Timed bromocriptine administration reduces body fat stores in obese subjects and hyperglycemia in type II diabetics.

Obese postmenopausal female volunteers were given timed daily oral dosages of bromocriptine, and tested for reduction of body fat stores. This dopamine agonist has been shown to reset circadian rhythms that are altered in obese animals and to reduce body fat levels in several animal models. The participants were instructed not to alter their existing exercise and eating behavior during treatment. Skinfold measurements were taken on 33 subjects as indices of body fat. The measurements (e.g., suprailiac) were reduced after six weeks by about 25%, which represents a reduction of 11.7% of the total body fat. These dramatic decreases in body fat, which are equivalent to that produced by severe caloric restriction, were accompanied by more modest reductions of body weight (2.5%), indicating a possible conservation of protein that is usually lost as a consequence of such caloric restriction. The effects of bromocriptine treatment on body fat and hyperglycemia were also examined in non-insulin dependent diabetics being treated with oral hypoglycemics (7 subjects) or insulin (7 subjects). Total body fat was reduced by 10.7% and 5.1% in diabetics on oral hypoglycemics and insulin, respectively, without any significant reductions in body weight. Hyperglycemia was reduced in most of the 15 diabetic subjects treated leading to euglycemia and even cessation of hypoglycemic drugs in 3 of the 7 subjects during 4-8 weeks of bromocriptine treatment. These findings support the hypothesis that obesity and type II diabetes may be treated effectively with bromocriptine when administered at the proper times and dosages.     

Nuclear localization and signalling activity of phosphoinositidase C beta in Swiss 3T3 cells.

The hydrolysis of phosphatidylinositol 4,5-bisphosphate (PtdInsP2) is a widespread receptor-coupled signalling system at the plasma membrane of most eukaryotic cells. The existence of an entirely separate nuclear phosphoinositide signalling system is suggested from evidence that purified nuclei synthesize PtdInsP2 and phosphatidylinositol 4-phosphate (PtdInsP) in vitro and that a transient decrease in the mass of these lipids occurs when Swiss 3T3 cells are cultured in the presence of insulin-like growth factor-1 (IGF-1). These IGF-1-dependent changes in inositol lipids coincide with an increase in nuclear diacyglycerol and precede translocation to the nucleus and activation of protein kinase C (refs 5, 6). Circumstantial evidence that links these changes with mitosis comes from the isolation of a 3T3 clone that expresses the type-1 IGF receptor and binds IGF-1 peptide but does not respond mitogenically or show transient mass changes in nuclear inositol lipids. A key question is how IGF-1 initiates the rapid breakdown of PtdInsP and PtdInsP2 in the nucleus. Here we present evidence that nuclei of 3T3 cells contain the beta-isozyme of phosphoinositidase C, whereas the gamma-isozyme is confined to the cytoplasm and that IGF-1 treatment stimulates exclusively the activity of nuclear phosphoinositidase C.     

Growth hormone signal transduction

Growth hormone (GH) promotes animal growth by stimulating bone and cartilage cell proliferation, and influences carbohydrate and lipid metabolism. Some of these effects are brought about indirectly via somatomedin induction in hepatocytes, others by acting directly on the target cells. In either case, GH first binds to specific receptors on cells to trigger a sequence of biochemical events culminating in a biological response. Recently much has been learnt about the molecular structure of GH receptor, its binding to ligand, and the ensuing signal transduction events.     

Periodic paralysis in quarter horses: a sodium channel mutation disseminated by selective breeding.

We recently reported on a linkage study within a Quarter Horse lineage segregating hyperkalaemic periodic paralysis (HYPP), an autosomal dominant condition showing potassium-induced attacks of skeletal muscle paralysis. HYPP co-segregated with the equine adult skeletal muscle sodium channel alpha subunit gene, the same gene that causes human HYPP. We now describe the Phe to Leu mutation in transmembrane domain IVS3 which courses the horse disease. This represents the first application of molecular genetics to an important horse disease, and the data will provide an opportunity for control or eradication of this condition.     

浙江沿海虾蛄生物学及其开发利用研究报告

本文根据浙江省教委、省基金、舟山市科委关于浙江沿海虾蛄生物学及其开发利用研究的要求，对四年多来的研究进行总结，主要包括资源与分布、生物学习性、暂养及运输技术、营养成份分析、开发利用等诸方面     

Targeted disruption of the mouse transforming growth factor-beta 1 gene results in multifocal inflammatory disease.

Transforming growth factor-beta 1 (TGF-beta 1) is a multifunctional growth factor that has profound regulatory effects on many developmental and physiological processes. Disruption of the TGF-beta 1 gene by homologous recombination in murine embryonic stem cells enables mice to be generated that carry the disrupted allele. Animals homozygous for the mutated TGF-beta 1 allele show no gross developmental abnormalities, but about 20 days after birth they succumb to a wasting syndrome accompanied by a multifocal, mixed inflammatory cell response and tissue necrosis, leading to organ failure and death. TGF-beta 1-deficient mice may be valuable models for human immune and inflammatory disorders, including autoimmune diseases, transplant rejection and graft versus host reactions.     

Short alanine-based peptides may form 3(10)-helices and not alpha-helices in aqueous solution.

Short alanine peptides, containing 16 or 17 residues, appear to form alpha-helices in aqueous solution. But the main spectroscopic analyses used on helical peptides (circular dichroism and nuclear magnetic resonance) cannot distinguish between an alpha-helix (in which the ith residue is hydrogen-bonded to residue i + 4; ref. 9) and the next most common peptide helix, the 3(10)-helix10 (i-->i + 3 hydrogen-bonding). To address this problem we have designed single and doubly spin-labelled analogues of alanine-based peptides in which the nitroxide spin label forms an unbranched side chain extending from the sulphur atom of a cysteine residue. Here we report the circular dichroism, Fourier-transform infrared and electron-spin resonance spectra of these peptides under helix-forming conditions. The infrared absorbance gives an amide I' band with a frequency that is substantially different from that observed for alpha-helices. The electron-spin resonance spectra of doubly labelled helices show that the ranking of distances between side chains, around a single turn (residues 4-8), is inconsistent with an alpha-helical structure. Our experiments suggest that the more likely peptide geometry is a 3(10)-helix.     

生物序列分析

这次演讲将回顾近 1 0多年来应用某些随机模型于生物序列分析的研究工作 .这些模型本身有很长的历史 ,可追溯到 3 0多年以前 ,尽管从那时起 ,这些模型已经产生了很多新的变种 .在生物序列分析中模型的作用是归总那些涉及到在生物信息学中已知的模体 (motif)或域 (domain)的信息 ,并且提供一种工具在另一序列片段中寻找模体或域的实例 (instance) .我们将逐步介绍模体模型 ,从非常简单的 ,非随机情况开始 ,进而是更复杂的情况 ,直至近来的关于模体的剖面隐马氏模型 .第二个例子是来自利用一个或两个物种的序列数据进行基因发现 ,其中广义隐马氏模型或广义成对 (pair)隐马氏模型已被证实非常有效