Publications by authors named "D H Wyllie"
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 PDFMutations in SYNGAP1 are a common genetic cause of intellectual disability (ID) and a risk factor for autism. SYNGAP1 encodes a synaptic GTPase-activating protein (GAP) that has both signaling and scaffolding roles. Most pathogenic variants of SYNGAP1 are predicted to result in haploinsufficiency.
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- Mutations in the CDKL5 gene, associated with severe neurological disorders, lead to issues like early-onset epilepsy, autism, and intellectual disability, prompting this study to explore their impact on hippocampal function.
- Using a rat model with a specific loss of function mutation, the researchers conducted various electrophysiological and biochemical assessments to understand how the absence of CDKL5 affects synaptic behavior in the brain.
- The findings revealed enhanced long-term potentiation in juvenile Cdkl5 rats without altering NMDA receptor function or silent synapse formation, suggesting CDKL5 plays a crucial role in maintaining normal synaptic plasticity in the hippocampus.
In recent times, pathogen genome sequencing has become increasingly used to investigate infectious disease outbreaks. When genomic data is sampled densely enough amongst infected individuals, it can help resolve who infected whom. However, transmission analysis cannot rely solely on a phylogeny of the genomes but must account for the within-host evolution of the pathogen, which blurs the relationship between phylogenetic and transmission trees.
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- - Adenoviral-vectored vaccines have been successfully used for SARS-CoV-2 and Ebola, but their effectiveness for bacterial proteins can be affected by how these proteins are expressed in eukaryotic cells, leading to issues like incorrect localization or glycosylation.
- - In this study, researchers explored using an adenoviral-vectored vaccine for capsular group B meningococcus (MenB) by creating candidates expressing the MenB antigen fHbp, which showed strong antigen-specific antibody and T cell responses in mice.
- - The optimized vaccine candidate, which included a genetic modification to improve its effectiveness in humans, has moved into clinical development, demonstrating the potential of genetic vaccines in generating effective immune responses against bacterial