Search

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.

Mass spectrometry facilitates the scalable identification of cancer-specific HLA-bound peptides; however, the clinical identification of targets remains challenging. Here, the authors present NeoDiscMS, an immunopeptidomics method that enhances the identification of neoantigens while maintaining maximal global coverage of the tumor immunopeptidome.

Familial cortical myoclonic tremor with epilepsy (FAME) is a slowly progressing cortical tremor mapping to various genomic loci, including intronic expansions in SAMD12 for FAME1. Here, Florian et al. describe mixed intronic TTTTA/TTTCA expansions of various lengths in the first intron of MARCH6 as a cause of FAME3.

This study used AI to map ~29,000 CDR studies—3–4 times more than expected—showing rapid but uneven growth. The map supports stronger evidence synthesis for climate goals and the IPCC. #CDR

The wave nature of light and particles is of interest to the fundamental quantum mechanics. Here the authors show the double-slit interference effect in the strong-field ionization of neon dimers by employing COLTRIMS method to record the momentum distribution of the photoelectrons in the molecular frame

The authors develop a machine learning approach to find structurally related chemicals in mass spectral libraries. Their method boosts the annotation rate and aids in assessing novelty in metabolomics datasets.

Whole-genome sequencing data for 2,778 cancer samples from 2,658 unique donors across 38 cancer types is used to reconstruct the evolutionary history of cancer, revealing that driver mutations can precede diagnosis by several years to decades.

Pathology-oriented multiplexing (PathoPlex) represents a framework for widespread access to multiplexed imaging and computational image analysis of clinical specimens at a relatively high throughput and subcellular resolution.

Micropollutant removal in polymeric nanofiltration membranes is difficult to characterise due to pore heterogeneity. A force interplay framework was developed to describe adsorption in VaCNT membranes with defined nanopores, providing insight for the design of membranes with improved selectivity.

Clock precision is thought to be fundamentally limited by entropy production in out-of-equilibrium systems. A theoretical work now introduces a quantum clock design where precision grows exponentially with dissipation.

Magic state distillation is achieved with logical qubits on a neutral-atom quantum computer using a dynamically reconfigurable architecture for parallel quantum operations.

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

The scaffold protein Scribble (Scrib) has roles in PCP and tight junction formation. Here the authors show that during embryo implantation in mouse, Scrib is needed to form the avascular primary decidual zone by transforming stromal cells into an epithelial cell-like barrier around the crypt, protecting the embryo from harmful infiltrations.

The slit-diaphragm is a cellular junction that is crucial for blood filtration in the kidney. Kocylowski et al. show that the junction-spanning components are embedded in a protein network for dynamic control of filtration; network disturbance leads to severe filtration defects with proteinuria.

The emergence of magnetically confined surface excitons enabled by antiferromagnetic spin correlations is reported, which leads to the confinement of excitons to the surface of layered antiferromagnet CrSBr.

Inhibition of YBX1, a downstream target of the Janus kinase JAK2, sensitizes myeloproliferative neoplasm cells to JAK and could provide a means to eradicate such cells in human haematopoietic cancers.

The International Brain Laboratory presents a brain-wide electrophysiological map obtained from pooling data from 12 laboratories that performed the same standardized perceptual decision-making task in mice.

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 automated synthesis of highly reactive compounds is challenging. Now a digital automated platform is developed for safer, inert-atmosphere synthesis of air-, moisture-, pressure- and temperature-sensitive compounds from across the periodic table.

RNA ligases are present across all forms of life. Here, the hitherto uncharacterised human protein C12orf29 was identified as a human enzyme promoting RNA ligation between 5′-PO₄ and 3′-OH termini. This data provides the groundwork for establishing a human RNA repair pathway.

Quasi-two-dimensional CdSe nanoplatelets are shown to grow in concentrated solvent-free melts, without mixed surfactants. A model explaining such results proposes that nanoscale instability triggers anisotropic growth of isotropic materials.

The critical floating phase can bridge crystalline orders and the disordered phase. Here, the authors experimentally observe the quantum floating phase in neutral atom qubit arrays, revealing domain walls and incommensurate quasi long-range order, and analyse its emergence via Fourier spectroscopy.

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.

In somatic cells the mechanisms maintaining the chromosome ends are normally inactivated; however, cancer cells can re-activate these pathways to support continuous growth. Here, the authors characterize the telomeric landscapes across tumour types and identify genomic alterations associated with different telomere maintenance mechanisms.

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.

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.

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.

In this study the authors consider the structural variants (SVs) present within cancer cases of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium. They report hundreds of genes, including known cancer-associated genes for which the nearby presence of a SV breakpoint is associated with altered expression.

Cancers evolve as they progress under differing selective pressures. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, the authors present the method TrackSig the estimates evolutionary trajectories of somatic mutational processes from single bulk tumour data.

The authors use in-situ high pressure nuclear magnetic resonance spectroscopy in diamond anvil cells to show that at all observed H-bond environments undergo a distinct maximum in hydrogen mobility regardless of the structure of the compounds.

The antiferromagnetic-to-paramagnetic phase transition in a two-dimensional semiconducting magnet, CrSBr, induces an exciton confinement transition from a strongly bound quasi-one-dimensional state to a weakly bound interlayer-delocalized state.

Analysis of 20 chemical and morphological plant traits at diverse sites across 6 continents shows that the transition from semi-arid to arid zones is associated with an unexpected 88% increase in trait diversity.

Using the game Gran Turismo, an agent was trained with a combination of deep reinforcement learning algorithms and specialized training scenarios, demonstrating success against championship-level human racers.

Bassani-Sternberg and colleagues perform multiregion immunopeptidomics, genomics and spatial transcriptomics in patient lung cancer samples, demonstrating heterogeneity in the immunopeptidome associated with degrees of immune cell infiltration.

Effective tumour-specific T cell immunity — and the success of cancer immunotherapies — relies on the presentation of antigens via human leukocyte antigen (HLA) molecules. In this Review, Bassani-Sternberg and Huber explore recent advances in understanding the repertoire of tumour-specific antigens, as well as how disruptions in antigen processing and presentation contribute to immune evasion and resistance to immune checkpoint blockade. The authors also highlight how these insights can inform the design of personalized neoantigen-based vaccines and combination therapies aimed at outpacing tumour immunoediting.

Near-infrared perovskite–polymer light-emitting diodes (LEDs) with external quantum efficiencies of up to 20.1% are reported.

Resistance to one antibiotic can make bacteria resistant or sensitive to another antibiotic, opening paths for combinatorial treatments. This study presents an approach to systematically discover and understand such antibiotic relationships.

IL-23 promotes tumor growth in preclinical cancer models and correlates with adverse clinical outcomes. Here, Becher and colleagues find that IL-23 produced by tumor-associated macrophages stabilizes T_reg cell identity, promoting immunosuppression and tumor growth.

LAMTOR2 is involved in mTOR and ERK signalling and plays a role in immunity, but its function in dendritic cells (DCs) is not clear. Here the authors show that deletion of LAMTOR2 in DCs results in increased mTOR signalling, accumulation of Flt3 on the cell surface and excessive DC proliferation in ageing mice.

The neoantigen discovery pipeline NeoDisc incorporates mass spectrometry immunopeptidomics data.

This article highlights the evolution in understanding of the podocyte slit diaphragm. Now appreciated as far more than a simple intercellular connection, the slit diaphragm controls the structure and function of the glomerular filtration barrier. However, several slit diaphragm properties remain unclear: its role in filtration, exact molecular structure, and the complex pathways initiated by this dynamic signalling hub.

Il-13 is expressed in neurons and IL-13 ko causes memory impairment. Here, authors show that IL-13 and its receptor IL-13Ra1 are pre- and post-synaptic proteins, respectively, involved in synaptic signaling, plasticity and neuroprotection.

Little is known about the interaction of different ecological factors in shaping adaptive evolution in natural habitats. This study found that plants evolved local adaption to different soils, but only when they interacted with aphid- herbivores and bumblebee-pollinators.

Understanding deregulation of biological pathways in cancer can provide insight into disease etiology and potential therapies. Here, as part of the PanCancer Analysis of Whole Genomes (PCAWG) consortium, the authors present pathway and network analysis of 2583 whole cancer genomes from 27 tumour types.