Polarization of Myosin II Refines Tissue Material Properties to Buffer Mechanical Stress

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Wound healing effects of methanol extract of Laurocerasus officinalis roem

Laurocerasus officinalis Roem. (syn: Prunus laurocerasus L.) is a member of Rosaceae family. We investigated the antimicrobial and antioxidant activity of L. officinalis Roem in wound healing both in vivo and in vitro using an excisional wound model model in mice. We used four groups of eight mice as follows: untreated (control), empty gel, extract + gel (L. officinalis + gel), and Madecassol® groups. All treatments were applied topically once daily. The scar area, percentage wound closure and epithelization time were measured. L. officinalis promoted wound healing and increased granulation tissue, epidermal regeneration and angiogenesis. L. officinalis extract, which is known for its antioxidant and antimicrobial activities, may be useful for promoting wound healing.     

Tailoring of recombinant FDH: effect of histidine tag location on solubility and catalytic properties of Chaetomium thermophilum formate dehydrogenase (CtFDH)

Abstract

Several protein expression systems can be used to get enzymes in required quantities and study their functions. Incorporating a polyhistidine tag is a beneficial way of getting various enzymes such as FDHs for industrial applications. The NAD⁺ dependent formate dehydrogenase from Chaetomium thermophilum (CtFDH) can be utilized for interconversion of formate to carbon dioxide coupled with the conversion of NAD⁺ to NADH. In this study, N-terminal His tagged CtFDH (N-CtFDH) and C-terminal His tagged CtFDH (C-CtFDH) was constructed to learn the effect of His tag location on the activity and kinetic parameters of the enzyme. The solubility of proteins was not affected by tag position, however, an interference on the N-terminal region caused a deterioration in specific activity and the kinetic ability of enzyme. The obtained results indicated that the C-terminus of the enzyme is an appropriate region for tag engineering. The C-CtFDH has an approximately three-fold larger specific activity and two-fold higher catalytic efficiency than N-CtFDH. The results suggest that insertion of a His-tag at the N-terminal or C-terminal end of CtFDH has different effects on the protein and the N-terminal fragment of the protein is crucial for the function of CtFDH.     

Resistance outside the substrate envelope: hepatitis C NS3/4A protease inhibitors

Direct acting antivirals have dramatically increased the efficacy and tolerability of hepatitis C treatment, but drug resistance has emerged with some of these inhibitors, including nonstructural protein 3/4?A protease inhibitors (PIs). Although many co-crystal structures of PIs with the NS3/4A protease have been reported, a systematic review of these crystal structures in the context of the rapidly emerging drug resistance especially for early PIs has not been performed. To provide a framework for designing better inhibitors with higher barriers to resistance, we performed a quantitative structural analysis using co-crystal structures and models of HCV NS3/4A protease in complex with natural substrates and inhibitors. By comparing substrate structural motifs and active site interactions with inhibitor recognition, we observed that the selection of drug resistance mutations correlates with how inhibitors deviate from viral substrates in molecular recognition. Based on this observation, we conclude that guiding the design process with native substrate recognition features is likely to lead to more robust small molecule inhibitors with decreased susceptibility to resistance.     

围产期干细胞库质量管理体系构建

围产期干细胞库质量管理体系（QMS）建设是保障干细胞产品和服务健康发展的基础工作。本文比较分析美国输血协会（AABB）、细胞疗法认证基金会（FACT）和ISO 9001的标准的架构、内容和侧重点,重点论述围产期干细胞库QMS构建的方法、步骤和参考模式。参照权威机构标准建立和运行QMS,能够保障我国围产期干细胞库标准化、规范化和科学化的建设和管理,提升我国干细胞库能力和信任水平。良好的QMS进一步促进干细胞与精准医疗战略性新兴产业升级,为建设健康中国提供动力。     

Sorting and pooling strategy: a novel tool to map a virus proteome for CD8 T-cell epitopes

Human cytomegalovirus (CMV) is a major cause of morbidity in immunocompromised individuals. However, no efficient vaccine has been developed to date. Identification of T-cell target proteins and epitopes is crucial not only for developing a successful immunization strategy, but also for new approaches using adoptive transfer of antigen-specific T-cells. The CMV genome has more than 200 open reading frames potentially coding for as many proteins. Here, we describe a robust, fast, and simple SPOT synthesis strategy, which allowed us to micro-synthesize every possible CD8 T-cell epitope in the entire potential CMV proteome. So far, 9069 of these peptides have been tested in an ex vivo T-cell stimulation assay. As well as confirming a number of previously known epitopes, we identified several new ones.     

Subspace projection approaches to classification and visualization of neural network-level encoding patterns

Recent advances in large-scale ensemble recordings allow monitoring of activity patterns of several hundreds of neurons in freely behaving animals. The emergence of such high-dimensional datasets poses challenges for the identification and analysis of dynamical network patterns. While several types of multivariate statistical methods have been used for integrating responses from multiple neurons, their effectiveness in pattern classification and predictive power has not been compared in a direct and systematic manner. Here we systematically employed a series of projection methods, such as Multiple Discriminant Analysis (MDA), Principal Components Analysis (PCA) and Artificial Neural Networks (ANN), and compared them with non-projection multivariate statistical methods such as Multivariate Gaussian Distributions (MGD). Our analyses of hippocampal data recorded during episodic memory events and cortical data simulated during face perception or arm movements illustrate how low-dimensional encoding subspaces can reveal the existence of network-level ensemble representations. We show how the use of regularization methods can prevent these statistical methods from over-fitting of training data sets when the trial numbers are much smaller than the number of recorded units. Moreover, we investigated the extent to which the computations implemented by the projection methods reflect the underlying hierarchical properties of the neural populations. Based on their ability to extract the essential features for pattern classification, we conclude that the typical performance ranking of these methods on under-sampled neural data of large dimension is MDA>PCA>ANN>MGD.     

Highly pathogenic H5N1 avian influenza: entry pathways into North America via bird migration

Given the possibility of highly pathogenic H5N1 avian influenza arriving in North America and monitoring programs that have been established to detect and track it, we review intercontinental movements of birds. We divided 157 bird species showing regular intercontinental movements into four groups based on patterns of movement-one of these groups (breed Holarctic, winter Eurasia) fits well with the design of the monitoring programs (i.e., western Alaska), but the other groups have quite different movement patterns, which would suggest the importance of H5N1 monitoring along the Pacific, Atlantic, and Gulf coasts of North America.