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Vocal fold cancer tumours lose some of their malignant traits when mechanically stimulated by physiological stretch or vibrations, mimicking the opening and closing of vocal folds and phonation.

Analysis of gene expression in the neural crest of vertebrate embryos supports the idea that gene regulatory circuits that define the cranial neural crest evolved gradually from a more trunk-like identity.

The authors describe the isolation and characterization of broadly cross-neutralizing monoclonal antibodies (mAbs) against diverse H5Nx viruses from individuals who received a monovalent H5N1 vaccine 15 years ago. They identify five mAbs that potently neutralized the majority of H5 clades and protected against lethal 2.3.4.4b H5N1 infection in mice.

Genomic analysis of Plasmodium DNA from 36 ancient individuals provides insight into the global distribution and spread of malaria-causing species during around 5,500 years of human history.

Embryonic patterning requires generation of positional information that defines where cells reside within the embryo. Here, Azambuja, Rothstein and colleagues report that the epigenome is spatially patterned during early development, showing that chromatin organization reflects the embryo’s emerging body plan.

The organizer is a signaling center in the embryo that orchestrates the formation of body axes. Here they show that Hensen’s Node contains two main cell types and that changes in their abundance alter its ability to induce head versus trunk structures.

Off-target activation of nerve fibers is an ongoing problem in bioelectronic medicines such as vagus nerve stimulation. Here, the authors show that high-frequency stimulation can selectively block nerve fibers in the vagus nerve in swine models.

Birds have evolved a unique sex chromosome dosage compensation mechanism involving the male-biased microRNA (miR-2954), which is essential for male survival by regulating the expression of dosage-sensitive Z-linked genes.

Precision functional mapping shows that the frontostriatal salience network occupies nearly twice as much of the cortex in people with depression, and this was unaffected by mood changes and detected in children before onset of symptoms.

The role of the cerebellar nuclei (CN) during associative learning remains debated. Here, the authors show that well-timed conditioned responses can result from stimulating CN inputs, and that learning coincides with structural and synaptic activity changes in vivo.

The collective activity of cells enables embryos to overcome various perturbations. Here, authors show that at the higher (population) level, embryos also communicate. This enables larger groups to resist chemical and molecular-genetic teratogens.

Cell migration through micrometric constraints is limited by low deformability of the nucleus. Here the authors show that in dendritic cells a perinuclear actin network nucleated by Arp2/3 increases nuclear deformation and allows the cells to pass through narrow constrictions, likely by rupturing the nuclear lamina.

Zonal positioning in the liver determines whether the CTNNB1 oncogene can induce liver cancer.

Cultivation of tropical soil microorganisms combined with physiological experiments and bioinformatics analyses identify a family of clade III lactonase-type nitrous oxide reductases with low sequence identity but high 3D structural similarity to known nitrous oxide reductases.

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).

Olfactory perception of food-derived odors influences feeding behavior, but the underlying neural pathways remain unclear. Here, the authors show that prolonged exposure to food odor suppresses food intake and body weight gain by activating an olfactory bulb–hypothalamus circuit.

The authors develop and characterise a selective Greatwall inhibitor, C-604, and show that its cytotoxicity stems from PP2A-B55α hyperactivation. They identify B55α and Greatwall levels as biomarkers of responses to Greatwall-targeted therapy.

A brain-imaging study in humans demonstrates that older age brain network decline varies in relation to an individual’s education and predicts future dementia severity beyond other markers of Alzheimer’s disease-related genetic risk and pathology.

This prospective cohort study of patients with cancer incorporated antemortem follow-up visits and rapid autopsy analyses, and reports that spikes—rapidly increasing levels—of circulating tumor cell clusters, observed immediately before and at the time of death, along with tumor masses infiltrating large vessels, were cancer-related events associated with patient mortality.

While metabolic reprogramming has been shown to drive changes in cell identity, the link between cellular metabolism and gene expression remains poorly characterized. Here they show that histone lactylation couples metabolism and transcription during neural crest cell differentiation in the early embryo.

The 'new head' hypothesis proposes that the advent of the neural crest and cranial placodes was crucial for the evolution of vertebrates. In this Review, Martik and Bronner discuss this hypothesis and how emerging data about gene regulatory networks in neural crest-like cell types in invertebrate chordates are providing insights into neural crest evolution.

A representation-learning strategy for machine-learning models applied to medical-imaging tasks improves model robustness and training efficiency and mitigates suboptimal out-of-distribution performance.

Mucosal melanoma (MM) is a cancer with poor prognosis derived from mucosal melanocytes. Here, the authors implement a combination of genetic changes that occur in MM patients in a zebrafish model, revealing the potential MM cell of origin and showing that patient and zebrafish MMs share a gene signature that is more metastatic and immune-evasive.

The variability in clinical outcomes of SARS-CoV-2 infection is partly due to deficiencies in production or response to type I interferons (IFN). Here, the authors describe a FIP200-dependent lysosomal degradation pathway, independent of canonical autophagy and type I IFN, that restricts SARS-CoV-2 replication, offering insights into critical COVID-19 pneumonia mechanisms.

We show that gain-of-function cancer mutations in the KBTBD4 E3 ligase promote neodegradation of substrates via a shape-complementarity-based mechanism, which converges with the mechanism of action of the UM171 molecular glue degrader and can be blocked by HDAC1/2 inhibitors.

Pneumococci can alternate between harmless and highly virulent forms. Here the authors show that such variation may be due to random rearrangements in a genetic locus encoding a restriction-modification system, resulting in epigenetic changes that affect expression of many genes.

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.

A state-dependent dopamine filter system in the male Drosophila brain balances threat perception against the drive to mate.

Modifications enhancing degradation resistance and albumin affinity enabled the delivery of an siRNA conjugate silencing MMP13 to guinea pig and murine arthritic joints, improving therapeutic outcomes following intravenous administration.

Albergaria et al. demonstrate that ongoing locomotor activity modulates cerebellum-dependent associative learning. Optogenetic circuit dissection reveals a site of locomotor modulation within the mossy fiber pathway in the cerebellum.

Silva et al. definitively establish climbing fiber-driven complex spike events as essential instructive signals for associative cerebellar learning while also revealing unexpected features of optogenetic manipulation.

The neural codes underlying working memory are not fully understood. Here the authors recorded neurons in the lateral prefrontal cortex of male macaque monkeys, during a working memory task, and identify activation sequences that encode target locations in the task.

The neural circuits underlying rewarding effects of drugs of abuse and natural rewards are not fully understood. Here the authors investigate the role of the infralimbic cortex to nucleus accumbens shell pathway during heroin or food choice in rats.

Waiblinger et al. investigate the role of primary sensory cortex in flexible behaviors. They show that neuronal signals in S1 are part of an adaptive and dynamic framework that facilitates flexible behavior as an individual gains experience, indicating a role for S1 in long-term adaptive strategies.

A preclinical safety study of adeno-associated viruses (AAVs) for RNA interference (RNAi) for spinocerebellar ataxia type 1 therapy showed toxicity in nonhuman primates but not rodents, due to unexpected AAV inverted terminal repeat transcriptional activity that was mitigated on altering the RNAi expression environment.

Protocadherin-1 (PCDH1) is a critical host factor for hantaviruses that can cause severe cardiopulmonary syndrome. Here, the authors map the binding site of the viral glycoprotein complex within PCDH1 and show that mutations engineered at this site can protect Syrian hamsters from viral challenge.

FlyWire presents a neuronal wiring diagram of the whole fly brain with annotations for cell types, classes, nerves, hemilineages and predicted neurotransmitters, with data products and an open ecosystem to facilitate exploration and browsing.

Snakebite toxins need to be transported through the lymphatic system before gaining access to the blood. By interfering with lymphatic system function, Megan Saul et al. found that nitric oxide donors delay the fatal effects of snake venom in rats. By giving snakebite victims more time to obtain medical care, this approach may be useful for the first-aid treatment of snakebites.

Induction of the cis form of phosphorylated tau (cis P-tau) has previously been shown to occur in animal models of traumatic brain injury (TBI), and blocking this form of tau using antibody was beneficial in a rodent model of severe TBI. Here the authors show that cis P-tau induction is a feature of several different forms of TBI in humans, and that administration of cis P-tau targeting antibody to rodents reduces or delays pathological features of TBI.

ABCB6 has been implicated in dyschromatosis universalis hereditaria, a condition that can present with hearing loss. Here, the authors use zebrafish and mice to perform experiments suggesting that ABCB6 plays a role in inner ear development.

The secreted aminopeptidase Pseudomonas aeruginosa aminopeptidase (PaAP) is required for nutrient recycling in biofilms. Using the information from protein structure and kinetics, a potent cyclic peptide inhibitor for PaAP was designed that killed cells in late-stage biofilms.

Here, Khurana et al. report the results of a phase 4 clinical trial with three FDA approved influenza vaccines and show that repeat influenza vaccination results in reduced antibody affinity maturation to hemagglutinin domain 1 irrespective of vaccine platform.

Radiation-therapy-induced DNA damage in oral and rectal epithelial cells can be reduced via the nanoparticle-mediated local delivery of messenger RNA encoding for a damage-suppressor protein found in radiation-resistant tardigrades.

Parhizkar et al. show that lemborexant, an orexin receptor antagonist, protects against neurodegeneration in male tau transgenic mice by preventing tau protein build-up and inflammation, highlighting its potential for preventing neurodegeneration.