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The Research Collaboratory for Structural Bioinformatics Protein Data Bank (RCSB PDB), founding member of the Worldwide Protein Data Bank (wwPDB), is the US data center for the open-access PDB archive. As wwPDB-designated Archive Keeper, RCSB PDB is also responsible for PDB data security. Annually, RCSB PDB serves >10 000 depositors of three-dimensional (3D) biostructures working on all permanently inhabited continents. RCSB PDB delivers data from its research-focused RCSB.org web portal to many millions of PDB data consumers based in virtually every United Nations-recognized country, territory, etc. This Database Issue contribution describes upgrades to the research-focused RCSB.org web portal that created a one-stop-shop for open access to ∼200 000 experimentally-determined PDB structures of biological macromolecules alongside >1 000 000 incorporated Computed Structure Models (CSMs) predicted using artificial intelligence/machine learning methods. RCSB.org is a ‘living data resource.’ Every PDB structure and CSM is integrated weekly with related functional annotations from external biodata resources, providing up-to-date information for the entire corpus of 3D biostructure data freely available from RCSB.org with no usage limitations. Within RCSB.org, PDB structures and the CSMs are clearly identified as to their provenance and reliability. Both are fully searchable, and can be analyzed and visualized using the full complement of RCSB.org web portal capabilities.

The honey bee genome has the capacity to produce three phenotypically distinct organisms (two diploid female castes: queen and worker, and a haploid male drone). Previous studies have implicated metabolic flux acting via epigenetic regulation in directing nutrition-driven phenotypic plasticity in the honey bee. However, the cis-acting DNA regulatory elements that establish tissue and polyphenism -specific epigenomes and gene expression programmes, remain unclear. Using a high resolution multiomic approach including assay for transposase-accessible chromatin by sequencing (ATAC-seq), RNA-seq and ChIP-seq, we produce the first genome-wide maps of the regulatory landscape across all three adult honey bee phenotypes identifying > 5000 regulatory regions in queen, 7500 in worker and 6500 in drone, with the vast majority of these sites located within intronic regions. These regions are defined by positive enrichment of H3K27ac and depletion of H3K4me3 and show a positive correlation with gene expression. Using ATAC-seq footprinting we determine queen, worker and drone -specific transcription factor occupancy and uncover novel phenotype-specific regulatory networks identifying two key nuclear receptors that have previously been implicated in caste-determination and adult behavioural maturation in honey bees; ecdysone receptor and ultraspiracle. Collectively, this study provides novel insights into key gene regulatory networks that are associated with these distinct polyphenisms in the honey bee.

Studies on native-speakerism in Japan have covered a variety of issues, and recent work has adopted a framing perspective to examine hidden strands of native-speakerist ideology within the profession which often go unrecognized. Defining a frame as an ideologically-constructed perceptual filter which influences how situations are interpreted, this research has attempted to break down the discourses of dominant or master frames to show the influence of native-speakerist ideology in particular contexts, and to investigate how counter frames have been constructed in resistance to this ideology. This paper will add to this work by focusing on the beliefs of teacher trainees. Through a qualitative study of a class based around critical issues in ELT, the complex web of framing and counter-framing on the part of trainee teachers is examined, and the pervasiveness of the ideology of native-speakerism is highlighted. Finally, some emergent possibilities for resistance are explored. 日本の母語話者中心主義に関する研究は様々な問題を扱ってきたが、最近の研究では、「フレーム理論」の視点を採用し、しばしば認識されることのない母語話者中心主義的イデオロギーの隠れた一面を検証している。本研究では、「フレーム」を、状況の解釈の仕方に影響を与えるイデオロギー的に構築された知覚のフィルターと定義した。また、特定の文脈における母語話者イデオロギーの影響を示すために、支配的または、「主要な（マスター）」フレームの言説を分解し、このイデオロギーに対する「逆の（カウンター）」フレームがいかに構築されてきたかを調査したものである。本論文は、教職課程を履修する学生の信念に注目することで、さらに研究を前進させることを目的としたものだ。ELTの重要な問題に焦点を当てた授業の質的研究を通して、教職課程の学生にあるフレームとカウンターフレームの複雑な関係性を検証し、母語話者中心主義のイデオロギーの広がりを示す。最後に、イデオロギーの影響への抵抗のためのいくつかの新しい可能性を探る。

Vitamin B12 has multiple biochemical functions including in the one-carbon cycle generating a methyl group for DNA methylation, and metabolism of fatty acids and amino acids to generate energy via the citric acid cycle. The aim of our study was to use a combined epigenomic and transcriptomic approach to identify novel genes mediating the effect of B12 on adipogenesis.\ud \ud Human pre-adipocytes (CHUB-S7) were treated with a range of B12 (0–500 nM) concentrations from the day of cell seeding until harvesting in discovery and validation experiments prior to genome-wide methylation analysis using the Illumina HumanMethylation 450Beadchip. For transcriptomic analysis, RNA-seq libraries were run on the Illumina HiSeq 2500. To further investigate the expression of any genes on human adipogenesis, a second human preadipocyte strain was studied (SGBS) by real-time quantitative PCR (qRT-PCR).\ud \ud A combined epigenetic and transcriptomic approach in differentiated human pre-adipocyte cell line, CHUB-S7, identified that the Human cartilage chitinase 3-like protein 2 (CHI3L2) gene was hypo-methylated and had increased expression in low B12 conditions. Furthermore, there was an approximately 1000-fold increase in CHI3L2 expression in the early days of adipocyte differentiation, which paralleled an increase of lipid droplets in differentiated SGBS cells and an increased expression level of markers of mature adipocytes.\ud \ud In summary, we have identified a potential role of the human cartilage chitinase 3-like protein 2 (CHI3L2) in adipocyte function in the presence of low B12 levels.

The Research Collaboratory for Structural Bioinformatics Protein Data Bank (RCSB PDB), funded by the US National Science Foundation, National Institutes of Health, and Department of Energy, has served structural biologists and Protein Data Bank (PDB) data consumers worldwide since 1999. RCSB PDB, a founding member of the Worldwide Protein Data Bank (wwPDB) partnership, is the US data center for the global PDB archive housing biomolecular structure data. RCSB PDB is also responsible for the security of PDB data, as the wwPDB-designated Archive Keeper. Annually, RCSB PDB serves tens of thousands of three-dimensional (3D) macromolecular structure data depositors (using macromolecular crystallography, nuclear magnetic resonance spectroscopy, electron microscopy, and micro-electron diffraction) from all inhabited continents. RCSB PDB makes PDB data available from its research-focused RCSB.org web portal at no charge and without usage restrictions to millions of PDB data consumers working in every nation and territory worldwide. In addition, RCSB PDB operates an outreach and education PDB101.RCSB.org web portal that was used by more than 800,000 educators, students, and members of the public during calendar year 2020. This invited Tools Issue contribution describes (i) how the archive is growing and evolving as new experimental methods generate ever larger and more complex biomolecular structures; (ii) the importance of data standards and data remediation in effective management of the archive and facile integration with more than 50 external data resources; and (iii) new tools and features for 3D structure analysis and visualization made available during the past year via the RCSB.org web portal.

The Protein Data Bank (PDB) archive is a rich source of information in the form of atomic-level 3D structures of biomolecules experimentally determined using macromolecular crystallography (MX), nuclear magnetic resonance (NMR) spectroscopy, and electron microscopy (3DEM). Originally established in 1971 as a resource for protein crystallographers to freely exchange data, today PDB data drive research and education across scientific disciplines. In 2011, the online portal PDB-101 was launched to support teachers, students, and the general public in PDB archive exploration (pdb101.rcsb.org). Maintained by the Research Collaboratory for Structural Bioinformatics PDB, PDB-101 aims to help train the next generation of PDB users and to promote the overall importance of structural biology and protein science to non-experts. Regularly published features include the highly popular Molecule of the Month series, 3D model activities, molecular animation videos, and educational curricula. Materials are organized into various categories (Health and Disease, Molecules of Life, Biotech and Nanotech, and Structures and Structure Determination) and searchable by keyword. A biennial health focus frames new resource creation and provides topics for annual video challenges for high school students. Web analytics document that PDB-101 materials relating to fundamental topics (e.g., hemoglobin, catalase) are highly accessed year-on-year. In addition, PDB-101 materials created in response to topical health matters (e.g., Zika, measles, coronavirus) are well-received. PDB-101 shows how learning about the diverse shapes and functions of PDB structures promotes understanding of all aspects of biology, from central dogma of biology to health and disease to biological energy. This article is protected by copyright. All rights reserved.

Juvenile Idiopathic Arthritis (JIA) broadly refers to a group of heterogenous diseases that share the common feature of chronic inflammatory arthritis of unknown cause lasting longer than 6 weeks with onset before 16 years of age [3]. Patients with autoimmune diseases such as JIA remain under-vaccinated due to hypothetical concern for infection development. However, it is crucial for these patients to be protected against vaccine-preventable illnesses due to their underlying immune dysfunction as well as the various immunomodulatory drugs that are used in its treatment. Current recommendations are out of date, as they clearly advise physicians to avoid giving these important vaccinations due to unsupported concerns that they are putting patients at risk of preventable death from infection arising from live vaccines. We performed a retrospective chart review and obtained data from patients via phone survey. Our results showed that the use of live-attenuated MMR and VZV vaccines is safe in pediatric patients with JIA being treated with biologics, as there were no serious adverse events reported.

Now in its 52nd year of continuous operations, the Protein Data Bank (PDB) is the premiere open-access global archive housing three-dimensional (3D) biomolecular structure data. It is jointly managed by the Worldwide Protein Data Bank (wwPDB) partnership. The Research Collaboratory for Structural Bioinformatics Protein Data Bank (RCSB PDB) is funded by the National Science Foundation, National Institutes of Health, and US Department of Energy and serves as the US data center for the wwPDB. RCSB PDB is also responsible for the security of PDB data in its role as wwPDB-designated Archive Keeper. Every year, RCSB PDB serves tens of thousands of depositors of 3D macromolecular structure data (coming from macromolecular crystallography, nuclear magnetic resonance spectroscopy, electron microscopy, and micro-electron diffraction). The RCSB PDB research-focused web portal (RCSB.org) makes PDB data available at no charge and without usage restrictions to many millions of PDB data consumers around the world. The RCSB PDB training, outreach, and education web portal (PDB101.RCSB.org) serves nearly 700 K educators, students, and members of the public worldwide. This invited Tools Issue contribution describes how RCSB PDB (i) is organized; (ii) works with wwPDB partners to process new depositions; (iii) serves as the wwPDB-designated Archive Keeper; (iv) enables exploration and 3D visualization of PDB data via RCSB.org; and (v) supports training, outreach, and education via PDB101.RCSB.org. New tools and features at RCSB.org are presented using examples drawn from high-resolution structural studies of proteins relevant to treatment of human cancers by targeting immune checkpoints.

Considering structural design at both the macro- and mesoscale can result in novel and non-intuitive solutions, especially for applications in which there exist multiple performance criteria and/or constraints across multiple physical fields. In such an approach, it is crucial that the bounds of the design space at the mesoscale are well-defined such that the response of the structure at the macroscale remains feasible. Previous work has demonstrated the use of radial basis function (RBF) interpolations to generate N-dimensional constraint surfaces using optimal responses from a single Pareto frontier obtained via an initial optimization study that considers mesoscale structural topologies generated using a parametric L-system approach. However, it has been determined that the responses from a single Pareto frontier allow for the RBF constraints to extrapolate into areas that remain infeasible and are thus inadequate to fully define the bounds of the design space. This work will explore the extension of this approach to consider the 2N Pareto frontiers that exist for a given problem and demonstrate that they result in more rigorous material property constraints. This method will then be applied to an academic example that considers both structural and thermal boundary conditions, and the effects of both the material property constraints and trade-offs between the two sets of boundary conditions will be detailed.

Motivation Membrane proteins are encoded by approximately one fifth of human genes but account for more than half of all US FDA approved drug targets. Thanks to new technological advances, the number of membrane proteins archived in the PDB is growing rapidly. However, automatic identification of membrane proteins or inference of membrane location is not a trivial task. Results We present recent improvements to the RCSB Protein Data Bank web portal (RCSB PDB, rcsb.org) that provide a wealth of new membrane protein annotations integrated from four external resources: OPM, PDBTM, MemProtMD and mpstruc. We have substantially enhanced the presentation of data on membrane proteins. The number of membrane proteins with annotations available on rcsb.org was increased by ∼80%. Users can search for these annotations, explore corresponding tree hierarchies, display membrane segments at the 1D amino acid sequence level, and visualize the predicted location of the membrane layer in 3D. Availability and implementation Annotations, search, tree data and visualization are available at our rcsb.org web portal. Membrane visualization is supported by the open-source Mol* viewer (molstar.org and github.com/molstar/molstar). Supplementary information Supplementary data are available at Bioinformatics online.

Communication and collaboration are key science competencies that support sharing of scientific knowledge with experts and non-experts alike. On the one hand, they facilitate interdisciplinary conversations between students, educators, and researchers, while on the other they improve public awareness, enable informed choices, and impact policy decisions. Herein, we describe an interdisciplinary undergraduate course focused on using data from various bioinformatics data resources to explore the molecular underpinnings of diabetes mellitus (Types 1 and 2) and introducing students to science communication. Building on course materials and original student-generated artifacts, a series of collaborative activities engaged students, educators, researchers, healthcare professionals and community members in exploring, learning about, and discussing the molecular bases of diabetes. These collaborations generated novel educational materials and approaches to learning and presenting complex ideas about major global health challenges in formats accessible to diverse audiences.

Despite a vast expansion in the availability of epigenomic data, our knowledge of the chromatin landscape at interspersed repeats remains highly limited by difficulties in mapping short-read sequencing data to these regions. In particular, little is known about the locus-specific regulation of evolutionarily young transposable elements (TEs), which have been implicated in genome stability, gene regulation and innate immunity in a variety of developmental and disease contexts. Here we propose an approach for generating locus-specific protein–DNA binding profiles at interspersed repeats, which leverages information on the spatial proximity between repetitive and non-repetitive genomic regions. We demonstrate that the combination of HiChIP and a newly developed mapping tool (PAtChER) yields accurate protein enrichment profiles at individual repetitive loci. Using this approach, we reveal previously unappreciated variation in the epigenetic profiles of young TE loci in mouse and human cells. Insights gained using our method will be invaluable for dissecting the molecular determinants of TE regulation and their impact on the genome.

It is a truism that whole energy system models underpin the development of policies for energy system decarbonisation. But recent reviews have thrown doubt on the appropriateness of such models for addressing the multiple goals for future energy systems, in the face of emergent real-world complexity and the evolution of stakeholder’s priorities. Without an understanding of the changing priorities of policy makers and expectations of stakeholders for future systems, system objectives and constraints are likely to be ill-defined, and there is a risk that models may be inadvertently instrumentalised. Adopting a system architecture perspective, the authors have undertaken a three-year programme of research to explore strategies for decarbonising heat in the UK, with interaction with and elicitation of needs from stakeholders at its heart. This paper presents the procedure, methods, and results of an exercise in which experts from stakeholder organisations across the energy system were interviewed. Analysis of interview data reveals two broad approaches to heat decarbonisation which can be broadly defined as either adaptive or transformative. Specific insights gained from these interviews enabled our modelling teams to refocus their work for exploration with a wider circle of stakeholders. Results suggests that this iterative approach to formalising model-policy interaction could improve the transparency and legitimacy of modelling and enhance its impact on policy making.

More than 70% of the experimentally determined macromolecular structures in the Protein Data Bank (PDB) contain small-molecule ligands. Quality indicators of ∼643,000 ligands present in ∼106,000 PDB X-ray crystal structures have been analyzed. Ligand quality varies greatly with regard to goodness of fit between ligand structure and experimental data, deviations in bond lengths and angles from known chemical structures, and inappropriate interatomic clashes between the ligand and its surroundings. Based on principal component analysis, correlated quality indicators of ligand structure have been aggregated into two largely orthogonal composite indicators measuring goodness of fit to experimental data and deviation from ideal chemical structure. Ranking of the composite quality indicators across the PDB archive enabled construction of uniformly distributed composite ranking score. This score is implemented at RCSB.org to compare chemically identical ligands in distinct PDB structures with easy-to-interpret two-dimensional ligand quality plots, allowing PDB users to quickly assess ligand structure quality and select the best exemplars.