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Understanding of diffusive and spreading processes in networks remains challenging when dynamics of the network is complex. The authors propose a quantity to reflect the potential of a network node to diffuse information, that may serve to develop interventions for improved network efficiency.

The QT interval is a heritable electrocardiographic measure associated with arrhythmia risk when prolonged. Here, the authors used a series of genetic analyses to identify genetic loci, pathways, therapeutic targets, and relationships with cardiovascular disease.

Fifteen years’ follow-up of clinical development and real-world data from 43 patients show that gammaretroviral gene therapy for adenosine deaminase deficiency has a positive long-term efficacy profile, warranting continued safety monitoring of patients receiving gene therapy.

In neural progenitor cells, recurrent DNA break clusters (RDCs) occur to genes crucial for brain function. Here the authors find that most RDCs emerge at long-traveling unidirectional replication forks, and often unrelated to R-loops.

Glioblastoma multiform (GBM) is a common and aggressive type of primary brain cancer that currently has no effective therapy. Here, the authors show, using a mouse GBM model and EGFRvIII-targeting chimeric antigen receptor (CAR)-T cells, that Intratumoral injection of interleukin-12 helps condition the microenvironment and promote anti-tumor immunity.

Changes in climate preconditioned large-scale, recurrent Miocene to Pleistocene Antarctic submarine landslides through variations in biological productivity, ice proximity and ocean circulation, posing tsunami risk to Southern Hemisphere populations.

Wnt signaling is necessary for colorectal cancer tumorigenesis and stem cell maintenance. Here, the authors identify MEK1/2 inhibitors as potent activators of Wnt/β-catenin signalling and show that clinically approved MEK inhibitors inadvertently induce stem cell plasticity in colorectal cancer

Astrocytes can have protective or detrimental effects on neurons during injury, but the molecular mechanisms that determine these different states are unresolved. Here the authors identify a pathway via neuronal EphB1 that induces neuroprotective signalling in astrocytes through ephrin-B1 mediated STAT3 activation, which is impaired in models of amyotrophic lateral sclerosis.

An analysis of 16 health-related quantitative traits in approximately 350,000 individuals reveals statistically significant associations between genome-wide homozygosity and four complex traits (height, lung function, cognitive ability and educational attainment); in each case increased homozygosity associates with a decreased trait value, but no evidence was seen of an influence on blood pressure, cholesterol, or ten other cardio-metabolic traits.

High-quality gRNA activity data is needed for accurate on-target efficiency predictions. Here the authors generate activity data for over 10,000 gRNA and build a deep learning model CRISPRon for improved performance predictions.

Engineered T cells are used for tumour immunotherapy but can have side effects and need multiple treatment rounds. Here during expansion of T cells from patients, the authors use an inhibitor of the epigenetic regulator G9a/GLP and show that this increases T cell cytotoxic function and tumour reduction in vitro and in vivo respectively.

Extracellular vesicles decorated with an antibody-binding moiety specific for the fragment crystallizable domain can be used as a modular delivery system for targeted cancer therapy.

This study performs a systematic review of empirical evidence for climate change adaptation in coastal cities around the world. It found that reported adaptation is mostly slow, narrow, and not transformative as coastal cities predominantly focus their adaptation on past and current challenges, and not future scenarios of risk.

The biosynthesis of N⁶-threonylcarbamoylated adenosine 37 in tRNA (t⁶A) involves the YRDC enzyme and the KEOPS complex. Here, the authors report mutations in YRDC and the KEOPS component GON7 in Galloway-Mowat syndrome and determine the crystal structure of a GON7-containg subcomplex that suggests a role in KEOPS complex stability.

The poor correlation between brain Aβ deposition and clinical symptoms in Alzheimer´s disease remains puzzling. Here, the authors show a temporal dissociation of Aβ deposition and neurodegeneration.

Here the authors apply machine learning approaches to Alzheimer’s genetics, confirm known associations and suggest novel risk loci. These methods demonstrate predictive power comparable to traditional approaches, while also offering potential new insights beyond standard genetic analyses.

Surfaces have an important role in solid–liquid phase transformations, but whereas melting is normally observed at surfaces, freezing usually originates in the bulk. Computational studies now predict surface-induced nucleation in supercooled liquid silicon and germanium, and the proposed nucleation mechanism could prove to be relevant for other tetrahedrally coordinated systems.

Genomic integration of an adeno-associated virus vector in a mouse model of Angelman syndrome unsilences paternal Ube3a and rescues anatomical and behavioural phenotypes, suggesting a pathway towards the treatment of this neurodevelopmental disorder.

Here the authors report the cryo-EM structure of heart-derived fibrils of an AL amyloidosis patient. Surprisingly, the fibrils form helical superstructures with collagen VI, potentially signifying a distinct pathophysiological mechanism for amyloidoses.

Human natural killer T (NKT) cells have been proposed as a cellular platform for CAR engineering. Here the authors report that IL-12 engineering reprograms CAR-expressing NKT cells to long-lived Th1-polarized cells with potent anti-tumor activity in leukemia and neuroblastoma preclinical models.

Thorough evaluation of CRISPR RNA-guided nucleases off-targets in cells is required for advancing gene therapies. Here the authors report SURRO-seq for the simultaneous investigation of thousands of off-target sites for therapeutic RNA-guided nucleases in cells.

Leukaemia therapy may benefit from the use of antigens that are less restricted to individual donors. Here the authors engineered T cells with a TCR specific for a CD1c restricted lipid leukaemia antigen and show that they can protect against disease progression in mouse leukaemia xenograft models.

Patterson, Firulyova, et al. report that TREM2 is a key regulator of foamy macrophage differentiation. Myeloid-specific deletion of Trem2 caused increased macrophage susceptibility to cholesterol-mediated toxicity and cell death and significantly attenuated atherosclerotic plaque progression in mice.

Sequence analysis identifies gain-of-function somatic mutations in GNA11 or GNAQ in CTNNB1-mutant aldosterone-producing adenomas. Most patients with these mutations presented during puberty, pregnancy or menopause, with elevated LHCGR expression.

A paper reports the development of a universal tool for studying cellular interactions in biological systems, and demonstrates its coupling with single-cell transcriptomics methods to provide insights into the biology of the interactions.

Tyrosine kinases are promising therapeutic targets in multiple cancer types; however, the formation and selection of tyrosine kinase fusions are not fully understood. Here, the authors develop a genome-wide fusion sequencing platform and identify mechanisms and patterns of fusion formation that have implication for targeted therapy.

Extrachromosomal circular DNAs (eccDNAs) affect gene expression and tumour progression. Here, the authors report a method, scCircle-seq, for eccDNA profiling in single cells, demonstrating the stochasticity, cell type specificity, and dynamics of eccDNAs in cell lines and primary tumour samples.

HSC mutations lead to diverse clonal hematopoiesis outcomes. This study shows how epigenetic traits can predispose clones for dominance. Sox4 increases sensitivity to Tet2 KO, offering insights into variable phenotypes despite identical mutations.

The kinetics and thermodynamics of the nucleation of magnetite crystals from primary particles are shown to be described by colloidal assembly theory, allowing for predictions of crystal sizes to be made.

Genetic variants associated with susceptibility to pancreatic cancer have been identified using genome wide association studies (GWAS). Here, the authors combine data from over 9000 patients and perform a meta-analysis to identify five novel loci linked to pancreatic cancer.

Little is known about people’s preferred responses to norm violations across countries. Here, in a study of 57 countries, the authors highlight cultural similarities and differences in people’s perception of the appropriateness of norm violations.

Myoglobin is a hemeprotein that reversibly binds oxygen and gives muscle its red color. Here, the authors report a genetic variant in the MB gene that associates with myoglobinopathy, an autosomal dominant progressive myopathy, and altered oxygen binding properties of the mutant protein.

Optical coherence microscopy with AI assisted algorithms is used to track organoids and their viability longitudinally. Photoacoustic imaging adds rare cell detection function to the 3D cell culture analysis toolbox.

The pathogenic function of XBP1-expressing astrocytes in experimental autoimmune encephalomyelitis and multiple sclerosis have been studied using FIND-seq, a new method combining microfluidics cytometry, PCR-based detection of nucleic acids and cell sorting for in-depth single-cell transcriptomics analyses of rare cells.

Replication fork degradation can result in genome instability. Here authors reveal a role for Rif1 protein in protecting stalled replication forks from undergoing extensive, DNA2-dependent, degradation.

The species threat abatement and restoration (STAR) metric quantifies the contributions that abating threats and restoring habitats offer towards reducing species’ extinction risk in specific places.

Comparison of non-invasive [¹¹C]metomidate PET-CT with adrenal vein sampling for predicting biochemical remission of primary aldosteronism showed non-superiority, suggesting that the non-invasive method is suitable for the diagnosis of unilateral primary aldosteronism.

The emergency of a high frequency of early memory T cells has been associated with clinical success of CAR T cell therapy. Here the authors show that target cancer cells stressed by disulfiram/copper complexes and ionizing radiation favour the reprogramming of CAR T cells that acquire memory-like characteristics, associated with prolonged anti-tumor response in preclinical solid tumor models.

A sex-distorter gene drive causes population collapse in the malaria mosquito.

Oncogene-induced senescence (OIS) is a barrier to tumour progression. Here the authors identify the long non-coding RNA MIR31HG as a regulator of cellular senescence using the oncogene-induced senescence triggered by B-RAF expression in immortalized fibroblasts.

Adoptive cell transfer (ACT) of T cells for tumor treatment often requires IL-2 administration. Here, the authors show that a modified IL-2 cytokine (NKTR-214) can outperform IL-2 in a melanoma mouse model.

Mammalian genomes are scattered with repetitive sequences, but their biology remains largely elusive. Here, the authors show that transcription can initiate from short tandem repetitive sequences, and that genetic variants linked to human diseases are preferentially found at repeats with high transcription initiation level.

IgE antibodies have shown anti-tumor activity, even superior to IgG, in preclinical models. However, all monoclonal antibodies in clinical use for cancer therapy are members of the IgG class. Here the authors report the results of a phase I clinical trial of a chimeric monoclonal IgE antibody, specific for the folate receptor-alpha, in patients with advanced solid cancer.

High-resolution molecular spectroscopy with cryogenic setups is hampered by the lack of a skilled interrogation tool. Here, the authors demonstrate absolute metrology of cold rovibrational spectra at 1 kHz accuracy level, by coupling a Lamb-dip saturated-absorption cavity ring-down spectrometer to a buffer-gas cooling source.

The causes of ALS remain unclear with many proposed pathomechanisms. Here, the authors integrate iPSC-derived motor neuron and post-mortem datasets and identify a heightened DNA damage response accompanied by accumulation of somatic mutations in ALS.

The authors identify a set of microRNAs regulated by EGFR and MET that are involved in the oncogenic signaling exerted by these receptors and also modulate the response of tumors to targeted EGFR inhibition. These results shed light on the known contribution of MET to therapy resistance and suggest that MET-regulated microRNAs can be key mediators of its effects and potential markers of clinical utility.

Phase 1 trial results reveal that intrathecal transplantation of human fetal neural precursor cells in patients with progressive multiple sclerosis is feasible, safe and tolerable.

Genomic and epidemiological analysis of carbapenem-resistant Klebsiella pneumoniae across Europe finds increased transmissibility of four clonal lineages, especially between hospitals within countries.

Chiea Chuen Khor, Tin Aung and colleagues report the results of a large genome-wide association study of primary angle closure glaucoma. They identify five new susceptibility loci and provide insights into disease pathogenesis.