Abstract OR-3: Integrative Structural Study of the Complex of Snake Toxin WTX with α7-type Nicotinic Acetylcholine Receptor

Background: Nicotinic acetylcholine receptors are ligand-gated ion channels present in the nervous system, epithelium, and the immune system. The α7-type nicotinic receptor (α7-nAChR) is a homopentameric membrane protein containing five ligand binding sites located at the interface between subunits in the extracellular domain of the receptor. α7-nAChR is considered a promising target for the treatment of cancer and cognitive dysfunction in Alzheimer's disease, schizophrenia, and depression. WTX is a non-conventional three-finger neurotoxin from the Naja kaouthia venom inhibiting α7-nAChR. WTX structure consists of three loops protruding from the “head” (core) stabilized by a system of disulfide bonds. Methods: The complex of the α7-nAChR extracellular domain with a recombinant analogue of WTX was studied by cryo-electron microscopy. The structure of the complex of full-length α7-nAChR with the toxin in the membrane environment was reconstructed by in silico molecular modeling. Interaction of WTX with the lipid membrane was confirmed by NMR-spectroscopy. Results: Analysis of electronic images confirmed the homopentameric organization of the extracellular domain with a diameter of ~ 9 nm and a height of ~ 7 nm. On the electron density map, additional regions corresponding to five WTX molecules located at the intersubunit interfaces of the domain were observed. Fitting the known spatial structures of the extracellular domain and the WTX toxin into the obtained electron density made it possible to reconstruct the structure of the complex (although with a low resolution of ~ 8 Ǻ due to the predominant orientation of particles in the ice) and to determine the topology of the toxin-receptor interaction. It was revealed that WTX interacts with the extracellular domain of α7-nAChR by the loop II, while the loop I and the toxin’s head seem to interact with the surface of the lipid membrane surrounding the receptor. Model of the complex of the full-length α7-nAChR receptor with WTX in the membrane environment corresponding to the neuronal membrane was constructed using computer simulation methods. Molecular dynamics for >1500 ns confirmed the stability of the complex. The predicted membrane-active site of the WTX molecule includes residues Lys13 and Arg18. The study of WTX and its mutants Lys13Ala and Arg18Ala by NMR-spectroscopy confirmed the importance of these residues for interaction with lipid membrane. Conclusion: Interaction mode of non-conventional neurotoxins with nAChR has been determined for the first time

Erratum to: "Double volume reflection of a proton beam by a sequence of two bent crystals" [Phys. Lett. B 658 (2008) 109]

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The Influence of Political Connection and Institutions to the Performance and Bank Loans of Private Listed Companies

我国有着不同于西方发达国家的制度背景和政治制度，政府对市场的管制力度较大，上市公司的高管具有一定的政治背景，其中国有企业本身大股东的政府背景性质，其政治关联很可能是与生俱来的，而民营企业政治关联的形成则具有主动性。改革开放以来，民营经济不断发展壮大，己成为我国经济增长的主要推动力量，因此，研究政治关联对民营公司的影响这一问题在中国更具有现实启发意义。 本文以民营上市公司的高级管理人员是否是前任或现任的政府官员、人大代表或政协委员来衡量公司是否具有政治关联，选取2004年—2008年中国沪深两市所有A股民营上市公司为样本，实证研究了政治关联与制度环境对民营上市公司经营绩效和银行贷款的影响。研究...Chinese current institution and political system are different from the Western developed countries. Under this system, many executives of private listed companies are relevant to politics. Therefore the study of political influence of private companies related to this issue in China is more realistic instructive. This paper focuses on whether the company has the political connection, which measu...学位：管理学硕士院系专业：管理学院财务学系_财务学学号：1762007115174

Development of Submicrocapsules Based on Co-Assembled Like-Charged Silica Nanoparticles and Detonation Nanodiamonds and Polyelectrolyte Layers

Capsules with shells based on nanoparticles of different nature co-assembled at the interface of liquid phases of emulsion are promising carriers of lipophilic drugs. To obtain such capsules, theoretically using the Derjaguin–Landau–Verwey–Overbeek (DLVO) theory and experimentally using dynamic light-scattering (DLS) and transmission electron microscopy (TEM) methods, the interaction of like-charged silica nanoparticles and detonation nanodiamonds in an aqueous solution was studied and their ratios selected for the formation of submicron-sized colloidosomes. The resulting colloidosomes were modified with additional layers of nanoparticles and polyelectrolytes, applying LbL technology. As a model anti-cancer drug, thymoquinone was loaded into the developed capsules, demonstrating a significant delay of the release as a result of colloidosome surface modification. Fluorescence flow cytometry and confocal laser scanning microscopy showed efficient internalization of the capsules by MCF7 cancer cells. The obtained results demonstrated a high potential for nanomedicine application in the field of the drug-delivery system development

High-efficiency deflection of high-energy negative particles through axial channeling in a bent crystal

Deflection due to axial channeling in a silicon crystal bent along the [111] axis was observed for 150 GeV/c negative particles, mainly π− mesons, at one of the secondary beams of the CERN SPS. The whole beam was deflected to one side with the efficiency of about 90% and with the peak position at the bend crystal angle α=43 μrad. The deflection occurs mainly due to doughnut scattering of above-barrier particles by the atomic strings of the crystal. However, due to a high probability of particle recapture into bound states with the atomic strings their contribution to the deflection should be about 15% for our case according to simulation results

High-Efficiency Deflection of High-Energy Protons through Axial Channeling in a Bent Crystal

Beam deflection due to axial channeling in a silicon crystal bent along the [111] axis was observed with 400  GeV/c protons at the CERN Super Proton Synchrotron. The condition for doughnut scattering of protons by the atomic strings of the crystal was attained. Such a condition allowed one to observe a beam deflection of 50  μrad with about 30% efficiency. The contribution of hyperchanneled states of protons to the observed beam deflection was less than 2% according to simulation results

Observation of channeling in bent crystals at the CERN LHC

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