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The efficient separation of chiral molecules is a fundamental challenge in the manufacture of pharmaceuticals and light-polarising materials. Here, the authors develop an approach that combines machine learning with a physics-based representation to predict resolving agents for chiral molecules, using a transformer-based neural network.

Many genetic loci have been identified to be associated with kidney disease, but the molecular mechanisms are not well understood. Here, the authors perform epigenome-wide association studies on kidney function measures to identify epigenetic marks and pathways involved in kidney function.

Cryo-electron and atomic force microscopy shed light on how fibrils of the protein tau, which accumulate in the brain of people with Alzheimer’s disease, can be disassembled by short peptides, providing a possible route towards developing treatments.

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

The Fermi-LAT Collaboration reports a significant γ-ray detection (5.2σ) from the coronae of radio-quiet active galactic nuclei, revealing compact (~10 gravitational radii) and extended (~2.7 × 10⁶ gravitational radii) corona regions, challenging existing models.

Severe congenital development defects such as Jeune syndrome can result from the malfunction of primary cilia and dynein. Here Schmidts et al. report unique biallelic null mutations in a gene encoding a dynein light chain, helping to explain the nature of ciliopathies in human patients.

Here authors demonstrate how a 2D hybrid perovskite melts and forms glass, uncovering atomic-scale structural and dynamic evolution across the crystal–liquid–glass transition. Local structural motifs are retained, advancing understanding of amorphous hybrid materials.

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.

The endoplasmic/sarcoplasmic reticulum (ER/SR) plays a crucial role in calcium signaling, but there are few methods capable of efficiently capturing ER/SR Ca²⁺ dynamics. Here authors develop a set of genetically encoded indicators enabling ratiometric super-resolution imaging and detection of elementary Ca²⁺ release in cardiomyocytes.

Sensing of cytosolic RNA or DNA can lead to innate responses, but little information is available for RNA/DNA dual sensors. Here the authors find SAMD9 as a potential dual sensor linked to pro-inflammatory responses, interferon induction and resistance to viral infection, as evidenced by in vitro overexpression and in vivo knockout mouse data.

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.

Whole genome sequences enable discovery of rare variants which may help to explain the heritability of common diseases. Here the authors find that ultra-rare variants explain ~50% of coronary artery disease (CAD) heritability and highlight several functional processes including cell type-specific regulatory mechanisms as key drivers of CAD genetic risk.

Investigating the inner structure of baryons is important to further our understanding of the strong interaction. Here, the BESIII Collaboration extracts the absolute value of the ratio of the electric to magnetic form factors and its relative phase for e + e − → J/ψ → ΛΣ decays, enhancing the signal thanks to the vacuum polarisation effect at the J/ψ peak.

The NEMO series of genetically encoded calcium indicators report calcium activity in neuronal and non-neuronal cells with high signal-to-baseline ratio, which is shown in neuronal culture, slice preparations, in vivo and in planta.

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.

Using data from a single time point, passenger-approximated clonal expansion rate (PACER) estimates the fitness of common driver mutations that lead to clonal haematopoiesis and identifies TCL1A activation as a mediator of clonal expansion.

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.

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.

Here the authors conduct a multi-ancestry meta-analysis of telomere length, used diverse approaches to identify genes underlying association signals, and experimentally validated POP5 and KBTBD6 as regulators of telomere length in human cells.

Genome recoding with quadruplet codons requires a +1-frameshift-suppressor tRNA able to insert an amino acid at quadruplet codons of interest. Here the authors identify the mechanisms resulting in +1 frameshifting and the steps of the elongation cycle in which it occurs.

Observations of γ-rays with energies up to 1.4 PeV find that 12 sources in the Galaxy are PeVatrons, one of which is the Crab Nebula.

The authors model likely outcomes for the 33 isolated populations reported in the Fourth National Giant Panda Census under multiple RCP scenarios and with the provision of the planned Giant Panda National Park. They find that, although the National Park may connect some fragmented habitats, most of the populations with high extinction risk fall outside the current plans.

Viral pathogen load in cancer genomes is estimated through analysis of sequencing data from 2,656 tumors across 35 cancer types using multiple pathogen-detection pipelines, identifying viruses in 382 genomic and 68 transcriptome datasets.

Tisza et al. carry out a sequencing-based analysis of wastewater samples from major cities, to detect and quantify hundreds of distinct pathogenic viruses, finding striking correlations between virus abundance and local clinical cases.

How plasma membrane Orai Ca²⁺ channels are activated by STIM proteins to activate Ca²⁺signals is still not fully known. Here the authors show that a nexus region located at the Orai1 C-terminus allows channel gating without a direct interaction of STIM1 with the channel pore.

A longitudinal analysis of viral expansion and clearance rates in 60 individuals sampled daily during acute infection reveals high inter-individual variation in infectious virus shedding, which may contribute to superspreading.

The death of massive stars has traditionally been discovered by explosive events in the gamma-ray band. Liu et al. show that the sensitive wide-field monitor on board Einstein Probe can reveal a weak soft-X-ray signal much earlier than gamma rays.

KRAS^G12D mutations frequently co-occur with mutated TP53 tumour suppressor in patients with pancreatic ductal adenocarcinoma (PDAC). Here the authors report the design of dual targeted therapeutic extracellular vesicles containing high copy numbers of TP53 mRNA and siKRAS^G12D, showing anti-tumor activity in PDAC preclinical models.

A base-editing approach optimized to target the retina shows high editing rates in a mouse model of Stargardt disease, as well as in nonhuman primates and ex vivo human retinal explants, paving the way for potential clinical applications.

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.

With the generation of large pan-cancer whole-exome and whole-genome sequencing projects, a question remains about how comparable these datasets are. Here, using The Cancer Genome Atlas samples analysed as part of the Pan-Cancer Analysis of Whole Genomes project, the authors explore the concordance of mutations called by whole exome sequencing and whole genome sequencing techniques.

The inverse spin-Hall effect is important in spintronics as it converts a spin current into charge current in nonmagnetic materials. Here, the authors show signatures of the inverse Rashba–Edelstein effect, a similar effect in two-dimensional interfacial states, in an Ag/Bi bilayer.

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.

The characterization of 4,645 whole-genome and 19,184 exome sequences, covering most types of cancer, identifies 81 single-base substitution, doublet-base substitution and small-insertion-and-deletion mutational signatures, providing a systematic overview of the mutational processes that contribute to cancer development.

Using globally consistent measurements and high-resolution modelling, this study finds that black carbon emissions are generally underestimated in the Global South.

Interferon-γ (IFNγ)-activated calcium/calmodulin-dependent protein kinase II (CAMK2) phosphorylates phosphoserine aminotransferase 1 (PSAT1) at serine 337 (S337), enabling glutathione peroxidase 4 (GPX4) interaction, promoting α-ketoglutarate-dependent PHD3-mediated GPX4 proline 159 (P159) hydroxylation and stabilizing GPX4 to counteract ferroptosis.

Follicular helper T cells play critical roles in the formation of high affinity antibody responses, but the signals involved in the development of these cells after initial differentiation are poorly understood. Here Podestà, Cavazzoni and colleagues characterise transitionary phases of follicular helper T cell development and how progression through these stages is linked to humoral immunity.

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.

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.

Some cancer patients first present with metastases where the location of the primary is unidentified; these are difficult to treat. In this study, using machine learning, the authors develop a method to determine the tissue of origin of a cancer based on whole sequencing data.

Many tumours exhibit hypoxia (low oxygen) and hypoxic tumours often respond poorly to therapy. Here, the authors quantify hypoxia in 1188 tumours from 27 cancer types, showing elevated hypoxia links to increased mutational load, directing evolutionary trajectories.