Introduction: Carriage of the HLA-DQA1*05 allele is associated with development of antidrug antibodies (ADAs) to antitumor necrosis factor (anti-TNF) therapy in patients with Crohn's disease. However, ADA is not uniformly associated with treatment failure. We aimed to determine the impact of carriage of HLA-DQA1*05 allele on outcome of biologic therapy evaluated by drug persistence.
View Article and Find Full Text PDFAlthough physiological data suggest that neuromuscular junction (NMJ) dysfunction is a principal mechanism underpinning sarcopenia, genetic studies have implicated few genes involved in NMJ function. Accordingly, we explored whether genes encoding agrin (AGRN) and neurotrypsin (PRSS12) were associated with sarcopenia phenotypes: muscle mass, strength and plasma C-terminal agrin fragment (CAF). PhenoScanner was used to determine if AGRN and/or PRSS12 variants had previously been implicated with sarcopenia phenotypes.
View Article and Find Full Text PDFBackground: Efforts to enhance diagnostic measures for sarcopenia have led to an increased focus on the screening utility of blood-based biomarkers. In this regard, circulating neurofilament light chain (NfL) levels are a potent indicator of axonal damage and have been linked with several neurological disorders. However, despite the strong neurogenic contribution to skeletal muscle health, no studies have explored the relevance of NfL concentrations to sarcopenia.
View Article and Find Full Text PDFWeak grip strength is a strong predictor of multiple adverse health outcomes and an integral diagnostic component of sarcopenia. However, the limited availability of normative data for certain populations impedes the interpretation of grip performance across adulthood. This study aimed to establish normative data and low grip strength thresholds in a large adult population, and to examine associations between grip strength and clinically relevant health variables.
View Article and Find Full Text PDFJ Gerontol A Biol Sci Med Sci
November 2021
Barriers associated with direct muscle quantification have prevented a consistent implementation of therapeutic measures for sarcopenia. Recently, the relevance of circulating C-terminal agrin fragment (CAF) as an accessible screening method alternative for sarcopenia has gained credence. Accordingly, this study aimed to verify the pertinence of plasma CAF as a biomarker for sarcopenia.
View Article and Find Full Text PDFA growing number of proteins with extracellular leucine-rich repeats (eLRRs) have been implicated in directing neuronal connectivity. We previously identified a novel family of eLRR proteins in mammals: the Elfns are transmembrane proteins with 6 LRRs, a fibronectin type-3 domain and a long cytoplasmic tail. The recent discovery that Elfn1 protein, expressed postsynaptically, can direct the elaboration of specific electrochemical properties of synapses between particular cell types in the hippocampus strongly reinforces this hypothesis.
View Article and Find Full Text PDFBackground: Leucine-rich repeats (LRRs) are highly versatile and evolvable protein-ligand interaction motifs found in a large number of proteins with diverse functions, including innate immunity and nervous system development. Here we catalogue all of the extracellular LRR (eLRR) proteins in worms, flies, mice and humans. We use convergent evidence from several transmembrane-prediction and motif-detection programs, including a customised algorithm, LRRscan, to identify eLRR proteins, and a hierarchical clustering method based on TribeMCL to establish their evolutionary relationships.
View Article and Find Full Text PDFThe transmembrane semaphorin protein Sema6A is broadly expressed in the developing nervous system. Sema6A repels several classes of developing axons in vitro and contributes to thalamocortical axon guidance in vivo. Here we show that during cerebellum development, Sema6A is selectively expressed by postmitotic granule cells during their tangential migration in the deep external granule cell layer, but not during their radial migration.
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