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991.
Molecular dynamics simulations of the 136 unique tetranucleotide sequences of DNA oligonucleotides. I. Research design and results on d(CpG) steps 下载免费PDF全文
Beveridge DL Barreiro G Byun KS Case DA Cheatham TE Dixit SB Giudice E Lankas F Lavery R Maddocks JH Osman R Seibert E Sklenar H Stoll G Thayer KM Varnai P Young MA 《Biophysical journal》2004,87(6):3799-3813
We describe herein a computationally intensive project aimed at carrying out molecular dynamics (MD) simulations including water and counterions on B-DNA oligomers containing all 136 unique tetranucleotide base sequences. This initiative was undertaken by an international collaborative effort involving nine research groups, the "Ascona B-DNA Consortium" (ABC). Calculations were carried out on the 136 cases imbedded in 39 DNA oligomers with repeating tetranucleotide sequences, capped on both ends by GC pairs and each having a total length of 15 nucleotide pairs. All MD simulations were carried out using a well-defined protocol, the AMBER suite of programs, and the parm94 force field. Phase I of the ABC project involves a total of approximately 0.6 mus of simulation for systems containing approximately 24,000 atoms. The resulting trajectories involve 600,000 coordinate sets and represent approximately 400 gigabytes of data. In this article, the research design, details of the simulation protocol, informatics issues, and the organization of the results into a web-accessible database are described. Preliminary results from 15-ns MD trajectories are presented for the d(CpG) step in its 10 unique sequence contexts, and issues of stability and convergence, the extent of quasiergodic problems, and the possibility of long-lived conformational substates are discussed. 相似文献
992.
Fiorentini D Prata C Maraldi T Zambonin L Bonsi L Hakim G Landi L 《Free radical biology & medicine》2004,37(9):1402-1411
Glucose transport activity and its possible regulation by reactive oxygen species in two Glut1-expressing megakaryocytic cell lines, MO7e and B1647, differing in cytokine sensitivity were compared. Results show that: (1) In MO7e cells, glucose transport rate increased in response to thrombopoietin, granulocyte-macrophage colony-stimulating factor, or stem cell factor, due to a decreased Km. (2) A higher Vmax value was determined in B1647 cells, owing to the relative higher abundance of Glut1 on the plasmalemma; in these cells no change in glucose transport rate was observed on cytokine treatment. (3) The basal level of intracellular ROS was higher in B1647 than in M07e cells, where ROS production was enhanced upon cytokine exposure. (4) Basal or stimulated ROS production and Glut1 activity were significantly reduced by pretreating both cell lines with EUK-134, a superoxide dismutase and catalase mimetic. (5) In MO7e cells, EUK-134 brought back to control levels the Km values obtained on cytokine treatment, whereas in B1647 cells the antioxidant drastically reduced Vmax by decreasing the Glut1 content of the plasma membrane. Our data suggest that differences in acute regulation of glucose transport activity in the two cell lines may be related to differences in amplitude and spatial organization of ROS production. 相似文献
993.
It is widely believed that synaptic modifications underlie learning and memory. However, few studies have examined what can be deduced about the learning process from the distribution of synaptic weights. We analyze the perceptron, a prototypical feedforward neural network, and obtain the optimal synaptic weight distribution for a perceptron with excitatory synapses. It contains more than 50% silent synapses, and this fraction increases with storage reliability: silent synapses are therefore a necessary byproduct of optimizing learning and reliability. Exploiting the classical analogy between the perceptron and the cerebellar Purkinje cell, we fitted the optimal weight distribution to that measured for granule cell-Purkinje cell synapses. The two distributions agreed well, suggesting that the Purkinje cell can learn up to 5 kilobytes of information, in the form of 40,000 input-output associations. 相似文献
994.
Hucke-Gaete R Osman LP Moreno CA Findlay KP Ljungblad DK 《Proceedings. Biological sciences / The Royal Society》2004,271(Z4):S170-S173
After the extensive exploitation that reduced the Southern Hemisphere blue whale (Balaenoptera musculus) populations to less than 3% of its original numbers, studies on its recovery have been compounded by the inaccessibility of most populations and the extensive migrations between low and high latitudes, thus ensuring that knowledge about blue whale ecology and status remains limited. We report the recent discovery of, arguably, the most important blue whale feeding and nursing ground known to date in the Southern Hemisphere, which is located near the fjords off southern Chile. Through aerial and marine surveys (n = 7) 47 groups, comprising 153 blue whales including at least 11 mother-calf pairs, were sighted during the austral summer and early autumn of 2003. The implications of this discovery on the biological understanding and conservation of this endangered species are discussed. 相似文献
995.
The Pseudomonas bacteriophage Pf1 is a long ( approximately 2000 nm) and thin ( approximately 6.5 nm) filament consisting of a covalently closed, single-stranded DNA genome of 7349 nucleotides coated by 7350 copies of a 46-residue alpha-helical subunit. The coat subunits are arranged as a superhelix of C(1)()S(5.4)() symmetry (class II). Polarized Raman and polarized FTIR spectroscopy of oriented Pf1 fibers show that the packaged single-stranded DNA genome is ordered specifically with respect to the capsid superhelix. Bases are nonrandomly arranged along the capsid interior, deoxynucleosides are uniformly in the C2'-endo/anti conformation, and the average DNA phosphodioxy group (PO(2)(-)) is oriented so that the line connecting the oxygen atoms (O.O) forms an angle of 71 degrees +/- 5 degrees with the virion axis. Raman and infrared amide band polarizations show that the subunit alpha-helix axis is inclined at an average angle of 16 degrees +/- 4 degrees with respect to the virion axis. The alpha-helical symmetry of the capsid subunit is remarkably rigorous, resulting in splitting of Raman-active helix vibrational modes at 351, 445 and 1026 cm(-)(1) into apparent A-type and E(2)()-type symmetry pairs. The subunit tyrosines (Tyr 25 and Tyr 40) are oriented with phenoxyl rings packed relatively close to parallel to the virion axis. The Tyr 25 and Tyr 40 orientations of Pf1 are surprisingly close to those observed for Tyr 21 and Tyr 24 of the Ff virion (C(5)()S(2)() symmetry, class I), suggesting a preferred tyrosyl side chain conformation in packed alpha-helical subunits, irrespective of capsid symmetry. The polarized Raman spectra also provide information on the orientations of subunit alanine, valine, leucine and isoleucine side chains of the Pf1 virion. 相似文献
996.
997.
Wolframin expression induces novel ion channel activity in endoplasmic reticulum membranes and increases intracellular calcium 总被引:10,自引:0,他引:10
Osman AA Saito M Makepeace C Permutt MA Schlesinger P Mueckler M 《The Journal of biological chemistry》2003,278(52):52755-52762
Wolfram syndrome is an autosomal recessive neuro-degenerative disorder associated with juvenile onset non-autoimmune diabetes mellitus and progressive optic atrophy. The disease has been attributed to mutations in the WFS1 gene, which codes for a protein predicted to possess 9-10 transmembrane segments. Little is known concerning the function of the WFS1 protein (wolframin). Endoglycosidase H digestion, immunocytochemistry, and subcellular fractionation studies all indicated that wolframin is localized to the endoplasmic reticulum in rat brain hippocampus and rat pancreatic islet beta-cells, and after ectopic expression in Xenopus oocytes. Reconstitution of wolframin from oocyte membranes into planar lipid bilayers demonstrated that the protein induced a large cation-selective ion channel that was blocked by Mg2+ or Ca2+. Inositol triphosphate was capable of activating channels in the fused bilayers that were similar to channel components induced by wolframin expression. Expression of wolframin also increased cytosolic calcium levels in oocytes. Wolframin thus appears to be important in the regulation of intracellular Ca2+ homeostasis. Disruption of this function may place cells at risk to suffer inappropriate death decisions, thus accounting for the progressive beta-cell loss and neuronal degeneration associated with the disease. 相似文献
998.
Guanine-uracil (G.U) wobble base-pairs are a detrimental lesion in DNA. Previous investigations have shown that such wobble base-pairs are more prone to base-opening than the normal G.C base-pairs. To investigate the sequence-dependence of base-pair opening we have performed 5ns molecular dynamics simulations on G.U wobble base-pairs in two different sequence contexts, TGT/AUA and CGC/GUG. Furthermore, we have investigated the effect of replacing the guanine base in each sequence with a fluorescent guanine analogue, 6-methylisoxanthopterin (6MI). Our results indicate that each sequence opens spontaneously towards the major groove in the course of the simulations. The TGT/AUA sequence has a greater proportion of structures in the open state than the CGC/GUG sequence. Incorporation of 6MI yields wobble base-pairs that open more readily than their guanine counterparts. In order of increasing open population, the sequences are ordered as CGC相似文献
999.
Syah YM Aminah NS Hakim EH Aimi N Kitajima M Takayama H Achmad SA 《Phytochemistry》2003,63(8):913-917
Two oligostilbenes, cis- and trans-diptoindonesin B, have been isolated from the tree bark of Dryobalanops oblongifolia (Dipterocarpaceae). The structures and relative configurations of both compounds were determined on the basis of spectroscopic evidence, including 2D-NMR spectroscopic analysis. 相似文献
1000.
Hakim?Boukhalfa Damon?S.?Anderson Timothy?A.?Mietzner Alvin?L.?CrumblissEmail author 《Journal of biological inorganic chemistry》2003,8(8):881-892
Ferric binding protein, Fbp, serves an essential biological function in shuttling naked (hydrated) Fe3+ across the periplasmic space of many Gram-negative bacteria. In this process, iron must be released at the cytoplasmic membrane to a permease. How iron is released from Fbp has yet to be resolved. Consequently, understanding the dynamics of iron release from Fbp is of both biological and chemical interest. Fbp requires an exogenous anion, e.g. phosphate when isolated from cell lysates, for tight iron sequestration. To address the role of exogenous anion identity and lability on Feaq
3+ dissociation from Fbp, the kinetics of PO4
3– exchange in Fe3+
nFbp(PO4) (nFbp=recombinant Fbp from Neisseria meningitidis) were investigated by dynamic 31P NMR and the kinetics of Fe3+ dissociation from Fe3+
nFbp(X) (X=PO4
3–, citrate anion) were investigated by stopped-flow pH-jump measurements. We justify the use of non-physiological low-pH conditions because a high [H+] will drive the Feaq
3+ dissociation reaction to completion without using competing chelators, whose presence may complicate or influence the dissociation mechanism. For perspective, these studies of nFbp (which has been referred to as a bacterial transferrin) are compared to new and previously published kinetic and thermodynamic data for mammalian transferrin. Significantly, we address the lability of the Fe3+ coordination shell in nFbp, Fe3+
nFbp(X) (X=PO4
3–, citrate), with respect to exogenous anion (X
n–) exchange and dissociation, and ultimately complete dissociation of the protein to yield naked (hydrated) Feaq
3+. These findings are a first step in understanding the process of iron donation to the bacterial permease for transport across the cytoplasmic membrane.Electronic Supplementary Material Supplementary material is available in the online version of this article at . Abbreviations DTPP
diethylenetriaminepenta(methylenephosphonic acid)
- Fbp
ferric binding protein
- H3cit
citric acid
-
hFbp
Fbp from Haemophilus influenzae
- H2ox
oxalic acid
-
hTf
human serum transferrin
- 3,4-LICAMS
N,N,N-tris(5-sulfo-2,3-dihydroxybenzoyl)-1,5,10-triazadecane
-
nFbp
recombinant Fbp from Neisseria meningitidis
- NTA
nitrilotriacetic acid
- TRENSOX
tris[2-aminoethyl(8-hydroxyquinoline-5-sulfonato-7-carbonyl)]amine 相似文献