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In this work, the authors reveal that three non-ribosomal peptides targeting a common protein quality system differentially alter the Mycobacterium tuberculosis proteome, providing new insight into the molecular mechanisms behind their antimycobacterial activity.

Humanity’s Last Exam, a multi-modal benchmark at the frontier of human knowledge, is designed to be an expert-level closed-ended academic benchmark with broad subject coverage.

After spinal cord injury, lesion-remote astrocytes acquire heterogeneous, spatially restricted reactivity states that shape neuroinflammation, neural repair and neurological recovery.

Double Asteroid Redirection Test (DART) mission impact on asteroid Dimophos resulted in an elliptical ejecta plume. Here, the authors show that this elliptical ejecta is due to the curvature of the asteroid and makes kinetic momentum transfer less efficient.

Phonon polaritons are promising for mid-infrared photonics but only longitudinal optical phonons are directly accessed by electrical currents. Here, the authors predict and experimentally confirm hybrid longitudinal-transverse excitations. This could lead to phonon polariton-based electrically pumped mid-infrared emitters.

Volumetric DNA microscopy captures spatial information of RNA within an intact organism.

An epsilon-near-zero medium is used to demonstrate ultrastrong coupling between phonons and gap plasmons. The approach may pave the path to exploitation of vibrational transitions.

Warm dense copper, created by an X-ray free-electron laser, features a transition from reverse saturable absorption to saturable absorption. The results can be used to benchmark non-equilibrium models of electronic structure in warm dense matter.

Chronic care manages long-term, progressive conditions, while acute care handles short-term ones. Here, authors show chronic conditions account for most of the global health burden, with 68% of DALYs and 93% of YLDs attributed to chronic care needs.

Employing nonlinear, time-resolved terahertz spectroscopy to study condensate dynamics on Ta₂NiSe₅—a narrow-bandgap semiconductor and putative excitonic insulator—the authors reveal enhanced terahertz reflectivity upon photoexcitation and condensation-like temperature dependence below the structural transition critical temperature.

High IL1RL1 correlates with poor survival in acute myeloid leukemia. A stress-driven IL-33/IL1RL1 loop induces leukemogenesis and a tolerogenic immune environment. Targeting this axis with bispecific antibodies offers a promising treatment.

In a post-hoc analysis of circulating tumor DNA (ctDNA) features from patients with metastatic prostate cancer treated with [¹⁷⁷Lu]Lu–PSMA-617 or cabazitaxel in the randomized phase 2 TheraP trial, low ctDNA levels at baseline were predictive of clinical benefit from [¹⁷⁷Lu]Lu–PSMA-617, and PTEN or ATM alterations were identified as potential biomarkers of response.

A thin liquid coating on a fibre can break up into droplets due to the Plateau–Rayleigh instability, as for instance on a spider web. Here, Haefner et al. show that the growth rate of the droplet undulations strongly depends on the fibre–liquid boundary condition and slip accelerates the instability.

The authors report on a temperate Earth-sized planet orbiting the cool M6 dwarf LP 791-18 with a radius of 1.03 ± 0.04 R_⊕ and an equilibrium temperature of 300–400 K, with the permanent night side plausibly allowing for water condensation.

Analyses of genome and exome sequencing data identify rare coding and structural variants associated with atrial fibrillation and highlight genetic links between atrial fibrillation and cardiomyopathies.

An analysis of the impact of logging intensity on biodiversity in tropical forests in Sabah, Malaysia, identifies a threshold of tree biomass removal below which logged forests still have conservation value.

Networks of miniaturized magnetoelectric wireless implantable devices can be individually powered and controlled by a single transmitter, show power and transfer data efficiencies that scale with the number of receivers and be used for spinal cord stimulation and cardiac pacing in large animals.

The rapid dissociation of methanetetrol has been suggested as an impediment to its observation, despite the stability of its substituted derivative orthocarbonates. The authors identify methanetetrol as a product of carbon dioxide and water reactions in space-simulation experiments via photoionization mass spectrometry working in tandem with computation quantum chemistry.

Haploinsufficiency in three genes associated with risk of autism spectrum disorder—KMT5B, ARID1B and CHD8—in cell lines from multiple donors results in cell-type-specific asynchronous development of GABAergic neurons and cortical deep-layer excitatory projection neurons.

BACH2 is required for lymphocyte differentiation. Afzali et al. describe mutations that cause BACH2 disruption, immunodeficiency and autoinflammatory disease via haploinsufficiency, a mechanism shared by other super-enhancer-regulated genes.

This work identified cyclic peptide inhibitors of a mammalian N-terminal cysteine oxidase, ADO, through mRNA display, one of which was used as a scaffold to graft substrate moieties, allowing key interactions to be assessed through structural and biochemical approaches.

In this study, Aggarwal and colleagues perform prospective sequencing of SARS-CoV-2 isolates derived from asymptomatic student screening and symptomatic testing of students and staff at the University of Cambridge. They identify important factors that contributed to within university transmission and onward spread into the wider community.

No method exists for real-time evaluation of the status of spinal implants. Here, the authors developed a bio-adhesive metal detector array (BioMDA) that provides a wearable, non-invasive solution for positional analyses of osseous implants within the spine.

Genotype and exome sequencing of 150,000 participants and whole-genome sequencing of 9,950 selected individuals recruited into the Mexico City Prospective Study constitute a valuable, publicly available resource of non-European sequencing data.

Shear phenomena in the infrared dielectric response of a monoclinic crystal are shown to unveil a new polariton class termed hyperbolic shear polariton that can emerge in any low-symmetry monoclinic or triclinic system.

Era+ breast cancer patients often develop resistance to endocrine therapy. Here, the authors show that FGFR1 amplification is a resistance mechanism to CDK4/6 inhibitor and endocrine therapy and that combined treatment with FGFR, CDK4/6, and anti-estrogens is a potential therapeutic strategy in Era+ breast cancer tumors.

Three distinct families of gut bacteria encode an unprecedented number of respiratory-like reductases per genome to perform anaerobic respiration of biomedically relevant substrates.

The process of protein crystallization is poorly understood and difficult to program through the primary sequence. Here the authors develop a computational approach to designing three-dimensional protein crystals with prespecified lattice architectures with high accuracy.

A large-scale field intervention experiment on 23,377 US Facebook users during the 2020 presidential election shows that reducing exposure to content from like-minded social media sources has no measurable effect on political polarization or other political attitudes and beliefs.

A series of early-time, multiwavelength observations of an optical transient, AT2022cmc, indicate that it is a relativistic jet from a tidal disruption event originating from a supermassive black hole.

Senegal has initiated a national sentinel surveillance program for malaria parasite genetics. Here, the authors report data from the first year of the program and use it to investigate local malaria incidence, patterns of transmission, and genetic loci under selection.

FUT10 and FUT11, originally annotated as α1,3-fucosyltransferases, are actually protein O-fucosyltransferases participating in a non-canonical ER quality control pathway for EMI domain-containing protein secretion.

Exome sequences from the first 49,960 participants in the UK Biobank highlight the promise of genome sequencing in large population-based studies and are now accessible to the scientific community.

The Omicron variant evades vaccine-induced neutralization but also fails to form syncytia, shows reduced replication in human lung cells and preferentially uses a TMPRSS2-independent cell entry pathway, which may contribute to enhanced replication in cells of the upper airway. Altered fusion and cell entry characteristics are linked to distinct regions of the Omicron spike protein.

A dataset of coding variation, derived from exome sequencing of nearly one million individuals from a range of ancestries, provides insight into rare variants and could accelerate the discovery of disease-associated genes and advance precision medicine efforts.

CDK4/6 inhibitors have improved outcomes for patients with ER+ breast cancer, however, those with loss of RB1 function often fail to respond. Here, the authors identify a vulnerability of ER + /RB1- breast cancer on PRMT5 and via dual blockade of ER and PRMT5 therapeutically target this in patient-derived xenograft models.

Current vaccines against SARS-CoV-2 reduce mortality but are less effective in preventing infection. Here the authors show that intranasal vaccination with a subunit vaccine including an TLR2-stimulating adjuvant induces strong neutralising antibody and T-cell responses against SARS-CoV-2 in the lungs that protect against infection.

The near-infrared spectrometer onboard JWST has detected CO₂ and CO ices on 56 and 29 trans-Neptunian objects, respectively, indicating two dominant compositional types among them. These compositional differences suggest varied formation regions in the protoplanetary disk.

Two-photon imaging and in situ transcriptomic analysis of the primary visual cortex in mice show that a single transcriptomic axis correlates with the state modulation of cortical inhibitory neurons.

Genome-wide meta-analysis of SARS-CoV-2 susceptibility and severity phenotypes in up to 756,646 samples identifies a rare protective variant proximal to ACE2. A 6-SNP genetic risk score provides additional predictive power when added to known risk factors.

A study of the evolution of the SARS-CoV-2 virus in England between September 2020 and June 2021 finds that interventions capable of containing previous variants were insufficient to stop the more transmissible Alpha and Delta variants.

Heart failure is a complex syndrome that is associated with many different underlying risk factors. Here, to increase power, the authors jointly analyse cases of heart failure of different aetiologies in a genome-wide association study and identify 11 loci of which ten had not been previously reported.

The spatial organization of cells in solid tumors is considered to be important for immune response and response to therapy. Here the authors use multiomics including spatial transcriptomics of human lung tumors prior to patients being treated and show among other things an association of stem-immunity hubs rich in stem-like CD8⁺ T cells with positive response to anti-PD-1 therapy.

Current outcomes are reported from the ongoing National Lung Matrix Trial, an umbrella trial for the treatment of non-small-cell lung cancer in which patients are triaged according to their tumour genotype and matched with targeted therapeutic agents.

So far, experimental results have favoured the often unstated assumption that quantum statistical properties of multiparticle systems are preserved in plasmonic platforms. Here, the authors show how multiparticle interference in photon-plasmon scattering can modify the excitation mode of plasmonic systems.

Tailoring the macroscopic properties of deep eutectic solvents requires knowing how these depend on the local structure and microscopic dynamics. The authors, with computational and experimental tools spanning a wide range of space- and timescales, shed light into the relationship between micro and macroscopic properties in glyceline and ethaline.

Genomic studies often lack representation from diverse populations, limiting equitable insights. Here, the authors show that the BIG Initiative captures extensive genetic diversity and reveals ancestry-linked health disparities in a community-based Mid-South cohort.

Comparison of association signals in UK Biobank using different strategies for assessing genetic variation shows that whole-exome sequencing combined with array genotyping and imputation offers similar performance to whole-genome sequencing at a reduced cost.