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Brinch Langballe posted an update 3 months, 2 weeks ago
CONCLUSIONS Nutrition has profound effects on microbial composition, in-turn, affecting wide-ranging metabolic, hormonal, and neurological processes. There is no consensus on what defines a “healthy” gut microbiome. Future research must consider individual responses to diet. Published by Oxford University Press on behalf of the International Life Sciences Institute 2020. This work is written by US Government employees and is in the public domain in the US.PURPOSE To systematically assess the validity of patient-reported outcome measures (PROMs) for patients undergoing inguinal hernia repair. DATA SOURCES A systematic review was performed according to the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) guideline for systematic reviews of PROMs. PubMed, EMBASE and PsycINFO were consulted. STUDY SELECTION Only studies explicitly aimed at validation of PROMs specific for patients with inguinal hernia were included. DATA EXTRACTION Data regarding measurement properties of PROMs were extracted from the included studies. Each study was critically assessed for methodological quality and each PROM was evaluated for sufficient measurement properties. RESULTS OF DATA SYNTHESIS We included 15 studies, covering 11 different PROMs. The Carolinas Comfort Scale was the most frequently investigated PROM, being covered in five of the included publications. The included PROMs were evaluated according to nine different measurement properties, of which internal consistency and construct validity were the most frequently assessed. Evidence regarding content validity and structural validity was universally inadequate, according to the criteria for good measurement properties, as defined by the COSMIN. CONCLUSION Based on the current evidence, it is not possible to formulate recommendations for application of PROMs for patients undergoing inguinal hernia repair. Further validation of the included PROMs is necessary especially regarding content validity and structural validity. © The Author(s) 2020. Published by Oxford University Press in association with the International Society for Quality in Health Care. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.Ataxia-telangiectasia (AT) and MRE11-defective Ataxia-telangiectasia-like disorder (ATLD) patients show progressive cerebellar ataxia. ATM, mutated in AT, can be activated in response to oxidative stress as well as DNA damage, which could be linked to disease-related neurodegeneration. However, the role of MRE11 in oxidative stress responses has been elusive. Here, we showed that MRE11 could participate in ATM activation during oxidative stress in an NBS1/RAD50-independent manner. learn more Importantly, MRE11 was indispensable for ATM activation. We identified FXR1 as a novel MRE11-binding partner by mass spectrometry. We confirmed that FXR1 could bind with MRE11 and showed that both localize to the cytoplasm. Notably, MRE11 and FXR1 partly localize to the mitochondria, which are the major source of cytoplasmic reactive oxygen species (ROS). The contribution of FXR1 to DNA double-strand break damage responses seemed minor and limited to HR repair, considering that depletion of FXR1 perturbed chromatin association of homologous recombination repair factors and sensitized cells to camptothecin. During oxidative stress, depletion of FXR1 by siRNA reduced oxidative stress responses and increased the sensitivity to pyocyanin, a mitochondrial ROS inducer. Collectively, our findings suggest that MRE11 and FXR1 might contribute to cellular defense against mitochondrial ROS as a cytoplasmic complex. © The Author(s) 2020. Published by Oxford University Press on behalf of The Japanese Radiation Research Society and Japanese Society for Radiation Oncology.The Drosophila Y-chromosome is gene poor and mainly consists of silenced, repetitive DNA. Nonetheless, the Y influences expression of hundreds of genes genome-wide, possibly by sequestering key components of the heterochromatin machinery away from other positions in the genome. To test the influence of the Y chromosome on the genome-wide chromatin landscape, we assayed the genomic distribution of histone modifications associated with gene activation (H3K4me3), or heterochromatin (H3K9me2 and H3K9me3) in fruit flies with varying sex chromosome complements (X0, XY and XYY males; XX and XXY females). Consistent with the general deficiency of active chromatin modifications on the Y, we find that Y gene dose has little influence on the genomic distribution of H3K4me3. In contrast, both the presence and the number of Y-chromosomes strongly influence genome-wide enrichment patterns of repressive chromatin modifications. Highly repetitive regions such as the pericentromeres, the dot, and the Y chromosome (if present) are enriched for heterochromatic modifications in wildtype males and females, and even more strongly in X0 flies. In contrast, the additional Y chromosome in XYY males and XXY females diminishes the heterochromatic signal in these normally silenced, repeat-rich regions, which is accompanied by an increase in expression of Y-linked repeats. We find hundreds of genes that are expressed differentially between individuals with aberrant sex chromosome karyotypes, many of which also show sex-biased expression in wildtype Drosophila. Thus, Y-chromosomes influence heterochromatin integrity genome-wide, and differences in the chromatin landscape of males and females may also contribute to sex-biased gene expression and sexual dimorphisms. © The Author(s) 2020. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.Despite its important biological role, the evolution of recombination rates remains relatively poorly characterized. This owes, in part, to the lack of high-quality genomic resources to address this question across diverse species. Humans and our closest evolutionary relatives, anthropoid apes, have remained a major focus of large-scale sequencing efforts, and thus recombination rate variation has been comparatively well-studied in this group – with earlier work revealing a conservation at the broad- but not the fine-scale. However, in order to better understand the nature of this variation, and the time-scales on which substantial modifications occur, it is necessary to take a broader phylogenetic perspective. I here present the first fine-scale genetic map for vervet monkeys based on whole genome population genetic data from ten individuals, and perform a series of comparative analyses with the great apes. The results reveal a number of striking features. Firstly, owing to strong positive correlations with diversity and weak negative correlations with divergence, analyses suggest a dominant role for purifying and background selection in shaping patterns of variation in this species.