Alzheimer’s disease is a neurodegenerative disease that affected over 6.5 million people in the United States in 2021,with this number expected to double in the next 40 years without any sort of treatment.Due to its ...Alzheimer’s disease is a neurodegenerative disease that affected over 6.5 million people in the United States in 2021,with this number expected to double in the next 40 years without any sort of treatment.Due to its heterogeneity and complexity,the etiology of Alzheimer’s disease,especially sporadic Alzheimer’s disease,remains largely unclear.Compelling evidence suggests that brain glucose hypometabolism,preceding Alzheimer’s disease hallmarks,is involved in the pathogenesis of Alzheimer’s disease.Herein,we discuss the potential causes of reduced glucose uptake and the mechanisms underlying glucose hypometabolism and Alzheimer’s disease pathology.Specifically,decreased O-Glc NAcylation levels by glucose deficiency alter mitochondrial functions and together contribute to Alzheimer’s disease pathogenesis.One major problem with Alzheimer’s disease research is that the disease progresses for several years before the onset of any symptoms,suggesting the critical need for appropriate models to study the molecular changes in the early phase of Alzheimer’s disease progression.Therefore,this review also discusses current available sporadic Alzheimer’s disease models induced by metabolic abnormalities and provides novel directions for establishing a human neuronal sporadic Alzheimer’s disease model that better represents human sporadic Alzheimer’s disease as a metabolic disease.展开更多
The advent of superficially porous particles （SPPs） for packed HPLC columns has changed the way that many practitioners have approached the problem of developing needed separations. The very high efficiency of such ...The advent of superficially porous particles （SPPs） for packed HPLC columns has changed the way that many practitioners have approached the problem of developing needed separations. The very high efficiency of such columns, combined with convenient operating conditions, modest back pressures and the ability to use conventional HPLC instruments has resulted in intense basic studies of SPP technology, and widespread applications in many sciences. This report contains an overview of the SPP technology first developed in 2006 by Advanced Materials Technology, Inc., for sub-3-11m particles, then expanded into a family of SPP products with different particle sizes, pore sizes and other physical parameters. This approach was designed so that each particle of the family could be optimized for separating a particular group of compounds, usually based on solute size.展开更多
Hyaluronan(HA)is a naturally occurring polysaccharide in the organism.As one of the main components of the extracellular matrix,it plays an important role in regulating various cellular processes,including proliferati...Hyaluronan(HA)is a naturally occurring polysaccharide in the organism.As one of the main components of the extracellular matrix,it plays an important role in regulating various cellular processes,including proliferation,differentiation,inflammation,and immunity,through interaction with HA receptors.HA is widely found in the human body,particularly in the skin and joints,thus playing a crucial role in the functioning of these tissues.The aging of the skin and the occurrence of osteoarthritis are related to the loss of HA.Supplementing HA in the appropriate areas can delay or prevent these processes.Common methods of HA supplementation include topical application to the skin or injection into the joint cavities,both of which have shown efficacy in restoring HA levels and improving tissue function.In recent years,studies have shown that oral administration of HA can also have similar effects.Oral HA first passes through the gastrointestinal tract and then enters the liver with the blood circulation.Therefore,in addition to supplementing the HA content in the body,oral HA can also exert beneficial effects on the gastrointestinal tract and the liver,such as enhancing the barrier function of the gastrointestinal tract,regulating the intestinal flora,and reducing inflammation.Supplementation of HA has numerous benefits for the skin,orthopedic disorders,gastrointestinal tract and liver.Therefore,it is important to understand the mechanisms through which HA exerts these effects.This article describes the basic properties of HA and reviews its relationship with skin,orthopedic diseases,gastrointestinal tract and liver,as well as its applications in these areas.展开更多
Galacturonosyltransferase 1 （GAUT1） is an α1,4-D-galacturonosyltransferase that transfers galacturonic acid from uridine 5＇-diphosphogalacturonic acid onto the pectic polysaccharide homogalacturonan （Sterling et ...Galacturonosyltransferase 1 （GAUT1） is an α1,4-D-galacturonosyltransferase that transfers galacturonic acid from uridine 5＇-diphosphogalacturonic acid onto the pectic polysaccharide homogalacturonan （Sterling et al., 2006）. The 25-member Arabidopsis thaliana GAUT1-related gene family encodes 15 GAUT and 10 GAUT-like （GATL） proteins with, respectively, 56-84 and 42-53% amino acid sequence similarity to GAUT1. Previous phylogenetic analyses of AtGAUTs indicated three clades： A through C. A comparative phylogenetic analysis of the Arabidopsis, poplar and rice GAUT families has sub-classified the GAUTs into seven clades： clade A-1 （GAUTs 1 to 3）; A-2 （GAUT4）; A-3 （GAUTs 5 and 6）; A-4 （GAUT7）; B-1 （GAUTs 8 and 9）; B-2 （GAUTs 10 and 11）; and clade C （GAUTs 12 to 15）. The Arabidopsis GAUTs have a distribution comparable to the poplar orthologs, with the exception of GAUT2, which is absent in poplar. Rice, however, has no orthologs of GAUTs 2 and 12 and has multiple apparent orthologs of GAUTs 1, 4, and 7 compared with eitherArabidopsis or poplar. The cell wall glycosyl residue compositions of 26 homozygous T-DNA insertion mutants for 13 of 15 Arabidopsis GAUTgenes reveal significantly and reproducibly different cell walls in specific tissues of gaut mutants 6, 8, 9, 10, 11, 12, 13, and 14 from that of wild-type Arabidopsis walls. Pectin and xylan polysaccharides are affected by the loss of GAUT function, as demonstrated by the altered galacturonic acid, xylose, rhamnose, galactose, and arabinose composition of distinct gaut mutant walls. The wall glycosyl residue compositional phenotypes observed among the gaut mutants suggest that at least six different biosynthetic linkages in pectins and/or xylans are affected by the lesions in these GAUTgenes. Evidence is also presented to support a role for GAUT11 in seed mucilage expansion and in seed wall and mucilage composition.展开更多
Several genes in Arabidopsis, including PARVUS/AtGATL1, have been implicated in xylan synthesis. However, the biosynthesis of xylan in woody plants, where this polysaccharide is a major component of wood, is poorly un...Several genes in Arabidopsis, including PARVUS/AtGATL1, have been implicated in xylan synthesis. However, the biosynthesis of xylan in woody plants, where this polysaccharide is a major component of wood, is poorly understood. Here, we characterize two Populus genes, PdGATL 1.1 and PdGATL 1.2, the closest orthologs to the Arabidopsis PARVUS/GATL1 gene, with respect to their gene expression in poplar, their sub-cellular localization, and their ability to complement the parvus mutation in Arabidopsis. Overexpression of the two poplar genes in the parvus mutant rescued most of the defects caused by the parvus mutation, including morphological changes, collapsed xylem, and altered cell wall monosaccharide composition. Quantitative RT-PCR showed that PdGATL1.1 is expressed most strongly in developing xylem of poplar. In contrast, PdGATL1.2 is expressed much more uniformly in leaf, shoot tip, cortex, phloem, and xylem, and the transcript level of PdGATL1.2 is much lower than that of PdGATL 1.1 in all tissues examined. Sub-cellular localization experiments showed that these two proteins are localized to both ER and Golgi in comparison with marker proteins resident to these sub-cellular compartments. Our data indicate that PdGATLI.1 and PdGATL1.2 are functional orthologs of PARVUS/ GATL1 and can play a role in xylan synthesis, but may also have role（s） in the synthesis of other wall polymers.展开更多
Virus-induced gene silencing （VIGS） is a powerful genetic tool for rapid assessment of plant gene functions in the post-genomic era. Here, we successfully implemented a Tobacco Rattle Virus （TRV）-based VlGS system...Virus-induced gene silencing （VIGS） is a powerful genetic tool for rapid assessment of plant gene functions in the post-genomic era. Here, we successfully implemented a Tobacco Rattle Virus （TRV）-based VlGS system to study functions of genes involved in either primary or secondary cell wall formation in Nicotiana benthamiana plants. A 3-week post- VIGS time frame is sufficient to observe phenotypic alterations in the anatomical structure of stems and chemical composition of the primary and secondary cell walls. We used cell wall glycan-directed monoclonal antibodies to demonstrate that alteration of cell wall polymer synthesis during the secondary growth phase of VIGS plants has profound effects on the extractability of components from woody stem cell walls. Therefore, TRV-based VlGS together with cell wall component profiling methods provide a high-throughput gene discovery platform for studying plant cell wall formation from a bioenergy perspective.展开更多
In insects and other ectotherms,cold temperatures cause a coma resulting from loss of neuromuscular function,during which ionic and metabolic homeostasis are progressively lost.Cold adaptation improves homeostasis dur...In insects and other ectotherms,cold temperatures cause a coma resulting from loss of neuromuscular function,during which ionic and metabolic homeostasis are progressively lost.Cold adaptation improves homeostasis during cold exposure,but the ultimate targets of selection are still an open question.Cold acclimation and adaptation remodels mitochondrial metabolism in insects,suggesting that aerobic energy production during cold exposure could be a target of selection.Here,we test the hypothesis that cold adaptation improves the ability to maintain rates of aerobic energy production during cold exposure by using^(31)P NMR on live flies.Using lines of Drosophila melanogaster artificially selected for fast and slow recovery from a cold coma,we show that cold exposure does not lower ATP levels and that cold adaptation does not alter aerobic ATP production during cold exposure.Cold-hardy and cold-susceptible lines both experienced a brief transition to anaerobic metabolism during cooling,but this was rapidly reversed during cold exposure,suggesting that oxidative phosphorylation was sufficient to meet energy demands below the critical thermal minimum,even in cold-susceptible flies.We thus reject the hypothesis that performance under mild low temperatures is set by aerobic ATP supply limitations in D.melanogaster,excluding oxygen and capacity limitation as a weak link in energy supply.This work suggests that the modulations to mitochondrial metabolism resulting from cold acclimation or adaptation may arise from selection on a biosynthetic product(s)of those pathways rather than selection on ATP supply during cold exposure.展开更多
基金supported by the Georgia Research Alliance and the University of Georgia(to GWH)。
文摘Alzheimer’s disease is a neurodegenerative disease that affected over 6.5 million people in the United States in 2021,with this number expected to double in the next 40 years without any sort of treatment.Due to its heterogeneity and complexity,the etiology of Alzheimer’s disease,especially sporadic Alzheimer’s disease,remains largely unclear.Compelling evidence suggests that brain glucose hypometabolism,preceding Alzheimer’s disease hallmarks,is involved in the pathogenesis of Alzheimer’s disease.Herein,we discuss the potential causes of reduced glucose uptake and the mechanisms underlying glucose hypometabolism and Alzheimer’s disease pathology.Specifically,decreased O-Glc NAcylation levels by glucose deficiency alter mitochondrial functions and together contribute to Alzheimer’s disease pathogenesis.One major problem with Alzheimer’s disease research is that the disease progresses for several years before the onset of any symptoms,suggesting the critical need for appropriate models to study the molecular changes in the early phase of Alzheimer’s disease progression.Therefore,this review also discusses current available sporadic Alzheimer’s disease models induced by metabolic abnormalities and provides novel directions for establishing a human neuronal sporadic Alzheimer’s disease model that better represents human sporadic Alzheimer’s disease as a metabolic disease.
基金the partial support of this study provided bythe NIH with SBIR Grants GM099355 and GM093747
文摘The advent of superficially porous particles （SPPs） for packed HPLC columns has changed the way that many practitioners have approached the problem of developing needed separations. The very high efficiency of such columns, combined with convenient operating conditions, modest back pressures and the ability to use conventional HPLC instruments has resulted in intense basic studies of SPP technology, and widespread applications in many sciences. This report contains an overview of the SPP technology first developed in 2006 by Advanced Materials Technology, Inc., for sub-3-11m particles, then expanded into a family of SPP products with different particle sizes, pore sizes and other physical parameters. This approach was designed so that each particle of the family could be optimized for separating a particular group of compounds, usually based on solute size.
基金supported by the Key Technologies Research and Development Program[2021YFC2103100]the Key Technology and Development Program of Shandong Province[2022SFGC0103]+2 种基金funded by Shandong Excellent Young Scientists(Overseas)Fund Program[2023HWYQ-002]Taishan Scholars Program[TSQN202312003]the Qilu Young Scholar Fund of Shandong University.
文摘Hyaluronan(HA)is a naturally occurring polysaccharide in the organism.As one of the main components of the extracellular matrix,it plays an important role in regulating various cellular processes,including proliferation,differentiation,inflammation,and immunity,through interaction with HA receptors.HA is widely found in the human body,particularly in the skin and joints,thus playing a crucial role in the functioning of these tissues.The aging of the skin and the occurrence of osteoarthritis are related to the loss of HA.Supplementing HA in the appropriate areas can delay or prevent these processes.Common methods of HA supplementation include topical application to the skin or injection into the joint cavities,both of which have shown efficacy in restoring HA levels and improving tissue function.In recent years,studies have shown that oral administration of HA can also have similar effects.Oral HA first passes through the gastrointestinal tract and then enters the liver with the blood circulation.Therefore,in addition to supplementing the HA content in the body,oral HA can also exert beneficial effects on the gastrointestinal tract and the liver,such as enhancing the barrier function of the gastrointestinal tract,regulating the intestinal flora,and reducing inflammation.Supplementation of HA has numerous benefits for the skin,orthopedic disorders,gastrointestinal tract and liver.Therefore,it is important to understand the mechanisms through which HA exerts these effects.This article describes the basic properties of HA and reviews its relationship with skin,orthopedic diseases,gastrointestinal tract and liver,as well as its applications in these areas.
文摘Galacturonosyltransferase 1 （GAUT1） is an α1,4-D-galacturonosyltransferase that transfers galacturonic acid from uridine 5＇-diphosphogalacturonic acid onto the pectic polysaccharide homogalacturonan （Sterling et al., 2006）. The 25-member Arabidopsis thaliana GAUT1-related gene family encodes 15 GAUT and 10 GAUT-like （GATL） proteins with, respectively, 56-84 and 42-53% amino acid sequence similarity to GAUT1. Previous phylogenetic analyses of AtGAUTs indicated three clades： A through C. A comparative phylogenetic analysis of the Arabidopsis, poplar and rice GAUT families has sub-classified the GAUTs into seven clades： clade A-1 （GAUTs 1 to 3）; A-2 （GAUT4）; A-3 （GAUTs 5 and 6）; A-4 （GAUT7）; B-1 （GAUTs 8 and 9）; B-2 （GAUTs 10 and 11）; and clade C （GAUTs 12 to 15）. The Arabidopsis GAUTs have a distribution comparable to the poplar orthologs, with the exception of GAUT2, which is absent in poplar. Rice, however, has no orthologs of GAUTs 2 and 12 and has multiple apparent orthologs of GAUTs 1, 4, and 7 compared with eitherArabidopsis or poplar. The cell wall glycosyl residue compositions of 26 homozygous T-DNA insertion mutants for 13 of 15 Arabidopsis GAUTgenes reveal significantly and reproducibly different cell walls in specific tissues of gaut mutants 6, 8, 9, 10, 11, 12, 13, and 14 from that of wild-type Arabidopsis walls. Pectin and xylan polysaccharides are affected by the loss of GAUT function, as demonstrated by the altered galacturonic acid, xylose, rhamnose, galactose, and arabinose composition of distinct gaut mutant walls. The wall glycosyl residue compositional phenotypes observed among the gaut mutants suggest that at least six different biosynthetic linkages in pectins and/or xylans are affected by the lesions in these GAUTgenes. Evidence is also presented to support a role for GAUT11 in seed mucilage expansion and in seed wall and mucilage composition.
文摘Several genes in Arabidopsis, including PARVUS/AtGATL1, have been implicated in xylan synthesis. However, the biosynthesis of xylan in woody plants, where this polysaccharide is a major component of wood, is poorly understood. Here, we characterize two Populus genes, PdGATL 1.1 and PdGATL 1.2, the closest orthologs to the Arabidopsis PARVUS/GATL1 gene, with respect to their gene expression in poplar, their sub-cellular localization, and their ability to complement the parvus mutation in Arabidopsis. Overexpression of the two poplar genes in the parvus mutant rescued most of the defects caused by the parvus mutation, including morphological changes, collapsed xylem, and altered cell wall monosaccharide composition. Quantitative RT-PCR showed that PdGATL1.1 is expressed most strongly in developing xylem of poplar. In contrast, PdGATL1.2 is expressed much more uniformly in leaf, shoot tip, cortex, phloem, and xylem, and the transcript level of PdGATL1.2 is much lower than that of PdGATL 1.1 in all tissues examined. Sub-cellular localization experiments showed that these two proteins are localized to both ER and Golgi in comparison with marker proteins resident to these sub-cellular compartments. Our data indicate that PdGATLI.1 and PdGATL1.2 are functional orthologs of PARVUS/ GATL1 and can play a role in xylan synthesis, but may also have role（s） in the synthesis of other wall polymers.
文摘Virus-induced gene silencing （VIGS） is a powerful genetic tool for rapid assessment of plant gene functions in the post-genomic era. Here, we successfully implemented a Tobacco Rattle Virus （TRV）-based VlGS system to study functions of genes involved in either primary or secondary cell wall formation in Nicotiana benthamiana plants. A 3-week post- VIGS time frame is sufficient to observe phenotypic alterations in the anatomical structure of stems and chemical composition of the primary and secondary cell walls. We used cell wall glycan-directed monoclonal antibodies to demonstrate that alteration of cell wall polymer synthesis during the secondary growth phase of VIGS plants has profound effects on the extractability of components from woody stem cell walls. Therefore, TRV-based VlGS together with cell wall component profiling methods provide a high-throughput gene discovery platform for studying plant cell wall formation from a bioenergy perspective.
基金This work was performed in the McKnight Brain Institute at the National High Magnetic Field Laboratory’s AMRIS Facility,which is supported by National Science Foundation Cooperative Agreement No.DMR-1157490 and the State of FloridaThis work was supported in part by an NIH award,S10RR031637,for magnetic resonance instrumentation,and by National Science Foundation(NSF)Grants IOS-1051770(to T.J.M.)+3 种基金IOS-1051890(to D.A.H,A.S.E and D.B.A.)and IOS-1558159 to CMW.A.S.Ereceived partial support from the Georgia Research Alliance,and D.A.H.received support from the IAEA/FAO CRP on Dormancy management to enable mass rearing and increase efficacy of sterile insects and natural enemiesDan Plant provided valuable assistance setting up NMR experiments in AMRIS.Stephanie Dickinson checked the statistical analysesD.B.A was supported by NIH grants U24AG056053 and P30AG050886.
文摘In insects and other ectotherms,cold temperatures cause a coma resulting from loss of neuromuscular function,during which ionic and metabolic homeostasis are progressively lost.Cold adaptation improves homeostasis during cold exposure,but the ultimate targets of selection are still an open question.Cold acclimation and adaptation remodels mitochondrial metabolism in insects,suggesting that aerobic energy production during cold exposure could be a target of selection.Here,we test the hypothesis that cold adaptation improves the ability to maintain rates of aerobic energy production during cold exposure by using^(31)P NMR on live flies.Using lines of Drosophila melanogaster artificially selected for fast and slow recovery from a cold coma,we show that cold exposure does not lower ATP levels and that cold adaptation does not alter aerobic ATP production during cold exposure.Cold-hardy and cold-susceptible lines both experienced a brief transition to anaerobic metabolism during cooling,but this was rapidly reversed during cold exposure,suggesting that oxidative phosphorylation was sufficient to meet energy demands below the critical thermal minimum,even in cold-susceptible flies.We thus reject the hypothesis that performance under mild low temperatures is set by aerobic ATP supply limitations in D.melanogaster,excluding oxygen and capacity limitation as a weak link in energy supply.This work suggests that the modulations to mitochondrial metabolism resulting from cold acclimation or adaptation may arise from selection on a biosynthetic product(s)of those pathways rather than selection on ATP supply during cold exposure.
