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排序方式: 共有178条查询结果,搜索用时 15 毫秒
1.
Vegetation change over a nine-year period was studied in Guadalupe Mountains, New Mexico. Permanent transects in desert shrub
vegetation were sampled in 1972 and 1980. Emphasis was given to shrubs because of their importance to big game diets. Univariate
paired t-tests and reciprocal averaging ordination were used to detect and display coordinated changes in species composition over
time. Despite apparently less browsing pressure in desert shrub vegetation in 1980 there were few significant changes in species
composition. In addition, preferred forage species showed reduced reproduction while species of intermediate and poor forage
value dis-played increased reproduction during this time. These data do not support traditional rangeland succession theory
which states that enhanced reproduction of preferred species should follow grazing or browsing pressure reduction. 相似文献
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Amino Acids - Solid-phase synthesis of cyclic, branched or side-chain-modified peptides typically involves introduction of a residue carrying a temporary side-chain protecting group that undergoes... 相似文献
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Che-Ying Kuo Mariya Shevchuk Justin Opfermann Ting Guo Marco Santoro John P. Fisher Peter CW Kim 《Biotechnology and bioengineering》2019,116(1):181-192
Trophoblast invasion and remodeling of the maternal spiral arteries are required for pregnancy success. Aberrant endothelium–trophoblast crosstalk may lead to preeclampsia, a pregnancy complication that has serious effects on both the mother and the baby. However, our understanding of the mechanisms involved in this pathology remains elementary because the current in vitro models cannot describe trophoblast–endothelium interactions under dynamic culture. In this study, we developed a dynamic three-dimensional (3D) placenta model by bioprinting trophoblasts and an endothelialized lumen in a perfusion bioreactor. We found the 3D printed perfusion bioreactor system significantly augmented responses of endothelial cells by encouraging network formations and expressions of angiogenic markers, cluster of differentiation 31 (CD31), matrix metalloproteinase-2 (MMP2), matrix metalloproteinase-9 (MMP9), and vascular endothelial growth factor A (VEGFA). Bioprinting favored colocalization of trophoblasts with endothelial cells, similar to in vivo observations. Additional analysis revealed that trophoblasts reduced the angiogenic responses by reducing network formation and motility rates while inducing apoptosis of endothelial cells. Moreover, the presence of endothelial cells appeared to inhibit trophoblast invasion rates. These results clearly demonstrated the utility and potential of bioprinting and perfusion bioreactor system to model trophoblast–endothelium interactions in vitro. Our bioprinted placenta model represents a crucial step to develop advanced research approach that will expand our understanding and treatment options of preeclampsia and other pregnancy-related pathologies. 相似文献
7.
Tsao CC Wester MR Ghanayem B Coulter SJ Chanas B Johnson EF Goldstein JA 《Biochemistry》2001,40(7):1937-1944
CYP2C19 is selective for the 4'-hydroxylation of S-mephenytoin while the highly similar CYP2C9 has little activity toward this substrate. To identify critical amino acids determining the specificity of human CYP2C19 for S-mephenytoin 4'-hydroxylation, we constructed chimeras by replacing portions of CYP2C9 containing various proposed substrate recognition sites (SRSs) with those of CYP2C19 and mutating individual residues by site-directed mutagenesis. Only a chimera containing regions encompassing SRSs 1--4 was active (30% of wild-type CYP2C19), indicating that multiple regions are necessary to confer specificity for S-mephenytoin. Mutagenesis studies identified six residues in three topological components of the proteins required to convert CYP2C9 to an S-mephenytoin 4'-hydroxylase (6% of the activity of wild-type CYP2C19). Of these, only the I99H difference located in SRS 1 between helices B and C reflects a change in a side chain that is predicted to be in the substrate-binding cavity formed above the heme prosthetic group. Two additional substitutions, S220P and P221T residing between helices F and G but not in close proximity to the substrate binding site together with five differences in the N-terminal portion of helix I conferred S-mephenytoin 4'-hydroxylation activity with a K(M) similar to that of CYP2C19 but a 3-fold lower K(cat). Three residues in helix I, S286N, V292A, and F295L, were essential for S-mephenytoin 4'-hydroxylation activity. On the basis of the structure of the closely related enzyme CYP2C5, these residues are unlikely to directly contact the substrate during catalysis but are positioned to influence the packing of substrate binding site residues and likely substrate access channels in the enzyme. 相似文献
8.
18F]Galacto-RGD: synthesis, radiolabeling, metabolic stability, and radiation dose estimates 总被引:3,自引:0,他引:3
Haubner R Kuhnast B Mang C Weber WA Kessler H Wester HJ Schwaiger M 《Bioconjugate chemistry》2004,15(1):61-69
It has been demonstrated in various murine tumor models that radiolabeled RGD-peptides can be used for noninvasive determination of alphavbeta3 integrin expression. Introduction of sugar moieties improved the pharmacokinetic properties of these peptides and led to tracer with good tumor-to-background ratios. Here we describe the synthesis, radiolabeling, and the metabolic stability of a glycosylated RGD-peptide ([18F]Galacto-RGD) and give first radiation dose estimates for this tracer. The peptide was assembled on a solid support using Fmoc-protocols and cyclized under high dilution conditions. It was conjugated with a sugar amino acid, which can be synthesized via a four-step synthesis starting from pentaacetyl-protected galactose. For radiolabeling of the glycopeptide, 4-nitrophenyl-2-[18F]fluoropropionate was used. This prosthetic group allowed synthesis of [18F]Galacto-RGD with a maximum decay-corrected radiochemical yield of up to 85% and radiochemical purity >98%. The overall radiochemical yield was 29 +/- 5% with a total reaction time including final HPLC preparation of 200 +/- 18 min. The metabolic stability of [18F]Galacto-RGD was determined in mouse blood and liver, kidney, and tumor homogenates 2 h after tracer injection. The average fraction of intact tracer in these organs was approximately 87%, 76%, 69%, and 87%, respectively, indicating high in vivo stability of the radiolabeled glycopeptide. The expected radiation dose to humans after injection of [18F]Galacto-RGD has been estimated on the basis of dynamic PET studies with New Zealand white rabbits. According to the residence times in these animals the effective dose was calculated using the MIRDOSE 3.0 program as 2.2 x 10(-2) mGy/MBq. In conclusion, [18F]Galacto-RGD can be synthesized in high radiochemical yields and radiochemical purity. Despite the time-consuming synthesis of the prosthetic group 185 MBq of [18F]Galacto-RGD, a sufficient dose for patient studies, can be produced starting with approximately 2.2 GBq of [18F]flouride. Moreover, the fast excretion, the suitable metabolic stability and the low estimated radiation dose allow to evaluate this tracer in human studies. 相似文献
9.
Structure of mammalian cytochrome P450 2C5 complexed with diclofenac at 2.1 A resolution: evidence for an induced fit model of substrate binding 总被引:2,自引:0,他引:2
Wester MR Johnson EF Marques-Soares C Dijols S Dansette PM Mansuy D Stout CD 《Biochemistry》2003,42(31):9335-9345
The structure of the anti-inflammatory drug diclofenac bound in the active site of rabbit microsomal cytochrome P450 2C5/3LVdH was determined by X-ray crystallography to 2.1 A resolution. P450 2C5/3LVdH and the related enzyme 2C5dH catalyze the 4'-hydroxylation of diclofenac with apparent K(m) values of 80 and 57 microM and k(cat) values of 13 and 16 min(-1), respectively. Spectrally determined binding constants are similar to the K(m) values. The structure indicates that the pi-electron system of the dichlorophenyl moiety faces the heme Fe with the 3'- and 4'-carbons located 4.4 and 4.7 A, respectively, from the Fe. The carboxyl moiety of the substrate is hydrogen bonded to a cluster of waters that are also hydrogen bonded to the side chains of N204, K241, S289, and D290 as well as the backbone of the protein. The proximity of the diclofenac carboxylate to the side chain of D290 together with an increased binding affinity at lower pH suggests that diclofenac is protonated when bound to the enzyme. The structure exhibits conformational changes indicative of an adaptive fit to the substrate reflecting both the hydration and size of the substrate. These results indicate how structurally diverse substrates are recognized by drug-metabolizing P450 enzymes. 相似文献
10.
Immunocalins: a lipocalin subfamily that modulates immune and inflammatory responses 总被引:9,自引:0,他引:9
A subset of the lipocalins, notably alpha(1)-acid glycoprotein, alpha(1)-microglobulin, and glycodelin, exert significant immunomodulatory effects in vitro. Interestingly, all three are encoded from the q32-34 region of human chromosome 9, together with at least four other lipocalins (neutrophil gelatinase-associated lipocalin, complement factor gamma-subunit, tear prealbumin, and prostaglandin D synthase) that also may have anti-inflammatory and/or antimicrobial activity. This review addresses important features of this genetically linked subfamily of lipocalins (involvement with the acute phase response, immunomodulatory and anti-inflammatory properties, the tissue localization, complex formation with other proteins and receptors, etc.). It is likely that these proteins have evolved to be an integrated part of the body's defense system as part of the extended cytokine network. Its members exert a regulatory, dampening influence on the inflammatory cascade, thereby protecting against tissue damage from excessive inflammation. That most major mammalian allergens are lipocalins may reflect this connection of lipocalins with the immune system. We propose that this immunologically active lipocalin subset be named the 'immunocalins', signifying not only the structural homology and close genetic linkage of its members, but also their protective involvement with immunological and inflammatory processes. As immune mediators, immunocalins appear to use at least three interactive sites: the lipocalin 'pocket', binding sites for other plasma proteins, and binding sites for cell surface receptors. 相似文献