Neurodegeneration is characteristically multifaceted, with limited therapeutic options. One of the chief pathophysiological mechanisms driving these conditions is neuroinflammation, prompting increasing clinical interest in immunomodulatory agents. Growth differentiation factor 15 (GDF15; previously also called macrophage inhibitory cytokine-1 or MIC-1), an anti-inflammatory cytokine with established neurotrophic properties, has emerged as a promising therapeutic agent in recent decades.
View Article and Find Full Text PDFProteome changes associated with APOE4 variant carriage that are independent of Alzheimer's disease (AD) pathology and diagnosis are unknown. This study investigated APOE4 proteome changes in people with AD, mild cognitive impairment, and no impairment. Clinical, APOE genotype, and cerebrospinal fluid (CSF) proteome and AD biomarker data was sourced from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database.
View Article and Find Full Text PDFNanopore sequencing enables detection of DNA methylation at the same time as identification of canonical sequence. A recent study validated low-pass nanopore sequencing to accurately estimate global methylation levels in vertebrates with sequencing coverage as low as 0.01x.
View Article and Find Full Text PDFLysine metabolism converges at α-aminoadipic semialdehyde dehydrogenase (ALDH7A1). Rare loss-of-function mutations in ALDH7A1 cause a toxic accumulation of lysine catabolites, including piperideine-6-carboxylate (P6C), that are thought to cause fatal seizures in children unless strictly managed with dietary lysine reduction. In this study, we perform metabolomics and expression analysis of tissues from Aldh7a1-deficient mice, which reveal tissue-specific differences in lysine metabolism and other metabolic pathways.
View Article and Find Full Text PDFBased on the phylogenetic placement of a near-complete mitogenome sequence of the holotype of Chelodina intergularis Fry, 1915 generated with hDNA approaches, we present evidence for the synonymy of this nominal species with Chelodina rugosa Ogilby, 1890. The type specimens of both taxa are housed in the Australian Museum, Sydney. Scrutinizing historical records, we conclude that the type locality of both taxa is most likely the vicinity of Somerset, at the northern extremity of Cape York Peninsula, Queensland, Australia.
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