Search

Computationally designing proteins with interfaces that bind small molecules has posed a long-standing challenge. Here, authors combine deep learning and physics-based approaches to design proteins that bind small molecules, and demonstrate their approach by designing a cortisol biosensor.

Noninvasive hippocampal modulation is key for addressing hippocampal dysfunction. Using multimodal brain recordings, the authors show that personalized connectivity-guided transcranial magnetic stimulation can causally alter hippocampal activity.

RNA editing influences gene regulation in cancer. Here, the authors show that EZH2 regulates RNA editing by ADAR1 through remodeling its interactome and nuclear transport, thereby promoting MDM2 expression and prostate cancer progression.

A global analysis of 1,412 studies shows that one in five women and one in six men experienced sexual violence as children, highlighting the urgent need for evidence-based prevention and intervention programmes worldwide.

Robustness checks and reproduction of analyses with existing and updated data based on 110 articles in economics and political science journals with data and code-sharing requirements found high levels of robustness and reproducibility and determined that robustness was not dependent on author characteristics or data availability.

A multiplexed RNA detection method exploits crRNA-dependent variability in Cas13a activity on RNA targets for kinetic barcoding and can be used to distinguish among SARS-CoV-2 variants in clinical samples.

A vagal reflex to blood volume changes in the heart involves PIEZO2 and helps to stabilize blood pressure in an upright posture and after blood loss.

This study presents an HDB (horizontal diagonal band) – mPFC (medial prefrontal cortex) – thalamus circuit and the cholinergic signaling in mPFC Foxp2⁺ neurons in modulating sensory and affective pain in male mice.

The APOE-ε4 allele is the strongest genetic risk factor for late-onset Alzheimer’s disease, but it is not deterministic. Here, the authors show that common genetic variation changes how APOE-ε4 influences cognition.

The ~200-Myr-old star TOI-2076 hosts a young four-planet system, the orbits and atmospheres of which are still evolving, showing signs of early dynamical reshaping and atmospheric sculpting and offering a rare glimpse of how planetary systems form and transform in their youth.

A fusion protein designed to comprise IL-2 and a helminth-derived TGFβ mimic activates IL-2 and TGFβ signalling pathways in IL-2 receptor-expressing T cells and induces stable antigen-specific regulatory T cells in peripheral lymphoid organs.

Estimates from the Global Burden of Disease study reveal declines in chronic respiratory disease mortality between 1990 and 2023—especially during the COVID-19 pandemic—but the burdens on people affected remain substantial.

Beta-arrestins are key transducers of G-protein coupled receptors, but the mechanisms of beta-arrestin signaling are poorly understood. Here, authors use cryo-electron microscopy to show how beta-arrestin 1 binds and activates Src kinase

Stable and cell-specific transgene expression can be achieved through in vivo site-specific integration of large DNA payloads using a two-vector system of enveloped delivery vehicles and adeno-associated viruses.

Smc5/6 association with DNA junctions can support genomic functions. Here, the authors show that Smc5/6 junction polarity preferences, targeting, and dwell times are determined by its structural modules as well as the RPA and PCNA genomic factors.

Precise and efficient CRISPR genome editing requires specialized delivery systems. Here, the authors develop Coomassie lipidoids that deliver purified adenine base editors into retinal tissues, making it possible to achieve robust genome editing with a defined, non-viral nanomedicine.

Identifying jets originating from heavy quarks plays a fundamental role in hadronic collider experiments. In this work, the ATLAS Collaboration describes and tests a transformer-based neural network architecture for jet flavour tagging based on low-level input and physics-inspired constraints.

In this study, long-read RNA sequencing achieves accurate single-nucleotide polymorphism calling, haplotype phasing and allele-specific expression analysis.

Large-effect variants in autism remain elusive. Here, the authors use long-read sequencing to assemble phased genomes for 189 individuals, identifying pathogenic variants in TBL1XR1, MECP2, and SYNGAP1, plus nine candidate structural variants missed by short-read methods.

A spatial and single-cell transcriptomics study across multiple mammalian species identifies epidermal BMP signalling as a functional requirement for rete ridge formation, providing insight into mechanisms underlying hair density loss and wound healing.

Whether multimorbidity accelerates brain Aβ deposition in humans remains largely unknown. Here, the authors demonstrate that higher self-reported multimorbidity burden predicts increased brain Aβ accumulation rates in the ADNI cohort.

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

This study demonstrates that the Drosophila proventriculus, the structure at the anterior of gut that synthesizes the peritrophic membrane, lacks stem cells but undergoes continual endocycling to compensate for cells loss during aging or damage.

A single-cell epigenomic atlas of human immune cells highlights cell-type-specific features associated with genetic or environmental exposures.

Genome-wide CRISPR screens map how genes support survival and contribute to diverse biological functions. Here, the authors use antiCRISPR to enhance genome-wide CRISPR screening in Drosophila and generate higher-resolution maps of cell fitness, toxin, and drug-resistance.

Bohlen and colleagues report that the E3 ubiquitin ligase CBL is necessary for the development, tolerance and activation of B cells in humans, unlike in mice where CBL deficiency results in loss of T cells.

Nguyen et al. show that the splenic environment provides sequential signals via lymphotoxin and retinoic acid that guide cDC2A development and retention.

Cellular state cooccurrence signatures, such as carcinoma ecotypes may serve as potential biomarkers of response to cancer immunotherapy, however, their clinical utility remains unexplored. Here, the authors analyse large real world immunotherapy cohorts and gene expression data and develop a predictive model for response.

Haematopoiesis is a classic process for understanding the genetic basis of human health and disease. In this Review, Poeschla and Sankaran discuss this history and more recent advances in our understanding of the roles of rare variants in monogenic blood diseases, germline and somatic variants in population-level variation, as well as emerging therapeutic applications.

The CMS Collaboration reports the measurement of the spin, parity, and charge conjugation properties of all-charm tetraquarks, exotic fleeting particles formed in proton–proton collisions at the Large Hadron Collider.

The combination of computational design, laboratory-based screening and biophysical validation enables the de novo generation of variable heavy-chain antibody fragments and antibodies that precisely target chosen disease-related molecules.

This paper presents TDAC-seq, a targeted chromatin-accessibility-profiling method using cytidine deaminases and long-read sequencing, to resolve the effects of CRISPR edits on single chromatin fibers.

The HKU25 clade MERS-related coronaviruses with broad distribution are shown to use ACE2 as a functional receptor, revealing unexpected receptor plasticity and offering new insights into coronavirus evolution, host range and potential zoonotic risk.

This research developed and compared firearm-specific and method-agnostic machine-learning models using data from 800,579 Army veterans, revealing that model choice and intervention thresholds impact predictive accuracy and fairness, guiding tailored suicide prevention efforts.