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Mapping of the neutrophil compartment using single-cell transcriptional data from multiple physiological and patological states reveals its organizational architecture and how cell state dynamics and trajectories vary during health, inflammation and cancer.

Live-cell imaging of mRNA encoding secretome proteins and translated nascent peptide markers show that secretome translation occurs at endoplasmic reticulum junctions near lysosomes, requires lunapark protein and is modulated by nutrient status.

Barcoding microbial ribosomal RNA creates a recording of gene transfer events without requiring translation.

Immune features and T cell characteristics that correlate with post-intervention control of HIV-1 viraemia inform the development of combination immunotherapies that may enhance the ability to elicit durable HIV remission.

Typical quantum error correcting codes assign fixed roles to the underlying physical qubits. Now the performance benefits of alternative, dynamic error correction schemes have been demonstrated on a superconducting quantum processor.

Light represses biofilm formation and production of virulence factors in the pathogenic bacterium Pseudomonas aeruginosa. Here, Manias et al. identify a periplasmic microprotein that regulates this process by activating the degradation of a component of the light-sensing pathway.

Targeted protein degradation using PROTACs doesn’t discriminate functional from disease-causing versions of the same protein. Here, we describe small molecule TRIMTACs that recruit the unique E3 ligase TRIM21 and allow state-selective protein degradation, including challenging substrates like tau.

In this study, the authors assess the global response to the toxic aldehyde glyoxal (GO) in Pseudomonas aeruginosa, suggesting that GO controls quorum sensing during infection through a mechanism involving a novel protein, ArqI.

Water window imaging with high-harmonic generation is achieved using soft X-ray coherence tomography (SXCT), revealing the cross-sectional structure of buried nanolayers with 12 nm axial resolution.

In this work authors demonstrate how photocontrolled tag-targeted degradation enables precise, spatiotemporal control of protein expression in tumor cells and CAR T cells, offering an esapproach for regulating engineered proteins with light.

Genome-wide CRISPRi screens for modulators of androgen receptor (AR) protein levels using live-cell quantitative endogenous AR fluorescence reporters identify PTGES3 as a new regulator of AR stability and function in prostate cancer.

Birth season has been associated with differences in epigenetic, developmental and health outcomes, but associations to developing metabolome are unclear. Here the authors report a secondary exploratory analysis of The Early Life Interventions for Childhood growth and development in Tanzania (ELICIT) trial showing that in rural Tanzania, an infant’s birth season shapes their metabolism up to 18 months of life, linked to rainfall, food insecurity and breastmilk composition.

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.

Therapeutic gene editing in vivo is an ongoing challenge. Here, authors demonstrate Cas9 nickase guided DNA ligation as a nonviral method for installing permanent genomic corrections with favorable on target edit profiles in model animal cell types and adult mice.

There is still a need for effective HIV vaccines. In this phase I clinical trial, the authors show that an HIV-1 vaccine candidate, ConM SOSIP.v7, is well-tolerated in HIV-negative adults and that it elicits a strain-specific neutralising antibody response that differed between female and male participants.

Starble, Sun, and colleagues identify an epigenetic priming mechanism that promotes oncogene amplification in acquired resistance to tyrosine kinase inhibitors and establishes a role of METTL7A in this process.

Imine reductases have been regarded as one of the most promising enzymes by the pharmaceutical industry—but their industrial application is still lacking. This work reports the successful industrial application of an imine reductase, enabled by directed evolution.

Authors show that all individuals have asymmetrically glycosylated IgGs—the glycans on each of the Fc protomers are not identical. Asymmetrically monofucosylated IgGs drive dengue disease and are functionally similar to afucosylated IgGs.

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.

The factors governing mouse decision-making strategies in changing environments remain unclear. Here the authors use a 4-state input-driven model to show that past stimuli/choices drive switches in bias, while past rewards drive switches in engagement.

The authors demonstrate that stable partial polarization control achieves more than 10¹⁰ write cycles in ferroelectric AlScN. Further, reducing capacitor diameter increases breakdown voltage, boosting endurance.

Antimicrobial resistance poses a significant global health threat, necessitating swift and precise diagnostic solutions. Here, the authors introduce a culture-free diagnostic platform integrating microfluidic cell enrichment, single-cell Raman spectroscopy, and deep learning, that identifies bacterial and fungal infections directly from clinical samples within 20 minutes.

Activity-based protein profiling identifies covalent small molecules that potentiate the activity of the METTL5:TRMT112 complex through binding to a complexoform-restricted allosteric pocket absent in other TRMT112:methyltransferase complexes

Hutchinson-Gilford Progeria Syndrome is characterized by premature aging with cardiovascular disease being the main cause of death. Here the authors show that inhibition of the NAT10 enzyme enhances cardiac function and fitness, and reduces age-related phenotypes in a mouse model of premature aging.

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.

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.

TUG protein localizes to the endoplasmic reticulum-Golgi intermediate compartment, forms biomolecular condensates, and organizes and stabilizes these membranes to support their function in diverse secretory and degradative trafficking pathways.

iGluSnFR4f and iGluSnFR4s are the latest generation of genetically encoded glutamate sensors. They are advantageous for detecting rapid dynamics and large population activity, respectively, as demonstrated in a variety of applications in the mouse brain.

Integrated multi-omic analyses using samples from the TRACERx study highlight cross-talk between DNA hypermethylation and genomic lesions in non-small cell lung cancer.

The common description of strong-field light–matter interaction neglects the quantum-optical nature of the driving field. Now signatures of strong-field photoemission appear in electron energy spectra when driving with non-classical light.

Scaling Si spin qubits relies on the uniform control of qubit-host interactions. This work finds correlations in qubit energy levels across a manufactured device arising from placement of Ge in the quantum well, consistent with atomistic modeling.

SARS-CoV-2 Omicron XEC variant, a recombinant of JN.1 progeny, shows increased viral fitness and pathogenicity. Here, the authors show that the nucleocapsid mutation R204P enhances inflammation and suggest a growing role of non-spike mutations in viral evolution.

Royer and colleagues find a principal dimension of neural dynamic similarity dissociating unimodal and association cortices. Systematic variations in local and macroscale constraints across the cortex also followed this pattern.

Reanalysis of radiometric data from Cassini indicates that Titan does not contain a subsurface ocean, as strong tidal dissipation observed in its gravity field is not consistent with the presence of a liquid layer.

Loss-of-function variants in thyroid hormone transporter MCT8 cause a neurodevelopmental and metabolic disorder. Here the authors identify genotype-phenotype relationships, advance insights in MCT8 (dys)function and create a pathogenicity-severity variant classifier.

The P2X4 receptor, an ATP-activated ion channel, plays a role in chronic pain, inflammation, and cancer. Authors in this work discover an extracellular allosteric binding site that interacts with anthraquinone derivatives, and is narrowed by ionic lock formation.

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.

Rotors are widespread in nature, but the collective behavior of heterogeneous populations remains poorly understood. Authors demonstrate that oppositely spinning rotors spontaneously self-assemble into active chains called gyromers, stabilized purely by fluid and steric interactions.

An analysis of 24,202 critical cases of COVID-19 identifies potentially druggable targets in inflammatory signalling (JAK1), monocyte–macrophage activation and endothelial permeability (PDE4A), immunometabolism (SLC2A5 and AK5), and host factors required for viral entry and replication (TMPRSS2 and RAB2A).

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.

A study of several longitudinal birth cohorts and cross-sectional cohorts finds only moderate overlap in genetic variants between autism that is diagnosed earlier and that diagnosed later, so they may represent aetiologically different conditions.

Hepatitis C virus (HCV) gains entry into host cells via envelope glycoproteins E1 and E2. Here, El Omari et al.present the crystal structure of the N terminus of the E1 ectodomain of HCV and show that it adopts a different fold than predicted.

Drug combination discovery remains slow and challenging. Here, the authors introduce Combocat, an open-source framework that combines acoustic liquid handling protocols with machine learning to achieve ultrahigh-throughput drug combination screening; as proof of concept, they use Combocat to screen 9,045 drug combinations in a neuroblastoma cell line.

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.

Resonant inelastic X-ray scattering can be used to measure the spin current carried by magnons in the presence of temperature gradients across a magnetic insulator.

Lymphatics maintain lipid transport, immunity, and fluid balance. Kim J and Chaudhary S et al. reveal an AIBP-driven cholesterol efflux mechanism that regulates lymphangiogenesis via VEGF signaling.

The One Thousand Plant Transcriptomes Initiative provides a robust phylogenomic framework for examining green plant evolution that comprises the transcriptomes and genomes of diverse species of green plants.