Solution Structure and Constrained Molecular Dynamics Study of Vitamin B12 Conjugates of the Anorectic Peptide PYY(3–36)

Vitamin B₁₂–peptide conjugates have considerable therapeutic potential through improved pharmacokinetic and/or pharmacodynamic properties imparted on the peptide upon covalent attachment to vitamin B₁₂ (B₁₂). There remains a lack of structural studies investigating the effects of B₁₂ conjugation on peptide secondary structure. Determining the solution structure of a B₁₂–peptide conjugate or conjugates and measuring functions of the conjugate(s) at the target peptide receptor may offer considerable insight concerning the future design of fully optimized conjugates. This methodology is especially useful in tandem with constrained molecular dynamics (MD) studies, such that predictions may be made about conjugates not yet synthesized. Focusing on two B₁₂ conjugates of the anorectic peptide PYY(3–36), one of which was previously demonstrated to have improved food intake reduction compared with PYY(3–36), we performed NMR structural analyses and used the information to conduct MD simulations. The study provides rare structural insight into vitamin B₁₂ conjugates and validates the fact that B₁₂ can be conjugated to a peptide without markedly affecting peptide secondary structure.     

Hyperphagia modifies FA profiles of plasma phospholipids,plasma FFA,and adipose tissue TAG

Hyperphagia was achieved by continuous intracerebroventricular infusion of a melanocortin receptor antagonist (HS024; Neosystem, Strasbourg, France) in rats. The effects of hyperphagia on FA composition and concentration of plasma phospholipids (PL), plasma FFA, and adipose tissue TAG were studied in rats for 8 d [short-term hyperphagia (STH); n=8], or 28 d [longterm hyperphagia (LTH); n=9]. The control rats were treated with artificial cerebrospinal fluid for 8 d (n=8) or 28 d (n=10). The rats were fed the same regular diet. In STH rats the plasma PL and fasting plasma FFA contained higher concentrations of saturated FA (SFA) and monounsaturated FA (MUFA), and plasma FFA contained lower n−6 PUFA than in the control rats. In LTH rats the plasma PL contained higher concentrations of SFA, MUFA, and n−3 PUFA and higher proportions of 16∶1n−7 and 18∶1n−9 at the expense of 18∶2n−6 than in the control rats. In LTH rats the abundant dietary intake of 18∶2n−6 did not enrich 18∶2n−6 of the plasma PL or adipose tissue TAG. In LTH rats the fasting plasma FFA contained more than twofold higher concentrations of SFA and MUFA, and higher proportions of 16∶1n−7 and 18∶1n−9 at the expense of 18∶2n−6 than in the control rats. This animal obesity model shows that LTH affects the FA composition and concentration of plasma PL, plasma FFA, and adipose tissue TAG, a result consistent with changes associated with increased risk of various diseases in humans. These results also demonstrate that LTH alters the FA composition of plasma PL and adipose tissue TAG in a way that does not reflect the FA composition of dietary fat.     

Do landscape factors affect brownfield carabid assemblages?

The carabid fauna of 28 derelict sites in the West Midlands (England) were sampled over the course of one growing season (April-October, 1999). The study aimed to investigate the relationship between carabid assemblages and five measures of landscape structure pertinent to derelict habitat. At each site measurements of landscape features pertinent to derelict habitat were made: (i) the proximity of habitat corridors; (ii) the density of surrounding derelict land; (iii) the distance between the site and the rural fringe; and (iv) the size of the site. Concurrent surveys of the soil characteristics, vegetation type, and land use history were conducted. The data were analysed using a combination of ordination (DCA, RDA), variance partitioning (using pRDA) and binary linear regression. The results suggest that: 1. There is very little evidence that the carabid assemblages of derelict sites were affected by landscape structure, with assemblages instead being principally related to within-site habitat variables, such as site age (since last disturbance), substrate type and vegetation community. 2. No evidence was found to support the hypothesis that sites away from railway corridors are impoverished in their carabid fauna than sites on corridors. 3. There are some suggestions from this study that rarer and non-flying specialist species may be affected by isolation, taking longer to reach sites. We infer from this that older sites with retarded succession, and sites in higher densities of surrounding derelict land may eventually become more species rich and that these sites may be important for maintaining populations of rarer and flightless species. 4. Conservation efforts to maintain populations of these species should focus principally on habitat quality issues, such as maintaining early successional habitats that have a diversity of seed producing annuals and perennial plants and enhancing substrate variability rather than landscape issues.     

一种新颖的双桥矩阵变换器控制策略

矩阵变换器是一种AC/AC变换器,它具有正弦输入电流、正弦输出电压、能量双向流动及体积小的优点,但存在着控制方法复杂,开关器件和保护元器件太多的问题.近年来提出的双桥矩阵变换器具有矩阵变换器的优点,同时其控制方法更简单,所用开关元件数目更少.论述了双桥矩阵变换器的原理,讨论了变换器的PWM控制策略以及基于线电压符号的换流方法,提出了整流级、逆变级单独控制,整流级开关频率为10kHz、逆变级开关频率为2kHz的新颖双桥矩阵变换器方案,给出了仿真和实验结果.     

Habitat fragmentation has interactive effects on the population genetic diversity and individual behaviour of a freshwater salmonid fish

Sufficient genetic diversity can aid populations to persist in dynamic and fragmented environments. Understanding which mechanisms regulate genetic diversity of riverine fish can therefore advance current conservation strategies. The aim of this study was to investigate how habitat fragmentation interacted with population genetic diversity and individual behaviour of freshwater fish in large river systems. We studied a population of the long‐distance migratory, iteroparous freshwater salmonid European grayling (Thymallus thymallus) in south‐eastern Norway. Genotyping (n = 527) and radio‐tracking (n = 54) of adult fish throughout a 169‐km river section revealed three major migration barriers limiting gene flow and depleting genetic diversity upstream. Individuals from upstream areas that had dispersed downstream of barriers showed different movement behaviour than local genotypes. No natal philopatry was found in a large unfragmented river section, in contrast to strong fidelity to spawning tributaries known for individuals overwintering in lakes. We conclude that (a) upstream sub‐populations in fragmented rivers show less genetic variation, making it less likely for them to adapt to environmental changes; (b) fish with distinct genotypes in the same habitat can differ in their behaviour; (c) spawning site selection (natal philopatry) can differ between fish of the same species living in different habitats. Together this implies that habitat loss and fragmentation may differently affect individual fish of the same species if they live in different types or sections of habitat. Studying behaviour and genetic diversity of fish can unravel their complex ecology and help minimize human impact.     

Characterization of polyacrylamides used in enhanced oil recovery

Polyacrylamides can be readily characterized using techniques such as IR spectroscopy, ¹³C-NMR, elementary analysis, TGA, and x-ray diffraction. The first three techniques can also be used quantitatively to measure the degree of hydrolysis of the polymers, without the need to know accurately the weight of the sample. The presence of inorganic salts, such as Na₂SO₄, Na₄(CO₃)SO₄, and Na₂CO₃, is readily detected via IR or wide-angle x-ray diffraction. No evidence of crystallinity is found in the samples studied.     

The Role of Plasma Extracellular Vesicles in Remote Ischemic Conditioning and Exercise-Induced Ischemic Tolerance

Ischemic conditioning and exercise have been suggested for protecting against brain ischemia-reperfusion injury. However, the endogenous protective mechanisms stimulated by these interventions remain unclear. Here, in a comprehensive translational study, we investigated the protective role of extracellular vesicles (EVs) released after remote ischemic conditioning (RIC), blood flow restricted resistance exercise (BFRRE), or high-load resistance exercise (HLRE). Blood samples were collected from human participants before and at serial time points after intervention. RIC and BFRRE plasma EVs released early after stimulation improved viability of endothelial cells subjected to oxygen-glucose deprivation. Furthermore, post-RIC EVs accumulated in the ischemic area of a stroke mouse model, and a mean decrease in infarct volume was observed for post-RIC EVs, although not reaching statistical significance. Thus, circulating EVs induced by RIC and BFRRE can mediate protection, but the in vivo and translational effects of conditioned EVs require further experimental verification.     

Phage‐mediated transfer of virulence genes

Bacteriophages as accessory genetic elements play a crucial role in the dissemination of genes and the promotion of genetic diversity within bacterial populations. Such horizontal transfer of DNA is critical in the emergence of new pathogenic organisms, through the dissemination of genes encoding virulence factors such as toxins, adhesins and agressins. Phages can transfer genes that are not necessary for bacteriophage persistence and are generally recognised by their ability to convert their host bacteria to new phenotypes. This phenomenon is known as phage conversion. If such converting genes encode for virulence factors, the consequences of phage infection may include increased virulence of the host bacteria, and the conversion of a non‐pathogenic strain to a potentially dangerous pathogen. A number of virulence factors in bacteria causing diseases in plants, animals and humans are encoded by converting phages, the vast majority of which are temperate as opposed to lytic in nature. © 2001 Society of Chemical Industry