POLYCHLORINATED BIPHENYL LIGANDS OF THE ARYL HYDROCARBON RECEPTOR PROMOTE ADIPOCYTE-MEDIATED DIABETES

Numerous epidemiology studies suggest a correlation between exposures to polychlorinated biphenyls (PCBs) and the development and severity of type 2 diabetes (T2D); however, mechanisms remain largely unknown. Previous studies demonstrated that PCBs that are ligands of the aryl hydrocarbon receptor (AhR) promote the expression of proinflammatory cytokines, including tumor necrosis factor-α (TNF-α), that are linked to insulin resistance in adipocytes. To explore potential mechanisms linking PCB exposures to diabetes, we developed a mouse model of glucose and insulin intolerance induced by acute and chronic exposures to PCB-77. We hypothesized that PCB ligands of AhR result in adipocyte-specific elevations in TNF-α and dysregulated glucose homeostasis. Results demonstrated that PCB77 resulted in rapid and sustained glucose and insulin intolerance in low fat (LF)-fed mice, and that these effects were associated with adipose-specific elevations in TNF-α. When mice were made obese from consumption of a high fat (HF) diet, effects of PCB77 were lost presumably due to concentration of the toxin in adipose lipids. However, upon weight loss, mice exposed to PCB77 exhibit impaired glucose homeostasis. These results suggest that lipophilic PCBs redistribute from adipose lipids with weight loss and mitigate beneficial effects to improve glucose homeostasis. To define the role of adipocyte AhR in PCB-induced diabetes, we created a mouse 3 model of adipocyte AhR deficiency using the Cre/LoxP system. Adipocyte-AhR deficiency conferred protection from the development of PCB-77-induced impairments in glucose and insulin tolerance in obese mice undergoing weight loss. Unexpectedly, adipocyte-AhR deficient mice fed the HF diet exhibited adipocyte hypertrophy, increased adipose mass and elevated body weight. These results suggest that (1) adipocyte AhRs are responsible for effects of PCB77 to impair glucose homeostasis during weight loss and (2) adipocyte AhRs respond to the HF diet to regulate adipose mass and body weight. We used resveratrol as a putative AhR antagonist to determine if the polyphenol confers protection against PCB-77-induced diabetes. Resveratrol abolished acute effects of PCB77 to impair glucose and insulin tolerance in LF-fed mice. Notably, PCB77 administration abolished insulin-induced phosphorylation of Akt in adipose tissue and these effects were abolished by resveratrol. Resveratrol also abolished marked suppressions in glucose uptake in adipocytes exposed to PCB77. These studies suggest the adipocyte AhR plays a potentially significant role in the development of diabetes and obesity, and that resveratrol may represent a novel therapeutic for PCB exposed populations

Mitigation of the LHC Inverse Problem

The LHC inverse problem refers to the difficulties in determining the parameters of an underlying theory from data (to be) taken by the LHC experiments: if they find signals of new physics, and an underlying theory is assumed, could its parameters be determined uniquely, or do different parameter choices give indistinguishable experimental signatures? This inverse problem was studied before for a supersymmetric Standard Model with 15 free parameters. This earlier study found 283 indistinguishable pairs of parameter choices, called degenerate pairs, even if backgrounds are ignored. We can resolve all but 23 of those pairs by constructing a true \chi^2 distribution using mostly counting observables. The elimination of systematic errors would even allow separating the residual degeneracies. Taking the Standard Model background into account we still can resolve 237 of the 283 "degenerate" pairs. This indicates that (some of) our observables should also be useful for the purpose of determining the values of SUSY parameters.Comment: 32 pages, 13 figures, typo in (3.6) corrected, version to appear in Phys. Rev.

Vol. 39, No. 2

Bargaining in the Time of Covid: How Collective Bargaining Impacts Schools and Their Mitigation Strategies By Nicki Bazer Fighting for the Living By Stephen A. Yokich Recent Developments By the Student Editorial Board: Bradley Kupiec, Carrie Kumiega, Damia Marshall, Sara Rashhttps://scholarship.kentlaw.iit.edu/iperr/1126/thumbnail.jp

Detection and Relative Distribution of Ringtails (Bassaricus astutus) in Zion National Park, Utah

Very little is known about ringtails (Bassariscus astutus) in Zion National Park), including their distribution within park boundaries. We combined trail cameras and a novel track plate method to determine the occupancy and distribution of ringtails in Zion National Park, in southwestern Utah. Both methods successfully detected ringtails in various habitats sampled

A diverse array of genetic factors contribute to the pathogenesis of Systemic Lupus Erythematosus

Systemic lupus erythematosus (SLE) is a chronic systemic autoimmune disease with variable clinical presentation frequently affecting the skin, joints, haemopoietic system, kidneys, lungs and central nervous system. It can be life threatening when major organs are involved. The full pathological and genetic mechanisms of this complex disease are yet to be elucidated; although roles have been described for environmental triggers such as sunlight, drugs and chemicals, and infectious agents. Cellular processes such as inefficient clearing of apoptotic DNA fragments and generation of autoantibodies have been implicated in disease progression. A diverse array of disease-associated genes and microRNA regulatory molecules that are dysregulated through polymorphism and copy number variation have also been identified; and an effect of ethnicity on susceptibility has been described.http://dx.doi.org/10.1186/1750-1172-8-2IS

Linking genes to diseases: it's all in the data

Genome-wide association analyses on large patient cohorts are generating large sets of candidate disease genes. This is coupled with the availability of ever-increasing genomic databases and a rapidly expanding repository of biomedical literature. Computational approaches to disease-gene association attempt to harness these data sources to identify the most likely disease gene candidates for further empirical analysis by translational researchers, resulting in efficient identification of genes of diagnostic, prognostic and therapeutic value. Existing computational methods analyze gene structure and sequence, functional annotation of candidate genes, characteristics of known disease genes, gene regulatory networks, protein-protein interactions, data from animal models and disease phenotype. To date, a few studies have successfully applied computational analysis of clinical phenotype data for specific diseases and shown genetic associations. In the near future, computational strategies will be facilitated by improved integration of clinical and computational research, and by increased availability of clinical phenotype data in a format accessible to computational approaches

Web-based counseling for problem gambling: exploring motivations and recommendations

Background:For highly stigmatized disorders, such as problem gambling, Web-based counseling has the potential to&nbsp;address common barriers to treatment, including issues of shame and stigma. Despite the exponential&nbsp;growth in the uptake of immediate synchronous Web-based counseling (ie, provided without&nbsp;appointment), little is known about why people choose this service over other modes of treatment.Objective:The aim of the current study was to determine motivations for choosing and recommending Web-based&nbsp;counseling over telephone or face-to-face services.Methods:The study involved 233 Australian participants who had completed an online counseling session for&nbsp;problem gambling on the Gambling Help Online website between November 2010 and February 2012.&nbsp;Participants were all classified as problem gamblers, with a greater proportion of males (57.4%) and&nbsp;60.4% younger than 40 years of age. Participants completed open-ended questions about their reasons&nbsp;for choosing online counseling over other modes (ie, face-to-face and telephone), as well as reasons for&nbsp;recommending the service to others.Results:A content analysis revealed 4 themes related to confidentiality/anonymity (reported by 27.0%),&nbsp;convenience/accessibility (50.9%), service system access (34.2%), and a preference for the therapeutic&nbsp;medium (26.6%). Few participants reported helpful professional support as a reason for accessing&nbsp;counseling online, but 43.2% of participants stated that this was a reason for recommending the service.Those older than 40 years were more likely than younger people in the sample to use Web-based&nbsp;counseling as an entry point into the service system (&lt;italic&gt;P&lt;/italic&gt;=.045), whereas those engaged in&nbsp;nonstrategic gambling (eg, machine gambling) were more likely to access online counseling as an entry&nbsp;into the service system than those engaged in strategic gambling (ie, cards, sports;&nbsp;&lt;italic&gt;P&lt;/italic&gt;=.01). Participants older than 40 years were more likely to recommend the service&nbsp;because of its potential for confidentiality and anonymity (&lt;italic&gt;P&lt;/italic&gt;=.04), whereas those&nbsp;younger than 40 years were more likely to recommend the service due to it being helpful&nbsp;(&lt;italic&gt;P&lt;/italic&gt;=.02).Conclusions:This study provides important information about why online counseling for gambling is attractive to&nbsp;people with problem gambling, thereby informing the development of targeted online programs,&nbsp;campaigns, and promotional material.</div

Improving gambling survey research using dual-frame sampling of landline and mobile phone numbers

Gambling prevalence studies are typically conducted within a single (landline)&nbsp;telephone sampling frame. This practice continues, despite emerging evidence that significant&nbsp;differences exist between landline and mobile (cell) phone only households. This study&nbsp;utilised a dual-frame (landline and mobile) telephone sampling methodology to cast light on&nbsp;the extent of differences across groups of respondents in respect to demographic, health, and&nbsp;gambling characteristics. A total of 2,014 participants from across Australian states and&nbsp;territories ranging in age from 18 to 96 years participated. Interviews were conducted using&nbsp;computer assisted telephone interviewing technology where 1,012 respondents from the&nbsp;landline sampling frame and 1,002 from the mobile phone sampling frame completed a&nbsp;questionnaire about gambling and other health behaviours. Responses across the landline&nbsp;sampling frame, the mobile phone sampling frame, and the subset of the mobile phone&nbsp;sampling frame that possessed a mobile phone only (MPO) were contrasted. The findings&nbsp;revealed that although respondents in the landline sample (62.7 %) did not significantly&nbsp;differ from respondents in the mobile phone sample (59.2 %) in gambling participation in the&nbsp;previous 12 months, they were significantly more likely to have gambled in the previous&nbsp;12 months than the MPO sample (56.4 %). There were no significant differences in internet&nbsp;gambling participation over the previous 12 months in the landline sample (4.7 %), mobile&nbsp;phone sample (4.7 %) and the MPO sample (5.0 %). However, endorsement of lifetime&nbsp;problem gambling on the NODS-CLiP was significantly higher within the mobile sample&nbsp;(10.7 %) and the MPO sample (14.8 %) than the landline sample (6.6 %). Our research&nbsp;supports previous findings that reliance on a traditional landline telephone sampling&nbsp;approach effectively excludes distinct subgroups of the population from being represented inresearch findings. Consequently, we suggest that research best practice necessitates the use&nbsp;of a dual- rame sampling methodology. Despite inherent logistical and cost issues, this&nbsp;approach &nbsp;needs to become the norm in gambling survey research.</span