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SRCAP depletion causes rapid replacement of H2A.Z by H2A, leading to upregulation of lineage-specific transcription factors. SRCAP also prevents pioneer transcription factor binding by steric hindrance, independently of its H2A.Z-depositing activity.

The mechanism(s) controlling CD8+ virtual memory T cell (TVM) development are still under investigation. Here, using uninfected or IAV-challenged Ikzf3-deficient mice, the authors identify the transcription factor Aiolos as a negative regulator of TVM cell development by repressing Eomes and IL-15/STAT5 signaling.

Many viral vaccine antigen candidates are transmembrane glycoproteins, and their development requires methods which allow their biophysical characterization. Here authors present an optimized nanodisc assembly platform which provides reproducible, scalable, and accurate replication of the vaccine candidates for detailed analysis.

Oligonucleotide-mediated proximity-interactome MAPping (O-MAP) enables precise multiomic characterization of biomolecular interaction networks at target RNAs. Distinct O-MAP workflows reveal RNA-adjacent proteins, transcripts and genomic loci.

By measuring charge exchange in a sphere/plate pair composed of identical amorphous silicon dioxide and controlling charging polarity using baking or plasma treatment, adventitious carbon is shown to break symmetry in oxide contact electrification.

1,3-Pr2-6-OTs GlcNAlk is a precursor uniquely targeting the essential glycosyltransferase MGAT1 to selectively tag hybrid N-glycan-modified proteins. Some hybrid-glycan tagged proteins move through a route from the Golgi to the nucleus/nucleolus.

C16orf74/ calcimembrin (CLMB), a lipidated microprotein with roles in cancer, targets the calcineurin phosphatase to membranes. Here, authors show how CLMB uses a composite motif to form multimeric complexes with calcineurin that are required for dephosphorylation.

Schief and colleagues show that germline-targeting epitope scaffolds can elicit responses from rare broadly neutralizing antibody precursor B cells with predefined binding specificities and genetic features.

Bats harbor diverse coronaviruses but temporal dynamics are less well studied. Here, the authors analyzed coronaviruses in Australian flying foxes over 3 years showing peak shedding and co-infections in juveniles and subadults and providing evidence of historical and contemporary recombination between viral clades.

Molecular drivers of sex-specific brain plasticity are unknown. Here, authors show estrogen-driven Egr1 controls chromatin accessibility sex-dependently, driving gene expression, structural plasticity, and anxiety- & depression-related behaviour.

Biologics can be specifically delivered to T cells by genetically engineering cells to secrete extracellular vesicles that actively load protein cargo and that display high-affinity T-cell-targeting domains and fusogenic glycoproteins.

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.

Global inhibition of NHEJ factors has been one strategy to improve CRISPR-Cas9 mediated HDR. Here the authors fuse a dominant-negative mutant of 53BP1 to Cas9 to enhance HDR frequency, reduce NHEJ specifically at the Cas9 cut sites, and reduce the toxicity associated with global NHEJ inhibition.

The regulation and direction of CD4⁺ T cells into phenotypic and functional lineages is coordinated by a complex set of mechanisms. Here the authors show a role for Aiolos as a regulator of the CD4⁺ cytotoxic and T follicular helper lineages.

Using single-molecule tracking of cohesin and CTCF during zebrafish embryogenesis, the molecular kinetics underlying chromatin architecture formation was revealed and gradual emergence of chromatin structure recapitulated by polymer simulations.

Activation of G_s signaling at mitochondria by mitoDREADD-G_s increases mitochondrial metabolism, leading to better memory in mouse models of dementia, directly linking brain mitochondrial deficits to cognitive symptoms of neurodegenerative diseases.

The neurobiological mechanisms underlying the fast acting and long-lasting effects of these drugs are not fully understood. Here authors show that the psychedelic psilocin increases reactivity in the paraventricular nucleus of the hypothalamus (PVN) in male rats but does not change acute stress response. Male reactivity changes are driven by active threat responding, with clinical implications.

Amino acid changes in the envelope and non-structural 2A protein attenuate the virulent yellow fever virus (YFV) and enhance host antiviral responses upon infection in vivo. These traits explain the potency of the YFV vaccine.

Drug efflux through ABC transporters is a common mechanism leading to chemoresistance in cancer. Here, the authors show that mitochondrial respiration provides ATP to allow ABC transporters activity so mitochondrial respiration inhibition overcomes chemoresistance in preclinical cancer models.

Wu, Harrison and colleagues visualize lactate production at subcellular resolution in migrating endothelial cells and identify hotspots of glycolytic activity, mediated by RhoA and the glucose transporter SLC2A3, that couple cellular energy metabolism with cytoskeleton remodelling and cell motility.

The underlying transcriptional and cellular events mediating the reduction of dendritic spines on medium spiny neurons of the nucleus accumbens (NAc) remains unknown. Here, authors demonstrate that heroin self-administration negatively regulates the actin-binding protein drebrin in the NAc, which is shown to be transcriptionally repressed by the histone modifier HDAC2, and that overexpression of drebrin is sufficient to decrease drug seeking and increase dendritic spine density

Wen and colleagues show that the transmembrane protein SUSD2 is a specific negative regulator of CD8⁺ T cells activation in the tumor environment by interacting with IL-2 receptor α and interfering with IL-2 binding to the receptor.

Here, in a follow-up of a clinical study, the authors show that protein pacing and intermittent fasting improves gut symptomatology and microbial diversity, as well as reduces visceral fat compared to a heart-healthy, calorie-restricted diet matched for overall energy intake and expenditure in free-living humans.

Dietary protein influences metabolic health and ageing. Here Solon-Biet et al. show that, rather than having a direct toxic effect, dietary branched-chain amino acids (BCAAs) appear to induce hyperphagia, owing to an imbalance between BCAAs and other amino acids, which reduces lifespan as a consequence of obesity.

Reliable detection of mutations below 0.5% variant allele frequency remains a key challenge for circulating tumor DNA sequencing assays.

Complete 5-methylcytidine substitution enhances the efficacy of self-amplifying RNA.

A protein platform rapidly develops peptide-focused major histocompatibility complex class I binders with high specificity.

Simpson and colleagues systematically interrogate the influence of dietary carbohydrate type and quality on the obesogenic impact of protein-diluted diets in mice.

pSABER combines the power of signal amplification by exchange reaction (SABER) with the deposition of fluorescent or colorimetric substrates by horseradish peroxidase to enable enhanced signals for in situ hybridization in cells and tissues.

Gangliosides play crucial roles in the nervous system, with aberrant metabolism linked to diseases like cancer and neurodegeneration, but tools to visualize and detect gangliosides remain limited and non-specific. Here, the authors introduce MM-JH-2, a dual fluorescent and Raman-active probe, enabling specific ganglioside labeling and differentiation between cells that differ in ganglioside biosynthetic flux.

In a phase 1b/2a trial, the combination of the oral PI3K inhibitor duvelisib and romidepsin had limited toxicity and exhibited encouraging clinical activity in patients with relapsed or refractory T cell lymphoma, suggesting an approach whereby PI3K inhibitors can be safely used in this patient population.

Targeted proteomics enables robust hypothesis-driven research. Here, Yu et al. present a multiplexed approach for targeted pathway proteomics and apply it to quantify protein families across 480 fully genotyped Diversity Outbred mice, revealing impacts of genetic variation on protein expression and lipid metabolism.

Natural isolates of Caenorhabditis elegans nematodes differ in their sensitivity to the anti-exploratory pheromone icas#9, yielding two distinct foraging strategies that possess different survival advantages depending on environmental conditions such as food distribution.

SIVmac239 infection of macaques is a favored model of human HIV infection, but antibody-mediated protection for SIVmac239 is insufficiently understood. Here, Zhao and Berndsen et al isolated nAbs and confirmed protection against SIVmac239 infection in passive transfer studies in macaques. The nAb was used to provide the first high-resolution structure of a rhesus SIV trimer by CryoEM. Analysis of the glycosylation pattern of this SIV trimer suggests a denser glycan shield on Env for rhesus SIV compared to chimpanzee SIV or HIV-1, which partially explains the poor nAb response of rhesus macaques to SIVmac239 infection.

Tumour evolution and heterogeneity in high grade serous ovarian cancer (HGSOC) remains poorly characterised. Here, the authors investigate the genomic landscape of HGSOC and reveal two distinct evolutionary trajectories associated with clinical outcomes.

Panos Deloukas, Nilesh Samani and colleagues report a large-scale association analysis using the Metabochip array in 63,746 coronary artery disease cases and 130,681 controls. They identify 15 susceptibility loci, refine previous associations and use network analysis to highlight biological pathways.

Comparisons of a chimeric recombinant version of SARS-CoV-2, the ancestral SARS-CoV-2 strain and an Omicron isolate show that the attenuated virulence of Omicron is caused by mutations in both the spike protein and nsp6.

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.

An intestine-critical region on human chromosome 16, and its regulation of PERCC1, a newly identified gene, is shown to underlie the genetic basis of a severe, inherited form of diarrhoea.

Myosin-binding protein C (MyBP-C) resides and interacts with the myosin filaments in striated muscle and regulates contraction via an unclear mechanism. Here, the authors demonstrate that MyBP-C regulates the performance of myosin heads.

Antibody based biologics are a rapidly growing class of therapeutics with interest to enhance their performance, distribution, longevity and effectivity. Here, authors report the engineering of human IgG Fc to enhance plasma half-life, mucosal distribution and killing of cancer cells and bacteria.

Hybrids have complex genomes that influence their adaptive potential. This study reveals that yeast hybrids adapt slower than their parental species in a new environment, primarily due to a reduced rate of loss of heterozygosity in key genes.

Dysregulation of intracellular calcium is reported in Alzheimer’s disease. Here the authors show that loss of the mitochondrial Na⁺ /Ca²⁺ exchanger, NCLX – primary route of mitochondrial calcium efflux, precedes neuronal pathology in experimental models and contributes to Alzheimer’s disease progression.

HIV-1 vaccine design aims to induce broadly neutralizing antibodies such as IOMA, the only described antibody in its class. Here, the authors present the isolation, characterisation and structure of three additional antibodies within the IOMA class

Accessibility into the distal vascular systems to treat various diseases remains challenging using medical catheters. Here, Wang et al. demonstrate that a stent-shaped wireless magnetic soft robot enables adaptive locomotion and medical functions into these distal vascular regions.

Human glial progenitor cells (hGPCs) lose mitotic competence with age. Here, the authors show that with maturation, adult hGPCs acquire a set of transcriptional repressors that actively suppress developmental gene expression.

Here the authors provide evidence that 3D chromatin structure in the mouse brain differs between males and females and undergoes dynamic remodelling during the female ovarian cycle. They show female-specific 3D genome dynamics affects neuronal gene expression and brain disorder-relevant genes, and could play a role in reproductive hormone-induced brain plasticity and female-specific risk for brain disorders.

Better analytical methods are needed to extract biological meaning from genome-wide association studies (GWAS) of psychiatric disorders. Here the authors take GWAS data from over 60,000 subjects, including patients with schizophrenia, bipolar disorder and major depression, and identify common etiological pathways shared amongst them.

A human–SARS-CoV-2 protein interaction map highlights cellular processes that are hijacked by the virus and that can be targeted by existing drugs, including inhibitors of mRNA translation and predicted regulators of the sigma receptors.

The development of native-like envelope trimers has been a major focus in the efforts to produce HIV vaccines. Here the authors demonstrate the production and characterization of virus-like nanoparticles displaying trimeric HIV-1 antigens with the potential to elicit broadly neutralizing antibodies.