Audrey Noguchi
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View article: Orthologs of <i>Drosophila pointed</i> and <i>Arginine kinase 1</i> impact sleep in mice
Orthologs of <i>Drosophila pointed</i> and <i>Arginine kinase 1</i> impact sleep in mice Open
Model organisms such as Drosophila are powerful tools to study the genetic basis of sleep. Previously, we identified the genes pointed and Arginine kinase 1 using selective breeding for long and short sleep duration in an outbred populatio…
View article: 988 Vagal-CD8+ T cell neuroimmune axis modulates liver cancer
988 Vagal-CD8+ T cell neuroimmune axis modulates liver cancer Open
Background Liver cancer remains the third leading cause of worldwide cancer-related deaths.1 Despite clinical advances, established immunotherapies largely fail patients due to poor immune responses.1 2 Peripheral nerves influence tumors, …
View article: A PARP inhibitor, rucaparib, improves cardiac dysfunction in<i>ADP-ribose-acceptor hydrolase 3</i>(<i>Arh3</i>) deficiency
A PARP inhibitor, rucaparib, improves cardiac dysfunction in<i>ADP-ribose-acceptor hydrolase 3</i>(<i>Arh3</i>) deficiency Open
Aims Patients with ADP-ribose-acceptor hydrolase 3 ( ARH3 ) deficiency exhibit stress-induced childhood-onset neurodegeneration with ataxia and seizures (CONDSIAS). ARH3 degrades protein-linked poly(ADP- ribose) (PAR) synthesized by poly(A…
View article: <i>ADP-ribose-acceptor hydrolase 2</i>(<i>Arh2</i>) deficiency results in cardiac dysfunction, tumorigenesis, inflammation, and decreased survival
<i>ADP-ribose-acceptor hydrolase 2</i>(<i>Arh2</i>) deficiency results in cardiac dysfunction, tumorigenesis, inflammation, and decreased survival Open
ADP-ribosylation is a reversible reaction with ADP-ribosyltransferases catalyzing the forward reaction and ADP-ribose-acceptor hydrolases (ARHs) hydrolyzing the ADP-ribose acceptor bond. ARH2 is a member of the 39-kDa ARH family (ARH1-3), …
View article: Loss of TMEM65 causes mitochondrial disease mediated by mitochondrial calcium
Loss of TMEM65 causes mitochondrial disease mediated by mitochondrial calcium Open
Transmembrane protein 65 (TMEM65) depletion in a patient carrying a homozygous variant in the Tmem65 splice site resulted in severe mitochondrial encephalomyopathy, indicating the clinical importance of TMEM65. However, the function of TME…
View article: Hyperactivation of mTOR and AKT in a cardiac hypertrophy animal model of Friedreich ataxia
Hyperactivation of mTOR and AKT in a cardiac hypertrophy animal model of Friedreich ataxia Open
Cardiomyopathy is a primary cause of death in Friedreich ataxia (FRDA) patients with defective iron-sulfur cluster (ISC) biogenesis due to loss of functional frataxin and in rare patients with functional loss of other ISC biogenesis factor…
View article: Mineralocorticoid receptor antagonist treatment of established pulmonary arterial hypertension improves interventricular dependence in the SU5416-hypoxia rat model
Mineralocorticoid receptor antagonist treatment of established pulmonary arterial hypertension improves interventricular dependence in the SU5416-hypoxia rat model Open
Treatment with mineralocorticoid receptor (MR) antagonists beginning at the outset of disease, or early thereafter, prevents pulmonary vascular remodeling in preclinical models of pulmonary arterial hypertension (PAH). However, the efficac…
View article: Therapeutic inhibition of HIF-2α reverses polycythemia and pulmonary hypertension in murine models of human diseases
Therapeutic inhibition of HIF-2α reverses polycythemia and pulmonary hypertension in murine models of human diseases Open
Polycythemia and pulmonary hypertension are 2 human diseases for which better therapies are needed. Upregulation of hypoxia-inducible factor-2α (HIF-2α) and its target genes, erythropoietin (EPO) and endothelin-1, causes polycythemia and p…
View article: PPARγ agonists delay age‐associated metabolic disease and extend longevity
PPARγ agonists delay age‐associated metabolic disease and extend longevity Open
Aging leads to a number of disorders caused by cellular senescence, tissue damage, and organ dysfunction. It has been reported that anti‐inflammatory and insulin‐sensitizing compounds delay, or reverse, the aging process and prevent metabo…
View article: A Mouse Homolog of a Human TP53 Germline Mutation Reveals a Lipolytic Activity of p53
A Mouse Homolog of a Human TP53 Germline Mutation Reveals a Lipolytic Activity of p53 Open
The physiological effects of the many germline mutations of TP53, encoding the tumor suppressor protein p53, are poorly understood. Here we report generating a p53 R178C knockin mouse modeling the human TP53 R181C mutation, which is notabl…
View article: Dietary Palmitoleic Acid Attenuates Atherosclerosis Progression and Hyperlipidemia in Low‐Density Lipoprotein Receptor‐Deficient Mice
Dietary Palmitoleic Acid Attenuates Atherosclerosis Progression and Hyperlipidemia in Low‐Density Lipoprotein Receptor‐Deficient Mice Open
Scope Palmitoleic acid (palmitoleate; C16:1 n‐7), an omega‐7 monounsaturated fatty acid (MUFA) found in plants and marine sources, has been shown to favorably modulate lipid and glucose metabolism. However, its impact on atherosclerosis ha…
View article: The Catalytic Subunit β of PKA Affects Energy Balance and Catecholaminergic Activity
The Catalytic Subunit β of PKA Affects Energy Balance and Catecholaminergic Activity Open
The protein kinase A (PKA) signaling system mediates the effects of numerous hormones, neurotransmitters, and other molecules to regulate metabolism, cardiac function, and more. PKA defects may lead to diverse phenotypes that largely depen…
View article: Conditional ablation and conditional rescue models for Casq2 elucidate the role of development and of cell-type specific expression of Casq2 in the CPVT2 phenotype
Conditional ablation and conditional rescue models for Casq2 elucidate the role of development and of cell-type specific expression of Casq2 in the CPVT2 phenotype Open
Cardiac calsequestrin (Casq2) associates with the ryanodine receptor 2 channel in the junctional sarcoplasmic reticulum to regulate Ca2+ release into the cytoplasm. Patients carrying mutations in CASQ2 display low resting heart rates under…
View article: Hepatic peroxisome proliferator‐activated receptor alpha mediates the major metabolic effects of Wy‐14643
Hepatic peroxisome proliferator‐activated receptor alpha mediates the major metabolic effects of Wy‐14643 Open
Background and Aim Peroxisome proliferator‐activated receptor alpha (PPARα) is a molecular target of various fibrate drugs clinically used to lower serum lipids. However, the tissue‐specific functions of PPARα remain to be elucidated. This…