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Researchers have identified a mechanism by which multidrug-resistant Salmonella Typhimurium strains evade immune system detection. The strains recently emerged in sub-Saharan Africa and are a major cause of ill-health and death in the region. Harnessing this mechanism may offer a therapeutic strategy to improve immunity
From pioneer to repressor: Bimodal foxd3 activity dynamically remodels neural crest regulatory landscapein vivo
The neural crest (NC) is a transient embryonic stem cell population characterised by its multipotency and broad developmental potential. Here, we perform NC-specific transcriptional and epigenomic profiling of foxd3 -mutant versus wild type cells in vivo to define the gene regulatory circuits controlling NC speci…
The spatiotemporal distribution of human pathogens in ancient Eurasia.
Infectious diseases have had devastating effects on human populations throughout history, but important questions about their origins and past dynamics remain1. To create an archaeogenetic-based spatiotemporal map of human pathogens, we screened shotgun-sequencing data from 1,313 ancient humans…
Fedratinib combined with ropeginterferon alfa-2b in patients with myelofibrosis (FEDORA): study protocol for a multicentre, open-label, Bayesian phase II trial.
BACKGROUND: Myelofibrosis (MF) is a clonal haematopoietic disease, with median overall survival for patients with primary MF only 6.5 years. The most frequent gene mutation found in patients is JAK2V617F, causing constitutive activation of the kinase and activation of downstream signalling. Fedratinib is a…
SFX-01 is therapeutic against myeloproliferative disorders caused by activating mutations in Shp2.
Activating mutations of Src homology-2 domain-containing protein tyrosine phosphatase-2 (Shp2) cause multiple childhood conditions for which there is an unmet therapeutic need, including juvenile myelomonocytic leukemia (JMML) and Noonan syndrome. SFX-01, an α-cyclodextrin-stabilized sulforaphane com…
Making it Personal - play script
Making it Personal is an innovative public and community engagement with research project at the University of Oxford. Theatre offers a unique platform to “set the scene” on an emotional and personal level, highlighting how individuals process risk and medical information—often in ways that differ significantly…
Tumor-Infiltrating Clonal Hematopoiesis.
BACKGROUND: Clonal hematopoiesis of indeterminate potential (CHIP) is an age-related condition associated with increased mortality among patients with cancer. CHIP mutations with high variant-allele frequencies can be detected in tumors, a phenomenon we term tumor-infiltrating clonal hematopoiesis (TI-C…
Predictive Performance of Cardiovascular Risk Scores in Cancer Survivors From the UK Biobank.
BACKGROUND: Cardiovascular preventive strategies are guided by risk scores with unknown validity in cancer cohorts. OBJECTIVES: This study aimed to evaluate the predictive performance of 7 established cardiovascular risk scores in cancer survivors from the UK Biobank. METHODS: The predictive perfor…
Early NK-cell and T-cell dysfunction marks progression to severe dengue in patients with obesity and healthy weight.
Dengue is a mosquito-borne virus infection affecting half of the world's population for which therapies are lacking. The role of T and NK-cells in protection/immunopathogenesis remains unclear for dengue. We performed a longitudinal phenotypic, functional and transcriptional analyses of T and NK-c…
Plants monitor the integrity of their barrier by sensing gas diffusion.
Barrier tissues isolate organisms from their surrounding environment. Maintaining the integrity of the tissues is essential for this function. In many seed plants, periderm forms as the outer barrier during secondary growth to prevent water loss and pathogen infection1. The periderm is regenerated when its i…
Detecting and quantifying clonal selection in somatic stem cells.
As DNA variants accumulate in somatic stem cells, become selected or evolve neutrally, they may ultimately alter tissue function. When, and how, selection occurs in homeostatic tissues is incompletely understood. Here, we introduce SCIFER, a scalable method that identifies selection in an individual tissue, with…