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Steroid units can facilitate membrane permeation and bioavailability in drugs. Here, using a medicinal chemistry program, Krieget al. identify an arylmethylamino steroid that kills Plasmodium parasites, likely through a chelate-based quinone methide mechanism, and has activity against Schistosoma mansoni.

The existence and properties of tetraquark states with two heavy quarks and two light antiquarks have been widely debated. Here, the authors use a unitarized model to study the properties of an exotic narrow state compatible with a doubly charmed tetraquark.

Kiourtis et al. show that liver senescence triggers senescence and dysfunction in other organs through TGFβ secretion from the liver.

JWST/NIRSpec spectra are used to analyse the surfaces of Centaurs, revealing two main compositions: those with refractory materials and water ice and those rich in carbon-based materials. Strong surface weathering due to thermal processing may be responsible.

Human TNF is required for respiratory-burst-dependent immunity to Mycobacterium tuberculosis in macrophages but seems to be largely redundant physiologically.

The genetics and clinical consequences of resting heart rate (RHR) remain incompletely understood. Here, the authors discover new genetic variants associated with RHR and find that higher genetically predicted RHR decreases risk of atrial fibrillation and ischemic stroke.

Genome-wide association meta-analyses of waist-to-hip ratio adjusted for body mass index in more than 224,000 individuals identify 49 loci, 33 of which are new and many showing significant sexual dimorphism with a stronger effect in women; pathway analyses implicate adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution.

Douglas Easton, Per Hall and colleagues report meta-analyses of genome-wide association studies for breast cancer, including 10,052 cases and 12,575 controls, followed by genotyping using the iCOGS array in an additional 52,675 cases and 49,436 controls from studies within the Breast Cancer Association Consortium (BCAC). They identify 41 loci newly associated with susceptibility to breast cancer.

Cellular uptake of copper(ii) by CD44 has a key role in regulating cellular plasticity via copper(ii)-dependent downstream signalling events.

The tumor suppressor BAP1 is activated by ASXL1 to deubiquitinate mono-ubiquitinated H2A at K119 in Polycomb gene repression. Here, the authors show how BAP1’s C-terminal extension auto-recruits it to nucleosomes, where the DEUBAD domain of ASXL1 increases BAP1’s affinity for ubiquitin to drive deubiquitination.

Regulatory T cells (Tregs) are known for suppressing inflammatory processes, but their full capacity for tissue regeneration is yet to be harnessed. Here, the authors demonstrate the efficiency of Tregs in facilitating tissue healing in mouse models of bone, muscle, and skin injury, with monocytes/macrophages and interleukin-10 playing a key mechanistic role in the process.

By leveraging diverse datasets from brain stimulation therapy for Tourette Syndrome and tic-inducing brain lesions, Baldermann et al. reveal a critical role of action-related functional networks in both the treatment and pathophysiology of tic disorders.

Single-nucleus RNA sequencing of human visceral and subcutaneous adipose tissues is used to identify adipocyte subpopulations and explore their developmental trajectories and interactions.

Analytis et al. study social learning strategies for matters of taste and test their performance on a large-scale dataset. They show why a strategy’s success depends both on people’s level of experience and how their tastes relate to those of others.

On-water surface synthesis, characterized by enhanced reactivity, distinct selectivity, and confined reaction geometry, offers potential for synthesis but is currently limited by the requirement for a stable air-water interface. Here the authors present an approach that mimics on-water surface chemistry using micelles.

Quantum error correction is essential for reliable quantum computing, but no single code supports all required fault-tolerant gates. The demonstration of switching between two codes now enables universal quantum computation with reduced overhead.

Fatty acid unsaturation by stearoyl-CoA desaturase 1 (SCD1) protects against cellular stress through unclear mechanisms. Here the authors show 1,2-dioleoyl-sn-glycero-3-phospho-(1’-myo-inositol) is an SCD1-derived signaling lipid that regulates stress-adaption, protects against cell death and promotes proliferation.

An expanded GWAS of birth weight and subsequent analysis using structural equation modeling and Mendelian randomization decomposes maternal and fetal genetic contributions and causal links between birth weight, blood pressure and glycemic traits.

The yeast Saccharomyces cerevisiae is the pre-eminent organism for the study of basic functions of eukaryotic cells¹. All of the genes of this simple eukaryotic cell have recently been revealed by an international collaborative effort to determine the complete DNA sequence of its nuclear genome. Here we describe some of the features of chromosome XII.

NASA’s Cold Atom Lab has operated on the International Space Station since 2018 to study quantum gases and mature quantum technologies in Earth’s orbit. Here, Williams et al., report on a series of pathfinding experiments exploring the first quantum sensor using atom interferometry in space.

Malik, Beaufort et al. show that rare and common genetic variations in HTRA1 associate with stroke and coronary artery disease outcomes via independent mechanisms.

The Large Hadron Collider beauty collaboration reports a test of lepton flavour universality in decays of bottom mesons into strange mesons and a charged lepton pair, finding evidence of a violation of this principle postulated in the standard model.

Bock and colleagues perform integrative analysis of JAK-STAT mutant mice and find JAK-STAT signaling regulates CD8⁺ T cell and macrophage homeostasis by contributing to a poised epigenetic and transcription-regulatory state, preparing cells to rapidly respond to stimuli.

The circadian rhythm has been linked to cancer cell sensitivity to therapy but tools to understand this further are limited. Here, by combining live-cell imaging and computational tools, the authors develop a high-throughput deep-phenotyping approach to evaluate circadian rhythms and use it to determine time-of-day drug sensitivity in cancer cell lines.

An approach combining electron energy-loss spectroscopy with image processing tools from single-particle cryo-electron microscopy enables elemental mapping in macromolecular complexes, paving the way for the accurate assignment of metals, ions, ligands and lipids.

Although diazoalkenes have been reported as reactive intermediates in organic chemistry, their detection and isolation remains challenging. Such species have previously only been detected at low temperatures in matrix-isolation studies. Now, a room-temperature stable diazoalkene has been reported, which shows dual-site nucleophilicity and can undergo N₂ exchange or lose dinitrogen under irradiation.

Klingelhuber, Frendo-Cumbo et al. develop a proteomic atlas elucidating the intracellular spatiotemporal changes in protein levels and localizations during human adipogenesis.

Semiconducting polymer nanoparticles can act as light-sensitive interfaces with retinal neurons, and on microinjection in the eye, rescue vision in retinas affected by photoreceptor degeneration, offering a potential new treatment option for inherited retinal dystrophies and late-stage age-related macular degeneration.

A genome-wide association meta-analysis of individuals with clinically assessed or self-reported depression identifies 44 independent risk loci. Comparisons with other psychiatric disorders and candidate gene analyses provide new insights into major depressive disorder.

Klebsiella oxytoca provides protection against Salmonella Typhimurium via toxin-dependent inhibition in nutrient-rich, low-competition environments but switches to substrate-driven competition when nutrients are limited.

Extracellular vesicles (EVs) convey inter-organ communication in health and disease. Here, the authors report that adipocyte-derived EVs isolated from insulin-resistant obese but not lean male mice stimulate insulin secretion via the targeted transfer of insulinotropic proteins from adipose tissue to β-cells.

When stars like our Sun die, they expel their outer layers in a dramatic stellar wind. This study of an unusual chemical signature in one particular stellar wind reveals that the signature is due to the presence of a binary system whose components had a close approach around 200 years ago.

Beta-adrenergic stimulation of brown adipose tissue leads to thermogenesis via the activating transcription factor 2 (ATF2) mediated expression of the thermogenic genes Ucp1 and Pgc-1α. Here, the authors show that the scaffold protein p62 regulates brown adipose tissue function through modifying ATF2 genomic binding and subsequent Ucp1 and Pgc-1α induction.

A conjugate drug consisting of GLP-1 receptor agonist and the PPARɑ/ɣ dual-agonist tesaglitazar is shown to have superior anti-diabetic effects than monotherapy.

Recent years have seen significant progress in the coherent control of collective excitations such as magnons and phonons in quantum materials using ultrafast laser pulses. Here the authors report evidence of coherent excitation of orbitals in a rare earth pyrochlore spin liquid material Tb2Ti2O7 by THz pulses.

Stig Bojesen, Georgia Chenevix-Trench, Alison Dunning and colleagues report common variants at the TERT-CLPTM1L locus associated with mean telomere length measured in whole blood. They also identify associations at this locus to breast or ovarian cancer susceptibility and report functional studies in breast and ovarian cancer tissue and cell lines.

The functions of many putative membrane transport proteins of malaria parasites are unknown. Here, Kenthirapalan et al. use mutant strains carrying targeted gene deletions to study the functions of 35 such proteins during the life cycle of Plasmodium bergheiin mosquito and mouse hosts.

Is there a critical period to deliver gene therapies in photoreceptor degeneration? Using a mouse model of retinitis pigmentosa, the authors show that once 70% of rods are lost, gene replacement fails to restore normal retinal output.

Magnetic cooling could be a radically different energy solution that could replace conventional vapour compression refrigeration in the future. It is now shown that a Heusler-type magnetocaloric alloy exhibits a remarkable cooling capability due to the effect of a sharp structural transformation at a specific temperature. The finding may be of relevance beyond Heusler alloys and represents an important step towards the implementation of cooling systems based on magnetocaloric materials.

The Alpha variant of SARS-CoV-2 outcompetes progenitor SARS-CoV-2 in upper respiratory tract replication competition in vivo.

Mycoplanecins show promising activity against tuberculosis. Here, the authors identify and study mycoplanecins’ biosynthesis, antibacterial effects, and binding mechanism to DnaN, suggesting potential for fighting multidrug-resistant tuberculosis.