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Paracrine signalling between tuft cells and enterochromaffin cells is a key mode of immune–sensory and gut–brain communication, and accounts for the pattern of gastrointestinal symptoms that occurs during parasite infections.

Antibody mediated prevention (AMP) trials with the broadly neutralizing antibody VRC01 showed protection against VRC01-sensitive viruses. Here, by deep sequencing plasma samples from 172 participants of the AMP trials, the authors show a high frequency of multilineage HIV infections (38%), including coinfection with both sensitive and resistant viruses, and demonstrate that VRC01 doesn’t alter the transmission bottleneck.

N-desethyl-fluornitrazene is a µ-opioid receptor agonist derived from nitazenes that has supramaximal intrinsic efficacy that produces analgesia with minimal adverse effects in rodent models.

Coronary artery disease has several genetic risk factors. Here, the authors develop a model that combines germline and somatic genetic drivers to predict coronary artery disease risk, identifying high-risk individuals not detected by polygenic risk scores alone.

AhR functions as a neuronal brake on axon regeneration, integrating environmental sensing, protein homeostasis and metabolic signalling to control the balance between stress adaptation and axonal repair.

When 100 social and behavioural science claims were examined, 34% of reanalyses closely matched the original results, with 74% reaching the same conclusion, revealing limited robustness of single-path analyses and the need to address analytical uncertainty.

Colonic stem cells retain a memory of inflammation following disease resolution and there is a mechanistic link between chronic inflammation and malignancy, suggesting potential strategies to mitigate cancer risk in patients with chronic inflammatory conditions.

Androgen activity in the male embryonic hindbrain prolongs hindbrain differentiation in male individuals and drives sex differences in the incidence and prognosis of posterior fossa type A (PFA) ependymoma, an aggressive childhood brain tumour.

A bioelectronic device incorporating triphylite (LiFePO₄) as electrode is used for lithium-ion-specific inhibition of peripheral and central nervous system activities in rats and in mice.

Plasmacytoid dendritic cells produce type I interferons in response to viral sensing. Here the authors show that amines inhibit these plasmacytoid dendritic cell responses through CXCR4 engagement.

The transcription factor ATF4 is shown to regulate double-stranded DNA repair within vulnerable CUX2⁺ upper-layer 2/3 cortical neurons, enabling their survival during development.

Ongoing chikungunya virus replication leads to the accumulation of inflammatory macrophages and CD4⁺ T cells in joint-associated tissues. Inhibition of chikungunya virus replication during chronic disease reduced viral RNA and joint inflammation in mice.

cellSTAAR advances noncoding rare variant association analysis by integrating single-cell genomics data.

European Commission's former chief scientific adviser, Anne Glover, also among those honoured by the Queen.

Using single-cell tissue imaging and spatial proteomics to study mitochondria–lipid droplet coupling in hepatocytes, PLIN5 phosphorylation is identified as a mediator of lipid flux and nutrient stress responses.

A screen of lung-targeting lipids revealed lipid nanoparticles offering improved delivery of mRNA and genome editors to lungs. Probing structure–activity relationships revealed a unique ‘tripod-like’ shape associated with the improvements.

The role of normally silenced transposable elements (TEs) in tumorigenesis remains unclear. Here, the authors show that increased expression of TEs in both patients and mice with colitis or by DNA hypomethylating drugs elicits a viral mimicry response that suppresses tumorigenesis. This viral mimicry response inhibits the stemness of cancer initiating cells in a cell autonomous manner.

Mitochondrial ROS are thought to be involved in NLRP3 inflammasome activation, but how this occurs is unclear. Here, the authors show that cofilin-1 negatively regulates NLRP3 activity by binding it at baseline, but cofilin-1 oxidation by ROS results in dissociation from the complex, thereby releasing NLRP3 activity.

Neville, Ferguson et al. show that non-canonical Polycomb repressive complex 1.1-mediated gene silencing is antagonized by DOT1L and is required for the therapeutic efficacy of Menin and DOT1L inhibitors in mixed-lineage leukaemia.

Insights into the mechanism by which phosphatidylserine functions as a non-classical inhibitory molecule during T cell exhaustion, and how phosphatidylserine-targeting antibodies enhance T cell responses are explored.

Brown adipocytes are embedded within an intricate network of blood vessels and sympathetic nerves that support their development and thermogenic function. This study shows that adipocyte progenitor cells control blood vessel growth and nerve wiring in brown fat during cold exposure. They do so by releasing Slit3, which is cleaved into fragments that coordinate angiogenesis and sympathetic innervation.

A study examines the effects of mutations that occur naturally in T cell cancers, reporting that such mutations can potentially be exploited to increase the potency of T cell therapies.

In mice, a low-protein diet leads to a gut-microbiota-driven remodelling of adipose tissue towards brown fat, showing that gut microorganisms have a role in detecting and responding to a lack of protein.

In mice, DHPS supports the maturation, maintenance and function of tissue-resident macrophages via the polyamine–hypusine axis, with implications for macrophage-targeting therapies.

Managing hydrocephalus relies on non-specific symptoms. Here, the authors report a 0.28-gram implant that measures intracranial pressure long term, tested in pediatric and adult patients.

The identification of ‘boosters’ that drive gene overexpression directly in a CAR construct provides a simple and scalable strategy for developing effective CAR-NK cell therapies for solid tumours.

Leveraging pythons as an extreme model of feeding and fasting behaviour, this study uncovers para-tyramine-O-sulphate as a conserved postprandial metabolite that links nutrient intake to energy balance by activating hypothalamic neurons and suppressing food intake in pythons and mice.

MultiSTAAR provides a general and flexible statistical framework for functionally informed multi-trait rare variant analysis of biobank-scale sequencing studies by jointly analyzing multiple traits and incorporating annotation information.

Mucida and colleagues developed Tracking Recently Activated Cell Kinetics (TRACK) mice, which allow spatial and temporal labeling of recently activated CD4⁺ T cells. Using these mice, they show that, during influenza infection, tissue-specific environments drive both divergent CD4⁺ T cell differentiation and clonal selection.

In this atlas paper, the authors provide a transcriptomic and spatial taxonomy of myeloid cells in the central nervous system of mice and humans in health and pathology.

Massively parallel reporter assays across five cell types identify thousands of causal, noncoding regulatory variants among 220,000 loci, revealing diverse regulatory mechanisms shaping complex traits and disease.

Most studies of the genetics of the metabolome have been done in individuals of European descent. Here, the authors integrate genomics and metabolomics in Black individuals, highlighting the value of whole genome sequencing in diverse populations and linking circulating metabolites to human disease.

Intracellular redox state orchestrates a self-reinforcing circuit connecting hypoxia inducible factor 1α-dependent signalling with post-translational regulation of the metabolic enzyme isocitrate dehydrogenase 1 to govern intestinal stem cell fate.

McGrail and colleagues report that high intratumoral bacteria abundance is associated with an immunosuppressive microenvironment and resistance to immune checkpoint blockade in head and neck squamous cell carcinoma.

Meningiomas are common brain tumors with variable behavior. This study reveals high STING expression across multiple cell types in the meningioma microenvironment. STING agonism triggers tumor cell death via programmed necrosis and pyroptosis, enhancing survival in preclinical models.

A comprehensive atlas platform integrating transcriptional and epigenetic data enables more precise engineering of T cell states, accelerating the rational design of more effective cellular immunotherapies.

T cell activation requires major metabolic adaptation. Here authors find that in mice and humans, expression of the NAD/H-synthesis enzyme nicotinamide riboside kinase 1 (NRK1) increases in CD4+ T cells upon activation, particularly within the cytoplasm, which impacts NADP/H and reactive oxygen species signalling, restraining activation and cytokine production while promoting CD4 + T cell survival during viral and fungal infections.

Metabolic and proteomic profiles derived from fossilized skeletal remains of animals enable inferences regarding physiological health and disease as well as diet to provide reconstructions of ancient soil, vegetation and palaeoclimate characteristics.

Intratumor heterogeneity (ITH) has been mainly studied at the genomic level. Here, the authors integrate multi-region proteomics of 280 tumor regions from 33 patients, exome sequencing, and imaging-based immune and stromal profiling to investigate functional spatial proteomic ITH in breast cancer and the interactions of cancer cells and the tumor microenvironment during cancer progression.

Microglia can alter their properties to adopt a wide spectrum of cellular phenotypes. Here, the authors show that remodeling of microglial mitochondria accompanies microglial responses to challenges and aging, and provide evidence that these organelles play a role in regulating basal microglial morphology, gene expression, and inflammatory profile.

This work describes three people living with HIV-1 who maintain long-term immune-mediated control of HIV-1 after pausing antiretroviral therapy. Autologous neutralizing antibodies and polyfunctional HIV-1-specific CD4⁺ and CD8⁺ T cell responses, pre-programmed for antigen response, were present before, and persisted during, ART interruption. This serves as a model of ART-free control of HIV-1 and informs new HIV-1 cure strategies.

Neurotrophic factor Nerve Growth Factor (NGF) is involved in bladder physiopathology. Here the authors report that mast-cell derived NGF sustains the pro-tumoral functions of ILC2s in bladder cancer (BC), showing that selective targeting of the NGF receptor TrkA improves survival and response to immune checkpoint blockade in BC models.

Shark teeth have short lifespans yet can be subject to significant mechanical damage. Here, the authors report on a site-specific damage mechanism in shark teeth enameloid, which maintains tooth functional shape, providing experimental evidence that tooth architecture may have influenced the diversification of shark ecologies over evolution.

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.

WIN332 is an HIV-1 Env protein designed to elicit a new class of Asn332-glycan-independent antibodies (type II) to the V3-glycan site of Env. WIN332 immunization rapidly induces type-II V3-glycan antibodies with low inhibitory activity indicative of a neutralization activity in macaques.

Human:pig embryos can be produced by deleting the MYF5, MYOD and MYF6 genes in pig embryos via CRISPR and somatic-cell nuclear transfer, followed by the delivery of TP53-null human induced pluripotent stem cells via blastocyst complementation.

Humanity’s Last Exam, a multi-modal benchmark at the frontier of human knowledge, is designed to be an expert-level closed-ended academic benchmark with broad subject coverage.

Tumour-antigen-pulsed mature dendritic cells (DC) have not been as efficient for cancer therapy as hoped to be, due to their sub-optimal antigen-presentation and migration capacities. Here the authors utilise DC progenitors, constitutively expressing IL-12 and an engineered extracellular vesicle-internalizing receptor (EVIR), which give rise to mature conventional type 1 DCs with improved antigen presenting capacities, resulting in improved anti-tumour immunity in a mouse model of melanoma.

Oligodendrogenesis is shown to be involved in reward learning, with dopaminergic neuronal activity-regulated myelin plasticity being an important reward circuit modification.