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Influenza A virus poses a constant challenge to human health. The highly conserved influenza matrix-2 (M2) protein is an attractive target for the development of a universal antibody-based drug. However, screening using antigens with subphysiological conformation in a nonmembrane environment significantly reduces the generation of efficient antibodies. Here, M2(1-46) was incorporated into nanodiscs (M2-nanodiscs) with M2 in a membrane-embedded tetrameric conformation, closely resembling its natural physiological state in the influenza viral envelope. M2-nanodisc generation, an antigen, was followed by

Rapid advent of the era of big data, deep integration of education and technology, and multidisciplinary nature of educational research are driving the application of knowledge graphs in educational research. We use CSSCI and CSCD journal articles as data sources and analyze the Knowledge Graph of education using the graph database Neo4j in this article. Result shows that the number of literatures in the research area show a clear upward trend and go from the stages of brewing. Highly cited literatures’ research topics, subject categories, and authors are widely distributed. From the perspective of core institutions and authors, multiple normal universities have strong competitiveness. Citespace, SPSS and Bicomb are the most commonly used data processing tools for scholars. In further study of the area of knowledge graph, we should fully combine with the cutting-edge computer technology, based on big data and artificial intelligence to improve the level and quality of education research.

In essay marking, manual grading will waste a lot of manpower and material resources, and the subjective judgment of marking teachers is easy to cause unfair phenomenon. Therefore, this paper proposes an automatic essay grading model combining multi-channel convolution and LSTM. The model adds a dense layer after the embedding layer, obtains the weight assignment of text through softmax function, then uses the multi-channel convolutional neural network to extract the text feature information of different granularities, and the extracted feature information is fused into the LSTM to model the text. The model is experimented on the ASAP composition data set. The experimental results show that the model proposed in this paper is 6% higher than the strong baseline model, and the automatic scoring effect is improved to a certain extent.

The Bcl-2 family of proteins, such as Bcl-xL and Bcl-2, play key roles in cancer cell survival. Structural studies of Bcl-xL formed the foundation for the development of the first Bcl-2 family inhibitors and FDA approved drugs. Recently

Summary Mutations in TREM2, a receptor expressed by microglia in the brain, are associated with an increased risk of neurodegeneration, including Alzheimer's disease. Numerous studies support a role for TREM2 in sensing damaging stimuli and triggering signaling cascades necessary for neuroprotection. Despite its significant role, ligands and regulators of TREM2 activation, and the mechanisms governing TREM2-dependent responses and its cleavage from the membrane, remain poorly characterized. Here, we present phage display generated antibody single-chain variable fragments (scFvs) to human TREM2 immunoglobulin-like domain. Co-crystal structures revealed the binding of two scFvs to an epitope on the TREM2 domain distal to the putative ligand-binding site. Enhanced functional activity was observed for oligomeric scFv species, which inhibited the production of soluble TREM2 in a HEK293 cell model. We hope that detailed characterization of their epitopes and properties will facilitate the use of these renewable binders as structural and functional biology tools for TREM2 research., Graphical abstract, Highlights • scFvs were generated against the immunoglobulin-like domain of the receptor TREM2 • Crystal structures revealed scFv binding to epitopes outside the TREM2 CDRs • Oligomeric scFv species reduced levels of shed TREM2 ectodomain in a HEK293 model • The scFvs form renewable structural and functional biology tools for TREM2 research, TREM2 variants are associated with an increased risk of dementia. Szykowska et al. generated scFv antibody fragments to TREM2 immunoglobulin-like domain and solved crystal structures of scFv-TREM2 complexes to reveal their binding modes. Oligomeric scFv species showed enhanced functional activity reducing levels of shed TREM2 ectodomain in a HEK293 model.

SIRT1, the founding member of the mammalian family of seven NAD+-dependent sirtuins, is composed of 747 amino acids forming a catalytic domain and extended N- and C-terminal regions. We report the design and characterization of an engineered human SIRT1 construct (mini-hSIRT1) containing the minimal structural elements required for lysine deacetylation and catalytic activation by small molecule sirtuin-activating compounds (STACs). Using this construct, we solved the crystal structure of a mini-hSIRT1-STAC complex, which revealed the STAC-binding site within the N-terminal domain of hSIRT1. Together with hydrogen-deuterium exchange mass spectrometry (HDX-MS) and site-directed mutagenesis using full-length hSIRT1, these data establish a specific STAC-binding site and identify key intermolecular interactions with hSIRT1. The determination of the interface governing the binding of STACs with human SIRT1 facilitates greater understanding of STAC activation of this enzyme, which holds significant promise as a therapeutic target for multiple human diseases., Sirtuins are NAD+-dependent deacylases implicated in the regulation of stress responses, bioenergetics and epigenetic control. Here the authors describe the crystal structure of a sirtuin-activating compounds (STAC)-sirtuin complex and begin to elucidate the mechanism of sirtuins activation by STACs.

Carba-NAD is a synthetic compound identical to NAD except for one substitution, where an oxygen atom adjacent to the anomeric linkage bearing nicotinamide is replaced with a methylene group. Because it is inert in nicotinamide displacement reactions, carba-NAD is an unreactive substrate analogue for NAD-consuming enzymes. SIRT3 and SIRT5 are NAD-consuming enzymes that are potential therapeutic targets for the treatment of metabolic diseases and cancers. We report an improved carba-NAD synthesis, including a pyrophosphate coupling method that proceeds in approximately 60% yield. We also disclose the X-ray crystal structures of the ternary complexes of SIRT3 and SIRT5 bound to a peptide substrate and carba-NAD. These X-ray crystal structures provide critical snapshots of the mechanism by which human sirtuins function as protein deacylation catalysts.

Synergistic Learning Tool Kits (SLTK) support coordinated individual development and effective group interaction during learning process. This article focused on interoperation between learning tools of SLTK. By analyzing existing problems in the interoperation process, we put forward Learning Footprints, a data transmission specification based on XML for SLTK, to solve the problem of data transmission of interoperation.

Self-regulated learning (SRL) plays an important role in most life-long training projects. Easy and flexible interaction with system is an important factor impacting learners' motivation and learning outcomes. This study was carried out during Shanghai Ganbu (SHGB) training platform's design and development process. The emphasis was placed on the applicability of the User-Centered Design (UCD) method for improving usability of online learning system. Data was collected from 26 surveys to investigate the system's interface design, effectiveness and satisfaction. Paired samples t-test was applied to pre-test and post-test results. Finding indicates that UCD is an effective method to improving SRL system design.

Self-regulated learning (SRL) plays an important role in most life-long training projects. In SRL, easy and flexible interaction with system is a primary factor impacting learners' motivation and outcomes. The purpose of this study is to evaluate a government training platform with Performance Analysis and User Perception methods to investigate the system's efficiency, effectiveness and satisfaction. In this study, efficiency and effectiveness were evaluated by Time on Task and Task Completion score, and satisfaction was evaluated by Questionnaire and Interviews. Based on our findings, this article identified the main design problems that frustrated learners and distracted them from learning tasks, and provided some suggestions for interface design of e-Learning platform.