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The products and dynamics in mutual neutralisation of \({{{{\rm{O}}}}_{2}}^{+}\) with O⁻ occurring in atmospheric sprites are unknown. Here, the authors reveal a dissociative two-step mechanism via intermediate Rydberg states and a dependence on the \({{{{\rm{O}}}}_{2}}^{+}\) vibrational state.

The Connectome 2.0 MRI scanner reconstructs the fine fibres in the human brain and determines cellular and axonal size at an ultra-high resolution.

How basolateral amygdala represents the specific value of rewards remains unclear. Here the authors find that basolateral amygdala neurons assign stimulus-specific values to different rewards and rapidly re-scale these signals with changing reward context, thirst or stress, illuminating how the brain guides flexible, state-dependent choices.

Non-antibiotic drugs from a wide range of therapeutic classes can alter the ability of gut commensals to resist invasion by enteropathogens, a previously underappreciated side effect of such drugs.

Müller-Tidow and colleagues perform a randomized clinical trial and show that administration of convalescent plasma improves COVID-19 outcome in patients with cancer who are unable to generate an adequate immune response.

CHIMERYS is a spectrum-centric and data acquisition method-agnostic algorithm for the analysis of MS2 spectra. It is capable of deconvoluting any MS2 spectrum, regardless of whether it was acquired by DDA, DIA or PRM, thus unifying the analysis of bottom-up proteomics data.

Urinary albumin-to-creatinine ratio (UCAR) is associated with various clinical outcomes such as kidney disease and cardiovascular disease. Here, the authors report genome-wide meta-analysis in over 500,000 individuals and find 68 UACR loci, followed by statistical fine-mapping, gene prioritization and experimental validation in flies.

Pigs are important large animal models for biomedical research. Here, the authors construct a single-cell landscape of pig tissues, unravelling the phenotypic heterogeneity of blood endothelial cells in adipose tissues and the evolutionally conserved regulons of microglia in brains.

Reduced glomerular filtration rate (eGFR) is a hallmark of chronic kidney disease. Here, Pattaro et al. conduct a meta-analysis to discover several new loci associated with variation in eGFR and find that genes associated with eGFR loci often encode proteins potentially related to kidney development.

In this phase 1 trial, patients with locally advanced or metastatic solid tumors were treated with the individualized mRNA neoantigen-specific immunotherapy (iNeST) autogene cevumeran alone or in combination with the anti-PD-L1 agent atezolizumab, showing long-lasting neoantigen-specific immune responses and preliminary clinical activity, supporting further development of this therapeutic approach.

varVAMP is open-source software for designing primers for tiled-amplicon sequencing and qPCR. It simplifies primer design for viral pathogens with high genomic variability by including sequence variations into primer sequences.

NADP(H) is a crucial cofactor, acting as a reducing agent in numerous pathways in living organisms. Here the authors report a ratiometric biosensor named NERNST, which can be used to estimate the NADP(H) redox status in bacterial, plant and animal cells and organelles.

Bock and colleagues perform integrative analysis of JAK-STAT mutant mice and find JAK-STAT signaling regulates CD8⁺ T cell and macrophage homeostasis by contributing to a poised epigenetic and transcription-regulatory state, preparing cells to rapidly respond to stimuli.

Glucagon is hormone that signals via a dedicated g-protein coupled receptor, but downstream signaling is poorly understood. Here, Wu et al. uncover liver glucagon signaling using phosphoproteomics and define a role for the vesicle trafficking protein SEC22B in distinct metabolic actions.

In hepatocellular carcinoma driven by non-alcoholic steatohepatitis, aberrant T cell activation and impaired immune surveillance seem to make hepatocellular carcinoma less responsive to anti-PD1 or anti-PDL1 immunotherapy.

The poor correlation between brain Aβ deposition and clinical symptoms in Alzheimer´s disease remains puzzling. Here, the authors show a temporal dissociation of Aβ deposition and neurodegeneration.

This study identifies candidate safeguard repressor transcription factors that repress alternate lineages in mature cell types and provides functional evidence that Prox1 performs such a function in hepatocytes during reprogramming, regeneration and in cancer.

A genome-wide association study and Metabochip meta-analysis of body mass index (BMI) detects 97 BMI-associated loci, of which 56 were novel, and many loci have effects on other metabolic phenotypes; pathway analyses implicate the central nervous system in obesity susceptibility and new pathways such as those related to synaptic function, energy metabolism, lipid biology and adipogenesis.

Post-translational modifications are important regulators of cellular pathways, but our understanding of these processes is limited. Here, the authors present a web tool that integrates various databases in order to allow scientists to study experimental PTM data from the perspective of pathways.

Patricia Munroe, Christopher Newton-Cheh, Andrew Morris and colleagues perform association studies in over 340,000 individuals of European ancestry and identify 66 loci, of which 17 are novel, involved in blood pressure regulation. The risk SNPs are enriched for cis-regulatory elements, particularly in vascular endothelial cells.

The mouse cancer model 'Multi-Hit' allows for the evaluation of oncogene cooperativities in tumor development based on stochastic Cre-recombination events. Cells with cooperating oncogenes are positively selected and give rise to tumors. The approach is used to study Ras downstream effector pathways in tumorigenesis.

Candida albicans, the most common human fungal pathogen, causes local and life-threatening systemic infection. Here, the authors show that absence of tyrosine kinase 2 protects from invasive cutaneous candidiasis.

Crosslinking mass spectrometry (XL-MS) has become a crucial tool for studying protein structures and interactions in their native environments, however, the current cleavable linkers are fraught with practical limitations. Here, the authors synthesize and characterize DiSPASO, a novel lysine-reactive, MS-cleavable, and membrane-permeable crosslinker with an alkyne-based click chemistry handle for affinity enrichment, showing potential for improving protein-protein interaction mapping.

Klebsiella oxytoca provides protection against Salmonella Typhimurium via toxin-dependent inhibition in nutrient-rich, low-competition environments but switches to substrate-driven competition when nutrients are limited.

Past genome-wide associate studies have identified hundreds of genetic loci that influence body size and shape when examined one trait at a time. Here, Jeff and colleagues develop an aggregate score of various body traits, and use meta-analysis to find new loci linked to body shape.

Liver resident CD8 T cells have an essential role in immunopathology in a mouse model of nonalcoholic steatohepatitis, by becoming auto-aggressive following sequential transcriptional and metabolic activation steps .

Cryo-EM structures of human Pol III in both apo- and elongating states reveal metazoan-specific differences in the regulation of transcription termination and identify mutations relevant to human disease.

At light levels where both rods and cones are active, their signals converge into shared downstream retinal circuitry. Using HCN1 deficient mice, this study shows that the signals from cone photoreceptors are overwhelmed when rod output is not regulated, suggesting a mechanism for how these systems interact.

The authors report that impaired hippocampal synchrony in a mouse model of schizophrenia is due to parvalbumin interneuron hypoexcitability. Rescuing interneuron excitability during adulthood restores wild-type-like network dynamics and behavior.

The authors analyse tree responses to an extreme heat and drought event across South America to understand long-term climate resistance. While no more sensitive to this than previous lesser events, forests in drier climates showed the greatest impacts and thus vulnerability to climate extremes.

Blockade of intrahepatic accumulation and function of platelets represents a potential approach to treat non-alcoholic steatohepatitis (NASH) and prevent subsequent progression to hepatocellular carcinoma

This study describes the transcriptional programming of yolk sac–derived microglia specification in the brain, in which c-kit–positive erythromyeloid cells are further modified into three developmental subpools of microglia progenitors and their microglia differentiation is mediated by the transcription factors Pu.1 and IRF8.

A transancestral exome-wide association study for body-fat distribution identifies protein-coding variants that are significantly associated with waist-to-hip ratio adjusted for body mass index.

A trans-ancestry genome-wide association study of serum urate levels identifies 183 loci influencing this trait. Enrichment analyses, fine-mapping and colocalization with gene expression in 47 tissues implicate the kidney and liver as key target organs and prioritize potential causal genes.

Chemical proteomics profiling of 1,183 kinase inhibitors from past drug discovery projects revealed a large number of reasonably selective compounds for several kinases such as SYK and CK2.

Cross-linking mass spectrometry is widely used to elucidate protein structures and interactions. Here, the authors generate an extensive peptide library to benchmark the most common cross-link search engines with frequently used cross-linking reagents in low and high complex sample systems.

A method and accompanying software tool enables automated modeling of large macromolecular complexes using experimental crosslinking mass spectrometry data as distance restraints, as demonstrated for the 17-subunit yeast RNA polymerase III complex.

Genome-wide association studies (GWAS) have become a key tool to discover genetic markers for complex traits; however, environmental factors that interact with genes are rarely considered. Here, the authors conduct a GWAS of obesity traits, and find that smoking may alter genetic susceptibilities.

Here the authors structurally investigate elongating human RNA polymerase I at 2.7 Å using cryo-electron microscopy, as well as an RNA polymerase I open complex at 3.3 Å and bound to initiation factor RRN3 at 3.2 Å.

Accurate phenotyping is key to deciphering behavior. Here, authors show the utility of the software package DeepOF in supervised and unsupervised identification of distinct individual and social behavioral patterns following chronic social stress.

S. aureus biofilms stimulate CXCL10 chemokine secretion, via the biofilm matrix compound PNAG, which also stimulates NF-κB, Dectin-1 and CARD9 expression, inducing monocyte formation, in turn triggering immune response at the site of infection.