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TDP-43 dysfunction in ALS/FTD causes faulty splicing of the KCNQ2 ion channel, leading to toxic protein buildup, neuron hyperactivity and a potential new biomarker and treatment target using RNA-based therapies.

A high-bandwidth neuromotor interface offers performant out-of-the-box generalization across people.

The formation of faults in lithium-ion batteries can significantly impact pack safety and performance. Pierre Lambert and colleagues propose a modelling and machine learning framework to detect these faults from the current oscillations found in parallel connected packs.

The Curie temperature of Fe_5+xGeTe₂ thin films can be modulated from 260 to 380 K via iron doping, allowing the two-dimensional material to be used to create planar spiral inductors and low-pass Butterworth filters.

Dopaminergic action prediction error signals are used by mice as a value-free teaching signal to reinforce stable sound–action associations in the tail of the striatum.

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.

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).

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.

Post-infectious myalgic encephalomyelitis/chronic fatigue syndrome (PI-ME/CFS) is a disabling disorder, yet the clinical phenotype is poorly defined and the pathophysiology unknown. Here, the authors conduct deep phenotyping of a cohort of PI-ME/CFS patients.

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.

The neural mechanisms underlying the antidepressant effects of nitrous oxide remain poorly understood. This study reveals that specific activation of layer V pyramidal neurons in the cingulate cortex rescues stress-associated hypoactivity states and is driven by inhibition of calcium-sensitive potassium channels rather than NMDA-receptor antagonism.

Changes in the sea-level annual cycle have a profound effect on the coast, yet little is known about their drivers. Here the authors show a considerable variability in the amplitude of the cycle along the United States Gulf and Southeast coasts and relate it to Atlantic Rossby waves.

A search for transient dark matter in the form of domain walls of axion-like particles finds no statistically significant signal. This places constraints on our theoretical understanding of such scenarios.

Here the authors describe a biophysical layer-5 pyramidal neuronal model linking microscale spiking to macroscale complex dynamics, that predicts distinct burst dynamics and information processing across unconscious, dreaming, and awake states.

The posterolateral cortical amygdala and other connected brain regions have a key role in mediating the transition from investigative to aggressive behaviour in male mice.

Meta-analyses in up to 1.3 million individuals identify 87 rare-variant associations with blood pressure traits. On average, rare variants exhibit effects ~8 times larger than the mean effects of common variants and implicate candidate causal genes at associated regions.

The basal ganglia direct and indirect pathways are classically described as anatomically segregated and functionally opposing. Here the authors describe a non-canonical direct pathway made of axon collaterals to the globus pallidus that promotes motor action.

Pooled and sex-specific genome-wide association analyses identify new risk loci for restless legs syndrome and candidates for drug repurposing. Machine learning models combining genetic and other information show improved risk prediction performance.

On timescales of centuries and longer, aerosol concentrations in Antarctic ice are controlled by changes in the nature of mid- and high-latitude precipitation, according to analyses of palaeoclimate data.

A genetic atlas of the human plasma proteome, comprising 1,927 genetic associations with 1,478 proteins, identifies causes of disease and potential drug targets.

Bioresorbable electronic stimulators can deliver electrical stimulation in rodents to enhance functional muscle recovery after nerve injury. Here, the authors present a bioresorbable dynamic covalent polymer that enables reliable, long-lived operation of soft, stretchable devices of this type.

A new ice core from West Antarctica shows that, during the last ice age, abrupt Northern Hemisphere climate variations were followed two centuries later by a response in Antarctica, suggesting an oceanic propagation of the climate signal to the Southern Hemisphere high latitudes.

Cichon et al. show that ketamine induces a switch in the active population of excitatory neurons across cortical layers and regions that contributes to impairments in sensory processing characteristic of a dissociative-like state.

Epileptic seizures are traditionally considered to reflect hypersynchronous neuronal activity arising from runaway excitation. Here the authors analyze spike train patterns of single neurons during seizures in human epilepsy patients, finding that spiking activity during seizure initiation was highly heterogeneous in small cortical patches and across the network.

A genome-wide association study in more than 400,000 individuals identifies 139 new signals for lung function. These variants can predict chronic obstructive pulmonary disease in independent, transancestral cohorts.

Atherosclerotic plaques with macrocalcification are stable, whereas microcalcification is a key feature of rupture-prone plaques. Here the authors show that¹⁸F-NaF PET/CT imaging can distinguish between macro- and microcalcification providing a potential, non-invasive imaging technique to identify patients with high-risk atheroma.

The measurement of the total cross-section of proton–proton collisions is of fundamental importance for particle physics. Here, the first measurement of the inelastic cross-section is presented for proton–proton collisions at an energy of 7 teraelectronvolts using the ATLAS detector at the Large Hadron Collider.

Three-photon microscopy provides access to most of the adult zebrafish brain for both structural and functional imaging, as well as to the Danionella dracula brain.

Vitamin D deficiency is associated with multiple human pathologic conditions. In a genome-wide association study of 79,366 individuals, Jiang et al. replicate four and identify two new genetic loci for serum levels of 25-hydroxyvitamin D and find evidence for a shared genetic basis with autoimmune diseases.

Sequencing data from two large-scale studies show that most of the genetic variation influencing the risk of type 2 diabetes involves common alleles and is found in regions previously identified by genome-wide association studies, clarifying the genetic architecture of this disease.