Healywestergaard1123

suggesting a more limited role for bacterial methionine metabolism genes in host lifespan effects. In a parallel set of experiments we created a distinct bacterial strain that expressed lifespan-extending methionine metabolism genes and show that this strain can extend fly lifespan. Therefore, this work identifies specific bacterial genes that influence host lifespan, including in ways that are consistent with the expectations of methionine restriction. Copyright © 2020 American Society for Microbiology.Enterotoxigenic Escherichia coli (ETEC) strains producing K88 (F4) or F18 fimbriae and enterotoxins are the predominant cause of pig post-weaning diarrhea (PWD). We recently identified neutralizing epitopes of fimbriae K88 and F18, heat-labile toxin (LT), heat-stable toxin type I (STa) and type II (STb), and Shiga toxin 2e (Stx2e). In this study, we explored novel epitope- and structure-based vaccinology platform multiepitope-fusion-antigen (MEFA) for PWD vaccine development. By using an epitope-substitution LT toxoid, which lacks enterotoxicity, but retains immunogenicity, as the backbone to present neutralizing epitopes of two ETEC fimbriae and four toxins, we generated PWD fimbria-toxin MEFA to mimic epitope native antigenicity. We then examined MEFA protein immunogenicity and evaluated MEFA application in PWD vaccine development. Mice subcutaneously immunized with PWD MEFA protein developed strong IgG responses to K88, F18, LT and STb and moderate responses to toxins Stx2e and STa. Importantly, MEFA-induc this fimbria-toxin MEFA in PWD vaccine development and further supporting the general application of this novel MEFA vaccinology platform for multivalent vaccine development. Copyright © 2020 American Society for Microbiology.Vibralactone, a hybrid compound derived from phenols and a prenyl group, is a strong pancreatic lipase inhibitor with a rare fused bicyclic β-lactone skeleton. Recently, researcher reported a vibralactone derivative (compound C1) that caused inhibition of pancreatic lipase with a half-maximal inhibitory concentration of 14 nM determined by structure-based optimization, suggesting a potential candidate as a new anti-obesity treatment. Etrumadenant solubility dmso In the present study, we sought to identify the main gene encoding prenyltransferase in Stereum vibrans, which is responsible for the prenylation of phenol leading to vibralactone synthesis. Two RNA silencing transformants of identified gene (vib-PT) were obtained through Agrobacterium tumefaciens-mediated transformation. Compared to wild-type strains, the transformants showed a decrease in vib-PT expression ranging from 11.0% to 56.0% at 5, 10, and 15 days in reverse transcription-quantitative PCR (RT-qPCR) analysis and along with a reduction in primary vibralactone production oin a basidiomycetes species that is responsible for the synthesis of vibralactone. The identified gene, vib-PT, was expressed in E. coli to obtain a soluble and enzymatically active fusion Vib-PT protein. In vitro characterization of the enzyme demonstrated the catalytic mechanism of prenylation and broad substrate range for different aromatic acceptors and prenyl donors. These characteristics highlight the possibility of Vib-PT to generate prenylated derivatives of aromatics and other compounds as improved bioactive agents or potential prodrugs. Copyright © 2020 American Society for Microbiology.BACKGROUND AND OBJECTIVES Cancer survival is improving along with an increase in the potential for adverse kidney effects from antineoplastic treatments or nephrectomy. We sought to describe recent trends in the incidence of kidney failure related to antineoplastic treatments and urinary tract cancers and evaluate patient survival and kidney transplantation access. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS We used the French Renal Epidemiology and Information Network registry to identify patients with kidney failure related to antineoplastic treatments or urinary tract cancer from 2003 to 2015. We identified 287 and 1157 cases with nephrotoxin- and urinary tract cancer-related kidney failure, respectively. The main study outcomes were death and kidney transplantation. After matching cases to two to ten controls (n=11,678) with other kidney failure causes for age, sex, year of dialysis initiation, and diabetes status, we estimated subdistribution hazard ratios (SHR) of each outcome separately for patients ffer significantly between cases and controls. CONCLUSIONS Cancer-related kidney failure is slowly but steadily increasing. Mortality does not appear to be increased among patients without active malignancy at dialysis start, but their access to kidney transplant remains limited. Copyright © 2020 by the American Society of Nephrology.BACKGROUND AND OBJECTIVES Walking while talking is a dual cognitive-motor task that predicts frailty, falls, and cognitive decline in the general elderly population. Adults with CKD have gait abnormalities during usual walking. It is unknown whether they have greater gait abnormalities and cognitive-motor interference during walking while talking. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS Community-dwelling, nondisabled adults (n=330) ≥65 years of age underwent quantitative gait analysis, including walking while talking. Differences in walking while talking performance by CKD status were evaluated, and relative changes between walking while talking and walking alone performance were computed to quantify cognitive-motor interference (dual-task cost). Associations were tested using multivariable linear spline regression models, and independent gait domains were derived using factor analysis. CKD was defined as an eGFR less then 60 ml/min per 1.73 m2. RESULTS CKD was present in 134 (41%) participants. Particr 1.73 m2 lower eGFR was associated with a poorer performance of 0.2 SD (95% confidence interval, 0.1 to 0.3) for walking while talking and 0.2 SD (95% confidence interval, 0.03 to 0.3) for dual-task cost. CONCLUSIONS During walking while talking, CKD is associated with gait abnormalities, possibly due to increased cognitive-motor interference. Copyright © 2020 by the American Society of Nephrology.