Caenorhabditis elegans expressed sequence tags identify gene families and potential disease gene homologues.

A database containing mapped partial cDNA sequences from Caenorhabditis elegans will provide a ready starting point for identifying nematode homologues of important human genes and determining their functions in C. elegans. A total of 720 expressed sequence tags (ESTs) have been generated from 585 clones randomly selected from a mixed-stage C. elegans cDNA library. Comparison of these ESTs with sequence databases identified 422 new C. elegans genes, of which 317 are not similar to any sequences in the database. Twenty-six new genes have been mapped by YAC clone hybridization. Members of several gene families, including cuticle collagens, GTP-binding proteins, and RNA helicases were discovered. Many of the new genes are similar to known or potential human disease genes, including CFTR and the LDL receptor.     

A comprehensive analysis of protein-protein interactions in Saccharomyces cerevisiae

Two large-scale yeast two-hybrid screens were undertaken to identify protein-protein interactions between full-length open reading frames predicted from the Saccharomyces cerevisiae genome sequence. In one approach, we constructed a protein array of about 6,000 yeast transformants, with each transformant expressing one of the open reading frames as a fusion to an activation domain. This array was screened by a simple and automated procedure for 192 yeast proteins, with positive responses identified by their positions in the array. In a second approach, we pooled cells expressing one of about 6,000 activation domain fusions to generate a library. We used a high-throughput screening procedure to screen nearly all of the 6,000 predicted yeast proteins, expressed as Gal4 DNA-binding domain fusion proteins, against the library, and characterized positives by sequence analysis. These approaches resulted in the detection of 957 putative interactions involving 1,004 S. cerevisiae proteins. These data reveal interactions that place functionally unclassified proteins in a biological context, interactions between proteins involved in the same biological function, and interactions that link biological functions together into larger cellular processes. The results of these screens are shown here.     

Development of City Transport System and Two-wheel Vehicles

Based on the study on the city transport systems of some typical cities worldwide, this paper put forward that each city transport system has its own development mode, which is influenced by the city development plan, economic development level, traveling vehicle composition etc.. When some problems occur, such as the congestions caused by contradiction between the road capacity and vehicle composition, the city transport system may come into temporary maturity period. If the improvement for road system is limited meanwhile, optimized structure of vehicle composition should be an effective solution in this case. With the development of economy-internationalization, the development speed of city transport modernization is rapid. When traveling easiness is conflicting with efficiency, the advantages of public transport system become more obvious. Correspondingly, the superiority of two-wheel vehicles will reappear. Though the important function of two-wheel vehicles for alleviating city traffic problems i     

Evidence that disinhibition of brain stem neurones contributes to morphine analgesia

Analgesia results when opiates are microinjected into the rostral ventromedial medulla (RVM). This region, which includes the nucleus raphe magnus and the adjacent reticular formation, is rich in immunoreactive enkephalin-containing neurones and terminals, and contains neurones that project to the spinal cord dorsal horn where they inhibit identified nociceptive spinothalamic tract neurones. Although opiates have previously been reported either to excite or inhibit RVM cells, the possibility of an opiate effect being consistent within a physiologically defined subclass has not been examined. Recently we described a class of neurone in the RVM (the off-cell) that abruptly pauses just before a heat-evoked tail-flick reflex. If off-cells are made to fire continuously by direct electrical stimulation of the RVM, the tail-flick reflex does not occur. We report here that analgesic doses of morphine completely eliminate the pause in firing that precedes the tail-flick reflex. We propose that this disinhibition of off-cells in the RVM is a primary process contributing to opiate inhibition of nociceptor-induced reflexes.     

Human immunodeficiency virus induces phosphorylation of its cell surface receptor

AIDS is an immunoregulatory disorder characterized by depletion of the CD4+, helper/inducer lymphocyte population. The causative agent of this disease is the human immunodeficiency virus, HIV, which infects CD4+ cells and leads to cytopathic effects characterized by syncytia formation and cell death. Recent studies have demonstrated that binding of HIV to its cellular receptor CD4 is necessary for viral entry. We find that binding of HIV to CD4 induces rapid and sustained phosphorylation of CD4 which could involve protein kinase C. HIV-induced CD4 phosphorylation can be blocked by antibody against CD4 and monoclonal antibody against the HIV envelope glycoprotein gp120, indicating that a specific interaction between CD4 and gp120 is required for phosphorylation. Electron microscopy shows that a protein kinase C inhibitor does not impair binding of HIV to CD4+ cells, but causes an apparent accumulation of virus particles at the cell surface, at the same time inhibiting viral infectivity. These results indicate a possible role for HIV-induced CD4 phosphorylation in viral entry and identify a potential target for antiviral therapy.     

Genetic and molecular mechanisms of viral pathogenesis: implications for prevention and treatment

The pathogenesis of infection of mice by the mammalian reoviruses involves several discrete steps. Each of the three viral outer capsid proteins has a highly distinct and specialized role: one protein (sigma 1) binds to cell surface receptors; a second protein (mu 1C) determines the capacity for viral growth at mucosal surfaces; and the third protein (sigma 3) is responsible for inhibiting cell macromolecular synthesis. A detailed picture of the molecular basis of reovirus virulence and attention is now emerging.