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Analysis of mitochondrial genomes (mtDNA) by using whole-genome sequencing data from 2,658 cancer samples across 38 cancer types identifies hypermutated mtDNA cases, frequent somatic nuclear transfer of mtDNA and high variability of mtDNA copy number in many cancers.

Here, using a mouse model, the authors report a previously undescribed role for medium-chain acyl-CoA dehydrogenase in host metabolism of gut microbiota metabolites, and show that circulating compounds, including the abundant organic acid hippurate, depend on host-microbe co-metabolism of phenylalanine by Clostridium sporogenes.

A randomized trial in patients hospitalized with COVID-19 showed no benefit and potentially increased harm associated with the use of convalescent plasma, with subgroup analyses suggesting that the antibody profile in donor plasma is critical in determining clinical outcomes.

Environmental drivers of soil carbon and its sensitivity to warming are poorly understood. The authors compare soil samples of paired urban and natural ecosystems and show that under warming, the microbiome is an essential driver of soil carbon in urban greenspace compared with natural ecosystems.

An investigation using various methods reports an association between adeno-associated virus 2 and paediatric hepatitis of unknown aetiology.

PPARg is differentially expressed in bladder cancer subtypes. Here, the authors show in mice that when an activated form of PPARg is expressed in basal bladder cells tumours do not form, however in the presence of injury the basal cells differentiate into luminal cells.

Many intracellular pathogens mimic extracellular matrix motifs to specifically interact with the host membrane which may influences virus particle uptake. Here authors use single molecule tension sensors to reveal the minimal forces exerted on single virus particles and demonstrate that the uptake forces scale with the adhesion energy.

Efficient, large-scale genomic analysis is facilitated on the cloud by a computational tool with error-diagnosing and self-healing capabilities.

Genomic and transcriptomic analysis of lung adenocarcinoma (LUAD) in Asia indicates that Asian LUADs have fewer mutations, lower driver prevalence and fewer copy number alterations than European LUADs.

Unilateral occipitotemporal resection in children with drug-resistant epilepsy reveals both typical and reorganized category maps, with word/face selectivity competing in the preserved ventral visual pathway over time, reflecting plasticity.

Deploying two unrelated CRISPR nucleases in tandem, with multiplexed CRISPR RNAs and a chemically stabilized activator, creates a simple, one-step assay that can rapidly detect attomolar concentrations of RNA without needing target amplification.

Vaccination is effective in protecting from COVID-19. Here the authors report immune responses and breakthrough infections in twice-vaccinated patients receiving anti-TNF treatments for inflammatory bowel disease, and find dampened vaccine responses that implicate the need of adapted vaccination schedules for these patients.

Analysis of whole-genome sequencing data across 2,658 tumors spanning 38 cancer types shows that chromothripsis is pervasive, with a frequency of more than 50% in several cancer types, contributing to oncogene amplification, gene inactivation and cancer genome evolution.

The authors report an efficacious vaccine for human metapneumovirus based on a prefusion-stabilized fusion protein trimer that does not require a trimerization domain, designed using an AI convolutional classifier trained to predict optimized complex polar interactions.

Temporalis muscle thickness is a promising marker of lean muscle mass but has had limited utility due to its unknown normal growth trajectory and lack of standardized measurement. Here, the authors develop an automated deep learning pipeline to accurately measure temporalis muscle thickness from routine brain magnetic resonance imaging.

The Cancer Genome Atlas presents an integrative genome-wide analysis of genetic alterations in 279 head and neck squamous cell carcinomas (HNSCCs), which are classified by human papillomavirus (HPV) status; alterations in EGFR, FGFR, PIK3CA and cyclin-dependent kinases are shown to represent candidate targets for therapeutic intervention in most HNSCCs.

The nuclear receptor Pparg regulates urothelial differentiation in vitro but its role in healthy urothelium is unclear. Here, the authors show that PPAR gamma mediates urothelial development during both homeostasis (via mitochondrial function) and following infection, via an inflammatory response.

Many tumors evade immunosurveillance by down-modulating expression of antigen-processing machinery and MHC molecules. Yang et al. report triple-negative tumor cell expression of the lncRNA LINK-A enhances degradation of antigen peptide-loading complex molecules and intrinsic tumor suppressors, which contribute to tumor persistence.

A graphene transistor integrated on-chip on a hexagonal boron nitride-capped TaS₂ layer provides a voltage-tunable, low-resistance load for controlling a TaS₂ metal–insulator transition, enabling a compact voltage-controlled oscillator operating at room temperature.

In a widespread sampling campaign across urban soils, the authors find that soil biodiversity, but not plant diversity, is positively related to multiple ecosystem functions in urban environments.

The directed evolution of antibodies yields important tools for research and therapy. Here the authors develop a periplasmic phage-assisted continuous evolution platform for improvement of protein-protein interactions in the disulfidecompatible E. coli periplasm.

A custom adenine base editor can edit the variant of the β-globin gene that causes sickle cell disease into a non-pathogenic variant in human and mouse cells, and transplantation of the edited cells rescues sickle cell disease in mice.

Rulla Tamimi and colleagues report a meta-analysis of five genome-wide association studies for percent mammographic density. They identify an associated locus at ZNF365, which has also been associated with susceptibility to breast cancer.

SARS-CoV-2 infection can result in severe lung inflammation and pathology, but host response remains incompletely understood. Here the authors show in Syrian hamsters that STAT2 signaling restricts systemic virus dissemination but also drives severe lung injury, playing a dual role in SARS-CoV-2 infection.

Alterations of locus coeruleus signal intensity have been associated with functional changes in health and disease. Here, the authors tested a pre-registered hypothesis on a large number of subjects as part of the Cam-CAN consortium.

Liquid water reforming of methanol is a promising method for on-demand hydrogen production. An atomic-level catalyst design strategy, using synergy between single atoms and nanodots, is now shown to demonstrate a high quantum efficiency for hydrogen production.

In this prospective cohort study, authors follow 328 households in Germany with at least one confirmed SARS-CoV-2 infection and find that children are more likely to seroconvert without symptoms and have higher specific antibody levels that persist longer than in adults.

Tamnes et al. explore the complex relationship between ill-being—including mental and behavioural disorders—and mental well-being.

EGFR mutant lung adenocarcinoma (LUAD) exhibit diverse clinical outcomes in response to targeted therapies. Here the authors show that these LUADs involve a complex genomic landscape with high intratumor heterogeneity, providing insights into the evolutionary trajectory of oncogene-driven LUAD and potential mediators of EGFR TKI resistance.

The Cancer Genome Atlas Research Network report integrated genomic and molecular analyses of 164 squamous cell carcinomas and adenocarcinomas of the oesophagus; they find genomic and molecular features that differentiate squamous and adenocarcinomas of the oesophagus, and strong similarities between oesophageal adenocarcinomas and the chromosomally unstable variant of gastric adenocarcinoma, suggesting that gastroesophageal adenocarcinoma is a single disease entity.

Genomic analysis of 491 medulloblastoma samples, including methylation profiling of 1,256 cases, effectively assigns candidate drivers to most tumours across all molecular subgroups.

Leidal et al. show that the LC3-conjugation pathway, which is part of the autophagy machinery, controls extracellular vesicle cargo loading and secretion of RNA-binding proteins.

Patient-derived xenograft models (PDX) have been extensively used to study the molecular and clinical features of cancers. Here the authors present a cohort of 536 PDX models from 25 cancers, as well as their genomic and evolutionary profiles and their suitability for clinical trials.

This paper reports integrative molecular analyses of urothelial bladder carcinoma at the DNA, RNA, and protein levels performed as part of The Cancer Genome Atlas project; recurrent mutations were found in 32 genes, including those involved in cell-cycle regulation, chromatin regulation and kinase signalling pathways; chromatin regulatory genes were more frequently mutated in urothelial carcinoma than in any other common cancer studied so far.

This paper describes molecular subtypes of cervical cancers, including squamous cell carcinoma and adenocarcinoma clusters defined by HPV status and molecular features, and distinct molecular pathways that are activated in cervical carcinomas caused by different somatic alterations and HPV types.

Through use of a split-intein pIII, soluble expression phage-assisted continuous evolution (SE-PACE) enables two simultaneous positive selections to rapidly evolve proteins with improved expression while maintaining their desired activities.

A systems-based approach to profile glucocorticoid (GC) receptor ligands in a broad range of assays representing different phenotypic responses linked these to transcriptional profiles and led to separation of GC therapeutic effects from side effects.

Adult forms of inflammatory bowel disease (IBD) are of a polygenic nature, but paediatric and very early onset (VEO) IBD also occur as monogenic forms. Here, using whole exome sequencing, the authors explore both the monogenic and polygenic contribution to VEO-IBD and characterize a rare somatic mosaic VEO-IBD patient.

SARS-CoV-2 S protein prematurely refolds to the post-fusion conformation, compromising immunogenic properties and prefusion trimer yield. Here, Juraszek et al. present a stable SARS-CoV-2 S-closed protein variant with increased expression and correct folding, predominantly in closed prefusion conformation.

Acupuncture can locally reduce pain, but it has remained unclear how it might work. Goldman et al. find that acupuncture elevates local tissue adenosine levels in a mouse model. The anti-nociceptive effect of acupuncture was absent in mice lacking the adenosine receptor A1.

A systematic review of evidence, across the key pillars of prevention, diagnosis, treatment and prognosis, outlines milestones that need to be met to enable the broad clinical implementation of precision medicine in diabetes care.

A global field survey that analyses samples of soil from all continents identifies hotspots for soil nature conservation, and shows that different ecological dimensions of soil are associated with different priority areas for conservation.

Investigating stimulus-evoked pupil size, blinking, and microsaccade dynamics as indicators of conscious awareness, conscious content, and visual sensory cortical processing in the blind visual field of people with cerebral blindness.

A COVID-19 test implemented in an automated microfluidic device and leveraging isothermal RNA amplification followed by T7 transcription and Cas13-mediated cleavage of a quenched fluorophore rapidly detects SARS-CoV-2 RNA in saliva samples.

The enzyme Atgl participates in the breakdown of lipids in adipose tissue. Here the authors show that pharmacological inhibition of Atgl reduces weight gain and improves metabolic health in mice fed a high-fat diet, without causing adverse effects in cardiac muscle associated with genetic depletion ofAtgl.