Generation of a novel mouse model of nemaline myopathy due to recurrent exon 55 deletion.

Biallelic pathogenic variants in the nebulin () gene lead to the congenital muscle disease nemaline myopathy. In-frame deletion of exon 55 (ΔExon55) is the most common disease-causing variant in . Previously, a mouse model of was developed; however, it presented an uncharacteristically severe phenotype with a near complete reduction in transcript expression that is not observed in exon 55 patients.

Discovery of Titin and Its Role in Heart Function and Disease.

This review examines the giant elastic protein titin and its critical roles in heart function, both in health and disease, as discovered since its identification nearly 50 years ago. Encoded by the TTN (titin gene), titin has emerged as a major disease locus for cardiac disorders. Functionally, titin acts as a third myofilament type, connecting sarcomeric Z-disks and M-bands, and regulating myocardial passive stiffness and stretch sensing.

Mechanism-based myofilament manipulation to treat diastolic dysfunction in HFpEF.

Heart failure with preserved ejection fraction (HFpEF) is a major public health challenge, affecting millions worldwide and placing a significant burden on healthcare systems due to high hospitalization rates and limited treatment options. HFpEF is characterized by impaired cardiac relaxation, or diastolic dysfunction. However, there are no therapies that directly treat the primary feature of the disease.

Increased cardiac myosin super-relaxation as an energy saving mechanism in hibernating grizzly bears.

Aim: The aim of the present study was to define whether cardiac myosin contributes to energy conservation in the heart of hibernating mammals.

Methods: Thin cardiac strips were isolated from the left ventricles of active and hibernating grizzly bears; and subjected to loaded Mant-ATP chase assays, X-ray diffraction and proteomics.

Main Findings: Hibernating grizzly bears displayed an unusually high proportion of ATP-conserving super-relaxed cardiac myosin molecules that are likely due to altered levels of phosphorylation and rod region stability.