Synthetic Chain Terminators Off‐Load Intermediates from a Type I Polyketide Synthase

Modular biocatalysis is responsible for the generation of countless bioactive products and its mining remains a major focus for drug discovery purposes. One of the enduring hurdles is the isolation of biosynthetic intermediates in a readily‐analysed form. We prepared a series of nonhydrolysable pantetheine and N‐acetyl cysteamine mimics of the natural (methyl)malonyl extender units recruited for polyketide formation. Using these analogues as competitive substrates, we were able to trap and off‐load diketide and triketide species directly from an in vitro reconstituted type I polyketide synthase, the 6‐deoxyerythronolide B synthase 3 (DEBS3). The putative intermediates, which were extracted in organic solvent and characterised by LC‐HR‐ESI‐MS, are the first of their kind and prove that small‐molecule chain terminators can be used as convenient probes of the biosynthetic process.     

Emphasis on Validation in Research: A Meta-Analysis

The emphasis of validity as a publication content was investigated in dissertations and journal articles. The time of first publication, longitudinal publication profile, ratio of articles to dissertations, and time lag between dissertations and articles emphasizing validity were compared within and among various fields. A three-decade gap separated the first field adopting validity-related contents in its dissertations from the latest fields that did so. The longitudinal data suggested three groups of fields (Agricultural Sciences, Applied Sciences and Social Sciences) which showed consistent differences among groups and consistent similarities within groups in their emphasis on validity-related content. Adoption of validity-related content in dissertations always preceded adoption of validity-related content in journal articles. On average, less than 4% of journal articles included validity-related content across fields. These findings support the hypothesis that validity has been introduced and disseminated within fields following patterns predicted by diffusion of innovations theory. It is argued that this pattern is inconsistent with an efficient and interdisciplinary utilization of available knowledge. Policy recommendations are made for developing strategic communication and education programs for academicians and journal reviewers.     

灯红酒绿中端坐菩萨像:巴黎酒吧即景

受亚洲文化影响所设计的“佛之吧”,在巴黎繁衍出不计其数的效仿者。具有摩洛哥风格的水池形成了一处清凉宁静的景致,与浅橙色的墙壁以及耀眼的金箔柱子形成了强烈对比。两具巨大的印度乐人雕像突出于墙壁位于水池的两侧,而这个水池又能够被覆盖,从而形成一个舞台来进行现场音乐表演。>这个酷似洞穴的酒吧内部处处彰显着受到亚洲影响的细节,从色彩斑斓的曼荼罗图案的天花板到印度乐人的雕塑,以及神色宁静的半身雕像也为两个大软椅增色不少。理念的融会与繁衍是一个自然的过程——比如酒馆从欧洲传入新大陆,又比如“迪斯科舞厅”一词来源于法…     

Study of the Ghrelin/LEAP-2 Ratio in Humans and Rats during Different Phases of Pregnancy

The Liver-Expressed Antimicrobial Peptide 2 (LEAP-2) has emerged as an endogenous GHS-R antagonist and blunts the orexigenic action of ghrelin. This study aimed to determine the Ghrelin/LEAP-2 ratio in humans and rats during pregnancy. In humans, we conducted a nested case-control study within an observational prospective cohort. Healthy and mild preeclamptic pregnant women were studied at each trimester of gestation and three months postpartum. In addition, a group of non-pregnant women was studied into the follicular and luteal phases of the menstrual cycle. Furthermore, Ghrelin/LEAP-2 ratio was investigated in non-pregnant rats and at different periods of rat pregnancy. Human and rat serum ghrelin and LEAP-2 levels were determined using the commercially available ELISA kits. The Ghrelin/LEAP-2 ratio peak around the second trimester of gestation in healthy pregnant women (p < 0.05). Additionally, there were no statistically significant differences in Ghrelin/LEAP-2 ratio between healthy and preeclamptic pregnant women at each trimester of gestation (p > 0.05). The Ghrelin/LEAP-2 ratio in pregnant rat reached the peak around mid-gestation with a similar pattern to the human pregnancy. LEAP-2 was visualized by immunohistochemistry in human term placenta and rat placentas on days 12, 16 and 21 of pregnancy. In conclusion, this study provides the first evidence of a Ghrelin/LEAP-2 ratio peak around the half-way point of pregnancy onwards during human and rat pregnancy, and it might be associated with increased rates of weight gain during pregnancy. Thus, this study suggests that LEAP-2 and Ghrelin/LEAP-2 ratio might play an important role in maternal physiology adaptation of weight gain during pregnancy.     

如何选择电流互感变压器

长期以来，电流互感变压器作为仪器设备中的一种标准器件一直用来测量精密电流。即使在恶劣的环境和高温条件下，这种器件也非常精确，使用方便可靠。     

Petrological and geochemical mass-balance equations: an algorithm for least-square fitting and general error analysis

Least-square fitting of petrological and geochemical overdetermined linear systems is carried out by means of a rapidly converging algorithm which allows a general treatment of coefficient uncertainties. Both constrained and unconstrained solutions are presented. The modal analysis of lunar rock 10022 and stoichiometric coefficients for two coronitic reactions are so determined, as an example, from application of the proposed procedure to available chemical analyses.     

A hand-held, two-channel stimulator-ophthalmoscope

A hand-held optical system for presenting focused stimuli on known retinal areas by direct ophthalmoscopy is described. The optical system provides a time-modulated stimulus beam of variable dimension, retinal illuminance, wave-length, and polarization, and a steady background beam of variable retinal illuminance and wavelength. Both beams enter the patient's eye in maxwellian-view for precise control of the ratio of stimulus to background retinal illuminance. The stimulator-ophthalmoscope allows the examiner to compensate easily for variable fixation.     

Berry antioxidants: small fruits providing large benefits

Small berry fruits are consumed because of their attractive colour and special taste, and are considered one of the richest sources of natural antioxidants. Their consumption has been linked to the prevention of some chronic and degenerative diseases. The term ‘berry fruits’ encompasses the so‐called ‘soft fruits’, primarily strawberry, currants, gooseberry, blackberry, raspberry, blueberry and cranberry. The objective of this review is to highlight the nutraceutical value of berries and to summarize the factors affecting berry fruit antioxidants. Particular attention is given to postharvest and processing operation factors that may affect fruit phytochemical content. The structure–antioxidant relationships for phenolic compounds – the main group of antioxidants in this fruit group – are presented and major areas for future research are identified. © 2013 Society of Chemical Industry     

QuEChERS Method for the Determination of 3‑Alkyl‑2‑Methoxypyrazines in Wines by Gas Chromatography-Mass Spectrometry

A new method for determining 3-isopropyl-2-methoxypyrazine, 3-sec-butyl-2-methoxypyrazine, and 3-isobutyl-2-methoxypyrazine in wines is presented. A modified quick, easy, cheap, effective, rugged, and safe method and gas chromatography-mass spectrometry (GC-MS) were used for sample preparation and compound determination, respectively. The analytes were extracted from wine (30 mL) with 1 mL toluene, in the presence of 12 g anhydrous MgSO₄ and 3 g NaCl. Cleanup of the toluene phase was performed by a miniaturized dispersive solid-phase extraction with a combination of anhydrous CaCl₂ (25 mg), anhydrous MgSO₄ (25 mg), and primary-secondary amine (10 mg), which was effective for minimizing co-extractives and matrix effects. GC-MS parameters were also tuned up to optimize limits of detection between 4.2 and 7.1 ng L^?1. The overall recoveries (trueness) of the method ranged between 71 and 87 % for the white and red wine samples, respectively, spiked at 40 and 100 ng L^?1, with relative standard deviations below 21 %. The method was applied for the determination of target methoxypyrazines in the samples of commercial wines from Argentina.