provide evidence regarding construct validity. In study 4, working adults who recently conducted a job search are surveyed to determine which individuals are more likely to commit resume fraud and whether resume fraud relates to critical work behaviors. We confirm the three-factor structure of our measure and offer evidence of construct validity by showing that socially desirable responding, Machiavellianism, moral identity, conscientiousness, emotional stability, and agreeableness are related to resume fraud. Additionally, we find that resume fraud predicts reduced job performance and increased workplace deviance beyond deceptive interviewing behavior. Resume fraud is rarely studied despite the negative impact it can have on job-related outcomes. Researchers can use this measure to explore further the antecedents and outcomes of resume fraud and to advise recruiters on how to minimize it. We develop a measure focusing on intentional resume misrepresentations designed to deceive recruiters. This is one of the first studies to examine the antecedents and outcomes of resume fraud.

Because thousands of pharmaceutical and industrial compounds are in use today and distributed into ecosystems via waste water, effective analysis of environmental risk needs to change as our understanding of the complexity of ecosystem services grows. Klaminder et al (2014 Environ. Res. Lett. 9 084003) now provide some important observations on a methodological bias in standardized ecotoxicological tests. First, the authors show that the formalized use of control species in risk assessment impacts how data is judged and valued. Reducing quantitative uncertainty may improve the rigor of toxicological assays, but may also increase the risk of missing likely ecosystem-scale impacts, essentially 'throwing the baby out with the bathwater'. Second, we should recognize the importance of integrating nature, complexity, and dynamics across temporal and spatial scales in relation to the unintended consequences of pharmaceuticals and their partial degradation products in the environment. Since ecosystems and our broader life support system are composed of various stability states with dynamic cycles, feedback can destabilize a system as we know it. Complex systems have emergent properties with high degrees of uncertainty and ecosystem risk assessments must report not only toxicological risks but also 'benefits'. In addition, risk assessment must expand its scale from the molecular and cellular to that of the ecosystem with real world conditions. The authors' findings that exposure to Oxazepam led to increased survival and aggressiveness should inform changes in standardized testing methodology as well as improvements in regulatory policy.