Small Amounts of α-Myosin Heavy Chain Isoform Expression Significantly Increase Power Output of Rat Cardiac Myocyte Fragments

The publisher's version of this article may be found at http://circres.ahajournals.org/cgi/content/abstract/90/11/1150?maxtoshow=&HITS=10&hits=10&RESULTFORMAT=&searchid=1049671889562_931&stored_search=&FIRSTINDEX=0&volume=90&firstpage=1150&search_url=http%3A%2F%2Fcircres.ahajournals.org%2Fcgi%2Fsearch&journalMyocardial performance is likely affected by the relative expression of the two myosin heavy chain (MyHC) isoforms, namely {alpha}-MyHC and ß-MyHC. The relative expression of each isoform is regulated developmentally and in pathophysiological states. Many pathophysiological states are associated with small shifts in the relative expression of each MyHC isoform, yet the functional consequence of these shifts remains unclear. The purpose of this study was to determine the functional effect of a small shift in the relative expression of {alpha}-MyHC. To this end, power output was measured in rat cardiac myocyte fragments that expressed {approx}12% {alpha}-MyHC and in myocyte fragments that expressed {approx}0% {alpha}-MyHC, as determined in the same cells by SDS-PAGE analysis after mechanical experiments. Myocyte fragments expressing {approx}12% {alpha}-MyHC developed {approx}52% greater peak normalized power output than myocyte fragments expressing {approx}0% {alpha}-MyHC. These results indicate that small amounts of {alpha}-MyHC expression significantly augment myocyte power output.This work was supported by National Heart, Lung, and Blood Institute Grant HL-57852 (K.S.M.) and a predoctoral fellowship granted by the Heartland Affiliate of the American Heart Association (T.J.H.)

Developing Non-Technical Aircraft Automation Management Skills: First Steps in an Organizational Intervention

The purpose of this study was to address a gap in training by providing a professional development program designed to provide corporate flight instructors information about non-technical aircraft automation management skills while, simultaneously, positively affecting their perceptions of the corporate education organization for which they work. Using organizational systems theory as a theoretical framework, it was hypothesized that the program would increase flight instructor knowledge about these non-technical skills, increase their teacher self-efficacy, improve their perceptions about the organization’s functioning as a learning organization, and contribute to their perceptions of organizational support. Delivered by seminar and through a book of best practices, the intervention components included social learning theory and its applicability to airmanship development, pilot monitoring skills, automation monitoring skills, and cockpit workload in a technically advanced aircraft. Statistical analyses indicated that the intervention did produce statistically significant increases in knowledge, but not in overall teacher self-efficacy or in overall learning organization functioning. There was a statistically significant increase in the organization’s use of concrete learning practices and processes, a learning organization sub-scale. Additionally, learning organization functioning contributed significantly to the prediction of perceived organizational support. Implications of these findings are presented, along with methodological limitations and future research directions

Power Output Is Increased After Phosphorylation of Myofibrillar Proteins in Rat Skinned Cardiac Myocytes

This work was supported by American Heart Association Beginning Grant-in-Aid 9914291 and NIH Grant HL57852.The publisher's version may be found at http://circres.ahajournals.org/cgi/content/full/89/12/1184ß-Adrenergic stimulation increases stroke volume in mammalian hearts as a result of protein kinase A (PKA)-induced phosphorylation of several myocyte proteins. This study investigated whether PKA-induced phosphorylation of myofibrillar proteins directly affects myocyte contractility. To test this possibility, we compared isometric force, loaded shortening velocity, and power output in skinned rat cardiac myocytes before and after treatment with the catalytic subunit of PKA. Consistent with previous studies, PKA increased phosphorylation levels of myosin binding protein C and troponin I, and reduced Ca2+ sensitivity of force. PKA also significantly increased both maximal force (25.4±8.3 versus 31.6±11.3 µN [P<0.001, n=12]) and peak absolute power output (2.48±1.33 versus 3.38±1.52 µW/mg [P<0.05, n=5]) during maximal Ca2+ activations. Furthermore, PKA elevated power output at nearly all loads even after normalizing for the increase in force. After PKA treatment, peak normalized power output increased {approx}20% during maximal Ca2+ activations (n=5) and {approx}33% during half-maximal Ca2+ activations (n=9). These results indicate that PKA-induced phosphorylation of myofibrillar proteins increases the power output-generating capacity of skinned cardiac myocytes, in part, by speeding the step(s) in the crossbridge cycle that limit loaded shortening rates, and these changes likely contribute to greater contractility in hearts after ß-adrenergic stimulation

Modulation of Cardiac Performance by Motor Protein Gene Transfer

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75444/1/annals.1420.011.pd

UAS Capabilities and Performance Modeling for Application Analysis

Our team of researchers from Embry-Riddle Aeronautical University-Worldwide has been actively compiling published performance data associated with commercially-off-the-shelf (COTS) group 1 to 3 fixed-wing and vertical takeoff and landing (VTOL) unmanned aircraft systems (UAS) in an effort to develop statistical models of each category. The captured data, which includes maximum speed, cruise speed, endurance, weights, wind limitations, and costs, is used to calculate capabilities including range (one-way and return), time to objective, station keeping duration, maneuver requirements, and derive limited missing information (e.g., component speeds and weights). The benefit from assembling such a unified collection of information and the calculation of associated derived capabilities is that these models are anticipated to accurately reflect the capabilities, limitations, and considerations necessary in the assessment of such platforms for various applications and operating environments. These models will be available for combination with simulation or analyses to better assess end usability of these categories of aircraft for a significant number of applications including, emergency response, disaster relief, precision agriculture, security, tactical, communications, environmental study, infrastructure inspection, cargo delivery, and mapping/surveying

Spatial gradients in action potential duration created by regional magnetofection of hERG are a substrate for wavebreak and turbulent propagation in cardiomyocyte monolayers

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/95178/1/jphysiol.2012.238758.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/95178/2/TJP_5439_sm_SuppMat.pd

Spatial gradients in action potential duration created by regional magnetofection of hERG are a substrate for wavebreak and turbulent propagation in cardiomyocyte monolayers

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/95178/1/jphysiol.2012.238758.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/95178/2/TJP_5439_sm_SuppMat.pd

Human Cardiomyocytes Prior to Birth by Integrationâ Free Reprogramming of Amniotic Fluid Cells

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/135525/1/Supplemental_Information.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/135525/2/sct320165121595.pd

A null mutation of the neuronal sodium channel NaV1.6 disrupts action potential propagation and excitation‐contraction coupling in the mouse heart

Evidence supports the expression of brain‐type sodium channels in the heart. Their functional role, however, remains controversial. We used global NaV1.6‐null mice to test the hypothesis that NaV1.6 contributes to the maintenance of propagation in the myocardium and to excitation‐contraction (EC) coupling. We demonstrated expression of transcripts encoding full‐length NaV1.6 in isolated ventricular myocytes and confirmed the striated pattern of NaV1.6 fluorescence in myocytes. On the ECG, the PR and QRS intervals were prolonged in the null mice, and the Ca2+ transients were longer in the null cells. Under patch clamping, at holding potential (HP) = –120 mV, the peak INa was similar in both phenotypes. However, at HP = –70 mV, the peak INa was smaller in the nulls. In optical mapping, at 4 mM [K+]o, 17 null hearts showed slight (7%) reduction of ventricular conduction velocity (CV) compared to 16 wild‐type hearts. At 12 mM [K+]o, CV was 25% slower in a subset of 9 null vs. 9 wild‐type hearts. These results highlight the importance of neuronal sodium channels in the heart, whereby NaV1.6 participates in EC coupling, and represents an intrinsic depolarizing reserve that contributes to excitation.—Noujaim, S. F., Kaur, K., Milstein, M., Jones, J. M., Furspan, P., Jiang, D., Auerbach, D. S., Herron, T., Meisler, M. H., Jalife, J. A null mutation of the neuronal sodium channel NaV1.6 disrupts action potential propagation and excitation‐contraction coupling in the mouse heart. FASEB J. 26, 63–72 (2012). www.fasebj.orgPeer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154524/1/fsb2fj10179770.pd