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The structure of a spontaneously activated immune protein is determined by cryo-electron microscopy. This reveals the passage of an entire domain through a transient opening. The authors investigate the mechanism by multiple biophysical approaches.

Polyamines prevent the action of kinases on acidic phosphorylatable motifs in spliceosomal proteins, thus providing a mechanism for metabolite-mediated regulation of alternative splicing in cells.

The severe threat of weeds to agriculture and ecosystems necessitates management practices on the scale of landscapes. This Perspective uses four case studies to examine the best practices for this collective dilemma.

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.

The authors use three-dimensional live-cell imaging of colorectal carcinoma organoids to show that chromosomal instability is widespread. Single-cell sequencing identifies heterogeneity of copy number alterations and shows clonal evolution.

Development of strategies for the synthesis of pi-conjugated polymers is hampered by limited solubility. Here, the authors report a synthetic protocol based on the search for specific vibrational modes through an appropriate tailoring of the p-conjugation of the precursors, in order to increase the attempt frequency of a chemical reaction.

Marine construction is sprawling globally. As of 2018, this study finds that the structures occupied 32,000 km² but affected 1 to 3 million km², a shadow expected to expand 50–70% by 2028.

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.

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.

Anbazhakan et al. use whole-organ imaging and three-dimensional computational fluid dynamics modeling to define spatial architecture and predict blood flow through collaterals in neonate and adult mouse hearts after injury, and compare their findings to the functionality of collaterals in human adult and fetal hearts.

Polymers commonly are semiconducting or insulating because of a sizable energy gap in the density of states around the Fermi level. Yet, the phase transition from topologically trivial to non-trivial in on-surface synthesized π-conjugated polymers, due to a change of resonant form, stabilizes narrow bandgaps and bears in-gap zero-energy edge states in the non-trivial phase.

It remains uncertain whether genetic variants and day–night cycles affect the efficacy of drugs in acute disease settings. Here, the authors show that metoprolol reduces risk only in patients who carry two Arg389 alleles of the beta-1 adrenoceptor, and specifically when myocardial infarction occurs at the beginning of the light cycle.

The exploration of voltage-gated potassium channels using cryo-electron microscopy and electrophysiology identifies a mechanism of inactivation involved in regulating neuron firing.

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.

Channelrhodopsins’ mechanism of light-gated ion conductance could be engineered for use in optogenetic tools. Here, structures of the slow-cycling mutant of HcKCR1, including an open state structure, provide insight into channel gating and selectivity.

Analysis of live-cell imaging and single-cell genome sequencing data of colorectal cancer organoids identifies temporal dynamics of sub-chromosomal copy-number amplifications.

Hepatitis B virus (HBV) infection and DNA integration is a frequent cause of hepatocellular carcinoma (HCC), but the consequences of this process are not fully understood. Here the authors use whole-genome and long-read sequencing data from HCC patient samples to study the timing and alterations induced by HBV insertions.

Here, authors provide a molecular view of a clustered saccharide patch on mucins as recognized by a bacterial binding module. This work provides insights into how microbes can remain attached to mucins in the mucus while grazing on their glycans.

The jumbo contractile bacteriophage, Kp24, has been isolated from clinical strains of Klebsiella pneumonia. Here, the authors present structural and functional insight into the capsid, tail and tail fibres and how this impacts infectivity.

This work presents GōMartini 3, an improved coarse-grained protein model combining physics- and structure-based approaches. It boosts computational efficiency and accuracy for structured soluble and membrane as well as disordered peptides/proteins.

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.

This study shows that liquid-liquid phase separation enhances the catalytic efficiency of peptides by up to 15,000-fold through the formation of peptide coacervates. These microreactors can also selectively recruit phosphorylated proteins, providing insights into the evolution of enzymatic activity.

How do sounds affect emotions? The authors reveal that noise can suppress the rewarding-dopamine system through a non-canonical auditory pathway, leading to negative emotions like aversion and anxiety.

Alkaline-earth phenoxides show promise as optical cycling centres; however, their properties when connected to larger structures is unclear. Now it has been shown that their optical cycling remains efficient despite increasing molecular complexity, enabling the scaling of laser-coolable molecules toward larger structures and surface-bound quantum systems.

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 Kv1.3 potassium channel is expressed abundantly on activated T cells and mediates the cellular immune responses. Here, the authors report structures of the Kv1.3 potassium channel with and without immunoglobulin modulators, shedding light on the mechanisms of Kv1.3 gating and modulation.

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

The BioDIGS project is a nationwide initiative involving students, researchers and educators across more than 40 research and teaching institutions. Participants lead sample collection, computational analysis and results interpretation to understand the relationships between the soil microbiome, environment and health.

Monoclonal antibodies from people after natural human parainfluenza virus type 3 infection can protect from infection in vitro and in vivo by targeting both pre-fusion F and haemagglutinin-neuraminidase HN proteins of the virus.

The benefits and risks of nature to human health have been studied, however, robust empirical research on forest biodiversity and health outcomes is still lacking. Here the authors use a unique dataset from 164 European forest stands to explore the associations between forest types and well-being.

This work highlights the technical issues in previous approaches and introduces a preprocessing approach along with a software package, MethSCAn, for single-cell bisulfite sequencing data analysis.

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 yeast NuA3 complex regulates gene transcription and the cell cycle. Nguyen et al. show that intersubunit interactions involving the Taf14, Yng1 and Sas3 subunits are essential in biological activities of the NuA3 complex.

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.

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.

Einav and colleagues characterize peripheral immune blood cells from pediatric patients with severe natural dengue infections. Their findings suggest that disease progression is associated with an inflammatory phenotype accompanied by impaired interferon response, defective antigen presentation and regulation of effector lymphocyte responses.

Recently discovered kalium channelrhodopsins (KCRs) are optogenetic tools for neuronal silencing. Here, authors report cryo-electron microscopy structures of KCR1 from Hyphochytrium catenoides and a highly homologous but sodium-selective channel from the same organism.

Thermal resistance at interfaces is a critical bottleneck for the thermal management of electronic devices. Here, authors report a high-performance liquid-infused nanostructured composite with thermal resistance under 1 mm² K W⁻¹ and reliability for advanced electronic cooling.

Kopal and colleagues built computational bridges between rare CNVs in a clinical dataset and their deep phenotypic profiling in ~40,000 UK Biobank participants. Results show that CNVs are associated with many organ systems across the entire body.

Cryogenic electron microscopy determines the structure of a fully assembled, MR1-reactive, human Vγ8Vδ3 TCR–CD3δγε₂ζ₂ complex bound by anti-CD3ε antibody Fab fragments.

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.

The synthesis of polycyclic conjugated hydrocarbons with antiaromatic moieties is realized by the thermal rearrangement of dibromomethylene-functionalized molecular precursors on a hot Au(111) metal surface.

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.

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.

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.

The switch from glucose- to fatty acid-dependent metabolism in cardiomyocytes of newborn mice is governed by γ-linolenic acid in maternal milk, which binds to retinoid X receptors, thereby causing a transcription-dependent metabolic transition.

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.