No abstract

Neuregulin (NRG) regulates synapse formation and synaptic plasticity, but little is known about the regulation of NRG signaling at synapses. Here we show that the NRG receptor ErbB4 was localized in anatomically defined postsynaptic densities in the brain. In cultured cortical neurons, ErbB4 was recruited to the neuronal lipid raft fraction after stimulation by NRG. Along with ErbB4, adaptor proteins Grb2 and Shc were translocated to lipid rafts by NRG stimulation. In transfected human embryonic kidney 293 cells, the partitioning of ErbB4 into a detergent-insoluble fraction that includes lipid rafts was increased by PSD-95 (postsynaptic density-95), through interaction of the ErbB4 C terminus with the PDZ [PSD-95/Discs large/zona occludens-1] domains of PSD-95. Disruption of lipid rafts inhibited NRG-induced activation of Erk and prevented NRG-induced blockade of induction of long-term potentiation at hippocampal CA1 synapses. Thus, our results indicate that NRG stimulation causes translocation of ErbB4 into lipid rafts and that lipid rafts are necessary for signaling by ErbB4.

Chronic hypobaric hypoxia can inhibit eryptosis by decreasing intracellular Ca and increasing integrin-associated protein CD47.

Alveolar echinococcosis is a zoonotic disease caused by the infection of the larval stage Echinococcus multilocularis with worldwide distribution especially in the northwest China. It is important to develop a well-tolerated immunoprophylaxis against E. multilocularis for alveolar echinococcosis control. In this study, a prokaryotic expression system for recombinant immunogen LTB-EMY162 was established, and the immunological features, sensitized lymphocyte, IL-4/IFN-γ secreted, prophylactic effect, and therapeutic effect were also evaluated. Arctic Express (DE3) system, Ni-charged and molecular sieve chromatography were used to obtain a high-purity 29 kDa protein. The ELISA and lymphocyte proliferation assay showed that LTB-EMY162 induced high-titer specific IgG against EMY162 and E. multilocularis protoscoleces protein in BALB/c mice and promoted sensitized T lymphocyte cell proliferation, and LTB-EMY162 stimulated Th cell to secrete IL-4 and IFN-γ and induced a Th1/Th2 mixed type immunological response. We also found that LTB-EMY162 significantly inhibited the cysts formation by challenging with 1000 E. multilocularis protoscoleces. The growth of protoscoleces and cysts were also significantly decreased by treating with LTB-EMY162 in 1000 protoscoleces intraperitoneal injection therapeutic mice model. In conclusion, we have constructed a subunit vaccine LTB-EMY162 which has prevention and therapeutic effect against E. multilocularis infection.