Lindegaardbloch0636

To estimate the efficacy of urethroplasty and rates of de novo stress urinary incontinence (SUI) in the specific setting of radiation-induced urethral stenosis.

A systematic search of databases (PubMed and EMBASE) was performed between 1980-2019 (CRD42020144845). Inclusion criteria were (1) prior pelvic radiotherapy; (2) surgical urethroplasty; (3) rates of successful treatment and/or SUI development and (4) total case number provided. The pooled summary of stenosis resolution rate and SUI were calculated using the random-effects model weighted by the inverse variance. Accessory analyses were performed by reconstructive technique and type of RT.

Ninety-six studies were identified, of which 8 retrospective studies met inclusion criteria, comprising 256 patients. Selleckchem CID-1067700 The proportion of cases treated with external beam RT (EBRT), brachytherapy (BT), or combination (EBRT+BT) were 52%, 33%, and 15%, respectively, of studies that specified modality. Most strictures involved the bulbomembranous region (n = 212; 83%). Sixty-one percent of cases (n = 157) entailed primary anastomosis, while the remainder underwent augmentation reconstruction (graft or flap). The mean follow-up time after urethroplasty varied from 10 to 50.5 months. The pooled stenosis resolution rate was 80% (95% CI 74%-86%). There were no significant associations between stenosis resolution rate and reconstructive technique (rho=0.20, P = .74) or RT modality (rho=-0.31, P = .53). Fifty-three cases developed subsequent SUI, with a pooled complication rate of 19% (95% CI 10%-31%).

Urethroplasty after radiation-induced urethral stenosis is effective for 80% of cases, independent of prior RT modality or urethroplasty technique; however, 1 out of every 5 patients develops SUI post-procedure.

Urethroplasty after radiation-induced urethral stenosis is effective for 80% of cases, independent of prior RT modality or urethroplasty technique; however, 1 out of every 5 patients develops SUI post-procedure.Cell penetration after recognition of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus by the ACE2 receptor and the fusion of its viral envelope membrane with cellular membranes are the early steps of infectivity. A region of the Spike protein of the virus, identified as the "fusion peptide" (FP), is liberated at its N-terminal site by a specific cleavage occurring in concert with the interaction of the receptor-binding domain of the Spike. Studies have shown that penetration is enhanced by the required binding of Ca2+ ions to the FPs of coronaviruses, but the mechanisms of membrane insertion and destabilization remain unclear. We have predicted the preferred positions of Ca2+ binding to the SARS-CoV-2-FP, the role of Ca2+ ions in mediating peptide-membrane interactions, the preferred mode of insertion of the Ca2+-bound SARS-CoV-2-FP, and consequent effects on the lipid bilayer from extensive atomistic molecular dynamics simulations and trajectory analyses. In a systematic sampling of the interactions of the Ca2+-bound peptide models with lipid membranes, SARS-CoV-2-FP penetrated the bilayer and disrupted its organization only in two modes involving different structural domains. In one, the hydrophobic residues F833/I834 from the middle region of the peptide are inserted. In the other, more prevalent mode, the penetration involves residues L822/F823 from the LLF motif, which is conserved in CoV-2-like viruses, and is achieved by the binding of Ca2+ ions to the D830/D839 and E819/D820 residue pairs. FP penetration is shown to modify the molecular organization in specific areas of the bilayer, and the extent of membrane binding of the SARS-CoV-2 FP is significantly reduced in the absence of Ca2+ ions. These findings provide novel mechanistic insights regarding the role of Ca2+ in mediating SARS-CoV-2 fusion and provide a detailed structural platform to aid the ongoing efforts in rational design of compounds to inhibit SARS-CoV-2 cell entry.During actin-based cell migration, the actin cytoskeleton in the lamellipodium both generates and responds to force, which has functional consequences for the ability of the cell to extend protrusions. However, the material properties of the lamellipodial actin network and its response to stress on the timescale of motility are incompletely understood. Here, we describe a dynamic wrinkling phenotype in the lamellipodium of fish keratocytes, in which the actin sheet buckles upward away from the ventral membrane of the cell, forming a periodic pattern of wrinkles perpendicular to the cell's leading edge. Cells maintain an approximately constant wrinkle wavelength over time despite new wrinkle formation and the lateral movement of wrinkles in the cell frame of reference, suggesting that cells have a preferred or characteristic wrinkle wavelength. Generation of wrinkles is dependent upon myosin contractility, and their wavelength scales directly with the density of the actin network and inversely with cell adhesion. These results are consistent with a simple physical model for wrinkling in an elastic sheet under compression and suggest that the lamellipodial cytoskeleton behaves as an elastic material on the timescale of cell migration despite rapid actin turnover.The plant acyl-acyl carrier protein (ACP) desaturases are a family of soluble enzymes that convert saturated fatty acyl-ACPs into their cis-monounsaturated equivalents in an oxygen-dependent reaction. These enzymes play a key role in biosynthesis of monounsaturated fatty acids in plants. ACPs are central proteins in fatty acid biosynthesis that deliver acyl chains to desaturases. They have been reported to show a varying degree of local dynamics and structural variability depending on the acyl chain size. It has been suggested that substrate-specific changes in ACP structure and dynamics have a crucial impact on the desaturase enzymatic activity. Using molecular dynamics simulations, we investigated the intrinsic solution structure and dynamics of ACP from spinach with four different acyl chains capric (C10), myristic (C14), palmitic (C16), and stearic (C18) acids. We found that the fatty acids can adopt two distinct structural binding motifs, which feature different binding free energies and influence the ACP dynamics in a different manner.