Large-scale single-nuclei profiling identifies role for ATRNL1 in atrial fibrillation.

Atrial fibrillation (AF) is the most common sustained arrhythmia in humans, yet the molecular basis of AF remains incompletely understood. To determine the cell type-specific transcriptional changes underlying AF, we perform single-nucleus RNA-seq (snRNA-seq) on left atrial (LA) samples from patients with AF and controls. From more than 175,000 nuclei we find that only cardiomyocytes (CMs) and macrophages (MΦs) have a significant number of differentially expressed genes in patients with AF.

Timing matters: The contribution of running during different periods of the light/dark cycle to susceptibility to activity-based anorexia in rats.

Individuals with anorexia nervosa (AN) exhibit dangerous weight loss due to restricted eating and hyperactivity. Those with AN are predominantly women and most cases have an age of onset during adolescence. Activity-based anorexia (ABA) is a rodent behavioral paradigm that recapitulates many of the features of AN including restricted food intake and hyperactivity, resulting in precipitous weight loss.

Single-nucleus RNA sequencing in ischemic cardiomyopathy reveals common transcriptional profile underlying end-stage heart failure.

Ischemic cardiomyopathy (ICM) is the leading cause of heart failure worldwide, yet the cellular and molecular signature of this disease is largely unclear. Using single-nucleus RNA sequencing (snRNA-seq) and integrated computational analyses, we profile the transcriptomes of over 99,000 human cardiac nuclei from the non-infarct region of the left ventricle of 7 ICM transplant recipients and 8 non-failing (NF) controls. We find the cellular composition of the ischemic heart is significantly altered, with decreased cardiomyocytes and increased proportions of lymphatic, angiogenic, and arterial endothelial cells in patients with ICM.

Activity-based anorexia in adolescent female rats causes changes in brain mitochondrial dynamics.

Anorexia Nervosa (AN) is associated with a high rate of morbidity and mortality as well as a high rate of relapse. The molecular mechanisms underlying the progression of the disorder or the relapses are largely unknown. Patients with AN have been shown to have increased oxidative stress, but its involvement in the development in the disease is unknown.

Discovery of Orally Bioavailable and Brain-Penetrable Prodrugs of the Potent nSMase2 Inhibitor DPTIP.

Extracellular vesicles (EVs) can carry pathological cargo and play an active role in disease progression. Neutral sphingomyelinase-2 (nSMase2) is a critical regulator of EV biogenesis, and its inhibition has shown protective effects in multiple disease states. 2,6-imethoxy-4-(5-henyl-4-hiophen-2-yl-1-midazol-2-yl)henol (DPTIP) is one of the most potent (IC = 30 nM) inhibitors of nSMase2 discovered to date.

Adolescent female rats prone to the activity based anorexia (ABA) paradigm have altered hedonic responses and cortical astrocyte density compared to resistant animals.

Objective: Anhedonia, which in part involves the lack of pleasure in consuming palatable food, is a long-lasting symptom observed in patients both when acutely ill and when long term recovered from Anorexia Nervosa. The neurocircuitry underlying this phenomenon is not well understood. Here we use the preclinical activity-based anorexia (ABA) model in adolescent female rats to assess the impact of excessive exercise, limited food intake and acute weight loss, on adolescent female rat orofacial responding to intraoral sucrose, as measured by the taste reactivity test (TRT).

Activity-based anorexia disrupts systemic oxidative state and induces cortical mitochondrial fission in adolescent female rats.

Objective: Patients with Anorexia Nervosa (AN) display increased levels of oxidative stress that correlates with disease severity. Unfortunately, the biological ramifications of AN-induced oxidative stress on the brain are largely unknown. Our lab uses the preclinical activity-based anorexia (ABA) paradigm to model symptoms of AN.