Structures of complement component C3 provide insights into the function and evolution of immunity

The mammalian complement system is a phylogenetically ancient cascade system that has a major role in innate and adaptive immunity. Activation of component C3 (1,641 residues) is central to the three complement pathways and results in inflammation and elimination of self and non-self targets. Here we present crystal structures of native C3 and its final major proteolytic fragment C3c. The structures reveal thirteen domains, nine of which were unpredicted, and suggest that the proteins of the alpha2-macroglobulin family evolved from a core of eight homologous domains. A double mechanism prevents hydrolysis of the thioester group, essential for covalent attachment of activated C3 to target surfaces. Marked conformational changes in the alpha-chain, including movement of a critical interaction site through a ring formed by the domains of the beta-chain, indicate an unprecedented, conformation-dependent mechanism of activation, regulation and biological function of C3.     

Stimulation of connective tissue cell growth by substance P and substance K

Connective tissue cells proliferate actively when cultured in the presence of serum. Platelet-derived growth factor (PDGF), a basic protein of relative molecular mass approximately 30,000, has been identified as the major serum mitogen for these cells; its main physiological/pathophysiological role may be to initiate wound healing in connection with tissue injury. However, growth of cultured cells is also influenced by several other factors, including epidermal growth factor, fibroblast growth factor, insulin and somatomedins. Furthermore, Rozengurt and Sinnett-Smith recently showed that bombesin, a neuroendocrine peptide isolated from frog skin, stimulates DNA synthesis and cell division in cultures of a specific subtype of 3T3 cells. Substance P and substance K (also known as neurokinin A or neuromedin L) are mammalian peptides belonging to the tachykinin family. Substance P has been studied extensively; it is distributed widely throughout the central and peripheral nervous system, including primary sensory neurones, and can be released in the periphery from axon collaterals of stimulated pain fibres and contribute to the inflammatory response. Substance K is a member of the tachykinin family isolated from mammalian spinal cord; Nawa et al. determined the primary structure of two types of substance P precursors, one of which contained a sequence homologous to substance K, as well as the sequence of substance P. We report here that substance P and substance K stimulate DNA synthesis in cultured arterial smooth muscle cells and human skin fibroblasts, and that this stimulation is inhibited by the substance P-antagonist spantide.     

Noxious arthropods as potential prey of the venomous Javan slow loris (Nycticebus javanicus) in a West Javan volcanic agricultural system

Arthropods play a significant role in ecosystems as prey for animals such as insectivorous primates. The venomous Javan slow loris (Nycticebus javanicus) is a nocturnal primate endemic to the island of Java, Indonesia. It remains unknown if its venom is partially sequestered from noxious arthropod prey. We studied the little-known arthropod community in a rural agriculture system in West Java, Indonesia, in order to investigate the potential prey and source for sequestration of venom. We found specimens of the partially noxious insect orders Lepidoptera, Hemiptera, Coleoptera, Hymenoptera, Orthoptera and of the class Arachnida in slow loris foraging trees in an agricultural area in West Java, Indonesia. To examine the effects of environmental conditions on the abundance of this food source, arthropods were trapped every two weeks for five months, using sweep net transects, Malaise and pitfall traps. Trap type had a significant effect on taxa caught. Wind strength negatively affected the number of Lepidoptera captured in the Malaise trap and humidity had a confounding effect on Orthoptera caught by sweep net. Despite the short-term nature of our study, by using a combination of trapping methods, we identified a relatively high diversity of insects in a human-dominated landscape. Our results can be used as a basis to understand the proximate and ultimate factors shaping the use of venom by the slow loris as a primate.     

Genetic mechanisms and evolutionary significance of natural variation in Arabidopsis

Genomic studies of natural variation in model organisms provide a bridge between molecular analyses of gene function and evolutionary investigations of adaptation and natural selection. In the model plant species Arabidopsis thaliana, recent studies of natural variation have led to the identification of genes underlying ecologically important complex traits, and provided new insights about the processes of genome evolution, geographic population structure, and the selective mechanisms shaping complex trait variation in natural populations. These advances illustrate the potential for a new synthesis to elucidate mechanisms for the adaptive evolution of complex traits from nucleotide sequences to real-world environments.     

电子束光刻制造亚微米栅长GaAs金属半导体场效应管(英文)

栅长短于0.2μm的砷化镓(GaAs)金属一半导体场效应晶体管已被我们研制成功。电子束光刻、金属剥离(lift-off)和双层及三层电子束光刻胶等先进技术的应用,获得了亚微米的T型栅,从而改进了场效应管的高频特性。直流测试显示,这种场效应管的跨导高达135ms/mm。     

Nonsense-mediated decay microarray analysis identifies mutations of EPHB2 in human prostate cancer

The identification of tumor-suppressor genes in solid tumors by classical cancer genetics methods is difficult and slow. We combined nonsense-mediated RNA decay microarrays and array-based comparative genomic hybridization for the genome-wide identification of genes with biallelic inactivation involving nonsense mutations and loss of the wild-type allele. This approach enabled us to identify previously unknown mutations in the receptor tyrosine kinase gene EPHB2. The DU 145 prostate cancer cell line, originating from a brain metastasis, carries a truncating mutation of EPHB2 and a deletion of the remaining allele. Additional frameshift, splice site, missense and nonsense mutations are present in clinical prostate cancer samples. Transfection of DU 145 cells, which lack functional EphB2, with wild-type EPHB2 suppresses clonogenic growth. Taken together with studies indicating that EphB2 may have an essential role in cell migration and maintenance of normal tissue architecture, our findings suggest that mutational inactivation of EPHB2 may be important in the progression and metastasis of prostate cancer.