MUNFLA CD-F949

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A TRP channel that senses cold stimuli and menthol

AbstractA distinct subset of sensory neurons are thought to directly sense changes in thermal energy through their termini in the skin. Very little is known about the molecules that mediate thermoreception by these neurons. Vanilloid Receptor 1 (VR1), a member of the TRP family of channels, is activated by noxious heat. Here we describe the cloning and characterization of TRPM8, a distant relative of VR1. TRPM8 is specifically expressed in a subset of pain- and temperature-sensing neurons. Cells overexpressing the TRPM8 channel can be activated by cold temperatures and by a cooling agent, menthol. Our identification of a cold-sensing TRP channel in a distinct subpopulation of sensory neurons implicates an expanded role for this family of ion channels in somatic sensory detection

CKLF and IL1B transcript levels at diagnosis are predictive of relapse in children with pre‐B‐cell acute lymphoblastic leukaemia

First published: 23 February 2021Disease relapse is the greatest cause of treatment failure in paediatric B‐cell acute lymphoblastic leukaemia (B‐ALL). Current risk stratifications fail to capture all patients at risk of relapse. Herein, we used a machine‐learning approach to identify B‐ALL blast‐secreted factors that are associated with poor survival outcomes. Using this approach, we identified a two‐gene expression signature (CKLF and IL1B) that allowed identification of high‐risk patients at diagnosis. This two‐gene expression signature enhances the predictive value of current at diagnosis or end‐of‐induction risk stratification suggesting the model can be applied continuously to help guide implementation of risk‐adapted therapies.Stephen Fitter, Alanah L. Bradey, Chung Hoow Kok, Jacqueline E. Noll, Vicki J. Wilczek, Nicola C. Venn ... et al