Magic™ Anti-Troponin I monoclonal antibody, clone TPC110

Defined as clinically unexplained hypertrophy of the left ventricle, hypertrophic cardiomyopathy (HCM) is traditionally understood as a disease of the cardiac sarcomere. Mutations in TNNC1-encoded cardiac troponin C (cTnC) are a relatively rare cause of HCM. Here, we report clinical and functional characterization of a novel TNNC1 mutation, A31S, identified in a pediatric HCM proband with multiple episodes of ventricular fibrillation and aborted sudden cardiac death. Diagnosed at age 5, the proband is family history-negative for HCM or sudden cardiac death, suggesting a de novo mutation. TnC-extracted cardiac skinned fibers were reconstituted with the cTnC-A31S mutant, which increased Ca2+ sensitivity with no effect on the maximal contractile force generation. Reconstituted actomyosin ATPase assays with 50% cTnC-A31S:50% cTnC-WT-demonstrated Ca2+ sensitivity that was intermediate between 100% cTnC-A31S and 100% cTnC-WT, whereas the mutant increased the activation of the actomyosin ATPase without affecting the inhibitory qualities of the ATPase. The secondary structure of the cTnC mutant was evaluated by circular dichroism, which did not indicate global changes in structure. Fluorescence studies demonstrated increased Ca2+ affinity in isolated cTnC, the troponin complex, thin filament, and to a lesser degree, thin filament with myosin subfragment 1. These results suggest that this mutation has a direct effect on the Ca2+ sensitivity of the myofilament, which may alter Ca2+ handling and contribute to the arrhythmogenesis observed in the proband. In summary, we report a novel mutation in the TNNC1 gene that is associated with HCM pathogenesis and may predispose to the pathogenesis of a fatal arrhythmogenic subtype of HCM.

Background: The aim of the current study was to screen differentially-expressed genes (DEGs) relevant to cancer progression and prognosis of squamous cell lung carcinoma (SqCLC). Methods: DEGs mRNA expression data of SqCLC was screened from the Oncomine database. This data was further analyzed by comparing tumor tissues to normal tissues. Prognostic values of DEGs relevant to SqCLC were investigated using the "Kaplan-Meier Plotter" (KM plotter) database. Bioinformation for included genes was analyzed by gene GO and KEGG enrichment, aiming to explain the potential roles of identified genes in SqCLC. Protein-protein interaction (PPI) of the genes was evaluated using the STRING database. Results: Four independent microarray datasets relevant to SqCLC were identified in the Oncomine database, with the top 10 consistently upregulated and top 10 consistently downregulated genes included in the present analysis. Significant differences of overall survival (OS) were correlated with SMC4, HIST2H2AA3, GMPS, CKS1B, POLR2H, PDCD10, PLOD2, DVL3, C-type CLEC3B, TNNC1, FAM107A, FYR, MEF2C, SLIT3, CX3CR1, C17orf91, LIM, and LIMCH1 (all P < 0.05). Possible protein-protein interaction analysis of the top 20 dysregulated genes showed that proteins of SMC4, POLR2H, and NCBP2 in upregulated genes and TNNC1 and MEF2C in downregulated genes interacted with more than 5 other proteins. This may play an important role in the development of SqCLC. Conclusion: MC4, POLR2H. TNNC1, and MEF2C genes were dysregulated in SqCLC. Thus, they may play an essential role in the development of SqCLC, as biomarkers for patient prognosis.