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Xia Li

Publications and source records attributed to Xia Li.

At least 145 records · Page 8Linked to original sources

Multivariate sib-pair linkage analysis of longitudinal phenotypes by three step-wise analysis approaches.

BACKGROUND: Current statistical methods for sib-pair linkage analysis of complex diseases include linear models, generalized linear models, and novel data mining techniques. The purpose of this study was to further investigate the utility and properties of a novel pattern recognition technique (step-wise discriminant analysis) using the chromosome 10 linkage data from the Framingham Heart Study and by comparing it with step-wise logistic regression and linear regression. RESULTS: The three step-wise approaches were compared in terms of statistical significance and gene localization. Step-wise discriminant linkage analysis approach performed best; next was step-wise logistic regression; and step-wise linear regression was the least efficient because it ignored the categorical nature of disease phenotypes. Nevertheless, all three methods successfully identified the previously reported chromosomal region linked to human hypertension, marker GATA64A09. We also explored the possibility of using the discriminant analysis to detect gene x gene and gene x environment interactions. There was evidence to suggest the existence of gene x environment interactions between markers GATA64A09 or GATA115E01 and hypertension treatment and gene x gene interactions between markers GATA64A09 and GATA115E01. Finally, we answered the theoretical question "Is a trichotomous phenotype more efficient than a binary?" Unlike logistic regression, discriminant sib-pair linkage analysis might have more power to detect linkage to a binary phenotype than a trichotomous one. CONCLUSION: We confirmed our previous speculation that step-wise discriminant analysis is useful for genetic mapping of complex diseases. This analysis also supported the possibility of the pattern recognition technique for investigating gene x gene or gene x environment interactions.

Adult Children↗

A rapid punishment procedure for detection of anxiolytic compounds in mice.

RATIONALE: Effects of compounds on punished responding have been predictive of anxiolytic efficacy in humans. The use of mice in these tests has been limited, but the utility of this species in drug discovery and for neurobiological inquiry would benefit from a rapid, reliable method. OBJECTIVES: The present experiments were designed to validate a new procedure in mice. METHODS: Male, NIH Swiss mice were food deprived and placed in an experimental chamber with two nose-poke holes. Every nose poke (FR1) produced a 20 mg food pellet. On the following day, a drug vehicle was administered and the mice were again exposed to the FR1 schedule. On day 3, a compound was given and the mice were run under a mixed FR1 (food), FR1 (food+shock) schedule in alternating, unsignalled periods of 4 and 10 min for three cycles. In the 10-min periods, nose-pokes produced both food plus brief electrification of the grid floor (0.5 mA for 100 ms). Effects of compounds on food intake were also evaluated in separate groups of mice. RESULTS: The introduction of shock substantially decreased responding during the 10-min punishment periods without significantly affecting responding during the non-punishment periods. The clinically effective anxiolytic agents chlordiazepoxide, pentobarbital, and bretazenil, but not buspirone, produced dose-dependent increases in suppressed responding, whereas d-amphetamine, chlorpromazine, and morphine were not effective. Chlordiazepoxide and bretazenil increased food consumption. CONCLUSIONS: The present method enables rapid and reliable evaluation of potential anxiolytic agents in mice with minimal training. Increases in food intake are not necessary for anxiolytic-like effects under these conditions.

Animals↗

[Exogenous nitric oxide inhibits the proliferation of mouse neural progenitor cells].

OBJECTIVE: To explore the inhibitive effect of exogenous nitric oxide (NO) on the proliferation of mouse neural progenitor cells (NPCs). METHODS: NPCs were cultured in medium containing EGF, and SNP was added as a donor of NO in vitro. The concentration of NO was measured by the Griess assay; The amount of living cells was measured by MTT assay. The NPCs were induced to differentiate in medium supplemented with serum. RESULT: The NO(-)2 concentrations in the supernatants of the experimental groups 1, 2, and 3 were 64.701 +/- 0.606, 82.659 +/- 0.394 and 93.648 +/- 0.394 micro mol/L respectively, 3.099 +/- 0.420 micro mol/L in th control group. After culture with SNP for 24 hours, MTT assay showed the A values of 0.546 +/- 0.016, 0.484 +/- 0.007, and 0.357 +/- 0.007 in the experimental groups 1, 2, and 3 respectively, 0.642 +/- 0.021 in th control group (all P < 0.01). After further culture in the medium without SNP for 24 hours, MTT assay showed the A values of 1.243 +/- 0.036, 1.064 +/- 0.097, and 0.834 +/- 0.031 in the experimental groups 1, 2, and 3 respectively, 1.581 +/- 0.072 in the control group (all P < 0.01). The differences between the A values of the supernatants in the same wells filled with the medium with and without SNP were all significant (P < 0.01). In the medium with serum the NPCs still proliferated actively and differentiated into neuron and glial cell after SNP was removed. CONCLUSION: Exogenous nitric oxide inhibits the proliferation of mice NPC in vitro.

Animals↗

Ascorbic acid spares alpha-tocopherol and decreases lipid peroxidation in neuronal cells.

Ascorbic acid is considered an antioxidant in the central nervous system, but direct evidence that ascorbate protects neuronal cells from oxidant stress is lacking. Differentiated SH-SY5Y cells in culture took up ascorbic acid on the sodium-dependent vitamin C transporter Type 2 and retained it much more effectively than dehydroascorbic acid. Intracellular ascorbate spared alpha-tocopherol, both in cells loaded with alpha-tocopherol in culture and in cells under oxidant stress due to extracellular ferricyanide. Sparing of alpha-tocopherol in response to ferricyanide was associated with protection against lipid peroxidation in cell membranes. These results show that neuronal cells concentrate ascorbate, and that intracellular ascorbate, either directly or through sparing of alpha-tocopherol, protects them against oxidant stress.

Ascorbic Acid↗

Recycling of vitamin C from its oxidized forms by human endothelial cells.

Endothelial cells encounter oxidant stress due to their location in the vascular wall, and because they generate reactive nitrogen species. Because ascorbic acid is likely involved in the antioxidant defenses of these cells, we studied the mechanisms by which cultures of EA.hy926 endothelial cells recycle the vitamin from its oxidized forms. Cell lysates reduced the ascorbate free radical (AFR) by both NADH- and NADPH-dependent mechanisms. Most NADH-dependent AFR reduction occurred in the particulate fraction of the cells. NADPH-dependent reduction resembled that due to NADH in having a high affinity for the AFR, but was mediated largely by thioredoxin reductase. Reduction of dehydroascorbic acid (DHA) required GSH and was both direct and enzyme dependent. The latter was saturable, half-maximal at 100 microM DHA, and comparable to rates of AFR reduction. Loading cells to ascorbate concentrations of 0.3-1.6 mM generated intracellular DHA concentrations of 20-30 microM, indicative of oxidant stress in culture. Whereas high-affinity AFR reduction is the initial and likely the preferred mechanism of ascorbate recycling, any DHA that accumulates during oxidant stress will be reduced by GSH-dependent mechanisms.

Ascorbic Acid↗

[Endovascular treatment of intracranial aneurysms with mechanical detachable spiral-neurological].

OBJECTIVE: To evaluate the efficacy of endovascular treatment of intracranial aneurysms with mechanical detachable spiral-neurological (MDS-N). METHODS: Thirty-six patients with intracranial aneurysms were treated with MDS-N by Seldinger's approaches through femoral artery puncture. A catheter was sent into the aneurysm with proper-size MDS-N system and a spiral was pushed into the aneurysmal lumen. RESULTS: The aneurysms were completely occluded in 32 cases while partial occlusion was obtained in 4 patients. The parent arteries remained unobstructed. Follow-up of 3 - 6 months showed that all patients recovered well. No death or permanent serious complication occurred. CONCLUSION: Simple, safe, and low-cost, treatment of intracranial aneurysm with MDS-N is effective and suitable for use in larger hospital.

Adult↗

Ascorbic acid blunts oxidant stress due to menadione in endothelial cells.

Endothelial cells are exposed to potentially damaging reactive oxygen species generated both within the cells and in the bloodstream and underlying vessel wall. In this work, we studied the ability of ascorbic acid to protect cultured human-derived endothelial cells (EA.hy926) from oxidant stress generated by the redox cycling agent menadione. Menadione caused intracellular oxidation of dihydrofluorescein, which required the presence of D-glucose in the incubation medium, and was inhibited by intracellular ascorbate and desferrioxamine. At concentrations of 100 microM and higher, menadione depleted the cells of both GSH and ascorbate, and ascorbate loading partially prevented the decrease in GSH due to menadione. Menadione increased L-arginine uptake by the cells, but inhibited endothelial nitric oxide synthase, an effect that was prevented by acute loading with ascorbate. Ascorbate blunts menadione-induced oxidant stress in EA.hy926 cells, which may help to preserve nitric oxide synthase activity under conditions of excessive oxidant stress.

Ascorbic Acid↗

Physiological and biochemical response of freshwater cryptomonads (Cryptophyceae) to Fe deficiency.

Cryptomonads show strong seasonal distribution in lakes yet little is known of their nutrient requirements. In this study, we examined the role of Fe nutrition in the growth and photosynthetic properties of two freshwater cryptomonads (Cryptomonas sp. UTCC 337 and C. erosa UTCC 446). Cryptomonas sp. appeared more tolerant to Fe deprivation compared with C. erosa. Growth rates calculated for Cryptomonas sp. provided 100 nM and 1 000 nM Fe did not vary (0.55 d(-1)). Only cultures provided 10 nM Fe displayed significantly lower rates of growth (0.26 d(-1)) and lower cellular yields of chlorophyll. In contrast, cultures of C. erosa provided 10 nM Fe failed to grow, whereas cultures provided 100 nM Fe exhibited a reduced rate of growth (30% reduction) and lower yields of cellular chlorophyll (19% reduction) compared to high Fe (1 000 nM) cultures. Photochemical competency, assessed by measuring DCMU-enhanced fluorescence, was high for cells of Cryptomonas sp. regardless of the level of Fe provided (F(v)/F(m) > 0.7). In contrast, photochemical competency was considerably reduced (F(v)/F(m) = 0.46) for C. erosa provided 100 nM Fe. Consistent with this, levels of the Fe-containing electron transfer catalyst ferredoxin were reduced by 2.5 times in C. erosa provided 100 nM Fe compared to Fe-replete cells. By comparison, ferredoxin levels varied only slightly in cells of Cryptomonas sp. provided either 100 nM or 1 000 nM Fe.

Diatoms↗

Loci on chromosomes 2, 4, 9, and 16 for body weight, body length, and adiposity identified in a genome scan of an F2 intercross between the 129P3/J and C57BL/6ByJ mouse strains.

Mice have proved to be a powerful model organism for understanding obesity in humans. Single gene mutants and genetically modified mice have been used to identify obesity genes, and the discovery of loci for polygenic forms of obesity in the mouse is an important next step. To pursue this goal, the inbred mouse strains 129P3/J (129) and C57BL/6ByJ (B6), which differ in body weight, body length, and adiposity, were used in an F2 cross to identify loci affecting these phenotypes. Linkages were determined in a two-phase process. In the first phase, 169 randomly selected F2 mice were genotyped for 134 markers that covered all autosomes and the X Chromosome (Chr). Significant linkages were found for body weight and body length on Chr 2. In addition, we detected several suggestive linkages on Chr 2 (adiposity), 9 (body weight, body length, and adiposity), and 16 (adiposity), as well as two suggestive sex-dependent linkages for body length on Chrs 4 and 9. In the second phase, 288 additional F2 mice were genotyped for markers near these regions of linkage. In the combined set of 457 F2 mice, six significant linkages were found: Chr 2 (Bwq5, body weight and Bdln3, body length), Chr 4 (Bdln6, body length, males only), Chr 9 (Bwq6, body weight and Adip5, adiposity), and Chr 16 (Adip9, adiposity), as well as several suggestive linkages (Adip2, adiposity on Chr 2, Bdln4 and Bdln5, body length on Chr 9). In addition, there was a suggestive linkage to body length in males on Chr 9 (Bdln4). For adiposity, there was evidence for epistatic interactions between loci on Chr 9 (Adip5) and 16 (Adip9). These results reinforce the concept that obesity is a complex trait. Genetic loci and their interactions, in conjunction with sex, age, and diet, determine body size and adiposity in mice.

Animals↗

Location and recycling of mitochondrial alpha-tocopherol.

Vitamin E in the form of alpha-tocopherol is crucial for mitochondrial integrity. We studied the distribution of alpha-tocopherol in rat muscle mitochondria in relation to the capacity of the electron transport chain to recycle the vitamin. Fractionation studies showed that almost 90% of the alpha-tocopherol in mitochondria is located in the outer membrane. This distribution was confirmed with the finding that ferricytochrome c, which does not penetrate the outer membrane, oxidized 70-80% of mitochondrial alpha-tocopherol in a time- and concentration-dependent manner. Despite the predominant outer membrane distribution of alpha-tocopherol, succinate and other mitochondrial respiratory substrates spared alpha-tocopherol from oxidative loss by both agents. Sparing of alpha-tocopherol by succinate was prevented by 2-thenoyltrifluoroacetone, but not by myxothiazol, which suggests that ubiquinol is the electron donor. Ferricytochrome c significantly increased total F2-isoprostanes, an effect that was prevented by succinate. Most alpha-tocopherol in muscle mitochondria is located in the outer membrane, where it is susceptible to oxidative loss. Nonetheless, alpha-tocopherol is partially spared by ubiquinol in the electron transport chain.

Journal Article↗

Enhancement of antidepressant potency by a potentiator of AMPA receptors.

1. AMPA receptor potentiators (ARPs) exhibit antidepressant-like activity in preclinical tests (for example, the forced swim test) that are highly predictive of efficacy in humans. Unlike most currently used antidepressants, ARPs do not elevate extracellular levels of biogenic amines (e.g., 5HT, NE) in prefrontal cortex at doses that are active in the forced swim test. 2. The present series of experiments examined the effects of combining the ARP, LY 392098, with biogenic amine-based antidepressants in the forced swim test. Male, NIH Swiss mice were placed in a cylinder of water and observed for attempted escape behaviors and immobility. 3. LY 392098 dose-dependently decreased immobility as did a range of classical antidepressants. At doses of LY 392098 below those that decreased immobility, this compound significantly increased the potency with which fluoxetine and citalopram (SSRI antidepressants), imipramine (tricyclic antidepressant), duoxetine (norepinephrine/serotonin uptake blocker), nisoxetine (norepinephrine uptake inhibitor), and rolipram (PDE4 inhibitor) decreased immobility in the forced swim test with potency shifts upward of 5-fold (fluoxetine, imipramine, and rolipram). Likewise, ineffective doses of the traditional antidepressants potentiated the effects LY 392098 with shifts in the dose-effect functions that were 10-fold or more for citalopram, fluoxetine, imipramine, and duloxetine. 4. Combined with other evidence for a role of AMPA receptors in the efficacy of antidepressants, the current data suggest that the addition of an ARP may augment the activity and perhaps the onset of the therapeutic effects of biogenic amine and second messenger-based antidepressants.

Animals↗

The CB1 receptor antagonist SR141716A selectively increases monoaminergic neurotransmission in the medial prefrontal cortex: implications for therapeutic actions.

1. In order to explore potential therapeutic implications of cannabinoid antagonists, the effects of the prototypical cannabinoid antagonist SR141716A on monoamine efflux from the medial prefrontal cortex and the nucleus accumbens of the rat were investigated by in vivo microdialysis. 2. SR141716A moderately increased serotonin efflux and concentrations of its metabolite 5-HIAA, both in the medial prefrontal cortex and the nucleus accumbens, and increased norepinephrine, dopamine and their metabolites in the medial prefrontal cortex. In contrast, it had no effect on norepinephrine, dopamine and their metabolites in the nucleus accumbens. 3. At the same doses, SR141716A increased acetylcholine efflux in the medial prefrontal cortex, in agreement with previous studies; contrary to the effects in cortex, SR141716A had no effect on acetylcholine efflux in the nucleus accumbens. 4. The efficacy of SR141716A in the psychostimulant-induced hyperlocomotion and the forced swimming paradigms was also explored in mice. SR141716A attenuated phenylcyclidine- and d-amphetamine-induced hyperlocomotion, without affecting locomotor activity when administered alone, and decreased immobility in the forced swimming test. 5. These results suggest that the cortical selectivity in the release of catecholamines, dopamine in particular, induced by the cannabinoid antagonist SR141716A, its procholinergic properties, together with its mild stimulatory effects on serotonin and norepinephrine efflux make similar compounds unique candidates for the treatment of psychosis, affective and cognitive disorders.

Animals↗

Combined deficiency of vitamins E and C causes paralysis and death in guinea pigs.

BACKGROUND: On the basis of in vitro studies, the antioxidant nutrients vitamins E and C are postulated to interact in vivo. OBJECTIVE: We developed a guinea pig model to evaluate the combined deficiency of vitamins E and C in vivo. DESIGN: Weanling guinea pigs were fed a control diet or a vitamin E-deficient diet for 14 d, after which one-half of each group had vitamin C removed from their diet, thus creating 4 diet groups. Some animals were observed for clinical signs. Others were killed for evaluation. RESULTS: Of 21 guinea pigs that were observed after being fed the diet deficient in both vitamins, 8 died 9 +/- 2 d (x +/- SD) after starting the diet. Eight additional guinea pigs developed a characteristic syndrome at 11 +/- 3 d. First, they became paralyzed in the hind limbs. Within a few hours, the paralysis progressed to include all 4 limbs and caused difficulty in breathing, which would have caused death had the animals not been euthanized. Histopathologic evaluation did not identify a lesion in the muscles or nervous system that could account for the paralysis. Biochemical measurements confirmed the deficiencies and indicated that the double deficiency caused lipid peroxidation in the central nervous system. CONCLUSIONS: A distinct clinical syndrome of combined vitamin E and vitamin C deficiency occurs in guinea pigs. This syndrome indicates that these antioxidant vitamins are related in vivo. We speculate that acute oxidative injury in the central nervous system underlies the clinical syndrome.

Animals↗

Female oxytocin-deficient mice display enhanced anxiety-related behavior.

Previous studies have suggested that oxytocin (OT) may be anxiolytic in female laboratory rats and mice. The elevated plus-maze was used to compare anxiety-related behaviors of OT-deficient (OT-/-) and wild-type (OT+/+) mice. Female OT-/- mice displayed increased anxiety-related behavior compared with OT+/+ mice. The percentage of entries (P < 0.0002) and time spent (P < 0.003) in the open arms was less in female OT-/- than OT+/+ mice. Administration of synthetic OT, 2 ng by intracerebroventricular (icv) injection to female OT-/- mice, increased the percentage of entries (P < 0.003) and time spent (P < 0.004) in the open arms compared with artificial cerebrospinal fluid female OT-/- mice. Administration of an OT receptor antagonist (Atosiban, d[Dtyr(Et)(2), Thr(4)]ornithine vasotocin) 100 ng icv, to female OT+/+ mice increased anxiety-related behavior by decreasing the percentage of entries (P < 0.01) and time spent (P < 0.04) in the open arms compared with artificial cerebrospinal fluid-treated controls. Central infusion of an OT receptor antagonist, 100 ng icv, before administration of synthetic OT, 2 ng icv, in female OT-/- mice blocked the anxiolytic affect of OT. In contrast, male OT-/- mice displayed decreased anxiety-related behavior compared with male OT+/+ mice. The percentage of entries (P < 0.007) and time spent (P < 0.004) in the open arms was greater in male OT-/- vs. OT+/+ mice. Our findings indicate that OT pathways play a role in modulating anxiety in female mice of the C57BL/6 background, and the effect is mediated by the OT receptor.

Animals↗

Characterization of molecular weight distribution of oligomers from autocatalyzed batch hydrolysis of xylan.

Oat spelt xylan was treated with water in a batch reactor at temperaturesof 180 and 200 degrees C. Ion-moderated partition (IMP) chromatography was thenapplied to separate oligomers in solution according to their molecular size. Calibration of the IMP measurements based on peak height was found toquantify dissolved monomer and oligomer yields well. Oligomer concentrationsin the liquid hydrolysate were also determined from the difference inxylose monomer concentrations measured by high-performance liquid chromatographybefore and after posthydrolysis of dissolved xylooligosaccharidesto xylose. Delayed formation and then rapid disappearance of oligomersfrom DP10 to DP2 was observed by IMP, and total oligomer yields measuredby IMP and posthydrolysis were very similar at these times. However, whileIMP detected virtually no oligomers initially, posthydrolysis measurementsgave significant amounts of soluble oligomers at these times, indicating thatoligomers with chain lengths >10 were in solution but not detectable by theIMP system used.

Avena↗

Cloning and sequence analysis of Bacillus thuringiensis gene fragments isolated by restriction digest PCR.

OBJECTIVE: To clone and analyze Bacillus thuringiensis gene fragments isolated by restriction digest PCR (RD-PCR). METHOD: Specific primers were designed to amplify the genes of Bacillus thuringiensis israelensis (Bti), and the PCR products were classified and re-amplified by RD-PCR to obtain the fragments for subsequent purification and cloning into the pMD18-T vectors, followed by rapid identification. The recombinant plasmids were extracted from positive clones and the target gene fragments were sequenced. RESULTS: Sequence analysis showed that all the fragments amplified were Bti genes. CONCLUSION: RD-PCR is reliable in breaking down large gene fragments into confined and shorter gene fragments for preparing microarray probes.

Bacillus thuringiensis↗