Applying the Research Domain Criteria to Rodent Studies of Sex Differences in Chronic Stress Susceptibility.

Women have a 2-fold increased rate of stress-associated psychiatric disorders such as depression and anxiety, but the mechanisms that underlie this increased susceptibility remain incompletely understood. Historically, female subjects were excluded from preclinical studies and clinical trials. Additionally, chronic stress paradigms used to study psychiatric pathology in animal models were developed for use in males.

Class I PI3K Biology.

This chapter is an introduction to phosphoinositide 3-kinases (PI3K), with class I PI3Ks as the central focus. First, the various PI3K isoforms in class I are presented with emphasis on their overall structure, subunits, subunit constitutive domains, domain-domain interactions, and functional relevance. This structural analysis is followed by a comprehensive history of seminal investigations into PI3K activity.

Genetic inhibition of nuclear factor of activated T-cell c2 prevents atrial fibrillation in CREM transgenic mice.

Aims: Abnormal intracellular calcium (Ca2+) handling contributes to the progressive nature of atrial fibrillation (AF), the most common sustained cardiac arrhythmia. Evidence in mouse models suggests that activation of the nuclear factor of activated T-cell (NFAT) signalling pathway contributes to atrial remodelling. Our aim was to determine the role of NFATc2 in AF in humans and mouse models.

Reversible cardiac disease features in an inducible CUG repeat RNA-expressing mouse model of myotonic dystrophy.

Myotonic dystrophy type 1 (DM1) is caused by a CTG repeat expansion in the DMPK gene. Expression of pathogenic expanded CUG repeat (CUGexp) RNA causes multisystemic disease by perturbing the functions of RNA-binding proteins, resulting in expression of fetal protein isoforms in adult tissues. Cardiac involvement affects 50% of individuals with DM1 and causes 25% of disease-related deaths.

Atrial-Specific Gene Delivery Using an Adeno-Associated Viral Vector.

Rationale: Somatic overexpression in mice using an adeno-associated virus (AAV) as gene transfer vectors has become a valuable tool to analyze the roles of specific genes in cardiac diseases. The lack of atrial-specific AAV vector has been a major obstacle for studies into the pathogenesis of atrial diseases. Moreover, gene therapy studies for atrial fibrillation would benefit from atrial-specific vectors.

Genetics of atrial fibrillation: an update.

Purpose Of Review: Atrial fibrillation is a common cardiac arrhythmia with a high morbidity and mortality affecting 34 million worldwide. Current therapies are inadequate and often fail to directly address molecular mechanisms of the disease. In this review, we will provide an overview of recent advances in our understanding of the genetic underpinnings of atrial fibrillation.

SPEG (Striated Muscle Preferentially Expressed Protein Kinase) Is Essential for Cardiac Function by Regulating Junctional Membrane Complex Activity.

Rationale: Junctional membrane complexes (JMCs) in myocytes are critical microdomains, in which excitation-contraction coupling occurs. Structural and functional disruption of JMCs underlies contractile dysfunction in failing hearts. However, the role of newly identified JMC protein SPEG (striated muscle preferentially expressed protein kinase) remains unclear.

Metabolomics of neurodegenerative diseases.

Neurodegenerative diseases are progressive, devastating, and terminal, carrying both personal and societal burden. Currently, their diagnosis depends on their clinical presentation. No quantitative biomarkers exist to enable early verdict and commencement of therapy.