Additionally, the TE domains preferentially cyclized polyketides that bore the expected oxidation state at the C-3 position, effectively bypassing non-cognate module directed reduction and altering the predicted catalytic sequence. Extending these findings led to formation of a novel metabolite containing a pyran ring instead of the predicted macrolactone. Collectively, these data provide new insights regarding the PKS TE as an important target for protein engineering to optimize polyketide analog assembly in engineered PKS pathways. © 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.Patients with coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus are at risk for acute kidney injury (AKI). Requirements of kidney replacement therapies (KRT) may be particularly intense for kidney transplant recipients with COVID-19 who develop AKI, due to their chronic use of steroids (1) and theoretically higher viral loads (2) that may lead to a catabolic state (3). Herein, we report the case of a kidney transplant recipient with COVID-19 infection, AKI, and a high catabolic state evidenced by refractory hyperkalemia and azotemia. This article is protected by copyright. All rights reserved.AIMS Red yeast rice (RYR), produced by inoculating Monascus strains to steamed rice, contains many kinds of physiologically bioactive compounds, among which monacolin K can be used as an antihypercholesterolemic agent. However, RYR can be polluted by the mycotoxin citrinin, which has nephrotoxic and hepatotoxic activities. To avoid the risk of citrinin contamination in Monascus fermented products, it is important to screen for Monascus strains that produce no or low citrinin. METHODS AND RESULTS Five autochthonous Monascus strains with high yield monacolin K and undetectable citrinin were obtained by using high performance liquid chromatography (HPLC). All five strains were identified as M. ruber based on Genealogical Concordance Phylogenetic Species Recognition criteria. Polymerase chain reaction (PCR) revealed that citrinin polyketide synthase (pksCT) gene was found in these strains, but transcriptional regulator (ctnA) was not found. CONCLUSIONS Five strains are potential strains for producing high quality RYR. The distribution of the pksCT gene was not restricted to M. purpureus and M. sanguineus, and M. ruber strains were diverse in pksCT and ctnA genes. SIGNIFICANCE AND IMPACT OF THE STUDY The integration of citrinin HPLC analysis and pksCT and ctnA genes amplification could provide a complementary approach in valuable Monascus strains screening. This article is protected by copyright. All rights reserved.Over the last century, Western societies experienced a demographic shift driven by increased lifespan and decreased fertility, resulting in the subversion of the world's demographic pyramid. In ageing societies, cardiovascular diseases are the major cause of morbidity and mortality, thus representing a major societal and economic burden. Indeed, ageing associates with the deterioration of a genetic network implicated in senescence and longevity, orchestrating deleterious cellular processes that converge in the structural and functional decline of both the myocardium and the vasculature. In this review, we revise a compendium of genes involved in these processes and delineate possible strategies to interfere with them. Dietary interventions (e.g. intermittent fasting) and sirtuin-activating compounds are among the most promising interventions shown to promote protective effects on the ageing cardiovascular system. We conclude that ageing and longevity genes modulate cardiovascular function by acting on deleterious downstream processes such as inflammation and oxidative stress, thus representing promising targets for the prevention and treatment of age-related cardiovascular dysfunction. This article is protected by copyright. All rights reserved.BACKGROUND Parkinson's disease (PD) etiology is not well understood.  https://www.selleckchem.com/products/zidesamtinib.html  Reported inverse associations with smoking and coffee consumption prompted the investigation of alcohol consumption as a risk factor, for which evidence is inconclusive. OBJECTIVE To assess the associations between alcohol consumption and PD risk. METHODS Within NeuroEPIC4PD, a prospective European population-based cohort, 694 incident PD cases were ascertained from 209,998 PD-free participants. Average alcohol consumption at different time points was self-reported at recruitment. Cox regression hazard ratios were estimated for alcohol consumption and PD occurrence. RESULTS No associations between baseline or lifetime total alcohol consumption and PD risk were observed. Men with moderate lifetime consumption (5-29.9 g/day) were at ~50% higher risk compared with light consumption (0.1-4.9 g/day), but no linear exposure-response trend was observed. Analyses by beverage type also revealed no associations with PD. CONCLUSION Our data reinforce previous findings from prospective studies showing no association between alcohol consumption and PD risk. © 2020 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society. © 2020 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.BACKGROUND AND OBJECTIVES The purpose of this study was to assess efficacy and safety of a new patterned theta burst stimulation algorithm of DBS with the aim of expanding the therapeutic window and clinical benefit in PD. METHODS In this single-center, randomized, double-blind, clinical short-term trial, unilateral conventional subthalamic DBS was compared with unilateral patterned stimulation algorithms with intraburst high- or low-frequency theta burst stimulation in 17 PD patients. RESULTS There were no serious adverse events with theta burst stimulation. During monopolar review, conventional subthalamic DBS and high-frequency theta burst stimulation were comparable, but low-frequency theta burst stimulation differed by requiring higher stimulation amplitudes for symptom reduction, but a larger therapeutic window. High- and low-frequency theta burst stimulation with adapted stimulation amplitude were effective in PD symptom reduction with differential effects on akinesia and tremor, depending on the theta burst stimulation mode.