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411.
《Journal of molecular biology》2023,435(9):167926
Cryogenic electron microscopy (cryo-EM) is now one of the most powerful and widely used methods to determine high-resolution structures of macromolecules. A major bottleneck of cryo-EM is to prepare high-quality vitrified specimen, which still faces many practical challenges. During the conventional vitrification process, macromolecules tend to adsorb at the air–water interface (AWI), which is known unfriendly to biological samples. In this review, we outline the nature of AWI and the problems caused by it, such as unpredictable or uneven particle distribution, protein denaturation, dissociation of complex and preferential orientation. We review and discuss the approaches and underlying mechanisms to deal with AWI: 1) Additives, exemplified by detergents, forming a protective layer at AWI and thus preserving the native folds of target macromolecules. 2) Fast vitrification devices based on the idea to freeze in-solution macromolecules before their touching of AWI. 3) Thin layer of continuous supporting films to adsorb macromolecules, and when functionalized with affinity ligands, to specifically anchor the target particles away from the AWI. Among these supporting films, graphene, together with its derivatives, with negligible background noise and mechanical robustness, has emerged as a new generation of support. These strategies have been proven successful in various cases and enable us a better handling of the problems caused by the AWI in cryo-EM specimen preparation. 相似文献
412.
Enterovirus 71 (EV71) is an emerging life‐threatening pathogen particularly in the Asia‐Pacific region. Apoptosis is a major pathogenic feature in EV71 infection. However, which molecular mechanism participating in EV71‐induced apoptosis is not completely understood. Long noncoding RNAs (lncRNAs), a newly discovered class of regulatory RNA molecules, govern a wide range of biological functions through multiple regulatory mechanisms. Whether lncRNAs involved in EV71‐induced apoptosis was investigated in this study. We conducted an apoptosis‐oriented approach by integrating lncRNA and mRNA profilings. lnc‐IRAK3‐3 is down‐regulated in EV71 infection and plays an important role in EV71 infection‐induced apoptosis. Compensation of lnc‐IRAK3‐3 in EV71 infection promoted cell apoptosis wherein GADD45β expression was increased and further triggered caspase3 and PARP cleavage. Using bioinformatics analysis and functional assays, lnc‐IRAK3‐3 could functionally sequester miR‐891b and GADD45β 3′UTR whereas miR‐891b showed the inhibitory activity on GADD45β expression. Taken together, lnc‐IRAK3‐3 has the ability capturing miR‐891b to enforce GADD45β expression and eventually promotes apoptosis. On the contrary, host cells suppress lnc‐IRAK3‐3 to relieve lnc‐IRAK3‐3‐sequestered miR‐891b, restrain GADD45β, and attenuate apoptosis in EV71 infection that prevent host cells from severe damages. We discover a new molecular mechanism by which host cells counteract EV71‐induced apoptosis through the lnc‐IRAK3‐3/miR‐891b/GADD45β axis partially. 相似文献
413.
Hand foot and mouth disease is a febrile sickness complex characterized by cutaneous eruption (exanthem) on the palms and soles with simultaneous occurrence of muco-cutanous vesiculo-ulcerative lesions (enanthem) affecting the mouth. The illness is caused by a number of enteroviruses with coxsackievirus A16 and enterovirus 71 as the main causative agents. Human enterovirus 71 (EV71) belongs to the species Human enterovirus A under the genus Enterovirus within the family Picornaviridae. EV71 has been associa... 相似文献