Matzen Hester (personvan20)

Consistent with poor oocyte quality, the majority of Chtf18-/- oocytes fail to progress to metaphase II following meiotic resumption and a significant percentage of those that do progress are aneuploid. Collectively, our findings indicate critical functions for CHTF18 in ensuring both the quantity and quality of the mammalian oocyte pool. © The Author(s) 2020. Published by Oxford University Press on behalf of Society for the Study of Reproduction.BACKGROUND Sequence-binning techniques enable the recovery of an increasing number of genomes from complex microbial metagenomes and typically require prior metagenome assembly, incurring the computational cost and drawbacks of the latter, e.g., biases against low-abundance genomes and inability to conveniently assemble multi-terabyte datasets. RESULTS We present here a scalable pre-assembly binning scheme (i.e., operating on unassembled short reads) enabling latent genome recovery by leveraging sparse dictionary learning and elastic-net regularization, and its use to recover hundreds of metagenome-assembled genomes, including very low-abundance genomes, from a joint analysis of microbiomes from the LifeLines DEEP population cohort (n = 1,135, >1010 reads). CONCLUSION We showed that sparse coding techniques can be leveraged to carry out read-level binning at large scale and that, despite lower genome reconstruction yields compared to assembly-based approaches, bin-first strategies can complement the more widely used assembly-first protocols by targeting distinct genome segregation profiles. Read enrichment levels across 6 orders of magnitude in relative abundance were observed, indicating that the method has the power to recover genomes consistently segregating at low levels. © The Author(s) 2020. Published by Oxford University Press.Senescence and mitochondrial stress are mutually reinforcing age-related processes that contribute to idiopathic pulmonary fibrosis (IPF); a lethal disease that manifests primarily in the elderly.  Whilst evidence is accumulating that GMP-AMP synthase (cGAS) is crucial in perpetuating senescence by binding damaged DNA released into the cytosol, its role in IPF is not known.  This study examines the contributions of cGAS and self DNA to the senescence of lung fibroblasts from IPF patients (IPF-LFs) and healthy controls (Ctrl-LFs).  cGAS immunoreactivity was observed in regions of fibrosis associated with fibroblasts in lung tissue of IPF patients. Pharmacological inhibition of cGAS or its knockdown by silencing RNA (siRNA) diminished the escalation of IPF-LF senescence in culture over 7 days as measured by decreased p21 expression, histone 2AXγ phosphorylation and/or IL-6 production (P less then 0.05, n=5-8).  The targeting of cGAS also attenuated etoposide-induced senescence in Ctrl-LFs (P less then 0.05, n=5-8).  Levels of mitochondrial DNA (mDNA) detected by qPCR in the cytosol and medium of IPF-LFs or senescence-induced Ctrl-LFs were higher than Ctrl-LFs at baseline (P less then 0.05, n=5-7).  The addition of DNAse I (100 U/mL) deaccelerated IPF-LF senescence (P less then 0.05, n=5), whereas ectopic mDNA or the induction of endogenous mDNA release augmented Ctrl-LF senescence in a cGAS-dependent manner (P less then 0.05, n=5). In conclusion, we provide evidence that cGAS reinforces lung fibroblast senescence involving damaged self DNA.  The targeting of cGAS to supress senescent-like responses may have potential important therapeutic implications in the treatment of IPF. Copyright 2020 The Author(s).The molecular mechanisms governing the secretion of the non-coding genome are poorly understood. We show herein that cyclin D1, the regulatory subunit of the cyclin-dependent kinase that drives cell-cycle progression, governs the secretion and relative proportion of secreted non-coding RNA subtypes (miRNA, rRNA, tRNA, CDBox, scRNA, HAcaBox. scaRNA, piRNA) in human breast cancer. Cyclin D1 induced the secretion of