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51.
A modular treatment of molecular traffic through the active site of cholinesterase 总被引:1,自引:0,他引:1
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We present a model for the molecular traffic of ligands, substrates, and products through the active site of cholinesterases (ChEs). First, we describe a common treatment of the diffusion to a buried active site of cationic and neutral species. We then explain the specificity of ChEs for cationic ligands and substrates by introducing two additional components to this common treatment. The first module is a surface trap for cationic species at the entrance to the active-site gorge that operates through local, short-range electrostatic interactions and is independent of ionic strength. The second module is an ionic-strength-dependent steering mechanism generated by long-range electrostatic interactions arising from the overall distribution of charges in ChEs. Our calculations show that diffusion of charged ligands relative to neutral isosteric analogs is enhanced approximately 10-fold by the surface trap, while electrostatic steering contributes only a 1.5- to 2-fold rate enhancement at physiological salt concentration. We model clearance of cationic products from the active-site gorge as analogous to the escape of a particle from a one-dimensional well in the presence of a linear electrostatic potential. We evaluate the potential inside the gorge and provide evidence that while contributing to the steering of cationic species toward the active site, it does not appreciably retard their clearance. This optimal fine-tuning of global and local electrostatic interactions endows ChEs with maximum catalytic efficiency and specificity for a positively charged substrate, while at the same time not hindering clearance of the positively charged products. 相似文献
52.
哈尔滨西郊赤狐冬季巢区的初步研究 总被引:5,自引:2,他引:3
本文利用雪地跟踪方法对哈尔滨西郊5只赤狐在1985-1986年冬季的巢区做了观察。结果表明,5只狐对巢区内各部分使用的强度是不等的,对巢区中部的某些地块使用强度要高于对外围的使用,并具有明显的方向性。5个巢区的平均活动半径为320±68米至557±82米,面积为1.44-4.O9平方公里,线性指数为1.079至2。5只狐相邻距离约1000米。 相似文献
53.
Nonglucosylated oligosaccharides are transferred to protein in MI8-5 Chinese hamster ovary cells 总被引:3,自引:2,他引:1
A CHO mutant MI8-5 was found to synthesize Man9-GlcNAc2-P-P-dolichol rather
than Glc3Man9GlcNAc2-P-P-dolichol as the oligosaccharide-lipid intermediate
in N-glycosylation of proteins. MI8-5 cells were incubated with labeled
mevalonate, and the prenol was found to be dolichol. The mannose-labeled
oligosaccharide released from oligosaccharide-lipid of MI8-5 cells was
analyzed by HPLC and alpha-mannosidase treatment, and the data were
consistent with a structure of Man9GlcNAc2. In addition, MI8-5 cells did
not incorporate radioactivity into oligosaccharide- lipid during an
incubation with tritiated galactose, again consistent with MI8-5 cells
synthesizing an unglucosylated oligosaccharide-lipid. MI8-5 cells had
parental levels of glucosylphosphoryldolichol synthase activity. However,
in two different assays, MI8-5 cells lacked dolichol-
P-Glc:Man9GlcNAc2-P-P-dolichol glucosyltransferase activity. MI8-5 cells
were found to synthesize glucosylated oligosaccharide after they were
transfected with Saccharomyces cerevisiae ALG 6, the gene for
dolichol-P-Glc:Man9GlcNAc2-P-P-dolichol glucosyltransferase. MI8-5 cells
were found to incorporate mannose into protein 2-fold slower than parental
cells and to approximately a 2-fold lesser extent.
相似文献
54.
Tur R Magraner J Catret M Elorriaga M Ivorra MD D'Ocon P Bermejo A Cabedo N Cortes D Anselmi E 《Life sciences》2000,67(13):1535-1548
In the present study we examine the mechanism by which thaligrisine, a bisbenzyltetrahydroisoquinoline alkaloid, inhibits the contractile response of vascular smooth muscle. The work includes functional studies on rat isolated aorta and tail artery precontracted with noradrenaline or KCl. In other experiments rat aorta was precontracted by caffeine in the presence or absence of extracellular Ca2+. In order to assess whether thaligrisine interacts directly with calcium channel binding sites or with alpha-adrenoceptors we examined the effect of the alkaloid on [3H]-(+)-cis diltiazem, [3H]-nitrendipine and [3H]-prazosin binding to cerebral cortical membranes. The functional studies showed that the alkaloid inhibited in a concentration-dependent manner the contractile response induced by depolarization in rat aorta (IC50 = 8.9+/-2.9 microM, n=5) and in tail artery (IC50 = 3.04+/-0.3 microM, n=6) or noradrenaline induced contraction in rat aorta (IC50 = 23.0+/-0.39 microM, n=9) and in tail artery (IC50 = 3.8+/-0.9 microM, n=7). In rat aorta, thaligrisine concentration-dependently inhibited noradrenaline-induced contraction in Ca2+-free solution (IC50 = 13.3 microM, n=18). The alkaloid also relaxed the spontaneous contractile response elicited by extracellular calcium after depletion of noradrenaline-sensitive intracellular stores (IC50 = 7.7 microM, n=4). The radioligand receptor-binding study showed that thaligrisine has higher affinity for [3H]-prazosin than for [3H]-(+)-cis-diltiazem binding sites, with Ki values of 0.048+/-0.007 microM and 1.5+/-1.1 microM respectively. [3H]-nitrendipine binding was not affected by thaligrisine. The present work provides evidence that thaligrisine shows higher affinity for [3H]-prazosin binding site than [3H]-(+)-cis-diltiazem binding sites, in contrast with tetrandrine and isotetrandrine that present similar affinity for both receptors. In functional studies thaligrisine, acted as an alpha1-adrenoceptor antagonist and as a Ca2+ channel blocker, relaxing noradrenaline or KCl-induced contractions in vascular smooth muscle. This compound specifically inhibits the refilling of internal Ca2+-stores sensitive to noradrenaline, by blocking Ca2+-entry through voltage-dependent Ca2+-channels. 相似文献
55.
Sarah Ivorra Muriel Gros‐Balthazard Sandrine Picq Margareta Tengberg Jean‐Christophe Pintaud 《Journal of Biogeography》2012,39(5):929-941
Aim The main purpose of this work is to understand the origin, history, historical biogeography and mechanisms of date palm (Phoenix dactylifera L.) domestication. Location Seeds of uncultivated Phoenix individuals from isolated Oman populations, cultivated date palm varieties of various geographical origins and other related Phoenix species were analysed. Additionally, well‐preserved seeds from Egyptian archaeological sites (14th century bc to 8th century ad ) were compared with the morphometric reference model based on the analysis of modern material. Methods Elliptic Fourier transforms (EFT), a morphometric method applied to shape outline analysis, were used to characterize seed shape and to quantify morphological diversity in P. dactylifera and related species. Results Analysis of seed outlines by EFT (1) showed that P. dactylifera can be differentiated from other Phoenix species and (2) enabled the quantification of patterns of shape differentiation in the genus Phoenix at different taxonomic, geographical and chronological levels. Date palm agrobiodiversity, partitioned in distinct morphotypes, appeared to be complex in terms of geographical structure. Allocation of archaeological seeds to different modern Phoenix forms and date palm morphotypes allowed us to reveal ancient forms consumed and/or exploited in Egypt and finally to determine spatial and temporal changes in agrobiodiversity. Main conclusions Based on the morphological diversity quantified in P. dactylifera and related species, we characterized ancestral seed shape features present in uncultivated populations. The geographical distribution pattern of seed shapes points to human dispersal routes that spread cultivation from one or more initial ‘domestication centres’. Finally, this work provides a powerful tool to identify ancient forms as demonstrated by the analysis of well‐preserved Egyptian archaeological seeds, dating from the 14th century bc to the 8th century ad . Results open new and fascinating perspectives on the investigation of the origins and chrono‐geographical fluctuation of date palm agrobiodiversity. 相似文献
56.
57.
Tarongi Miguel Bonhomme Vincent Evin Allowen Ivorra Sarah López Dani Alonso Natàlia Bouby Laurent 《Vegetation History and Archaeobotany》2021,30(1):77-87
Vegetation History and Archaeobotany - This study applied size and shape analyses through traditional and geometric morphometrics to quantify the differences between three taxa: Lathyrus sativus... 相似文献
58.
Margrete Solheim Mari C Brekke Lars G Snipen Rob JL Willems Ingolf F Nes Dag A Brede 《BMC microbiology》2011,11(1):3
Background
Enterococci rank among the leading causes of nosocomial infections. The failure to identify pathogen-specific genes in Enterococcus faecalis has led to a hypothesis where the virulence of different strains may be linked to strain-specific genes, and where the combined endeavor of the different gene-sets result in the ability to cause infection. Population structure studies by multilocus sequence typing have defined distinct clonal complexes (CC) of E. faecalis enriched in hospitalized patients (CC2, CC9, CC28 and CC40). 相似文献59.
Duijnisveld BJ Bigot A Beenakker KG Portilho DM Raz V van der Heide HJ Visser CP Chaouch S Mamchaoui K Westendorp RG Mouly V Butler-Browne GS Nelissen RG Maier AB 《Arthritis research & therapy》2011,13(6):R207-10
Introduction
Chronic inflammation is a profound systemic modification of the cellular microenvironment which could affect survival, repair and maintenance of muscle stem cells. The aim of this study was to define the role of chronic inflammation on the regenerative potential of satellite cells in human muscle.Methods
As a model for chronic inflammation, 11 patients suffering from rheumatoid arthritis (RA) were included together with 16 patients with osteoarthritis (OA) as controls. The mean age of both groups was 64 years, with more females in the RA group compared to the OA group. During elective knee replacement surgery, a muscle biopsy was taken from the distal musculus vastus medialis. Cell populations from four RA and eight OA patients were used for extensive phenotyping because these cell populations showed no spontaneous differentiation and myogenic purity greater than 75% after explantation.Results
After mononuclear cell explantation, myogenic purity, viability, proliferation index, number of colonies, myogenic colonies, growth speed, maximum number of population doublings and fusion index were not different between RA and OA patients. Furthermore, the expression of proteins involved in replicative and stress-induced premature senescence and apoptosis, including p16, p21, p53, hTERT and cleaved caspase-3, was not different between RA and OA patients. Mean telomere length was shorter in the RA group compared to the OA group.Conclusions
In the present study we found evidence that chronic inflammation in RA does not affect the in vitro regenerative potential of human satellite cells. Identification of mechanisms influencing muscle regeneration by modulation of its microenvironment may, therefore, be more appropriate. 相似文献60.
Pauline Burger Jean-Frederic Terral Marie-Pierre Ruas Sarah Ivorra Sandrine Picq 《Vegetation History and Archaeobotany》2011,20(5):447-458
Abundant and diverse Prunus fruitstone remains from cherries, plums, sloes, peaches, etc. are frequently recovered from archaeological waterlogged contexts
such as wells, latrines, lake dwellings etc. in Europe. The distinction between most of the Prunus species, based on traditional morphological characters of the fruit stones, is usually not problematic. However the discrimination
between P. avium L., P. cerasus L. and related cherry species, based on classical criteria alone, often turns out to be ambiguous because of the increasing
number of varieties which have been bred since Roman times. By combining geometric and traditional morphometrical approaches,
the overall variation in shape and size of stones from French and Swiss excavations dating from the 1st century to the 16th
century a.d. were assessed. Among these important archaeobotanical data, the detailed examination of 100 waterlogged stones from the 16th
century H?tel-Dieu cesspit at Tours, France, revealed that the morphological diversity is structured into two distinct morphotypes
which diverge mainly according to geometrical features. Finally, the comparison between morphological features of these well-preserved
archaeological stones and modern reference material including P. avium, P. cerasus and P. × gondouinii, suggests that these two morphotypes, which have been initially attributed to P. avium (long stones) and P. avium/cerasus (rounded stones) according to traditional morphological parameters, would correspond to two different cultivated varieties,
both belonging to Prunus avium. Results presented in this work constitute new and preliminary data obtained during the development of this project that
throw light on morphological variability and biosystematic aspects. 相似文献