28,207 research outputs found

    Differential dynamics and activity-dependent regulation of alpha- and beta-neurexins at developing GABAergic synapses

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    Neurexins (NRXs) and neuroligins are key synaptic adhesion molecules that also recruit synaptic signaling machineries. Neurexins consist of alpha- and beta-isoforms, but how they couple synaptic transmission and adhesion to regulate activity-dependent synapse development remains unclear, in part because of poor understanding of their cell biology and regulation in the relevant neurons. Here, we examined the subaxonal localization, dynamics, and regulation of NRX1alpha and NRX1beta in cortical perisomatic inhibitory synapses. Both isoforms are delivered to presynaptic terminals but show significant and different turnover rate at the membrane. Although NRX1alpha is highly diffuse along developing axons and filopodia, NRX1beta is strictly anchored at terminals through binding to postsynaptic ligands. The turnover rate of NRX1beta is attenuated by neural activity and presynaptic GABA(B) receptors. NRXs, thus, are intrinsically dynamic but are stabilized by local transmitter release. Such an activity-adjusted adhesion system seems ideally suited to rapidly explore and validate synaptic partners guided by synaptic transmission

    ZIKV infection activates the IRE1-XBP1 and ATF6 pathways of unfolded protein response in neural cells.

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    BACKGROUND: Many viruses depend on the extensive membranous network of the endoplasmic reticulum (ER) for their translation, replication, and packaging. Certain membrane modifications of the ER can be a trigger for ER stress, as well as the accumulation of viral protein in the ER by viral infection. Then, unfolded protein response (UPR) is activated to alleviate the stress. Zika virus (ZIKV) is a mosquito-borne flavivirus and its infection causes microcephaly in newborns and serious neurological complications in adults. Here, we investigated ER stress and the regulating model of UPR in ZIKV-infected neural cells in vitro and in vivo. METHODS: Mice deficient in type I and II IFN receptors were infected with ZIKV via intraperitoneal injection and the nervous tissues of the mice were assayed at 5 days post-infection. The expression of phospho-IRE1, XBP1, and ATF6 which were the key markers of ER stress were analyzed by immunohistochemistry assay in vivo. Additionally, the nuclear localization of XBP1s and ATF6n were analyzed by immunohistofluorescence. Furthermore, two representative neural cells, neuroblastoma cell line (SK-N-SH) and astrocytoma cell line (CCF-STTG1), were selected to verify the ER stress in vitro. The expression of BIP, phospho-elF2α, phospho-IRE1, and ATF6 were analyzed through western blot and the nuclear localization of XBP1s was performed by confocal immunofluorescence microscopy. RT-qPCR was also used to quantify the mRNA level of the UPR downstream genes in vitro and in vivo. RESULTS: ZIKV infection significantly upregulated the expression of ER stress markers in vitro and in vivo. Phospho-IRE1 and XBP1 expression significantly increased in the cerebellum and mesocephalon, while ATF6 expression significantly increased in the mesocephalon. ATF6n and XBP1s were translocated into the cell nucleus. The levels of BIP, ATF6, phospho-elf2α, and spliced xbp1 also significantly increased in vitro. Furthermore, the downstream genes of UPR were detected to investigate the regulating model of the UPR during ZIKV infection in vitro and in vivo. The transcriptional levels of atf4, gadd34, chop, and edem-1 in vivo and that of gadd34 and chop in vitro significantly increased. CONCLUSION: Findings in this study demonstrated that ZIKV infection activates ER stress in neural cells. The results offer clues to further study the mechanism of neuropathogenesis caused by ZIKV infection

    Hydrostatic pressure effects on the static magnetism in Eu(Fe0.925_{0.925}Co0.075_{0.075})2_{2}As2_{2}

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    The effects of hydrostatic pressure on the static magnetism in Eu(Fe0.925_{0.925}Co0.075_{0.075})2_{2}As2_{2} are investigated by complementary electrical resistivity, ac magnetic susceptibility and single-crystal neutron diffraction measurements. A specific pressure-temperature phase diagram of Eu(Fe0.925_{0.925}Co0.075_{0.075})2_{2}As2_{2} is established. The structural phase transition, as well as the spin-density-wave order of Fe sublattice, is suppressed gradually with increasing pressure and disappears completely above 2.0 GPa. In contrast, the magnetic order of Eu sublattice persists over the whole investigated pressure range up to 14 GPa, yet displaying a non-monotonic variation with pressure. With the increase of the hydrostatic pressure, the magnetic state of Eu evolves from the canted antiferromagnetic structure in the ground state, via a pure ferromagnetic structure under the intermediate pressure, finally to a possible "novel" antiferromagnetic structure under the high pressure. The strong ferromagnetism of Eu coexists with the pressure-induced superconductivity around 2 GPa. The change of the magnetic state of Eu in Eu(Fe0.925_{0.925}Co0.075_{0.075})2_{2}As2_{2} upon the application of hydrostatic pressure probably arises from the modification of the indirect Ruderman-Kittel-Kasuya-Yosida (RKKY) interaction between the Eu2+^{2+} moments tuned by external pressure.Comment: 9 pages, 6 figure

    The effect of pre-processing and grain structure on the bio-corrosion and fatigue resistance of magnesium alloy AZ31

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    Magnesium alloys are broadly used for structural applications in the aerospace and automotive industries as well as in consumer electronics. While a high specific strength is the forte of magnesium alloys, one serious limitation for Mg alloys is their corrosion performance. Unlike aluminium, it does not form a stable passive film to provide long-term protection from further corrosion. The poor corrosion resistance of magnesium and magnesium alloys is regarded as a major drawback, and significant effort has been focused on improving this.[1-3] However, the high reactivity of magnesium alloys in corrosive media can be used to advantage in biomedical applications, particularly in temporary implants where the capacity of a material for bio-degradation is one of the most sought after properties. Indeed, permanent implant materials, such as stainless steel, titanium alloys or Nitinol (55Ni-45Ti), are the only choices currently available for hard tissue implantation. They can cause permanent physical irritation, long-term endothelial dysfunction and chronic inflammatory local reaction. Sometimes a second operation is needed for the implant to be removed. Given the ability of the human body to gradually recover and regenerate damaged tissue, the ideal solution would thus be a degradable implant, which would offer a physiologically less invasive repair and temporary support during tissue recovery. After fulfilling its function, this implant would be obliterated, being absorbed by the body. This philosophy of implant surgery would also be of particular interest for endovascular stent
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