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A working group of Academia Europaea proposes the addition of a ‘ring diagram’ in clinical publications for the quick evaluation of translational implications.

Analysis of snRNA genes in individuals with rare disorders identifies de novo and recurrent variants in RNU5B-1 and RNU5A-1, in addition to previously unreported cases with pathogenic or likely pathogenic variants in RNU4-2.

A set of CRISPR–Cas9-based genetic screens in a haploid human cell line identifies more than 200 gene–drug associations involving solute carriers (SLCs), transporters important for the uptake and activity of cytotoxic drugs.

The pore-forming toxin pneumolysin is responsible for the high mortality seen in pneumococcal infections unresponsive to antibiotics. In this work, authors report a small molecule inhibitor targeting pneumolysin and related ones as an anti-virulence strategy protecting human cells during infection.

The wheat Pm4 gene conferring race-specific powdery mildew resistance is identified to encode a chimeric kinase-MCTP protein. Its two alternative splice variants interact to form an ER-associated complex and are both essential for resistance function.

Peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS) is a heterogeneous and aggressive type of T-cell lymphoma. Here, the authors perform single-cell analyses of human and murine PTCL-NOS tumors, and identify a subtype defined by the loss of SMARCB1 that could be targeted with HDAC-inhibitor combination therapies.

Histone H3 lysine 14 is propionylated and butyrylated in vivo in a metabolic-state-dependent manner and these modifications promote high levels of transcription.

The biogenesis of nuclear pores imposes a logistic challenge for cells. Here, the authors investigate structural motifs for co-translational interactions in nucleoporins and find that co-translational assembly events differ between paralogous assembly pathways thus contributing to faithful assembly.

Long non-coding RNAs (lncRNAs) can contribute to cancers that are driven by Sonic hedgehog (SHH) signaling. Here the authors report that lncRNA HHIP-AS1 stabilises the mRNA of dynein complex 1, thereby, promoting the pro-mitotic effects of SHH-driven tumors.

Outer membrane protein HopQ binds human CEACAMs and serves as an adhesin for Helicobacter pylori.

Deep learning holds a great promise for the discovery and design of bioactive peptides, but experimental approaches to validate candidates in high throughput and at low cost are needed. Here, the authors combine deep learning and cell free biosynthesis for antimicrobial peptide (AMP) development and identify 30 functional AMPs, of which six with broad-spectrum activity against drug-resistant pathogens.

M. tuberculosis cytochrome bd oxidase is of interest as a TB drug target. Here, the authors present the 2.5 Å cryo-EM structure of M. tuberculosis cytochrome bd oxidase and identify a disulfide bond within the canonical quinol binding and oxidation domain (Q-loop) and a menaquinone-9 binding site at heme b₅₉₅.

The full-length structure of HUWE1 reveals the bipartite organization of a giant E3 ubiquitin ligase, comprising a catalytic HECT domain and a large, ring-shaped scaffold that provides docking sites for various substrates and regulates E3 activity.

Repression of gene expression contributes to lineage-specific transcriptional signatures. Here Lackner et al. demonstrate that the Erf-NCoR1/2 complex controls trophoblast differentiation by linking signalling with transcriptional repression

Krönke and colleagues show that the cytokine IL-23 controls the glycosylation profile and inflammatory activity of autoantibodies through control of sialyltransferase activity in plasma cells mediated by the T_H17 subset of helper T cells.

OPA1 regulates the formation of the distinct mitochondrial morphology observed in T helper 17 cells, which influences cytokine expression via LKB1.

Chondroitin sulfate proteoglycan 4 (CSPG4) is a potential receptor for C. difficile toxin B (TcdB) during C. difficile infections (CDIs). Here, the cryo-EM structure of a TcdB–CSPG4 complex and CDI mouse models offer insights into CSPG4 role in CDIs and suggest a therapeutic strategy targeting TcdB.

Fine-scale geospatial mapping of overweight and wasting (two components of the double burden of malnutrition) in 105 LMICs shows that overweight has increased from 5.2% in 2000 to 6.0% in children under 5 in 2017. Although overall wasting decreased over the same period, most countries are not on track to meet the World Health Organization’s Global Nutrition Target of <5% in over half of LMICs by 2025.

Evolutionarily conserved gene modules mediate neurodegenerative dementia in a variety of mouse models and in postmortem brain tissue from patients.

Studying the dynamics of electrons is important for understanding fundamental processes in materials. Here the ionization of a pair of electrons in argon atoms is explored on attosecond timescales, offering insight into their correlated emission and the double ionization mechanism.

Previous studies have shown that both rare pathogenic mutations and common genetic variants contribute to the familial risk of developing colorectal cancer. Here, the authors carry out a two-stage genome-wide association study and identify six new loci associated with colorectal cancer.

Superantigens are bacterial toxins that interact with host immunoreceptors. Salineet al.report the X-ray structure of staphylococcal enterotoxin H in complex with its human receptors, MHC class II and the T-cell receptor, providing new insights into superantigenic T-cell activation.

Wear-resistant metals have long been a pursuit of reducing wear-related energy and material loss. Here the authors present the ‘reactive wear protection’ strategy via friction-induced in situ formation of strong and deformable oxide nanocomposites on a surface.

Methane is abundant in marine sediments. Analysis of sediment cores and seismic images of marine sediments obtained off the coast of Pakistan show fracturing of gas hydrates and an increase in upward methane flux in the decades following a large earthquake in the Arabian Sea in 1945, suggesting that quakes can trigger hydrocarbon seepage.

The COSIMA mass spectrometer on the Rosetta spacecraft has analysed the solid organic matter found in dust particles emitted by comet 67P/Churyumov–Gerasimenko; this matter is similar to the insoluble organic matter extracted from carbonaceous chondrites such as the Murchison meteorite, but is perhaps more primitive.

Effective therapeutic platforms should combine serum stability, selective targeting, and controlled drug release. Here, the authors self-assemble an aptamer-based nanoscaffold that contains separate cell-targeting and photo-regulated drug-carrying domains, realizing multiple therapeutic functionalities in a single construct.

Cytokine storm seems to be a common feature of severe COVID-19 pathology. Here, the authors show a reduced rate of SARS-CoV2 positivity in a large population of patients with immune-mediated inflammatory diseases if they are already being treated with cytokine or JAK inhibitors, indicating these treatments are safe to continue and are possibly protective against COVID19.

VirtualFlow, an open-source drug discovery platform, enables the efficient preparation and virtual screening of ultra-large ligand libraries to identify molecules that bind with high affinity to target proteins.

By comparing data from real-world grassland communities with data from two of the longest-running grassland biodiversity–ecosystem functioning experiments, the authors show that conclusions derived from experimental systems are robust to the removal of unrealistic experimental communities.

Certain plants in the nightshade family contain withanolides, defensive chemicals known to be harmful to most insect herbivores. Here, Barthel et al. show that a moth species that is a specialist herbivore of these plants benefits from the compounds by gaining increased immunity to a pathogen.

Environmental DNA from unculturable microorganisms contains genes with useful functions that remain difficult to identify and isolate. Here Colin, Kintses et al.demonstrate the screening of millions of samples in pL volumes to directly identify new enzymatic activities and complements sequence-based approaches.

Activins are members of the TGF-β family of growth factors that are processed from precursors into the mature proteins. Here, the authors use structural biology and biochemistry to examine the protein domain organisation and gain insights into the activation of pro-activin A.

Survival outcomes in Burkitt lymphoma differ between adult and paediatric patients. Here, the authors show differences in mutational frequencies between age groups, and a transition between mutational profiles which occurs between 25 and 40 years.

Lake Tanganyika’s cichlid radiation is the main source of East African cichlid diversity. Irisarri et al. resolve its phylogenetic backbone using anchored phylogenomics and identify trans-lineage hybridization prior to major speciation bursts and adaptive loci underlying ecological innovations.

Though people learn that certain choices may be more advantageous, they often do not choose this option. Here, the authors explain this behaviour: people learn how good a choice is relative to the choices it has been associated with previously, and this learning takes place in the striatum.

Nanocrystals - such as quantum dots and magnetic nanoparticles - embedded in lipoproteins can be used to image and quantify the kinetics of lipid metabolism in vivo in a non-invasive manner using fluorescence and dynamic magnetic resonance imaging.