The β3-integrin endothelial adhesome regulates microtubule-dependent cell migration

Integrin β3 is seen as a key anti-angiogenic target for cancer treatment due to its expression on neovasculature, but the role it plays in the process is complex; whether it is pro- or anti-angiogenic depends on the context in which it is expressed. To understand precisely β3's role in regulating integrin adhesion complexes in endothelial cells, we characterised, by mass spectrometry, the β3-dependent adhesome. We show that depletion of β3-integrin in this cell type leads to changes in microtubule behaviour that control cell migration. β3-integrin regulates microtubule stability in endothelial cells through Rcc2/Anxa2-driven control of active Rac1 localisation. Our findings reveal that angiogenic processes, both in vitro and in vivo, are more sensitive to microtubule targeting agents when β3-integrin levels are reduced

ADAMTS19-associated heart valve defects: Novel genetic variants consolidating a recognizable cardiac phenotype

Recently, ADAMTS19 was identified as a novel causative gene for autosomal recessive heart valve disease (HVD), affecting mainly the aortic and pulmonary valves. Exome sequencing and data repository (CentoMD) analyses were performed to identify patients with ADAMTS19 variants (two families). A third family was recognized based on cardiac phenotypic similarities and SNP array homozygosity. Three novel loss of function (LoF) variants were identified in six patients from three families. Clinically, all patients presented anomalies of the aortic/pulmonary valves, which included thickening of valve leaflets, stenosis and insufficiency. Three patients had (recurrent) subaortic membrane, suggesting that ADAMTS19 is the first gene identified related to discrete subaortic stenosis. One case presented a bi-commissural pulmonary valve. All patients displayed some degree of atrioventricular valve insufficiency. Other cardiac anomalies included atrial/ventricular septal defects, persistent ductus arteriosus, and mild dilated ascending aorta. Our findings confirm that biallelic LoF variants in ADAMTS19 are causative of a specific and recognizable cardiac phenotype. We recommend considering ADAMTS19 genetic testing in all patients with multiple semilunar valve abnormalities, particularly in the presence of subaortic membrane. ADAMTS19 screening in patients with semilunar valve abnormalities is needed to estimate the frequency of the HVD related phenotype, which might be not so rare

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

New regularity criteria for the 3D hall-MHD equations

We prove some regularity criteria for smooth solutions of the three-dimensional incompressible Hall-magnetohydrodynamic equations involving only two components of the velocity and magnetic fields. © Instytut Matematyczny PAN, 2018

A regularity criterion of weak solutions to the 3D Boussinesq equations

In this note, a regularity criterion of weak solutions to the 3D-Boussinesq equations with respect to Serrin type condition under the framework of Besov space : B-infinity(r),(infinity). It is shown that the weak solution (u; theta) is regular on (0; T] if u satisfies integral(T)(0) parallel to u(center dot, t)parallel to(2/1+r)r(B infinity,infinity) dt < infinity, for 0 < r < 1. This result improves some previous works

On the Blow-Up Criterion for Incompressible Stokes–MHD Equations

Our aim is to establish a blow-up criterion for the local strong solutions in terms of the gradient of the magnetic field only in BMO spaces. © 2018, Springer Nature Switzerland AG

Beale-kato-majda’s criterion for magneto-hydrodynamic equations with zero viscosity

This paper is concerned with studying the blow-up criterion of smooth solutions to the three dimensional magneto-hydrodynamic equations with zero viscosity. We prove that the smooth solution may be extended by standard energy method, provided the norm of the gradient of velocity in a space much bigger than Ḃ0∞,∞. The result obtained in this manuscript improves the former corresponding result. © 2020, Institute of Mathematics. All rights reserved

A regularity criterion of smooth solution for the 3D viscous Hall-MHD equations

In this work, we investigate the regularity criterion for the solution of the Hall-MHD system in three-dimensions. It is proved that if the pressure pi and the gradient of magnetic field del B satisfies some kind of space-time integrable condition on [0, T], then the corresponding solution keeps smoothness up to time T. This result improves some previous works to the Morrey space M-2,M- 3/r for 0 <= r < 1 which is larger than L-3/r

A regularity criterion for local strong solutions to the 3D stokes-mhd equations

We prove a regularity criterion for local strong solutions of the Stokes-MHD equations in terms of the velocity field in Besov space Ḃ0 ∞,∞. © Instytut Matematyczny PAN, 2020

On the Blow-Up Criterion for Incompressible Stokes–MHD Equations

Our aim is to establish a blow-up criterion for the local strong solutions in terms of the gradient of the magnetic field only in BMO spaces. © 2018, Springer Nature Switzerland AG