Search

Adrenocortical carcinomas (ACC) are aggressive and often resistant to therapy. Here, the authors provide a single-nucleus transcriptomic atlas of ACCs and normal adrenal glands, finding ecotypes in steroid and microenvironment cells that are associated with clinical outcomes.

Providing detailed structural descriptions of the ultrafast photochemical events that occur in light-sensitive proteins is key to their understanding. Now, excited-state structures in the reversibly switchable fluorescent protein rsEGFP2 have been solved by time-resolved crystallography using an X-ray laser. These structures enabled the design of a mutant with improved photoswitching quantum yields.

Dengue is a major public health threat in the Americas including the French Caribbean Islands, in which an epidemic has been ongoing since August 2023. Here, the authors investigate the genetic composition of the strain responsible for the epidemic and find evidence that it is resistant to the main dengue antiviral in current development.

Large-footprint, low-sensitivity charge sensors hinder scaling semiconductor quantum dot arrays for quantum computation. Here the authors present a potentially scalable approach using multiplexed gate-based readout and operation in a foundry-fabricated quantum dot array, demonstrating single-electron occupancy.

How cells use biophysical processes to interpret complex input signals is not well understood. This study reveals limits to the computational power of generic non-equilibrium systems and shows how they can be overcome through features like enzymes acting on multiple targets.

Meta-analysis of genome-wide association studies on Alzheimer’s disease and related dementias identifies new loci and enables generation of a new genetic risk score associated with the risk of future Alzheimer’s disease and dementia.

Results of the phase 2 trial of CD19 CAR T cell therapy lisocabtagene maraleucel in patients with relapsed or refractory follicular lymphoma, most of whom were treated in a third-line or later setting, show encouraging objective response rates in these high-risk patients.

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.

Kim and colleagues perform a phase 2 clinical trial (ELM-2) of odronextamab monotherapy in patients with relapsed/refractory diffuse large B cell lymphoma and report on the primary analyses of the efficacy and safety profile.

Prokaryotic translation initiation involves mRNA-ribosomal RNA base pairing interactions. Here, the authors provide evidence for a similar base pairing interactions occurring between the human h4 mRNA and helix 16 of the small subunit rRNA to position the correct AUG codon in the decoding site.

Individuals with the disease hereditary hemorrhagic telangiectasia have vascular defects that lead to frequent hemorrhages. Franck Lebrin et al. now show that thalidomide, tested as a therapy in a small set of individuals with this disease, lowers the frequency of hemorrhaging and the need for blood transfusions. The authors tie the antihemorrhagic effects of thalidomide to its ability to promote blood vessel maturation through effects on PDGF-B expression by endothelial cells and on pericyte cell proliferation (pages 370–372).

Extracellular vesicles (EVs) play a role in intercellular communication, however the precise biogenesis of different populations of EVs are not clear. Here, the authors follow the intracellular trafficking of two proteins before their secretion in EVs and report the biogenesis and protein markers of EV subtypes: ectosomes budding from the plasma membrane as well as exosomes from late endosomes.

Analysis of 20 chemical and morphological plant traits at diverse sites across 6 continents shows that the transition from semi-arid to arid zones is associated with an unexpected 88% increase in trait diversity.

It has been proposed that the equilibration time of many-body systems is limited by a timescale determined by Planck’s constant and temperature. A bound of this kind has now been identified for a universal definition of equilibration time.

Atypical teratoid rhabdoid tumors (ATRT) are divided into three molecular subgroups, which could have different lineages of origin. Here, the authors use tumour imaging, multi-omics and genetically engineered mouse models to determine the anatomical region and cell lineage of origin of ATRT subtypes.

The development of active solids based on centimetre-scale building blocks incorporating odd elasticity shows that they can spontaneously undergo limit cycles of shape changes, leading to adaptive locomotion such as rolling and crawling.

The Hsp90 chaperone is responsible for the stabilization of a large variety of regulatory proteins. Single-molecule FRET was used to examine the conformational dynamics of Hsp90 in its different nucleotide-bound states. The findings suggest that, in the absence of substrate and cochaperone proteins, Hsp90's conformational changes are not strongly coupled to ATP hydrolysis.

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

Single-cell technologies are increasingly prominent in clinical applications, but predictive modelling with such data in large cohorts has remained computationally challenging. We developed a new algorithm, ‘VoPo’, for predictive modelling and visualization of single cell data for translational applications.

Plasma turbulence is the main driver to deteriorate the performance of fusion power plants. This work presents an unprecedented comparison of plasma turbulence between experiment and simulation, proving that the gyrokinetic model GENE reached a high level of maturity to predict core turbulence.

It is reported using a consistent climate model that pure steam atmospheres are commonly shaped by radiative layers, making their thermal structure strongly dependent on the stellar spectrum and internal heat flow.

Analyses of primary and relapse samples of embryonal tumours with multilayered rosettes provide insights into the molecular mechanisms that underlie the development and opportunities for the treatment of this deadly disease.

rsEGFP2 is a reversibly photoswitchable fluorescent protein used in super-resolution light microscopy. Here the authors present the structure of an rsEGFP2 ground-state intermediate after excited state-decay that was obtained by nanosecond time-resolved serial femtosecond crystallography at an X-ray free electron laser, and time-resolved absorption spectroscopy measurements complement their structural analysis.

SMARCB1 inactivation is prevalent in human atypical teratoid/rhabdoid tumours but a mouse model that accurately phenocopies the human disease is lacking. Here, the authors show that inactivation of SMARCB1between E6 and E10 in mice results in tumours that better recapitulate the human phenotype, compared to previously reported models.

Bagnat, Martín-Belmonte and colleagues reveal that plasmolipin (PLLP) is upregulated in the zebrafish midgut during development and controls epithelial patterning by promoting polarized endocytosis.

The SPECULOOS project detected an Earth-sized planet in a short orbit around a nearby Jupiter-sized star. This planet, SPECULOOS-3 b, is one of the most promising rocky exoplanets for detailed emission spectroscopy characterization with JWST.

Glucocorticoids (GC) are commonly used to suppress undesirable inflammatory responses. Here the authors show, using hi-dimensional flow cytometry data, that GC treatment following major surgeries alters adaptive immunity without significant modulation of innate immune responses or pain/functional impairment.

High-resolution measurements of Martian atmospheric dust, water and semiheavy water, obtained by the ExoMars Trace Gas Orbiter during a global dust storm on Mars, are reported.

Stabl selects sparse and reliable biomarker candidates from predictive models.

Although continuous activity of Foxo transcription factors substantially increase the life span of species such as Hydra vulgaris, these proteins have never been implicated in mammalian aging. In this study, the authors demonstrate that, with age, Foxo1 is down-regulated in mouse T lymphocytes and associated with exhaustion.

Mitochondrial Ca2+ homeostasis is reported to influence cellular senescence. Here the authors show that TRPC3 limits senescence by inhibiting IP3R-mediated Ca2+ release and ER mitochondria Ca2+ transfer and that the downregulation of TRPC3 in stromal cells affects SASP production and tumour progression.

Primary open-angle glaucoma (POAG) is highly heritable, yet not well understood from a genetic perspective. Here, the authors perform a meta-analysis of genome-wide association studies in 34,179 POAG cases, identifying 44 previously unreported risk loci and mapping effects across multiple ethnicities.

The influence of X chromosome genetic variation on blood lipids and coronary heart disease (CHD) is not well understood. Here, the authors analyse X chromosome sequencing data across 65,322 multi-ancestry individuals, identifying associations of the Xq23 locus with lipid changes and reduced risk of CHD and diabetes mellitus.

The complex interactions arising in mixtures of bosons and fermions make it hard to understand their coupled dynamics. The collective oscillations of fermions embedded in a boson condensate have now been characterized in an ultracold-atom experiment.

Standard ways of characterising quantum states incur exponential overhead. Here, the authors consider the task of reconstructing density matrices of multimode continuous variable systems, and demonstrate a method which scales polynomially with the system size, provided the state lies in a polynomial dimensional subspace.

Favipiravir (T-705) is an inhibitor of viral RNA-dependent-RNA-polymerases (RdRp) and clinical trials for the treatment of COVID-19 are ongoing. Here, the authors show that SARS-CoV nsp12 is the fastest known viral RdRp and they provide insights into the mechanism of action of Favipiravir, demonstrating that its antiviral effect on SARS-CoV-2 is primarily mediated through lethal mutagenesis.

Myelofibrosis is a chronic degenerative disorder characterized by progressive bone marrow fibrosis. Here, the authors show that the chaperone HSP27 contributes to myelofibrosis via regulation of the JAK2/STAT5 pathway, and that antisense oligonucleotides targeting HSP27 are effective in two mouse models of the disease

The climatic response to the 1257 Samalas eruption is unclear. Analyses of proxy data and medieval archives suggest that the eruption triggered some of the coldest summers of the past millennium, but only in some Northern Hemisphere regions.

Here, applying an ecological framework to cross-sectional and longitudinal data, the authors identify major branches of the human gut microbiome across the lifespan that connect local ecological states, allowing to better capture associations with health, diet, and lifestyle.

Ewing sarcoma (EWS) is a rare pediatric bone cancer typically involving the EWSR1-FLI1 fusion. Here the authors perform a genome-wide association study and report three new EWS risk loci that reside near GGAA repeat sequences, and identify candidate genes (RREB1 and KIZ) from eQTL analysis.

Negatively-charged boron vacancy centers in hBN have short coherence times, hindering their potential as quantum sensors. By employing dynamical decoupling, the authors achieve an ensemble coherence time approaching the fundamental relaxation limit, enabling sensitive detection of MHz range electromagnetic fields.