Mechanical forces shape the development,function,and survival of every cell within the central nervous system(CNS)but are particularly important for astroglia,a subtype of glial cell that mediates communication betwee...Mechanical forces shape the development,function,and survival of every cell within the central nervous system(CNS)but are particularly important for astroglia,a subtype of glial cell that mediates communication between neurons and blood vessels.展开更多
Unesterified cholesterol controls the fluidity, permeability and electrical properties of eukaryotic cell mem- branes. Consequently, cholesterol levels in the retina and the brain are tightly regulated whereas depleti...Unesterified cholesterol controls the fluidity, permeability and electrical properties of eukaryotic cell mem- branes. Consequently, cholesterol levels in the retina and the brain are tightly regulated whereas depletion or oversupply caused by diet or heredity contribute to neurodegenerative diseases and vision loss. Astrog- lia play a central role in the biosynthesis, uptake and transport of cholesterol and also drive inflammatory signaling under hypercholesterolemic conditions associated with high-fat diet (diabetes) and neurodegen- erative disease. A growing body of evidence shows that unesterified membrane cholesterol modulates the ability of glia to sense and transduce ambient information. Cholesterol-dependence of Mfiller glia - which function as retinal sentinels for metabolic, mechanical, osmotic and inflammatory signals - is mediated in part by transient receptor potential V4 (TRPV4) channels. Cholesterol supplementation facilitates, where- as depletion suppresses, TRPV4-mediated transduction of temperature and lipid agonists in Mfiller cells. Acute effects of cholesterol supplementation/depletion on plasma membrane ion channels and calcium ho- meostasis differ markedly from the effects of chronic dyslipidemia, possibly due to differential modulation of modality-dependent energy barriers associated with the functionality of polymodal channels embedded within lipid rafts. Understanding of cholesterol-dependence of TRP channels is thus providing insight into dyslipidemic pathologies associated with diabetic retinopathy, glaucoma and macular degeneration.展开更多
Built environments can induce contemplative states, but direct evidence for their impact on the brain is lacking. This exploratory work investigated brain correlates of internal states elicited by architecture designe...Built environments can induce contemplative states, but direct evidence for their impact on the brain is lacking. This exploratory work investigated brain correlates of internal states elicited by architecture designed for contemplative experience. Functional MRI and self-reports of 12 architects were assessed to study their responses to photographs of ordinary and contemplative architectures. Images of contemplative buildings: (1) induced attentive, receptive, and absorbing experiences and diminished internal dialogue; (2) involved decreased engagement of prefrontal cortex; and (3) activated the occipital lobe, precentra[ gyrus, and inferior parietal lobule. They suggest that viewing buildings designed for contemplation may evoke experiential and brain signatures that consistently differ from those induced by buildings that serve everyday functions. The depth of such externally induced states was inversely correlated with the engagement of the Default Mode Network. Our study points toward a novel avenue for investigating how contemplation can be cultivated in the human brain/mind.展开更多
基金supported by the National Institutes of Health(R01EY027920:Cellular and Molecular Mechanisms that Contribute to Pressure-Induced Retinal Inflammation to DK),EY027920Molecular mechanisms of mechanotransduction in the aqueous outflow pathway(to DK),T32EY024234+3 种基金Vision Research Training award(to JMB and CNR),P30EY014800Vision Core Grant at the University of Utah(to DK)Stauss-Rankin Foundation(to DK)an Unrestricted Grant from Research to Prevent Blindness to the Department of Ophthalmology at the University of Utah。
文摘Mechanical forces shape the development,function,and survival of every cell within the central nervous system(CNS)but are particularly important for astroglia,a subtype of glial cell that mediates communication between neurons and blood vessels.
基金supported by the NIH(R01EY022076,R01EY027920P30EY014800)+1 种基金the Willard Eccles Foundation,Glaucoma Research Foundationthe Diabetes and Metabolism Center at the University of Utah and unrestricted support from Research to Prevent Blindness to the Moran Eye Institute at the University of Utah,USA
文摘Unesterified cholesterol controls the fluidity, permeability and electrical properties of eukaryotic cell mem- branes. Consequently, cholesterol levels in the retina and the brain are tightly regulated whereas depletion or oversupply caused by diet or heredity contribute to neurodegenerative diseases and vision loss. Astrog- lia play a central role in the biosynthesis, uptake and transport of cholesterol and also drive inflammatory signaling under hypercholesterolemic conditions associated with high-fat diet (diabetes) and neurodegen- erative disease. A growing body of evidence shows that unesterified membrane cholesterol modulates the ability of glia to sense and transduce ambient information. Cholesterol-dependence of Mfiller glia - which function as retinal sentinels for metabolic, mechanical, osmotic and inflammatory signals - is mediated in part by transient receptor potential V4 (TRPV4) channels. Cholesterol supplementation facilitates, where- as depletion suppresses, TRPV4-mediated transduction of temperature and lipid agonists in Mfiller cells. Acute effects of cholesterol supplementation/depletion on plasma membrane ion channels and calcium ho- meostasis differ markedly from the effects of chronic dyslipidemia, possibly due to differential modulation of modality-dependent energy barriers associated with the functionality of polymodal channels embedded within lipid rafts. Understanding of cholesterol-dependence of TRP channels is thus providing insight into dyslipidemic pathologies associated with diabetic retinopathy, glaucoma and macular degeneration.
文摘Built environments can induce contemplative states, but direct evidence for their impact on the brain is lacking. This exploratory work investigated brain correlates of internal states elicited by architecture designed for contemplative experience. Functional MRI and self-reports of 12 architects were assessed to study their responses to photographs of ordinary and contemplative architectures. Images of contemplative buildings: (1) induced attentive, receptive, and absorbing experiences and diminished internal dialogue; (2) involved decreased engagement of prefrontal cortex; and (3) activated the occipital lobe, precentra[ gyrus, and inferior parietal lobule. They suggest that viewing buildings designed for contemplation may evoke experiential and brain signatures that consistently differ from those induced by buildings that serve everyday functions. The depth of such externally induced states was inversely correlated with the engagement of the Default Mode Network. Our study points toward a novel avenue for investigating how contemplation can be cultivated in the human brain/mind.