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The ability to accurately diagnose the presence of an infective micro-organism is not only important for individual human and animal health and wellbeing, but is also central to surveillance programmes. Effective and sustainable control of many diseases in the developing world depends on the availability of field applicable diagnostics that are cheap, reliable, simple in design and application, and which provide immediate results. This review examines how the genome sequences can be used in the selection of potential candidate proteins for developing new serodiagnostics for African trypanosomiasis. 相似文献
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Rodrigo MC Martin DS Eyster KM 《American journal of physiology. Regulatory, integrative and comparative physiology》2003,285(4):R754-R761
This study was designed to identify new gene targets of estrogen in the mesenteric arteries and to determine whether the soy phytoestrogens could mimic estrogen effects. Ovariectomized rats were treated with estradiol, genistein, or daidzein for 4 days. The mesenteric arteries were harvested, total RNA was extracted, mRNA was reverse transcribed in the presence of [33P]dCTP, and the labeled probes were hybridized with DNA microarrays. Analysis of the microarray data identified biglycan as a target of estrogenic regulation. Semiquantitative RT-PCR was used to confirm and quantitate the decrease in biglycan gene expression in response to estrogen (-37%), genistein (-15%), and daidzein (-10%). Treatment with the pure estrogen receptor antagonist ICI-182,780 reversed the inhibition of biglycan gene expression. The decrease in biglycan gene expression in response to estrogens was paralleled with a decrease in biglycan protein expression. Biglycan protein was localized to the media of the mesenteric arteries by immunohistochemistry. Collectively, these data suggest that biglycan is a vascular protein regulated at the genomic level by estrogens. 相似文献
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Martin DS Williams JL Breitkopf NP Eyster KM 《Canadian journal of physiology and pharmacology》2002,80(12):1180-1186
Dietary soy may attenuate the development of arterial hypertension. In addition, some soy-containing foods exhibit angiotensin-converting enzyme (ACE) inhibitory properties. Accordingly, we tested the hypothesis that ACE inhibition contributes to the antihypertensive effect of dietary soy. Mean arterial blood pressure (MAP) was recorded from conscious spontaneously hypertensive rats (SHR) at least 24 h after the implantation of catheters. Cumulative dose-response curves to intravenous angiotensin I (AI) (5-100 ng x kg(-1) x min(-1)) and angiotensin II (AII) (1-20 ng x kg(-1) x min(-1)) were constructed for male, sham-operated female, and ovariectomized female (OVX) SHR that were maintained on either casein or soy diets. The soy diet was associated with a significant reduction in baseline MAP in the OVX SHR (approximately 20 mmHg, 1 mmHg = 133.322 Pa). AI and AII infusions caused graded increases in MAP in all groups. However, there was no significant attenuation of the pressor responses to AI in the soy-fed SHR. Conversely, we observed a significant rightward displacement of the AII dose-response curves in the soy-fed sham-operated and OVX SHR. We conclude that ACE inhibition does not account for the antihypertensive effect of dietary soy in mature SHR. 相似文献
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Sheng Y Cross JA Shen Y Smith CA Bognar AL 《Archives of biochemistry and biophysics》2002,402(1):94-103
Site-directed mutagenesis was performed on Glu143, an essential amino acid in Lactobacillus casei folylpolyglutamate synthetase (FPGS) and the structurally equivalent residue, Glu146, in Escherichia coli FPGS. Glu143 is positioned near the P-loop and interacts with the Mg(2+) of Mg NTP-binding proteins. We have solved the structure of the E143A mutant of L. casei FPGS in the presence of AMPPCP and Mg(2+). The structure showed a water molecule at the place where Mg(2+) bound to the wild type enzyme. Mutant proteins E143A, and even E143D and E143Q with conservative mutations, lacked enzyme activity and failed to complement the methionine auxotrophy of the E. coli folC mutant SF4, showing that Glu143 is an essential residue. Both the L. casei and the E. coli FPGS mutant proteins bound methylene-tetrahydrofolate diglutamate and dihydropteroate normally. The E. coli E146Q mutant FPGS bound ADP with the same affinity as the wild type enzyme but bound ATP with much lower affinity and had higher ATPase activity than the wild type enzyme. The mutant enzyme was defective in forming the acyl-phosphate reaction intermediate from ATP and dihydropteroate. The E. coli FPGS requires activation by dihydropteroate or tetrahydrofolate binding to allow full activity. In the absence of a pteroate substrate, only 30% of the total enzyme binds ATP. We suggest that dihydropteroate causes a conformational change to allow increased ATP binding. The mutant enzyme was similarly activated by dihydropteroate resulting in increased ADP binding. 相似文献
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