Nicotinamide adenine dinucleotide(NAD^(+))/reduced NAD^(+)(NADH)and nicotinamide adenine dinucleotide phosphate(NADP^(+))/reduced NADP^(+)(NADPH)are essential metabolites involved in multiple metabolic pathways and ce...Nicotinamide adenine dinucleotide(NAD^(+))/reduced NAD^(+)(NADH)and nicotinamide adenine dinucleotide phosphate(NADP^(+))/reduced NADP^(+)(NADPH)are essential metabolites involved in multiple metabolic pathways and cellular processes.NAD^(+)and NADH redox couple plays a vital role in catabolic redox reactions,while NADPH is crucial for cellular anabolism and antioxidant responses.Maintaining NAD(H)and NADP(H)homeostasis is crucial for normal physiological activity and is tightly regulated through various mechanisms,such as biosynthesis,consumption,recycling,and conversion between NAD(H)and NADP(H).The conversions between NAD(H)and NADP(H)are controlled by NAD kinases(NADKs)and NADP(H)phosphatases[specifically,metazoan SpoT homolog-1(MESH1)and nocturnin(NOCT)].NADKs facilitate the synthesis of NADP^(+)from NAD^(+),while MESH1 and NOCT convert NADP(H)into NAD(H).In this review,we summarize the physiological roles of NAD(H)and NADP(H)and discuss the regulatory mechanisms governing NAD(H)and NADP(H)homeostasis in three key aspects:the transcriptional and posttranslational regulation of NADKs,the role of MESH1 and NOCT in maintaining NAD(H)and NADP(H)homeostasis,and the influence of the circadian clock on NAD(H)and NADP(H)homeostasis.In conclusion,NADKs,MESH1,and NOCT are integral to various cellular processes,regulating NAD(H)and NADP(H)homeostasis.Dysregulation of these enzymes results in various human diseases,such as cancers and metabolic disorders.Hence,strategies aiming to restore NAD(H)and NADP(H)homeostasis hold promise as novel therapeutic approaches for these diseases.展开更多
Sleep is essential for animals,and receives inputs from circadian,homeostasis,and environment,yet the mechanisms of sleep regulation remain elusive.Discovery of molecules in living systems and demonstration of their f...Sleep is essential for animals,and receives inputs from circadian,homeostasis,and environment,yet the mechanisms of sleep regulation remain elusive.Discovery of molecules in living systems and demonstration of their functional roles are pivotal in furthering our understanding of the molecular basis of biology.Here,we report that guanosine-50-diphos-phate,30-diphosphate(ppGpp)is present in Drosophila,and plays an important role in regulation of sleep and starvation-induced sleep loss(SISL).ppGpp is detected in germ-free Drosophila and hydrolyzed by an enzyme encoded by the mesh1 gene in Drosophila.Nighttime sleep and SISL were defected in mesh1 mutant flies,and rescued by expression of wildtype Mesh1,but not the enzymatically defective mutant Mesh1E66A.Ectopic expression of RelA,the Escherichia coli synthetase for ppGpp,phenocopied mesh1 knockout mutants,whereas overexpression of Mesh1 resulted in the opposite phenotypes,supporting that ppGpp is both necessary and sufficient in sleep regulation.A chemo connectomic screen followed by genetic intersection experiments implicates the Dilp2 neurons in the pars intercerebralis(PI)brain region as the site of ppGpp function.Our results have thus validated the presence of ppGpp in Drosophila and revealed a physiological role of ppGpp in sleep regulation for the first time.展开更多
In this paper we study the convergence of adaptive finite element methods for the gen- eral non-attine equivalent quadrilateral and hexahedral elements on 1-irregular meshes with hanging nodes. Based on several basic ...In this paper we study the convergence of adaptive finite element methods for the gen- eral non-attine equivalent quadrilateral and hexahedral elements on 1-irregular meshes with hanging nodes. Based on several basic ingredients, such as quasi-orthogonality, estimator reduction and D6fler marking strategy, convergence of the adaptive finite element methods for the general second-order elliptic partial equations is proved. Our analysis is effective for all conforming Qm elements which covers both the two- and three-dimensional cases in a unified fashion.展开更多
文摘Nicotinamide adenine dinucleotide(NAD^(+))/reduced NAD^(+)(NADH)and nicotinamide adenine dinucleotide phosphate(NADP^(+))/reduced NADP^(+)(NADPH)are essential metabolites involved in multiple metabolic pathways and cellular processes.NAD^(+)and NADH redox couple plays a vital role in catabolic redox reactions,while NADPH is crucial for cellular anabolism and antioxidant responses.Maintaining NAD(H)and NADP(H)homeostasis is crucial for normal physiological activity and is tightly regulated through various mechanisms,such as biosynthesis,consumption,recycling,and conversion between NAD(H)and NADP(H).The conversions between NAD(H)and NADP(H)are controlled by NAD kinases(NADKs)and NADP(H)phosphatases[specifically,metazoan SpoT homolog-1(MESH1)and nocturnin(NOCT)].NADKs facilitate the synthesis of NADP^(+)from NAD^(+),while MESH1 and NOCT convert NADP(H)into NAD(H).In this review,we summarize the physiological roles of NAD(H)and NADP(H)and discuss the regulatory mechanisms governing NAD(H)and NADP(H)homeostasis in three key aspects:the transcriptional and posttranslational regulation of NADKs,the role of MESH1 and NOCT in maintaining NAD(H)and NADP(H)homeostasis,and the influence of the circadian clock on NAD(H)and NADP(H)homeostasis.In conclusion,NADKs,MESH1,and NOCT are integral to various cellular processes,regulating NAD(H)and NADP(H)homeostasis.Dysregulation of these enzymes results in various human diseases,such as cancers and metabolic disorders.Hence,strategies aiming to restore NAD(H)and NADP(H)homeostasis hold promise as novel therapeutic approaches for these diseases.
基金National Natural Science Foundation of China (32061143017 to Y.R.)the Research Unit of Medical Neurobi-ology,Chinese Academy of Medical Sciences (No.2019RU003)for grant support.
文摘Sleep is essential for animals,and receives inputs from circadian,homeostasis,and environment,yet the mechanisms of sleep regulation remain elusive.Discovery of molecules in living systems and demonstration of their functional roles are pivotal in furthering our understanding of the molecular basis of biology.Here,we report that guanosine-50-diphos-phate,30-diphosphate(ppGpp)is present in Drosophila,and plays an important role in regulation of sleep and starvation-induced sleep loss(SISL).ppGpp is detected in germ-free Drosophila and hydrolyzed by an enzyme encoded by the mesh1 gene in Drosophila.Nighttime sleep and SISL were defected in mesh1 mutant flies,and rescued by expression of wildtype Mesh1,but not the enzymatically defective mutant Mesh1E66A.Ectopic expression of RelA,the Escherichia coli synthetase for ppGpp,phenocopied mesh1 knockout mutants,whereas overexpression of Mesh1 resulted in the opposite phenotypes,supporting that ppGpp is both necessary and sufficient in sleep regulation.A chemo connectomic screen followed by genetic intersection experiments implicates the Dilp2 neurons in the pars intercerebralis(PI)brain region as the site of ppGpp function.Our results have thus validated the presence of ppGpp in Drosophila and revealed a physiological role of ppGpp in sleep regulation for the first time.
基金supported by the Special Funds for Major State Basic Research Project (No. 2005CB321701)
文摘In this paper we study the convergence of adaptive finite element methods for the gen- eral non-attine equivalent quadrilateral and hexahedral elements on 1-irregular meshes with hanging nodes. Based on several basic ingredients, such as quasi-orthogonality, estimator reduction and D6fler marking strategy, convergence of the adaptive finite element methods for the general second-order elliptic partial equations is proved. Our analysis is effective for all conforming Qm elements which covers both the two- and three-dimensional cases in a unified fashion.
