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Typical development of synaptic and neuronal properties can proceed without microglia in the cortex and thalamus.
Nat Neurosci
January 2025
Centre for Discovery Brain Sciences, University of Edinburgh, Edinburgh, UK.
Brain-resident macrophages, microglia, have been proposed to have an active role in synaptic refinement and maturation, influencing plasticity and circuit-level connectivity. Here we show that several neurodevelopmental processes previously attributed to microglia can proceed without them. Using a genetically modified mouse that lacks microglia (Csf1r), we find that intrinsic properties, synapse number and synaptic maturation are largely normal in the hippocampal CA1 region and somatosensory cortex at stages where microglia have been implicated.
View Article and Find Full Text PDFThe Challenges and Lessons Learned Building a New UK Infrastructure for Finding and Accessing Population-Wide COVID-19 Data for Research and Public Health Analysis: The CO-CONNECT Project.
J Med Internet Res
November 2024
School of Medicine, University of Nottingham, Nottingham, United Kingdom.
The COVID-19-Curated and Open Analysis and Research Platform (CO-CONNECT) project worked with 22 organizations across the United Kingdom to build a federated platform, enabling researchers to instantaneously and dynamically query federated datasets to find relevant data for their study. Finding relevant data takes time and effort, reducing the efficiency of research. Although data controllers could understand the value of such a system, there were significant challenges and delays in setting up the platform in response to COVID-19.
View Article and Find Full Text PDFAssociations between sex and lifestyle activities with cognitive reserve in mid-life adults with genetic risk for Alzheimer's disease.
Alzheimers Res Ther
November 2024
Trinity College Institute of Neuroscience, School of Psychology, Trinity College Dublin, Dublin, Ireland.
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Autoinflammation in patients with leukocytic CBL loss of heterozygosity is caused by constitutive ERK-mediated monocyte activation.
J Clin Invest
October 2024
Laboratory of Human Genetics of Infectious Diseases, Necker Hospital for Sick Children, Paris, France.
Patients heterozygous for germline CBL loss-of-function (LOF) variants can develop myeloid malignancy, autoinflammation, or both, if some or all of their leukocytes become homozygous for these variants through somatic loss of heterozygosity (LOH) via uniparental isodisomy. We observed an upregulation of the inflammatory gene expression signature in whole blood from these patients, mimicking monogenic inborn errors underlying autoinflammation. Remarkably, these patients had constitutively activated monocytes that secreted 10 to 100 times more inflammatory cytokines than those of healthy individuals and CBL LOF heterozygotes without LOH.
View Article and Find Full Text PDFPlasma exchange does not improve overall survival in patients with acute liver failure in a real-world cohort.
J Hepatol
October 2024
Leeds Liver Unit, Leeds NHS Teaching Hospitals Trust, Leeds, UK; Leeds Institute for Medical Research, University of Leeds, Leeds, UK. Electronic address:
Background & Aims: Therapeutic plasma exchange (PEX) has emerged as a potential treatment option for patients with acute liver failure (ALF). The effect of PEX on survival outcomes outside of clinical trials is not yet well established. In this study we aimed to evaluate the real-world use and outcomes of PEX for the treatment of ALF.
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