A large amount of nicotinamide adenine dinucleotide phosphate(NADPH) is required for fatty acid synthesis and maintenance of the redox state in cancer cells.Malic enzyme 1(ME1)-dependent NADPH production is one of the...A large amount of nicotinamide adenine dinucleotide phosphate(NADPH) is required for fatty acid synthesis and maintenance of the redox state in cancer cells.Malic enzyme 1(ME1)-dependent NADPH production is one of the three pathways that contribute to the formation of the cytosolic NADPH pool.ME1 is generally considered to be overexpressed in cancer cells to meet the high demand for increased de novo fatty acid synthesis.In the present study,we found that glucose induced higher ME1 activity and that repressing ME1 had a profound impact on glucose metabolism of nasopharyngeal carcinoma(NPC) cells.High incorporation of glucose and an enhancement of the pentose phosphate pathway were observed in ME1-repressed cells.However,there were no obvious changes in the other two pathways for glucose metabolism:glycolysis and oxidative phosphorylation.Interestingly,NADPH was decreased under low-glucose condition in ME1-repressed cells relative to wild-type cells,whereas no significant difference was observed under high-glucose condition.ME1-repressed cells had significantly decreased tolerance to low-glucose condition.Moreover,NADPH produced by ME1 was not only important for fatty acid synthesis but also essential for maintenance of the intracellular redox state and the protection of cells from oxidative stress.Furthermore,diminished migration and invasion were observed in ME1-repressed cells due to a reduced level of Snail protein.Collectively,these results suggest an essential role for ME1 in the production of cytosolic NADPH and maintenance of migratory and invasive abilities of NPC cells.展开更多
The pathogenic mechanisms underlying Batten disease are unclear. Patients unif ormly possess autoantibodies against glutamic acid decarboxylase (GAD) that are predominantly reactive with a region of GAD (amino acids 1...The pathogenic mechanisms underlying Batten disease are unclear. Patients unif ormly possess autoantibodies against glutamic acid decarboxylase (GAD) that are predominantly reactive with a region of GAD (amino acids 1 to 20) distinct from subjects with autoimmune type 1 diabetes or stiff-person syndrome.Batten patien ts did not possess autoantibodies against other type 1 diabetes-associated auto antigens and human leukocyte antigen genotypes revealed no specific associations with this disease.展开更多
Objectives The study assessed racia l differences in vaginal pH among women without bacterial vag inosis.Study design Data from the Vaginal Infections and Prematurity(VIP)Study were analyzed.From 1984to 1989,13,917lar...Objectives The study assessed racia l differences in vaginal pH among women without bacterial vag inosis.Study design Data from the Vaginal Infections and Prematurity(VIP)Study were analyzed.From 1984to 1989,13,917largely low -income women were enrolled during routine prenatal visits from 23to 26weeks’gestation.Vaginal cultures,Gram stains,and pH levels were colle cted.Comparisons of pH by race were made among women with G ram stain scores<7and without trichomoniasis before and after ad-justment for actual Gram stain score.Results Amongwomen with Gram stain scores<7,there was a modest but statis-tically significant racial differe nce in vaginal pH level.However,after controlling for diff erence in Gram stain score,age,and study site,there was no longer a signifi-cant difference in vaginal pH.Conclusion There is no sig-nificant difference in vaginal pH le vel between black and white women after controlling for di fferences in confounding factors,particularly vaginal flora.展开更多
To improve the prediction accuracy of semiparametric additive partial linear models(APLM) and the coverage probability of confidence intervals of the parameters of interest,we explore a focused information criterion f...To improve the prediction accuracy of semiparametric additive partial linear models(APLM) and the coverage probability of confidence intervals of the parameters of interest,we explore a focused information criterion for model selection among ALPM after we estimate the nonparametric functions by the polynomial spline smoothing,and introduce a general model average estimator.The major advantage of the proposed procedures is that iterative backfitting implementation is avoided,which thus results in gains in computational simplicity.The resulting estimators are shown to be asymptotically normal.A simulation study and a real data analysis are presented for illustrations.展开更多
基金supported by grants from the Major State Basic Research Program (973 Project) of China(No.2006CB910104 and 2010CB912201)the National High Technology Research and Development Program of China (863 Program) (No.20060102A4002)+1 种基金the State Key Program of National Natural Science Foundation of China (No.81030043)the Guangdong Province-National Natural Science Foundation of China Cooperation Program (No.u0732005)
文摘A large amount of nicotinamide adenine dinucleotide phosphate(NADPH) is required for fatty acid synthesis and maintenance of the redox state in cancer cells.Malic enzyme 1(ME1)-dependent NADPH production is one of the three pathways that contribute to the formation of the cytosolic NADPH pool.ME1 is generally considered to be overexpressed in cancer cells to meet the high demand for increased de novo fatty acid synthesis.In the present study,we found that glucose induced higher ME1 activity and that repressing ME1 had a profound impact on glucose metabolism of nasopharyngeal carcinoma(NPC) cells.High incorporation of glucose and an enhancement of the pentose phosphate pathway were observed in ME1-repressed cells.However,there were no obvious changes in the other two pathways for glucose metabolism:glycolysis and oxidative phosphorylation.Interestingly,NADPH was decreased under low-glucose condition in ME1-repressed cells relative to wild-type cells,whereas no significant difference was observed under high-glucose condition.ME1-repressed cells had significantly decreased tolerance to low-glucose condition.Moreover,NADPH produced by ME1 was not only important for fatty acid synthesis but also essential for maintenance of the intracellular redox state and the protection of cells from oxidative stress.Furthermore,diminished migration and invasion were observed in ME1-repressed cells due to a reduced level of Snail protein.Collectively,these results suggest an essential role for ME1 in the production of cytosolic NADPH and maintenance of migratory and invasive abilities of NPC cells.
文摘The pathogenic mechanisms underlying Batten disease are unclear. Patients unif ormly possess autoantibodies against glutamic acid decarboxylase (GAD) that are predominantly reactive with a region of GAD (amino acids 1 to 20) distinct from subjects with autoimmune type 1 diabetes or stiff-person syndrome.Batten patien ts did not possess autoantibodies against other type 1 diabetes-associated auto antigens and human leukocyte antigen genotypes revealed no specific associations with this disease.
文摘Objectives The study assessed racia l differences in vaginal pH among women without bacterial vag inosis.Study design Data from the Vaginal Infections and Prematurity(VIP)Study were analyzed.From 1984to 1989,13,917largely low -income women were enrolled during routine prenatal visits from 23to 26weeks’gestation.Vaginal cultures,Gram stains,and pH levels were colle cted.Comparisons of pH by race were made among women with G ram stain scores<7and without trichomoniasis before and after ad-justment for actual Gram stain score.Results Amongwomen with Gram stain scores<7,there was a modest but statis-tically significant racial differe nce in vaginal pH level.However,after controlling for diff erence in Gram stain score,age,and study site,there was no longer a signifi-cant difference in vaginal pH.Conclusion There is no sig-nificant difference in vaginal pH le vel between black and white women after controlling for di fferences in confounding factors,particularly vaginal flora.
基金supported by US National Science Foundation (Grant No.DMS-0806097)
文摘To improve the prediction accuracy of semiparametric additive partial linear models(APLM) and the coverage probability of confidence intervals of the parameters of interest,we explore a focused information criterion for model selection among ALPM after we estimate the nonparametric functions by the polynomial spline smoothing,and introduce a general model average estimator.The major advantage of the proposed procedures is that iterative backfitting implementation is avoided,which thus results in gains in computational simplicity.The resulting estimators are shown to be asymptotically normal.A simulation study and a real data analysis are presented for illustrations.
