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A large-scale study on the replicability of claims from social and behavioural science journals reports that about half of the results replicate in the same patterns as the original study.

Here, the authors reveal that the mitotic motor KIF11 functions in postmitotic neurons as a microtubule-dynamics rheostat to regulate dendritic arborization. Additionally, they show how MCLID mutations impair KIF11 oligomerization, ATP hydrolysis, neuronal structure, and communication.

Robustness checks and reproduction of analyses with existing and updated data based on 110 articles in economics and political science journals with data and code-sharing requirements found high levels of robustness and reproducibility and determined that robustness was not dependent on author characteristics or data availability.

The efficacy of CAR-T cells against solid tumors is still limited by immunosuppressive factors. Here, the authors show that engineering of CAR T cells with A1R enhances their efficacy against solid tumors in vitro and in vivo.

RFdiffusion2, an extension of the RFdiffusion framework, builds de novo enzyme active sites using atom-level functional group constraints.

Computational methods are becoming an increasingly important part of biological research. Using the Rosetta framework as an example, the authors demonstrate how community-driven development of computational methods can be done in a reproducible and reliable fashion.

Lactone monomers for recyclable polyesters are conventionally synthesized via endergonic, non-oxidative dehydrocyclization of fossil-derived diols in the vapor phase over precious-metal catalysts at elevated temperatures. Here, the authors demonstrate a low-temperature, solvent-free, oxidative route to lactones from bio-derivable liquid diols using earth-abundant calcium-copper mixed-metal oxide catalysts.

Thermal imaging lenses are typically made from expensive materials such as germanium and silicon. Here, the authors synthesise a sulfur-based polymer with high mid-wave infrared and long-wave infrared transparencies, presenting a high-performing, low-cost alternative to traditional thermal imaging lens materials.

Boronic acids are promising catalysts for the direct functionalization of alcohols without requiring precious metals. Here, the authors report an easily synthesized class of cyclic hemiboronic acid catalysts which are applicable in both nucleophilic and electrophilic modes of alcohol activation.

C4ʹ-modified nucleoside analogues attract global attention, but current approaches for the synthesis involve lengthy, nonmodular routes. Herein, the authors report a modular 5-step process to a diverse collection of C4ʹ-modified nucleoside analogues through a sequence of intramolecular trans-acetalizations of polyhydroxylated frameworks.

A global network of researchers was formed to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity; this paper reports 13 genome-wide significant loci and potentially actionable mechanisms in response to infection.

V-domain immunoglobulin suppressor of T cell activation (VISTA) selectively engages P-selectin glycoprotein ligand-1 (PSGL-1) and suppresses T cells at acidic pH similar to those in tumour microenvironments, thereby mediating resistance to anti-tumour immune responses.

Uranium oxo groups are very inert, in contrast with many transition metal oxo compounds that can carry out reactions that are difficult to achieve with other reagents. Now, the controlled lithiation of a ‘Pacman’ complex is shown to activate the uranium oxo group towards functionalization and single electron transfer.

Mass-wasting deposits that accumulated against mid-ocean ridge faults have high porosity in which calcium carbonate precipitated, storing seawater carbon dioxide, as revealed by cores of a 61-million-year-old seafloor talus deposit.

¹³⁴Ce and ¹³⁴La have great potential as companion diagnostic isotopes for radiotherapeutics labelled with α-emitting ²²⁵Ac and ²²⁷Th. Now, by controlling the Ce^III/Ce^IV redox couple, the large-scale production, purification and characterization of ¹³⁴Ce- and ¹³⁴La-based radiolabels has been achieved and their use for in vivo positron emission tomography is demonstrated.

Mitochondria with mutations in their DNA from cancer cells can be transferred to T cells in the tumour microenvironment, which leads to T cell dysfunction and impaired antitumour immunity.

Genomic analyses applied to 14 childhood- and adult-onset psychiatric disorders identifies five underlying genomic factors that explain the majority of the genetic variance of the individual disorders.

Compounds bearing a carbonyl group, such as aldehydes and ketones, are important industrial chemicals and widespread in pharmaceuticals and natural products. Here, the authors report a strategy for visible-light photoredox-catalyzed umpolung carboxylation of diverse carbonyl compounds with CO₂, to generate valuable α-hydroxycarboxylic acids.

A combination of high-resolution spatial imaging, spatial proteomics and transcriptional data reveals sparse and heterogeneous bacterial signals in gliomas and brain metastases.

An analysis of 24,202 critical cases of COVID-19 identifies potentially druggable targets in inflammatory signalling (JAK1), monocyte–macrophage activation and endothelial permeability (PDE4A), immunometabolism (SLC2A5 and AK5), and host factors required for viral entry and replication (TMPRSS2 and RAB2A).

Sera from vaccinated individuals and some monoclonal antibodies show a modest reduction in neutralizing activity against the B.1.1.7 variant of SARS-CoV-2; but the E484K substitution leads to a considerable loss of neutralizing activity.

This study describes a simple catalyst that can be used to protect secondary alcohols with a silyl protecting group. High yields and enantioselectivies for a number of substrates were obtained. This, and related, catalysts may be used to synthesize, in a more practical and efficient manner, important organic molecules.

Chronic infection with SARS-CoV-2 leads to the emergence of viral variants that show reduced susceptibility to neutralizing antibodies in an immunosuppressed individual treated with convalescent plasma.

Cyanide is thought to be crucial for the origin of life. Here, the authors showed that iron cyanocarbonyl complexes are present in meteorites and propose that these compounds were a source of free cyanide on early Earth and served as precursors to the active sites of ancient hydrogenases.

Here the authors provide an explanation for 95% of examined predicted loss of function variants found in disease-associated haploinsufficient genes in the Genome Aggregation Database (gnomAD), underscoring the power of the presented analysis to minimize false assignments of disease risk.

With the generation of large pan-cancer whole-exome and whole-genome sequencing projects, a question remains about how comparable these datasets are. Here, using The Cancer Genome Atlas samples analysed as part of the Pan-Cancer Analysis of Whole Genomes project, the authors explore the concordance of mutations called by whole exome sequencing and whole genome sequencing techniques.

Analyses of genome and exome sequencing data identify rare coding and structural variants associated with atrial fibrillation and highlight genetic links between atrial fibrillation and cardiomyopathies.

A CRISPR knock-in strategy that uses endogenous gene regulatory mechanisms can engineer ‘armoured’ CAR T cells that secrete proinflammatory cytokines directly within a tumour without causing toxicity, leading to prolonged survival in mice.

HIV binding is mediated via CD4 and chemokine co-receptors, but this does not explain the preferential infection of central memory CD4+ T cells. Here the authors show HIV targets L-selectin, induces shedding from the infected cell, and inhibition of L-selectin reduces HIV infection and release.

Combining cycloaddition and carbon–carbon cross-coupling offers a way of simplifying the enantioselective preparation of chemical building blocks, natural products and medicines such as the antipsychotic asenapine.

The rat is a widely-used model for human biology, but we must be aware of metabolic differences. Here, the authors reconstruct the genome-scale metabolic network of the rat, and after reconciling it with an improved human metabolic model, demonstrate the power of the models to integrate toxicogenomics data, providing species-specific biomarker predictions in response to a panel of drugs.

Radiotherapy induces expression of the EGFR ligand amphiregulin, which promotes metastasis growth at remote sites in mouse models and human patients by shifting myeloid cells towards an immunosuppressive state.

The flagship paper of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes Consortium describes the generation of the integrative analyses of 2,658 cancer whole genomes and their matching normal tissues across 38 tumour types, the structures for international data sharing and standardized analyses, and the main scientific findings from across the consortium studies.

Whole-genome sequencing, transcriptome-wide association and fine-mapping analyses in over 7,000 individuals with critical COVID-19 are used to identify 16 independent variants that are associated with severe illness in COVID-19.

Trastuzumab deruxtecan (T-DXd) is an antibody-drug conjugate targeting HER2 but paradoxically efficient even in breast cancers expressing HER2 at very low levels. Here authors show that invasive breast cancers, even if their HER2 expression is negligible, secrete extracellular proteases, such as cathepsin L, which cleave the specialized linker of T-DXd, releasing the drug in the tumour microenvironment, while in HER2 positive breast cancers, T-DXd engages Fcγ receptors to promote phagocytosis of HER2-expressing cells and triggers payload-induced immunogenic cell death.

The authors present SVclone, a computational method for inferring the cancer cell fraction of structural variants from whole-genome sequencing data.

Analysis of cancer genome sequencing data has enabled the discovery of driver mutations. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium the authors present DriverPower, a software package that identifies coding and non-coding driver mutations within cancer whole genomes via consideration of mutational burden and functional impact evidence.

Using well-calibrated statistical methods the authors jointly analyze Undiagnosed Diseases Network genomes, identifying known and novel disease genes. Software is publicly available to support future cross-cohort rare disease discovery efforts.

A study of the evolution of the SARS-CoV-2 virus in England between September 2020 and June 2021 finds that interventions capable of containing previous variants were insufficient to stop the more transmissible Alpha and Delta variants.

Integrative analyses of transcriptome and whole-genome sequencing data for 1,188 tumours across 27 types of cancer are used to provide a comprehensive catalogue of RNA-level alterations in cancer.

Cancers evolve as they progress under differing selective pressures. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, the authors present the method TrackSig the estimates evolutionary trajectories of somatic mutational processes from single bulk tumour data.

Understanding deregulation of biological pathways in cancer can provide insight into disease etiology and potential therapies. Here, as part of the PanCancer Analysis of Whole Genomes (PCAWG) consortium, the authors present pathway and network analysis of 2583 whole cancer genomes from 27 tumour types.

Analyses of 2,658 whole genomes across 38 types of cancer identify the contribution of non-coding point mutations and structural variants to driving cancer.

Some cancer patients first present with metastases where the location of the primary is unidentified; these are difficult to treat. In this study, using machine learning, the authors develop a method to determine the tissue of origin of a cancer based on whole sequencing data.

Multi-omics datasets pose major challenges to data interpretation and hypothesis generation owing to their high-dimensional molecular profiles. Here, the authors develop ActivePathways method, which uses data fusion techniques for integrative pathway analysis of multi-omics data and candidate gene discovery.

Oncolytic viruses create an inflamed tumour microenvironment allowing T cells to respond to immune checkpoint blockade therapy more efficiently. Authors here show that in a hepatocellular carcinoma model, a dominant anti-viral rather than anti-tumour T cell response is elicited by an oncolytic vesicular stomatitis virus, unless the virus is designed to express tumour antigens, which restores therapeutic benefit.