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Chd5 Manages MuERV-L/MERVL Appearance in Mouse Embryonic Stem Tissues Through H3K27me3 Modification as well as Histone H3.1/H3.Two.
We also highlight that E and M induce a specific maturation of N-glycosylation of S, independently of the regulation of its localization, with a profile that is observed both in infected cells and in purified viral particles. Finally, we show that E, M and N are required for optimal production of virus- like-particles. Altogether, these results highlight how E and M proteins may influence the properties of S proteins and promote the assembly of SARS-CoV-2 viral particles.Cell-extracellular matrix (ECM) detachment is known to down-regulate ERK signalling, an intracellular pathway that is central for control of cell behaviour. How cell-ECM detachment is linked to downregulation of ERK signalling, however, is incompletely understood. We show here that focal adhesion protein Ras Suppressor 1 (RSU1) plays a critical role in cell-ECM detachment induced down-regulation of ERK signalling. We have identified prohibitin 2 (PHB2), a component of membrane lipid rafts, as a novel binding protein of RSU1, and mapped a major RSU1-binding site to PHB2 amino acids 150-206 in the C-terminal region of the PHB/SPFH (stomatin/prohibitin/flotillin/HflKC) domain. The PHB2-binding is mediated by multiple sites located in the N-terminal leucine-rich repeat (LRR) region of RSU-1. Depletion of PHB2 suppressed cell-ECM adhesion induced ERK activation. Furthermore, cell-ECM detachment increased RSU1 association with membrane lipid rafts and interaction with PHB2. Finally, knockout of RSU1 or inhibition of RSU1 interaction with PHB2 by overexpression of the major RSU1-binding PHB2 fragment (amino acids 150-206) effectively suppressed the cell-ECM detachment induced down-regulation of ERK signalling. Expression of venus-tagged wild-type RSU1, but not that of venus-tagged PHB2-binding defective RSU1 mutant in which the N-terminal LRR region is deleted, restored cell-ECM detachment induced down-regulation of ERK signalling. Our results identify a novel RSU1-PHB2 signalling axis that senses cell-ECM detachment and links it to down-regulation of ERK signalling.Poly-N-acetyl-lactosamine (poly-LacNAc) structures are composed of repeating [-Galβ(1,4)-GlcNAcβ(1,3)-]n glycan extensions. They are found on both N- and O--glycoproteins and glycolipids, and play an important role in development, immune function, and human disease. The majority of mammalian poly-LacNAc is synthesized by the alternating iterative action of β1,3-N-acetylglucosaminyltransferase 2 (B3GNT2) and β1,4-galactosyltransferases. B3GNT2 is in the largest mammalian glycosyltransferase family, GT31, but little is known about the structure, substrate recognition, or catalysis by family members. Here we report the structures of human B3GNT2 in complex with UDPMg2+, and in complex with both UDPMg2+ and a glycan acceptor, lacto-N-neotetraose. The B3GNT2 structure conserves the GT-A fold and the DxD motif that coordinates a Mg2+ ion for binding the UDP-GlcNAc sugar donor. NP-12 The acceptor complex shows interactions with only the terminal Galβ(1,4)-GlcNAcβ(1,3)- disaccharide unit, which likely explains the specificity for both N- and O-glycan acceptors. Modeling of the UDP-GlcNAc donor supports a direct displacement inverting catalytic mechanism. Comparative structural analysis indicates that nucleotide sugar donors for GT-A fold glycosyltransferases bind in similar positions and conformations without conserving interacting residues, even for enzymes that use the same donor substrate. In contrast, the B3GNT2 acceptor binding site is consistent with prior models suggesting that the evolution of acceptor specificity involves loops inserted into the stable GT-A fold. These observations support the hypothesis that GT-A fold glycosyltransferases employ co-evolving donor, acceptor, and catalytic subsite modules as templates to achieve the complex diversity of glycan linkages in biological systems.
Among patients with Coronavirus disease 2019 (COVID-19), coronary artery disease (CAD) has been identified as a high-risk condition. We aimed to assess the clinical outcomes and mortality among patients with COVID-19 according to CAD status.

We retrospectively analysed data from patients with COVID-19 admitted to the Cremona Hospital (Lombardy region, Italy) between February and March 2020. The primary outcome was all-cause mortality. CAD was defined as a history of prior myocardial infarction (MI), prior percutaneous coronary intervention (PCI), prior coronary artery bypass grafting (CABG) or CAD that was being medically treated.

Of 1252 consecutive patients with COVID-19, 124 (9.9%) had concomitant CAD. Patients with CAD were older and had a higher prevalence of comorbidities compared with those without CAD. Although patients with CAD had a higher risk of all-cause mortality than patients without CAD (HR 3.01, 95% CI 2.27 to 3.99), this difference was no longer significant in the adjusted model (HR 1.14, 95% CI 0.79 to 1.63). Results were consistent among patients with prior MI (adjusted HR (aHR) 0.87, 95% CI 0.54 to 1.41), prior PCI (aHR 1.10, 95% CI 0.75 to 1.62), prior CABG (aHR 0.91, 95% CI 0.45 to 1.82), or CAD medically treated (aHR 0.84, 95% CI 0.29 to 2.44). Multivariable analysis showed that age (aHR per 5 year increase 1.62, 95% CI 1.53 to 1.72) and female sex (aHR 0.63, 95% CI 0.49 to 0.82) were the only two independent correlates of mortality.

Patients with COVID-19 and CAD have an exceedingly higher risk of mortality, which is mainly attributable to the burden of comorbidities rather than to a direct effect of CAD per se.
Patients with COVID-19 and CAD have an exceedingly higher risk of mortality, which is mainly attributable to the burden of comorbidities rather than to a direct effect of CAD per se.Hox genes instruct positional identity along the anterior-posterior axis of the animal body. A new paper in Development addresses the question of how similar Hox genes can define diverse cell fates, using mouse motor neurons as a model. To hear more about the work, we caught up with the paper's two first authors, PhD students Milica Bulajić and Divyanshi Srivastava, and their respective supervisors Esteban Mazzoni (Associate Professor of Biology at New York University, USA) and Shaun Mahony (Assistant Professor of Biochemistry & Molecular Biology at Penn State University, USA).
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