D. A. Kass

The structural OFF and ON states of myosin can be decoupled from the biochemical super-relaxed and disordered-relaxed states.

This study decouples structural OFF/ON states from biochemical SRX/DRX states in myosin using X-ray diffraction and ATP assays in porcine myocardium.

Right Ventricular Sarcomere Contractile Depression and the Role of Thick Filament Activation in Human Heart Failure with Pulmonary Hypertension

This study identifies contractile deficits in right ventricular myocytes of HFrEF-PH patients, showing reduced calcium-activated tension and altered myosin ATP turnover, with implications for targeted therapies.

Signaling Node at TSC2 S1365 Potently Regulates T-Cell Differentiation and Improves Adoptive Cellular Cancer Therapy

This study shows that mutating TSC2 at S1365 enhances T-cell effector function and memory formation, improving adoptive T-cell therapy for cancer.

Constitutive Inhibition of Transient Receptor Potential CanonicalType 6 (TRPC6) by O-GlcNAcylation at Threonine-221

This study identifies O-GlcNAcylation at Thr221 as a constitutive inhibitor of TRPC6 channel conductance and NFAT signaling, showing its conservation and functional importance across TRPC family members.

Single Serine on TSC2 Exerts Biased Control over mTORC1 Activation by ERK1/2 but Not Akt

The paper shows that a single serine on TSC2 selectively controls mTORC1 activation by ERK1/2 but not Akt, with implications for pathological versus physiological mTOR signaling.

PDE9 Inhibition Activates PPARa to Stimulate Mitochondrial Fat Metabolism and Reduce Cardiometabolic Syndrome

This study shows PDE9 inhibition activates PPARa to enhance mitochondrial fat metabolism and reduce cardiometabolic syndrome in mice, with potential for treating obesity in men and postmenopausal women.

Increased energy expenditure and protection from diet-induced obesity in mice lacking the cGMP-specific phosphodiesterase, PDE9

This study shows that mice lacking PDE9 are resistant to obesity and have increased energy expenditure on a high-fat diet, with improved glucose handling and reduced hepatic steatosis.

PDE1 inhibition modulates Cav1.2 channel to stimulate cardiomyocyte contraction

This paper investigates how PDE1 inhibition increases cardiac contractility by enhancing Cav1.2 channel conductance through PKA, with less intracellular calcium rise and arrhythmia compared to beta-ARs or PDE3i.