Depression of fast excitatory synaptic transmission in large aspiny neurons of the neostriatum after transient forebrain ischemia

Spiny neurons in the neostriatum die within 24 hr after transient global ischemia, whereas large aspiny (LA) neurons remain intact. To reveal the mechanisms of such selective cell death after ischemia, excitatory neurotransmission was studied in LA neurons before and after ischemia. The intrastriatally evoked fast EPSCs in LA neurons were depressed < or =24 hr after ischemia. The concentration-response curves generated by application of exogenous glutamate in these neurons were approximately the same before and after ischemia. A train of five stimuli (100 Hz) induced progressively smaller EPSCs, but the proportion of decrease in EPSC amplitude at 4 hr after ischemia was significantly smaller compared with control and at 24 hr after ischemia. Parallel depression of NMDA receptor and AMPA receptor-mediated EPSCs was also observed after ischemia, supporting the involvement of presynaptic mechanisms. The adenosine A1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine blocked the inhibition of evoked EPSCs at 4 hr after ischemia but not at 24 hr after ischemia. Electron microscopic studies demonstrated that the most presynaptic terminals in the striatum had a normal appearance at 4 hr after ischemia but showed degenerating signs at 24 hr after ischemia. These results indicated that the excitatory neurotransmission in LA neurons was depressed after ischemia via presynaptic mechanisms. The depression of EPSCs shortly after ischemia might be attributable to the enhanced adenosine A1 receptor function on synaptic transmission, and the depression at late time points might result from the degeneration of presynaptic terminals

Pakistan-China Economic Corridor (CPEC): Opportunities, Threats and Challenges

The China-Pakistan Economic Corridor (CPEC) is the centerpiece of China Pakistan relations.  Between the two, it is a full package of economic cooperation and geo-strategic partnership which will transform Pakistan into a transportation hub via Gawader port and link China with Asia, Europe, Middle East and Africa. Along with hopes and interests CPEC has also become the victim of the political tensions and controversies. However, on the local level, this mega project faces certain challenges with respect to the impacts, route feasibility, implementation and Indian concerns in the region. Therefore, this research paper intends to highlight first, OBOR ‘’One Belt One road” CPEC features, diplomatic, military and economic relations between the two neighbors, Opportunities threats and challenges and regional politics afterwards. Keywords: Pak-China relations, Energy, Economic Corridor, Gawader Port, terrorism, Threats and Challenges

Characterization of Conserved Combined T and B Cell Epitopes in Leptospira interrogans Major Outer Membrane Proteins OmpL1 and LipL41

<p>Abstract</p> <p>Background</p> <p><it>Leptospira interrogans </it>are bacterial pathogens of animal that cause zoonotic infections in human. Outer membrane proteins of leptospire are among the most effective antigens which can stimulate remarkable immune responses during the infection processes, and thus are currently considered leading candidate vaccine antigens. The objective of the present study is to predict and confirm major combined B and T cell epitopes of leptospiral outer membrane proteins OmpL1 and LipL41, as well as to evaluate their capacity in the induction of immune responses in BALB/c mice.</p> <p>Results</p> <p>In this study, four epitopes from OmpL1 and four from LipL41 conserved regions were evaluated for their potential utilization in leptospire vaccines. Firstly, combined B and T cell epitopes were predicted by softwares and expressed using a phage display system. OmpL1 residues 87-98 and 173-191 (OmpL1_87-98and OmpL1_173-191) and LipL41_30-48, LipL41_233-256of LipL41 were identified as immunodominant B cell epitopes by Western blot. Epitopes OmpL1_173-191, OmpL1_297-320of OmpL1 and LipL41_233-256, LipL41_263-282of LipL41 were identified as immunodominant CD4⁺T cell epitopes through proliferation analysis of splenocytes from recombinant OmpL1 (rOmpL1) or recombinant LipL41 (rLipL41)-immunized BALB/c (H-2^d) mice. These epitopes induced responses of CD4⁺T cells and Th1 (T helper cells) type cytokine responses during the infection.</p> <p>Conclusion</p> <p>This work identified combined T and B cell immunodominant epitopes in outer membrane proteins OmpL1 and LipL41 of <it>Leptospira interrogans</it>. OmpL1_173-191of OmpL1 and LipL41_233-256of LipL41 could be useful in a vaccine against <it>Leptospira</it>. The findings could also contribute to the development of effective cross-protective vaccine strategies for leptospirosis.</p

Inverse Geometry Design of Radiative Enclosures Using Particle Swarm Optimization Algorithms

Three different Particle Swarm Optimization (PSO) algorithms—standard PSO, stochastic PSO (SPSO) and differential evolution PSO (DEPSO)—are applied to solve the inverse geometry design problems of radiative enclosures. The design purpose is to satisfy a uniform distribution of radiative heat flux on the designed surface. The design surface is discretized into a series of control points, the PSO algorithms are used to optimize the locations of these points and the Akima cubic interpolation is utilized to approximate the changing boundary shape. The retrieval results show that PSO algorithms can be successfully applied to solve inverse geometry design problems and SPSO achieves the best performance on computational time. The influences of the number of control points and the radiative properties of the media on the retrieval geometry design results are also investigated