A Grounded Theory Model of Relationship Decision-Making in Non-Offending Partners of Individuals Accused of Sexual Offending

Non-offending partners of individuals who have committed sexual offenses often choose to end their relationship given the many negative consequences they face as a result of their partner’s offending behavior. Despite a focus on relationships in rehabilitation frameworks and the importance of the relationship for the individual who has offended and their partner, research has thus far failed to examine the process underlying why non-offending partners decide to stay in or leave their relationship following an offense. In this study we developed the first descriptive model of relationship decision-making in non-offending partners. Twenty-three individuals whose current or previous partners were accused of sexual offending were interviewed about affective, behavioral, cognitive, and contextual factors contributing to their decision to stay with or leave their partner. Participants’ narrative accounts were analyzed using Grounded Theory. Our resulting model consists of four main periods: (1) background factors, (2) relationship factors, (3) finding out, and (4) relationship decision-making. Clinical implications, limitations, and directions for future research are discussed

Die Fußball-Weltmeisterschaft 1978 in Argentinien

Nach der Klärung des Begriffes "sportswashing" und einer Einführung in die Zeitgeschichte Argentiniens wendet sich Kamitz auf der Grundlage zeitgenössischer Pressemedien der schichtenübergreifend emotionalisierenden und nationale Identität stiftenden Wirkung des WM-Turniergeschehens im Jahr 1978 zu. Auf dieser Grundlage erläutert und analysiert er die von einer US-amerikanischen Marketingagentur unterstützte politische Instrumentalisierung der WM durch die Militärdiktatur Videla. Kamitz verdeutlicht und belegt die systemstabilisierende Wirkung des "sportswashings" und analysiert in diesem Kontext die unkritische Haltung des DFB und seiner Repräsentanten, aber auch der damaligen sozial-liberalen bundesdeutschen Koalitionsregierung gegenüber dem argentinischen Unrechtssystem. Erst seit den 2000er Jahren erfolgte ein öffentlich wirksamer Bewusstseinswandel mit Blick auf die sportpolitische Instrumentalisierung der Fußball-WM 1978 in Argentinien auf Seiten des DSB/DOSB

Identification of four mouse diabetes candidate genes altering β-cell proliferation.

Beta-cell apoptosis and failure to induce beta-cell regeneration are hallmarks of type 2-like diabetes in mouse models. Here we show that islets from obese, diabetes-susceptible New Zealand Obese (NZO) mice, in contrast to diabetes-resistant C57BL/6J (B6)-ob/ob mice, do not proliferate in response to an in-vivo glucose challenge but lose their beta-cells. Genome-wide RNAseq based transcriptomics indicated an induction of 22 cell cycle-associated genes in B6-ob/ob islets that did not respond in NZO islets. Of all genes differentially expressed in islets of the two strains, seven mapped to the diabesity QTL Nob3, and were hypomorphic in either NZO (Lefty1, Apoa2, Pcp4l1, Mndal, Slamf7, Pydc3) or B6 (Ifi202b). Adenoviral overexpression of Lefty1, Apoa2, and Pcp4l1 in primary islet cells increased proliferation, whereas overexpression of Ifi202b suppressed it. We conclude that the identified genes in synergy with obesity and insulin resistance participate in adaptive islet hyperplasia and prevention from severe diabetes in B6-ob/ob mice

Identification of two novel candidate genes for insulin secretion by comparative genomics of multiple backcross populations

To identify novel disease genes for type 2 diabetes (T2D) we generated two backcross populations of obese and diabetes-susceptible New Zealand Obese (NZO/HI) mice with the two lean mouse strains 129P2/OlaHsd and C3HeB/FeJ. Subsequent whole-genome linkage scans revealed 30 novel quantitative trait loci (QTL) for T2D-associated traits. The strongest association with blood glucose [12 cM, logarithm of the odds (LOD) 13.3] and plasma insulin (17 cM, LOD 4.8) was detected on proximal chromosome 7 (designated Nbg7p, NZO blood glucose on proximal chromosome 7) exclusively in the NZOxC3H crossbreeding, suggesting that the causal gene is contributed by the C3H genome. Introgression of the critical C3H fragment into the genetic NZO background by generating recombinant congenic strains and metabolic phenotyping validated the phenotype. For the detection of candidate genes in the critical region (30-46 Mb), we used a combined approach of haplotype and gene expression analysis to search for C3H-specific gene variants in the pancreatic islets, which appeared to be the most likely target tissue for the QTL. Two genes, Atp4a and Pop4, fulfilled the criteria from our candidate gene approaches. The knockdown of both genes in MIN6 cells led to decreased glucose-stimulated insulin secretion, indicating a regulatory role of both genes in insulin secretion, thereby possibly contributing to the phenotype linked to Nbg7p In conclusion, our combined- and comparative-cross analysis approach has successfully led to the identification of two novel diabetes susceptibility candidate genes, and thus has been proven to be a valuable tool for the discovery of novel disease genes

A collective diabetes cross in combination with a computational framework to dissect the genetics of human obesity and Type 2 diabetes.

© The Author(s) 2018. To explore the genetic determinants of obesity and Type 2 diabetes (T2D), the German Center for Diabetes Research (DZD) conducted crossbreedings of the obese and diabetes-prone New Zealand Obese mouse strain with four different lean strains (B6, DBA, C3H, 129P2) that vary in their susceptibility to develop T2D. Genome-wide linkage analyses localized more than 290 quantitative trait loci (QTL) for obesity, 190 QTL for diabetes-related traits and 100 QTL for plasma metabolites in the outcross populations. A computational framework was developed that allowed to refine critical regions and to nominate a small number of candidate genes by integrating reciprocal haplotype mapping and transcriptome data. The efficiency of the complex procedure was demonstrated for one obesity QTL. The genomic interval of 35 Mb with 502 annotated candidate genes was narrowed down to six candidates. Accordingly, congenic mice retained the obesity phenotype owing to an interval that contains three of the six candidate genes. Among these the phospholipase PLA2G4A exhibited an elevated expression in adipose tissue of obese human subjects and is therefore a critical regulator of the obesity locus. Together, our broad and complex approach demonstrates that combined- and comparative-cross analysis exhibits improved mapping resolution and represents a valid tool for the identification of disease genes

Immunity-related GTPase induces lipophagy to prevent excess hepatic lipid accumulation.

BACKGROUND & AIMS: Currently, only a few genetic variants explain the heritability of fatty liver disease. Quantitative trait loci (QTL) analysis of mouse strains has identified the susceptibility locus Ltg/NZO (liver triglycerides from New Zealand obese [NZO] alleles) on chromosome 18 as associating with increased hepatic triglycerides. Herein, we aimed to identify genomic variants responsible for this association.; METHODS: Recombinant congenic mice carrying 5.3 Mbp of Ltg/NZO were fed a high-fat diet and characterized for liver fat. Bioinformatic analysis, mRNA profiles and electrophoretic mobility shift assays were performed to identify genes responsible for the Ltg/NZO phenotype. Candidate genes were manipulated invivo by injecting specific microRNAs into C57BL/6 mice. Pulldown coupled with mass spectrometry-based proteomics and immunoprecipitation were performed to identify interaction partners of IFGGA2.; RESULTS: Through positional cloning, we identified 2 immunity-related GTPases (Ifgga2, Ifgga4) that prevent hepatic lipid storage. Expression of both murine genes and the human orthologue IRGM was significantly lower in fatty livers. Accordingly, liver-specific suppression of either Ifgga2 or Ifgga4 led to a 3-4-fold greater increase in hepatic fat content. In the liver of low-fat diet-fed mice, IFGGA2 localized to endosomes/lysosomes, while on a high-fat diet it associated with lipid droplets. Pulldown experiments and proteomics identified the lipase ATGL as a binding partner of IFGGA2 which was confirmed by co-immunoprecipitation. Both proteins partially co-localized with the autophagic marker LC3B. Ifgga2 suppression in hepatocytes reduced the amount of LC3B-II, whereas overexpression of Ifgga2 increased the association of LC3B with lipid droplets and decreased triglyceride storage.; CONCLUSION: IFGGA2 interacts with ATGL and protects against hepatic steatosis, most likely by enhancing the binding of LC3B to lipid droplets.; LAY SUMMARY: The genetic basis of non-alcoholic fatty liver disease remains incompletely defined. Herein, we identified members of the immunity-related GTPase family in mice and humans that act as regulators of hepatic fat accumulation, with links to autophagy. Overexpression of the gene Ifgga2 was shown to reduce hepatic lipid storage and could be a therapeutic target for the treatment of fatty liver disease. Copyright © 2020 European Association for the Study of the Liver. All rights reserved