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Polypoidal choroidal vasculopathy (PCV), a subtype of ‘wet’ age-related macular degeneration (AMD), constitutes up to 55% of cases of wet AMD in Asian patients. In contrast to the choroidal neovascularization (CNV) subtype, the genetic risk factors for PCV are relatively unknown. Exome sequencing analysis of a Han Chinese cohort followed by replication in four independent […]
Osteoblast-derived VEGF is important for bone development and postnatal bone homeostasis. Previous studies have demonstrated that VEGF affects bone repair and regeneration; however, the cellular mechanisms by which it works are not fully understood. In this study, we investigated the functions of osteoblast-derived VEGF in healing of a bone defect. The results indicate that osteoblast-derived […]
https://vblwp.azureedge.net/wordpress/2017/06/JCI.png100100Haig Didizianhttps://vblwp.azureedge.net/wordpress/2017/09/vbl_logo_no_icon.pngHaig Didizian2016-01-01 00:00:002017-06-01 16:35:30Osteoblast-derived VEGF regulates osteoblast differentiation and bone formation during bone repair
Cystic fibrosis (CF) is caused by mutations in the gene that encodes the cystic fibrosis transmembrane conductance regulator (CFTR) anion channel. In humans and pigs, the loss of CFTR impairs respiratory host defenses, causing airway infection. But CF mice are spared. We found that in all three species, CFTR secreted bicarbonate into airway surface liquid. […]
Low oxygen tension (hypoxia) regulates chondrocyte differentiation and metabolism. Hypoxia-inducible factor 1a (HIF1a) is a crucial hypoxic factor for chondrocyte growth and survival during development. The major metalloproteinase matrix metalloproteinase 13 (MMP13) is also associated with chondrocyte hypertrophy in adult articular cartilage, the lack of which protects from cartilage degradation and osteoarthritis (OA) in mice. […]
https://vblwp.azureedge.net/wordpress/2017/06/PNAS.png100100Haig Didizianhttps://vblwp.azureedge.net/wordpress/2017/09/vbl_logo_no_icon.pngHaig Didizian2016-01-01 00:00:002017-06-01 16:36:02Interaction of HIF1a and ß-catenin inhibits matrix metalloproteinase 13 expression and prevents cartilage damage in mice
Inflammation-associated pathways are active in intestinal epithelial cells (IECs) and contribute to the pathogenesis of colorectal cancer (CRC). Calcineurin, a phosphatase required for the activation of the nuclear factor of activated T cells (NFAT) family of transcription factors, shows increased expression in CRC. We therefore investigated the role of calcineurin in intestinal tumor development. We […]
Inhibition or genetic deletion of poly(ADP-ribose) (PAR) polymerase-1 (PARP-1) is protective against toxic insults in many organ systems. The molecular mechanisms underlying PARP-1–dependent cell death involve release of mitochondrial apoptosis-inducing factor (AIF) and its translocation to the nucleus, which results in chromatinolysis. We identified macrophage migration inhibitory factor (MIF) as a PARP-1–dependent AIF-associated nuclease (PAAN). […]
https://vblwp.azureedge.net/wordpress/2017/06/Science-5930814724b38.png101100Haig Didizianhttps://vblwp.azureedge.net/wordpress/2017/09/vbl_logo_no_icon.pngHaig Didizian2016-01-01 00:00:002017-06-02 11:12:59A nuclease that mediates cell death induced by DNA damage and poly(ADP-ribose) polymerase-1
Survival in threatening situations depends on the selection and rapid execution of an appropriate active or passive defensive response, yet the underlying brain circuitry is not understood. Here we use circuit-based optogenetic, in vivo and in vitro electrophysiological, and neuroanatomical tracing methods to define midbrain periaqueductal grey circuits for specific defensive behaviours. We identify an […]
Insulin signaling regulates many facets of animal physiology. Its dysregulation causes diabetes and other metabolic disorders. The spindle checkpoint proteins MAD2 and BUBR1 prevent precocious chromosome segregation and suppress aneuploidy. The MAD2 inhibitory protein p31comet promotes checkpoint inactivation and timely chromosome segregation. Here, we show that whole-body p31comet knockout mice die soon after birth and […]
A missense variant in FGD6 confers increased risk of polypoidal choroidal vasculopathy
Polypoidal choroidal vasculopathy (PCV), a subtype of ‘wet’ age-related macular degeneration (AMD), constitutes up to 55% of cases of wet AMD in Asian patients. In contrast to the choroidal neovascularization (CNV) subtype, the genetic risk factors for PCV are relatively unknown. Exome sequencing analysis of a Han Chinese cohort followed by replication in four independent […]
Osteoblast-derived VEGF regulates osteoblast differentiation and bone formation during bone repair
Osteoblast-derived VEGF is important for bone development and postnatal bone homeostasis. Previous studies have demonstrated that VEGF affects bone repair and regeneration; however, the cellular mechanisms by which it works are not fully understood. In this study, we investigated the functions of osteoblast-derived VEGF in healing of a bone defect. The results indicate that osteoblast-derived […]
Airway acidification initiates host defense abnormalities in cystic fibrosis mice
Cystic fibrosis (CF) is caused by mutations in the gene that encodes the cystic fibrosis transmembrane conductance regulator (CFTR) anion channel. In humans and pigs, the loss of CFTR impairs respiratory host defenses, causing airway infection. But CF mice are spared. We found that in all three species, CFTR secreted bicarbonate into airway surface liquid. […]
Interaction of HIF1a and ß-catenin inhibits matrix metalloproteinase 13 expression and prevents cartilage damage in mice
Low oxygen tension (hypoxia) regulates chondrocyte differentiation and metabolism. Hypoxia-inducible factor 1a (HIF1a) is a crucial hypoxic factor for chondrocyte growth and survival during development. The major metalloproteinase matrix metalloproteinase 13 (MMP13) is also associated with chondrocyte hypertrophy in adult articular cartilage, the lack of which protects from cartilage degradation and osteoarthritis (OA) in mice. […]
Epithelial calcineurin controls microbiota-dependent intestinal tumor development
Inflammation-associated pathways are active in intestinal epithelial cells (IECs) and contribute to the pathogenesis of colorectal cancer (CRC). Calcineurin, a phosphatase required for the activation of the nuclear factor of activated T cells (NFAT) family of transcription factors, shows increased expression in CRC. We therefore investigated the role of calcineurin in intestinal tumor development. We […]
A nuclease that mediates cell death induced by DNA damage and poly(ADP-ribose) polymerase-1
Inhibition or genetic deletion of poly(ADP-ribose) (PAR) polymerase-1 (PARP-1) is protective against toxic insults in many organ systems. The molecular mechanisms underlying PARP-1–dependent cell death involve release of mitochondrial apoptosis-inducing factor (AIF) and its translocation to the nucleus, which results in chromatinolysis. We identified macrophage migration inhibitory factor (MIF) as a PARP-1–dependent AIF-associated nuclease (PAAN). […]
Midbrain circuits for defensive behaviour
Survival in threatening situations depends on the selection and rapid execution of an appropriate active or passive defensive response, yet the underlying brain circuitry is not understood. Here we use circuit-based optogenetic, in vivo and in vitro electrophysiological, and neuroanatomical tracing methods to define midbrain periaqueductal grey circuits for specific defensive behaviours. We identify an […]
Mitotic Checkpoint Regulators Control Insulin Signaling and Metabolic Homeostasis
Insulin signaling regulates many facets of animal physiology. Its dysregulation causes diabetes and other metabolic disorders. The spindle checkpoint proteins MAD2 and BUBR1 prevent precocious chromosome segregation and suppress aneuploidy. The MAD2 inhibitory protein p31comet promotes checkpoint inactivation and timely chromosome segregation. Here, we show that whole-body p31comet knockout mice die soon after birth and […]