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排序方式: 共有1071条查询结果,搜索用时 15 毫秒
81.
82.
Walden M Accardi A Wu F Xu C Williams C Miller C 《The Journal of general physiology》2007,129(4):317-329
The CLC-family protein CLC-ec1, a bacterial homologue of known structure, stoichiometrically exchanges two Cl(-) for one H(+) via an unknown membrane transport mechanism. This study examines mutations at a conserved tyrosine residue, Y445, that directly coordinates a Cl(-) ion located near the center of the membrane. Mutations at this position lead to "uncoupling," such that the H(+)/Cl(-) transport ratio decreases roughly with the volume of the substituted side chain. The uncoupled proteins are still able to pump protons uphill when driven by a Cl(-) gradient, but the extent and rate of this H(+) pumping is weaker in the more uncoupled variants. Uncoupling is accompanied by conductive Cl(-) transport that is not linked to counter-movement of H(+), i.e., a "leak." The unitary Cl(-) transport rate, measured in reconstituted liposomes by both a conventional initial-velocity method and a novel Poisson dilution approach, is approximately 4,000 s(-1) for wild-type protein, and the uncoupled mutants transport Cl(-) at similar rates. 相似文献
83.
Alessio Mortelliti Giovanni Amori Giampiero Sammuri Luigi Boitani 《Acta theriologica》2007,52(1):75-84
We studied the factors affecting the distribution of an endemic shrewSorex samniticus Altobello, 1926 in the Province of Siena, central Italy. Distribution data were obtained by examining pellets from 31 barn
owlTyto alba sites (roosts) over a period spanning from 1974 to 2005. We constructed a model using logistic regression analysis on presence/absence
data. Results show that an increase in forest dominated byQuercus cerris andCastanea sativa led to the local extinction of this species. Results were confirmed through the examination of one box, with 3044 prey items
deposited in layers, that documents the expansion of the species in that area following increased logging ofQuercus cerris andCastanea sativa forests. Cessation of logging has again led to the absence of the species from the area. We discuss these results from the
perspective of ecological network planning, showing that utilisation of non-detailed maps, such as Corine Land Cover, that
do not distinguish between the various kind of broadleaved forests is inadequate to describe the finer grade of habitat selection
of this small mammal. 相似文献
84.
Parazzini M Ravazzani P Tognola G Thuróczy G Molnar FB Sacchettini A Ardesi G Mainardi LT 《Bioelectromagnetics》2007,28(2):122-129
In this study, 26 healthy young volunteers were submitted to 900 MHz (2 W) GSM cellular phone exposure and to sham exposure in separate sessions. The study was designed to assess cardiac regulatory mechanism in different autonomic nervous system (ANS) states during exposure to low-intensity EMF. Rest-to-stand protocol was applied to evaluate ANS in quiet condition (rest, vagal prevalence) and after a sympathetic activation (stand). The procedure is conducted twice in a double-blind design: once with a genuine EMF exposure and once with a sham exposure (at least 24 h apart). During each session three-leads electrocardiograms were recorded and RR series extracted off-line. Time domain and frequency domain HRV parameters were calculated in every phase of the protocol and during different exposures. The analysis of the data show there was no statistically significant effect due to EMF exposure both on main (i.e., RR mean) and most of the other HRV parameters. A weak interaction between some HRV parameters (i.e., SDNN, TINN, and triangular index in time domain and LF power in frequency domain analysis) and RF exposure was observed and this effect seems to be gathered around the sympathetic response to stand. 相似文献
85.
Nuti E Orlandini E Nencetti S Rossello A Innocenti A Scozzafava A Supuran CT 《Bioorganic & medicinal chemistry》2007,15(6):2298-2311
A series of sulfonylated hydroxamates were synthesized and evaluated as dual inhibitors of both human carbonic anhydrases (hCAs) and matrix metalloproteinases (MMPs), two metalloenzyme families involved in carcinogenesis and tumor invasion processes. The new derivatives were tested on three CA isozymes, the cytosolic isozymes I and II, and the transmembrane, tumor-associated isozyme IX, and also on human gelatinases (MMP-2 and MMP-9). Some of the new derivatives proved to be potent and selective inhibitors of CA II, but only compounds 3b and 6b, devoid of the arylsulfonyl moiety, proved to have a better inhibitory activity on hCA IX than on hCA I and II, in the micromolar range. 相似文献
86.
Nishimori I Onishi S Vullo D Innocenti A Scozzafava A Supuran CT 《Bioorganic & medicinal chemistry》2007,15(15):5351-5357
The secretory isozyme of human carbonic anhydrase (hCA, EC 4.2.1.1), hCA VI, has been cloned, expressed, and purified in a bacterial expression system. The kinetic parameters for the CO(2) hydration reaction proved hCA VI to possess a k(cat) of 3.4 x 10(5)s(-1) and k(cat)/K(M) of 4.9 x 10(7)M(-1)s(-1) (at pH 7.5 and 20 degrees C). hCA VI has a significant catalytic activity for the physiological reaction, of the same order of magnitude as the ubiquitous isoform CA I or the transmembrane, tumor-associated isozyme CA IX. A series of amino acids and amines were shown to act as CA VI activators, with variable efficacies. l-His, l-Trp, and dopamine showed weak CA VI activating effects (K(A)s in the range of 21-42 microM), whereas d-His, d-Phe, l-DOPA, l-Trp, serotonin, and some pyridyl-alkylamines were better activators, with K(A)s in the range of 13-19 microM. The best CA VI activators were l-Phe, d-DOPA, l-Tyr, 4-amino-l-Phe, and histamine, with K(A)s in the range of 1.23-9.31 microM. All these activators enhance k(cat), having no effect on K(M), participating thus in the rate determining step in the catalytic cycle, the proton transfer reactions between the enzyme active site and the environment. 相似文献
87.
Endogenous microRNA can be broadly exploited to regulate transgene expression according to tissue, lineage and differentiation state 总被引:2,自引:0,他引:2
Brown BD Gentner B Cantore A Colleoni S Amendola M Zingale A Baccarini A Lazzari G Galli C Naldini L 《Nature biotechnology》2007,25(12):1457-1467
We have shown previously that transgene expression can be suppressed in hematopoietic cells using vectors that are responsive to microRNA (miRNA) regulation. Here we investigate the potential of this approach for more sophisticated control of transgene expression. Analysis of the relationship between miRNA expression levels and target mRNA suppression suggested that suppression depends on a threshold miRNA concentration. Using this information, we generated vectors that rapidly adjust transgene expression in response to changes in miRNA expression. These vectors sharply segregated transgene expression between closely related states of therapeutically relevant cells, including dendritic cells, hematopoietic and embryonic stem cells, and their progeny, allowing positive/negative selection according to the cells' differentiation state. Moreover, two miRNA target sites were combined to restrict transgene expression to a specific cell type in the liver. Notably, the vectors did not detectably perturb endogenous miRNA expression or regulation of natural targets. The properties of miRNA-regulated vectors should allow for safer and more effective therapeutic applications. 相似文献
88.
MOTIVATION: Several kernel-based methods have been recently introduced for the classification of small molecules. Most available kernels on molecules are based on 2D representations obtained from chemical structures, but far less work has focused so far on the definition of effective kernels that can also exploit 3D information. RESULTS: We introduce new ideas for building kernels on small molecules that can effectively use and combine 2D and 3D information. We tested these kernels in conjunction with support vector machines for binary classification on the 60 NCI cancer screening datasets as well as on the NCI HIV data set. Our results show that 3D information leveraged by these kernels can consistently improve prediction accuracy in all datasets. AVAILABILITY: An implementation of the small molecule classifier is available from http://www.dsi.unifi.it/neural/src/3DDK. 相似文献
89.
Martini C Pallottini V Cavallini G Donati A Bergamini E Trentalance A 《Journal of cellular biochemistry》2007,101(1):235-243
Ageing has been defined as a progressive decrease in physiological capacity and a reduced ability to respond to environmental stresses. It has been observed that diet-restricted animals show a minor morbidity in age-related disease. Among these age-related diseases, hypercholesterolemia is the most recurring one and it is often associated with cardiac failure. Several studies have been published indicating age-dependent changes in circulating levels of cholesterol in both humans and in rodents; recently changes have also been reported in the proteins involved in cholesterol homeostasis, that is, 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoAR), Insig-induced gene (Insig) protein, SREBP cleavage activating protein (SCAP), sterol regulatory element binding protein (SREBP), and low density lipoprotein receptor (LDLr). Most age-related modifications of biochemical parameters are normalized or very improved in food-restricted animals, so the aim of this work is to examine whether or not alterations of the factors involved in cholesterol homeostasis which occur during ageing could be counteracted by caloric restriction (CR). The data show that the diet restrictions used attenuate the age-related effects on the factors involved in the synthesis and the degradation rate of HMG-CoAR; in spite of this, CRs have a good effect on the age-related hypercholesterolemia whose reduction seems to depend both on the correct membrane LDLr localization and on the proper restored HMG-CoAR activity. 相似文献
90.
Pietraforte D Matarrese P Straface E Gambardella L Metere A Scorza G Leto TL Malorni W Minetti M 《Free radical biology & medicine》2007,42(2):202-214
CO(2) changes the biochemistry of peroxynitrite basically in two ways: (i) nitrating species is the CO(3)(-) / ()NO(2) radical pair, and (ii) peroxynitrite diffusion distance is significantly reduced. For peroxynitrite generated extracellularly this last effect is particularly dramatic at low cell density because CO(3)(-) and ()NO(2) are short-lived and decay mostly in the extracellular space or at the cell surface/membrane. This study was aimed to distinguish between peroxynitrite-induced extra- and intracellular modifications of red blood cells (RBC). Our results show that at low cell density and in the presence of CO(2) peroxynitrite induced the oxidation of surface thiols, the formation of 3-nitrotyrosine and DMPO-RBC adducts, and the down-regulation of glycophorins A and C (biomarkers of senescence). Reactivation of glycolysis reversed only the oxidation of surface thiols. Without CO(2) peroxynitrite also induced the oxidation of hemoglobin and glutathione, the accumulation of lactate, a decrease in ATP, the clustering of band 3, the externalization of phosphatidylserine, and the activation of caspases 8 and 3 (biomarkers of apoptosis). The latter biomarkers were all reversed by reactivation of glycolysis. We hypothesize that cell senescence could (generally) be derived by irreversible radical-mediated oxidation of membrane targets, while the appearance of apoptotic biomarkers could be bolstered by oxidation of intracellular targets. These results suggest that, depending on extracellular homolysis or diffusion to the intracellular space, peroxynitrite prompts RBCs toward either senescence or apoptosis through different oxidation mechanisms. 相似文献