Search

An anti-HIV-1 antibody that targets an N332_gp120 glycan-independent V3 epitope, a site of Env vulnerability, can decline viremia in HIV-1-infected humanized mice while overcoming classical V3 escape mutations.

Predicting gene expression from H&E slides is a cost-effective alternative to Spatial Transcriptomics for clinical use. Here the authors introduce a Multiple Instance Learning approach to infer single-cell expression, unlike prior methods which operate at coarser patch level.

JWST’s COSMOS-Web survey is used to create an ultra-high-detail dark matter map, revealing hidden filaments, clusters and distant structures. By tracing features out to z = 2, this map shows how dark and luminous matter build the cosmic web across cosmic time.

More frequent fires in the North American boreal are causing shifts from conifer to deciduous forests. This study finds that when deciduous forests burn, their carbon losses are driven by weather, but are lower than in conifer forests, potentially dampening climate–fire feedbacks.

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.

Risk associated with genetically defined forms of autism spectrum disorder (ASD) can propagate by means of transcriptional regulation to affect convergently dysregulated pathways, providing insight into the convergent impact of ASD genetic risk on human neurodevelopment.

Analysis of cancer genome sequencing data has enabled the discovery of driver mutations. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium the authors present DriverPower, a software package that identifies coding and non-coding driver mutations within cancer whole genomes via consideration of mutational burden and functional impact evidence.

Analysis of 14,106 tumor genomes highlights recurrent mutations in mitochondrial ribosomal RNA encoded within the mitochondrial genome. Mutations occur at hotspot positions and are under strong purifying selection in the germline.

Geospatial estimates of the prevalence of anemia in women of reproductive age across 82 low-income and middle-income countries reveals considerable heterogeneity and inequality at national and subnational levels, with few countries on track to meet the WHO Global Nutrition Targets by 2030.

Hutchinson-Gilford Progeria Syndrome is characterized by premature aging with cardiovascular disease being the main cause of death. Here the authors show that inhibition of the NAT10 enzyme enhances cardiac function and fitness, and reduces age-related phenotypes in a mouse model of premature aging.

Here, the authors examine the mechanisms behind cheatgrass’s successful invasion of North American ecosystems. Their genetic analyses and common garden experiments demonstrate that multiple introductions and migrations facilitated cheatgrass local adaptation.

In Caenorhabditis tropicalis, three toxin–antidote elements arose via gene duplication from the essential tRNA-synthetase subunit FARS-3. The ancestral antidote probably acquired affinity for FARS-3, enabling presuppression of toxicity and allowing otherwise deleterious mutant alleles to evolve into selfish genes.

Dehingia, Milewska-Puchała and colleagues find a pervasive lncRNA-mediated increase in interactions between CTCF and RNA-binding proteins during embryonic stem cell differentiation. These interactions reinforce chromatin architecture in neural cells.

Together with a companion paper, molecular details of immune responses in a pig-to-human xenotransplantation are identified through dense longitudinal multi-omics profiling of the xenograft and the host recipient, across the 61-day procedure.

RUFY proteins are known to regulate autophagy, cytoskeletal dynamics, migration and endosomal trafficking. Here, Char et al. show that iRUFY3 plays a role in perinuclear positioning, phagocyte migration and antigen presentation during Salmonella infection.

Pulmonary type 2 inflammation is associated with type 2 innate lymphoid cells. Here the authors use the Collaborative Cross mouse panel to show that ILC2 abundance during type 2 lung inflammation is different across the panel and identify free-fatty acid receptor 3 (Ffar3) as a gene responsible and show cytokine and ILC2 functional changes.

In social settings, people need to establish how much they contribute to shared outcomes. Here, the authors show that people strategically alter their actions to establish their level of control and identify neural activity underlying this process.

Integrative analyses of transcriptome and whole-genome sequencing data for 1,188 tumours across 27 types of cancer are used to provide a comprehensive catalogue of RNA-level alterations in cancer.

In this single-arm phase 2 trial in patients with HR⁺HER2⁻ advanced breast cancer, treatment with the HER3-targeting antibody–drug conjugate paritumab deruxtecan led to encouraging objective response rates, and comprehensive exploratory analyses indicate potential biomarkers of response.

Colonic goblet cell-associated passages allow translocation of live bacteria to other organs in early life, potentially leading to beneficial impacts.

Glitches in video calls can have a negative effect on the judgement of the people involved and correspond to worse outcomes in major areas of life such as job interviews and parole hearings.

This study explores the impact of mood and individual differences on trading off between possible rewards and checking for the presence for threat and escaping to safety in a gamified foraging task.

The study provides a comprehensive transcriptomic atlas of the human gastrointestinal tract across the lifespan, highlighting inflammation-induced changes in epithelial stem cells that alter mucosal architecture and promote further inflammation.

GABA is the primary inhibitory neurotransmitter in the central nervous system. Using two-photon GABA imaging, Matsumoto et al. reveal over 40 GABA neuron types in the mouse retina, each uniquely filtering visual features.

Early alcohol drinking confers greater risk for alcohol use disorder in women than men. Here authors show that ovarian-derived estrogen rapidly drives binge alcohol drinking via signaling with membrane-associated estrogen receptors in the extended amygdala.

As large-scale neurodevelopmental MRI studies gain prominence, the authors identify tradeoffs between sample size and quality control that can dramatically affect results, and they evaluate a range of approaches to mitigate risk for error.

High-dimensional cytometry is a powerful technology for studying single-cell phenotypes in complex biological systems. Here, the authors develop cyCONDOR, a computational framework for high-dimensional cytometry data analysis, covering a comprehensive suite of features in an easy-to-use format.

The flagship paper of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes Consortium describes the generation of the integrative analyses of 2,658 cancer whole genomes and their matching normal tissues across 38 tumour types, the structures for international data sharing and standardized analyses, and the main scientific findings from across the consortium studies.

The topographical organization of cells in the hippocampus reflects its ability to regulate mood and cognition. Here the authors generate a spatially resolved gene expression map in the human hippocampus to enable cross-species and functional interpretation.

Editorial Summary: fMRI, multi-omics, and cellular assays reveal that an intensive mind-body retreat intervention modulates brain network connectivity and plasma signaling pathways linked to neuroplasticity, metabolism, and neurotransmission in healthy adults.

Ocana-Santero and colleagues show that serotonin is a key regulator of sensory programming. Early life SSRI exposure alters the developmental trajectory of interneurons to impact on neural dynamics in both the formative and adult sensory cortex.

The authors identify thousands of genetic variants affecting RNA splicing in primary human chondrocytes and link several of them to osteoarthritis risk using genome editing and computational approaches.

The authors present SVclone, a computational method for inferring the cancer cell fraction of structural variants from whole-genome sequencing data.

Single-cell transcriptomics excel in cell subset classification and can be augmented by suitable genotype information. Here the authors devise a long-read sequencing workflow, termed nanoranger, for detection of molecular barcodes from single-cell cDNA and apply this to clonal tracking of acute myeloid leukemia and identification of complex immune phenotypes.

A pan-cancer genomic analysis reports the effects of structural variations on chromatin domains (TADs). Most TAD disruptions do not result in appreciable changes in expression of nearby genes.

The role of opioids in the neural systems of maladaptive behavioral suppression is unclear. Here, authors identify a thalamoaccumbal brain circuit that is required for the suppression of reward seeking and is rapidly disengaged by opioids leading to unrestricted behavioral actions.

Wastewater is a promising source of data for continuous monitoring of pathogens in communities, but analysis protocols and methods are still being established. Here, the authors develop sequencing and analysis protocols and use them to evaluate the microbial content of longitudinal wastewater samples from Miami-Dade County, USA.

Synaptic vesicle dysfunction in Parkinson’s disease is unexplored. Here, using electron microscopy, lipidomic and proteomic analyses, Gao et al. provide insights into synaptic vesicle biology and disease mechanisms.

Transcriptomic data and functional experiments on macaque retina are used to identify the ON-type direction-selective ganglion cells responsible for detecting moving images and initiating gaze-stabilization mechanisms.

Here the authors show that dihydroorotate dehydrogenase in the de novo pyrimidine synthesis pathway functions as a cell fate checkpoint that can be targeted to specifically diminish the number and function of effector T cells without affecting the memory T cell pool and response to infection.

Optical pooled CRISPR screening is improved by combinatorial oligo hybridization for barcode detection.

There’s an emerging body of evidence to show how biological sex impacts cancer incidence, treatment and underlying biology. Here, using a large pan-cancer dataset, the authors further highlight how sex differences shape the cancer genome.

A retrospective analysis using PCR testing, viral enrichment-based sequencing and agnostic metagenomic sequencing finds an association between adeno-associated virus type 2 and paediatric hepatitis of unknown cause.

Analyses of 2,658 whole genomes across 38 types of cancer identify the contribution of non-coding point mutations and structural variants to driving cancer.

Multi-omics profiling of the blood and heart of two human decedents receiving pig heart xenografts, including single-cell studies, reveals early immune responses and perioperative cardiac xenograft dysfunction in one of the two decedents, which may be due to mismatched heart size and/or insufficient immunosuppression.

Ferber et al. present an autonomous artificial intelligence agent system for deployment of specialized medical oncology computational tools, validating their system across various clinical scenarios representative of typical patient care workflows.