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Induction of CD4 T follicular helper (Tfh) cells is important for antibody responses to viral infections. Here, the authors show in a rhesus macaque model of mild COVID-19 that SARS-CoV-2 infection results in transient accumulation of proliferating Tfh cells with a Th1 profile in peripheral blood and generation of germinal center Tfh cells specific for viral proteins.

Water molecules are crucial for protein stability and interactions, yet predicting their precise positions around protein structures remain challenging. Here, the authors present SuperWater, a generative AI framework combining a score-based diffusion model and equivariant graph neural networks, to achieve unprecedented accuracy in water placement, demonstrating the capabilities involving protein hydration, protein-ligand binding and protein-protein interactions.

In this phase 1 trial of a personalized, neoantigen-specific autologous T cell therapy, BNT221, when given as monotherapy in patients with metastatic melanoma refractory to PD-1 and CTLA-4 inhibitor regimens, the therapy was safe and showed preliminary clinical activity and neoantigen-specific T cell responses.

Mi et al. report epitaxial surface coverage of single CsPbBr3 quantum dots with size ranging from 3.6 nm to 14 nm using low steric ligand tails with attractive π-π stacking, leading to nearly non-blinking single photon emission with high purity of 98% and photostability over 12-hour irradiation.

Here the authors show that BTLA on effector T cells interacts with HVEM on other immunosuppressive cells in the tumor microenvironment. The authors also present evidence that overcoming this checkpoint can ehance CAR T functionality.

In this study, Massachusetts Consortium for Pathogen Readiness (MassCPR) investigators assess the relationship between SARS-CoV-2 viral load and COVID-19 disease severity and report that the levels of detectable viral RNA, especially in plasma, correlates with severity of respiratory disease, inflammatory markers and predicted risk of death.

Common genetic variants associated with plasma lipids have been extensively studied for a better understanding of common diseases. Here, the authors use whole-genome sequencing of 16,324 individuals to analyze rare variant associations and to determine their monogenic and polygenic contribution to lipid traits.

Mutations in the gene HADHA result in mitochondrial tri-functional protein (MTP) deficiency and can result in sudden infant death syndrome for which there is no treatment. Here the authors show that the MTP deficient pathology in human cardiomyocytes leads to an abnormal cardiolipin pattern and suggests that cardiolipin affecting compounds may serve as a potential therapy.

Here the authors present a deep learning framework for dementia diagnosis, which can identify persons with normal cognition, mild cognitive impairment, Alzheimer’s disease, and dementia due to other etiologies.

Platelet aggregation is associated with myocardial infarction and stroke. Here, the authors have conducted a whole genome sequencing association study on platelet aggregation, discovering a locus in RGS18, where enhancer assays suggest an effect on activity of haematopoeitic lineage transcription factors.

The expression of each of the roughly 22,000 genes of the mouse genome has been mapped, at cellular resolution, across all major structures of the mouse brain, revealing that 80% of all genes appear to be expressed in the brain.

An approximately 2-million-year-old male Paranthropus robustus cranium from Drimolen Main Quarry in South Africa refutes influential ideas of sexual dimorphism in this taxon and instead suggests local microevolution within robust australopiths.

Federated learning, a method for training artificial intelligence algorithms that protects data privacy, was used to predict future oxygen requirements of symptomatic patients with COVID-19 using data from 20 different institutes across the globe.

Polygenic Priority Score (PoPS) prioritizes candidate effector genes at complex trait loci by integrating genome-wide association summary statistics with other data types. Combining PoPS with methods that leverage local genetic signals further improves the performance.

The authors report an in-situ x-ray diffraction study of pressure and strain-induced phase transformations in silicon, an essential electronic material. They observe several different plastic strain-induced transformation phenomena which may inspire practical applications.

Knockout studies using CRISPR–Cas9 identify PCDH10 as a selective host cellular receptor for western equine encephalitis virus.

Organic aerosol particles are important to climate and human health but remain poorly characterized on account of their immense chemical complexity. Here, using both field and laboratory measurements of organic aerosol, we demonstrate the use of average carbon oxidation state for describing aerosol chemical properties and atmospheric transformations.

Methylome-based clustering and cross-modality integration with companion datasets from the BRAIN Initiative Cell Census Network enabled the construction of a 3D multi-omic genome atlas of the adult mouse brain featuring thousands of cell-type-specific profiles.

The BRAIN Initiative Cell Census Network has constructed a multimodal cell census and atlas of the mammalian primary motor cortex in a landmark effort towards understanding brain cell-type diversity, neural circuit organization and brain function.

This study describes the integrative analysis of 111 reference human epigenomes, profiled for histone modification patterns, DNA accessibility, DNA methylation and RNA expression; the results annotate candidate regulatory elements in diverse tissues and cell types, their candidate regulators, and the set of human traits for which they show genetic variant enrichment, providing a resource for interpreting the molecular basis of human disease.

An examination of motor cortex in humans, marmosets and mice reveals a generally conserved cellular makeup that is likely to extend to many mammalian species, but also differences in gene expression, DNA methylation and chromatin state that lead to species-dependent specializations.

Reanalysis of bipedal trackways from Laetoli site A in Tanzania suggest that the footprints were made by a hominin that coexisted with at least one other hominin species.

This work describes the identification and characterization of novel small molecule activators of SIRT1, an NAD⁺-dependent deacetylase that mediates the beneficial effects of caloric restriction. These small molecules are structurally unrelated to, and much more potent than, resveratrol, and improve metabolic function in animal models of diabetes and obesity.

Circulating lipoprotein(a) is an important risk factor for cardiovascular disease and shows variability between different ethnic groups. Here, Zekavat et al. perform whole-genome sequencing in individuals of European and African ancestries and find ancestry-specific genetic determinants for lipoprotein(a) levels.

Diversification of Neotropical birds is not directly linked to the Andean uplift, the major landscape change of the Neogene period; instead, most diversification is post-Neogene and species diversity is dependent on how long lineages have persisted in the landscape and how easily they disperse.

A 16-member diastereoisomer library known to contain macrosphelides A and E is synthesized as a mixture with the aid of a new encoding strategy for fluorous mixture synthesis. A simple process of sequential demixing and tag removal provides each of the isomers in individual, pure form. Analysis of the other library members ultimately leads to a structural reassignment for macrosphelide D.

Pressure causes profound changes in the properties of atoms and chemical bonding leading to unusual materials. Here, the authors investigate the Ca-C system and find that it becomes increasingly complex and develops a multitude of phases with various compositions and new structures at higher pressures.

Analysing whole-genome sequences from 68 rattlesnakes, the authors show a role of long-term balancing selection in maintaining diversity of multiple venom gene families and find reduced selective interference of venom genes with neighbouring loci.

Neuroinflammation is observed in Alzheimer’s disease. Here the authors show that 15 proteins related to inflammation found in CSF can potentially be used as a prognostic biomarker.

COVID-19 disease is less common in children than adults, but the extent to which SARS-CoV-2 infections are missed through symptom-driven testing is not well understood. In this study, the authors show that approximately 1% of children seeking care for reasons other than COVID-19 at a Seattle hospital in March/April 2020 were seropositive for SARS-CoV-2.

Atmospheric organic compounds are central to key chemical processes that influence air quality. Concurrent measurements of a wide range of these compounds, including previously unmeasured ones, provide closure on OH reactivity.

Protein methyltransferase PRMT5 symmetrically dimethylates arginine residues in proteins, including histones, and has been associated with tumorigenesis. The identification of EPZ015666 as a potent chemical probe of PRMT5 could promote understanding of the role of PRMT5 in human disease both in cells and in vivo.

MetaSTAAR enables functionally informed rare variant association analysis in biobank-scale cohorts using an efficient, sparse matrix approach for summary statistic storage.

The GREGoR consortium provides foundational resources and substrates for the future of rare disease genomics.

A high-resolution reference panel based on whole-genome sequencing data enables accurate imputation of HLA alleles across diverse populations and fine-mapping of HLA association signals for HIV-1 host response.

EZH2 is a protein methyltransferase component of the polycomb repressive complex 2 (PRC2) that installs the H3K27me3 chromatin mark. EPZ005687 inhibits EZH2 function and H3K27 trimethylation in cells and selectively kills lymphoma cells that require EZH2 for proliferation.

Muscle-invasive bladder cancer (MIBC) is a potentially lethal disease. Here the authors characterize diverse genetic alterations in MIBC that convergently lead to constitutive activation of PPARgamma/RXRalpha and result in immunosurveillance escape by inhibiting CD8+ T-cell recruitment.

A monobody was identified that binds to an allosteric lobe at the α4-β6-α5 interface to block H- and K-RAS signaling and transformation by disrupting RAS dimerization and nanoclustering.

Squeezed states of light have been experimentally demonstrated to improve the performance of the Laser Interferometer Gravitational-wave Observatory (LIGO) in astrophysically relevant frequency regions. This enhanced performance may help to reach the sensitivity required for detecting gravitational waves.

The Cancer Genome Atlas Research Network reports an integrative analysis of more than 400 samples of clear cell renal cell carcinoma based on genomic, DNA methylation, RNA and proteomic characterisation; frequent mutations were identified in the PI(3)K/AKT pathway, suggesting this pathway might be a potential therapeutic target, among the findings is also a demonstration of metabolic remodelling which correlates with tumour stage and severity.

Theta oscillations are thought to propagate unidirectionally along the hippocampal circuitry, from CA3 to CA1 and the subiculum. In this paper, Jackson and colleagues demonstrate that, in the intact rat hippocampus, theta activity can also flow in reverse from subiculum to CA3, and find that this phenomenon depends on long-range GABAergic inhibition.

Boulting et al. profile activity-dependent gene expression and regulatory elements in human induced pluripotent stem cell-derived GABAergic neurons and uncover a possible role for calcium-responsive gene promoters of these neurons in autism risk.

Socially synchronized rhythms in shorebirds were assessed during biparental incubation under natural circumstances and were exceptionally diverse, often not following the 24-h day, whereby risk of predation, not starvation, determined some of the variation in incubation rhythms.

This analysis provides 108 noncoding CRISPR screens collated by the ENCODE4 consortium and establishes experimental guidelines for future CRISPRi screens characterizing functional cis-regulatory elements.

Associations between corals and symbiotic microorganisms could be driven by the environment or shared evolutionary history. Here, the authors examine relationships between coral phylogenies and associated microbiomes, finding evidence of phylosymbiosis in microbes from coral skeleton and tissue, but not mucus.