H2AZ is a widely conserved histone variant that is implicated in protecting euchromatin from the spread of heterochromatin. H2AZ is incorporated into nucleosomes as a heterodimer with H2B, by the SWR1 ATP-dependent chromatin-remodeling complex. We have identified a homolog of H2AZ in the protozoan parasite Trypanosoma brucei, along with a novel variant of histone H2B (H2BV) that shares ∼38% sequence identity with major H2B. Both H2AZ and H2BV are essential for viability. H2AZ localizes within the nucleus in a pattern that is distinct from canonical H2A and is largely absent from sites of transcription visualized by incorporation of 5-bromo-UTP (BrUTP). H2AZ and H2BV colocalize throughout the cell cycle and exhibit nearly identical genomic distribution patterns, as assessed by chromatin immunoprecipitation. H2AZ co-immunoprecipitates with H2BV but not with histones H2B or H2A nor with the variant H3V. These data strongly suggest that H2AZ and H2BV function together within a single nucleosome, marking the first time an H2AZ has been shown to associate with a non-canonical histone H2B.

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Zusammenfassung Ziel der Studie Der Artikel beschreibt Evaluationsergebnisse eines Modellprojekts zur Unterstützung psychisch belasteter Geflüchteter durch geschulte Laien. Ziel der Evaluation war eine Beurteilung hinsichtlich Notwendigkeit, Nützlichkeit und Effektivität des Projekts. Methodik Es wurden involvierte und außenstehende Akteure mittels validierter sowie selbst entworfener Instrumente befragt und die Ergebnisse durch statistische Datenanalyse ausgewertet. Bei den Stichproben handelte es sich um 197 in Sammelunterkünften lebende Geflüchtete, 18 im Projekt arbeitende Laienhelfer (LH) sowie 16 Sozialarbeiter und Verwalter aus zwölf Flüchtlingsunterkünften. Ergebnisse Mehr als die Hälfte der befragten Geflüchteten gaben eine psychisch auffällige Belastung an. Die Laienhilfe, die primär aus individualisierten Einzelangeboten bestand, wurde von den Geflüchteten positiv bewertet. 58,5 % der Klienten der LH wurden in die Regelversorgung weitervermittelt. Schulung, Koordination und Supervision wurden von den LH als gut bewertet. Im Projektverlauf änderte sich die Belastung der LH nicht. Sozialarbeiter und Verwalter der Flüchtlingsunterkünfte sahen die Arbeit der LH als hilfreich an. Schlussfolgerung Das Konzept des Modellprojekts erweist sich als notwendig und sinnvoll. Psychisch belastete Geflüchtete profitieren von dem niedrigschwelligen Angebot in den Flüchtlingsunterkünften, und die LH leisten eine wertvolle muttersprachliche Hilfestellung. Gute Schulung, Koordination und Supervision als Rahmenbedingungen ermöglichen den erfolgreichen Einsatz von Laien zur effektiven Unterstützung von psychisch belasteten Geflüchteten.

Despite compelling evidence that victimization and offending co-occur, it remains unclear what types of victimization are linked to specific forms of perpetration. Here we examined the relationship between physical, psychological, and sexual violence with respect to influencing variables including mental health, risk-taking behaviors, and coping strategies. Data from 5385 men were collected as part of an epidemiological study on violence experience. A classification and regression tree analysis identified the main predictors of violence perpetration and classified violent offending into high-and low-risk groups.Results indicate that violence is best predicted by previous exposure to violence and polyvictimization. Physical violence is best predicted by prior exposure to physical violence and this is further influenced by the frequency of and the age at which violence was experienced. Drug use was a strong predictor of physical and psychological violence. The latter is best predicted by a history of polyvictimization, the severity and the originator of violence. Sexual violence is strongly predicted by one's sexual violence experience. Other factors such as demographic characteristics are less predictive. Our results may contribute to the development of early prevention and intervention approaches that account for different risk factors. The significance of violence exposure suggest that intervention measures must focus on victims of early and prolonged experience of violence. On the strength of the link between drug use and violence, exposure to violence should be considered in drug prevention and intervention and vice versa. K E Y W O R D S classification and regression tree analysis, exposure to violence, perpetration, polyvictimization, risk factors, violent offending This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

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Blastocyst-derived stem cell lines were shown to self-organize into embryo-like structures in 3D cell culture environments. Here, we provide evidence that embryo-like structures can be generated solely based on transcription factor-mediated reprogramming of embryonic stem cells in a simple 3D co-culture system. Embryonic stem cells in these cultures self-organize into elongated, compartmentalized embryo-like structures reflecting aspects of the inner regions of the early post-implantation embryo. Single-cell RNA-sequencing reveals transcriptional profiles resembling epiblast, primitive-/visceral endoderm, and extraembryonic ectoderm of early murine embryos around E4.5–E5.5. In this stem cell-based embryo model, progression from rosette formation to lumenogenesis accompanied by progression from naïve- to primed pluripotency was observed within Epi-like cells. Additionally, lineage specification of primordial germ cells and distal/anterior visceral endoderm-like cells was observed in epiblast- or visceral endoderm-like compartments, respectively. The system presented in this study allows for fast and reproducible generation of embryo-like structures, providing an additional tool to study aspects of early embryogenesis.

Activating mutations in the human KIT receptor is known to drive severe hematopoietic disorders and tumor formation spanning various entities. The most common mutation is the substitution of aspartic acid at position 816 to valine (D816V), rendering the receptor constitutively active independent of ligand binding. As the role of the KIT receptor in placental signaling cascades is poorly understood, we analyzed the impact of KITD816V expression on placental development using a humanized mouse model. Placentas from KITD816V animals present with a grossly changed morphology, displaying a reduction in labyrinth and spongiotrophoblast layer and an increase in the Parietal Trophoblast Giant Cell (P-TGC) layer. Elevated differentiation to P-TGCs was accompanied with reduced differentiation to other Trophoblast Giant Cell (TGC) subtypes and by severe decrease in proliferation. The embryos display growth retardation and die in utero. KITD816V-trophoblast stem cells (TSC) differentiate much faster compared to wild type (WT) controls. In undifferentiated KITD816V-TSCs, levels of Phosphorylated Extracellular-signal Regulated Kinase (P-ERK) and Phosphorylated Protein Kinase B (P-AKT) are comparable to wildtype cultures differentiating for 3–6 days. Accordingly, P-TGC markers Placental Lactogen 1 (PL1) and Proliferin (PLF) are upregulated as well. The results reveal that KIT signaling orchestrates the fine-tuned differentiation of the placenta, with special emphasis on P-TGC differentiation. Appropriate control of KIT receptor action is therefore essential for placental development and nourishment of the embryo.

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