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Circadian clock in adipocytes maintains metabolic health by regulating mitochondrial complex I respiration.

Studies in zebra finches show that dopamine has a key role as a reinforcement signal in the trial-and-error process of learning that underlies complex natural behaviours.

Engineering motif-specific 'hot spots' into an antibody scaffold yields antibodies with high affinity to targets containing phosphoserine, phosphothreonine or phosphotyrosine.

Genome-wide association meta-analysis identifies 58 independent risk loci for major anxiety disorders among individuals of European ancestry and implicates GABAergic signaling as a potential mechanism underlying genetic risk for these disorders.

Engineered mucus-tethering bispecific nanobodies neutralize and entrap viruses to enhance mucosal immunity, preventing influenza infection and limiting SARS-CoV-2 transmission.

An algorithm that combines deep learning, Bayesian optimization and computer vision techniques can be used to autonomously tune a semiconductor spin qubit from a grounded device to Rabi oscillations.

A combination of mouse model data and data from a randomized phase 2 trial in patients with breast cancer in remission demonstrates feasibility, safety and a reduction in residual tumor cells following treatment with hydroxychloroquine and/or everolimus.

The ~500-metre-thick Prudhoe Dome in northwestern Greenland completely deglaciated 7,000 years ago, highlighting the sensitivity of the ice sheet to mid-Holocene warming, according to luminescence and geochemical data from sub-ice sediments and ice cores.

Systematic screening of transcription factors reveals conserved mechanisms governing cortical radial glia lineage progression across primates and provides a framework for functional dissection of gene regulatory networks in human cortical neurogenesis.

Using magnetoencephalography, this study reveals hippocampal and cortical oscillatory dynamics supporting semantic processing in healthy adults, highlighting distinct functional roles for theta and gamma oscillations.

One of three back-to-back papers to show that dosage of BACH2 can modulate T cell differentiation and function and how we might apply this to enhance CAR T cell therapies for cancer.

Despite the growing literature and widespread interest in transformational adaptation, its definition remains contested. The results of a global expert survey reveal broad agreement on 13 key elements that should be included in defining transformational adaptation.

In this work, authors show that retro-inversion of host-defense peptides markedly improves their antitubercular potency and selectivity, highlighting the potential of this simple chemical modification to advance the design of novel antimycobacterial biotherapeutics.

The tolerogenic activity of type 1 conventional dendritic cells (cDC1s) is determined by EPOR, which is preferentially expressed in cDC1s and induces antigen-specific FOXP3-expressing regulatory T cells.

Virus-like particles are engineered to edit human hematopoietic cells in vivo.

It remains unknown why only some sickle cell disease (SCD) patients develop lung thrombosis. Here, the authors show that an extracellular vesicle-dependent mechanism prevents lung thrombosis in SCD and how a CD39 polymorphism impairs this protection to promote lung thrombosis in subset of patients.

Xenotransplantation of a genetically edited pig kidney with a thymic autograft into a brain-dead human for 61 days with immunosuppression resulted in stable kidney function without proteinuria, and xenograft rejection was treated and reversed by the end of the study.

CaBLAM is a bioluminescent genetically encoded calcium indicator that delivers high-contrast signals as shown in cell culture, in the in vivo mouse brain and in zebrafish larvae.

MYC-driven medulloblastoma is an aggressive pediatric tumor with limited treatment options. Here, the authors show that CDK8 regulates ribosome biogenesis and that combined inhibition of CDK8 and mTOR demonstrates therapeutic efficacy in mouse models of this cancer.

The authors show in an animal model and in a study in patients with dementia with Lewy bodies (DLB) that the drug neflamapimod has potential to treat diseases, such as DLB, associated with loss of neurons that produce the neurotransmitter acetylcholine.

XCR1+ type 1 conventional DCs (cDC1s) are crucial to mount anti-tumor immune responses, however their infiltration within tumours is often limited. Here the authors show that cDC1 infiltration could be expanded by intratumoral delivery of mesenchymal stromal cells engineered to express the membrane bound form of FLT3L in combination with poly(I:C) or CXCL9 and CCL5, improving anti-tumor immunity in preclinical models.

MYC-driven medulloblastoma is highly aggressive and associated with poor survival. Here, the authors perform single nuclei multi-omic analysis of matched primary and recurrent tumours and identify potential resistance mechanisms and targetable pathways.

Regrowth of lost enamel in tooth decay and sensitivity is a major obstacle to overcome. Here, the authors report on a protein-based material that mimics features of natural enamel formation, allowing for epitaxial growth of apatite nanocrystals to restore enamel structure and function.

Walmsley and colleagues report that systemic hypoxia induces persistent loss of histone H3K4me3 marks and epigenetic reprogramming in neutrophil progenitors, resulting in long-term impairment of subsequent neutrophil effector functions.

This Review outlines the science behind psychedelic medicine and integrates mechanistic knowledge with clinical evidence across neuropsychiatric indications, highlighting challenges, controversies and opportunities.

In a phase 2 randomized control trial, intermittent senolytic therapy administered to postmenopausal women did not result in a reduction in the bone resorption marker, serum CTx, compared to control at 20 weeks.

Quantifying genomic aberrations resulting from designer nucleases activity is essential for gene therapy clinical translation. Here, the authors present a modular digital PCR technique that profiles DNA repair precision and cut-repair cycles at the edited loci, exposing current evaluation biases.

The thalamus is important for neocortical functional specialization. Here the authors show its shifting role in shaping large-scale functional organization during early life in humans, particularly in developing the internal–external cortical hierarchy.

It is unclear which aspects of experience shape sleep’s contributions to learning. Here, by combining neural recordings in rats with reinforcement learning, the authors show that reward-prediction signals support sleep-dependent learning over multiple days.

Previous studies suggested that glycogen metabolism played a role in beiging of subcutaneous adipocytes. This work identifies a β-adrenergic–driven transcriptional program that promotes glycogen synthesis and turnover during thermogenic activation of adipocytes. PGC1α and estrogen-related receptors (ERRs) cooperatively sustain this program by regulating chromatin accessibility and gene expression.

Reovirus mRNAs lack polyadenylated tails yet are efficiently translated. Here, the authors identify host protein ataxin-2-like (ATXN2L) as a mediator of reovirus nonpolyadenylated mRNA translation.

ERα^vlVMH neurons mediate the inhibitory role of 17β-oestradiol on prolactin production, and this inhibition is lifted in lactating mice to promote lactation-associated metabolic adaptations.

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

In this study, the authors show that gut dysbiosis in African children with severe malaria may contribute to the pathogenesis of malaria, including an increased risk of post-discharge mortality.

Benito-Martínez, Salavessa and colleagues show that keratin intermediate filaments and microtubules control the three-dimensional perinuclear position of melanin-containing organelles, shielding the DNA from photodamage.

Restoration of sight by subretinal photovoltaic prosthesis could be improved with next generation devices with smaller pixels. Here, the authors demonstrate safe removal and replacement of implants in rats, retinal integrity preservation and improved grating acuity with 22 μm pixel devices.

Ramadoss et al. show that bone-marrow-derived macrophages contribute to heart repair following myocardial infarction by secreting GPNMB, which binds to the orphan receptor GPR39 to improve myocyte contractility and reduce fibroblast activation.

Profiling transcriptional crosstalk between promoters and cell-type-specific enhancers allows large gene cargo delivery.

Metformin may serve as a non-toxic intervention to inhibit mitochondrial metabolism and slow DNMT3A-R882 clonal haematopoiesis expansion, thus delaying or averting progression to acute myeloid leukaemia.

Ramachandran et al. identify a previously unappreciated function for transcriptional repressor B cell lymphoma 6 (BCL6) in muscle proteostasis and strength, and provide mechanistic insight into the molecular underpinnings of this function.

Seshadri, Davis and colleagues show that individuals who do not develop an infection with Mycobacterium tuberculosis (Mtb), despite exposure to the bacteria and expansion of CD4⁺ T cell clones specific to Mtb antigens, show enrichment of T_H17 cell and T regulatory functional programs.

Mouse models of lung and colorectal cancer with sporadic DNA mismatch repair deficiency clarify that the intratumor heterogeneity and clonal architecture rather than tumor mutational burden are powerful determinants of immunotherapy response.

This study characterised the landscapes and changes of RNA m6A in brains of individuals with or without Alzheimer’s disease, and revealed roles of a promoter antisense RNA next to MAPT in neuronal gene regulation that promote neuronal survival.