免疫毒素的抗肿瘤研究

免疫毒素是由具有导向能力的载体（抗体或细胞因子）和具有细胞毒性的分子（毒素）偶联而成的具有特异性细胞杀伤能力的杂合分子,是一种靶向药物。免疫毒素首先利用肿瘤细胞上导向分子的受体与细胞结合,然后进入细胞,再由毒素发挥蛋白质合成抑制作用,最终导致靶细胞死亡。与其他抗肿瘤药物相比,免疫毒素具有毒性强和特异性高的优点,在肿瘤治疗中显示出巨大的应用前景。简要概述了免疫毒素的作用机理、制备及其抗肿瘤研究进展。     

Kappa-chain constant-region gene sequences in genus Rattus: coding regions are diverging more rapidly than noncoding regions

We have determined the nucleotide sequence of a 1,200-base pair (bp) genomic fragment that includes the kappa-chain constant-region gene (C kappa) from two species of native Australian rodents, Rattus leucopus cooktownensis and Rattus colletti. Comparison of these sequences with each other and with other rodent C kappa genes shows three surprising features. First, the coding regions are diverging at a rate severalfold higher than that of the nearby noncoding regions. Second, replacement changes within the coding region are accumulating at a rate at least as great as that of silent changes. Third, most of the amino acid replacements are localized in one region of the C kappa domain--namely, the carboxy-terminal "bends" in the alpha-carbon backbone. These three features have previously been described from comparisons of the two allelic forms of C kappa genes in R. norvegicus. These data imply the existence of considerable evolutionary constraints on the noncoding regions (based on as yet undetermined functions) or powerful positive selection to diversify a portion of the constant-region domain (whose physiological significance is not known). These surprising features of C kappa evolution appear to be characteristic only of closely related C kappa genes, since comparison of rodent with human sequences shows the expected greater conservation of coding regions, as well as a predominance of silent nucleotide substitutions within the coding regions.      

A library of siRNA duplexes targeting the phosphoinositide 3-kinase pathway: determinants of gene silencing for use in cell-based screens

Gene silencing through RNA interference (RNAi) has been established as a means of conducting reverse genetic studies. In order to better understand the determinants of short interfering RNA (siRNA) knockdown for use in high-throughput cell-based screens, 148 siRNA duplexes targeting 30 genes within the PI3K pathway were selected and synthesized. The extent of RNA knockdown was measured for 22 genes by quantitative real-time PCR. Analysis of the parameters correlating with effective knockdown showed that (i) duplexes targeting the middle of the coding sequence silenced significantly poorer, (ii) silencing by duplexes targeting the 3′UTR was comparable with duplexes targeting the coding sequence, (iii) pooling of four or five duplexes per gene was remarkably efficient in knocking down gene expression and (iv) among duplexes that achieved a >70% knockdown of the mRNA there were strong nucleotide preferences at specific positions, most notably positions 11 (G or C) and 19 (T) of the siRNA duplex. Finally, in a proof-of-principle pathway-wide cell-based genetic screen, conducted to detect negative genetic regulators of Akt S473 phosphorylation, both known negative regulators of this phosphorylation, PTEN and PDK1, were found. These data help to lay the foundation for genome-wide siRNA screens in mammalian cells.     

Nutritional Support from the Intestinal Microbiota Improves Hematopoietic Reconstitution after Bone Marrow Transplantation in Mice

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Growth of a Molecular Base for Feeding: The Mind Body Dualism

It is often difficult to identify the ‘who, when, and where’ of advances in medicine and surgery because it's a rare advance indeed (such as the use of digitalis by William Withering) that can be clearly related to the astuteness of one person at one time and place.     

A Hidden Markov Model approach to variation among sites in rate of evolution

The method of Hidden Markov Models is used to allow for unequal and unknown evolutionary rates at different sites in molecular sequences. Rates of evolution at different sites are assumed to be drawn from a set of possible rates, with a finite number of possibilities. The overall likelihood of phylogeny is calculated as a sum of terms, each term being the probability of the data given a particular assignment of rates to sites, times the prior probability of that particular combination of rates. The probabilities of different rate combinations are specified by a stationary Markov chain that assigns rate categories to sites. While there will be a very large number of possible ways of assigning rates to sites, a simple recursive algorithm allows the contributions to the likelihood from all possible combinations of rates to be summed, in a time proportional to the number of different rates at a single site. Thus with three rates, the effort involved is no greater than three times that for a single rate. This "Hidden Markov Model" method allows for rates to differ between sites and for correlations between the rates of neighboring sites. By summing over all possibilities it does not require us to know the rates at individual sites. However, it does not allow for correlation of rates at nonadjacent sites, nor does it allow for a continuous distribution of rates over sites. It is shown how to use the Newton-Raphson method to estimate branch lengths of a phylogeny and to infer from a phylogeny what assignment of rates to sites has the largest posterior probability. An example is given using beta-hemoglobin DNA sequences in eight mammal species; the regions of high and low evolutionary rates are inferred and also the average length of patches of similar rates.      

Variability in responses to thermal stress in parasitoids

Abstract 1. To study phenotypic effects of stress, a stress is applied to cohorts of organisms with an increasing intensity. In the absence of mortality the response of traits will be a decreasing function of stress intensity because of increasing physiological costs. We call such decreasing functions type A responses. 2. However, when stress caused mortality, some studies have found that for high stress intensities, survivors performed as well as control individuals (type B responses). We proposed that type A responses are caused by the physiological cost of stress whereas type B responses are caused by a mixture of physiological costs and selection. 3. The present study exposed Aphidius picipes wasps to an increasing duration of cold storage (cold stress), and obtained variable responses as predicted when both physiological costs and selection of resistant individuals determine the outcome. 4. When cold storage of parasitoids for biological control is desirable, research should be carried out to find (i) the temperature regime and duration of storage and (ii) the least sensitive stage for storage to minimise losses from mortality and reduction of fitness of survivors. 5. Selection by cold stress as observed in the present study could result in rapid adaptation of populations exposed to such stress.     

缟蝇科昆虫生物学和地理分布分析

本文概述了缟蝇科昆虫的生活史、食性、访花习性、栖居环境等生物学特性,并对缟蝇科属、种的地理分布进行了分析。缟蝇科在世界动物地理区的分布统计结果表明,同脉缟蝇亚科为亚世界性分布,其属级阶元在东洋界丰富度最高,其次为澳洲界;其种级阶元在东洋界最为丰富,其次为澳洲界。缟蝇亚科为世界性分布,其属级阶元在新热带界丰富度最高,并且高度特化,其次是东洋界和澳洲界;其种级阶元在新热带界最为丰富,其次为古北界和澳洲界。缟蝇科在中国动物地理区和亚区的分布统计结果显示,其属、种级阶元在华南区最为丰富;同脉缟蝇亚科的种级阶元以海南岛亚区最为丰富,其次为台湾亚区;缟蝇亚科的种级阶元在台湾亚区最为丰富,西部山地高原亚区次之。