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Here the authors show that extremes in the summer jet stream position over Europe create a beech forest productivity dipole between northwestern and southeastern Europe and can result in regional anomalies in forest carbon uptake and growth.

The molecular diversity of microglia has been described. Here the authors show that ARG1-expressing microglia are enriched in phagocytic inclusions and are involved in hippocampal innervation and spine maturation in mice. ARG1-expressing microglia also modulate cognition in a sex-dependent manner.

Neural stem cells in the adult mammalian brain derive from proliferating precursors that are spared as dormant reservoirs during development. Here, the authors show that autophagy is required for neural stem cells to transition to the adult quiescent state.

Analyses of expression profiles from whole blood of 31,684 individuals identify cis-expression quantitative trait loci (eQTL) effects for 88% of genes and trans-eQTL effects for 37% of trait-associated variants.

New treatments are essential for methicillin-susceptible Staphylococcus aureus bacteremia, but progress is slow. In this phase III–IV trial, cloxacillin plus fosfomycin failed to show superiority over cloxacillin alone, underscoring the challenges to improving patient outcomes.

Substrate reduction therapies (SRT) are a promising therapeutic approach for monogenic inherited metabolic diseases. Here the authors evaluate the therapeutic potential of an in vivo CRISPR/Cas9-mediated SRT to treat primary hyperoxaluria type I and demonstrate its safety and efficacy.

CDK4/6 inhibitors have improved outcomes for patients with ER+ breast cancer, however, those with loss of RB1 function often fail to respond. Here, the authors identify a vulnerability of ER + /RB1- breast cancer on PRMT5 and via dual blockade of ER and PRMT5 therapeutically target this in patient-derived xenograft models.

Archaerhodopsin-3 (AR3) mutants are commonly used in optogenetics for neuron silencing and membrane voltage sensing. High-resolution crystal structures show that desensitization of the AR3 photoreceptor occurs when internal hydrogen-bonded water networks are modified in response to changes in chromophore isomerization.

Mazzone and Liang-Guallpa et al. demonstrate that consuming high-fat foods rapidly and durably tunes parallel brain circuits to drive intake of a high-fat diet while devaluing a nutritionally balanced, standard diet even under states of intense hunger.

The structural connectome is the complete set of anatomical connections between brain cells. Here, the authors perform a genome-wide association study of white-matter structural connectivity in the human brain, finding 30 variants influencing the density of myelinated connections between brain regions.

HER2-enriched breast cancers within the HER2-positive subtype are addicted to the HER2 pathway. Here, the authors analyse gene expression before, during, and after treatment with anti-HER2-based therapies in the phase II PAMELA clinical trial, finding phenotypic changes induced by treatment.

Antibody mediated immunity to SARS-CoV-2 will affect future transmission and disease severity. This systematic review on antibody response to coronaviruses, including SARS-CoV-2, SARS-CoV, MERS-CoV and endemic coronaviruses provides insights into kinetics, correlates of protection, and association with disease severity.

HRO761 is a potent, selective, allosteric WRN inhibitor that binds at the interface of the D1 and D2 helicase domains, locking WRN in an inactive conformation.

IFNγ-inducible guanylate binding proteins (GBPs) recognize the Toxoplasma gondii vacuole during infection. Here, the authors report that inducible nitric oxide synthase (iNOS) is necessary for efficient parasite clearance by GBPs and that reactive nitrogen species produced by iNOS lead to nitration of the parasite vacuole and collapse of the intravacuolar network space, preventing parasite escape from GBP targeting.

Kranzler et al. examine the association between adverse childhood events and mood and anxiety disorders and substance dependence. The results show that adverse childhood events are associated with risk of substance dependence, with this effect mediated by mood and anxiety disorders. Similar associations were found for the risk of mood and anxiety disorders with substance dependence as a mediator.

Inhibition of specific metabolic pathways often drives metabolic adaptation. Here, the authors show that FLT3-ITD + acute myeloid leukemia cells are OXPHOS-driven, and inhibition of complex II activity results in increased lactate influx to drive respiration, which creates a targetable vulnerability.

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.

Following cell division, phase separation of the transmembrane adaptor LEM2 ensures that the ESCRT machinery remodels microtubules and seals the nuclear envelope.

A transcriptome-wide association study identifies associations of genetically predicted gene expression with breast cancer risk. This analysis finds 48 candidate genes implicated in breast cancer susceptibility, including 14 at novel loci.

A deep learning and data-driven modelling study finds that microbial carbon use efficiency is a major determinant of soil organic carbon storage and its spatial variation across the globe.

Investigating malaria transmission at three sites in Uganda, the authors identify super-spreaders and show that super-spreading is more prominent at low-intensity transmission, and that seasonality and environmental stochasticity have a greater influence on super-spreading.

Quantification of planktonic fossils from the past 40 million years shows that the present-day diversity gradient arose only 15 million years ago as the climate started to cool.

Increased risk of premature cardiovascular disease in systemic lupus erythematosus (SLE) is not well understood, but in animal models, the Janus kinase inhibitor tofacitinib improves related phenotypes. Here the authors report a Phase 1 double-blind randomized trial that shows tofacitinib is safe and well tolerated in in patients with SLE.

Known genetic loci account for only a fraction of the genetic contribution to Alzheimer’s disease. Here, the authors have performed a large genome-wide meta-analysis comprising 409,435 individuals to discover 6 new loci and demonstrate the efficacy of an Alzheimer’s disease polygenic risk score.

Plastic pollution in seas is widespread, but some areas lack the high concentrations of plastic debris. Here the authors identified places where large amounts of plastic debris pass in the Mediterranean Sea thus helping to study plastic dispersion in regions where plastic debris does not accumulate, and a tool for mitigation strategies.

Mechanical properties and forces sculpt the behaviour of cells in living organisms. Silicon-based nanochips implanted into mouse one-cell embryos have been used to reveal mechanical changes during the early onset of embryonic development.

MALT1 regulates NFκB signalling both as a scaffolding protein and as a protease. Here the authors show that during T cell activation the expression of MALT1 gene switches to an alternatively spliced variant, which increases TCR signal transduction due to enhanced TRAF6 binding.

In a prospective international cohort of 1,127 patients with non-small-cell lung cancer and ctDNA-guided therapy, ctDNA detection was associated with shorter survival, independently of clinicopathologic features and metabolic tumor volume.

Skeletal muscle plays a key role in regulating systemic glucose and metabolic homeostasis. Here, the authors show that the catalytic activity of Vav2, an activator of Rho GTPases, modulates those processes by favoring the responsiveness of this tissue to insulin and related factors.

The molecular mechanisms underlying metastasis in pheochromocytoma/paraganglioma (mPPGL) remain to be explored. Here, the authors perform genomic and immunogenomic profiling of mPPGL tumors and suggest potential biomarkers for risk of metastasis and immunotherapy response.

Hypothalamic AgRP neurons are shown to control peripheral and central levels of lysophospholipids in association with food deprivation, which leads to cortical excitability, hyperphagia and body weight gain.

Trypanosoma brucei relies on uptake and conversion of purines from the host, which constitutes a potential drug target. Here, Hulpia et al. combine structural elements from known trypanocidal nucleoside analogues and develop a potent trypanocide with curative activity in animal models of acute and late stage sleeping sickness.

Notch signaling is essential for the maintenance of adult neural stem cells in vivo. Here, Andreu-Agulló and colleagues show that PEDF, released from endothelial cells, enhances Notch signaling in the mouse subependymal zone by inactivating a repressor of Notch target genes.

In a phase I/II dose-escalation clinical trial, the mRNA COVID-19 vaccine BNT162b1 elicits specific T cell and antibody responses that suggest it has protective potential.

Macias et al. generated a mouse model recapitulating the electrophysiological features of Andersen–Tawil syndrome type 1 (ATS1), a disease associated with life-threatening arrhythmias, via AAV-mediated in vivo expression of trafficking-deficient mutant Kir2.1^Δ314-315 channel. The authors identify functional Kir2.1 receptors in sarcoplasmic reticulum (SR) microdomains and report that the ATS1 arrhythmogenic phenotype is due to the dysfunction of Kir2.1 receptors both in the sarcolemma and in the SR domains.

It is unclear whether climate driven phenological shifts of tundra plants are consistent across the plant growing season. Here the authors analyse data from a network of field warming experiments in Arctic and alpine tundra, finding that warming differentially affects the timing and duration of reproductive and vegetative phenology.

Endoribonuclease PA-X allows influenza A virus to discriminate between viral and host transcripts by cleaving GCUG tetramers.

mRNAs associated with differentiated cells are already detected in adult neural stem cells. Here the authors show how intron detention prevents their translation, solving conflicts in fate decisions while priming stem cells for timely differentiation.

Metabolites can distinguish pathogenic from healthy cells, but they are hard to couple to current photosensitizers without altering their biological activity. Here the authors design a new family of photosensitizers that retain metabolite function to target pathogenic cells and ablate them by photodynamic therapy.

In this work, authors provide a proof-of-concept study showing that deubiquitinating enzyme inactivation in MERS-CoV leads to attenuation in mice, and protection against a lethal challenge.

Antenatal glucocorticoid therapy is indicated for mothers at risk of preterm delivery. Here, the authors show that the circadian phase of antenatal glucocorticoid treatment affects the risk of behavioral disorders later in life in mice and in a retrospective observational study in human infants.

B cells are playing an active role in shaping the tumour immune microenvironment and the anti-tumour immune response in melanomas. Here authors show that intra-tumoral B cells are aberrantly activated and produce antibodies that are potentially autoreactive.

Recurrent de novo mutations at nucleotide positions 4 and 35 of RNU2-2 cause a neurodevelopmental disorder whose prominent features include intellectual disability, developmental delay and a complex seizure phenotype.

Here, the authors show that mouse medial entorhinal cortex encodes three-dimensional head movement as well as eye position and velocity. These self-motion signals are represented conjunctively in individual neurons alongside body position, running speed, and azimuthal head direction.

Studying the physical interaction of stem cells with their niche has previously been difficult. Using a fluorescence-based reporter, Michelet al. are able to show that bone morphogenetic protein signalling occurs between Drosophilatestes germline stem cells and their niche and is via adherens junctions.