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Genomic structural variations (SVs) promote the evolution of Saccharomyces cerevisiae, and play an important role in phenotypic diversities. Yeast genomic structures can be remodeled by design and bottom-up synthesis. The synthesis of yeast genome creates novel copy number variations (CNVs) and SVs and develops new strategies to discover gene functions. Further, an inducible evolution system SCRaMbLE, consisted of 3,932 loxPsym sites, was incorporated on synthetic yeast genome. SCRaMbLE enables genomic rearrangements at will and rapidly generates chromosomal number variations, and massive SVs under customized conditions. The impacts of genetic variations on phenotypes can be revealed by genome analysis and chromosome restructuring. Yeast genome synthesis and SCRaMbLE provide a new research paradigm to explore the genotypic mechanisms of phenotype diversities, and can be used to improve biological traits and optimize industrial chassis. © FEMS 2020.The clostridial fermentation caused by the outgrowth of Clostridia was mainly responsible for the silage anaerobic deterioration. Our previous results showed that Clostridium perfringens dominated the clostridial community in poor-fermented alfalfa silage. This study was conducted to further examine the role of C. perfringens in silage anaerobic deterioration through fermentation products and the microbial community analyses. Direct-cut alfalfa was ensiled with C. perfringens contamination (CKC) or with the addition of Lactobacillus plantarum, sucrose, and C. perfringens (LSC). Contamination with C. perfringens enhanced the clostridial fermentation in CKC silage, as indicated by high contents of butyric acid, ammonia nitrogen and Clostridia, while LSC silage was well preserved. The genera Bifidobacterium, Garciella and Clostridium dominated the bacterial community in CKC silage, while predominate genus was replaced by Lactobacillus in LSC silage. The clostridial community in CKC silage was dominated by Garciella sp. read more (26.9% to 58.1%) and C. tyrobutyricum (24.4% to 48.6%), while the relative abundance of C. perfringens was below 5.0%. Therefore, the effect of Clostridia contamination on ensiling fermentation was dependent on the ensilability of the silage material. Garciella sp. and C. tyrobutyricum, rather than C. perfringens, played dominant role in the clostridial fermentation in CKC silage. © FEMS 2020.INTRODUCTION Most descriptions of tobacco withdrawal have not changed in >30 years despite new research. This meta-analysis tested whether abstinence leads to decreased positive affect (PA) because abstinence-induced symptom changes are a core feature of the tobacco withdrawal syndrome. In addition, we examined whether reduced PA was due to withdrawal (ie, temporary decrease in a "U-shaped" curve) or offset (ie, return to baseline) effect. METHODS Our main inclusion criterion was a prospective within-participant test of change in PA during abstinence conditions among people who smoke cigarettes daily who were not using a cessation medication. Our search of PubMed, PsycINFO, and personal libraries yielded a total of 32 tests with 2054 participants. RESULTS There was a medium effect size indicating an overall decrease in PA following abstinence from cigarettes (Cohen's d = -0.40, 95% CI = -0.30 to -0.49). There was large heterogeneity (I2 = 70.7%). Most (79%) of the 24 trials that conducted significance tests rrch on Nicotine and Tobacco. All rights reserved.For permissions, please e-mail journals.permissions@oup.com.Polyphenols derived from a variety of plants have demonstrated antimicrobial activity against diverse microbial pathogens. link2 Legionella pneumophila is an intracellular bacterial pathogen that opportunistically causes a severe inflammatory pneumonia in humans, called Legionnaires' Disease, via replication within macrophages. Previous studies demonstrated that tea polyphenols attenuate L. pneumophila intracellular replication within mouse macrophages via increased tumor necrosis factor (TNF) production. Sorghum bicolor is a sustainable cereal crop that thrives in arid environments and is well-suited to continued production in warming climates. Sorghum polyphenols have anticancer and antioxidant properties, but their antimicrobial activity has not been evaluated. Here, we investigated the impact of sorghum polyphenols on L. pneumophila intracellular replication within RAW 264.7 mouse macrophages. Sorghum high-polyphenol extract (HPE) attenuated L. pneumophila intracellular replication in a dose-dependent manner but did not impair either bacterial replication in rich media or macrophage viability. Moreover, HPE treatment enhanced both TNF and IL-6 secretion from L. pneumophila infected macrophages. Thus, polyphenols derived from sorghum enhance macrophage restriction of L. pneumophila, likely via increased pro-inflammatory cytokine production. This work reveals commonalities between plant polyphenol-mediated antimicrobial activity and provides a foundation for future evaluation of sorghum as an antimicrobial agent. © FEMS 2020.West Nile virus (family Flaviviridae, genus Flavivirus) first caused human and veterinary disease, and was isolated from Culex pipiens pipiens L. and Aedes vexans (Meigen) (Diptera Culicidae) in the United States in 1999. We report that a Connecticut strain of Ae. vexans was competent to transmit West Nile virus both horizontally to suckling mice and vertically to its progeny in the laboratory. Horizontal transmission was first observed on day 6 post-exposure (pe). Daily horizontal transmission rates generally increased with the day post-virus exposure with highest rates of 67-100% recorded on days 28-30 pe. One female vertically transmitted West Nile virus on day 21 pe, but only after it had taken its third bloodmeal. Horizontal and vertical transmission may contribute to West Nile virus infection rates in Ae. vexans in summer, and vertical transmission provides a means of survival of West Nile virus during winter. © The Author(s) 2020. Published by Oxford University Press on behalf of Entomological Society of America.All rights reserved. For permissions, please e-mail journals.permissions@oup.com.BACKGROUND There are limited data on immune restoration of young adults living with virologically suppressed human immunodeficiency virus (HIV). We investigated recovery rates of CD4/CD8 ratio among Thai children and adolescents after they initiated combination antiretroviral therapy (cART). METHODS Children and adolescents who started cART at age of ≥ 5 years were eligible in this study if they achieved HIV RNA  less then  50 copies/mL and had a CD4/CD8 ratio  less then  0.8 at the time of virological suppression. Normalization of CD4/CD8 ratio was defined as 2 consecutive values ≥ 1. Using group-based trajectory analysis, low- and high-recovery groups were identified in terms of CD4/CD8 ratio recovery. RESULTS One hundred thirty-eight children and adolescents (101 perinatally infected and 37 behaviorally infected) with median age of 10.6 years at cART treatment initiation were included. After 559 person-years of follow-up (PYFU), overall incidence rate of CD4/CD8 ratio normalization was 4.1 (95% confidence missions@oup.com.BACKGROUND A landmark legal judgment in March 2015 (Montgomery) changed the test for determining negligence due to failing to inform patients before consent, by moving away from asking what a reasonable doctor should disclose and asking instead what a reasonable patient would expect to know. AIM We sought to determine the effect Montgomery has had on settled claims due to failure to inform compared with claims for other reasons and whether legal firms are adding contributory claims of failure to inform to other principal allegations of negligence. METHODS A Freedom of Information request to NHS Resolution provided data on the number of settled claims against the NHS (2005-19) for any cause and where failure to inform before consent was the principal or contributory cause. Time-series regression was used to compare trends before and after 31 March 2015. RESULTS The trend in claims/year increased 4-fold for failure to inform (an increase of 9.8/year before 2015 vs. 39.5/year after 2015, P  less then  0.01), 2.7-fold when failure to inform was the principal cause (7.9/year vs. 21.2/year, P = 0.02) and 9.9-fold as a contributory cause (1.9/year vs. 18.3/year, P  less then  0.01). There was no material difference in claims due to other causes (334/year vs. 318/year, P = 0.84). CONCLUSIONS Montgomery has led to a substantial increase in settled claims of failure to inform before consent, with no coincident change in claims for other causes. The increase in contributory compared with principal causes suggests that lawyers are using the judgment to increase the chances of a successful claim against the NHS. © The Author(s) 2020. link3 Published by Oxford University Press on behalf of the Association of Physicians. All rights reserved. For permissions, please email journals.permissions@oup.com.Nitrogen (N) fixing soybean plants use the ureides allantoin and allantoic acid as major long-distance transport forms of N, but in non-fixing, non-nodulated plants amino acids mainly serve in source-to-sink N allocation. However, some ureides are still synthesized in roots of non-fixing soybean and our study addresses the role of ureide transport processes in those plants. In previous work, legume ureide permeases (UPS) were identified that are involved in cellular import of allantoin and allantoic acid. Here, UPS1 from common bean was expressed in the soybean phloem, which resulted in enhanced source-to-sink transport of ureides in the transgenic plants. This was accompanied by increased ureide synthesis and elevated allantoin and allantoic acid root-to-sink transport. Interestingly, amino acid assimilation, xylem transport and phloem partitioning to sinks were also strongly upregulated. In addition, photosynthesis and sucrose phloem transport were improved in the transgenic plants. These combined changes in source physiology and assimilate partitioning resulted in increased vegetative growth and improved seed numbers. Overall, the results support that ureide transport processes in non-fixing plants affect source N and carbon acquisition and assimilation as well as source-to-sink translocation of N and carbon assimilates with consequences for plant growth and seed development. © The Author(s) 2020. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email journals.permissions@oup.com.BACKGROUND LATITUDE was a randomized, double-blind, international and phase 3 study of abiraterone acetate plus prednisone in patients with high-risk metastatic hormone-naïve prostate cancer. In the first interim analysis of LATITUDE (clinical cutoff date 31 October 2016), significant prolongation in overall survival and radiographic progression-free survival (co-primary endpoints) was observed when compared with placebo. The results of the Japanese subgroup analysis of LATITUDE first interim analysis were consistent with those of the overall population. In this study, overall survival and safety results from the final analysis of the Japanese subgroup of the LATITUDE study are presented (clinical cutoff date 15 August 2018). METHODS Abiraterone acetate (1000 mg/day) and prednisone (5 mg/day) were administered orally in the abiraterone acetate plus prednisone group, and matching placebos in the placebo group. RESULTS Of the 1199 patients included in LATITUDE, 70 constituted the Japanese subgroup (abiraterone acetate plus prednisone n = 35, placebo n = 35).

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