Medicine and Health Sciences Commons^™

The Circadian E3 Ligase Fbxl21 Regulates Myoblast Differentiation And Sarcomere Architecture Via Myoz1 Ubiquitination And Nfat Signaling, Ji Ye Lim, Eunju Kim, Collin M Douglas, Marvin Wirianto, Chorong Han, Kaori Ono, Sun Young Kim, Justin H Ji, Celia K Tran, Zheng Chen, Karyn A Esser, Seung-Hee Yoo

Journal Articles

Numerous molecular and physiological processes in the skeletal muscle undergo circadian time-dependent oscillations in accordance with daily activity/rest cycles. The circadian regulatory mechanisms underlying these cyclic processes, especially at the post-transcriptional level, are not well defined. Previously, we reported that the circadian E3 ligase FBXL21 mediates rhythmic degradation of the sarcomere protein TCAP in conjunction with GSK-3β, and Psttm mice harboring an Fbxl21 hypomorph allele show reduced muscle fiber diameter and impaired muscle function. To further elucidate the regulatory function of FBXL21 in skeletal muscle, we investigated another sarcomere protein, Myozenin1 (MYOZ1), that we identified as an FBXL21-binding protein from …

Risk Factors For Thoracic Aortic Dissection, Zhen Zhou, Alana C Cecchi, Siddharth K Prakash, Dianna M Milewicz

Journal Articles

Thoracic aortic aneurysms involving the root and/or the ascending aorta enlarge over time until an acute tear in the intimal layer leads to a highly fatal condition, an acute aortic dissection (AAD). These Stanford type A AADs, in which the tear occurs above the sinotubular junction, leading to the formation of a false lumen in the aortic wall that may extend to the arch and thoracoabdominal aorta. Type B AADs originate in the descending thoracic aorta just distal to the left subclavian artery. Genetic variants and various environmental conditions that disrupt the aortic wall integrity have been identified that increase …

A Genome-Wide Association Study Of Obstructive Heart Defects Among Participants In The National Birth Defects Prevention Study, Sara R Rashkin, Mario Cleves, Gary M Shaw, Wendy N Nembhard, Eirini Nestoridi, Mary M Jenkins, Paul A Romitti, Xiang-Yang Lou, Marilyn L Browne, Laura E Mitchell, Andrew F Olshan, Kevin Lomangino, Sudeepa Bhattacharyya, John S Witte, Charlotte A Hobbs

Journal Articles

Obstructive heart defects (OHDs) share common structural lesions in arteries and cardiac valves, accounting for ~25% of all congenital heart defects. OHDs are highly heritable, resulting from interplay among maternal exposures, genetic susceptibilities, and epigenetic phenomena. A genome-wide association study was conducted in National Birth Defects Prevention Study participants (N

Acylcarnitines And Genetic Variation In Fat Oxidation Genes In Hiv-Infected, Antiretroviral-Treated Children With And Without Myopathy, Brian Kirmse, Charlotte Hobbs, Lisa Aaron, Grace Montepiedra, Marshall Summar, Paige L Williams, Caitlin J Smith, Russell Van Dyke, Chunli Yu, Kelli K Ryckman, William Borkowsky

Journal Articles

BACKGROUND: Mitochondrial toxicity resulting in myopathy and lactic acidosis has been described in antiretroviral (ARV)-exposed patients. We hypothesized that myopathy in HIV-infected, ARV-treated children would be associated with metabolic (acylcarnitines) and genetic (variants in metabolic genes) markers of dysfunctional fatty acid oxidation (FAO).

METHODS: Acylcarnitine profiles (ACP) were analyzed for 74 HIV-infected children on nucleoside reverse transcriptase inhibitor (NRTI)-containing ARV. Thirty-seven participants with ≥2 creatine kinase measurements >500 IU (n = 18) or evidence of echocardiographic cardiomyopathy (n = 19) were matched with 37 participants without myopathy. Single nucleotide polymorphisms (SNPs) in FAO genes were also evaluated.

RESULTS: Abnormal ACP …