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951.
An equation is found relating the fractional activity, (v/v0), of an enzyme assay mixture to the total concentrations of metalloenzyme, active site metal ion, metal-binding ligand and substrate and the stability constants of the complexes present. When (v/v0) is measured as a function of the total ligand concentration, this equation offers a way of data-plotting which yields straight lines and permits the calculation of the metal-binding constant KME from either the slope or the intercept, provided that mixed complexes (enzyme-metal ion-ligand) do not contribute significantly to the change in (v/v0). Since deviations from linearity occur in the latter case, the proposed inhibition plot serves as a diagnostic tool for the recognition of such complexes. Application to the inhibition of thermolysin by 1,10-phenanthroline gives a value of 2.1 × 1011m−1 for KZnE, the binding constant of the active site zinc ion, at pH 7.50, 25°C and ionic strength 0.1. The equation also allows the rapid calculation of the ligand concentration necessary to attain a desired degree of inhibition when the total enzyme and active site metal ion concentrations of the solution are known. 相似文献
952.
Evolving from the endosymbiosis of a green algal cell by a filose amoeba or amoeboflagellate, the chimearic chlorarachniophytes combine unique features retained from both of their ancestral units. They have preserved from the endosymbiont only the nucleomorph and chloroplast. Four strains from three genera of this algal class were studied to identify a set of non‐phosphorous‐containing polar lipids and their associated fatty acids using the techniques of positive‐ion electrospray ionization/mass spectrometry (ESI/MS) and electrospray ionization/mass spectrometry/mass spectrometry (ESI/MS/MS). Fourteen non‐phosphorous‐containing polar lipids, classified as betaine lipids were primarily identified as forms of diacylglyceryl‐N,N,N‐trimethylhomoserine (DGTS) and its structural isomer diaclyglycerylhydroxymethyl‐N,N,N‐trimethyl‐β‐alanine (DGTA). Though the number of forms of DGTA and DGTA were roughly equal, DGTS composed more of the polar lipid portion present in three of the strains tested, while the fourth, Lotharella globosa, was dominated by forms of DGTA. In addition, a lipid tentatively identified as diacylglycerylcarboxyhydroxymethylcholine (DGCC) was observed twice in minor amounts. The polar lipid‐associated fatty acids of the aforementioned algal strains generally included dodecanoic acid (12:0), tetradecanoic acid (14:0), hexadecanoic acid (16:0), octadecanoic acid (18:0), octadecenoic acid (18:1), and eicosapentaenoic acid [20:5(n‐3)]. The differences in betaine lipid content among the species studied may allow for further conclusions to be drawn regarding the taxonomy of chlorarachniophytes. 相似文献
953.
Phospholipids isolated from hardened and unhardened cells of the living bark of the black locust tree and from the cells of winter rye seedlings were analyzed by differential scanning calorimetry. In accord with previously reported data which showed little differences in the fatty acid unsaturation of phospholipids obtained from unhardy summer and very hardy winter bark of the black locust, only small differences were found in the temperature and enthalpies of the liquid-crystalline gel phase transitions of the isolated phospholipids of these respective tissues. In the case of winter rye, where fatty acid unsaturation was observed to increase with hardening, the differences in phase transition properties of the phospholipids isolated from hardened and unhardy rye also were found to be minor. In any event, the transition temperatures of the rye phospholipids were well above and that of the locust phospholipids far above the freeze-killing temperatures for these tissues. These results would suggest that both unsaturation and bulk fluidity of the isolated lipids from these plants bear little relationship to their degree of freezing tolerance. 相似文献
954.
Trials were carried out on 1184 dairy cows calved at least six weeks before treatment and 255 heifers to determine effectiveness of the prostaglandin analogue, cloprostenol to control estrus. In trial 1, following two injections of cloprostenol given 12 days apart, there was no difference in calving rate following AI either at 72 and 96 hr after treatment (71 163 ) or at a detected estrus (53 118 ) compared to control cows bred at estrus (54 110 ). In trial 2, treated cows were injected once after 5 to 7 days of estrous detection and AI. The calving rate following AI either at 72 and 96 hr after cloprostenol (46 100 ) or at a detected estrus (39 71 ) was similar to that in control cows bred at estrus (45 86 ). In trial 3, cows were bred at a detected estrus after the first cloprostenol injection. Twelve days after this injection, cows not bred were given a second injection and bred 72 and 96 hr later. The calving rate in treated cows bred at estrus after the first injection (66 138 ) was similar to calving rate in controls (55 95 ). However, calving rate in cows given a second injection and bred 72 and 96 hr later was significantly (P angle 0.05) lower (30 98 ). Similar results were obtained in heifers, except calving rate in trial 3 after the second cloprostenol injection was not reduced. 相似文献
955.
José Manuel García-Martínez Annarica Calcabrini Lorena González Esther Martín-Forero María Teresa Agulló-Ortuño Valérie Simon Harriet Watkin Steve M. Anderson Serge Roche Jorge Martín-Pérez 《Cellular signalling》2010,22(3):415-426
The cytokine prolactin (PRL) plays important roles in the proliferation and differentiation of the mammary gland and it has been implicated in tumorigenesis. The prolactin receptor (PRLR) is devoid of catalytic activity and its mitogenic response is controlled by cytoplasmic tyrosine kinases of the Src (SFK) and Jak families. How PRLR uses these kinases for signaling is not well understood. Previous studies indicated that PRLR-induced Jak2 activation does not require SFK catalytic activity in favor of separate signaling operating on this cellular response. Here we show that, nevertheless, PRLR requires Src-SH2 and -SH3 domains for Jak2 signaling. In W53 lymphoid cells, conditional expression of two c-Src non-catalytic mutants, either SrcK295M/Y527F or Src?K, whose SH3 and SH2 domains are exposed, controls Jak2/Stat5 activation by recruiting Jak2, avoiding its activation by endogenous active SFK. In contrast, the kinase inactive SrcK295M mutant, with inaccessible SH3 and SH2 domains, does not. Furthermore, all three mutants attenuate PRLR-induced Akt and p70S6K activation. Accordingly, PRLR-induced Jak2/Stat5 signaling is inhibited in MCF7 breast cancer cells by Src depletion, expression of SrcK295M/Y527F or active Src harboring an inactive SH2 (SrcR175L) or SH3 domain (SrcW118A). Finally, Jak2/Stat5 pathway is also reduced in Src?/? mice mammary glands. We thus conclude that, in addition to Akt and p70S6K, SFK regulate PRLR-induced Jak2 signaling through a kinase-independent mechanism. 相似文献
956.
957.
Background
The Timed Up and Go (TUG) test is widely used to assess locomotion in patients with stroke and is considered to predict the risk of falls. The analysis of locomotor trajectories during the TUG appears pertinent in stroke patients. The aims of this study were i) to analyze locomotor trajectories in patients with stroke during the walking and turning sub-tasks of the TUG, and to compare them with healthy subjects, ii) to determine whether trajectory parameters provide additional information to that provided by the conventional measure (performance time), iii) to compare the trajectory parameters of fallers and non-fallers with stroke and of patients with right and left hemisphere stroke, and iv) to evaluate correlations between trajectory parameters and Berg Balance Scale scores.Methods
29 patients with stroke (mean age 54.2±12.2 years, 18 men, 8 fallers) and 25 healthy subjects (mean age 51.6±8.7 years, 11 men) underwent three-dimensional analysis of the TUG. The trajectory of the center of mass was analyzed by calculation of the global trajectory length, Hausdorff distance and Dynamic Time Warping. The parameters were compared with a reference trajectory during the total task and each sub-task (Go, Turn, Return) of the TUG.Results
Values of trajectory parameters were significantly higher for the stroke group during the total TUG and the Go and Turn sub-tasks (p<0.05). Moreover, logistic regression indicated that these parameters better discriminated stroke patients and healthy subjects than the conventional timed performance during the Go sub-task. In addition, fallers were distinguished by higher Dynamic Time Warping during the Go (p<0.05). There were no differences between patients with right and left hemisphere stroke.Discussion and Conclusion
The trajectories of the stroke patients were longer and more deviated during the turn and the preceding phase. Trajectory parameters provided additional information to timed performance of this locomotor task. Focusing rehabilitation programs on lead-up to turn and turning could be relevant for stroke patients since the Turn was related to the balance and the phase preceding the turn seemed to distinguish fallers. 相似文献958.
Binhui Ren Zoulikha Azzegagh Ana?M. Jaramillo Yunxiang Zhu Ana Pardo-Saganta Rustam Bagirzadeh Jose?R. Flores Wei Han Yong-jun Tang Jing Tu Denise?M. Alanis Christopher?M. Evans Michele Guindani Paul?A. Roche Jayaraj Rajagopal Jichao Chen C.?William Davis Michael?J. Tuvim Burton?F. Dickey 《Bioscience reports》2015,35(3)
Airway mucin secretion is important pathophysiologically and as a model of polarized epithelial regulated exocytosis. We find the trafficking protein, SNAP23 (23-kDa paralogue of synaptosome-associated protein of 25 kDa), selectively expressed in secretory cells compared with ciliated and basal cells of airway epithelium by immunohistochemistry and FACS, suggesting that SNAP23 functions in regulated but not constitutive epithelial secretion. Heterozygous SNAP23 deletant mutant mice show spontaneous accumulation of intracellular mucin, indicating a defect in baseline secretion. However mucins are released from perfused tracheas of mutant and wild-type (WT) mice at the same rate, suggesting that increased intracellular stores balance reduced release efficiency to yield a fully compensated baseline steady state. In contrast, acute stimulated release of intracellular mucin from mutant mice is impaired whether measured by a static imaging assay 5 min after exposure to the secretagogue ATP or by kinetic analysis of mucins released from perfused tracheas during the first 10 min of ATP exposure. Together, these data indicate that increased intracellular stores cannot fully compensate for the defect in release efficiency during intense stimulation. The lungs of mutant mice develop normally and clear bacteria and instilled polystyrene beads comparable to WT mice, consistent with these functions depending on baseline secretion that is fully compensated. 相似文献
959.
Bending and unwinding of nucleic acid by prion protein 总被引:1,自引:0,他引:1
Nucleic acid induces conformational changes in the prion protein (23-231 amino acids) to a structure resembling its pathological isoform. The prion protein, in turn, facilitates DNA strand transfer and acts as a DNA chaperone which is modulated by the N-terminal unstructured basic segment of the protein. Here we have studied the prion protein induced conformational changes in DNA using oligonucleotides covalently labeled with the energy donor fluorescein and the acceptor rhodamine moieties by fluorescence resonance energy transfer (FRET) and by thermal stability of the unlabeled oligonucleotides. The protein induces a strong FRET effect in the oligonucleotides evidenced from the simultaneous quenching of fluorescence intensity of the donor and increase in the fluorescence intensity of the acceptor, which indicate bending of the oligonucleotides by the prion protein. The energy transfer efficiency induced by the protein is greater for the larger oligonucleotide. The prion protein also induces significant structural destabilization of the oligonucleotides observed from the lowering of their melting temperatures in the presence of the protein. The truncated globular prion protein 121-231 fragment neither induces FRET effect on the oligonucleotides nor destabilizes their structures, indicating that the N-terminal segment of the prion protein is essential for the DNA bending process. Equilibrium binding and kinetics of FRET show that the protein binding to the oligonucleotides and their bending occur simultaneously. The DNA structural changes observed in the presence of the prion protein are similar to those caused by proteins involved in initiation and regulation for protein synthesis. 相似文献
960.
Thomas M Rivault F Tranoy-Opalinski I Roche J Gesson JP Papot S 《Bioorganic & medicinal chemistry letters》2007,17(4):983-986
The beta-O-glucuronide and beta-O-galactoside of SAHA have been prepared and evaluated as prodrugs for selective cancer chemotherapy (ADEPT, PMT). These new compounds are stable under physiological conditions and do not exhibit any antiproliferative activity compared to the parent drug after a 48-h treatment of H661 cells. The glucuronide derivative did not lead to the release of the drug in the presence of either Escherichia coli or bovine liver beta-glucuronidase. On the other hand, under enzymatic cleavage of galactoside prodrug by the corresponding enzyme, a rapid release of SAHA was observed demonstrating that the beta-O-galactoside of SAHA is a promising candidate for in vivo investigations. 相似文献