Targeting abnormal calcium (Ca) handling in ventricular cardiomyocytes emerged as a new paradigm for human heart failure (HF) therapy. Cardiomyocytes come with an extensive Ca signaling toolkit consisting of various Ca transporters, Ca channels, Ca buffer, and sensor proteins. Organized into self-contained signaling modules in which Ca signaling functions within highly localized environments, t...

Abstract Background Left atrial (LA) function has a central role in maintaining optimal cardiac output despite impaired left ventricular (LV) diastolic through reservoir, conduit and contractile functions. In normal subjects, the contribution of LA volume (conduit contractile) to LV filling is approximately 60–70% rest completed by (CV) defined as blood flow from pulmonary veins during passive ...

Uniaxial stretch is an important biophysical regulator of cell morphology (or shape) and functions of vascular endothelial cells (ECs). However, it is unclear whether and how cell shape can independently regulate EC mechanotransductive properties under uniaxial stretch. Herein, utilizing a novel uniaxial cell-stretching device integrated with micropost force sensors, we reported the first exper...

Pseudomonas aeruginosa has three type VI secretion systems (T6SSs), H1-, H2-, and H3-T6SS, each belonging to a distinct group. The two T6SS components, TssB/VipA and TssC/VipB, assemble to form tubules that conserve structural/functional homology with tail sheaths of contractile bacteriophages and pyocins. Here, we used cryoelectron microscopy to solve the structure of the H1-T6SS P. aeruginosa...

Cytoplasmic dynein-1 is a minus-end-directed motor protein that transports cargo over long distances and organizes the intracellular microtubule (MT) network. How dynein motor activity is harnessed for these diverse functions remains unknown. Here, we have uncovered a mechanism for how processive dynein-dynactin complexes drive MT-MT sliding, reorganization, and focusing, activities required fo...

Targeting abnormal calcium (Ca) handling in ventricular cardiomyocytes emerged as a new paradigm for human heart failure (HF) therapy. Cardiomyocytes come with an extensive Ca signaling toolkit consisting of various Ca transporters, Ca channels, Ca buffer, and sensor proteins. Organized into self-contained signaling modules in which Ca signaling functions within highly localized environments, t...

Myo51, a class V myosin in fission yeast, localizes to and assists in the assembly of the contractile ring, a conserved eukaryotic actomyosin structure that facilitates cytokinesis. Rng8 and Rng9 are binding partners that dictate the cellular localization and function of Myo51. Myo51 was expressed in insect cells in the presence or absence of Rng8/9. Surprisingly, electron microscopy of negativ...

During cell division, chromosome segregation must be coordinated with cell cleavage so that cytokinesis occurs after chromosomes have been safely distributed to each spindle pole. Polo-like kinase 1 (Plk1) is an essential kinase that regulates spindle assembly, mitotic entry and chromosome segregation, but because of its many mitotic roles it has been difficult to specifically study its post-an...

Prostacyclin, also termed as prostaglandin I2 (PGI2), evokes contraction in vessels with limited expression of the prostacyclin receptor. Although the thromboxane-prostanoid receptor (TP) is proposed to mediate such a response of PGI2, other unknown receptor(s) might also be involved. TP knockout (TP-/-) mice were thus designed and used to test the hypothesis. Vessels, which normally show contr...

Introduction Diabetes mellitus is associated with increased cardiac morbidity and mortality. Cardiomyopathy occurs commonly in diabetics independent of known risk factors such as coronary artery disease or hypertension. Although the underlying mechanism is multifactorial, evidences are emerging towards metabolic disturbance that may play a causal role in modulating myocardial contractile perfor...