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.

No abstract

IntroductionThe objective of this study is to construct a multi-epitope vaccine GILE containing B-cell and T-cell epitopes against Echinococcus Multilocularis (E. multilocularis) infection based on the dominant epitopes of E. multilocularis EMY162, LAP, and GLUT1.MethodsThe structure and hydrophobicity of GILE were predicted by SWISSMODEL, pyMOL, SOPMA and VMD, and its sequence was optimized by Optimum™ Codon. The GILE gene was inserted into pCzn1 and transformed into Escherichia coli Arctic express competent cells. IPTG was added to induce the expression of recombinant proteins. High-purity GILE recombinant protein was obtained by Ni-NTA Resin. BALB/c mice were immunized with GILE mixed with Freund’s adjuvant, and the antibody levels and dynamic changes in the serum were detected by ELISA. Lymphocyte proliferation was detected by MTS. The levels of IFN-g and IL-4 were detected by ELISpot and flow cytometry (FCM). T cells were detected by FCM. The growth of hepatic cysts was evaluated by Ultrasound and their weights were measured to evaluate the immune protective effect of GILE.ResultsThe SWISS-MODEL analysis showed that the optimal model was EMY162 95-104―LAP464-479―LAP495-510―LAP396-410―LAP504-518―EMY162112-126. The SOPMA results showed that there were Alpha helix (14.88%), Extended strand (26.25%), Beta turn (3.73%) and Random coil (45.82%) in the secondary structure of GILE. The restriction enzyme digestion and sequencing results suggested that the plasmid pCzn1-GILE was successfully constructed. The SDSPAGE results indicated that the recombinant protein was 44.68 KD. The ELISA results indicated that mice immunized with GILE showed higher levels of serum antibodies compared to the PBS group. The FCM and ELISpot results indicated that mice immunized with GILE secreted more IFN-g and IL-4. Immunization with GILE also led to a significant decrease in the maximum diameter and weight of cysts and stimulated the production of CD4+ and CD8+ T Cell.DiscussionA multi-epitope vaccine GILE with good immunogenicity and antigenicity has been successfully constructed in this study, which may provide important theoretical and experimental bases for the prevention and treatment of E. multilocularis infection.

No abstract

The ultrasound-guided transversus abdominis plane block and ilioinguinal-iliohypogastric nerve block have been shown to provide pain relief after abdominal surgery. A combination of the 2 blocks may provide acceptable surgical anesthesia for cesarean delivery. We describe 4 women who had contraindications to neuraxial anesthesia, who underwent cesarean delivery with ultrasound-guided bilateral transversus abdominis plane block combined with ilioinguinal-iliohypogastric nerve block using 40 mL 0.5% ropivacaine. Breakthrough pain during the delivery of the fetus was treated with small doses of IV ketamine and propofol. We suggest that this technique may be an alternative to local anesthesia for cesarean delivery in clinical practice.