Search

In a large single-arm phase 2 trial, the anti-PD-1 inhibitor tislelizumab combined with the next-generation BTK inhibitor zanubrutinib had an overall response rate of 58.3% and was well tolerated in patients with Richter’s transformation.

Mitotic DNA synthesis (MiDAS) has been proposed to utilize break-induced DNA replication, a form of homology-directed DNA repair (HDR). Here, the authors find that core DNA end-resection factors required for HDR, including MRE11, CtIP and BRCA1, and a RecQ family helicase, WRN, are essential for MiDAS.

How TGF-β family members regulate sex determination in teleost fish is unclear. Here they use turquoise killifish to show that Gdf6Y, in addition to its role in skeletal development, specifies the male sex in somatic supporting cells by autocrine signaling.

The authors developed a neuromorphic chip with on-chip learning and support for diverse memory devices. It bridges brain-inspired computing and emerging tech, enabling efficient, flexible testing and advancing next-gen neuromorphic architectures.

Identifying reaction pathways is a major challenge in chemistry, and proves particularly difficult for surface reactions. Here the authors show that imaging the molecular orbitals with photoemission tomography provides insight into the structure of surface intermediates allowing their identification.

The contribution of ligands for cytokine receptor dimerization is still not fully understood. Here, the authors show the efficient ligand-induced dimerization of type II interleukin-4 receptor at the plasma membrane and the kinetic trapping of signalling complexes by actin-dependent membrane microdomains.

The antisense oligonucleotide rugonersen has acceptable safety and tolerability in children with Angelman syndrome and shows partial normalization of electroencephalogram abnormalities and clinical improvements relative to natural history.

Sinonasal tumour diagnosis can be complicated by the heterogeneity of disease and classification systems. Here, the authors use machine learning to classify sinonasal undifferentiated carcinomas into 4 molecular classe with differences in differentiation state and clinical outcome.

Atomically thin transition metal dichalcogenides host excitons and trions, however higher-order states, although possible, are difficult to identify experimentally. Here, the authors perform polarization-resolved coherent spectroscopy to unveil the signature of neutral and charged inter-valley biexcitons in monolayer MoSe₂.

The advantage of living in cities compared with rural areas with respect to height and BMI in children and adolescents has generally become smaller globally from 1990 to 2020, except in sub-Saharan Africa.

Aircraft measurements over the Amazon show that new particle formation in the upper troposphere emerges when isoprene, emitted by forests, undergoes oxidation in the presence of nitrogen oxides produced by lightning.

Niche crosstalk with Haematopoietic cells underlies normal haematopoiesis and myeloid disorders. Here the authors report a Stabilin2-Cre driver mouse with Cre-activity restricted to bone marrow sinusoidal endothelial cells, and that Stabilin2-Cre driven overactivation of b-catenin leads to erythroid differentiation defects and anaemia.

RNA modifications are key regulators of RNA functions. Here, the authors identify METTL8 as the enzyme installing m³C₃₂ in mitochondrial tRNA^Thr/Ser(UCN). Lack of these modifications affects tRNA structure and impairs mitochondrial translation.

Using brain organoids models, Prigione and colleagues uncovered the impact of Huntington’s disease on human brain developmental and identified early dysregulation of CHCHD2, which disrupted mitochondria and might serve as a therapeutic target.

Early stages of embryogenesis are known to depend on subcellular localization and transport of maternal mRNA, but systematic analyses have been hindered by a lack of methods for tracking of RNA. Here the authors combine spatially-resolved transcriptomics and single-cell RNA labeling to perform a spatio-temporal analysis of the transcriptome during early zebrafish development, revealing insights into this process.

Epigenome profiling in combination with imaging-based chemosensitivity and integrative bioinformatic analysis establishes a method for detecting therapy-induced vulnerabilities, as shown here for ibrutinib-treated chronic lymphocytic leukemia.

Legacies of past ecological disturbances are expected but challenging to demonstrate. Here the authors report a 10-year field experiment in a mountain grassland that shows ecological memory of soil microbial community and functioning in response to recurrent drought.

Dewald et al. show a high Spike-IgG seroprevalence (95%) in a multicenter study with 1,411 participants. They determined a substantially reduced serum neutralization against the SARS-CoV-2 VOCs BA.4/5 and BQ.1.1. and explored predictive factors of neutralizing activity.

Biochemical and biophysical analyses of eye lenses from mouse strains that develop cataract due to mutations in α-, β-, or γ-crystallin proteins reveal that the mutant protein levels are largely reduced, but other crystallin proteins, including α-crystallins, precipitate.

The circadian clock and the cell cycle systems coordinate global physiology. Here the authors show that MYC represses the clock genes, together with MIZ1, and induces proliferation, suggesting that MYC inversely modulates cell cycle and circadian clock genes.

A combination of cellular and genome-wide mapping approaches reveal that RTEL1 helicase functions with SLX4 to resolve R-loops and G-quadruplex structures that impede DNA replication fork progression in human cells.

A quantitative atlas of the transcriptomes, proteomes and phosphoproteomes of 30 tissues of the model plant Arabidopsis thaliana provides a valuable resource for plant research.

Neutralization of the SARS-CoV-2 Omicron variant is markedly impaired in sera from recipients of two doses of the COVID-19 vaccine BNT162b2 or from convalescent individuals, but is robustly increased in both groups following a booster vaccine dose.

Survival outcomes in Burkitt lymphoma differ between adult and paediatric patients. Here, the authors show differences in mutational frequencies between age groups, and a transition between mutational profiles which occurs between 25 and 40 years.

Plasmablastic lymphoma (PBL) is an aggressive lymphoma subtype characterized by poor prognosis but the molecular knowledge of the disease is limited. Here, the authors perform whole exome sequencing and copy number determination of primary samples highlighting IRF4 and JAK-STAT pathways as therapeutic targets for PBL.

The engagement of immunological memory is a key component to the protective anti-SARS-CoV-2 B and T cell responses. Here the authors assess the B and T cells of a cohort of UK healthcare workers in response to infection and longitudinally track the compartment showing distinct trajectories following early priming.

Single-cell RNA sequencing and spatiotemporal analysis of the regenerating zebrafish heart identify transient proregenerative fibroblast-like cells that are derived from the epicardium and the endocardium. Wnt signalling regulates the endocardial fibroblast response.

It has been commonly believed that the driving force at the donor-acceptor heterojunction is vital to efficient charge separation in organic solar cells. Here Zhong et al. show that the driving force can be as small as 0.05 eV without compromising the charge transfer rate and efficiency.

Comparing pelvic sex differences across modern humans and chimpanzees reveals a similar pattern despite differences in magnitude of pelvis shape dimorphism, suggesting that this pattern did not evolve de novo in modern humans but was present in the last common ancestor of humans and chimpanzees.

Thaumarchaeota isolates are capable of utilizing urea and cyanate for nitrification in vitro. Here, the authors show that this occurs in situ and that Thaumarchaeota are able to use urea and cyanate as an energy and nitrogen source in the marine environment.

Modern mammals are endothermic, but it has not been clear when this type of metabolism evolved. Here, Newham et al. analyse tooth and bone structure in Early Jurassic stem-mammal fossils to estimate lifespan and blood flow rates, which inform about basal and maximum metabolic rates, respectively, and show these stem-mammals had metabolic rates closer to modern ectothermic reptiles than to endothermic mammals.

Understanding the effect of vaccination on emerging SARS-CoV-2 variants of concern is of increasing importance. Here, James et al. report that two doses of vaccination with the Pfizer-BioNTech vaccine induce more robust immune responses to the B.1.1.7 and B.1.351 SARS-CoV-2 lineages than does natural infection.

Various preventive measures are used to avoid non-target species or bycatch in fishing operations, but the success of such measures is not well understood. This study evaluates the effects of technical mitigation measures on both vulnerable marine fauna bycatch and target catch.

The continents are thought to insulate and heat the underlying mantle. Geochemical analyses of lava samples formed at a mid-ocean ridge in the Atlantic Ocean immediately after continental breakup show that the mantle was up to 150 °C hotter than today and took about 70 million years to cool.

A hybrid approach merges networks of time-correlated distances determined by single-molecule FRET to uncover local and global dynamics of the multidomain protein Hsp90 in solution at multiple timescales.

RT-FDC combines the specificity of fluorescent probes with functional readout of a cell's mechanical properties. The resulting correlation of fluorescence-based cell identity with mechanical measurements in real time allows the development of label-free, mechanical cell sorting.

Considering the interdependence of performance measures and the lack of a basic reference system for all-solid-state batteries, Jürgen Janek and co-workers analyse literature performance data for major types of all-solid-state batteries and benchmark them against minimalistic reference cells.

The use of an in vitro system in which key proteins involved in cell division are attached to supported lipid bilayers reveals that membrane-bound cytosolic peptides of FtsN and FtsQ co-migrate with treadmilling FtsZ–FtsA filaments via a diffusion-and-capture mechanism, elucidating how FtsZ dynamics regulate the distribution of peptidoglycan synthases.

Sorting RT-FDC combines real-time fluorescence and deformability cytometry with sorting based on standing surface acoustic waves to transfer molecular specificity to label-free, image-based cell sorting using an efficient deep neural network.

Anaplastic large cell lymphomas (ALCL) often express the oncoprotein NPM-ALK. This study shows that the activator protein 1 family members JUN and JUNB promote lymphoma development through platelet-derived growth factor receptor-β (PDGFRB). Inhibition of PDGFRB prolonged survival of NPM-ALK transgenic mice and increased the efficacy of an ALK-specific inhibitor against transplanted NPM-ALK tumors. Inhibition of PDGFR in a patient with ALCL also resulted in rapid, complete and sustained remission.

Generating and detecting neutral biomolecular beams is an important analytical challenge, particularly for high-mass peptides. Here, femtosecond laser desorption is shown to enable the intact volatilization of complex polypeptides that can still be photoionized at masses beyond 20 kDa, because they are tryptophan-rich.