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71.
DsbA from Escherichia coli is the most oxidizing member of the thiol-disulfide oxidoreductase family (E(o)' = -122 mV) and is required for efficient disulfide bond formation in the periplasm. The reactivity of the catalytic disulfide bond (Cys(30)-Pro(31)-His(32)-Cys(33)) is primarily due to an extremely low pK(a) value (3.4) of Cys(30), which is stabilized by the partial positive dipole charge of the active-site helix alpha1 (residues 30-37). We have randomized all non-cysteine residues of helix alpha1 (residues 31, 32, and 34-37) and found that two-thirds of the resulting variants complement DsbA deficiency in a dsbA deletion strain. Sequencing of 98 variants revealed a large number of non-conservative replacements in active variants, even at well conserved positions. This indicates that tertiary structure context strongly determines alpha-helical secondary structure formation of the randomized sequence. A subset of active and inactive variants was further characterized. All these variants were more reducing than wild type DsbA, but the redox potentials of active variants did not drop below -210 mV. All inactive variants had redox potentials lower than -210 mV, although some of the inactive proteins were still re-oxidized by DsbB. This demonstrates that efficient oxidation of substrate polypeptides is the crucial property of DsbA in vivo. 相似文献
72.
Shealy DJ Wooley PH Emmell E Volk A Rosenberg A Treacy G Wagner CL Mayton L Griswold DE Song XY 《Arthritis research》2002,4(5):R7
Anti-tumor-necrosis-factor-alpha (TNF-alpha) monoclonal antibody was used to treat Tg197 transgenic mice, which constitutively produce human TNF-alpha (hTNF-alpha) and develop a progressive polyarthritic disease. Treatment of both young (7- or 8-week-old) and aged (27- or 28-week-old) mice commenced when at least two limbs showed signs of moderate to severe arthritis. The therapeutic efficacy of anti-TNF-alpha antibody was assessed using various pathological indicators of disease progression. The clinical severity of arthritis in Tg197 mice was significantly reduced after anti-TNF-alpha treatment in comparison with saline-treated mice and in comparison with baseline assessments in both young and aged mice. The treatment with anti-TNF-alpha prevented loss of body weight. Inflammatory pathways as reflected by elevated circulating hTNF-alpha and local expression of various proinflammatory mediators were all diminished by anti-TNF-alpha treatment, confirming a critical role of hTNF-alpha in this model of progressive polyarthritis. More importantly, the amelioration of the disease was associated with reversal of existing structural damage, including synovitis and periosteal bone erosions evident on histology. Repair of cartilage was age dependent: reversal of cartilage degradation after anti-TNF-alpha treatment was observed in young mice but not in aged mice. 相似文献
73.
Membrane fluidity and overall protein secondary structure of human erythrocytes were studied in situ using Fourier transform infrared spectroscopy (FTIR). Erythrocyte membranes were found to have weakly cooperative phase transitions at 14 degrees C and at 34 degrees C, which were tentatively assigned to the melting of the inner membrane leaflet and the sphingolipid rich outer leaflet, respectively. Cholesterol depletion by methyl-beta-cyclodextrin (MbetaCD) resulted in a large increase in the cooperativity of these transitions, and led to the appearance of another phospholipid transition at 25 degrees C. Multiple, sharp membrane phase transitions were observed after 5 days cold storage (4 degrees C ), which indicated phase separation of the membrane lipids. Using fluorescence microscopy, it was determined that the lipid probe 1,1'-dioctadecyl-3,3,3',3-tetramethyl-indocarbocyanine perchlorate (dil-C18) remained homogeneously distributed in the erythrocyte membrane during cold storage, suggesting that lipid domains were below the resolution limit of the microscope. Using thin layer chromatography, changes in the membrane lipid composition were detected during cold storage. By contrast, assessment of the amide-II band with FTIR showed that the overall protein secondary structure of haemoglobin was stable during cold storage. 相似文献
74.
The function of the binuclear Cu(A) center in cytochrome c oxidase (CcO) was studied using two Rhodobacter sphaeroides CcO mutants involving direct ligands of the Cu(A) center, H260N and M263L. The rapid electron-transfer kinetics of the mutants were studied by flash photolysis of a cytochrome c derivative labeled with ruthenium trisbipyridine at lysine-55. The rate constant for intracomplex electron transfer from heme c to Cu(A) was decreased from 40000 s(-1) for wild-type CcO to 16000 s(-1) and 11000 s(-1) for the M263L and H260N mutants, respectively. The rate constant for electron transfer from Cu(A) to heme a was decreased from 90000 s(-1) for wild-type CcO to 4000 s(-1) for the M263L mutant and only 45 s(-1) for the H260N mutant. The rate constant for the reverse reaction, heme a to Cu(A), was calculated to be 66000 s(-1) for M263L and 180 s(-1) for H260N, compared to 17000 s(-1) for wild-type CcO. It was estimated that the redox potential of Cu(A) was increased by 120 mV for the M263L mutant and 90 mV for the H260N mutant, relative to the potential of heme a. Neither mutation significantly affected the binding interaction with cytochrome c. These results indicate that His-260, but not Met-263, plays a significant role in electron transfer between Cu(A) and heme a. 相似文献
75.
Markaverich BM Alejandro MA Markaverich D Zitzow L Casajuna N Camarao N Hill J Bhirdo K Faith R Turk J Crowley JR 《Biochemical and biophysical research communications》2002,291(3):692-700
A mitogenic agent in corncob bedding and fresh corn products disrupts sexual behavior and estrous cyclicity in rats. The mitogenic activity resides in an isomeric mixture of linoleic acid derivatives with a tetrahydrofuran ring and two hydroxyl groups (THF-diols) that include 9, (12)-oxy-10,13-dihydroxystearic acid and 10, (13)-oxy-9,12-dihydroxystearic acid. Synthetic THF-diols stimulated breast cancer cell proliferation in vitro and disrupted the estrous cycle in female rats at oral doses of approximately 0.30 mg/kg body weight/day. Exposure to THF-diols may disrupt endocrine function in experimental animals at doses approximately 200 times lower than classical phytoestrogens, promote proliferation of breast or prostate cancer, and adversely affect human health. 相似文献
76.
McKinley J Buchanan-Smith HM Bassett L Morris K 《Journal of applied animal welfare science : JAAWS》2003,6(3):209-220
The first author trained 12 laboratory-housed common marmosets (Callithrix jacchus) in pairs to assess the practicality of positive reinforcement training as a technique in the management of these nonhuman animals. Behaviors taught were (a) target training to allow in homecage weighing and (b) providing urine samples. Between 2 to 13, 10-minute training sessions established desired behaviors. Training aggressive animals only after they had been fed eliminated aggression during training. Trained animals proved extremely reliable, and data collection using trained animals was considerably faster than collection using current laboratory techniques. The results suggest that positive reinforcement training is a practical option in the management of laboratory-housed marmosets. 相似文献
77.
A mid-abdominal mass was discovered during routine physical examination of a rhesus macaque (Macaca mulatta). Further diagnostics and exploratory laparotomy were performed, revealing a fluid-filled cyst attached to the caudal free margin of the greater omentum. Formation and pulsatile movement of white-colored circumferential bands within the wall of the cyst were observed during surgery. The cyst was removed and later was dissected. The discovery of a single invaginated scolex identified the cyst as a cysticercus. The location and characteristics of the cysticercus were consistent with the larval form of Taenia hydatigena. 相似文献
78.
Guidot DM Modelska K Lois M Jain L Moss IM Pittet JF Brown LA 《American journal of physiology. Lung cellular and molecular physiology》2000,279(1):L127-L135
We determined that rats fed a liquid diet containing ethanol (36% of calories) for 6 wk had decreased (P < 0.05) net vectorial fluid transport and increased (P < 0.05) bidirectional protein permeability across the alveolar epithelium in vivo compared with rats fed a control diet. However, both groups increased (P < 0.05) fluid transport in response to epinephrine (10(-5) M) stimulation, indicating that transcellular sodium transport was intact. In parallel, type II cells isolated from ethanol-fed rats and cultured for 8 days formed a more permeable monolayer as reflected by increased (P < 0.05) leak of [(14)C]inulin. However, type II cells from ethanol-fed rats had more sodium-permeant channels in their apical membranes than type II cells isolated from control-fed rats, consistent with the preserved response to epinephrine in vivo. Finally, the alveolar epithelium of ethanol-fed rats supplemented with L-2-oxothiaxolidine-4-carboxylate (Procysteine), a glutathione precursor, had the same (P < 0.05) net vectorial fluid transport and bidirectional protein permeability in vivo and permeability to [(14)C]inulin in vitro as control-fed rats. We conclude that chronic ethanol ingestion via glutathione deficiency increases alveolar epithelial intercellular permeability and, despite preserved or even enhanced transcellular sodium transport, renders the alveolar epithelium susceptible to acute edematous injury. 相似文献
79.
Lois Bragg 《American anthropologist》1998,100(1):177-180
Extraordinary Bodies: Figuring Physical Disability in American Culture and Literature. Rosemarie Garland Thomson. New York: Columbia University Press, 1997. 200 pp.
Freakery: Cultural Spectacles of the Extraordinary Body. Rosemarie Garland Thomson. ed. New York: New York University Press, 1996. 400 pp.
Monster Theory: Reading Culture. Jeffrey Jerome Cohen. ed. Minneapolis: University of Minnesota Press, 1996.315pp. 相似文献
Freakery: Cultural Spectacles of the Extraordinary Body. Rosemarie Garland Thomson. ed. New York: New York University Press, 1996. 400 pp.
Monster Theory: Reading Culture. Jeffrey Jerome Cohen. ed. Minneapolis: University of Minnesota Press, 1996.315pp. 相似文献
80.
Graham R Stirling Linda J Smith Kerrie A Licastro Lois M Eden 《Biological Control》1998,11(3):224-230
Arthrobotrys dactyloidesgrew readily in shaken flasks containing glucose corn steep powder and 8–10 g dry wt of fungal biomass/liter medium was usually produced in 5–6 days. However, it was difficult to convert this biomass into a viable, granulated product suitable for commercial use in biological control. Formulations prepared using kaolin and vermiculite as carriers and gum arabic as a binder showed poor viability when biomass was harvested from liquid culture, mixed with formulation ingredients, granulated, and then dried to a moisture content of less than 5%. Inclusion of a solid-phase incubation step following granulation and prior to drying (incubation of moist granules for 3 days at 25°C in a sterile plastic bag aerated with sterile air) markedly improved biological activity. When granules produced in this manner were placed on a glass slide in field soil, hyphae proliferated from granules and always produced traps. Seven experiments in soil microcosms showed that formulations which had been subjected to solid phase incubation prior to drying consistently reduced numbers ofMeloidogyne javanicajuveniles by more than 90%. In seven glasshouse experiments in which field soils were treated with granules (10 g/liter) and planted to tomatoes, the number of galls induced by the nematode was reduced by 57–96%. 相似文献