Search

The replication stress response ensures genomic stability throughout DNA duplication. Here, the authors show that VCP/p97 extracts the DNA polymerase α/Primase complex from chromatin, preventing excessive priming in the lagging strand and reducing the activation of the replication stress response.

Yeast surface display technology enables real-time monitoring and effective screening of libraries of millions of disulfide-cyclised peptides against diverse protein targets. Selected ligands are characterised rapidly and quantitatively without the need for chemical synthesis and purification.

Chronic care manages long-term, progressive conditions, while acute care handles short-term ones. Here, authors show chronic conditions account for most of the global health burden, with 68% of DALYs and 93% of YLDs attributed to chronic care needs.

Women of reproductive age may have specific concerns relating to perceived impacts on fertility and menstrual cycles that make them hesitant to receive COVID-19 vaccination. In this study, the authors explore COVID-19 vaccine uptake rates in women of reproductive age using linked data for ~13 million women in England.

A parallel experimental and computational approach was used to predict and prepare intercalated, layered hybrid perovskites, highlighting the breadth and flexibility of intercalation.

ACTA2 p.R179 variants cause pediatric strokes due to moyamoya disease (MMD)-like occlusions. Here, the authors show that Acta2^R179C/+ smooth muscle cells are immature, causing MMD-like lesions that are reversed by altering cellular metabolism.

Here, the authors report on the thermal and mechanical properties of Ruddlesden-Popper phases (Ban+1ZrnS3n+1, n = 2 and 3) of a perovskite chalcogenide (BaZrS3) that push to extreme limits and defy the century-old relation between thermal conductivity and interatomic bond strength.

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.

The activation and infiltration of immune cells to the vasculature is intimately linked to the immunopathology of hypertension. Here the authors implicate PI3Kγ signalling in the trafficking of CD8⁺ T cells between lymphoid and non-lymphoid organs, and the development of hypertension in a murine model.

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

Impaired gut barrier function is a central driver of alcohol-related liver disease. This study indicates that the postbiotic ReFerm® improves gut barrier function and reduce liver stiffness and liver fibrosis, suggesting the gut barrier function as a potential treatment target.

Silencing of endogenous retroviral elements (ERVs) is mediated by KAP1. Here, the authors describe the molecular mechanism by which KAP1 induces structural reorganization and multimerization of HP1α and maintains inaccessible chromatin at ERVs in mouse embryonic stem cells.

Pocock et al. reveal that transient activation of 5′ AMP-activated protein kinase and estrogen-related receptor drives robust maturation of multicellular human cardiac organoids, enabling modeling of desmoplakin cardiomyopathy dysfunction, which could be rescued using the bromodomain and extra-terminal inhibitor INCB054329.

Structural, pharmacological and computational studies reveal how different classes of positive allosteric modulators bind to distinct allosteric sites and use noncanonical mechanisms to activate the free-fatty acid receptor FFA2.

Low formate dehydrogenase (FDH) activity limits formate assimilation via the synthetic reductive glycine pathway. In this study, the authors introduce a faster FDH in synthetic formatotrophic E. coli, which boosts growth rates and bioproduction titers from formate as sole carbon source.

How signaling pathways recruit SWI/SNF chromatin remodeling complexes is not known. Here the authors suggest a ubiquitin directed mechanism targeting SWI/SNF for Wnt pathway dependent transcription, important for development and cancer.

Natural Killer cells are key mediators of anti-tumour immunosurveillance and anti-viral immunity. Here, the authors map regulatory genetic variation in primary Natural Killer cells, providing new insights into their role in human health and disease.

Analysis combining multiple global tree databases reveals that whether a ___location is invaded by non-native tree species depends on anthropogenic factors, but the severity of the invasion depends on the native species diversity.

Tracking biomolecules in living cells requires fast but gentle labeling. Here, authors introduce inCu-click, a DNA-conjugated ligand that localizes copper to enable efficient intracellular CuAAC, allowing live-cell fluorescent labeling of lipids and proteins without toxicity.

Preeclampsia is a leading cause of morbidity and mortality in pregnancy and has multiple causes. Here the authors examine how changes in the gut microbiota alter pregnancy outcome and show changes in fetal reabsorption along with reduction in placental NK cell IFN-γ production accompanied by perturbation of placental carbohydrate metabolism.

POLG mutations impair mitochondrial DNA replication and cause diverse mitochondrial diseases. Here, the authors show that structural differences in the POLγB subunit between humans and mice modulate mutation severity.

Whether multimorbidity accelerates brain Aβ deposition in humans remains largely unknown. Here, the authors demonstrate that higher self-reported multimorbidity burden predicts increased brain Aβ accumulation rates in the ADNI cohort.

Transcription-replication conflicts (TRCs) promote tumor aggressiveness by affecting genome stability. Here, the authors identify ANP32E as driver of TRCs in breast cancer, causing R-loop accumulation and genomic instability, which elicit vulnerability to ATR inhibition.

This work identified immune signatures of COVID-19 including broad Interferon signatures that are unique to infants. Compared with infected adults, infants display similar Interferon signatures in monocytes but enhanced signatures in T and B cells.

Human proteases TMPRSS2 and TMPRSS11D can be highjacked to mediate cell entry of respiratory viruses. This study examines the biochemical and structural basis of TMPRSS11D auto-activation and substrate specificity, informing peptidomimetic inhibitor development.

Stem cell interactions involve biochemical and biophysical cues, but the transcriptional control of biophysical traits is unclear. This study identifies ETVs as regulators of adhesion in hPSCs and pancreatic progenitors, shaping lineage decisions.

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.

This work presents SUM-seq, an ultra-high-throughput method for co-profiling chromatin accessibility and gene expression in single nuclei across multiplexed samples, advancing the study of gene regulation in diverse biological systems.

An expert-elicitation process identifies current methodological barriers for monitoring terrestrial biodiversity, and how technological and procedural development of robotic and autonomous systems may contribute to overcoming these challenges.

In CHIP, somatic mutations in a hematopoietic stem cell lead to a clonal subpopulation of blood cells. Here, the authors perform a CHIP meta-EWAS to establish its epigenetic features and age-related outcomes.

Ten people who mattered this year.

Here authors demonstrate Ziapin2, a membrane-targeted photoswitch, reinstates physiological ON/OFF light responses in retinal ganglion cells from degenerate retinas, and restores light-driven behavior and optomotor reflexes in fully blind rd10 mice.

Liver macrophages are a major obstacle to extrahepatic drug delivery. This study identifies the receptor–ligand interactions that they use to capture circulating nanoparticles and leverages this understanding to engineer nanoparticles that escape macrophage uptake.

Roeck et al. show that ferroptosis spreads between neighboring cells via lipid peroxidation across adjacent membranes. Cell contact and extracellular iron are key factors, highlighting a potential mechanism for tissue necrosis propagation.

In this work, the authors performed a single-cell genotyping and transcriptomics analysis, revealing cell-type-specific and nonautonomous effects of mTOR pathway mutations in mosaic focal cortical dysplasia.

Monkeypox virus genomic data from Nigeria and Cameroon, sampled between 2018 and 2023, indicate that the virus spread through repeated zoonoses in Cameroon, whereas in Nigeria, it spread mainly through human–human transmission, predominantly originating in Rivers State.

DeepSPT is a deep learning framework for the automated temporal analysis of behavior in 2D and 3D single-particle tracking. After extensive validation, DeepSPT was shown to work on diverse subcellular tracking, mapping and classification applications.

The authors show that brain inflammation in COVID-19 correlates with viral load, systemic inflammation and virus-sensing pattern recognition receptors. Microglial dysfunction occurs at sites of vascular inflammation with myelin injury and synapse loss.

Kao et al. provide insight into the metabolic requirements of IL-17A-producing γδ T cells, offering an actionable target to treat psoriasis by inhibiting fatty acid synthesis.

Here, the authors use single-cell spatial transcriptomics to profile the airway wall landscape in health and during asthma. Discrete proinflammatory ecosystems containing alarmins, chemokines and a unique combination of stromal cells were identified in healthy individuals, and these were spatially dysregulated in asthma.

Immune checkpoint blockade activates T cell immunity by reprogramming the STAT3 and STAT5 transcriptional pathways in dendritic cells, and STAT3 degradation is effective for treating tumours of multiple cancer types in mouse models.

Dendritic cell-based therapies have been exploited as immunotherapeutic approaches for cancer treatment. Here the authors report a platform integrating antigen-capturing nanoparticles and type 1 conventional dendritic cells for in situ cancer immunization, promoting anti-tumor immunity in preclinical models.

Cells change gene expression in response to stress to promote survival. Here, the authors map the transcriptional dynamics of osmoadaptation in yeast, showing that isogenic populations respond to stress using different transcriptional strategies.

Previous work has identified a link between obesity and breast cancer metastasis. Here, using preclinical mouse models, the authors show that high-fat diet promotes platelet and endothelial cell activation in the lungs resulting in the development premetastatic niches, enhancing tumor cell homing and metastasis.