Interaction of the oncoprotein transcription factor MYC with its chromatin cofactor WDR5 is essential for tumor maintenance.

The oncoprotein transcription factor MYC is overexpressed in the majority of cancers. Key to its oncogenic activity is the ability of MYC to regulate gene expression patterns that drive and maintain the malignant state. MYC is also considered a validated anticancer target, but efforts to pharmacologically inhibit MYC have failed. The dependence of MYC on cofactors creates opportunities for therapeutic intervention, but for any cofactor this requires structural understanding of how the cofactor interacts with MYC, knowledge of the role it plays in MYC function, and demonstration that disrupting the cofactor interaction will cause existing cancers to regress. One cofactor for which structural information is available is WDR5, which interacts with MYC to facilitate its recruitment to chromatin. To explore whether disruption of the MYC-WDR5 interaction could potentially become a viable anticancer strategy, we developed a Burkitt\u27s lymphoma system that allows replacement of wild-type MYC for mutants that are defective for WDR5 binding or all known nuclear MYC functions. Using this system, we show that WDR5 recruits MYC to chromatin to control the expression of genes linked to biomass accumulation. We further show that disrupting the MYC-WDR5 interaction within the context of an existing cancer promotes rapid and comprehensive tumor regression in vivo. These observations connect WDR5 to a core tumorigenic function of MYC and establish that, if a therapeutic window can be established, MYC-WDR5 inhibitors could be developed as anticancer agents

“I should have …”:A Photovoice Study With Women Who Have Lost a Man to Suicide

While the gendered nature of suicide has received increased research attention, the experiences of women who have lost a man to suicide are poorly understood. Drawing on qualitative photovoice interviews with 29 women who lost a man to suicide, we completed a narrative analysis, focused on describing the ways that women constructed and accounted for their experiences. We found that women’s narratives drew upon feminine ideals of caring for men’s health, which in turn gave rise to feelings of guilt over the man’s suicide. The women resisted holding men responsible for the suicide and tended to blame themselves, especially when they perceived their efforts to support the man as inadequate. Even when women acknowledged their guilt as illogical, they were seemingly unable to entirely escape regret and self-blame. In order to reformulate and avoid reifying feminine ideals synonymous with selflessly caring for others regardless of the costs to their own well-being, women’s postsuicide bereavement support programs  hould integrate a critical gender approach

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

Using 3D Printing To Understand Vertebrate Form and Function

Using 3D Printing To Understand Vertebrate Form and Function

Chemosensory Detection by Black Widow Spiders (Latrodectus Mactans)

Chemosensory Detection by Black Widow Spiders (Latrodectus mactans)

Study of Catalytic Activity of Mutated Aldose Reductase, YDL124w, Employing Steric and Electrostatic Hindrance Within the Active Site

Study of Catalytic Activity of Mutated Aldose Reductase, YDL124w, Employing Steric and Electrostatic Hindrance Within the Active Sit

Using 3D Printing To Understand Vertebrate Form and Function

Using 3D Printing To Understand Vertebrate Form and Function

Patient beliefs and behaviors about genomic risk for type 2 diabetes: Implications for prevention

Copyright © Taylor & Francis Group, LLC 2015.Type 2 diabetes is a major health burden in the United States, and population trends suggest this burden will increase. High interest in, and increased availability of, testing for genetic risk of type 2 diabetes presents a new opportunity for reducing type 2 diabetes risk for many patients; however, to date, there is little evidence that genetic testing positively affects type 2 diabetes prevention. Genetic information may not fit patients illness representations, which may reduce the chances of risk-reducing behavior changes. The present study aimed to examine illness representations in a clinical sample who are at risk for type 2 diabetes and interested in genetic testing. The authors used the Common Sense Model to analyze survey responses of 409 patients with type 2 diabetes risk factors. Patients were interested in genetic testing for type 2 diabetes risk and believed in its importance. Most patients believed that genetic factors are important to developing type 2 diabetes (67%), that diet and exercise are effective in preventing type 2 diabetes (95%), and that lifestyle changes are more effective than drugs (86%). Belief in genetic causality was not related to poorer self-reported health behaviors. These results suggest that patients interest in genetic testing for type 2 diabetes might produce a teachable moment that clinicians can use to counsel behavior change