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Anna Kutschenko Selma Staege Karen Grütz Hannes Glaß Norman Kalmbach Thomas Gschwendtberger Lisa M. Henkel Johanne Heine Anne Grünewald Andreas Hermann Philip Seibler Florian Wegner 《International journal of molecular sciences》2021,22(7)
Myoclonus-dystonia (DYT-SGCE, formerly DYT11) is characterized by alcohol-sensitive, myoclonic-like appearance of fast dystonic movements. It is caused by mutations in the SGCE gene encoding ε-sarcoglycan leading to a dysfunction of this transmembrane protein, alterations in the cerebello-thalamic pathway and impaired striatal plasticity. To elucidate underlying pathogenic mechanisms, we investigated induced pluripotent stem cell (iPSC)-derived striatal medium spiny neurons (MSNs) from two myoclonus-dystonia patients carrying a heterozygous mutation in the SGCE gene (c.298T>G and c.304C>T with protein changes W100G and R102X) in comparison to two matched healthy control lines. Calcium imaging showed significantly elevated basal intracellular Ca2+ content and lower frequency of spontaneous Ca2+ signals in SGCE MSNs. Blocking of voltage-gated Ca2+ channels by verapamil was less efficient in suppressing KCl-induced Ca2+ peaks of SGCE MSNs. Ca2+ amplitudes upon glycine and acetylcholine applications were increased in SGCE MSNs, but not after GABA or glutamate applications. Expression of voltage-gated Ca2+ channels and most ionotropic receptor subunits was not altered. SGCE MSNs showed significantly reduced GABAergic synaptic density. Whole-cell patch-clamp recordings displayed elevated amplitudes of miniature postsynaptic currents and action potentials in SGCE MSNs. Our data contribute to a better understanding of the pathophysiology and the development of novel therapeutic strategies for myoclonus-dystonia. 相似文献
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Diana Salikhova Tatiana Bukharova Elvira Cherkashova Daria Namestnikova Georgy Leonov Maria Nikitina Ilya Gubskiy Gevorg Akopyan Andrey Elchaninov Konstantin Midiber Natalia Bulatenco Victoria Mokrousova Andrey Makarov Konstantin Yarygin Vladimir Chekhonin Liudmila Mikhaleva Timur Fatkhudinov Dmitry Goldshtein 《International journal of molecular sciences》2021,22(9)
Transplantation of various types of stem cells as a possible therapy for stroke has been tested for years, and the results are promising. Recent investigations have shown that the administration of the conditioned media obtained after stem cell cultivation can also be effective in the therapy of the central nervous system pathology (hypothesis of their paracrine action). The aim of this study was to evaluate the therapeutic effects of the conditioned medium of hiPSC-derived glial and neuronal progenitor cells in the rat middle cerebral artery occlusion model of the ischemic stroke. Secretory activity of the cultured neuronal and glial progenitor cells was evaluated by proteomic and immunosorbent-based approaches. Therapeutic effects were assessed by overall survival, neurologic deficit and infarct volume dynamics, as well as by the end-point values of the apoptosis- and inflammation-related gene expression levels, the extent of microglia/macrophage infiltration and the numbers of formed blood vessels in the affected area of the brain. As a result, 31% of the protein species discovered in glial progenitor cells-conditioned medium and 45% in neuronal progenitor cells-conditioned medium were cell type specific. The glial progenitor cell-conditioned media showed a higher content of neurotrophins (BDNF, GDNF, CNTF and NGF). We showed that intra-arterial administration of glial progenitor cells-conditioned medium promoted a faster decrease in neurological deficit compared to the control group, reduced microglia/macrophage infiltration, reduced expression of pro-apoptotic gene Bax and pro-inflammatory cytokine gene Tnf, increased expression of anti-inflammatory cytokine genes (Il4, Il10, Il13) and promoted the formation of blood vessels within the damaged area. None of these effects were exerted by the neuronal progenitor cell-conditioned media. The results indicate pronounced cytoprotective, anti-inflammatory and angiogenic properties of soluble factors secreted by glial progenitor cells. 相似文献
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Toughening modification of poly(l -lactide) (PLLA) with rubber particles is often realized at the cost of transparency, mechanical strength, and modulus because high rubber loadings are generally required for toughening. In this work, a promising strategy to simultaneously improve the transparency and stiffness–toughness performance of poly(butyl acrylate)-poly(methyl methacrylate) (BAMMA) core-shell rubber nanoparticles toughened PLLA blends by utilizing the stereocomplex (SC) crystallization between PLLA and poly(d -lactide) (PDLA) is devised. The results reveal that the construction of SC crystallites in PLLA matrix via melt-mixing PLLA/BAMMA blends with PDLA can prevent BAMMA nanoparticles from aggregation and promote them to form network-like structure at lower contents. As a result, not only higher toughening efficiency with less rubber contents but also superior transparency is achieved in the PLLA/PDLA/BAMMA blends as compared with the PLLA/BAMMA ones where large aggregated BAMMA clusters are formed. Moreover, the outstanding reinforcement of SC crystallites network for PLLA can impart an enhanced tensile strength and modulus to PLLA/PDLA/BAMMA blends, thus improving the stiffness–toughness performance of PLLA/PDLA/BAMMA blends to a higher degree. This work demonstrates that SC crystallization is a promising solution to solve the contradiction between transparency and mechanical properties and then obtain superior comprehensive performances in rubber toughened PLLA blends. 相似文献
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为了分析硅镍合金化奥氏体基低密度钢在中温环境下的拉伸变形行为,采用Instron电子拉力试验机对Fe-28.64Mn-8.99Al-1.68Si-1.39Ni-1.0C(Mn29Al9Si2Ni,质量分数/%)低密度钢在23~300 ℃下进行了温拉伸试验,研究了该钢的温拉伸力学行为,并采用SEM、TEM和热力学计算对该钢的强韧化机制进行了研究。结果表明,随着应变的增加,温拉伸应力-应变曲线主要包括弹性变形、均匀塑性变形和断裂等几个过程,没有明显的屈服现象。随着温度的提高,该钢的强度逐渐降低,塑性(断后伸长率)先增加后减小再升高,于200 ℃时出现塑性低谷,此时该钢的应力-应变曲线和应变硬化率曲线均具有明显的锯齿状特征,应变硬化率随应变的增加变化不大。而该钢在其他温度下的应力-应变曲线和应变硬化率曲线没有发现明显的“锯齿状”特征,应变硬化率随应变的增加而平缓下降。试验钢在23~300 ℃下的主要强韧化机制为κ-碳化物强化、应变强化、孪生诱发塑性和动态应变时效强化。较低温度下位错可动性较差对孪生诱发的促进作用、镍元素和硅元素对孪生的抑制作用、较高温度下孪生现象的减弱和温度对动态应变时效的促进或抑制作用等使得试验钢在23、100和300 ℃时存在明显的孪生诱发塑性,而在200 ℃时存在明显的动态应变时效强化的主要原因。动态应变时效强化是该钢在200 ℃时出现塑性低谷的主要原因。 相似文献
78.
汽车是日常生活中主要交通工具之一,其用钢质量的优劣直接关系到汽车本身及乘坐人员的安全,因此研发高性能汽车用钢至关重要。微合金化是有效改善汽车用钢性能的手段之一,微合金元素铌可细化晶粒,提高材料的强韧性及氢致延迟断裂性能,备受研究者的青睐。总结了微合金元素铌对汽车用TWIP钢组织的影响,综述了铌对汽车TWIP钢力学性能、耐磨性能及抗氢致延迟断裂性能等的作用及相应机制,并提出了现阶段铌微合金化汽车用TWIP钢研究过程中存在的问题,为后续低成本、高效地发挥铌元素在高强度汽车钢中的应用提供参考依据。 相似文献
79.
为了了解我国分析仪器的发展,推动冶金分析领域定量检测技术的进步,文章以北京分析测试学术报告会暨展览会(BCEIA)在国内的展示成果为依托,选择电感耦合等离子体发射光谱(ICP-OES)、电感耦合等离子体质谱(ICP-MS)、X射线荧光光谱(XRF)、激光诱导击穿光谱(LIBS)等基础定量检测仪器为主要分析对象,归纳总结了这些仪器的发展过程、基本原理和主要结构。从分析检测人员的视角,讨论了该检测仪器的优势特点及应用效果;展望了定量分析检测技术的发展趋势;提出了以定量检测仪器为基础的新型高端科学仪器的发展前景。又以激光剥蚀电感耦合等离子体质谱(LA-ICP-MS)、辉光放电质谱(GD-MS)、电子探针X射线显微分析仪(EPMA)等拓展联用检测仪器为例,介绍了设备的主要特点及应用,最终总结出LA-ICP-MS为固体样品中微量元素分析的常用技术,GD-MS技术是痕量元素分析的重要手段,EPMA技术因具有与其他仪器结合包容性高的优点,虽然在使用过程中存在一定的缺陷,但已成为通用的分析手段。而我国定量分析检测技术正朝着现场化、专用化及标准化的方向发展。 相似文献
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摘要:为探索低温贝氏体钢的断裂行为,研究应变速率对低温贝氏体钢TRIP效应的影响,采用不同应变速率的拉伸试验对低温贝氏体钢的强塑性进行研究。利用扫描电镜(SEM)、透射电镜(TEM)及X射线衍射(XRD)等试验方法对低温贝氏体钢的微观组织、断口形貌及裂纹走向进行表征。结果表明,随着应变速率的提高,试验钢的屈服强度由771MPa上升至806MPa,抗拉强度由1554MPa上升至1606MPa,断后伸长率由13.5%下降至9.0%。主要原因是高应变速率拉伸引发的绝热温升抑制了残余奥氏体的马氏体相变,对试验钢塑性造成负面影响。 相似文献