eFGF and its mode of action in the community effect during Xenopus myogenesis

The community effect is an interaction among a group of many nearby precursor cells, necessary for them to maintain tissue-specific gene expression and differentiate co-ordinately. During Xenopus myogenesis, the muscle precursor cells must be in group contact throughout gastrulation in order to develop into terminally differentiated muscle. The molecular basis of this community interaction has not to date been elucidated. We have developed an assay for testing potential community factors, in which isolated muscle precursor cells are treated with a candidate protein and cultured in dispersion. We have tested a number of candidate factors and we find that only eFGF protein is able to mediate a community effect, stimulating stable muscle-specific gene expression in demonstrably single muscle precursor cells. In contrast, Xwnt8, bFGF, BMP4 and TGF(&bgr;)2 do not show this capacity. We show that eFGF is expressed in the muscle precursor cells at the right time to mediate the community effect. Moreover, the time when the muscle precursor cells are sensitive to eFGF corresponds to the period of the endogenous community effect. Finally, we demonstrate that FGF signalling is essential for endogenous community interactions. We conclude that eFGF is likely to mediate the community effect in Xenopus myogenesis.     

PDZ domain suppression of an ER retention signal in NMDA receptor NR1 splice variants

The NMDA receptor NR1 subunit has four splice variants that differ in their C-terminal, cytoplasmic domain. We investigated the contribution of the C-terminal cassettes, C0, C1, C2, and C2', to trafficking of NR1 in heterologous cells and neurons. We identified an ER retention signal (RRR) in the C1 cassette of NR1, which is similar to the RXR motif in ATP-sensitive K(+) channels (Zerangue et al., 1999). We found that surface expression of NR1-3, which contains C1, is due to a site on the C2' cassette, which includes the terminal 4 amino acid PDZ-interacting domain. This site suppresses ER retention of the C1 cassette and leads to surface expression. These findings suggest a role for PDZ proteins in facilitating the transition of receptors from an intracellular pool to the surface of the neuron.     

Docking of protein molecular surfaces with evolutionary trace analysis

We have developed a new method to predict protein- protein complexes based on the shape complementarity of the molecular surfaces, along with sequence conservation obtained by evolutionary trace (ET) analysis. The docking is achieved by optimization of an object function that evaluates the degree of shape complementarity weighted by the conservation of the interacting residues. The optimization is carried out using a genetic algorithm in combination with Monte Carlo sampling. We applied this method to CAPRI targets and evaluated the performance systematically. Consequently, our method could achieve native-like predictions in several cases. In addition, we have analyzed the feasibility of the ET method for docking simulations, and found that the conservation information was useful only in a limited category of proteins (signal related proteins and enzymes).     

The path of least resistance: aggressive or moderate treatment?

The evolution of resistance to antimicrobial chemotherapy is a major and growing cause of human mortality and morbidity. Comparatively little attention has been paid to how different patient treatment strategies shape the evolution of resistance. In particular, it is not clear whether treating individual patients aggressively with high drug dosages and long treatment durations, or moderately with low dosages and short durations can better prevent the evolution and spread of drug resistance. Here, we summarize the very limited available empirical evidence across different pathogens and provide a conceptual framework describing the information required to effectively manage drug pressure to minimize resistance evolution.     

静磁场对单株人体体表正常菌生长影响的研究

本文通过40mT和120mT两种静磁场作用下表皮葡萄球菌生长过程的研究,发现试验所选强度静磁场加速了表皮葡萄球菌在对数生长期的生长速率,而在进入稳定生长期后其生长速率反而低于对照组,但就整个生长周期而言,静磁场作用下表皮葡萄球菌的总量大于对照组,表明了试验所选静磁场对表皮葡萄球菌生长有一定促进作用.