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51.
The contribution of electrostriction of the solvent to the stabilization of the negatively charged tetrahedral transition state of a trypsin-catalyzed reaction was probed by means of kinetic studies involving high-pressure and solvent dielectric constant. A good correlation was observed between the increased catalytic efficiency of trypsin and the decreased solvent dielectric constant. When the dielectric constant of the solvents was lowered by 4.68 units, the loss of activation energy and that of free energy of activation were 2.26 kJ/mol and 3.09 kJ/mol, respectively. The activation volume for k(cat) decreased significantly as the dielectric constant of the solvent decreased, indicating that the degree of electrostriction of the solvent around the charged tetrahedral transition state has been enhanced. These observations demonstrate that the increase in the catalytic efficiency of the trypsin reaction with decreasing dielectric constant resulted from the stabilization of electrostatic energy for the formation of an oxyanion hole, and this stabilization was caused by the increase of electrostricted water around the charged tetrahedral transition state. Therefore, we conclude that control of the solvent dielectric constant can stabilize the tetrahedral transition state, and this lowers the activation energy. 相似文献
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M Ryan 《BMJ (Clinical research ed.)》1980,281(6238):501-502
54.
Ryan K. Cheu Andrew T. Gustin Christina Lee Luca Schifanella Charlene J. Miller Avie Ha Casey Kim Violeta J. Rodriguez Margaret Fischl Adam D. Burgener Kelly B. Arnold Maria L. Alcaide Nichole R. Klatt 《PLoS pathogens》2020,16(12)
Despite the efficacy of antiretroviral-based pre-exposure prophylactics (PrEP) in men who have sex with men, studies in women have produced widely varying outcomes. Recent evidence demonstrates that vaginal microbial communities are associated with increased HIV acquisition risk and may impact PrEP efficacy. Here, we investigate the mechanisms underlying how vaginal bacteria alter PrEP drug levels and impact HIV infection rates ex vivo. Using cervicovaginal lavages (CVLs) from women with or without bacterial vaginosis (BV), we identified microbial metabolism of PrEP drugs in BV samples through LC-MS/MS analysis of soluble drug levels and metabolite formation in dual T-cell cultures. CVL samples were assessed for microbiome analysis using sequencing of bacterial 16S rRNA genes. We also observed non-Lactobacillus bacteria that are associated with BV may potentially impact PrEP efficacy through increased HIV infection rates in co-cultures containing Lactobacillus or BV bacteria, PrEP drugs, CEM-GFP cells, and HIV-1LAI virus. Finally, we used these data to develop a novel predictive mathematical simulation modeling system to predict these drug interactions for future trials. These studies demonstrate how dysbiotic vaginal microbiota may impact PrEP drugs and provides evidence linking vaginal bacteria to PrEP efficacy in women. 相似文献
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Deon. C. Nel Peter G. Ryan Jeanne L. Nel Norbert T. W. Klages Rory P. Wilson Graham Robertson & Geoff N. Tuck 《Ibis》2002,144(3):E141-E154
Wandering Albatrosses Diomedea exulans are frequently killed when they attempt to scavenge baited hooks deployed by long-line fishing vessels. We studied the foraging ecology of Wandering Albatrosses breeding on Marion Island in order to assess the scale of interactions with known long-line fishing fleets. During incubation and late chick-rearing, birds foraged further away from the island, in warmer waters, and showed high spatial overlap with areas of intense tuna Thunnus spp. long-line fishing. During early chick-rearing, birds made shorter foraging trips and showed higher spatial overlap with the local Patagonian Toothfish Dissostichus eleginoides long-line fishery. Tracks of birds returning with offal from the Toothfish fishery showed a strong association with positions at which Toothfish long-lines were set and most diet samples taken during this stage contained fishery-related items. Independent of these seasonal differences, females foraged further from the islands and in warmer waters than males. Consequently, female distribution overlapped more with tuna long-line fisheries, whereas males interacted more with the Toothfish long-line fishery. These factors could lead to differences in the survival probabilities of males and females. Non-breeding birds foraged in warmer waters and showed the highest spatial overlap with tuna long-line fishing areas. The foraging distribution of Marion Island birds showed most spatial overlap with birds from the neighbouring Crozet Islands during the late chick-rearing and non-breeding periods. These areas of foraging overlap also coincided with areas of intense tuna long-line fishing south of Africa. As the population trends of Wandering Albatrosses at these two localities are very similar, it is possible that incidental mortality during the periods when these two populations show the highest spatial overlap could be driving these trends. 相似文献
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Dr. M. P. Pistillo N. Tanigaki O. Mazzoleni E. Ciccone U. Hämmerling M. Park P I. Terasaki G. B. Ferrara 《Immunogenetics》1987,25(3):145-151
Peripheral B lymphocytes obtained from three healthy individuals who had been immunized against peripheral blood lymphocytes from appropriate HLA-incompatible donors were transformed by the use of Epstein-Barr virus. The transformed blastoid B cells were repeatedly subcultured by means of cluster picking, and the HLA antibody-producing cultures were identified by testing the culture supernatants by means of the cytotoxicity assay, using the corresponding donor cells. Thus far, four cell lines that secrete cytotoxic HLA antibodies (MP1, 3, 4, and 5) have been established. Specific immunoabsorption experiments revealed that the antibody activity is carried by lambda-type IgM for MP1, by kappa-type IgM for MP3 and MP5, and by both for MP4. Specificity analysis of a panel of HLA-pretyped cells indicated that MP1 detects DQw2, whereas MP5 recognizes B7. The specificity of MP3 was similar to a DQ specificity termed DC5 (probably equivalent to TA10) but not the same. In the case of MP4, both of the lambda-type and kappa-type antibodies appeared to be directed toward new HLA class 11 determinants.Abbreviations used in this paper HLA
human major histocompatibility
- EBV
Epstein-Barr virus
- B-LCL
Blymphoblastoid cell line
- NA
not absorbed
- PBS
phosphate-buffered saline
- SPA
Sepharose protein A
- NRS
normal rabbit serum 相似文献
60.