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Osteopontin triggers osteogenic distinction through human being nicotine gum ligament tissue by means of calcium presenting domain-ALK-1 interaction.
© 2020 Jumaa et al.Several events during normal development of the mammalian neocortex depend on N-cadherin, including the radial migration of immature projection neurons into the cortical plate. Remarkably, radial migration requires the N-cadherin extracellular domain but not N-cadherin-dependent homophilic cell-cell adhesion, suggesting that other N-cadherin-binding proteins may be involved. We used proximity ligation and affinity purification proteomics to identify N-cadherin-binding proteins. Both screens detected MycBP2 and SPRY-domain protein Fbxo45, two components of an intracellular E3 ubiquitin ligase. Fbxo45 appears to be secreted by a non-classical mechanism, not involving a signal peptide and not requiring endoplasmic reticulum to Golgi transport. Fbxo45 binding requires N-cadherin SPRY motifs that are not involved in cell-cell adhesion. SPRY-mutant N-cadherin does not support radial migration in vivo. Radial migration was similarly inhibited when Fbxo45 expression was suppressed. The results suggest that projection neuron migration requires both Fbxo45 and binding of Fbxo45 or another protein to SPRY motifs in the extracellular domain of N-cadherin. Copyright © 2020 American Society for Microbiology.Upon replication fork arrest, the replication checkpoint kinase Cds1 is stimulated to preserve genome integrity. Robust activation of Cds1 in response to hydroxyurea prevents endonuclease Mus81 from cleaving the stalled replication fork inappropriately. However, we find that the response is different in temperature sensitive mcm4 mutants, affecting a subunit of the MCM replicative helicase. We show that Cds1 inhibition of Mus81 promotes genomic instability and allows mcm4-dg cells to evade cell cycle arrest. Cds1 regulation of Mus81 activity also contributes to formation of replication-stress-induced DNA damage markers RPA and Ku. These results identify a surprising role for Cds1 in driving DNA damage and disrupted chromosomal segregation under certain conditions of replication stress. Copyright © 2020 American Society for Microbiology.Pathological cardiac hypertrophy is driven by neurohormonal activation of specific G protein-coupled receptors (GPCRs) in cardiomyocytes and is accompanied by large-scale changes in cardiomyocyte gene expression. These transcriptional changes require activity of positive transcription elongation factor b (P-TEFb), which is recruited to target genes by the bromodomain protein Brd4 or the Super Elongation Complex (SEC). Here we describe GPCR-specific regulation of these P-TEFb complexes and a novel mechanism for activating Brd4 in primary neonatal rat cardiomyocytes. The SEC was required for the hypertrophic response downstream of either the α1-adrenergic receptor (α1-AR) or the endothelin receptor (ETR). In contrast, Brd4 inhibition selectively impaired the α1-AR response. This was corroborated by the finding that activation of α1-AR, but not ETR, increased Brd4 occupancy at promoters and super enhancers of hypertrophic genes. Transcriptome analysis demonstrated that activation of both receptors initiated similar gene expression programs, but that Brd4 inhibition attenuated hypertrophic genes more robustly following α1-AR activation. Finally, we show that protein kinase A (PKA) is required for α1-AR stimulation of Brd4 chromatin occupancy. The differential role of the Brd4/P-TEFb complex in response to distinct GPCR pathways has potential clinical implications as therapies targeting this complex are currently being explored for heart failure. Copyright © 2020 American Society for Microbiology.Extravasation is the leakage of intravenously administered solution into surrounding tissues, which can cause serious damage to the patient. The impact of extravasation is mostly determined by the localisation and volume of extravasation, but the physicochemical properties of the drugs are also important. In this paper a stepwise approach to managing an extravasation is described, with recommendations on the role of the pharmacist. Information on osmolality, pH, pKa and the buffering capacity of drugs is given in relation to extravasation, which is summarised in a practical crash card that can be used in clinical practice. © European Association of Hospital Pharmacists 2020. No commercial re-use. See rights and permissions. Published by BMJ.IMPORTANCE With the surge in COVID-19 cases worldwide, the medical community should be aware of atypical clinical presentations to help with correct diagnosis, to take the proper measures to place the patient in isolation and to avoid healthcare professionals being infected by coronavirus (SARS-CoV-2). OBJECTIVE To report that patients who subsequently test positive for COVID-19 may present with acute abdominal pain and no pulmonary symptoms, although they already have typical lung lesions on computed tomography (CT) scan. DESIGN, SETTING AND PARTICIPANTS This case series is about three patients who presented to the emergency department of a community hospital in Montpellier, France, with acute abdominal pain. RESULTS The three patients had an elevated C-reactive protein level. CT scans demonstrated no abdominal anomaly, but bilateral lung lesions at the lung bases, typical of COVID-19 lesions, were observed. COVID-19 RT-PCR tests were positive for the three patients.The patients were transferred to the COVID-19 centre for disease control at Montpellier University Hospital. As of 29 March 2020, two of those patients are still intubated in the intensive care unit (ICU) and the third was discharged home. CONCLUSION AND RELEVANCE COVID-19 infections may present as an acute abdominal pain. In our case series, CT scan findings helped us to suspect the correct diagnosis, which was subsequently confirmed with COVID-19 RT-PCR tests. selleck chemicals © Royal College of Physicians 2020. All rights reserved.The coronavirus disease of 2019 (COVID-19) pandemic has placed many healthcare systems, including the NHS, under unprecedented pressure. Mortality appears to be highest among older people and those with comorbidities, who are also often the most at risk of undernutrition in society. Despite international efforts to identify a specific treatment, therapy remains supportive and is principally focused on optimising respiratory function. However, the timely identification and correction of undernutrition also have the potential to improve outcomes cost-effectively, and should not be forgotten. This piece outlines why nutritional status may be particularly compromised during this crisis, among both the population and hospital inpatients. Practical steps to improve nutritional status at a time when hospital services are particularly stretched are also considered. Finally, the case is made for behaviour change at all levels including government, the general population and healthcare professionals. © Royal College of Physicians 2020.
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