Article
Chemistry, Physical
Shengjie Sun, Chitra Karki, Bruce Z. Gao, Lin Li
Summary: This study reveals the importance of the binding and dissociation processes in the kinetic cycle of cardiac myosin, providing a new direction for future genetic disease studies.
JOURNAL OF CHEMICAL PHYSICS
(2022)
Review
Biochemistry & Molecular Biology
Kasturi Markandran, Jane Wenjin Poh, Michael A. Ferenczi, Christine Cheung
Summary: RLCs play a critical role in cardiac function, with phosphorylation levels affecting muscle contraction force significantly. While their role in cardiac development and disease is gradually being understood, the mechanisms triggering changes in RLC phosphorylation levels remain unclear.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Physiology
Katherine L. Dominic, Joohee Choi, Joshua B. Holmes, Mandeep Singh, Michael J. Majcher, Julian E. Stelzer
Summary: This study investigated the in vivo consequences of expressing a N-terminal truncated form of cardiac myosin binding protein C (cMyBPC). The results showed that expression of the truncated cMyBPC improved cardiac function, but did not affect the recruitment or detachment rate of cross-bridges, unlike the full-length cMyBPC.
JOURNAL OF GENERAL PHYSIOLOGY
(2023)
Article
Cardiac & Cardiovascular Systems
Tatsuro Hitsumoto, Osamu Tsukamoto, Ken Matsuoka, Junjun Li, Li Liu, Yuki Kuramoto, Shuichiro Higo, Shou Ogawa, Noboru Fujino, Shohei Yoshida, Hidetaka Kioka, Hisakazu Kato, Hideyuki Hakui, Yuki Saito, Chisato Okamoto, Hijiri Inoue, Jo Hyejin, Kyoko Ueda, Takatsugu Segawa, Shunsuke Nishimura, Yoshihiro Asano, Hiroshi Asanuma, Akiyoshi Tani, Riyo Imamura, Shinsuke Komagawa, Toshio Kanai, Masayuki Takamura, Yasushi Sakata, Masafumi Kitakaze, Jun-ichi Haruta, Seiji Takashima
Summary: This study demonstrates that dysregulation of cMLCK contributes to the development of cardiac systolic dysfunction in humans, and restoring cMLCK activity could serve as a novel myotropic therapy for advanced systolic heart failure.
Article
Geriatrics & Gerontology
Nicole Mazara, Derek P. Zwambag, Alex M. Noonan, Erin Weersink, Stephen H. M. Brown, Geoffrey A. Power
Summary: This study investigated the relationship between impaired Ca2+ sensitivity and rapid force production in single muscle fibers of young and older adults. The findings showed impaired Ca2+ sensitivity in older adults, but no difference in rapid force production between young and old muscle fibers.
EXPERIMENTAL GERONTOLOGY
(2021)
Article
Biology
Matthew H. Doran, William Lehman
Summary: Actin, a highly conserved protein, plays diverse roles in cellular processes by interacting with actin-binding proteins. The ATP-dependent cycle of myosin attachment and detachment drives muscle contraction and cellular transport. The variations in actin function are influenced by myosin isoforms and other actin-binding proteins.
Review
Biochemistry & Molecular Biology
Ashley A. Martin, Brian R. Thompson, Dongwoo Hahn, Addeli Bez Batti Angulski, Nora Hosny, Houda Cohen, Joseph M. Metzger
Summary: This review emphasizes the signaling components and regulatory mechanisms that impact cardiac sarcomere function, with a focus on the roles of the thick and thin filaments. The emerging field of inter-myofilament signaling and its important mediators are also discussed. Additionally, recent methods for studying the sarcomere under intact, physiologically relevant conditions are reviewed.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Multidisciplinary Sciences
Yongtae Hwang, Takumi Washio, Toshiaki Hisada, Hideo Higuchi, Motoshi Kaya
Summary: The molecular properties of cardiac myosin have a strong impact on cardiac contraction and relaxation, especially in terms of force production. Cardiac myosin exhibits unique collective behaviors compared to fast skeletal myosin, with a higher frequency of reverse strokes during interactions with actin filaments. A simulation model suggests that the reversal of the cardiac myosin power stroke is crucial for understanding the force output of cardiac myosin ensembles and potentially facilitating heart contractions.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Cardiac & Cardiovascular Systems
Hussam E. Salhi, Vikram Shettigar, Lorien Salyer, Sarah Sturgill, Elizabeth A. Brundage, Joel Robinett, Zhaobin Xu, Eaman Abay, Jeovanna Lowe, Paul M. L. Janssen, Jill A. Rafael-Fortney, Noah Weisleder, Mark T. Ziolo, Brandon J. Biesiadecki
Summary: Troponin I (TnI) is crucial for regulating cardiac function through its phosphorylation at Ser-23/24. Investigating mice with TnI Ser-23/24 mutated to alanine (TnI S23/24A), which cannot be phosphorylated, it was found that decreased TnI Ser-23/24 phosphorylation impairs systolic and diastolic cardiac function, as well as the response to physiological and pathological stress. These findings suggest that TnI Ser-23/24 phosphorylation serves as a modulator of cardiac function in vivo.
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
(2023)
Article
Physics, Multidisciplinary
Esteban Vazquez-Hidalgo, Carly M. Farris, Amy C. Rowat, Parag Katira
Summary: Cellular traction forces, dependent on actin-myosin activity, are crucial for developmental and physiological processes. This study presents a unified modeling framework to explain force generation in response to specific conditions. The simulation results show that substrate stiffness and myosin motor quantity contribute to the maximum actin-myosin forces, but bonding dynamics between the cell and substrate are equally important. The force transmitted to the surface per cell-substrate attachment is only a fraction of the maximum force, and traction stress varies with substrate stiffness and myosin motor quantity. Adhesions smaller than 1 μm^2 generate widely variable traction forces, and impulse is a key limitation factor in traction stress.
FRONTIERS IN PHYSICS
(2022)
Article
Cardiac & Cardiovascular Systems
Fady I. Malik, Laura A. Robertson, Danielle R. Armas, Edward P. Robbie, Anna Osmukhina, Donghong Xu, Hanbin Li, Scott D. Solomon
Summary: This phase 1 study investigated the pharmacologically active range, safety, and tolerability of aficamten in healthy adults. The results showed that aficamten exhibited a safe profile and was well tolerated at pharmacologically active doses. The pharmacokinetics of aficamten were not affected by food intake or the presence of a specific genetic phenotype.
JACC-BASIC TO TRANSLATIONAL SCIENCE
(2022)
Review
Physiology
Walter E. Knight, Hadi R. Ali, Stephanie J. Nakano, Cortney E. Wilson, Lori A. Walker, Kathleen C. Woulfe
Summary: This review discusses the current ex vivo methods for quantifying cardiac muscle performance, highlighting the value of each method and how they can be used in conjunction for a more comprehensive understanding of cardiac function.
FRONTIERS IN PHYSIOLOGY
(2021)
Review
Cell Biology
Jacopo Di Russo, Thomas M. Magin, Rudolf E. Leube
Summary: We suggest that the human body can be seen as a textile structure composed of interconnected fiber systems, forming highly dynamic scaffolds that respond to environmental changes at different scales. This is particularly important at the junctions between epithelial cells and connective tissue regions exposed to dynamic microenvironments. We propose a keratin code hypothesis, stating that the heterogeneity and adaptability of epithelial tissues are based on cell-specific expression and posttranslational modification of keratin isotypes, defining unique cytoskeletal intermediate filament networks that are connected across cells and to the diverse fibers of the underlying extracellular matrix.
CURRENT OPINION IN CELL BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Simon T. T. Abrams, Yasir Alhamdi, Min Zi, Fengmei Guo, Min Du, Guozheng Wang, Elizabeth J. J. Cartwright, Cheng-Hock Toh
Summary: Reduction in cardiac contractility is common in severe sepsis, and the mechanism behind it is still not fully understood. Recent findings suggest that circulating histones released after immune cell death play a role in cardiomyocyte injury and contractility reduction. However, the specific mechanism by which histones cause cardiac dysfunction is still unclear.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Mitchell J. George, Julia Litvinov, Kevin Aroom, Leland J. Spangler, Henry Caplan, Charles E. Wade, Charles S. Cox, Brijesh S. Gill
Summary: The relationship between platelet contraction force and MLC phosphorylation was investigated using a novel MEMS clot contraction sensor. The force of platelet contraction was found to be linearly related to levels of phosphorylated MLC.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)