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The authors show how Vγ1⁺ γδ T cells produce IL-4 to drive early CD8⁺ T cell and dendritic cell responses to malaria infection in mice.

Scourzic et al. show that germinal centre B cells display an enhanced ability to reprogram to induced pluripotent stem cells compared to mature B cells. This ability indicates their higher plasticity level and is T follicular helper cell-dependent.

The high-plasticity cell state (HPCS) is a critical hub that enables reciprocal transitions between cancer cell states, and targeting the HPCS may suppress cancer progression and eradicate treatment resistance.

Kathiriya et al. identify a cardiac progenitor lineage with expression of Tbx5 and anterior heart field-specific expression of Mef2c that bisects the intraventricular septum during development and show that alterations in this lineage lead to congenital heart defects in mice.

The variability in clinical outcomes of SARS-CoV-2 infection is partly due to deficiencies in production or response to type I interferons (IFN). Here, the authors describe a FIP200-dependent lysosomal degradation pathway, independent of canonical autophagy and type I IFN, that restricts SARS-CoV-2 replication, offering insights into critical COVID-19 pneumonia mechanisms.

Synthetic receptors are a powerful approach for engineering cell-based therapies that can sense and respond to their environment. Here cytokine receptor domains have been repurposed to develop engineered T cells that can sense and respond to cues associated with cancer or immune dysfunction.

The xylosyltransferase isoenzymes XT1 and XT2 catalyze the first glycosylation step in the biosynthesis of proteoglycans. Now, bump-and-hole engineering of XT1 and XT2 enables substrate profiling and modification of proteins as designer proteoglycans to modulate cellular behavior.

Specific pain-sensing nociceptors and chemosensory tuft cells form a circuit to promote type 2 immune responses in the intestine.

Researchers discovered five phases of brain rewiring across the lifespan. The eras of childhood, adolescence, adulthood, early aging, and late aging each have characteristic rewiring of structural connections across the whole brain.

This study identifies key neurocognitive domains that distinguish patients with schizophrenia from healthy individuals using machine learning. Analyzing data from 1,304 participants, it demonstrates that verbal learning and emotion identification effectively classify conditions, promoting efficient neurocognitive profiling strategies.

Zhang et al. show that bone marrow fatty acid metabolism fuels expanded leukocyte production after myocardial infarction and, based on mouse, pig and human data, suggest that lipolysis in marrow adipocytes provides fatty acids to hematopoietic stem cells.

Chemotherapeutic antifolates, such as methotrexate (MTX), impair cancer cell proliferation by inhibiting nucleotide synthesis. Here, the authors show that MTX sustains an autarkic mitochondrial one-carbon metabolism leading to serine synthesis to promote cancer cell migration and metastasis.

Ulcerative colitis (UC) is associated with epithelial metabolic derangements which exacerbate gut inflammation. Here the authors report that colonoids from children with ulcerative colitis exhibit hypermetabolism and cellular stress primarily driven by lipid dysregulation. Pharmacological inhibition of PPAR-a, a transcriptional regulator of lipid metabolism, alleviates epithelial stress and inflammation.

Shrestha et al. reveal that rice PHYTOENE SYNTHASE 2 (OsPSY2) coordinates the carotenoid-derived biosynthesis of abscisic acid and strigolactones, which independently govern iron plaque deposition and aerenchyma development, respectively.

Kalluri and colleagues use mammary carcinoma models to study the causes of metastatic organotropism and find an organ-specific role for angiopoietin 2 in driving lung metastasis through the suppression of the tight junction protein Claudin 5.

Mesocosm experiments revealed that both phytoplankton community composition and cellular acclimation influence marine particulate C:N:P ratios, with community shifts more sensitive to nitrogen supply and acclimation to the nutrient N:P supply ratio

The molecular mechanisms that regulate postnatal termination of neurogenesis remain poorly described. Here authors report Prdm16 deletion leads to the retention of radial glia in adulthood and prolonged postnatal neuroblast production.

Multimodal transcriptomics unveil the molecular dynamics of neural stem cells and their surrounding niche in the aging mouse hippocampus and provide a resource to understand age-related molecular changes.

In patients with advanced cancer, the development of brain metastasis (BM) often signals a worsening prognosis with limited therapeutic options. Here, the authors assemble a large, open-source neuroimaging dataset of BM and perform spatial and morphological analysis which they use to develop a framework for function-sparing brain radiotherapy design.

Clonal haematopoiesis of indeterminate potential is driven by somatic mutations in hematopoietic stem/progenitor cells and may progress to myelodysplastic syndromes (MDS). Here authors show that the two conditions share a similar pattern of bone marrow remodeling, characterized by the emergence of inflammatory mesenchymal stromal cells and IFN-responsive T cells, reinforcing their shared etio-pathology.

Regulation of tissue growth is crucial for development, but the underlying mechanisms remain unclear. Here, the authors identify a role for deubiquitylating enzymes in the regulation of the function of the atypical cadherin Fat and Hippo signalling.

The neural mechanisms driving seizure development in peritumoral brain regions remain incompletely defined. Here, using patient tissue, glioma mouse model, and computational simulation, the authors identify early pathological activities that are predictive of tumor-associated seizures.

The evolution of insecticide resistance in the major malaria vector, Anopheles gambiae, remains an important issue in sustainable malaria control in Africa. Here, the authors present a framework for identifying resistance mechanisms before they arise in field mosquito populations. The findings have implications for public health surveillance and vector control.

Affinity-proteomics platforms often yield poorly correlated measurements. Here, the authors show that protein-altering variants drive a portion of inter-platform inconsistency and that accounting for genetic variants can improve concordance of protein measures and phenotypic associations across ancestries.

The gut microbiota-derived metabolite indole-3-propionic acid (IPA) is found to enhance mitochondrial fatty acid and amino acid oxidation in CD4⁺ T cells. In mice, IPA-mediated metabolic reprogramming of CD4⁺ T cells exerts anti-inflammatory effects and protects against colitis.

Here the authors show that transposable element-mediated rearrangements impact more than 500 kbp of an average human genome, are a source of individual variation, a substrate for evolutionary change, and can occur through diverse mechanisms.

Childhood neuroblastoma can be separated into high and low risk groups, with prognosis depending on age at diagnosis. Here, the authors show that low and high risk neuroblastoma tumours are composed of different cell types with different malignancy potential.

Taylor et al. show that tumor cells promote white adipose tissue (WAT) wasting and cachexia by overactivation of Notch1 signaling and retinoic acid production in distant WAT endothelium, which can be therapeutically targeted to inhibit wasting.

Traumatic brain injury is associated with changes to the metabolome. Here the authors show that acute traumatic brain injury has distinctive serum metabolic patterns which may suggest protective changes of systemic lipid metabolism aiming to maintain lipid homeostasis in the brain.

Plasmacytoid dendritic cells monitor the bone marrow for apoptotic megakaryocytes (MKs) and deliver IFNα to the MK niche, triggering local on-demand proliferation and maturation of MK progenitors.

Deep brain stimulation is a neuroelectronic therapy for Parkinson’s disease. Here, the authors present the bidirectional capability of reduced graphene oxide to deliver high-density focal stimulation and to record high-fidelity signals enabling the visualization of local modulation of multiunit biomarkers.

The CMS Collaboration reports the measurement of the spin, parity, and charge conjugation properties of all-charm tetraquarks, exotic fleeting particles formed in proton–proton collisions at the Large Hadron Collider.

Using a season-long field manipulation with an established model fish system on the Great Barrier Reef, this study demonstrates that limiting motorboat activity on reefs leads to faster growth and survival of more fish offspring compared to reefs experiencing busy motorboat traffic. Noise mitigation and abatement could therefore present a valuable opportunity for enhancing ecosystem resilience.

A family of host-derived bile acid–methylcysteamine conjugates functions as FXR antagonists, forming part of a microbiota-dependent metabolic network that regulates FXR-dependent physiology.

Sick heart and vessels skew hematopoiesis toward inflammatory myeloid cells. Rhode et al. show that hypertension, atherosclerosis and myocardial infarction cause endothelial dysfunction in bone marrow (BM), which in return causes overproduction of inflammatory myeloid cells and systemic leukocytosis in mice. This process is mediated by VEGF signaling, IL-6 and versican production by the BM endothelium.

Organs develop unique vascular architectures to support physiological functions. Here, authors show that organo-typical vascular networks may arise from specific parenchymal cues activating unique endothelial subtypes and angiogenic sprouting processes.

Here, the authors exploit the genetic information encoded in Klebsiella prophages to model the interplay between bacteria, prophages, and their depolymerases, using a directed acyclic graph-model and a sequence clustering-based model.

Whilst estrogen is known to be tumorigenic in some breast cancer, in some contexts it can be protective against invasion and dissemination. Here, the authors show estrogen can promote generation of Suppressive Cortical Actin Bundles that can inhibit motility dynamics through EVL-mediated actin cytoskeletal remodeling.

A barcoded CRISPR base editing system isolates target clones from complex mammalian, yeast and bacterial populations.

An analysis of prescription medications shows that several non-antibiotic drugs, such as the heart medication digoxin, can reduce the immune response to pathogens and increase the risk of gastrointestinal infections by altering the composition of the microbiome.

The sodium-calcium exchanger (NCX1) is the primary calcium extrusion mechanism of cardiac myocytes. Here, the authors show that removal of a long questioned allosteric regulation of NCX1 by intracellular sodium alters cardiac excitation-contraction coupling.

Interact-omics, a high-throughput cytometry-based framework, resolves the cellular interaction landscape.

Gene signatures that predict response to immune checkpoint blockade (ICB) therapies in melanoma have been based on preclinical models and pre-treatment samples. Here the authors develop pathway-based signatures to predict ICB response in melanoma using on-treatment samples, leading to improved performance.

Retinal vein occlusion can cause blindness, and features neuronal dysfunction, inflammation and breakdown of vascular integrity. Here the authors report a non-apoptotic role of endothelial caspase-9 in regulating blood-retina barrier integrity and neuronal survival, which can be therapeutically targeted in a mouse model of retinal vein occlusion.

Biosynthesis of all androgens from cholesterol first requires cytochrome P450 (CYP) 11A1 for generation of pregnanes and then CYP17A1 for biosynthesis of androgens, but CYP17A1 inhibition cannot completely inhibit androgen biosynthesis in prostate cancer. Here, the authors identify a role for CYP51A1 in the biosynthesis of androgens that completely bypasses the requirement for CYP17A1 and demonstrate that CYP51A1 is essential for the biosynthesis of ¹³C-testosterone from ¹³C-cholesterol in prostate cancer cells.

Happloinsufficiency of Myc delays onset of cancers in mice. Here, the authors generated a mouse model of reversible cMyc hypomorphism and show that metronomic reduction of c-Myc in adult mice confers protection against cancers without side effects and that the bottleneck in early cancer evolution is dependent upon Myc.

Human activities affect marine predators in complex ways, yet we lack spatial understanding of cumulative impacts across key habitats. Here the authors analyse distribution and movements of eight marine predators, and find that species and human impacts vary across space and overlap within marine sanctuaries.

Engineering mammalian cellular functions requires a toolkit of orthogonal and well-characterized genetic components. Here the authors develop COMET: an ensemble of transcription factors, promoters, and accompanying models for the design and construction of genetic programs.

Tissue fluidification in invasive breast carcinoma is accompanied by mechanical stresses that compromise nuclear integrity and liberate DNA, resulting in the activation of a pro-inflammatory response that shape tumour evolution and progression.