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Thiohemiacetals are key intermediates in the active sites of many enzymes catalyzing a variety of reactions. In the case of Pseudomonas mevalonii3-hydroxy-3-methylglutaryl coenzyme A reductase (PmHMGR), this intermediate connects the two hydride transfer steps where a thiohemiacetal is the product of the first hydride transfer and its breakdown forms the substrate of the second one, serving as the intermediate during cofactor exchange. Despite the many examples of thiohemiacetals in a variety of enzymatic reactions, there are few studies that detail their reactivity. Here, we present computational studies on the decomposition of the thiohemiacetal intermediate in PmHMGR using both QM-cluster and QM/MM models. This reaction mechanism involves a proton transfer from the substrate hydroxyl to an anionic Glu83 followed by a C–S bond elongation stabilized by a cationic His381. The reaction provides insight into the varying roles of the residues in the active site that favor this multistep mechanism.

This paper includes different analytical methods available for the estimation of the Perindopril Erbumine. Perindopril Erbumine is an Angiotensin-Converting Enzyme (ACE) inhibitor used to treat hypertension and heart failure. The drug is officially listed in the monograph of USP, BP & EP. This drug is available in various marketed formulations. There are so many methods reported for the estimation of Perindopril Erbumine and its related substances. Various methods including UVspectroscopic method, stability-indicating liquid chromatography method, Thermo-Radio, and Photostability study, Stability indicating UHPLC-DAD method, LC-MS/MS electrospray ionization validated method, and LC-MS/MS bioanalytical method are discussed in this paper.

The relationship between historical climate change and past agricultural production contributes to a better understanding of the impacts of projected climate change by providing empirical data for resilient human responses. This study explores the periods of dynastic transitions and crop production at the urban site of Vadnagar, in semi-arid northwest India through several climate events, generally characterised by weakening summer monsoon precipitation during the Late Holocene. Artefacts from the site present an unbroken sequence of seven successive cultures from the first century BCE to the nineteenth century CE. Archaeobotanical data indicate the sufficient water availability during the Historic and Medieval periods, allowing crop production dominated large-grained cereals (C3plants). However, during the Post-Medieval period (ca.1300−1850 CE) a resilient crop economy based on small-grained cereals (C4plants) dominated, representing a human adaptation to prolonged weakening of monsoonal precipitation. Isotopic and phytolith data at the site present a clear signal of changing local environmental conditions over two millennia, consistent with regional palaeoclimate records, providing and interpretive context for agricultural evidence at Vadnagar. Despite long-term reduction in summer humidity, we argue that an adaptable agricultural package coupled with suitable water management systems allowed for the resilience of the urban settlement at Vadnagar.

ABSTRACTThe number of emergency department (ED) visits within 30 days after elective surgery has been utilized as a quality measure by many institutions. The significance of the measure as a postoperative complication in foot and ankle surgery, and risk factors for it, are unknown. We conducted a retrospective cohort study involving 386 patients to determine risk factors associated with ED visits after outpatient foot and ankle surgeries. After adjusting for clinically relevant covariates, we found that previous ED visits within 6 months of surgery, and nonelective surgeries were associated with the postoperative ED visit. Having private insurance was protective against postoperative ED visits. Though these risk factors may not be easily modifiable by surgeons, understanding them may improve patient education and transitional care to prevent overcrowding of the ED.

The left-right organizer in zebrafish embryos, Kupffer's Vesicle (KV), is a simple organ that undergoes programmed asymmetric cell shape changes that are necessary to establish the left-right axis of the embryo. We use simulations and experiments to investigate whether 3D mechanical drag forces generated by the posteriorly-directed motion of the KV through the tailbud tissue are sufficient to drive such shape changes. We develop a fully 3D vertex-like (Voronoi) model for the tissue architecture, and demonstrate that the tissue can generate drag forces and drive cell shape changes. Furthermore, we find that tailbud tissue presents a shear-thinning, viscoelastic behavior consistent with those observed in published experiments. We then perform live imaging experiments and particle image velocimetry analysis to quantify the precise tissue velocity gradients around KV as a function of developmental time. We observe robust velocity gradients around the KV, indicating that mechanical drag forces must be exerted on the KV by the tailbud tissue. We demonstrate that experimentally observed velocity fields are consistent with the viscoelastic response seen in simulations. This work also suggests that 3D viscoelastic drag forces could be a generic mechanism for cell shape change in other biological processes.