Search

Chromatin states need to be maintained during DNA damage repair. Here, the authors expand the histone chaperone network involved in repair-coupled chromatin restoration and highlight a mechanistic coordination between old and new histone dynamics.

The ultrafast and mode-specific infrared excitation of several donor–bridge–acceptor (DBA) assemblies in solution has been shown to modulate their light-induced electron transfer properties. New insights are afforded into the role of vibrational processes immediately following light absorption in charge-transfer molecules and a recipe for efficient ‘vibrational control’ of electron transfer is proposed.

Manipulating chemical reactions using laser pulses to control electron transfer is an attractive goal, however much of the underlying physics remains unexplored. Here the authors analyse and explain the intramolecular electronic transfer occurring during charge-separation in acetylene, a model donor-bridge-acceptor molecule.

Single-molecule and biochemistry approaches are used to investigate how ultra-fine DNA bridges, which form between sister chromatids during anaphase, are recognized and processed by cellular factors PICH, BLM, TopoIIIα and RPA.

CRISPR gene targeting in multicellular organisms results in genetic mosaics, limiting knockout efficiency. Here, the authors develop an improved system using Cas12a with multiple guides per gene, and demonstrate high accuracy and superior knockout efficiency in fruit flies.

Benito-Martínez, Salavessa and colleagues show that keratin intermediate filaments and microtubules control the three-dimensional perinuclear position of melanin-containing organelles, shielding the DNA from photodamage.

Oncogenic viruses cause 15% of all human cancers. Cats, which are naturally susceptible to cancers caused by feline homologues of human tumour viruses, represent an opportunity to develop treatment and prevention strategies for viral cancers using comparative oncology. Increased investment in this approach could benefit both pets and people.

An analysis of 2,954 genomes from 38 cancer subtypes identified 19,166 retrotransposition events in 35% of samples. Aberrant LINE-1 retrotranspositions can lead to the deletion of tumor-suppressor genes as well as the amplification of oncogenes.

Here authors identify GluN2D-containing NMDA receptors on interneurons as a specific target for rapid antidepressant action. Blocking GluN2D restores stress-impaired plasticity and mimics the effects of ketamine with fewer side effects.

The authors use spatial and single-cell transcriptomics to examine spatial dynamics during early human cardiogenesis, yielding insights into the development of the cardiac pacemaker-conduction system, autonomic innervation, heart valves and atrial septum, and heterogeneity of cardiac mesenchymal cells.

The main protease, a key enzyme of SARS-CoV-2, can protect itself from oxidative damage. Here, Reinke, Schubert, and colleagues used XFEL radiation to image the enzyme, revealing the disulfide and NOS/SONOS bonds that form in response to oxygen.

TRPC3 regulates neuronal excitability via its constitutive activity. Using MD simulations and patch clamp techniques, Clarke et al. show that PIP2 controls TRPC3 via a salt bridge formed between the TRP helix and the S4-S5 linker, affecting both stimulated and constitutive TRPC3 activities.

Four-coordinate cobalt(II) complexes possess high energy barriers toward inversion of the magnetic moment, but not the magnetic bistability needed for magnetic data storage. Here, the authors report an air-stable radical-bridged binuclear cobalt(II) complex with improved magnetic properties.

A conserved feature of metazoan meiosis is that it occurs in a syncytium. Here, the authors show that intercellular bridges that connect germ cells in a syncytium are critical for ensuring proper meiotic progression and fertility in male mice.

Joint injury and disease are leading causes of disability, with mammalian joints exhibiting poor regenerative capacity. Here the authors showed that after loss of a whole joint, adult zebrafish regenerate de novo articular cartilage, ligament, and synovium into a complex joint organ.

Organisms vary in their nitrogen and phosphorus content, shaping ecological and evolutionary processes. This study shows that nitrogen deposition is a consistent global factor associated with plant and animal stoichiometry.

Telomeric entanglements arising from stalled telomeric replication forks can cause mitotic catastrophe in dividing cells. Here, the authors show that resolution of such entanglements in fission yeast requires rapid exposure of the DNA to the cytoplasm during anaphase.

Synthetic cells have huge potential in model systems. Here, the authors engineer synthetic–living hybrid tumoroids that replicate tumour-immune interactions in 3D, study synthetic cells integration, and demonstrate systematic studies of immune evasion and T cell engager therapies.

The literature assumes that intergroup contact is naturally occurring, positive and consistently associated with positive outcomes, but these premises are inconsistent with everyday intergroup contact experiences. In this Perspective, Paolini et al. propose that variations in contact valence and environmental affordances for self-selection influence segregation dynamics, leading to stable trajectories of contact and intergroup bias.

Whole-genome sequencing data from more than 2,500 cancers of 38 tumour types reveal 16 signatures that can be used to classify somatic structural variants, highlighting the diversity of genomic rearrangements in cancer.

Soil biodiversity is poorly studied compared to aboveground biodiversity, but is an important driver of ecosystem functioning. This Review discusses advances in research into the relationships between soil biodiversity and ecosystem functioning, highlighting that integrative and causal study approaches will be needed to fill the gaps in our understanding.

Characterisation of monoclonal antibodies against SARS-CoV-2 are useful for potential therapeutics or to understand more about the immune response to this virus. Here the authors characterise a monoclonal antibody that has a broad range of reactivity against SARS-CoV-2 variants and measure how it binds to its specific target region of the receptor binding domain.

A combination of genome-wide functional screening, imaging and chromatin profiling identifies a new class of highly prevalent genomic elements that help retain extrachromosomal DNA copies in dividing cells and persist across generations.

The mechanical properties of central nervous system (CNS) scar tissue are considered to contribute to axon regeneration failure. Here, the authors identify members of the small leucine-rich proteoglycan family as modulators of the inhibitory viscoelastic response of CNS lesions.

We present a protocol for the design, fabrication and use of a microfluidic probe for nanospray desorption electrospray ionization mass spectrometry imaging (nano-DESI MSI) that achieves a spatial resolution of 8–10 µm and 10-fold improvement in experimental throughput.

WGS data were used from 347,630 individuals with European ancestry in the UK Biobank to obtain high-precision estimates of coding and non-coding rare variant heritability for 34 complex traits and diseases.

The spin–orbit interaction and the two-dimensional honeycomb structure of iridium-based oxides are promising for exotic electronic states. Here, the authors find an iridium oxide with a three-dimensional structure that preserves the features of the honeycomb systems, creating new material possibilities.

The authors reveal that probenecid, an FDA-approved drug, uniquely modulates TRPV2 through an intracellular pocket. Probenecid drives the channel into an activated conformation, providing insights into potential therapeutic applications.

Despite frequent AKT/mTOR pathway activation in patient’s rhabdomyosarcoma (RMS), success of AKT inhibitors in the clinical has been limited. Here, using RMS patient-derived models, the authors demonstrate that the efficacy of the AKT inhibitor, ipatasertib, is in part due to its off-target effects on PRKG1, identifying PRKG1 as a potential biomarker for ipatasertib response.

Protein kinase transition between different conformational states is controlled by autophosphorylation. Here, the authors demonstrate that the c-terminal Tyr530 is a de facto c-Src autophosphorylation site  and identify a critical c-terminal palindromic phospho-motif that controls the interplay between substrate and enzyme-acting kinases during autophosphorylation.

Foundation models enable rapid adaptation to various downstream tasks and are hence about to become a new paradigm in biomedicine. Here, the authors develop LLaVA-Rad, a small AI that bests larger models in chest X-ray interpretation, and CheXprompt, a radiologist-aligned factuality metric, to enable scalable, privacy-preserving image analysis.

ESCRT filaments drive the final abscission between two daughter cells but how they physically interact with the membrane is unclear. Using proteomics, the authors show that syndecan-4/syntenin/ALIX couples the ESCRT machinery to the abscission site and thus promotes efficient abscission.

Here the authors demonstrate that the SARS-CoV-2 main protease (Mpro) is subject to redox regulation in vitro, reversibly switching between the enzymatically active dimer and the functionally dormant monomer through redox modifications of cysteine residues.

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.

The number of ligand binding sites in the dopamine transporter is enigmatic due to conflicting data from structures and molecular pharmacology. Here, force spectra reveal the position and dynamics of a previously invisible transient site.

They determine four cryo-EM structures of NiV polymerases from different strains and establish RdRp enzymatic assays for anti-NiV drug discovery. A back-priming RdRp activity and the binding between RdRp core and CD domains in NiV L were identified.

Proteins SegA and SegB are important for chromosome segregation and organization in archaea of the order Sulfolobales, but mechanisms are unclear. Here, Kabli et al. uncover patterns and mechanisms that the SegAB system employs to link chromosome organization to genome segregation.

The authors explore the impact of MC4R deficiency on lipid metabolism in humans, based on two large cohorts. Findings indicate that individuals with obesity due to MC4R deficiency have lower cholesterol and triglyceride levels, as well as reduced cardiovascular risk.

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.

Chromothripsis—a process during which chromosomes are ‘shattered’—drives the evolution of gene amplification and subsequent drug resistance in cancer cells.

Trained and validated on multimodal data from 14.5 million images from multicountry datasets, a foundation model is shown to increase diagnostic and referral accuracy of clinicians when used as an assistant in a trial involving 16 ophthalmologists and 668 patients.

Tau aggregation, a hallmark of Alzheimer’s disease, disrupts neuron structure. Aging weakens chaperone defenses like Hsp90. This study designs β-Hsp90, a small peptide mimicking Hsp90, to prevent Tau aggregation, offering promise for new amyloid disease drugs.

To celebrate the journal’s 25th anniversary, we asked 13 researchers to offer a glimpse of what their research field might look like in 2050. They consider how technological breakthroughs — for example, artificial intelligence-powered virtual cells — could transform our understanding of how molecules, organelles and cells behave in different contexts, revolutionize therapies and enable the design of resilient crops.

Monoclonal antibodies targeting the conserved neuraminidase catalytic site mimic sialic acid and use coordinated water molecules to inhibit diverse influenza A and B viruses, including H5N1, providing broad prophylactic protection in mice.

Manju Kurian and colleagues report heterozygous variants in KMT2B in 27 unrelated individuals with a complex progressive childhood-onset dystonia, often associated with a typical facial appearance. Their findings highlight a clinically recognizable form of dystonia and demonstrate a crucial role for KMT2B in the physiological control of voluntary movement.

Drivers of viral evolution in SARS-CoV-2 are insufficiently understood. In this study, the authors show how a key SARS-CoV-2 mutation, NSP4 T492I, is potentially responsible for accelerating genome evolution to develop adaptive variants (e.g. Omicron).