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481.
Two 3D-QSAR methods--CoMFA and CoMSIA--were applied to a set of 38 angiotensin receptor (AT1) antagonists. The conformation and alignment of molecules were obtained by a novel method - consensus dynamics. The representation of biological activity, partial charge formalism, absolute orientation of the molecules in the grid, and grid spacing were also studied for their effect on the CoMFA models. The models were thoroughly validated through trials using scrambled activities and bootstrapping. The best CoMFA model had a cross-validated correlation coefficient ( q2) of 0.632, which improved with "region focusing" to 0.680. This model had a "predictive" r2 of 0.436 on a test series that was unique and with little representation in the training set. Although the "predictive" r2 of the best CoMSIA model, which included steric, electrostatic, and hydrogen bond acceptor fields was higher than that of the best CoMFA model, the other statistical parameters like q2, r2, F value, and s were unsatisfactory. The contour maps generated using the best CoMFA model were used to identify the structural features important for biological activity in these compounds. 相似文献
482.
Java language has been demonstrated to be an effective tool in supporting medical image viewing in Russia. This evaluation was completed by obtaining a maximum of 20 images, depending on the client's computer workstation from one patient using a commercially available computer tomography (CT) scanner. The images were compared against standard CT images that were viewed at the site of capture. There was no appreciable difference. The client side is a lightweight component that provides an intuitive interface for end users. Each image is loaded in its own thread and the user can begin work after the first image has been loaded. This feature is especially useful on slow connection speed, 9.6 Kbps for example. The server side, which is implemented by the Java Servlet Engine works more effective than common gateway interface (CGI) programs do. Advantages of the Java Technology place this program on the next level of application development. This paper presents a unique application of Java in telemedicine. 相似文献
483.
Photosynthesis research in India can be traced back several thousand years, with the mention of the Sun energizing the plants,
which form food for all living creatures on the earth (from the Mahabharata, the great epic, ca. 2600 B.C.) and the report
of Sage Parasara (ca. 100 B.C.) on the ability of plants to make their own food, due to their pigments. With the pioneering
studies by Sir Jagdish Chandra Bose, work on photosynthesis proceeded steadily during the first half of the 20th century.
Some of the classic reports during this period are: malate metabolism in Hydrilla, spectrophotometric estimation of chlorophylls, importance of spectral quality for photosynthesis – an indication of two
photosystems, photoinactivation of photosynthesis, and importance of flag leaf photosynthesis to grain yield. After the 1960s,
there was a burst of research in the areas of physiology and biochemistry of carbon assimilation and photochemistry. A significant
transition occurred, before the beginning of new millennium, into the area of molecular biology of chloroplasts, regulation
of photosynthesis and stress tolerance. Future research work in India is geared to focus on the following aspects of photosynthesis:
elucidation/analysis of genes, molecular biology/evolution of enzymes, development/use of transgenics and modeling.
This revised version was published online in August 2006 with corrections to the Cover Date. 相似文献
484.
Sharma VM Adi Seshu KV Vamsee Krishna C Prasanna P Chandra Sekhar V Venkateswarlu A Rajagopal S Ajaykumar R Deevi DS Rao Mamidi NV Rajagopalan R 《Bioorganic & medicinal chemistry letters》2003,13(10):1679-1682
A series of 6,7-diphenyl-2,3,8,8a-tetrahydro-1H-indolizin-5-one analogues were synthesized and evaluated for cytotoxic activity against eight human cancer cell lines. Compounds 18, 21, 28, 29, 30 and 31 showed cytotoxic activity with GI(50) values in the range of 2.1-8.1 microM concentration. Among these, compounds 21 and 28 exhibited good pharmacokinetic properties. These compounds were further evaluated for their in vivo efficacy in modified hollow fibre assay (HFA). 相似文献
485.
O'Neill GM Prasanna Murthy SN Lorand L Khanna R Liu SC Hanspal M Hanada T Chishti AH 《Biochemical and biophysical research communications》2003,307(2):327-331
Intracellular transglutaminases (protein-glutamine: amine gamma-glutamyltransferase, EC 2.3.2.13) are calcium-dependent thiol enzymes that catalyze the covalent cross-linking of proteins, including those in the erythrocyte membrane. Several studies suggest that the activation of some transglutaminases is positively regulated by the calcium-dependent cysteine protease, mu-calpain. Using mu-calpain null (Capn1(-/-)) mouse erythrocytes, we demonstrate that the activation of soluble as well as membrane-bound forms of transglutaminase (TG2) in mouse erythrocytes was independent of mu-calpain. Also, the absence of mu-calpain or any detectable cysteine protease did not affect the transglutaminase activity in the erythrocyte lysate. Our studies also identify physiological substrates of mu-calpain in the erythrocyte membrane and show that their cleavage has no discernible effect on the transglutaminase mediated cross-linking of membrane proteins. Taken together, these data suggest the existence of a calpain-independent mechanism for the activation of transglutaminase 2 by calcium ions in the mouse erythrocytes and presumably also in non-erythroid cells. 相似文献
486.
Fast anterograde transport of herpes simplex virus: role for the amyloid precursor protein of alzheimer's disease 总被引:1,自引:0,他引:1
Anterograde transport of herpes simplex virus (HSV) from its site of synthesis in the neuronal cell body out the neuronal process to the mucosal membrane is crucial for transmission of the virus from one person to another, yet the molecular mechanism is not known. By injecting GFP-labeled HSV into the giant axon of the squid, we reconstitute fast anterograde transport of human HSV and use this as an assay to uncover the underlying molecular mechanism. HSV travels by fast axonal transport at velocities four-fold faster (0.9 µm/sec average, 1.2 µm/sec maximal) than that of mitochondria moving in the same axon (0.2 µm/sec) and ten-fold faster than negatively charged beads (0.08 µm/sec). Transport of HSV utilizes cellular transport mechanisms because it appears to be driven from inside cellular membranes as revealed by negative stain electron microscopy and by the association of TGN46, a component of the cellular secretory pathway, with GFP-labeled viral particles. Finally, we show that amyloid precursor protein (APP), a putative receptor for the microtubule motor, kinesin, is a major component of viral particles, at least as abundant as any viral encoded protein, while another putative motor receptor, JIP 1/2, is not detected. Conventional kinesin is also associated with viral particles. This work links fast anterograde transport of the common pathogen, HSV, with the neurodegenerative Alzheimer"s disease. This novel connection should prompt new ideas for treatment and prevention strategies. 相似文献
487.
Allakhverdiev SI Tsvetkova N Mohanty P Szalontai B Moon BY Debreczeny M Murata N 《Biochimica et biophysica acta》2005,1708(3):342-351
Irreversible photoinhibition of photosystem II (PSII) occurred when Synechocystis sp. PCC 6803 cells were exposed to very strong light for a prolonged period. When wild-type cells were illuminated at 20 degrees C for 2 h with light at an intensity of 2,500 micromol photons m(-2) s(-1), the oxygen-evolving activity of PSII was almost entirely and irreversibly lost, whereas the photochemical reaction center in PSII was inactivated only reversibly. The extent of irreversible photoinhibition was enhanced at lower temperatures and by the genetically engineered rigidification of membrane lipids. Western and Northern blotting demonstrated that, after cells had undergone irreversible photoinhibition, the precursor to D1 protein in PSII was synthesized but not processed properly. These observations may suggest that exposure of Synechocystis cells to strong light results in the irreversible photoinhibition of the oxygen-evolving activity of PSII via impairment of the processing of pre-D1 and that this effect of strong light is enhanced by the rigidification of membrane lipids. 相似文献
488.
pH and salts have a marked effect on the stability, structure, and function of many globular proteins due to their ability to influence the electrostatic interactions. In this work, calorimetry, CD, and fluorescence studies have been carried out to understand the pH-dependent conformational changes of the two-domain protein yeast hexokinase A. In conjunction with the crystal structural data available, the present results have enabled the complete characterization and analysis of the pH-dependent conformational changes of the enzyme that have strong implications in understanding its structure-function relationship. The calorimetric profiles show a single thermal transition in the acidic pH range, whereas two independent transitions were observed in the alkaline pH range, suggesting the structural merger of the domains at the acidic pH. Comparison of the thermal transitions at pH 8.5 studied by different techniques suggests that the first transition corresponds to the smaller domain, and the second transition corresponds to the larger domain. The acid-denatured state of hexokinase A has high secondary structure content with little or no tertiary interactions and binds to the hydrophobic dye 8-anilinonaphthalene-1-sulfonic acid, suggesting that it is a molten globule-like state, whereas the alkali-denatured state is less structured than the acid-denatured state but more structured than the urea-denatured state, suggestive of a premolten globule-like state. Structural analysis using the published hexokinase B structure as well as the hexokinase A structure with the revised amino acid sequence in conjunction with the results obtained by us suggests that the ionization state of the acidic residues at the active site could regulate domain movements that are responsible for the opening and the closure of the cleft between the two domains and in turn affect the structure and function of the enzyme. 相似文献
489.
Hairpin poly(amide)s (HPs) are sequence specific DNA-binding compounds that have engendered considerable interest as potential pharmacological agents to manipulate the expression of specific genes. However, recent reports have indicated that the ability of HP conjugates to pass through cell membranes is sensitive to the cell type employed and the nature of the conjugate. Furthermore, while binding of HPs to DNA sequences in vitro is relatively well understood, packing of DNA into chromatin in living cells makes predicting the efficiency with which a given poly(amide) will bind its cognate site less certain. Previous methods to evaluate HP permeability and binding in vivo, while effective, are somewhat tedious and qualitative. We report here two related reporter gene-based assays that provide a more convenient and quantitative measure of poly(amide) permeability and DNA binding activity in living cells. We anticipate that these methods will complement existing tools and facilitate the development of HP conjugates with the desired biological activity. 相似文献
490.