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101.
Nelson JF da Silveira Helen A Arcuri Carlos E Bonalumi Fátima P de Souza Isabel MVGC Mello Paula Rahal Jo?o RR Pinho Walter F de Azevedo 《BMC structural biology》2005,5(1):1
Background
Hepatitis C virus (HCV) currently infects approximately three percent of the world population. In view of the lack of vaccines against HCV, there is an urgent need for an efficient treatment of the disease by an effective antiviral drug. Rational drug design has not been the primary way for discovering major therapeutics. Nevertheless, there are reports of success in the development of inhibitor using a structure-based approach. One of the possible targets for drug development against HCV is the NS3 protease variants. Based on the three-dimensional structure of these variants we expect to identify new NS3 protease inhibitors. In order to speed up the modeling process all NS3 protease variant models were generated in a Beowulf cluster. The potential of the structural bioinformatics for development of new antiviral drugs is discussed. 相似文献102.
In our studies of the health effects of internalized depleted uranium, we developed a simple and rapid light microscopic method to stain specifically intracellular uranium deposits. Using J774 cells, a mouse macrophage line, treated with uranyl nitrate and the pyridylazo dye 2-(5-bromo-2- pyridylazo)-5-diethylaminophenol, uranium uptake by the cells was followed. Specificity of the stain for uranium was accomplished by using masking agents to prevent the interaction of the stain with other metals. Prestaining wash consisting of a mixture of sodium citrate and ethylenediaminetetraacetic acid eliminated staining of metals other than uranium. The staining solution consisted of the pyridylazo dye in borate buffer along with a quaternary ammonium salt, ethylhexadecyldimethylammonium bromide, and the aforementioned sodium citrate/ethylene-diaminetetraacetic acid mixture. The buffer was essential for maintaining the pH within the optimum range of 8 to 12, and the quaternary ammonium salt prevented precipitation of the dye. Staining was conducted at room temperature and was complete in 30 min. Staining intensity correlated with both uranyl nitrate concentration and incubation time. Our method provides a simple procedure for detecting intracellular uranium deposits in macrophages. 相似文献
103.
Background
The brain-derived protein S100B has been shown to be a useful marker of brain injury of different etiologies. Cognitive dysfunction after cardiac surgery using cardiopulmonary bypass has been reported to occur in up to 70% of patients. In this study we tried to evaluate S100B as a marker for cognitive dysfunction after coronary bypass surgery with cardiopulmonary bypass in a model where the inflow of S100B from shed mediastinal blood was corrected for. 相似文献104.
Tarrant AM Blomquist CH Lima PH Atkinson MJ Atkinson S 《Comparative biochemistry and physiology. Part B, Biochemistry & molecular biology》2003,136(3):473-485
Estrogens and androgens are steroids that act as reproductive hormones in vertebrates. These compounds have also been detected in reef-building corals and other invertebrates, where they are hypothesized to act as bioregulatory molecules. Experiments were conducted using labeled steroid substrates to evaluate metabolism of estrogens and androgens by coral homogenates. GC-MS analysis of 13C-labeled steroids showed that Montipora capitata coral homogenates or fragments could convert estradiol to estrone and testosterone to androstenedione and androstanedione, evidence that M. capitata contains 17beta-hydroxysteroid dehydrogenase and 5alpha-reductase. When homogenates from three coral species and symbiotic dinoflagellates (zooxanthellae) were incubated with tritiated steroid substrates, metabolites separated by thin-layer chromatography confirmed that 17beta-hydroxysteroid dehydrogenase activity occurred in all species tested. NADP+ was the preferred cofactor in dehydrogenation reactions with coral homogenates. Reduction of estrone and androstenedione occurred at lower rates and aromatization of androgens was not observed. It is unclear whether estrogens detected previously in coral tissues are produced endogenously or sequestered in coral tissue from dietary or environmental sources. Previous studies have demonstrated that corals can take up estrogens from the water column overlying coral reefs. Considered in total, these observations suggest corals could alter the concentration or form of steroids available to reef organisms. 相似文献
105.
Hsieh M Collins ED Blomquist T Lustig B 《Journal of biomolecular structure & dynamics》2002,20(2):243-251
A new approach in determining local residue flexibility from base-amino acid contact frequencies is applied to the twelve million lattice chains modeling BIV Tat peptide binding to TAR RNA fragment. Many of the resulting key features in flexibility correspond to RMSD calculations derived from a set of five NMR derived structures (X. Ye, R. A. Kumar, and D. J. Patel, Protein Data Bank: Database of three-dimensional structures determined from NMR (1996)) and binding studies of mutants (L. Chen and A. D. Frankel, Proc. Natl. Acad. Sci. USA 92, 5077-5081 (1995)). The lattice and RMSD calculations facilitate the identification of peptide hinge regions that can best utilize the introduction of Gly or other flexible residues. This approach for identifying potential sites amenable to substitution of more flexible residues to enhance peptide binding to RNA targets could be a useful design tool. 相似文献
106.
107.
Glycosylation sites and site-specific glycosylation in human Tamm- Horsfall glycoprotein 总被引:4,自引:1,他引:3
The N-glycosylation sites of human Tamm-Horsfall glycoprotein from one
healthy male donor have been characterized, based on an approach using
endoproteinase Glu-C (V-8 protease, Staphylococcus aureus ) digestion and a
combination of chromatographic techniques, automated Edman sequencing, and
fast atom bombardment mass spectrometry. Seven out of the eight potential
N-glycosylation sites, namely, Asn52, Asn56, Asn208, Asn251, Asn298,
Asn372, and Asn489, turned out to be glycosylated, and the potential
glycosylation site at Asn14, being close to the N-terminus, is not used.
The carbohydrate microheterogeneity on three of the glycosylation sites was
studied in more detail by high-pH anion-exchange chromatographic profiling
and 500 MHz1H-NMR spectroscopy. Glycosylation site Asn489 contains mainly
di- and tri-charged oligosaccharides which comprise, among others, the
GalNAc4 S (beta1-4)GlcNAc terminal sequence. Only glycosylation site Asn251
bears oligomannose-type carbohydrate chains ranging from Man5GlcNAc2to
Man8GlcNAc2, in addition to a small amount of complex- type structures.
Profiling of the carbohydrate moieties of Asn208 indicates a large
heterogeneity, similar to that established for native human Tamm-Horsfall
glycoprotein, namely, multiply charged complex-type carbohydrate
structures, terminated by sulfate groups, sialic acid residues, and/or the
Sda-determinant.
相似文献
108.
B Kornmatitsuk E Dahl E Ropstad JF Beckers H Gustafsson H Kindahl 《Acta veterinaria Scandinavica》2004,45(1):47
The high incidence of stillbirth in Swedish Holstein heifers has increased continuously during the last 15 years to an average
of 11% today. The pathological reasons behind the increased incidence of stillbirth are unknown. The present experiment was
undertaken to investigate possible causes of stillbirth and to study possible physiological markers for predicting stillbirth.
Twenty Swedish Holstein dairy heifers sired by bulls with breeding values for a high risk of stillbirth (n = 12) (experimental
group) and a low risk of stillbirth (n = 8) (control group, group B) were selected based on information in the Swedish AI-data
base. The experimental group consisted of 2 subgroups of heifers (groups A1 and A2) inseminated with 2 different bulls with
3.5% and 9% higher stillbirth rates than the average, and the control group consisted of heifers pregnant with 5 different
bulls with 0%–6% lower stillbirth rates than the average. The bull used for group A1 had also calving difficulties due to
large calves as compared to the bull in group A2 showing no calving difficulties. The heifers were supervised from 6–7 months
of pregnancy up to birth, and the pregnancies and parturitions were compared between groups regarding hormonal levels, haematology,
placental characteristics and calf viability. In group A1, 1 stillborn, 1 weak and 4 normal calves were recorded. In group
A2, 2 stillborn and 4 normal calves were registered. All animals in the control group gave birth to a normal living calf without
any assistance. The weak calf showed deviating profiles of body temperature, saturated oxygen and heart rates, compared with
the normal living calves. No differences of the placentome thickness, measured in vivo by ultrasonography were seen between the groups. The number of leukocytes and differential cell counts in groups A1 and A2
followed the profiles found in the control group. In group A1, a slight decrease of oestrone sulphate (E1SO4) levels was found
in the animal delivering a stillborn calf from the first 24-h blood sampling at 6 weeks to the second at 3 weeks prior to
delivery, while the levels of E1SO4 at both periods in the animal delivering a weak calf followed the profile in animals delivering
a normal living calf. During late pregnancy and at the time of parturition, the levels of E1SO4 and PAGs in animals delivering
a stillborn or weak calf (from group A1) followed the normal profiles found in animals delivering a normal living calf. In
group A2, low levels of E1SO4 and pregnancy associated glycoproteins (PAGs) over 24 h at both 3 and 6 weeks prior to parturition
(<1.5 nmol/L) were recorded in animals delivering a stillborn calf. During late pregnancy and parturition, the levels of E1SO4
and PAGs were slightly lower during 30–50 days prior to delivery and increased with a lower magnitude at the time of parturition.
In conclusion, our results indicate that the aetiology behind stillbirth varies depending on the AI-bulls used and is associated
with dystocia or low viability of the calves. Deviating profiles of oestrone sulphate (E1SO4) and pregnancy associated glycoproteins
(PAGs) in animals delivering a stillborn calf not caused by dystocia were observed, suggesting placental dysfunction as a
possible factor. The finding suggests that the analyses of E1SO4 and PAGs could be used for monitoring foetal well-being in
animals with a high risk of stillbirth at term. 相似文献
109.
110.
Charles H. Blomquist Benjamin S. Leung Ruoping Zhang Youyang Zhu Patricia M. Chang 《Journal of cellular biochemistry》1995,59(4):409-417
Although there is a growing body of evidence that 17β-hydroxysteroid oxidoteductase plays a role the regulation of steroid levels in epithelial tumors of the endometrium and breast, out knowledge of its role in other gynecologic tumors is limited. In this investigation, the 17β-hydroxysteroid oxidoreductase activity of cell lines derived from two ovarian tumors (OVCAR-3, CAOV-3) and an epidermoid tumor of the vulva (A431) was assayed under conditions which differentiate between 17β-hydroxysteriod oxidoreductase type 1, a cytosolic isoform highly specific for estradiol, and type 2, a membrane bound isoform reactive with both estradiol and testosterone. On the basic of estradiol/testosterone activity ratios, all three cell lines appear to have type 2-like activity, with the specific activity of A431 markedly greater than that of the other cell lines. Estradiol, progesterone, or EGE, alone or in combination, were without effect on the enzymatic activity of OVCAR-3 cells. EGE decreased the activity of CAOV-3 cells slightly. In contrast, EGE stimulated A431 17β-hydroxysteriod oxidoreductase activity 7–8-fold over a 5-day exposure. Estradiol or progesterone, singly or in combination, also did not effect the enzymatic activity of A431 cells. However, progesterone inhibited the increase in activity seen in the presence of EGE. With EGE, estradiol, and progesterone together, the increase in enzymatic activity was comparable to that with EGE alone. The effects of estradiol and progesterone appear to result from steroid actions following binding of EGE to low-affinity receptors on A431 cells. © 1995 Wiley-Liss, Inc. 相似文献