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Simultaneous recordings were made of hundreds of neurons in the rat frontal cortex and striatum, showing that decision commitment involves a rapid, coordinated transition in dynamical regime and neural mode.

Wastewater surveillance can be used to track infectious diseases. A six-plex digital PCR assay is shown to provide information on four respiratory diseases at the same time, with data that have a high level of agreement with reported case numbers.

Aggregates of misfolded proteins are sequestered in the aggresome via dynein transport in an aggregate size-dependent manner. Here, authors find episodic transport kinetics mediated by aggresome-dynein adapters are central to this size-filter effect.

Human pathogenic-like Th17 cells express the chemokine receptor CCR6, but how CCR6, together with other chemokine receptors, modulate Th17 functions is still unclear. Here the authors show that CCR2 is coexpressed with CCR6 on these cells, and specifically mediates transendothelial migration, while CCR6 and other chemokine receptors induce T cell arrest on activated endothelial cells.

Here the authors perform a trans expression quantitative trait locus meta-analysis study of over 3,700 people and link a USP18 variant to expression of 50 inflammation genes and lupus risk, highlighting how genetic regulation of immune responses drives autoimmune disease and informs new therapies.

Spontaneous parthenogenesis in sunflower has been used to develop a scalable doubled haploid breeding system.

GPC2 and GD2 have been described as immunotherapeutic targets in neuroblastoma. Here the authors engineer T cells to simultaneously express a GPC2-directed CAR and a bispecific innate immune cell engager targeting GD2 and CD16a, showing antitumor activity in neuroblastoma preclinical models.

Vascular cells express various G-protein-coupled receptors (GPCRs) with yet unknown function, among them orphan receptor GPR153. GPR153 is upregulated in injured vessels, where it promotes smooth muscle proliferation and endothelial inflammation, and its inactivation protects mice in models of vascular diseases.

EchoNext, a deep learning model for electrocardiograms trained and validated in diverse health systems, successfully detects many forms of structural heart disease, supporting the potential of artificial intelligence to expand access to heart disease screening at scale.

Neuropixels 1.0 NHP is a 45-mm, high-density silicon probe capable of recording large numbers of neurons with single-neuron resolution from most areas in a macaque’s brain.

Parkinson’s disease (PD) involves toxic protein buildup and energy failure in neurons. Continuously breathing low-oxygen air protected mice from PD-like neuronal loss and reversed symptoms, even after they began, suggesting that hypoxia may protect neurons.

Chagas disease, caused by Trypanosoma cruzi, lacks an effective vaccine. Here, the authors report the cryo-EM structure of TcPOP, a potential vaccine antigen, in open and closed states and validate its immunogenic potential for invasion-blocking antibodies.

β cells derived from stem cells improve blood glucose control in patients with diabetes.

Polygenic scores for body mass index and obesity constructed using data from 5 million people with different ancestries were associated with distinct weight gain trajectories from early childhood to adulthood.

The rate at which third-order olfactory neurons integrate synaptic inputs to spike threshold is thought to determine the speed of odor discrimination in Drosophila. Here, authors compare the impact of subthreshold optogenetic membrane potential manipulations on decision-making.

Here, the authors develop hydrocarbon-stapled paxillin-mimetic peptides that act as selective and potent focal adhesion kinase (FAK) scaffold inhibitors to displace FAK from focal adhesions. Treatment shows reduced cancer cell survival in vitro and reduced tumor burden in vivo.

Anthropogenic ground-level ozone substantially reduces the productivity of tropical forests and so their carbon drawdown, according to ozone susceptibility experiments and dynamic global vegetation modelling.

Todd et al. show a daily rhythm in aggression propensity in male mice and reveal a novel polysynaptic circuit within the hypothalamus by which the central circadian clock (the suprachiasmatic nucleus) influences neurons that regulate attack behavior.

Electrochemical CO₂ capture is an emerging field in electrical decarbonization but limiting unwanted side reactivity remains a challenge. Here, authors present an electrochemical capture swing that is decoupled from redox carrier generation, enabling CO₂ capture from O₂-containing gas streams.

Biofilm formation and antibiotic tolerance are regulated in Pseudomonas aeruginosa by the protein PA1396, which responds to diffusible signal factors (DSFs) produced by other bacteria. Here, An et al. synthesize DSF analogues that modulate PA1396 activity and thus biofilm formation and antibiotic tolerance.

A novel antiviral targeting the SARS-CoV-2 PLpro protease shows strong efficacy in a mouse model, preventing lung pathology and reducing brain dysfunction. The study provides proof-of-principle that PLpro inhibition may be a viable strategy for preventing and treating long COVID.

Methane production is traditionally not found in oxygenated soils, a paradigm incorporated in global greenhouse gas modelling efforts. Here the authors show geochemical and biological evidence of active methanogenesis in bulk-oxic wetland soils, attributing up to 80% of the total methane budget for the site.

John Chambers and colleagues identify common variants at four loci associated with serum creatinine levels, a marker of kidney function. Their findings provide insight into the pathways underlying susceptibility to chronic kidney disease.

Neurons in the ventral hippocampus project to parvalbumin inhibitory interneurons in the infralimbic (IL) region of medial prefrontal cortex. Activation of this projection produces feed-forward inhibition of IL and causes relapse of extinguished fear.

Dynein is a microtubule motor the motility of which is affected by the microtubule-associated protein She1. Here, the authors show that She1 alters dynein stepping behavior and increases its microtubule affinity through simultaneous interactions with the microtubule and dynein microtubule binding domain.

Inhibiting the cytosolic enzyme histone deacetylase 6 in the periphery is sufficient to improve leptin sensitivity and metabolic outcomes in diet-induced obese mice.

Guided by miRNA, Argonaute proteins silence mRNA in multiple ways that are not well understood. Here, the authors develop live-cell biosensors to image the impact tethered regulatory factors, such as Argonaute, have on single-mRNA translation dynamics.

Knock-in mice conditionally or constitutively expressing Cas12 variants enable a wide range of ex vivo and in vivo applications requiring multiplexed genome engineering.

Previously, authors have identified GW461484A (GW) as an inhibitor of the kinase Yck2 in the fungal pathogen Candida albicans. Here, they report the synthesis of GW analogs with improved pharmacological properties and activity in mouse models of systemic candidiasis.

Apolipoprotein L1 genetic variants contribute to a subtype of proteinuric kidney disease referred to as APOL1-mediated kidney disease (AMKD). Here the authors report the discovery and characterization of potent and selective APOL1 ion channel inhibitors for the potential treatment of AMKD.

Doan et al. show that loss of cardiac NAD⁺ is sufficient to drive metabolic derangements, hypertrophic remodeling and lethal arrhythmias in adult mouse hearts, despite maintenance of ejection fraction and bioenergetics.

The authors find that mice fed a diet with reduced levels of branched-chain amino acids have improved metabolic health, and in males but not females, lifelong feeding of such a diet reduces frailty and extends life span.

Until now, no tools existed to selectively manipulate the small number of sparsely distributed neurons activated during a drug-related learned behavior. Here the authors describe a new method for selectively inactivating only those neurons activated by cocaine in an environment repeatedly paired with drug injections.

A mitochondrial complex I inhibitor exhibited dose-limiting toxicities, including neurotoxicity, in patients with acute myeloid leukemia and solid tumors, warranting further studies to evaluate the mechanism linking oxidative phosphorylation inhibition and neurotoxicity.

This study uses a transgenic mouse line expressing Cre-inducible astro-hM3Dq to study astrocytes’ role in neuroinflammation and cognition without the use of viral transduction, mitigating the potential side effects associated with standard techniques.

The prefrontal cortex in monkeys controls working memory in a similar way to attention, by selectively transforming the representations of remembered items.

Multicellular organisms, particularly their immune systems, rely on complex cell-to-cell communication, mediated by signalling molecules that form spatiotemporal concentration gradients. Here, high-throughput microfluidic cell culture and fluorescence microscopy, together with quantitative gene expression analysis and mathematical modelling, have been used to investigate how mammalian cells respond to different levels of TNF-α and signal to NF-κB. Both digital and analogue responses are revealed.

Hunt, Malalasekera et al. recorded populations of prefrontal neurons from monkeys performing a visual attention-guided-choice task. The results revealed that distinct computations in three PFC subregions as information was sampled guided the eventual decision.

Timothy Frayling, Joel Hirschhorn, Peter Visscher and colleagues report a meta-analysis of genome-wide association studies for adult height in 253,288 individuals. They identify 697 variants in 423 loci significantly associated with adult height and find that these variants cluster in pathways involved in growth and together explain one-fifth of the heritability for this trait.

The IRE1α-XBP1 arm of the unfolded protein response (UPR) has been associated with immunosuppression and cancer progression. Here the authors show that IRE1α-XBP1 activation is associated with poor overall survival in patients with non-small cell lung cancer and that IRE1α loss in cancer cells promotes anti-tumor immune responses in lung cancer preclinical models.

A peritumourally implanted macroporous scaffold releasing small molecules and antibodies to suppress regulatory T cells and to attract and stimulate effector T cells enhanced endogenous antitumoural responses in mice bearing aggressive tumours.