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Notch1 is frequently activated promoting T-cell acute lymphoblastic leukaemia (T-ALL). Here, the authors show that Notch1 induces oxidative phosphorylation dependency in T-ALL and synergism when inhibiting both mitochondrial complex I and glutaminolysis in preclinical murine and human xenograft models.

Chronic obstructive pulmonary disease is a progressive and incurable chronic condition that involves accumulation of inflammatory macrophages in the lung tissue. Authors here show in mouse models of lung disease that PRMT7, a protein arginine methyltransferase, is an important regulator of recruitment and the pro-inflammatory phenotype of macrophages.

Periprosthetic osteolysis is a cause of arthroplasty failure without available therapies. Here the authors show that Annexin A1 (AnxA1) is involved in in periprosthetic osteolysis and exerts potential therapeutic effects through suppressing NFκB signaling and promoting the PPAR-γ pathway resulting in inhibition of inflammation and osteoclasts differentiation induced by wear debris.

The efficacy of cancer drugs is profiled by measuring changes in the mass of single tumor cells.

Therapeutic modulation of Janus kinase family enzymes is an established approach for inflammatory and autoimmune skin diseases. Here the authors rationally design small interfering RNAs to enable single Janus kinase targeting and test this new therapeutic approach in a skin disease model for maintaining efficacy and improving selectivity.

Dimethoxy-1,4-benzoquinone signalling occurs in Arabidopsis and in the root parasite Phtheirospermum japonicum via increases in cytosolic Ca²⁺ concentration mediated by the leucine-rich-repeat receptor-like kinase CARD1 in Arabidopsis, or by its homologues in P. japonicum.

Pulmonary arterial hypertension is a progressive fatal disease characterized by pathological pulmonary artery remodeling. Here the authors show that the dysregulation of the activin A-bone morphogenetic protein receptor type 2 link in the endothelium is involved in the progression of pulmonary hypertension.

Clonal subpopulations in human tumors are identified from single-cell RNA-seq data.

Here the authors develop a neonatal mouse model for SARS-CoV-2 transmission, characterize differences in viral replication and shedding of variants of concerns, and show that deletion of ORF8 shifts viral replication to the lower respiratory tract and delays transmission.

The Human Breast Cell Atlas identifies 12 major breast cell types and 58 biological cell states, revealing abundant pericyte, endothelial and immune cell populations, and highly diverse luminal epithelial cell states.

Isolation and characterization of an archaeon that is most closely related to eukaryotes reveals insights into how eukaryotes may have evolved from prokaryotes.

The naked mole-rat exhibits an exceptional resistance to cancer. Here, the authors show that induced pluripotent stem cells derived from the naked mole-rat lack teratoma-forming tumorigenicity due to a naked mole-rat-specific ARF-dependent tumour-suppression mechanism.

Highly concentrated trehalose induces beneficial senescence-like state in fibroblasts and accelerates the proliferation of keratinocytes and angiogenesis to promote optimal wound repair, demonstrating its therapeutic potential in modulating fibroblast functions.

Acute respiratory distress in macaques and baboons recapitulates COVID-19 disease progression in humans, making them suitable as models to test vaccines and therapies.

Cell death is a critical process in health and disease, yet available markers record later stages of cell death once a cell has already begun to decompose. Here the authors show the use of a genetically encoded calcium indicator that demarcates an irreversible stage of cell death earlier than previously possible.

Genomic aberrations disrupting chromosome spatial domains can lead to disease. Here, the authors investigate the impact of DNA damage response and repair on 3D genome folding, comparing wild type cells and ataxia telangiectasia mutated patient cells, and characterise both cell type-specific and shared changes to genome organization during the response to damage.

Spinal cord neural stem cells are generated from human pluripotent stem cells via a chemically defined, xeno-free method, and exhibit efficient and functional engraftment in rat spinal cord lesions.

During embryonic development, neural progenitor cells undergo numerous cell divisions. Here, the authors show that ABHD4-mediated developmental anoikis distinguishes the physiological delamination and the pathological detachment of progenitor cells with relevance to fetal alcohol-induced apoptosis.

Only praziquantel is available for treating schistosomiasis, a disease affecting >200 million people. Here, the authors identify compounds active against schistosome infections meeting the criteria for lead progression indicated by WHO with better activity against juvenile worms than praziquantel.

How APCs encounter T cells in the periphery remains unclear. Kabashima and colleagues show that dendritic cells form macrophage-dependent clusters in dermal perivascular areas for efficient in situ proliferation and activation of T cells.

The regulation and direction of CD4⁺ T cells into phenotypic and functional lineages is coordinated by a complex set of mechanisms. Here the authors show a role for Aiolos as a regulator of the CD4⁺ cytotoxic and T follicular helper lineages.

This study uses a new method of profiling cell type–specific gene expression to identify genes expressed in fruitfly clock neurons. Such profiling yields two novel circadian genes, in separate sets of clock neurons and with differing circadian functions.

This protocol describes how to design and build a centrifuge force microscope that is 3D printed to fit within an existing benchtop centrifuge and enables the simultaneous probing of hundreds to thousands of single-molecule interactions using tethered particles.

Despite methodological improvements, it remains extremely difficult to routinely establish cell lines from human primary tumours. Here, the authors develop a culture medium that allows efficient cell line establishment and use this to generate 25 ovarian cancer cell lines.

Talins are essential for integrin activation, focal adhesion formation and mesenchymal cell migration. The E3 ubiquitin ligase Smurf1 regulates talin head degradation and Cdk5-mediated phosphorylation of the head prevents Smurf1 action on talin.

Bioresorbable electronic stimulators can deliver electrical stimulation in rodents to enhance functional muscle recovery after nerve injury. Here, the authors present a bioresorbable dynamic covalent polymer that enables reliable, long-lived operation of soft, stretchable devices of this type.

A hexanucleotide repeat expansion of C9orf72 is translated to dipeptide repeat proteins in amyotrophic lateral sclerosis and frontotemporal dementia patients. Here the authors generate a C. elegans model of C9orf72-mediated ALS/FTD and show that translation initiation factor eIF2D regulates the dipeptide repeat protein expression.

Snail is a transcription factor that induces epithelial-mesenchymal transition. Here the authors show that, in the mesenchymal subtype of ovarian cancer, Snail expression promotes tumorigenesis by inducing immune evasion through CXCR2-ligands-mediated recruitment of myeloid-derived suppressor cells.

Chemoproteomic studies have revealed that a Wnt-pathway inhibitor, CCT251545, is a potent and selective small-molecule chemical probe that inhibits the Mediator complex–associated protein kinases CDK8 and CDK19 through a type 1 binding mode and modulates the growth of Wnt-dependent tumors.

Heterogeneity in growth phenotypes and drug susceptibility in bacterial and mammalian cells are assayed at the single-cell level using multiplexed resonant mass sensors.

A manipulative experiment in which a reef is alkalinized in situ shows that calcification rates are likely to be lower already than they were in pre-industrial times because of acidification.

Baba et al. analyzed the transcriptomes from quadriceps type IIB fibers of untreated, gonadectomized, and sex steroid-treated mice of both sexes and identified Pfkfb3 and Pdk4 as differentially regulated genes between males and diestrus females. The authors found that Pfkfb3 and Pdk4 may act as metabolic switches, showed male-enriched and estradiol-enhanced expression, respectively and contributed to sexually dimorphic metabolism.