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101.
In the present study we observed that lipopolysaccharide (LPS) administration provoked a characteristic reduction in body weight gain, food consumption, saccharin (but not water) consumption and nocturnal locomotor activity. It has been previously suggested that the ability of LPS to suppress the consumption of, and preference for, a palatable solution such as saccharin without altering water consumption, may represent an anhedonic response. The results of the present study demonstrate that chronic treatment with the tricyclic antidepressant (TCA) desipramine (7.5 mg/kg; i.p.) prevented LPS-induced anorexia, loss of body weight, the antidipsogenic effect and hypoactivity. In contrast, chronic treatment with the antidepressants paroxetine (7.5 mg/kg; i.p.) and venlafaxine (10 mg/kg; i.p.) failed to alter any of the LPS-induced behavioural responses. Furthermore, chronic treatment with desipramine (and to a lesser extent paroxetine) reduced the consumption of, and preference for, saccharin suggesting that these antidepressant treatments induce an "anhedonic" response in their own right. In conclusion, chronic desipramine treatment attenuated LPS-induced depressive-like behavioural symptoms in the rat. However, chronic treatment with paroxetine and venlafaxine did not significantly alter LPS-induced behavioural responses. The results of the present study support the hypothesis that TCA's may exert part of their anti-depressive efficacy through their effects on the immune system. However, this property does not appear to be shared by newer antidepressants which possess a better side effect profile than the TCA's. The suppressive effect of TCA's on proinflammatory cytokine secretion is discussed as a mechanism by which these agents alter LPS-induced behavioural responses. 相似文献
102.
An expanded comparative map of bovine chromosome 27 targeting dairy form QTL regions 总被引:1,自引:0,他引:1
At present, the density of genes on the bovine maps is extremely limited and current resolution of the human-bovine comparative map is insufficient for selection of candidate genes controlling many economic traits of interest in dairy cattle. This study describes the chromosomal mapping of 10 selected gene-associated markers to bovine linkage and radiation hybrid maps to improve the breakpoint resolution in the human-bovine comparative map near two previously identified quantitative trait loci for the linear type trait, dairy form. Two regions of conserved synteny not previously described are reported between the telomeric region of bovine chromosome 27 (BTA27) and human chromosome 3 (HSA3) p24 region and between the HSA4q34.1 region and BTA8. These data increase the number of genes positioned on the bovine gene maps, refine the human-bovine comparative map, and should improve the efficiency of candidate gene selection for the dairy form trait in cattle. 相似文献
103.
Remko?de Knikker Youjun?Guo Jin-long?Li Albert?KH?Kwan Kevin?Y?Yip David?W?Cheung Kei-Hoi?CheungEmail author 《BMC bioinformatics》2004,5(1):25
Background
Very often genome-wide data analysis requires the interoperation of multiple databases and analytic tools. A large number of genome databases and bioinformatics applications are available through the web, but it is difficult to automate interoperation because: 1) the platforms on which the applications run are heterogeneous, 2) their web interface is not machine-friendly, 3) they use a non-standard format for data input and output, 4) they do not exploit standards to define application interface and message exchange, and 5) existing protocols for remote messaging are often not firewall-friendly. To overcome these issues, web services have emerged as a standard XML-based model for message exchange between heterogeneous applications. Web services engines have been developed to manage the configuration and execution of a web services workflow. 相似文献104.
Visual attention is attracted by salient stimuli that 'pop out' from their surroundings. Attention can also be voluntarily directed to objects of current importance to the observer. What happens in the brain when these two processes interact? 相似文献
105.
Li JJ Carson KG Trivedi BK Yue WS Ye Q Glynn RA Miller SR Connor DT Roth BD Luly JR Low JE Heilig DJ Yang W Qin S Hunt S 《Bioorganic & medicinal chemistry》2003,11(17):3777-3790
Interleukin-8 modulation is implicated in many inflammatory and cancer diseases. Starting from a mass-screening hit, the synthesis and structure-activity relationship of 2-amino-3-heteroarylquinoxalines as non-peptide, small molecule interleukine-8 receptor antagonists have been developed. The optimized derivatives, PD 0210293 (13y) and PD 0220245 (13r), show inhibition of both IL-8 receptor binding and IL-8-mediated neutrophil chemotaxis. 相似文献
106.
107.
Opioid agonists have different efficacy profiles for G protein activation,rapid desensitization,and endocytosis of mu-opioid receptors 总被引:2,自引:0,他引:2
Borgland SL Connor M Osborne PB Furness JB Christie MJ 《The Journal of biological chemistry》2003,278(21):18776-18784
The differential ability of various mu-opioid receptor (MOP) agonists to induce rapid receptor desensitization and endocytosis of MOP could arise simply from differences in their efficacy to activate G proteins or, alternatively, be due to differential capacity for activation of other signaling processes. We used AtT20 cells stably expressing a low density of FLAG-tagged MOP to compare the efficacies of a range of agonists to 1) activate G proteins using inhibition of calcium channel currents (ICa) as a reporter before and after inactivation of a fraction of receptors by beta-chlornaltrexamine, 2) produce rapid, homologous desensitization of ICa inhibition, and 3) internalize receptors. Relative efficacies determined for G protein coupling were [Tyr-D-Ala-Gly-MePhe-Glyol]enkephalin (DAMGO) (1) > or = methadone (0.98) > morphine (0.58) > pentazocine (0.15). The same rank order of efficacies for rapid desensitization of MOP was observed, but greater concentrations of agonist were required than for G protein activation. By contrast, relative efficacies for promoting endocytosis of MOP were DAMGO (1) > methadone (0.59) > morphine (0.07) > or = pentazocine (0.03). These results indicate that the efficacy of opioids to produce activation of G proteins and rapid desensitization is distinct from their capacity to internalize mu-opioid receptors but that, contrary to some previous reports, morphine can produce rapid, homologous desensitization of MOP. 相似文献
108.
Blood plasma is the major vehicle by which metabolites are transported around the body in mammalian species, and chemical analysis of plasma can provide a wealth of information relating to the biochemical status of an individual and is important for diagnostic purposes. However, plasma is very complex in physicochemical terms because it is composed of a range of organic and inorganic constituents with a wide range of molecular weights and chemical classes and this makes analysis non-trivial. It is now well established that high-resolution (1)H NMR spectroscopy of blood plasma provides useful qualitative and quantitative biochemical information relating to metabolic disorders. However, one of the problems encountered in NMR spectroscopic analysis of blood plasma is the extensive peak overlap or presence of broad macromolecule peaks in the (1)H NMR spectrum, which can severely limit the amount of obtainable information. Even with spectroscopic editing, information relating to low-molecular-weight (MW) metabolites is frequently lost. Therefore, the efficiency of a range of conventional protein removal methods, in combination with the use of one- and two-dimensional NMR spectroscopic methods for evaluation, have been compared for the extraction of NMR-observable low-MW metabolites. It has been shown that these "deproteinization" methods vary considerably in recovery of low MW metabolites and a judicious choice is crucial for optimal extraction of a given analyte. The results presented here show that while ultrafiltration provides the "safest" method of plasma deproteinization, the signal-to-noise ratio of the resultant (1)H NMR spectra is poor. On the other hand, acetonitrile precipitation at physiological pH allows the detection of more low-MW metabolites and at higher concentrations than any other method and provides the further advantages of being a rapid and simple procedure. 相似文献
109.
Dell EJ Connor J Chen S Stebbins EG Skiba NP Mochly-Rosen D Hamm HE 《The Journal of biological chemistry》2002,277(51):49888-49895
A yeast two-hybrid approach was used to discern possible new effectors for the betagamma subunit of heterotrimeric G proteins. Three of the clones isolated are structurally similar to Gbeta, each exhibiting the WD40 repeat motif. Two of these proteins, the receptor for activated C kinase 1 (RACK1) and the dynein intermediate chain, co-immunoprecipitate with Gbetagamma using an anti-Gbeta antibody. The third protein, AAH20044, has no known function; however, sequence analysis indicates that it is a WD40 repeat protein. Further investigation with RACK1 shows that it not only interacts with Gbeta(1)gamma(1) but also unexpectedly with the transducin heterotrimer Galpha(t)beta(1)gamma(1). Galpha(t) alone does not interact, but it must contribute to the interaction because the apparent EC(50) value of RACK1 for Galpha(t)beta(1)gamma(1) is 3-fold greater than that for Gbeta(1)gamma(1) (0.1 versus 0.3 microm). RACK1 is a scaffold that interacts with several proteins, among which are activated betaIIPKC and dynamin-1 (1). betaIIPKC and dynamin-1 compete with Gbeta(1)gamma(1) and Galpha(t)beta(1)gamma(1) for interaction with RACK1. These findings have several implications: 1) that WD40 repeat proteins may interact with each other; 2) that Gbetagamma interacts differently with RACK1 than with its other known effectors; and/or 3) that the G protein-RACK1 complex may constitute a signaling scaffold important for intracellular responses. 相似文献
110.
Hypotransferrinemic (HP) mice have a splicing defect inthe transferrin gene, resulting in <1% of the normal plasma levels of transferrin. They have severe anemia, suggesting that transferrin is essential for iron uptake by erythroid cells in the bone barrow. To clarify the significance of transferrin on iron delivery to the bone marrow, iron concentration and 59Fe distribution were determined in 7-day-old HP mice. Iron concentration in the femur, bone containing the bone marrow, of HP mice was approximately twice higher than in wild type mice. Twenty-four h after injection of 59FeCl3, 59Fe concentration in the bone and bone marrow of HP mice was also twice higher than in wild type mice. The present findings indicate that iron is abnormally delivered to the bone marrow of HP mice. However, the iron seems to be unavailable for the production of hemoglobin. These results suggest that transferrin-dependent iron uptake by erythroid cells in the bone marrow is essential for the development of erythrocytes. 相似文献