Search

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.

Immune features and T cell characteristics that correlate with post-intervention control of HIV-1 viraemia inform the development of combination immunotherapies that may enhance the ability to elicit durable HIV remission.

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.

Most human genes undergo alternative splicing, but population-level variation is poorly understood. Here, the authors map over 57,000 naturally variable exons across 838 individuals, revealing widespread splicing diversity and its impact on gene expression and genetic interpretation.

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.

How inflammation spreads from the skin to the joints in psoriatic disease is unclear. Here, the authors show that joint-resident fibroblasts can control differentiation of infiltrating skin-derived myeloid precursors that can become inflammatory macrophages.

Here Jaster et al., show a single psilocybin dose produce sex-specific post-acute changes in opioid reward and withdrawal via 5-HT2A receptors in frontal cortex-to–nucleus accumbens circuits, with epigenetic and synaptic changes shaping therapeutic potential.

A large genome-wide association study of more than 5 million individuals reveals that 12,111 single-nucleotide polymorphisms account for nearly all the heritability of height attributable to common genetic variants.

Together with an accompanying paper presenting a transcriptomic atlas of the mouse lemur, interrogation of the atlas provides a rich body of data to support the use of the organism as a model for primate biology and health.

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.

A meta-analysis of genome-wide association studies of type 2 diabetes (T2D) identifies more than 600 T2D-associated loci; integrating physiological trait and single-cell chromatin accessibility data at these loci sheds light on heterogeneity within the T2D phenotype.

It is uncertain how much life expectancy of the Chinese population would improve under current and greater policy targets on lifestyle-based risk factors for chronic diseases and mortality behaviours. Here we report a simulation of how improvements in four risk factors, namely smoking, alcohol use, physical activity and diet, could affect mortality. We show that in the ideal scenario, that is, all people who currently smokers quit smoking, excessive alcohol userswas reduced to moderate intake, people under 65 increased moderate physical activity by one hour and those aged 65 and older increased by half an hour per day, and all participants ate 200 g more fresh fruits and 50 g more fish/seafood per day, life expectancy at age 30 would increase by 4.83 and 5.39 years for men and women, respectively. In a more moderate risk reduction scenario referred to as the practical scenario, where improvements in each lifestyle factor were approximately halved, the gains in life expectancy at age 30 could be half those of the ideal scenario. However, the validity of these estimates in practise may be influenced by population-wide adherence to lifestyle recommendations. Our findings suggest that the current policy targets set by the Healthy China Initiative could be adjusted dynamically, and a greater increase in life expectancy would be achieved.

Analysis of soundscape data from 139 globally distributed sites reveals that sounds of biological origin exhibit predictable rhythms depending on location and season, whereas sounds of anthropogenic origin are less predictable. Comparisons between paired urban–rural sites show that urban green spaces are noisier and dominated by sounds of technological origin.

Whole-genome sequencing, transcriptome-wide association and fine-mapping analyses in over 7,000 individuals with critical COVID-19 are used to identify 16 independent variants that are associated with severe illness in COVID-19.

Together with a companion paper, the generation of a transcriptomic atlas for the mouse lemur and analyses of example cell types establish this animal as a molecularly tractable primate model organism.

mRNA vaccines targeting SARS-CoV-2 also sensitize tumours to immune checkpoint inhibitors.

Here, the authors suggest that nitric oxide (NO) is an endogenous epigenetic regulator of gene expression by inhibiting DNA demethylation enzymes (TET and ALKBH2) and increasing DNA methylation at gene regulatory loci throughout the genome.

Optineurin is linked to ALS and glaucoma, but the mechanism is unknown. Here, the authors show that optineurin mutation causes deficits in axonal mitochondria transport and neurodegeneration, enhancing of which achieves axon protection and regeneration.

Enzymatic recycling is an emerging technology to circularize the ubiquitous polyester poly(ethylene terephthalate). Here the authors evaluate and implement multiple process changes to improve the scalability and viability of this recycling technology. Process modeling demonstrates that these changes could enable cost competitiveness and greatly reduce overall life cycle impacts.

Chang et al. performed a pan-cancer multimodal data integration analysis and devised a model, LORIS, that can predict objective responses to immunotherapy and patient survival across many cancer types and allow for patient stratification.

An integrated analysis of de novo and inherited coding variants in 42,607 individuals with autism spectrum disorder identifies 60 risk genes of which five have not previously been associated with neurodevelopmental disorders.

Here, the authors perform a genome-wide association study to identify 157 significant testosterone genetic variants in male veterans, of which 8 are ancestry-specific. Men with higher testosterone genetic scores have lower odds of diabetes, hyperlipidemia, gout, and cardiac disorders.

An adversarial domain translation framework is presented for scalable integration of single-cell atlases across samples, technical platforms, data modalities and species.

Using cryo-EM, Chung et al. investigate conformational states of mammalian respiratory complex I to reveal an ubiquinone-10 molecule occupying the full length of the Q-binding channel. Molecular dynamics simulations suggest how the charge states of key residues influence the substrate binding pose.

GIANT, a genetically informed brain atlas, integrates genetic heritability with neuroanatomy. It shows strong neuroanatomical validity and surpasses traditional atlases in discovery power for brain imaging genomics.

Adenomyoepithelioma is a rare tumor of the breast with an unknown genetic basis. Here the authors perform a genomic analysis of adenomyoepitheliomas revealing that their repertoire of somatic mutations vary according to the estrogen receptor (ER) status, and that ER-negative tumors harbor recurrent mutations in HRAS and PI3K pathway genes.

The process of protein crystallization is poorly understood and difficult to program through the primary sequence. Here the authors develop a computational approach to designing three-dimensional protein crystals with prespecified lattice architectures with high accuracy.

A meta-analysis of genome-wide association study data from 77,418 individuals of East Asian ancestry with type 2 diabetes identifies novel variants associated with increased risk of type 2 diabetes.

Adaptation requires limiting exposure to climate threats, and policies should focus on curbing development in risky areas. By examining the Coastal Barrier Resources Act, researchers demonstrate that removing financial incentives for development can lower climate risks and damages.

Petrels are wide-ranging, highly threatened seabirds that often ingest plastic. This study used tracking data for 7,137 petrels of 77 species to map global exposure risk and compare regions, species, and populations. The results show higher exposure risk for threatened species and stress the need for international cooperation to tackle marine litter.

It is unclear how often genetic mosaicism of chromosome X arises. Here, the authors examine women with cancer and cancer-free controls and show that X chromosome mosaicism occurs more frequently than on autosomes, especially on the inactive X chromosome, but is not linked to non-haematologic cancer risk

Chromatin organization is measured in single cells using droplet microfluidics.

Designing and manufacturing eco/bioresorbable electronic systems remains a challenge. The authors introduce a picosecond-pulsed laser-based scheme that exploits controlled patterning, thinning, and/or cutting to manipulate multilayers of eco/bioresorbable materials for a wide range of advanced electronic systems.

Circular extrachromosomal DNA in high-risk medulloblastoma contributes to tumor heterogeneity and associates with relapse and survival. Enhancer rewiring events involving known oncogenes are frequent events, affecting transcription and proliferation.

SPNS2 exports S1P and FTY720-P to control immune cell migration. Here, the authors use cryo-EM, immunofluorescence, in vitro binding and in vivo S1P export, and MD simulations to uncover the mechanisms of SPNS2’s transport and inhibition.

The role of dopamine in the cerebellum remains relatively unexplored. Here, the authors report a dopamine system in the cerebellum in mice, where Purkinje cells supply dopamine and Bergmann glia express D1 receptors. Activation of D1 receptors is found to modulate Purkinje cell activity and to affect locomotor and social behaviors.

Endocrinologists have traditionally focused on studying one hormone or organ system at a time. Here the authors use transcriptomic data from the mouse lemur to globally characterize primate hormonal signaling, describing hormone sources and targets, identifying conserved and primate specific regulation, and elucidating principles of the network.

Gli and Hedgehog genes compound knockout fish exhibited a combination of actinopterygian fish and stem-tetrapod pectoral girdle characteristics, suggesting the evolutionary origin of terrestrial girdles as a tuning of a deeply conserved developmental program.

Prevotella copri, together with other microbiota members, plays a key role in mediating the beneficial effects of a gut microbiota-directed complementary food for malnourished children on microbiota and host functions.

The molecular atlas of soluble organic compounds from Ryugu shows unprecedented molecular complexity and diversity resulting from alteration on a low temperature, water rich parent body.

A single-cell multiomics analysis of over 200,000 cells of the primary motor cortex of human, macaque, marmoset and mouse shows that divergence of transcription factor expression corresponds to species-specific epigenome landscapes, and conserved and divergent gene regulatory features are reflected in the evolution of the three-dimensional genome.

The authors develop an RNA sequencing-based platform, PERSIST-seq, to simultaneously delineate in-cell mRNA stability, ribosome load, and in-solution stability of a diverse mRNA library to derive design principles for improved mRNA therapeutics.

Two Prevotella copri metagenome-assembled genomes that are positively associated with ponderal growth are the principal contributors to MDCF-2-induced expression of metabolic pathways involved in utilizing the component glycans of MDCF-2—a microbiome-directed complementary food.

Learning to predict reward is thought to be driven by dopaminergic prediction errors, which reflect discrepancies between actual and expected value. Here the authors show that learning to predict neutral events is also driven by prediction errors and that such value-neutral associative learning is also likely mediated by dopaminergic error signals.

Inborn errors of the alternative NF-κB pathway in humans impair the development of AIRE-expressing medullary thymic epithelial cells, thereby underlying the production of autoantibodies against type I IFNs and predisposition to viral diseases

Serological detection of antibodies against SARS-CoV-2 can help establish rates of seroconversion. Here the authors develop a red cell agglutination test to detect antibodies against the receptor binding domain for distribution free of charge to qualified research groups.