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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.

The ability of BCG vaccination to prevent pulmonary tuberculosis could be improved by targeting mucosal immunity within the lung. Here the authors compare latent Mtb-infected donors with intradermal or oral BCG vaccine recipients to show distinct systemic and pulmonary immune responses are induced by differing routes of natural infection or vaccination.

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.

Targeted sequencing panels such as MSK-IMPACT have been successfully used to profile solid tumours in clinical settings. Here, the authors develop and implement the MSK-IMPACT Heme sequencing panel and platform to profile haematologic malignancies using paired tumor and normal tissues.

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.

Very slow cooling, over several days, of solutions of complementary-DNA-modified nanoparticles through the melting temperature of the system produces nanoparticle assemblies with the Wulff equilibrium crystal structure, thus showing that DNA hybridization can direct nanoparticle assembly along a pathway that mimics atomic crystallization.

Dynamics of type I interferon (IFN) following infection with SARS-CoV-2 are critical in determining disease severity in humans but have been difficult to model in mice. Here, infection of genetically diverse mice reveals how delayed or immediate IFN signaling coordinates antiviral immunity.

An initial draft of the human pangenome is presented and made publicly available by the Human Pangenome Reference Consortium; the draft contains 94 de novo haplotype assemblies from 47 ancestrally diverse individuals.

Optical aberrations can hinder fluorescence imaging of thick samples, reducing image signal, contrast, and resolution. Here, the authors introduce a deep learning-based strategy for aberration compensation, improving image quality without slowing image acquisition or introducing more optics.

Many climate models overestimate the snow amount in the Northern Hemisphere despite strong warming. Here the authors find that light snowfall and snow melting processes drive this mismatch and use these relationships to constrain future projections of snow water resources.

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.

Subgenome dominance is widely observed in allopolyploid species, but the molecular mechanisms remain unclear. Here, the authors generate genome-wide map of accessible chromatin regions (ACRs) in allo-octoploid cultivated strawberry and reveal that dynamics of the ACRs play an important role in its subgenome dominance.

LKB1 is frequently mutated in lung squamous cell carcinomas. Here, the authors show that sole LKB1 depletion is sufficient to drive the development of this cancer, where downstream defective MKK7-JNK1/2 signalling activates the ∆Np63/p63 pathway to induce subsequent epithelial cells transformation and tumour progression.

Broadband Fabry–Pérot etalons are used as calibration sources in radial velocity exoplanet detection. This Article explores their performance limits and models the physical mechanism behind their complex measured chromatic drift.

Combining geographic information, climate data and colour mechanism at broad phylogenetic and spatial scales, the authors determine how transitions between pigmentary and structural colours influence bird speciation dynamics.

Analysis of shared chromosomal segments is applied to identify distantly related, previously undiagnosed carriers of a rare KCNE1 variant. The carriers are shown to have the Long QT Syndrome phenotype with incomplete penetrance.

Single-cell data analysis is challenging due to inherent noise and sparsity. Here, authors introduce scMINER, a mutual information-based integrative tool to enhance clustering and reveal regulatory networks and hidden biological drivers by transforming scRNA-seq expression into activity profiles.

A new study from Moritz Wussow and colleagues assesses solar deployment equity across residential and non-residential sectors and discusses pathways for policy action to promote non-residential solar in disadvantaged communities.

Cone photoreceptors signal to several bipolar cell types at one of the most structurally complex synapses in the central nervous system. Here, the authors show how the 3D organization of this synapse creates different signals in the postsynaptic OFF bipolar cell types.

The stability and performance of organic electrochemical transistors can be improved using a two-step technique in which oxygen is first removed from the solvent and then a chemical dopant is introduced into the organic mixed ionic–electronic conductor.

A deep, ancient, and uranium-rich brine in South Africa reveals evidence of radiolytically oxidized kerogen and C₁–C₃ hydrocarbons with abiotic isotopic signatures that support a low biomass microbial community over time.

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.

Multi-omics datasets pose major challenges to data interpretation and hypothesis generation owing to their high-dimensional molecular profiles. Here, the authors develop ActivePathways method, which uses data fusion techniques for integrative pathway analysis of multi-omics data and candidate gene discovery.

A study reports the development of a structural derivative of amphotericin B with broad antifungal activity in mice but without the renal toxicity associated with amphotericin B.

Data from multiple satellite sensors show that Antarctica lost almost 37,000 km² of ice-shelf area from 1997 to 2021, and that calving losses are as important as ice-shelf thinning.

This phase I/II clinical trial was designed to assess safety and efficacy of gene therapy for Bothnia dystrophy, an inherited retinal degeneration leading to blindness. Kvanta et al. show interim results from 12 patients with meaningfully improved visual function in dim light.

Genome-wide association and fine-mapping analyses in ancestrally diverse populations implicate candidate causal genes and mechanisms underlying type 2 diabetes. Trans-ancestry genetic risk scores enhance transferability across populations.

Haspin phosphorylates histone H3 threonine 3 (H3T3) to ensure proper progression through mitosis. Here the authors describe how Haspin engages a nucleosomal DNA supergroove, using electrostatic interactions, thereby promoting H3T3 phosphorylation.

Type 2 inflammation drives the formation of pathologic mucus in patients with asthma. Here, authors reveal a role for intelectin-1 in IL-13-induced mucus properties, and that an ITLN1 eQTL is associated with protection from the formation of mucus plugs in T2-high asthma.

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.

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.

The most common oxidation state for lanthanide elements is +3, and, beyond cerium, examples of these elements exhibiting higher oxidation states remain scarce. Now, a molecular complex of praseodymium in the +5 oxidation state has been synthesized; this compound exhibits a unique electronic structure driven by N 2p and Pr 4f orbital contributions.

Microbial natural products represent a large reservoir of potential pharmaceutical agents. Here, Johnston et al. describe a computer-automated programme for connecting genome sequences with identified and isolated natural products.

There is growing interest in designing electrolytes to enable Li-metal batteries. Here the authors show that asymmetric solvents improve lithium redox kinetics and achieve long cycle life in anode-free cells under electric vertical take-off and landing conditions, demonstrating potential for future high-power applications.

Analysis of mitochondrial genomes (mtDNA) by using whole-genome sequencing data from 2,658 cancer samples across 38 cancer types identifies hypermutated mtDNA cases, frequent somatic nuclear transfer of mtDNA and high variability of mtDNA copy number in many cancers.

Safely reducing the necessary duration of quarantine for COVID-19 could lessen the economic impacts of the pandemic. Here, the authors demonstrate that testing on exit from quarantine is more effective than testing on entry, and can enable quarantine to be reduced from fourteen to seven days.

Authors employ a cynomolgus macaque model to explore the protective potential of mucosal vaccination with Mycobacterium tuberculosis ΔsigH.

Somatic structural variants (SVs) in cancer can impact DNA methylation-mediated transcriptional regulation. Here, the authors analyse multi-omics data from over 2400 samples from the Children’s Brain Tumor Network and report SVs that are associated with altered gene expression or DNA methylation, including some with prognostic relevance.

The most common protein modification in eukaryotes is N-terminal acetylation, but its functional impact has remained enigmatic. Here, the authors find that a key role for N-terminal acetylation is shielding proteins from ubiquitin ligase-mediated degradation, mediating motility and longevity.

How expectations of reward influence spatial memories remains unclear. Here, the authors reveal a dopamine pathway to the hippocampus that increases activity with proximity to expected rewards, thus stabilizing spatial representations of trajectories that lead to rewards.

The precise boundaries and flow compartments of perivascular spaces in the brain are incompletely understood. Here the authors show that pia is perforated and permissive to CSF flow, forming three types of perivascular spaces that remodel with age, with an abnormal type arising in Alzheimer’s disease and correlating with β-amyloid burden and differential macrophage uptake.

Endogenous retroviruses constitute 5–10% of mammalian genome space. This study characterize the bovine ERVK[2-1- LTR] clade showing that its activity varies between individuals as a function of the number of inherited autonomous elements, yet that most de novo insertions are non-autonomous elements lacking functional genes.

Human milk oligosaccharides (HMOs) are essential carbohydrates for the early development of infants. In this study, the intrinsic carbohydrate anabolism of plants is leveraged to produce a variety of HMOs, highlighting the potential of this method for commercial applications.

Naturally occurring peptides with high membrane permeability often have backbone ester bonds. Here, the authors investigated the effect of an amide-to-ester substitution on membrane permeability of peptides and found the substitution is useful for improving membrane permeability of cyclic peptides.

COVID-19 can result in neurological manifestations and animal models could provide insights into the mechanisms. Here, the authors describe neuroinflammation, microhemorrhages and brain hypoxia in SARS-CoV-2 infected non-human primates, including in animals that don’t develop severe respiratory disease.

Glioma tumours are known to be heterogenous in mutation and gene expression patterns, but sampling limitations can lead to inaccurate detection of evolutionary events. Here, the authors carry out multi-omics analysis of multi-regional biopsies from 68 patients and show differential mutations in non-enhancing regions.

Kim et al. show that NAD⁺ kinase 2 serves as a source of mitochondrial NADPH to support mitochondrial fatty acid synthesis, protein lipoylation and mitochondrial oxidative metabolism.