Search

In the non-randomized phase 3b/4 DESTINY-Breast12 study, trastuzumab deruxtecan (T-DXd) treatment of patients with HER2⁺ advanced breast cancer and active or stable brain metastases showed consistent intracranial activity and systemic efficacy of T-DXd.

Achieving the Paris Agreement’s climate goals depends on safeguarding and monitoring the permanence of forest carbon stocks, as delays in addressing their vulnerability to disturbances drastically increase mitigation costs and efforts.

Species sharing a common enemy such as a parasitoid or predator can indirectly affect one another. Here, Frost et al. use quantitative food-web data from communities of caterpillar hosts to show experimentally that apparent competition is important in predicting food-web structure across habitats.

Here the authors combine a multimodal imaging-snRNAseq transcriptomics strategy to provide insight into the distribution of a neurotropic tick-borne flavivirus in the brain, and show that absence of interferon signaling increases infection of resident microglia.

Combining the kinase inhibitor sorafenib with allogeneic stem cell transplantation boosts immune responses against a subtype of acute myelogenous leukemia, suggesting potential clinical benefit.

Ruth Loos and colleagues report a meta-analysis of genome-wide association studies in 181,171 individuals identifying 14 new loci associated with heart rate and test these for association with cardiac conduction, rhythm disorders and cardiovascular disease. Their experimental studies in Drosophila melanogaster and zebrafish models provide support for a role for 20 candidate genes at 11 of these loci in regulation of heart rate.

Using upgraded hardware of the multiuser Cold Atom Lab (CAL) aboard the International Space Station (ISS), Bose–Einstein condensates (BECs) of two atomic isotopes are simultaneously created and used to demonstrate interspecies interactions and dual species atom interferometry in space.

By modelling the radio, optical, UV and X-ray data of the unusually bright cosmological explosion AT 2022cmc, Pasham et al. argue for the presence of a highly collimated jet moving at ≳99.99% the speed of light.

Variation in infection dynamics and host cell sensing kinetics shape human antiviral response.

The authors report genome-wide data from 34 ancient individuals spanning the Holocene, from what is now Brazil, illuminating connections and disjoints between Sambaqui shellmound societies and preceding and later peoples.

Examining drivers of the latitudinal biodiversity gradient in a global database of local tree species richness, the authors show that co-limitation by multiple environmental and anthropogenic factors causes steeper increases in richness with latitude in tropical versus temperate and boreal zones.

This article describes a mechanism through which CD4⁺ T cells can eradicate MHC-deficient tumours that escape direct CD8⁺ T cell targeting and thereby complement the activity of CD8⁺ T cells and natural killer cells to advance cancer immunotherapies.

The LHCb collaboration reports an improved measurement of the oscillation frequency of mesons consisting of a bottom quark and strange quark, which is then combined with previous results.

Abnormal PR interval duration is associated with risk for atrial fibrillation and heart block. Here, van Setten et al. identify 44 PR interval loci in a genome-wide association study of over 92,000 individuals and find genetic overlap with QRS duration, heart rate and atrial fibrillation.

Metabolic complications are common in patients suffering PCOS, including obesity, insulin resistance and type-2 diabetes. Here the authors show the efficacy of GLP1-based multi-agonists, and superiority of GLP1/E, for managing metabolic complications of PCOS in preclinical models, with improvement also of some reproductive traits.

Polyether ionophores are natural products that display antibacterial activity—but they also show activity against mammalian cells, which has limited their development as clinical antibiotics. Now, a semisynthesis principle of recycling substructures from highly abundant natural polyether ionophores has been used to prepare analogues with enhanced selectivity towards bacterial cells.

Taylor et al. show that tumor cells promote white adipose tissue (WAT) wasting and cachexia by overactivation of Notch1 signaling and retinoic acid production in distant WAT endothelium, which can be therapeutically targeted to inhibit wasting.

The structure of the lithosphere and its impact on mantle flow significantly influence the impact of Earth’s interior dynamics on surface topography, suggest statistical analyses of Earth’s topography.

Exome sequencing within a structured diagnostic process for rare diseases in Germany shows how facial image analysis and machine learning can guide variant prioritization and uncover many ultrarare diseases.

In contrast to previously reported findings, M2-like polarized macrophages are not a source of catecholamines and do not contribute to browning of the fat.

Nucleoside diphosphates and triphosphates impact nearly every aspect of biochemistry. Now, a modular, reagent-based platform has been developed to enable the stereocontrolled and scalable synthesis of a library of such molecules. This operationally simple approach provides access to pure stereoisomers of nucleoside α-thiodiphosphates and α-thiotriphosphates.

Genome-wide analysis identifies variants associated with the volume of seven different subcortical brain regions defined by magnetic resonance imaging. Implicated genes are involved in neurodevelopmental and synaptic signaling pathways.

Although the role of Notch signaling in CNS glial development is well established, its participation in peripheral glial development is still unclear. This paper shows that Notch signaling regulates the differentiation of Schwann cell precursors and the proliferation of Schwann cells, and acts as a break on myelination of peripheral nerves.

Chemical proteomics identified covalent ligands targeting an isoform-restricted allosteric cysteine in JAK1. The compounds inhibit JAK1-dependent signaling in immune cells with unprecedented selectivity.

In this study, Tai et al. provide insights into the metabolic and bioenergetic responses in the axonal compartment in the context of multiple sclerosis. Moreover, they show how upregulating the tricarboxylic acid cycle confers protection against neuroinflammation-induced energy deprivation.

In a post-approval study including more than 17,000 patients on the safety of pulsed field ablation, a new method for treatment of atrial fibrillation, the procedure was found to have a low rate of adverse events but was associated with some unexpected rare complications that will need further study.

Increased expression of MITF transcription factor is thought to promote melanoma progression and kinase inhibitor resistance. Here Muller et al. show that MITF loss is also common in melanomas and confers kinase inhibitor resistance due to upregulation of AXL and other receptor tyrosine kinases.

The genetic basis of atopic dermatitis is not fully understood. Here, the authors find 91 genetic loci associated with atopic dermatitis in a GWAS of >1million individuals, which highlight the importance of systemic immune regulation.

A transancestral exome-wide association study for body-fat distribution identifies protein-coding variants that are significantly associated with waist-to-hip ratio adjusted for body mass index.

Genome-wide association meta-analyses identify 26 risk loci for epilepsy, including 19 loci specific to genetic generalized epilepsy. Prioritized candidate genes implicate synaptic processes and overlap with targets of antiseizure medications.

Past genome-wide associate studies have identified hundreds of genetic loci that influence body size and shape when examined one trait at a time. Here, Jeff and colleagues develop an aggregate score of various body traits, and use meta-analysis to find new loci linked to body shape.

Precise mass and radius measurements of giant planet WASP-193 b find an extremely low density of 0.059 ± 0.014 g cm⁻³. Current evolutionary models cannot fully explain such a low density, but the extended atmosphere makes WASP-193 b very suitable for high-precision characterization via JWST.

Cachexia is associated with poor prognosis in heart failure. Here the authors show that mice and patients with cardiac cachexia display reduced skeletal muscle expression and circulating levels of Musclin. Musclin ablation in skeletal muscle worsens, while its muscle-specific overexpression ameliorates heart failure in mice.

The authors analyse tree responses to an extreme heat and drought event across South America to understand long-term climate resistance. While no more sensitive to this than previous lesser events, forests in drier climates showed the greatest impacts and thus vulnerability to climate extremes.

CP violation has deep implications for particle physics and cosmology. Previously observed only in meson decays, signs of CP violation have now been spotted in baryon decays by analysing the proton–proton collision data from the LHCb detector.

The iconic image of ‘the public square’ typifies many cities in Europe and elsewhere, but they transcend spaces for socializing and public deliberation. Focusing on Munich, this study analyzes whether and how design features of public urban squares affect the broader biodiversity living there, finding that greenness matters but that different taxa respond differently to design elements.

Water scarcity threatens a growing number of global catchments. Here, the authors examine how human interventions (HI) affected water scarcity between 1971 and 2010 and find that HI caused increases in the average duration and occurrence of water scarcity for 32% and 34% of the global population, respectively.