Inferential Statistics

The reliability of neuropsychologic changes after cardiac surgery and a deeper problem posed by practice effects

Statistical errors in immunologic research

Guidelines for improving the use and presentation of P values

Phacotrabeculectomy Meta-analysis

Resuscitation highlights in 2013: Part 2

Comparison of the systemic pharmacodynamic effects and pharmacokinetics of salmeterol delivered by CFC propellant and non-CFC propellant metered dose inhalers in healthy subjects

CaV1.2 interacts with the Ca(2+) sensor proteins, calmodulin (CaM) and calcium-binding protein 1 (CaBP1), via multiple, partially overlapping sites in the main subunit of CaV1.2, α1C. Ca(2+)/CaM mediates a negative feedback regulation of Cav1.2 by incoming Ca(2+) ions (Ca(2+)-dependent inactivation (CDI)). CaBP1 eliminates this action of CaM through a poorly understood mechanism. We examined the hypothesis that CaBP1 acts by competing with CaM for common interaction sites in the α1C- subunit using Förster resonance energy transfer (FRET) and recording of Cav1.2 currents in Xenopus oocytes. FRET detected interactions between fluorescently labeled CaM or CaBP1 with the membrane-attached proximal C terminus (pCT) and the N terminus (NT) of α1C. However, mutual overexpression of CaM and CaBP1 proved inadequate to quantitatively assess competition between these proteins for α1C. Therefore, we utilized titrated injection of purified CaM and CaBP1 to analyze their mutual effects. CaM reduced FRET between CaBP1 and pCT, but not NT, suggesting competition between CaBP1 and CaM for pCT only. Titrated injection of CaBP1 and CaM altered the kinetics of CDI, allowing analysis of their opposite regulation of CaV1.2. The CaBP1-induced slowing of CDI was largely eliminated by CaM, corroborating a competition mechanism, but 15-20% of the effect of CaBP1 was CaM-resistant. Both components of CaBP1 action were present in a truncated α1C where N-terminal CaM- and CaBP1-binding sites have been deleted, suggesting that the NT is not essential for the functional effects of CaBP1. We propose that CaBP1 acts via interaction(s) with the pCT and possibly additional sites in α1C.

Magnetic endoscope imaging colonoscope: a new modality for hypothesis testing in unsedated colonoscopy

Climate Change and the Health of the Public

Female overweight is not associated with a higher embryo euploidy rate in first trimester miscarriages karyotyped by hysteroembryoscopy

Action Video Games Make Dyslexic Children Read Better

Insulin resistance impairs sustained response rate to peginterferon plus ribavirin in chronic hepatitis C patients

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Sky blue or murky waters: The diagnostic utility of methylene blue

Decoding the Enigma of Urticaria and Angioedema