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Here Schwämmle et al. develop CRISPR reporter screens to map transcription-factor-regulatory element interactions at the Xist locus, revealing a two-step mechanism integrating developmental and X-dosage signals to initiate X-chromosome inactivation.

Transcription factors shape cell identity, but mapping their genomic targets remains challenging. Here the authors present DynaTag, a modified CUT&Tag method for profiling TF occupancy in bulk and single cells, and apply it to assess changes in TF activity in SCLC tumours following chemotherapy.

Treatment of Clostridioides difficile infections (CDI) with vancomycin is associated with high relapse rates. In this study, the experimental glycopeptide antibiotic EVG7 was found to effectively treat CDI without relapse in a murine model of recurrent CDI.

Small cell lung cancer cells form functional synapses with glutamatergic neurons, receiving synaptic transmissions and deriving a proliferative advantage from these interactions.

Proteomic data from natural isolates of Saccharomyces cerevisiae provide insight into how these cells tolerate aneuploidy (an imbalance in the number of chromosomes), and reveal differences between lab-engineered aneuploids and diverse natural yeasts.

The GAIN domain of adhesion G protein-coupled receptors, a class of biological mechanosensors, was thought to be sufficient for its self-cleavage. Here, the authors show that the event also depends on the seven-transmembrane region of the receptors.

Studies in mice show that acute stress activates hyperglycaemia via activation of a medial amygdala–ventral hypothalamic circuit that controls glucose metabolic responses in the liver, independently of adrenal and pancreatic hormones.

Human transplantation with allogeneic donor organs results in non-matching of MHC and differential presentation of T cell antigens. Here the authors show that in a lung transplanted SARS-CoV-2 infected patient T cell responses generated from the host may not be able to recognise infected cells within the graft and this may contribute to virus persistence.

Embryonal tumour with multilayered rosettes (ETMR) is a rare and aggressive paediatric brain tumour. Here, the authors analyse intratumour heterogeneity and the tumour microenvironment in ETMR using single-cell and spatial transcriptomics, in vitro cultures, and a 3D forebrain organoid model, finding important aspects – such as the communication with pericytes – for ETMR development and response to therapy.

In this Protocol, three dual adeno-associated viral strategies for delivery of large transgenes are presented—by reconstitution at the genomic, transcript or protein level—together with instructions for the design, production and evaluation of dual adeno-associated viral vectors.

The slit diaphragm is a key component of the glomerular filter. This study reveals that the slit diaphragm of Drosophila nephrocytes exhibits a fishnet architecture, offering insights into the molecular basis of renal filtration.

Glyphosate pollution of water bodies so far has exclusively been attributed to herbicide applications, but analysis of the half-life of the aminomonophosphonate as well as usage rates suggests that this may be an incomplete explanation. Here, the authors show that glyphosate is a stable transformation product of diethylenetriamine penta(methylenephosphonate) (DTPMP), a chelating agent widely used in household and industrial applications.

The authors introduce the Neurolipid Atlas, a dynamic resource for the community to gain insight into lipid alterations in neurodegenerative disease, and they leverage the platform to show how cholesterol alterations in astrocytes can dysregulate neuroinflammatory pathways in Alzheimer disease.

This study reveals widespread mosaic mutations in early human placentas, showing that genetic variation arises and expands over gestation. The findings highlight the importance of confirmatory testing when using placental tissue for prenatal diagnosis.

Federated learning (FL) algorithms have emerged as a promising solution to train models for healthcare imaging across institutions while preserving privacy. Here, the authors describe the Federated Tumor Segmentation (FeTS) challenge for the decentralised benchmarking of FL algorithms and evaluation of Healthcare AI algorithm generalizability in real-world cancer imaging datasets.

The enzymatic breakdown of the lipid sphingomyelin is associated with various infectious diseases. Here, the authors introduce trifunctional sphingomyelin derivatives for the visualisation of sphingomyelin distribution and sphingomyelinase activity in infection processes.

Augmin is essential for microtubule nucleation during cell division. This study reveals how the conserved calponin homology domain of the augmin subunit HAUS6 binds to microtubules to orient augmin for microtubule branching.

Sarcomas are a group of mesenchymal malignancies which are molecularly heterogeneous. Here, the authors develop an in vivo muscle electroporation system for gene delivery to generate distinct subtypes of orthotopic genetically engineered mouse models of sarcoma, as well as syngeneic allograft models with scalability for preclinical assessment of therapeutics.

Striatal neural circuits control reward-associated behaviors but the role of astrocytes is still unclear. Here, the authors show that chemogenetic manipulation of striatal astrocyte in mice restore obesity-associated cognitive defect and exert a control on whole-body metabolism.

Gross et al. show that Atg13 and Atg17 are dispensable for pexophagy during phosphate starvation in yeast. Instead, the metabolite sensor Pho81 binds the Atg1 kinase complex via Atg11 to promote Atg11 phosphorylation by Atg1 and pexophagy.

Activation of G_s signaling at mitochondria by mitoDREADD-G_s increases mitochondrial metabolism, leading to better memory in mouse models of dementia, directly linking brain mitochondrial deficits to cognitive symptoms of neurodegenerative diseases.

Analyzing Feret diameter is a straightforward way to assess the quality of unguided brain organoids. Low-quality brain organoids show a high Feret diameter, accompanied by a higher proportion of unintended mesenchymal cells.

Amyloid fibrils can adopt a range of distinct conformations, yet it is challenging to rapidly discriminate between these polymorphs. Now methods have been developed to screen large, diverse libraries of turn-on fluorescent dyes to rapidly identify probes that recognize fibril subsets.

Single, self-amplifying RNA molecules condensed by an oppositely charged polyelectrolyte self-assemble into compact globular nanoparticles that can be used as vaccines to generate potent immunological responses at low doses.

Bat influenza viruses use MHCII, not sialic acids, for entry. Using high-resolution microscopy. on live cells, the authors show at the nanoscale that viral particles attach to clusters of MHCII. and attract additional molecules to the attachment site.

Pathology-oriented multiplexing (PathoPlex) represents a framework for widespread access to multiplexed imaging and computational image analysis of clinical specimens at a relatively high throughput and subcellular resolution.

Using viral barcode tracing to detect interactions between glioblastoma cells and non-malignant astrocytes in patient samples, investigators discovered a pathway that reduces tumour-specific immunity and identified potential therapeutic targets.

New biomarkers are required to improve the assessment of aortic wall integrity and risk of rupture. Here the authors report the development of an imaging probe for ADAMTS4, which they test in an abdominal aortic aneurysm mouse model and show in vivo prediction of aneurysm and rupture.

It is unclear how cell compartmentalization emerged in prebiotic conditions. Now it is shown that a temperature gradient in a confined space can bring the core components of a cell together.

B cell maturation antigen (BCMA) has long been viewed as essential for plasma cell survival via APRIL-mediated signalling. Here, using two independent BCMA-deficient mouse models, the authors show that both the generation and long-term maintenance of plasma cells are unaffected by BCMA deficiency, and these plasma cells express normal levels of survival genes, thereby overturning the prevailing paradigm of the APRIL–BCMA axis as critical for plasma cell longevity.

Hypothalamus participates in systemic metabolic processes, while high calorie intake increases immune activation in the central nervous system. Here the authors show that reduced regulatory T cells in the hypothalamus contribute to elevated immune activation in a high calorie environment, thereby prompting a potential therapy target for metabolic diseases.

The epigenetic and transcriptional roles of Nucleoporin 98 (NUP98) fusion oncoproteins in driving pediatric acute myeloid leukemia (AML) remain to be explored. Here, the authors identify a core set of genes regulated by NUP98::KDM5A and suggest CDK12 as a potential therapeutic vulnerability.

Multidrug-resistant pathogens have become increasingly common in hospital settings. Here, the authors investigate the efficacy of adjunctive antibiotic and phage therapy in a human cell model and a murine model of ventilator-associated pneumonia.

By using cryo-EM and biochemical assays, Loeff et al. reveal the mechanistic basis for the protective function of the oxidoreductase PYROXD1 that maintains the activity of the tRNA ligase complex under aerobic conditions.

Recent studies show that targeting CXCL12 can improve the effect of radiotherapy (RT) in preclinical models of glioblastoma (GBM). Here, the authors report the safety and preliminary efficacy of a phase I/II clinical trial investigating an L-RNA aptamer-based CXCL12 inhibitor (NOX-A12) in combination with RT in patients with newly-diagnosed GBM.

Maturation of innate immune cells is a graded stereotypic process which is often conserved across species. Here authors label distinct neutrophil leukocyte developmental stages via generating combinations of transgenic zebrafish reporter strains, followed by transcriptome analysis of different neutrophil maturation stages and comparison to the gene expression profile of developing neutrophils from humans and mice.

The enzymatic activity of caspase-8 controls apoptosis, necroptosis and pyroptosis, and prevents tissue damage during embryonic development and adulthood in mice.

Detailed mapping of the distribution of water and semiheavy water in the coma of Halley-type comet 12P implies a D/H ratio that is consistent with that of Earth’s water, indicating a common heritage.

Cytoskeletal breakdown is a hallmark of synapse elimination. Here, the authors show that a post-translational modification on microtubules encodes activity-dependent signals instructing neuronal remodeling in the central and peripheral nervous system.

Tim17 contains conserved negative charges close to the intermembrane space side of the bilayer, which are essential to initiate presequence protein translocation along a distinct transmembrane cavity of Tim17 for both classes of preproteins.

Cellular senescence plays a crucial role in cancer therapy, influencing how tumours respond to treatment. Here, the authors show that therapy-induced senescence in B-cell lymphoma leads to myeloid-like plasticity, enhancing T-cell recognition and improving patient outcomes.