Dataset Information

Analytical comparison of natural and pharmaceutical ventricular myosin activators.

ABSTRACT: Ventricular myosin (?Mys) is the motor protein in cardiac muscle generating force using ATP hydrolysis free energy to translate actin. In the cardiac muscle sarcomere, myosin and actin filaments interact cyclically and undergo rapid relative translation facilitated by the low duty cycle motor. It contrasts with high duty cycle processive myosins for which persistent actin association is the priority. The only pharmaceutical ?Mys activator, omecamtive mecarbil (OM), upregulates cardiac contractility in vivo and is undergoing testing for heart failure therapy. In vitro ?Mys step-size, motility velocity, and actin-activated myosin ATPase were measured to determine duty cycle in the absence and presence of OM. A new parameter, the relative step-frequency, was introduced and measured to characterize ?Mys motility due to the involvement of its three unitary step-sizes. Step-size and relative step-frequency were measured using the Qdot assay. OM decreases motility velocity 10-fold without affecting step-size, indicating a large increase in duty cycle converting ?Mys to a near processive myosin. The OM conversion dramatically increases force and modestly increases power over the native ?Mys. Contrasting motility modification due to OM with that from the natural myosin activator, specific ?Mys phosphorylation, provides insight into their respective activation mechanisms and indicates the boilerplate screening characteristics desired for pharmaceutical ?Mys activators. New analytics introduced here for the fast and efficient Qdot motility assay create a promising method for high-throughput screening of motor proteins and their modulators.

SUBMITTER: Wang Y

PROVIDER: S-EPMC4139156 | biostudies-literature | 2014 Aug

REPOSITORIES: biostudies-literature

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Analytical comparison of natural and pharmaceutical ventricular myosin activators.

Wang Yihua Y Ajtai Katalin K Burghardt Thomas P TP

Biochemistry 20140807 32

Ventricular myosin (βMys) is the motor protein in cardiac muscle generating force using ATP hydrolysis free energy to translate actin. In the cardiac muscle sarcomere, myosin and actin filaments interact cyclically and undergo rapid relative translation facilitated by the low duty cycle motor. It contrasts with high duty cycle processive myosins for which persistent actin association is the priority. The only pharmaceutical βMys activator, omecamtive mecarbil (OM), upregulates cardiac contractil ...[more]

PMID: 25068717

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Project description:BackgroundSocial media has become one of the primary information sources for medical professionals and patients. Pharmaceutical companies are committed to using various social media platforms to provide stakeholders with digital medical information services (DMISs), which remain experimental and immature. In China, WeChat tops the list of popular social media platforms. To date, little is known about the service model of DMISs delivered by pharmaceutical companies via WeChat.ObjectiveThis study aims to explore the emerging service model of DMISs delivered by pharmaceutical companies via WeChat in China.MethodsThis study applied a qualitative research design combining case study and documentary analysis to explore the DMISs of 6 leading pharmaceutical companies in China. Materials were collected from their official WeChat platforms. Thematic analysis was conducted on the data.ResultsThe DMISs of 6 pharmaceutical companies were investigated. Themes emerged regarding 2 essential information services delivered by pharmaceutical companies via WeChat: business operation services and DMISs (ie, public information services, professional services, science and education services, and e-commerce services). Business operation services mainly function to assist or facilitate the company's operations and development trends for general visitors. Public-oriented information services are realized through health science popularization, academic frontiers, product information, and road maps to hospitals and pharmacies. Internet hospital and pharmacy services are the main patient-oriented professional services. Medical staff-oriented science and education services commonly include continuing education, clinical assistance, academic research, and journal searching. Public-oriented e-commerce services include health products and health insurance.ConclusionsPharmaceutical companies in China use WeChat to provide stakeholders with diversified DMISs, which remain in the exploratory stage. The service model of DMISs requires more distinct innovations to provide personalized digital health and patient-centric services. Moreover, specific regulations on the DMISs of pharmaceutical companies need to be established to guard public health interests.

Dataset Information

Analytical comparison of natural and pharmaceutical ventricular myosin activators.

Publications

Analytical comparison of natural and pharmaceutical ventricular myosin activators.

Similar Datasets

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