Fragile X Messenger Ribonucleoprotein 1(FMR1)gene mutations lead to fragile X syndrome,cognitive disorders,and,in some individuals,scoliosis and craniofacial abnormalities.Four-month-old(mo)male mice with deletion of ...Fragile X Messenger Ribonucleoprotein 1(FMR1)gene mutations lead to fragile X syndrome,cognitive disorders,and,in some individuals,scoliosis and craniofacial abnormalities.Four-month-old(mo)male mice with deletion of the FMR1 gene exhibit a mild increase in cortical and cancellous femoral bone mass.However,consequences of absence of FMR1 in bone of young/aged male/female mice and the cellular basis of the skeletal phenotype remain unknown.We found that absence of FMR1 results in improved bone properties with higher bone mineral density in both sexes and in 2-and 9-mo mice.The cancellous bone mass is higher only in females,whereas,cortical bone mass is higher in 2-and 9-mo males,but higher in 2-and lower in 9-mo female FMR1-knockout mice.Furthermore,male bones show higher biomechanical properties at 2mo,and females at both ages.Absence of FMR1 increases osteoblast/mineralization/bone formation and osteocyte dendricity/gene expression in vivo/ex vivo/in vitro,without affecting osteoclasts in vivo/ex vivo.Thus,FMR1 is a novel osteoblast/osteocyte differentiation inhibitor,and its absence leads to age-,site-and sex-dependent higher bone mass/strength.展开更多
OVER 2,000 years ago,silk was the symblol of China;1,000 ago,porcelain was the symblol of China;500 years ago,tea was the symblol of China;today,with human beings’increasing awarness in ecological preservation,the gi...OVER 2,000 years ago,silk was the symblol of China;1,000 ago,porcelain was the symblol of China;500 years ago,tea was the symblol of China;today,with human beings’increasing awarness in ecological preservation,the giant panda has become a symblol of China.In 1869,the French naturalist Armand David discovered the giant panda in Ya’an,and since then,the flagship species of biodiversity conservation has since stepped onto the world stage.展开更多
AIM:To assess effects of heme on messenger RNA(mRNA) and microRNA(miRNA) profiles of liver cells derived from humans.METHODS:We exposed human hepatoma cell line Huh-7 cells to excess iron protoporphyrin(heme)(10 μmol...AIM:To assess effects of heme on messenger RNA(mRNA) and microRNA(miRNA) profiles of liver cells derived from humans.METHODS:We exposed human hepatoma cell line Huh-7 cells to excess iron protoporphyrin(heme)(10 μmol/L) or induced heme deficiency by addition of 4,6-dioxoheptanoic acid(500 μmol/L),a potent inhibitor of aminolevulinic acid dehydratase,for 6 h or 24 h.We harvested total RNA from the cells and performed both mRNA and miRNA array analyses,with use of Affymetrix chips,reagents,and instruments(human genome U133 plus 2.0 and miRNA 2.0 arrays).We assessed changes and their significance and interrelationships with Target Scan,Pathway Studios,and Ingenuity software.RESULTS:Changes in mRNA levels were most numerous and striking at 6 h after heme treatment but were similar and still numerous at 24 h.After 6 h of heme exposure,the increase in heme oxygenase 1 gene expression was 60-fold by mRNA and 88-fold by quantitative reverse transcription-polymerase chain reaction.We found striking changes,especially up-regulation by heme of nuclear erythroid-2 related factor-mediated oxidative stress responses,protein ubiquitination,glucocorticoid signaling,P53 signaling,and changes in RNAs that regulate intermediary metabolism.Fewer mRNAs were down-regulated by heme,and the fold decreases were less exuberant than were the increases.Notable decreases after 24 h of heme exposure were patatin-like phospholipase domain-containing protein 3(-6.5-fold),neuronal PAS domain protein 2(-1.93-fold),and protoporphyrinogen oxidase(-1.7-fold).CONCLUSION:Heme excess exhibits several toxic effects on liver and kidney,which deserve study in humans and in animal models of the human porphyrias or other disorders.展开更多
2014年5月13日，Avid宣布．获奖后期制作公司Kill The Messenger，同时也是终极格斗锦标赛（UFC）的唯一音频制作公司选择了AvidS5Fusion数字音频？昆音调音台作为其圣莫妮卡公司的顶梁柱。这款强大的混合调音台及控制平台将助力公司满...2014年5月13日，Avid宣布．获奖后期制作公司Kill The Messenger，同时也是终极格斗锦标赛（UFC）的唯一音频制作公司选择了AvidS5Fusion数字音频？昆音调音台作为其圣莫妮卡公司的顶梁柱。这款强大的混合调音台及控制平台将助力公司满足体育赛事制作中制作周期短的需求．以求用最快的速度向不断增长的电视、网络及移动终端交付制作内容。展开更多
基金supported by the National Institutes of Health R01-AR053643Veterans Research Administration Merit Award I01BX00515+7 种基金a Research Support Funds Grant(RSFG),Indiana University Purdue University Indianapolis-Office of the Vice Chancellor for Research,Indianapolis to LIP.supported by ASBMR Fund for Research and Education Research and Collaborative Grant Programsupported by the National Institutes of Health R01AG067997 to CJHsupported by the IUPUI Diversity Scholars Research Program(DSRP)Diversity Summer Undergraduate Research Opportunity Program(DS-UROP)Indiana CTSI Student Summer Research ProgramIUPUI work study programsupported by the Life Health Science Internship(LHSI)。
文摘Fragile X Messenger Ribonucleoprotein 1(FMR1)gene mutations lead to fragile X syndrome,cognitive disorders,and,in some individuals,scoliosis and craniofacial abnormalities.Four-month-old(mo)male mice with deletion of the FMR1 gene exhibit a mild increase in cortical and cancellous femoral bone mass.However,consequences of absence of FMR1 in bone of young/aged male/female mice and the cellular basis of the skeletal phenotype remain unknown.We found that absence of FMR1 results in improved bone properties with higher bone mineral density in both sexes and in 2-and 9-mo mice.The cancellous bone mass is higher only in females,whereas,cortical bone mass is higher in 2-and 9-mo males,but higher in 2-and lower in 9-mo female FMR1-knockout mice.Furthermore,male bones show higher biomechanical properties at 2mo,and females at both ages.Absence of FMR1 increases osteoblast/mineralization/bone formation and osteocyte dendricity/gene expression in vivo/ex vivo/in vitro,without affecting osteoclasts in vivo/ex vivo.Thus,FMR1 is a novel osteoblast/osteocyte differentiation inhibitor,and its absence leads to age-,site-and sex-dependent higher bone mass/strength.
文摘OVER 2,000 years ago,silk was the symblol of China;1,000 ago,porcelain was the symblol of China;500 years ago,tea was the symblol of China;today,with human beings’increasing awarness in ecological preservation,the giant panda has become a symblol of China.In 1869,the French naturalist Armand David discovered the giant panda in Ya’an,and since then,the flagship species of biodiversity conservation has since stepped onto the world stage.
基金Supported by A Grant from NIH/NIDDK (DK38825) to Bonkovsky HLInstitutional Funds from the Carolinas Health Care Foundation and Carolinas Medical Center
文摘AIM:To assess effects of heme on messenger RNA(mRNA) and microRNA(miRNA) profiles of liver cells derived from humans.METHODS:We exposed human hepatoma cell line Huh-7 cells to excess iron protoporphyrin(heme)(10 μmol/L) or induced heme deficiency by addition of 4,6-dioxoheptanoic acid(500 μmol/L),a potent inhibitor of aminolevulinic acid dehydratase,for 6 h or 24 h.We harvested total RNA from the cells and performed both mRNA and miRNA array analyses,with use of Affymetrix chips,reagents,and instruments(human genome U133 plus 2.0 and miRNA 2.0 arrays).We assessed changes and their significance and interrelationships with Target Scan,Pathway Studios,and Ingenuity software.RESULTS:Changes in mRNA levels were most numerous and striking at 6 h after heme treatment but were similar and still numerous at 24 h.After 6 h of heme exposure,the increase in heme oxygenase 1 gene expression was 60-fold by mRNA and 88-fold by quantitative reverse transcription-polymerase chain reaction.We found striking changes,especially up-regulation by heme of nuclear erythroid-2 related factor-mediated oxidative stress responses,protein ubiquitination,glucocorticoid signaling,P53 signaling,and changes in RNAs that regulate intermediary metabolism.Fewer mRNAs were down-regulated by heme,and the fold decreases were less exuberant than were the increases.Notable decreases after 24 h of heme exposure were patatin-like phospholipase domain-containing protein 3(-6.5-fold),neuronal PAS domain protein 2(-1.93-fold),and protoporphyrinogen oxidase(-1.7-fold).CONCLUSION:Heme excess exhibits several toxic effects on liver and kidney,which deserve study in humans and in animal models of the human porphyrias or other disorders.
文摘2014年5月13日，Avid宣布．获奖后期制作公司Kill The Messenger，同时也是终极格斗锦标赛（UFC）的唯一音频制作公司选择了AvidS5Fusion数字音频？昆音调音台作为其圣莫妮卡公司的顶梁柱。这款强大的混合调音台及控制平台将助力公司满足体育赛事制作中制作周期短的需求．以求用最快的速度向不断增长的电视、网络及移动终端交付制作内容。
