Mitochondrial and Neuromuscular Disorders Unit, Vall d'Hebron Institut de Recerca, Universitat Autònoma de Barcelona, Barcelona 08035, Spain
Published: January 2020
AI Article Synopsis
Article Abstract
McArdle disease is an autosomal recessive disorder caused by the absence of muscle glycogen phosphorylase, which leads to blocked muscle glycogen breakdown. We used three different cellular models to evaluate the efficiency of different read-through agents (including amlexanox, Ataluren, RTC13 and G418) in McArdle disease. The first model consisted of HeLa cells transfected with two different GFP- constructs presenting the p.R50X mutation (GFP- p.R50X and Ex1-GFP p.R50X). The second cellular model was based on the creation of HEK293T cell lines stably expressing the Ex1-GFP p.R50X construct. As these plasmids encode murine cDNA without any intron sequence, their transfection in cells would allow for analysis of the efficacy of read-through agents with no concomitant nonsense-mediated decay interference. The third model consisted of skeletal muscle cultures derived from the McArdle mouse model (knock-in for the p.R50X mutation in the gene). We found no evidence of read-through at detectable levels in any of the models evaluated. We performed a literature search and compared the premature termination codon context sequences with reported positive and negative read-through induction, identifying a potential role for nucleotide positions -9, -8, -3, -2, +13 and +14 (the first nucleotide of the stop codon is assigned as +1). The p.R50X mutation presents TGA as a stop codon, G nucleotides at positions -1 and -9, and a C nucleotide at -3, which potentially generate a good context for read-through induction, counteracted by the presence of C at -2 and its absence at +4.
Introduction: Elevated blood pressure (BP) is the major contributor to mortality and disease burden worldwide. May Measurement Month (MMM) is a global BP screening campaign, which aims to raise awareness of BP measurement and provide evidence to inform and influence related health policy.
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Background: People hospitalised for coronavirus disease 2019 (COVID-19) have elevated incidence of diabetes. However, it is unclear whether this is due to shared risk factors, confounding or stress hyperglycaemia in response to acute illness.
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* The paper emphasizes the importance of addressing disparities like ageism and stigma, especially for minoritized communities, while providing examples of how PPI can be integrated throughout the research process.
* Recommendations for researchers include fostering collaborative relationships with communities, starting partnerships early, and ensuring that factors like choice, respect, and inclusion are prioritized.
Glycogen Storage Disease type 5 (GSD5), or McArdle disease, is characterized by a lack of glycogen phosphorylase enzyme in muscles, resulting in symptoms such as muscle pain and fatigue during physical activity.
The study explored the experiences of 13 individuals with GSD5 through in-depth interviews, analyzing their challenges, diagnosis process, and coping strategies.
Four main themes emerged, highlighting major difficulties in daily life, the importance of diagnosis for understanding their condition, management techniques like the ‘second wind’ phenomenon, and the crucial role of support networks for improving life quality.
