Astrocyte glypicans 4 and 6 promote formation of excitatory synapses via GluA1 AMPA receptors

In the developing central nervous system (CNS), the control of synapse number and function is critical to the formation of neural circuits. We previously demonstrated that astrocyte-secreted factors powerfully induce the formation of functional excitatory synapses between CNS neurons. Astrocyte-secreted thrombospondins induce the formation of structural synapses, but these synapses are postsynaptically silent. Here we use biochemical fractionation of astrocyte-conditioned medium to identify glypican 4 (Gpc4) and glypican 6 (Gpc6) as astrocyte-secreted signals sufficient to induce functional synapses between purified retinal ganglion cell neurons, and show that depletion of these molecules from astrocyte-conditioned medium significantly reduces its ability to induce postsynaptic activity. Application of Gpc4 to purified neurons is sufficient to increase the frequency and amplitude of glutamatergic synaptic events. This is achieved by increasing the surface level and clustering, but not overall cellular protein level, of the GluA1 subunit of the AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) glutamate receptor (AMPAR). Gpc4 and Gpc6 are expressed by astrocytes in vivo in the developing CNS, with Gpc4 expression enriched in the hippocampus and Gpc6 enriched in the cerebellum. Finally, we demonstrate that Gpc4-deficient mice have defective synapse formation, with decreased amplitude of excitatory synaptic currents in the developing hippocampus and reduced recruitment of AMPARs to synapses. These data identify glypicans as a family of novel astrocyte-derived molecules that are necessary and sufficient to promote glutamate receptor clustering and receptivity and to induce the formation of postsynaptically functioning CNS synapses.     

Catalytic nucleation of a meta-stabled phase in phase-seeded undercooled Fe75Ni25 melts

Undercooled Fe75Ni25 melts were phase-seeded by a high purity iron. It was found that above a critical undercooling,△Tc = 135 K, a metastable δ phase (b.c.c) solidifies from the iron-seeded melts instead of a thermodynamically stable γ phase (f.c.c). While undercooling of the melt (△T ) is below △Tc, solidification of the γ phase prevails in the iron-seeded melts. For the undercooled melts subjected to spontaneous nucleation, the γ phase always solidifies. After solidification, the as-solidified γ phase transforms completely to martensite; whereas the as-solidified metastable δ phase partially transforms to the γ phase, and then to martensite. The untransformed δ phase retains as a -ferrite particles in the microstructures. Based on the classical nucleation theory, catalytic nucleation of the metastable δ phase in the phase-seeded undercooledFe75Ni25 melts was analyzed. It was quantitatively demonstrated that when△T>△Tc, the formation of the δ phase can be ascribed to a better catalytic effect of the iron on its nucleation than that on the nucleation of the γphase.     

A facile and green preparation of durian shell-derived carbon electrodes for electrochemical double-layer capacitors

A facile and green preparation of high surface area activated carbons with mixed microporosity and mesoporosity from durian shell waste is reported in this work. The pore structure and surface chemistry of the parent carbon were modified by the combination of ultrasonication and microwave irradiation techniques. The effects of temperature and time in the ultrasonication treatment and power output and time in the microwave irradiation were studied. The electrochemical performance of carbon electrodes for supercapacitors was tested by cyclic voltammeter (CV) and galvanostatic charge–discharge. The results show that the capacitive energy storage of electrodes is critically dependent on the microporosity and surface chemistry of activated carbons. The highest electrode capacitance in this work was 103.6 F/g that prepared from activated carbon modified at an ultrasonication temperature of 323.15 K for 10 min and microwave power output of 900 W for 10 min.     

Crystal structure of an HIV-binding recombinant fragment of human CD4

CD4 glycoprotein on the surface of T cells helps in the immune response and is the receptor for HIV infection. The structure of a soluble fragment of CD4 determined at 2.3 A resolution reveals that the molecule has two intimately associated immunoglobulin-like domains. Residues implicated in HIV recognition by analysis of mutants and antibody binding are salient features in domain D1. Domain D2 is distinguished by a variation on the beta-strand topologies of antibody domains and by an intra-sheet disulphide bridge.     

Novel regulation and function of Src tyrosine kinase

Src tyrosine kinase is a critical signal transducer that modulates a wide variety of cellular functions. Misregulation of Src leads to cell transformation and cancer. Heterotrimeric guanine-nucleotide-binding proteins (G proteins) are another group of signaling molecules that transduce signals from cell-surface receptors to generate physiological responses. Recently, it was discovered that Gαs and Gαi could directly stimulate Src family tyrosine kinase activity. This novel regulation of Src tyrosine kinase by G proteins provides insights into the adenylyl cyclase-independent signaling mechanisms involved in ligand-induced receptor desensitization, internalization and other physiological processes. Received 17 August 2001; received after revision 22 October 2001; accepted 24 October 2001