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As the central pacemaker, the suprachiasmatic nucleus (SCN) has long been considered the primary regulator of blood pressure circadian rhythm; however, this dogma has been challenged by the discovery that each of the clock genes present in the SCN is also expressed and functions in peripheral tissues. The involvement and contribution of these peripheral clock […]
Mitochondrial homeostasis is critical for tissue health, and mitochondrial dysfunction contributes to numerous diseases, including heart failure. Here, we have shown that the transcription factor Kruppel-like factor 4 (KLF4) governs mitochondrial biogenesis, metabolic function, dynamics, and autophagic clearance. Adult mice with cardiac-specific Klf4 deficiency developed cardiac dysfunction with aging or in response to pressure overload […]
https://vblwp.azureedge.net/wordpress/2017/06/JCI.png100100Haig Didizianhttps://vblwp.azureedge.net/wordpress/2017/09/vbl_logo_no_icon.pngHaig Didizian2015-01-01 00:00:002017-06-01 16:45:48Kruppel-like factor 4 is critical for transcriptional control of cardiac mitochondrial homeostasis
Dietary restriction (DR) without malnutrition encompasses numerous regimens with overlapping benefits including longevity and stress resistance, but unifying nutritional and molecular mechanisms remain elusive. In a mouse model of DR-mediated stress resistance, we found that sulfur amino acid (SAA) restriction increased expression of the transsulfuration pathway (TSP) enzyme cystathionine ¿-lyase (CGL), resulting in increased hydrogen […]
https://vblwp.azureedge.net/wordpress/2017/01/Cell.png100100Haig Didizianhttps://vblwp.azureedge.net/wordpress/2017/09/vbl_logo_no_icon.pngHaig Didizian2015-01-01 00:00:002017-06-01 17:09:25Endogenous Hydrogen Sulfide Production Is Essential for Dietary Restriction Benefits
Huntington’s disease (HD) is a progressive neurodegenerative disease caused by a glutamine repeat expansion in mutant huntingtin (mHtt). Despite the known genetic cause of HD, the pathophysiology of this disease remains to be elucidated. Inositol polyphosphate multikinase (IPMK) is an enzyme that displays soluble inositol phosphate kinase activity, lipid kinase activity, and various noncatalytic interactions. […]
Neurodegenerative diseases have been linked to inflammation, but whether altered immunomodulation plays a causative role in neurodegeneration is not clear. We show that lack of cytokine interferon-b (IFN-b) signaling causes spontaneous neurodegeneration in the absence of neurodegenerative disease-causing mutant proteins. Mice lacking Ifnb function exhibited motor and cognitive learning impairments with accompanying a-synuclein-containing Lewy bodies […]
Changes in cell fate and identity are essential for endothelial-to-haematopoietic transition (EHT), an embryonic process that generates the first adult populations of haematopoietic stem cells (HSCs) from hemogenic endothelial cells. Dissecting EHT regulation is a critical step towards the production of in vitro derived HSCs. Yet, we do not know how distinct endothelial and haematopoietic […]
https://vblwp.azureedge.net/wordpress/2017/06/Nature-Comm.png100100Haig Didizianhttps://vblwp.azureedge.net/wordpress/2017/09/vbl_logo_no_icon.pngHaig Didizian2015-01-01 00:00:002017-06-01 17:10:15Repression of arterial genes in hemogenic endothelium is sufficient for haematopoietic fate acquisition
Although stem cell populations mediate regeneration of rapid turnover tissues, such as skin, blood, and gut, a stem cell reservoir has not been identified for some slower turnover tissues, such as the pancreatic islet. Despite lacking identifiable stem cells, murine pancreatic ß cell number expands in response to an increase in insulin demand. Lineage tracing […]
https://vblwp.azureedge.net/wordpress/2017/06/JCI.png100100Haig Didizianhttps://vblwp.azureedge.net/wordpress/2017/09/vbl_logo_no_icon.pngHaig Didizian2015-01-01 00:00:002017-06-01 17:11:10Insulin demand regulates ß cell number via the unfolded protein response
Obesity, and the associated disturbed glycerolipid/fatty acid (GL/FA) cycle, contribute to insulin resistance, islet ß-cell failure, and type 2 diabetes. Flux through the GL/FA cycle is regulated by the availability of glycerol-3-phosphate (Gro3P) and fatty acyl-CoA. We describe here a mammalian Gro3P phosphatase (G3PP), which was not known to exist in mammalian cells, that can […]
https://vblwp.azureedge.net/wordpress/2017/06/PNAS.png100100Haig Didizianhttps://vblwp.azureedge.net/wordpress/2017/09/vbl_logo_no_icon.pngHaig Didizian2015-01-01 00:00:002017-06-01 17:10:53Identification of a mammalian glycerol-3-phosphate phosphatase: Role in metabolism and signaling in pancreatic ß-cells and hepatocytes
Smooth-muscle BMAL1 participates in blood pressure circadian rhythm regulation
As the central pacemaker, the suprachiasmatic nucleus (SCN) has long been considered the primary regulator of blood pressure circadian rhythm; however, this dogma has been challenged by the discovery that each of the clock genes present in the SCN is also expressed and functions in peripheral tissues. The involvement and contribution of these peripheral clock […]
Kruppel-like factor 4 is critical for transcriptional control of cardiac mitochondrial homeostasis
Mitochondrial homeostasis is critical for tissue health, and mitochondrial dysfunction contributes to numerous diseases, including heart failure. Here, we have shown that the transcription factor Kruppel-like factor 4 (KLF4) governs mitochondrial biogenesis, metabolic function, dynamics, and autophagic clearance. Adult mice with cardiac-specific Klf4 deficiency developed cardiac dysfunction with aging or in response to pressure overload […]
Endogenous Hydrogen Sulfide Production Is Essential for Dietary Restriction Benefits
Dietary restriction (DR) without malnutrition encompasses numerous regimens with overlapping benefits including longevity and stress resistance, but unifying nutritional and molecular mechanisms remain elusive. In a mouse model of DR-mediated stress resistance, we found that sulfur amino acid (SAA) restriction increased expression of the transsulfuration pathway (TSP) enzyme cystathionine ¿-lyase (CGL), resulting in increased hydrogen […]
Huntingto’s disease: Neural dysfunction linked to inositol polyphosphate multikinase
Huntington’s disease (HD) is a progressive neurodegenerative disease caused by a glutamine repeat expansion in mutant huntingtin (mHtt). Despite the known genetic cause of HD, the pathophysiology of this disease remains to be elucidated. Inositol polyphosphate multikinase (IPMK) is an enzyme that displays soluble inositol phosphate kinase activity, lipid kinase activity, and various noncatalytic interactions. […]
Lack of Neuronal IFN-b-IFNAR Causes Lewy Body- and Parkinson’s Disease-like Dementia
Neurodegenerative diseases have been linked to inflammation, but whether altered immunomodulation plays a causative role in neurodegeneration is not clear. We show that lack of cytokine interferon-b (IFN-b) signaling causes spontaneous neurodegeneration in the absence of neurodegenerative disease-causing mutant proteins. Mice lacking Ifnb function exhibited motor and cognitive learning impairments with accompanying a-synuclein-containing Lewy bodies […]
Repression of arterial genes in hemogenic endothelium is sufficient for haematopoietic fate acquisition
Changes in cell fate and identity are essential for endothelial-to-haematopoietic transition (EHT), an embryonic process that generates the first adult populations of haematopoietic stem cells (HSCs) from hemogenic endothelial cells. Dissecting EHT regulation is a critical step towards the production of in vitro derived HSCs. Yet, we do not know how distinct endothelial and haematopoietic […]
Insulin demand regulates ß cell number via the unfolded protein response
Although stem cell populations mediate regeneration of rapid turnover tissues, such as skin, blood, and gut, a stem cell reservoir has not been identified for some slower turnover tissues, such as the pancreatic islet. Despite lacking identifiable stem cells, murine pancreatic ß cell number expands in response to an increase in insulin demand. Lineage tracing […]
Identification of a mammalian glycerol-3-phosphate phosphatase: Role in metabolism and signaling in pancreatic ß-cells and hepatocytes
Obesity, and the associated disturbed glycerolipid/fatty acid (GL/FA) cycle, contribute to insulin resistance, islet ß-cell failure, and type 2 diabetes. Flux through the GL/FA cycle is regulated by the availability of glycerol-3-phosphate (Gro3P) and fatty acyl-CoA. We describe here a mammalian Gro3P phosphatase (G3PP), which was not known to exist in mammalian cells, that can […]