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     

A calcium sensor in the sodium channel modulates cardiac excitability.

Sodium channels are principal molecular determinants responsible for myocardial conduction and maintenance of the cardiac rhythm. Calcium ions (Ca2+) have a fundamental role in the coupling of cardiac myocyte excitation and contraction, yet mechanisms whereby intracellular Ca2+ may directly modulate Na channel function have yet to be identified. Here we show that calmodulin (CaM), a ubiquitous Ca2+-sensing protein, binds to the carboxy-terminal 'IQ' domain of the human cardiac Na channel (hH1) in a Ca2+-dependent manner. This binding interaction significantly enhances slow inactivation-a channel-gating process linked to life-threatening idiopathic ventricular arrhythmias. Mutations targeted to the IQ domain disrupted CaM binding and eliminated Ca2+/CaM-dependent slow inactivation, whereas the gating effects of Ca2+/CaM were restored by intracellular application of a peptide modelled after the IQ domain. A naturally occurring mutation (A1924T) in the IQ domain altered hH1 function in a manner characteristic of the Brugada arrhythmia syndrome, but at the same time inhibited slow inactivation induced by Ca2+/CaM, yielding a clinically benign (arrhythmia free) phenotype.     

Microbial degradation of bitumen

Summary A blown bitumen Mexphalte R 90/40 with a high content of saturated hydrocarbons was degraded by several microorganisms to the same extent. In batch cultures ofSaccharomycopsis lipolytica, maximal biodegradation was estimated to be about 9% w/w, 3.2·10^–3 g/cm² and 3.1·10^–3 cm of degraded bitumen. The Mexphalte R 90/40 degradation rate was closely coupled to biofilm formation. The microbial activity concerned predominantly the oxidation of saturated hydrocarbons. A direct distillation bitumen 80/100 with a low content of saturated hydrocarbons and a high content of aromatic hydrocarbons and resins was more resistant to biodegradation.     

用测量模态阻尼和振型的方法对复合材料薄平板进行无损质量检测

复合材料薄平板经热压制成后,都需要进行质量检测。本文探索用测量模态阻尼和振型的方法,对复合材料薄平板的制作质量进行无损检测,作为对其它昂贵的无损检测方法的补充。略述用振动方法进行无损检测的原理,测量薄平板阻尼的方法以及提高测量精度的措施。还讨论在测量薄平板阻尼时可能遇到的一些特殊问题(如非线性刚度、拍、模态密集等问题);以云母基复合材料薄平板作为例子,从测量其阻尼和振型的结果,对这种板的制作质量进行讨论。     

Effect of 15(R)-15-methyl-prostaglandin E2 on iron absorption in the rat

Summary The administration of 15(R)-15-methyl prostaglandin E₂ (15(R)-15-M-PGE₂) in vivo significantly diminished the uptake of⁵⁹Fe into blood, spleen, liver, femur and dried intestine of rats, whereas acetylsalicylic acid (ASA) increased the counts significantly. This effect of ASA was counteracted by 15(R)-15-M-PGE₂. It is suggested that prostaglandins (PGs) might play an important role in inhibiting iron absorption at the intestinal level.This work was supported by grant No.6638 from CONICET (Argentina). The technical assistance of Mrs María E. Castro and Norma Rizzo is gratefully acknowleged.     

Host cell reactivation of ozone-treated T3 bacteriophage by different strains ofEscherichia coli

Summary Host cell reactivation capacity for ozone T3 phage was determined for differentE. coli strains deficient in one or more of the DNA repair mechanisms. The results indicate that DNA polymerase I appears to play a key role in the repair of damage produced on the DNA by ozone while thelexA gene product seems to play a minor one.This research was sponsored by the National Sciences and Engineering Council of Canada. One of us (PLH) acknowledges a scholarship from the NSERCof Canada.     

Studies on the Dd antigen-antibody system. I. The nature of antigen Dd and its antibodies

Summary The nature of antigen Dd, an antigen present in the extracts of human dandruff which precipitates human sera selectively, and antibodies reacting with it are reported.This work was supported through U.G.C. Grant No. F.23-230/75/SR II. H.K. participated in this study, first as J.R.F. of U.G.C. and then as S.R.F. of I.C.M.R. We are grateful to Dr Baruch S. Blumberg for his invaluable suggestions and to Professor H. Walter for the gift of IgG, IgM and IgA immune sera.     

Fibulin-5/DANCE is essential for elastogenesis in vivo.

The elastic fibre system has a principal role in the structure and function of various types of organs that require elasticity, such as large arteries, lung and skin. Although elastic fibres are known to be composed of microfibril proteins (for example, fibrillins and latent transforming growth factor (TGF)-beta-binding proteins) and polymerized elastin, the mechanism of their assembly and development is not well understood. Here we report that fibulin-5 (also known as DANCE), a recently discovered integrin ligand, is an essential determinant of elastic fibre organization. fibulin-5-/- mice generated by gene targeting exhibit a severely disorganized elastic fibre system throughout the body. fibulin-5-/- mice survive to adulthood, but have a tortuous aorta with loss of compliance, severe emphysema, and loose skin (cutis laxa). These tissues contain fragmented elastin without an increase of elastase activity, indicating defective development of elastic fibres. Fibulin-5 interacts directly with elastic fibres in vitro, and serves as a ligand for cell surface integrins alphavbeta3, alphavbeta5 and alpha9beta1 through its amino-terminal domain. Thus, fibulin-5 may provide anchorage of elastic fibres to cells, thereby acting to stabilize and organize elastic fibres in the skin, lung and vasculature.     

The melatonin rhythm: both a clock and a calendar

The paper briefly reviews the data which shows that the circadian production and secretion of melatonin by the pineal gland can impart both daily, i.e., clock, and seasonal, i.e., calendar, information to the organism. The paper summarizes the 3 patterns of nocturnal melatonin production that have been described. Clearly, regardless of the pattern of nocturnal melatonin production a particular species normally displays, the duration of nightime elevated melatonin is proportional to the duration of the night length. Since daylength under natural conditions changes daily the melatonin rhythm, which adjusts to the photoperiod sends time of year information to the organism. The melatonin receptors which subserve the clock message sent by the pineal gland in the form of a melatonin cycle may reside in the biological clock itself, namely, the suprachiasmatic nuclei (SCN). The melatonin receptors that mediate seasonal changes in reproductive physiology are presumably those that are located on the pars tuberalis cells of the anterior pituitary gland. Besides these receptors which likely mediate clock and calendar information, melatonin receptors have been described in other organs. Interestingly, the distribution of melatonin receptors is highly species-specific. Whereas the clock and calendar information that the melatonin cycle imparts to the organism relies on cell membrane receptors, a fact that is of some interest considering the high lipophilicity of melatonin, recent studies indicate that other functions of melatonin may require no receptor whatsoever.