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51.
52.
Abstract— Analysis of whole autopsy brain from a patient with fucosidosis (α-fucosidase deficiency) revealed minor storage of H-antigen glycolipid [Fuc (α, 1→2) Gal-GlcNAc-Gal-Glc-Ceramide] and a slightly abnormal ganglioside composition in the form of a two-fold elevation of GM1 and the presence of a fucose-containing glycolipid (a minor component) which co-migrated with GD1a. The major storage materials in fucosidosis brain were an oligosaccharide (Fuc-Gal-GlcNAc-Man[Fuc-Gal-GlcNAc-Man]-ManGlcNAc) and a disaccharide [Fuc(α, 1→6)-GlcNAc] in the approximate ratio of 5:1. Lesser amounts of a related oligosaccharide (Gal-GlcNAc-Man[Gal-GlcNAc-Man]-Man-GlcNAc) were isolated from the brain of patients with GM1-gangliosidosis (Types I and II) where the major storage material is known to be GM1-ganglioside (Gal (β, 1→3)GalNAc(β, 1→4) [NeuNAcf(α, 2→3) Gal(β, 1→4)Glc-Ceramide). Similarly, a related oligosaccharide (GlcNAc-Man [GlcNAc-Man]-Man-GlcNAc) was isolated from the brain of a patient with a total deficiency of N-acetyl-β-d -hexosaminidase (Sandhoff variant of GM2-gangliosidosis) where the major storage products are known to be GM2-ganglioside (GalNAc (β 1→4) [NeuNAc (α, 2→3)Gal(β, 1→4)Glc-Ceramine) and its asialo derivative. These studies indicate that glycoproteins containing at least 2 mol of l -fucose per oligosaccharide unit are normally catabolized in human brain. Further, it appears that such glycoproteins are initially catabolized by an endo-N-acetylglucosaminidase to release an oligosaccharide which is then degraded by the sequential action of exo-glycosidases. 相似文献
53.
Populations of the freshwater copepod Mesocyclops edax inhabiting Michigan lakes are dormant during winter, whereas populations inhabiting Florida lakes develop and reproduce continuously throughout the year. A Michigan and a Florida population were exposed to dormancy inducing conditions (low temperature and short photoperiod) in the laboratory and observed for indications of dormancy. All Michigan individuals and a small percentage of the Florida individuals entered dormancy as indicated by prolonged duration of the fourth copepodid instar and cessation of feeding. I suggest that in these population these observations represent diapause, rather than quiescence. The two populations were crossbred to examine the nature of inheritance of dormancy. The F1 hybrids exhibited an incidence of diapause approximately intermediate between the Florida and Michigan parental stocks. The backcrosses of F1 individuals to the Michigan and Florida stocks, respectively, exhibited a high and an intermediate incidence of diapause. Survival of the F2 crosses was very low. The present study presents evidence of genetic differentiation between the Michigan and Florida populations of M. edax with respect to ability to diapause. 相似文献
54.
Optimal pH, temperature, and concentration of enzyme conditions for the rate of hydrolysis of five isoflavone conjugates (daidzein, O-desmethylangolensin, equol, genistein, and glycitein) and two lignans (enterodiol and enterolactone) from two biological matrices (urine and plasma) were studied using beta-glucuronidase from Helix pomatia. In addition, the use of mixtures of beta-glucuronidase and sulfatase enzymes from different sources was investigated to find enzyme preparations that contained lower amounts of naturally present phytoestrogens. Quantification of aglycones spiked with (13)C(3)-labeled internal standards was carried out by LC-MS/MS. In urine, all of the phytoestrogen conjugates hydrolyzed within 2h under standard hydrolysis conditions (24mul H. pomatia, pH 5, 37 degrees C). Hydrolysis rates were improved at 45 degrees C and by doubling the enzyme concentration and may be used to further reduce hydrolysis times down to 100min. In plasma, a 16-h hydrolysis was required to ensure complete hydrolysis of all conjugates. As with urine, the use of increased temperature or increased enzyme concentration reduced hydrolysis times for most analytes. However, the rate of hydrolysis in plasma was significantly slower than that in urine for all analytes except enterodiol, for which the reverse was true. Neither increased temperature nor increased enzyme concentration increased the rate of hydrolysis of enterolactone. Hydrolysis at pH 6 proved to be detrimental to hydrolysis of phytoestrogen conjugates, especially those in plasma. Other enzyme preparations from different sources, such as beta-glucuronidase from Escherichia coli, were found to contain lower amounts of contaminating phytoestrogens and showed increased enzyme activity for isoflavones, but lower activity for lignans, when used with other sulfatase enzymes. In addition, this involved complicating the analytical procedure through using mixtures of enzymes. Therefore, the use of beta-glucuronidase from H. pomatia combined with an enzyme "blank" to correct for phytoestrogen contamination was shown to be a suitable method for hydrolysis of phytoestrogens. 相似文献
55.
The present study was undertaken for the purpose of evaluating the solvent perturbation technique as a method to identify enzyme catalytic residues. For establishment of expected directions and sizes of pKa perturbations for different types of acids in different classes of solvents, a study of the pKa of a series of acids in mixed solvent systems was carried out. Consistent with previous findings, the presence of organic solvents (25% v/v) increased the pKa values of neutral acids while it decreased or did not change the pKa values of cationic acids. The size of the perturbation observed was dependent on the nature of the organic solvent and on the polarity of the neutral form of the acid. The solvent perturbation studies were then extended to the catalytic aspartate residue of yeast hexokinase. The pKa of this residue was determined from the MgATP V/K profile measured in the presence and absence of organic solvents (25% v/v). While dimethylformamide and methanol induced small but perhaps significant increases in the observed pKa, dimethyl sulfoxide and propylene glycol did not. The pKa values, from the MgATP V/K profiles measured in the presence of fully saturating glucose, were not significantly increased by the organic solvents. The pKi vs. pH profile for the competitive inhibitor lyxose was also measured in the presence and absence of organic solvents. While methanol (25% v/v), dimethylformamide (25% v/v), and dioxane (17.5% v/v) induced a large increase in the pKa, propylene glycol and dimethyl sulfoxide (25% v/v) did not. The results from this investigation indicate that the solvent perturbation technique should not be relied upon indiscriminately. 相似文献
56.
Agnes Simonyi Yan He Wenwen Sheng Albert Y. Sun W. Gibson Wood Gary A. Weisman Grace Y. Sun 《Molecular neurobiology》2010,41(2-3):73-86
Alzheimer’s disease (AD) is marked by an increase in the production of extracellular beta amyloid plaques and intracellular neurofibrillary tangles associated with a decline in brain function. Increases in oxidative stress are regarded as an early sign of AD pathophysiology, although the source of reactive oxygen species (ROS) and the mechanism(s) whereby beta amyloid peptides (Aβ) impact oxidative stress have not been adequately investigated. Recent studies provide strong evidence for the involvement of NADPH oxidase and its downstream oxidative signaling pathways in the toxic effects elicited by Aβ. ROS produced by NADPH oxidase activate multiple signaling pathways leading to neuronal excitotoxicity and glial cell-mediated inflammation. This review describes recent studies demonstrating the neurotoxic effects of Aβ in conjunction with ROS produced by NADPH oxidase and the downstream pathways leading to activation of cytosolic phospholipase A2 (PLA2) and secretory PLA2. In addition, this review also describes recent studies using botanical antioxidants to protect against oxidative damage associated with AD. Investigating the metabolic and signaling pathways involving Aβ NADPH oxidase and PLA2 can help understand the mechanisms underlying the neurodegenerative effects of oxidative stress in AD. This information should provide new therapeutic approaches for prevention of this debilitating disease. 相似文献
57.
58.
The pathophysiology of Alzheimer's disease (AD) is comprised of complex metabolic abnormalities in different cell types in the brain. To date, there are not yet effective drugs that can completely inhibit the pathophysiological event, and efforts have been devoted to prevent or minimize the progression of this disease. Much attention has focused on studies to understand aberrant functions of the ionotropic glutamate receptors, perturbation of calcium homeostasis, and toxic effects of oligomeric amyloid beta peptides (Aβ) which results in production of reactive oxygen and nitrogen species and signaling pathways, leading to mitochondrial dysfunction and synaptic impairments. Aberrant phospholipase A(2) (PLA(2)) activity has been implicated to play a role in the pathogenesis of many neurodegenerative diseases, including AD. However, mechanisms for their modes of action and their roles in the oxidative and nitrosative signaling pathways have not been firmly established. In this article, we review recent studies providing a metabolic link between cytosolic PLA(2) (cPLA(2)) and neuronal excitation due to stimulation of ionotropic glutamate receptors and toxic Aβ peptides. The requirements for Ca(2+) binding together with its posttranslational modifications by protein kinases and possible by the redox-based S-nitrosylation, provide strong support for a dynamic role of cPLA(2) in serving multiple functions to neurons and glial cells under abnormal physiological and pathological conditions. Therefore, understanding mechanisms for cPLA(2) in the oxidative and nitrosative pathways in neurons will allow the development of novel therapeutic targets to mitigate the detrimental effects of AD. 相似文献
59.
Carbon dioxide exchange and canopy conductance of two coniferous forests under various sky conditions 总被引:1,自引:0,他引:1
Sky conditions play an important role in the Earth’s climate system and CO2 uptake by plants. We used eddy covariance and meteorological data, including global and diffuse photosynthetic photon flux
density (PPFD), recorded over the 2008 and 2009 growing season at two Sitka spruce [Picea sitchensis (Bong.) Carr.] forest sites in northern Britain, in order to establish relationships between physiological properties under diverse sky
conditions, i.e. (1) sunny, (2) cloudy, and (3) overcast, and several canopy activity-related properties. These properties
are: (1) response to PPFD, (2) photosynthetic light use efficiency, and (3) canopy stomatal conductance. We found that Sitka
spruce forests utilise PPFD in a more efficient way when solar radiation is dominated by diffuse radiation. Furthermore, our
results show that diffuse radiation enhances canopy stomatal conductance, an effect which may be the result of both blue light
enrichment within the canopy and the reduction in vapour pressure deficit during cloudy and overcast weather. Diffuse radiation
does not only influence short-term (hourly, daily, monthly) canopy activity but also long-term forest growth. 相似文献
60.