Tetanus and botulinum-B neurotoxins block neurotransmitter release by proteolytic cleavage of synaptobrevin.

Clostridial neurotoxins, including tetanus toxin and the seven serotypes of botulinum toxin (A-G), are produced as single chains and cleaved to generate toxins with two chains joined by a single disulphide bond (Fig. 1). The heavy chain (M(r) 100,000 (100K)) is responsible for specific binding to neuronal cells and cell penetration of the light chain (50K), which blocks neurotransmitter release. Several lines of evidence have recently suggested that clostridial neurotoxins could be zinc endopeptidases. Here we show that tetanus and botulinum toxins serotype B are zinc endopeptidases, the activation of which requires reduction of the interchain disulphide bond. The protease activity is localized on the light chain and is specific for synaptobrevin, an integral membrane protein of small synaptic vesicles. The rat synaptobrevin-2 isoform is cleaved by both neurotoxins at the same single site, the peptide bond Gln 76-Phe 77, but the isoform synaptobrevin-1, which has a valine at the corresponding position, is not cleaved. The blocking of neurotransmitter release of Aplysia neurons injected with tetanus toxin or botulinum toxins serotype B is substantially delayed by peptides containing the synaptobrevin-2 cleavage site. These results indicate that tetanus and botulinum B neurotoxins block neurotransmitter release by cleaving synaptobrevin-2, a protein that, on the basis of our results, seems to play a key part in neurotransmitter release.     

多层膜样品的背散射/沟道、溅射剥层/背散射和二次离子质谱分析

用背散射／沟道、溅射剥层／背散射和二次离子质谱方法分析了分子束外延生长的Si/GexSi1-x多层膜。由2MeV^4He^ 离子背散射／沟道分析，确定了外延生长薄膜的厚度、组分和晶格结构的完美性；用低能Ar^ 离子溅射剥层，减薄样品外延层厚度后，再做背散射分析，可获得有关较深层薄膜与基体界面和溅射剥层的信息；二次离子质谱分析清晰地显示出溅射剥层前后样品的交替层周期性结构。     

建设先进文化推进人的全面发展——厦门经济特区应当确立的奋斗目标

厦门经济特区在两个文明建设方面已经取得了举世瞩目的成就 ,为促进特区人民素质的提高 ,促进特区人的全面发展提供了必要的条件。展望未来 ,厦门经济特区应当确立人的全面发展的奋斗目标。厦门经济特区各项社会事业的发展 ,先进文化的建设 ,推进了特区人的全面发展 :促进了特区人观念的变革 ,形成了新的伦理道德规范 ,提高了全体特区人科学文化水平 ,弘扬了科学理性精神。特区人的全面发展不仅是经济特区发展所追求的目标 ,而且是厦门经济特区发展最具潜力的基本要素 ,是厦门经济特区再创新优势的基础、跨上新台阶的需要     

Identifying antigenic T-cell sites.

Computer algorithms that have been used successfully on protein sequences for the prediction of antigenic T-cell sites have been collected into a single computer software package called TSites.     

The penetrance of dominant erythropoietic protoporphyria is modulated by expression of wildtype FECH.

Erythropoietic protoporphyria (EPP) is an inherited disorder of heme biosynthesis caused by a partial deficiency of ferrochelatase (FECH, EC 4.99.1.1). EPP is transmitted as an autosomal dominant disorder with an incomplete penetrance. Using haplotype segregation analysis, we have identified an intronic single nucleotide polymorphism (SNP), IVS3-48T/C, that modulates the use of a constitutive aberrant acceptor splice site. The aberrantly spliced mRNA is degraded by a nonsense-mediated decay mechanism (NMD), producing a decreased steady-state level of mRNA and the additional FECH enzyme deficiency necessary for EPP phenotypic expression.     

Retinoic acid causes an anteroposterior transformation in the developing central nervous system

All-trans retinoic acid (RA) is well known as a biologically active form of vitamin A and a teratogen. The identification of nuclear receptors for this ligand suggests strongly that it is an endogenous signal molecule, and measurements of RA and teratogenic manipulations suggest further that RA is a morphogen specifying the anteroposterior axis during limb development. Besides the limb, RA and other retinoids affect development of other organs, including the central nervous system (CNS). None of these other effects has been investigated in detail. Our purpose here was to begin analysing the effects of RA on CNS development in Xenopus laevis. We find that RA acts on the developing CNS, transforming anterior neural tissue to a posterior neural specification. These and other findings raise the possibility that RA mediates an inductive interaction regulating anteroposterior differentiation within the CNS. Following recent reports implicating transforming growth factor-beta 2-like and fibroblast growth factor-like factors in mesoderm induction, this indicates that a different type of signal molecule (working through a nuclear receptor, not a plasma membrane receptor) might mediate inductive cell interactions during early embryonic development.     

中国建筑企业如何应对新形势的挑战

在分析当前新形势下中国建筑企业面临的机遇与挑战的基础上，提出了针对性的应对措施，深入探讨和研究了国企改革发展的途径和国企经营管理战略的实施问题。     

Puff activity after heat shock in two species of the Drosophila obscura group

When individuals of Drosophila guanche are submitted to heat shock, five new puffs are induced. These puffs usually do not appear during normal development. Comparing these results with those obtained in Drosophila subobscura, also belonging to the obscura group, differences between the induced puffing pattern of both species have been found.     

Strontium isotope evidence for landscape use by early hominins

Ranging and residence patterns among early hominins have been indirectly inferred from morphology, stone-tool sourcing, referential models and phylogenetic models. However, the highly uncertain nature of such reconstructions limits our understanding of early hominin ecology, biology, social structure and evolution. We investigated landscape use in Australopithecus africanus and Paranthropus robustus from the Sterkfontein and Swartkrans cave sites in South Africa using strontium isotope analysis, a method that can help to identify the geological substrate on which an animal lived during tooth mineralization. Here we show that a higher proportion of small hominins than large hominins had non-local strontium isotope compositions. Given the relatively high levels of sexual dimorphism in early hominins, the smaller teeth are likely to represent female individuals, thus indicating that females were more likely than males to disperse from their natal groups. This is similar to the dispersal pattern found in chimpanzees, bonobos and many human groups, but dissimilar from that of most gorillas and other primates. The small proportion of demonstrably non-local large hominin individuals could indicate that male australopiths had relatively small home ranges, or that they preferred dolomitic landscapes.