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Single-cell DNA methylome profiling allows the study of epigenomic heterogeneity in tissues but has been impeded by library quality. Here the authors demonstrate snmC-seq2 which improves mapping, throughput and library complexity.

BRCA1 and BRCA2 are well known breast cancer predisposition genes, however, many variants have not yet been classified for their pathogenicity. Here, the authors analyse a large combined cohort to provide evidence of variant pathogenicity.

Viruses such as coxsackievirus B (CVB) have been associated with type I diabetes (T1D) and islet destruction. Here the authors show that Yes-associated protein (YAP) is upregulated in the whole pancreas in T1D and at-risk autoantibody (AAb + ) organ donors and that YAP over-expression enhances CVB replication, islet inflammation and β-cell apoptosis and suggest exocrine-islet-immune interactions as targeted interventions for T1D.

A gene therapy phase 1 trial in patients with β-thalassemia shows transplantation of autologous CD34⁺ cells transduced with a lentiviral globin vector after reduced-intensity conditioning achieves long-term engraftment, albeit not transfusion independence, with benign clonal expansions, warranting cautious monitoring of patients.

Resolution of G4s has been suggested to be required for efficient DNA replication. Here, the authors show that the nuclease DNA2 and the DNA repair complex MutSα (MSH2-MSH6) are required to remove G4 stabilized by environmental compounds to allow efficient telomere replication.

Mouse tumor organoids are characterized as a model to study tumor biology and drug resistance.

Cardiovascular function declines with age. In this study, the authors show that the BAT-derived lipokine 12,13-diHOME preserves cardiac function in aged mice by attenuating pathological CaMKII activity.

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.

Mesopelagic fishes dominate the global fishes biomass, yet there exist major uncertainties regarding their global biomass. Irigoien et al.analyse acoustic data collected during a circumglobal cruise and show that biomass estimates should be raised by an order of magnitude.

The lithospheric mantle may be delaminating from the crust in an oceanic plate segment offshore Southwest Iberia, which could be the ultimate cause of the 1755 Great Lisbon Earthquake, according to seismic imaging and numerical simulations.

Rubio-Navarro et al. identify a subset of pancreatic beta cells marked by high CD63 levels with enhanced glucose-stimulated insulin secretion. CD63-high beta cells are diminished in mouse models of and in humans with type 2 diabetes.

BRCA1 ligase activity is tightly regulated to maintain genome stability and confer DNA double strand repair. Here the authors identify USP48 as a H2A deubiquitinating enzyme that acts as a BRCA1 E3 ligase antagonist and characterize its role during DNA repair.

This study reconstructs the evolution of leaf venation networks, describing the transition from fewer, corrugated veins to high vein density and smoother loops. It also suggests herbivory as a potential driver of venation architectural changes.

The receptor-like kinase NIK1 is phosphorylated in response to multiple biotic and abiotic signals, activating the NIK1/RPL10/LIMYB signaling circuit, which coordinately regulates translation and photosynthesis in response to environmental changes.

Breast cancer cells interact with neighbouring adipocytes, but the mechanisms are not fully understood. Here, the authors show that triple-negative breast cancer (TNBC) cells transfer cAMP through gap junctions, activating lipolysis in tumour-associated adipocytes to promote TNBC growth.

In this study, the authors describe SANA, a nitroalkene derivative of salicylate, as a potential activator of creatine-dependent energy expenditure and thermogenesis in adipose tissue. Preclinical and clinical data from this paper also suggest that SANA improves glucose homeostasis and promotes weight loss in mice and humans.

The thymus is sensitive to acute insults including infection, as well as to injury from chemotherapy and myeloablative conditioning before hematopoietic cell transplantation. Here, Granadier et al. describe a role for IL-18 in limiting thymic regeneration by stimulating NK cells, which then target thymic epithelial cells.

It’s unclear how fragmented habitats affect species coexistence in bacterial communities. Here, using microfluidic chip experiments and simulations, the authors find that fragmentation leads to more diverse ecological outcomes mostly due to underlying phenotypic variation in founder cells and their stochastic assembly.

Tacrolimus is a critical immunosuppressant for liver transplant recipients, but its dosing is challenging due to individual variability. Here, the authors show that a phenotypic personalized medicine approach improves tacrolimus dosing precision, reducing large deviations from target levels and shortening hospital stays in a Phase 2 randomized trial.

To understand the potential for seaweed as a Blue Carbon strategy, the authors quantify carbon burial under 20 globally distributed seaweed farms. They attribute an average of 1.06 ± 0.74 tCO₂e ha⁻¹ yr⁻¹ to seaweed farms, and show increased accumulation of carbon with farm age.

Macrophage-augmented organoids integrate macrophages into organoids that are cultured from human liver tissue for analysis of immune responses during three different viral infections.

Estimates from the Global Dietary Database indicated that 2.2 million new type 2 diabetes and 1.2 million new cardiovascular disease cases were attributable to sugar-sweetened beverages worldwide in 2020, with the highest burdens in sub-Saharan Africa, Latin America and the Caribbean.

A strategy to control HIV-1 infection is to stably repress HIV-1 and induce “deep latency”. Here the authors show that a recombinant anti-HIV-1-1 protein can be packaged as mRNA into exosomes and delivered systemically to repress HIV-1-1 within the context of virus infected mice and achieve long term silencing of HIV-1-1 expression.

Using metabolic dysfunction-associated steatohepatitis-driven hepatocellular carcinoma mouse models, an ATP citrate lyase inhibitor reduces tumour burden and enhances efficacy of current standards of care.

The bacterial complex QrcABCD plays a key role in the bioenergetics of sulfate respiration. Here, Duarte et al. show that this complex is electrogenic, with protons and electrons required for quinone reduction being extracted from opposite sides of the membrane.

A first-in-human phase I clinical trial demonstrates the feasibility and safety of non-viral precision genome-engineering of a personalized adoptive cell transfer anticancer therapeutic.

Pathogenesis of steroid-resistant gut acute graft-versus-host-disease (SR-Gut-aGVHD) remains unclear., Here the authors show in mouse models that dysbiosis caused by the expansion of Th/Tc22, as well as depletion of CX3CR1^hi mononuclear phagocytes resulted from the reduction of Th/Tc1, contributes to SR-Gut-aGVHD onset.

An analysis of 24,202 critical cases of COVID-19 identifies potentially druggable targets in inflammatory signalling (JAK1), monocyte–macrophage activation and endothelial permeability (PDE4A), immunometabolism (SLC2A5 and AK5), and host factors required for viral entry and replication (TMPRSS2 and RAB2A).

BRCA1–BARD1 has a role in replication fork protection that is mediated by a mechanism of phosphorylation-targeted isomerization of BRCA1 and is independent of the canonical interaction between BRCA1 and PALB2.

The CMS Collaboration reports evidence for off-shell Higgs boson contributions in the production of Z boson pairs, and measures the width of the Higgs boson, which is inversely related to its lifetime.

Mutations in the homologous recombination proteins BRCA1 and BRCA2 can sensitize cells to treatment with inhibitors of poly-ADP-ribose polymerase 1 (PARPi), but resistance to the treatment can occur. Here the authors by genome-wide CRISPR knockout and activation screens reveal novel pathways of PARPi resistance in BRCA2-deficient cells.

Neurons form synapses onto glioma cells, and depolarization of glioma membranes promotes glioma growth in vivo, whereas blocking electrochemical signalling blocks tumour growth.

The most up-to-date combination of results on the properties of the Higgs boson is reported, which indicate that its properties are consistent with the standard model predictions, within the precision achieved to date.

The CMS Collaboration reports the study of three simultaneous hard interactions between quarks and gluons in proton–proton collisions. This manifests through the concurrent production of three J/ψ mesons, which consist of a charm-quark–antiquark pair.

Fine-mapping of causal variants and integration of epigenetic and chromatin conformation data identify likely target genes for 150 breast cancer risk regions.

Protection of replication forks against nucleolytic degradation is crucial for genome stability. Here, Dhoonmoon et al identify PARP14 and the KU complex as essential regulators of fork degradation by MRE11 and EXO1 nucleases in BRCA-deficient cells.

Extensive disturbances of blue carbon ecosystems deplete soil carbon to 0.5-2 m, while limited disturbances affect only surface layers or cause minimal loss. This global synthesis refines greenhouse gas estimates for climate policy and reporting.