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Bioactivity-guided isolation of specialized metabolites is an iterative process. Here, the authors demonstrate a native metabolomics approach that allows for fast screening of complex metabolite extracts against a protein of interest and simultaneous structure annotation.

Genomic and transcriptomic analysis of samples from patients with multiple myeloma, followed by in vitro validation, indicate mechanisms of antigen escape in response to GPRC5D T cell-engager talquetamab, including biallelic deletions, small nucleotide variants, insertion-deletions and chromatin silencing.

Engineered mucus-tethering bispecific nanobodies neutralize and entrap viruses to enhance mucosal immunity, preventing influenza infection and limiting SARS-CoV-2 transmission.

Here the authors perform longitudinal sampling of lymphoid organs along with fate mapping and matched single-cell RNA sequencing and TCR sequencing to define the developmental dynamics of follicular regulatory T (T_FR) cells. They find that T_FR cells undergo clonal expansion and progressive differentiation in a process that requires follicular helper T cells.

Ionic liquid additives increase the power conversion efficiency of perovskite solar cells, but their effect on perovskite crystallization remains unclear. Xu et al. provide mechanistic insights and demonstrate improved operational stability under continous illumination and 90 °C thermal stress.

Clonal hematopoiesis is driven by the selective advantage of mutant hematopoietic stem cells. Here, authors discover that elevated mitochondrial activity is a targetable mechanism by which mutant hematopoietic stem cells gain a selective advantage.

mRNA vaccines targeting SARS-CoV-2 also sensitize tumours to immune checkpoint inhibitors.

Pathogenic variants in UNC13A underlie a novel neurodevelopmental syndrome, with three subtypes defined by distinct genotypes with varying clinical and functional impacts characterized in cellular and animal models.

Polygenic scores for body mass index and obesity constructed using data from 5 million people with different ancestries were associated with distinct weight gain trajectories from early childhood to adulthood.

Dorsal striatal dopamine release develops plateau responses to reward cues, but lacks outcome release medially and transitions to both outcome and rewarded cue laterally. Here the authors suggest the need for reconsideration of reward prediction error models for striatal dopamine release.

The authors find that TDP-43 loss of function—the pathology defining the neurodegenerative conditions ALS and FTD—induces novel mRNA polyadenylation events, which have different effects, including an increase in RNA stability, leading to higher protein levels.

Here the authors develop a novel statistical method for quantifying mutation burden from whole genome sequencing data and use it to discover the genetic, genomic, and phenotypic correlates of clonal hematopoiesis without known driver genetic lesions.

Female subfertility is highly associated with endometriosis. Here the authors show that progesterone-induced MIG-6 is reduced in endometrium of infertile women and non-human primates with endometriosis, and in a mouse model find that Erbb2 is the key mediator of Mig-6 loss induced endometriosis-related infertility.

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

Light trapped in the active polymeric layer limits the total efficiency of polymer light-emitting diodes. Here, Lee et al.get round this bottleneck by enhancing light extraction in waveguide optical modes via ripple-shaped nanostructures that spontaneously form on ZnO electrode surfaces.

Using multi-ancestry genome-wide association study and fine-mapping, 298 loci and 36 credible genes are identified in the aetiology of bipolar disorder.

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.

A genome-wide association meta-analysis study of blood lipid levels in roughly 1.6 million individuals demonstrates the gain of power attained when diverse ancestries are included to improve fine-mapping and polygenic score generation, with gains in locus discovery related to sample size.

Methods to increase nuclear spin polarization can enhance the sensitivity of magnetic resonance techniques however they are often limited to unfavourable conditions. Here, the authors achieve room temperature hyperpolarization of bulk ¹³C nuclear spins by exploiting the optical response of nitrogen vacancy centers in diamond crystals.

In an observational study comparing individuals with type 2 diabetes and obesity who underwent metabolic surgery with similar individuals who received GLP-1 receptor agonist treatment, metabolic surgery was associated with a lower risk of macrovascular and microvascular outcomes, including major adverse cardiovascular events, nephropathy, retinopathy and all-cause mortality.

A global network of researchers was formed to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity; this paper reports 13 genome-wide significant loci and potentially actionable mechanisms in response to infection.

Ni, Wei, Vona and colleagues use human brain organoids to dissect patient AIRIM variants associated with neurodevelopmental features. A subset of variants impaired ribosome production and protein synthesis, and delayed radial glial cell specification.

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.

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.

Approaches making virtual and experimental screening more resource-efficient are vital for identifying effective inhibitors from a vast pool of potential drugs but remain elusive. Here, the authors address this issue by developing an active learning framework leveraging high-throughput molecular dynamics simulations to identify potential inhibitors for therapeutic applications.

The properties of magnetic, crystalline solids can be described in terms of quantum particles of spin-wave and lattice-vibration energy, known as magnons and phonons respectively. Here, the authors show that strong magnon-phonon coupling in a noncollinear antiferromagnet can create magnetoelastic excitations.

Biochemical and biophysical analyses of eye lenses from mouse strains that develop cataract due to mutations in α-, β-, or γ-crystallin proteins reveal that the mutant protein levels are largely reduced, but other crystallin proteins, including α-crystallins, precipitate.

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.

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.

Kaluba, Rogers et al. show that in cancer cells that can metabolize ketones, they may reroute them to produce cytosolic acetyl-CoA and support tumour growth.

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.

Biofuel cells can be used as power sources for implantable biomedical devices, but suffer from limited power and lifetime. Here, Kwon et al.fabricate biscrolled carbon nanotube yarn electrodes, and demonstrate high fuel cell performances when used for glucose energy harvesting.

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.

While Bell inequalities have been violated several times—mostly in photonic systems—their violations within particle physics experiments are less explored. Here, the BESIII Collaboration showcases Bell-violating nonlocal correlations between entangled hyperon pairs.

Exome sequencing of 851 trios from more than 2,500 individuals finds 187 genes with de novo mutations that contribute to meningomyelocele (spina bifida) and highlights critical pathways required for neural tube closure.

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.

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.

The ATLAS Collaboration reports a measurement of the ratio of the decay rates of W bosons to τ leptons and muons, in agreement with universal lepton couplings as postulated in the standard model of particle physics.

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.

Han et al. report the existence of neural stem cells (NSCs) outside the central nervous system and show that these peripheral NSCs display features similar to brain NSCs, including the ability to differentiate into mature neurons.

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.

Fibroblastic reticular cells (FRC) are important for lymph node (LN) structure and function. Here the authors show that the YAP/TAZ complex downstream of Hippo signalling regulates FRC commitment and maturation, with YAP/TAZ deficiency impairing FRC differentiation, while hyperactivation of YAZ/TAZ inducing myofibroblastic FRCs and LN fibrosis.

Heat is a form of energy that is transported from a hot to a cold region, but it is not a notion that is associated with the microscopic measurement of electronic properties. It is now shown that local thermoelectric measurements can be used for imaging structural disorder in graphene, with high sensitivity, on the atomic and nanometre scales, uncovering soliton-like domain-wall line-patterns separating different graphene regions.

Genome-wide association analyses of 41,917 bipolar disorder cases and 371,549 controls of European ancestry provide new insights into the etiology of this disorder and identify novel therapeutic leads and potential opportunities for drug repurposing.