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A purpose-built implantable system based on biomimetic epidural electrical stimulation of the spinal cord reduces the severity of hypotensive complications in people with spinal cord injury and improves quality of life.

By studying dynamic folding intermediates on the human ribosome, Pellowe et al. show that newly made domains help each other to fold but do not stably interact until synthesis is complete, avoiding interdomain misfolding.

A study reports whole-genome sequences for 490,640 participants from the UK Biobank and combines these data with phenotypic data to provide new insights into the relationship between human variation and sequence variation.

Neural mechanisms underlying state-dependent flexible selection are not fully understood. Here authors show that NPY homologues in Drosophila larva differentially modulate reciprocally connected inhibitory neurons to bias non-feeding decisions, favoring escape-type actions (Head Cast), over protective-type actions (Hunch), in response to a mechanical cue.

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 free-living trial in people with overweight or obesity found that minimally processed diets led to greater weight loss and cardiometabolic improvements than ultraprocessed diets following UK healthy eating guidelines at 8 weeks.

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 study reveals a gut–brain sensory pathway through which the microbial component flagellin activates neuropod cells in the colon to signal the brain and reduce feeding in mice.

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.

uMAIA is an analytical framework designed to enable the construction of metabolic atlases at high resolution using mass spectrometry imaging data.

The non-coding RNA RNU4-2, which is highly expressed in the developing human brain, is identified as a syndromic neurodevelopmental disorder gene, and, using RNA sequencing, 5′ splice-site use is shown to be systematically disrupted in individuals with RNU4-2 variants.

A method termed ac⁴C-seq is introduced for the transcriptome-wide mapping of the RNA modification N⁴-acetylcytidine, revealing widespread temperature-dependent acetylation that facilitates thermoadaptation in hyperthermophilic archaea.

What is the state of trust in scientists around the world? To answer this question, the authors surveyed 71,922 respondents in 68 countries and found that trust in scientists is moderately high.

Analysis of snRNA genes in individuals with rare disorders identifies de novo and recurrent variants in RNU5B-1 and RNU5A-1, in addition to previously unreported cases with pathogenic or likely pathogenic variants in RNU4-2.

Microglia are proposed to have a role in brain development through synaptic engulfment and paracrine signaling. O’Keeffe et al. show that certain neurodevelopmental processes attributed to microglia can proceed normally even in the absence of these cells.

Experiments in mice identify a neural circuit that relays information about infant cries from the maternal auditory thalamus to hypothalamic oxytocin neurons to induce the release of oxytocin and modulate maternal behaviour.

Proximity ferroelectricity is reported in wurtzite heterostructures, which enables polarization reversal in wurtzites without the chemical or structural disorder that accompanies elemental substitution.

Photoreceptor outer segment abnormalities cause retinitis pigmentosa, a form of blindness. Here, authors show that the disease-associated gene RPGR regulates actin-mediated outer segment turnover through its interaction with the actin severer, cofilin.

Bacteria represent an unexploited reservoir of biosensing proteins. Here the authors use genomic screens and functional assays to isolate a progesterone sensing allosteric transcription factor and use a FRET-based method to develop an optical progesterone sensor.

Combined intraocular injection of an adeno-associated viral vector, encoding an optogenetic sensor, with light stimulation via engineered goggles enables partial recovery of visual function in a blind patient.

In a multivariate genetic analysis including 282,271 adults, Merino et al. identified 26 genomic regions associated with carbohydrate, protein and fat intake. The identified loci implicate brain regions and neuronal subtypes in influencing eating behaviour.

Behavioural studies and neural recordings in mice show that virgin mice can acquire maternal behaviour through an oxytocin-dependent mechanism.

Anti-cancer fluoropyrimidine drugs have antibacterial effects on the gut microbiome, and these drugs can be metabolized by gut bacteria via conserved pathways also found in mammalian hosts.

Results from the phase 2 MATCH01 clinical trial of autologous monocyte-derived macrophage therapy for liver cirrhosis revealed no liver-related severe adverse events or deaths in the treatment group.

A comprehensive multi-omics reference atlas of prenatal human skin shows that innate immune cells crosstalk with non-immune cells to perform pivotal roles in skin morphogenesis, including the formation of hair follicles.

An antibody screen of two distinct multiple sclerosis cohorts reveals an autoantibody signature that is detectable years before symptom onset and linked to a common microbial motif.

Here the authors find that erythroblasts of myelodysplastic syndromes with SF3B1 mutation leading to inefficient erythropoiesis show DNA replication stress with accelerated forks and reduced R-loops. Restoring R-loops by a histone deacetylase inhibitor rescues erythroid differentiation.

The TRPM7 channel enables endosomal acidification, which is vital for the entry of many enveloped viruses. Here, the authors show that loss of TRPM7 protects cells from various pandemic-threat viruses, pointing to a new strategy for broad-spectrum antiviral drugs.

Yellow fever is a public health threat in the Americas but has not recently been reported in the Caribbean despite presence of the mosquito vector Aedes aegypti. Here, the authors show through experimental infection that populations of Aedes aegypti from the Caribbean and surrounding areas are competent of yellow fever transmission.

Cognitive performance is impaired after prolonged wakefulness, yet the contribution of circadian rhythms for proper brain function remains unclear. Here the authors show that cortical excitability measured using TMS exhibits robust circadian dynamics which is correlated with cognitive performance.

A γδ T cell–IL-3 signalling axis is defined that controls the allergen responsiveness of cutaneous sensory neurons, leading to evidence for an immune rheostat that governs sensory neuronal responses to allergens on first exposure.

Prenatal bisphenol A exposure is associated with an increased risk of ASD in boys through a mechanism involving aromatase suppression. These resulting ASD-related behaviors and brain abnormalities may be reversed through postnatal intervention with 10HDA in mice.

A sparsely connected network, organized in clusters, identified in the rat lateral amygdala shows potentiation between recruited neurons after fear conditioning. This implies a mechanism for encoding multiple memories with a small number of neurons.

The ability to differentiate human pluripotent stem cells (hPSCs) into insulin producing cells holds potential for diabetes treatments, but many of these approaches lack the complexity needed for in vitro disease modeling. Here they develop an hPSC-derived islet spheroid system, offering an experimental model to study pancreatic budding and islet morphogenesis with human cells.

Large genome-wide meta-analysis of clinically diagnosed late-onset Alzheimer’s disease (LOAD) from 94,437 individuals identifies new LOAD risk loci and implicates Aβ formation, tau protein binding, immune response and lipid metabolism.

A first-in-human, phase 1 dose-escalation trial demonstrates the safety and feasibility of autologous macrophage therapy in adults with liver cirrhosis.

A simple machine learning algorithm combines evolutionary and experimental data for improved protein fitness prediction.

It has been proposed that the amygdala is required for the familiarity aspect of item recognition. By studying the performance of monkeys with selective amygdala lesions on four converging memory paradigms, the authors demonstrate that the amygdala is not necessary for familiarity memory, but confirm its role in reward processing.

To overcome challenges posted by vast number of GPCR genes and redundancy, the authors disrupted nearly all GPCR-encoding genes in C. elegans, enabling effective examination of GPCR signaling and offering a valuable resource for the research community.

Light-inducible dimerization tags are engineered to rapidly recruit proteins to precise points in living yeast and mammalian cells. The affinities and response time of the interactions are tunable, and the authors used the system to activate cell signaling and to direct cell polarization in yeast.

Human adenoviruses (HAd) cause respiratory, gastrointestinal and ocular infections. Here, the authors provide insights into the early stages of adenovirus infection by determining the cryo-EM structure of the trimeric HAd type 3 fibre knob bound to its cellular receptor human desmoglein 2, which reveals residues critical for HAd-receptor interactions.

When a cue is provided, people can rapidly attend to a changing scene and remember how it looked right after the cue appeared, but if the scene changes gradually, there is a delay in what we remember. Here the authors model these effects as prolonged attentional engagement.

LEAFY is a master transcription factor that regulates flower development through interaction with other proteins such as the F-box UFO. This study shows that UFO unexpectedly acts as a transcriptional cofactor that drives LEAFY to new genomic locations.

JAK2V617F mutation is associated with an increased risk for athero-thrombotic cardiovascular disease, but its role in aortic disease development remains unknown. Here, the authors show that JAK2V617F mutation drives vascular resident macrophages toward a pathogenic phenotype and promotes dissecting aortic aneurysm.

Three-dimensional imaging of the fetal heart and quantification of blood flow in the surrounding vessels is very challenging because the heart is small and the fetus is free to move in the womb. Here, the authors demonstrate motion-corrected 4D flow MRI of the whole fetal heart and major vessels.

In mice, sleep loss increases sensitivity to painful stimuli. Restoration of normal sleep or acute treatment with wake-promoting agents can normalize pain sensitivities.

Genome-wide association studies have only revealed a handful of genetic loci for longevity. Here, in a case–control design based on phenotype definitions of individuals surviving at or beyond the age corresponding to the 90th and 99th survival percentile, the authors report two additional loci located in the APOE locus and near GPR78.