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Different Mechanisms (different + mechanism)
Kinds of Different Mechanisms Selected AbstractsBrowning Prevention by Ascorbic Acid and 4-Hexylresorcinol: Different Mechanisms of Action on Polyphenol Oxidase in the Presence and in the Absence of SubstratesJOURNAL OF FOOD SCIENCE, Issue 9 2007E. Arias ABSTRACT:, We have investigated the mechanism of action of 4-hexylresorcinol (4-HR) and ascorbic acid (AA) on the polyphenol oxidase (PPO) catalyzed oxidation of phenolic substrates. Incubation of PPO with 4-HR diminishes strongly PPO activity. This effect can be erroneously interpreted, due to the high affinity of 4-HR for PPO, as irreversible inactivation of PPO. However, PPO activity can be recovered by dialysis after incubation with 4-HR. 4-hexylresorcinol is a canonical enzyme inhibitor that binds preferentially to the oxy form of PPO. It is a mixed-type inhibitor, because it influences both apparent Vmax (1.26 compared with 0.4 units in the absence and presence of 4-HR, respectively) and Km values (0.28 mM compared with 0.97 mM in the absence and in the presence of 4-HR, respectively) of PPO. AA can prevent browning by 2 different mechanisms: In the absence of PPO substrates it inactivates PPO irreversibly, probably through binding to its active site, preferentially in its oxy form. In the presence of PPO substrates, AA reduces PPO oxidized reaction products, which results in a lag phase when measuring PPO activity by monitoring dark product formation but not when monitoring O2 consumption. The simultaneous use of both 4-HR and AA on PPO results in additive prevention of browning. [source] End-Anchored Polymers: Compression by Different Mechanisms and Interpenetration of Apposing LayersMACROMOLECULAR THEORY AND SIMULATIONS, Issue 2 2005Mark D. Whitmore Abstract Summary: This paper presents a systematic study of the compression of end-anchored polymer layers by a variety of mechanisms. We treat layers in both good and , solvents, and in the range of polymer densities that is normally encountered in experiments. Our primary technique is numerical self-consistent field (NSCF) theory. We compare the NSCF results for the different mechanisms with each other, and with those of the analytic SCF theory. For each mechanism, we calculate the density profiles, layer thicknesses, and free energies, all as functions of the degree of polymerization and surface coverage. The free energy and the deformation of each layer depend on the compression mechanism, and they can be very different from the ASCF theory. For example, the energy of compression can be as much as three times greater than the analytical SCF (ASCF) prediction, and it does not reduce to simple, universal functions of the reduced distance between the surfaces. The overall physical picture simplifies if the free energy is expressed in terms of the layer deformation, rather than the reduced surface separation. We also examine and quantify the interpenetration of layers, discuss why ASCF theory applies better to some compression mechanisms than others, and end with comments on the difficulties in extracting quantitative information from surface-forces experiments. Comparisons of forces of compression in a good solvent for the three different systems, as functions of D/nb. The lower three curves are for ,*,=,3, and the upper three are for ,*,=,23. [source] Different Mechanisms of Cardiac Allograft Rejection in Wildtype and CD28-deficient MiceAMERICAN JOURNAL OF TRANSPLANTATION, Issue 1 2001Gregory L. Szot Although CD28 blockade results in long-term cardiac allograft survival in wildtype mice, CD28-deficient mice effectively reject heart allografts. This study compared the mechanisms of allogeneic responses in wildtype and CD28-deficient mice. Adoptive transfer of purified CD28-deficient T cells into transplanted nude mice resulted in graft rejection. However, this model demonstrated that the allogeneic T cell function was severely impaired when compared with wildtype T cells, despite similar survival kinetics. Cardiac allograft rejection depended on both CD4+ and CD8+ T cell subsets in CD28-deficient mice, whereas only CD4+ T cells were necessary in wildtype recipients. These results suggested that CD8+ T cells were more important in CD28-deficient than wildtype mice. In addition to the CD8+ T cell requirement, allograft rejection in CD28-deficient mice was dependent on a sustained presence of CD4+ T cells, whereas it only required the initial presence of CD4+ T cells in wildtype mice. Taken together, these data suggest that CD4+ T cells from CD28-deficient mice have impaired responses to alloantigen in vivo, thus requiring long-lasting cooperation with CD8+ T cell responses to facilitate graft rejection. These results may help to explain the failure to promote graft tolerance in some preclinical and clinical settings. [source] Two Nucleophilic Mutants of the Micromonospora viridifaciens Sialidase Operate with Retention of Configuration by Two Different MechanismsCHEMBIOCHEM, Issue 11 2005Jacqueline N. Watson Dr. Abstract Mutants of the Micromonospora viridifaciens sialidase, Y370E and Y370F, are catalytically active retaining enzymes that operate by different mechanisms. Previous substitutions with smaller amino acids, including Y370D, yielded inverting sialidases. At least one water molecule can fit into the active-site cavity of this mutant and act as a nucleophile from the face opposite the leaving group (Biochemistry 2003, 42, 12,682). Thus, addition of a CH2 unit (Asp versus Glu) changes the mechanism from inversion back to retention of configuration. Based on Brønsted ,lgvalues, it is proposed that the Y370E mutant reacts by a double-displacement mechanism (,lgon kcat/Km,0.36±0.04) with Glu370 acting as the nucleophile. However, the Y370F mutant (,lgon kcat/Km,0.79±0.12) reacts via a dissociative transition state. The crystal structure of the Y370F mutant complexed with 2-deoxy-2,3-dehydro- N -acetylneuraminic acid shows no significant active-site perturbation relative to the wild-type enzyme. [source] Entanglement of two atomsFORTSCHRITTE DER PHYSIK/PROGRESS OF PHYSICS, Issue 2-3 2003R. Tana We discuss the problem of creation of entangled states in a system of two two-level atoms which are separated by an arbitrary distance r12 and interact with each other via the dipole-dipole interaction and both are driven by a laser field. The entangled antisymmetric state of the system is included throughout, even for small inter-atomic separations. Different mechanisms leading to effective transfer of population to the antisymmetric state are identified. The steady-state values of concurrence which is a measure of entanglement are calculated showing that perfect entanglement can be reached in case of two non-identical atoms. [source] Induction and mechanism of action of transforming growth factor-,-secreting Th3 regulatory cellsIMMUNOLOGICAL REVIEWS, Issue 1 2001Howard L. Weiner Summary: Th3 CD4+ regulatory cells were identified during the course of investigating mechanisms associated with oral tolerance. Different mechanisms of tolerance are induced following oral antigen administration, including active suppression, clonal anergy and deletion. Low doses favor active suppression whereas high doses favor anergy/deletion. Th3 regulatory cells form a unique T-cell subset which primarily secretes transforming growth factor (TGF)-,, provides help for IgA and has suppressive properties for both Th1 and Th2 cells. Th3 type cells are distinct from the Th2 cells, as CD4+ TGF-,-secreting cells with suppressive properties have been generated from interleukin (IL)-4-deficient animals. In vitro differentiation of Th3 cells from Th precursors from T-cell antigen receptor (TCR) transgenic mice is enhanced by culture with TGF-,, IL-4, IL-10, and anti-IL-12. Th3 CD4+ myelin basic protein regulatory clones are structurally identical to Th1 encephalitogenic clones in TCR usage, MHC restriction and epitope recognition, but produce TGF-, with various amounts of IL-4 and IL-10. Because Th3 regulatory cells are triggered in an antigen-specific fashion but suppress in an antigen-non-specific fashion, they mediate "bystander suppression" when they encounter the fed autoantigen at the target organ. In vivo induction of Th3 cells and low dose oral tolerance is enhanced by oral administration of IL-4. Anti-CD86 but not anti-CD80 blocks the induction of Th3 cells associated with low dose oral tolerance. Th3 regulatory cells have been described in other systems (e.g. recovery from experimental allergic encephalomyelitis) but may be preferentially generated following oral antigen administration due to the gut immunologic milieu that is rich in TGF-, and has a unique class of dendritic cells. CD4+CD25+ regulatory T-cell function also appears related to TGF-,. [source] Properties of methanol bound to a defect of zeolitic structureINTERNATIONAL JOURNAL OF QUANTUM CHEMISTRY, Issue 2 2005Nikolai F. Stepanov Abstract Different mechanisms of Brønsted acidity formation upon the adsorption of a methanol molecule on a model Lewis acid site within zeolitic structure are evaluated by means of density functional theory in cluster approximation. The properties of the Brønsted acid sites formed are examined through studying their interaction with such probe molecules as methanol, ammonia, and ethylene. The results obtained are used to comment on a possible role of Lewis acid sites in methanol reactions catalyzed by zeolites. © 2005 Wiley Periodicals, Inc. Int J Quantum Chem, 2005 [source] Human Heart Cytosolic Reductases and Anthracycline CardiotoxicityIUBMB LIFE, Issue 1 2001Alvaro Mordente Abstract Anthracyclines are a class of antitumor drugs widely used for the treatment of a variety of malignancy, including leukemias, lymphomas, sarcomas, and carcinomas. Different mechanisms have been proposed for anthracycline antitumor effects including freeradical generation, DNA intercalation/binding, activation of signaling pathways, inhibition of topoisomerase II and apoptosis. A life-threatening form of cardiomyopathy hampers the clinical use of anthracyclines. According to the prevailing hypothesis, anthracyclines injure the heart by generating damaging free radicals through iron-catalyzed redox cycling. Although the "iron and freeradical hypothesis" can explain some aspects of anthracycline acute toxicity, it is nonetheless disappointing when referred to chronic cardiomyopathy. An alternative hypothesis implicates C-13 alcohol metabolites of anthracyclines as mediators of myocardial contractile dysfunction ("metabolite hypothesis"). Hydroxy metabolites are formed upon two-electron reduction of the C-13 carbonyl group in the side chain of anthracyclines by cytosolic NADPH-dependent reductases. Anthracycline alcohol metabolites can affect myocardial energy metabolism, ionic gradients, and Ca 2+ movements, ultimately impairing cardiac contraction and relaxation. In addition, alcohol metabolites can impair cardiac intracellular iron handling and homeostasis, by delocalizing iron from the [4Fe-4S] cluster of cytoplasmic aconitase. Chronic cardiotoxicity induced by C-13 alcohol metabolite might be primed by oxidative stress generated by anthracycline redox cycling ("unifying hypothesis"). Putative cardioprotective strategies should be aimed at decreasing C-13 alcohol metabolite production by means of efficient inhibitors of anthracycline reductases, as short-chain coenzyme Q analogs and chalcones that compete with anthracyclines for the enzyme active site, or by developing novel anthracyclines less susceptible to reductive metabolism. [source] Different mechanisms influencing permeation of PDGF-AA and PDGF-BB across the blood,brain barrierJOURNAL OF NEUROCHEMISTRY, Issue 1 2003Abba J. Kastin Abstract Platelet-derived growth factor (PDGF) exerts neurotrophic and neuromodulatory effects on the CNS. To determine the permeability of the blood,brain barrier (BBB) to PDGF, we examined the blood-to-brain influx of radioactively labeled PDGF isoforms (PDGF-AA and PDGF-BB) by multiple-time regression analysis after intravenous (i.v.) injection and by in-situ perfusion, and also determined the physicochemical characteristics which affect their permeation across the BBB, including lipophilicity (measured by octanol:buffer partition coefficient), hydrogen bonding (measured by differences in octanol : buffer and isooctane : buffer partition coefficients), serum protein binding (measured by capillary electrophoresis), and stability of PDGF in blood 10 min after i.v. injection (measured by HPLC). After i.v. bolus injection, neither 125I-PDGF-AA nor 125I-PDGF-BB crossed the BBB, their influx rates being similar to that of the vascular marker 99mTc-albumin. 125I-PDGF-AA degraded significantly faster in blood than 125I-PDGF-BB. PDGF-BB, however, was completely bound to a large protein in serum whereas PDGF-AA showed no binding. Thus, degradation might explain the poor blood-to-brain influx of PDGF-AA, whereas protein binding could explain the poor influx of circulating PDGF-BB. Despite their lack of permeation in the intact mouse, both 125I-PDGF-AA and 125I-PDGF-BB entered the brain by perfusion in blood-free buffer, and the significantly faster rate of 125I-PDGF-AA than 125I-PDGF-BB may be explained by the lower hydrogen bonding potential of 125I-PDGF-AA. Thus, the lack of significant distribution of PDGF from blood to brain is not because of the intrinsic barrier function of the BBB but probably because of degradation and protein binding. Information from these studies could be useful in the design of analogues for delivery of PDGF as a therapeutic agent. [source] Different mechanisms of action of antimicrobial peptides: insights from fluorescence spectroscopy experiments and molecular dynamics simulations,JOURNAL OF PEPTIDE SCIENCE, Issue 9 2009Gianfranco Bocchinfuso Abstract Most antimicrobial peptides exert their activity by interacting with bacterial membranes, thus perturbing their permeability. They are investigated as a possible solution to the insurgence of bacteria resistant to the presently available antibiotic drugs. However, several different models have been proposed for their mechanism of membrane perturbation, and the molecular details of this process are still debated. Here, we compare fluorescence spectroscopy experiments and molecular dynamics (MD) simulations regarding the association with lipid bilayers and lipid perturbation for two different amphiphilic helical antimicrobial peptides, PMAP-23 and trichogin GA IV. PMAP-23, a cationic peptide member of the cathelicidin family, is considered to induce membrane permeability according to the Shai-Matsuzaki-Huang "carpet" model, while trichogin GA IV is a neutral peptide, member of the peptaibol family. Although several lines of evidence suggest a "barrel-stave" mechanism of pore formation for the latter peptide, its length is only half the normal thickness of a lipid bilayer. Both fluorescence spectroscopy experiments and MD simulations indicated that PMAP-23 associates with membranes close to their surface and parallel to it, and in this arrangement it causes a severe perturbation to the bilayer, both regarding its surface tension and lipid order. By contrast, trichogin GA IV can undergo a transition from a surface-bound state to a transmembrane orientation. In the first arrangement, it does not cause any strong membrane perturbation, while in the second orientation it might be able to span the bilayer from one side to the other, despite its relatively short length, by causing a significant thinning of the membrane. Copyright © 2009 European Peptide Society and John Wiley & Sons, Ltd. [source] Exciton localization in MgxZnyCd1,x,ySe alloyPHYSICA STATUS SOLIDI (B) BASIC SOLID STATE PHYSICS, Issue 3 2004O. Maksimov Abstract We report photoluminescence and reflectivity measurements of MgxZnyCd1,x,ySe epitaxial layers (0 < x < 0.53) grown by molecular beam epitaxy on InP (100) substrates. Significant emission line broadening, increase in activation energy and Stokes shift are monitored with increasing Mg content. For MgxCdyZn1,x,ySe samples with large Mg content (x > 0.3), we observe an anomalous temperature dependence of both the emission energy and line broadening. This behavior is assigned to the emission from localized states. Different mechanisms of carrier localization are discussed and exciton localization on statistical CdSe clusters is proposed to be the most likely one. (© 2004 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim) [source] Taurine deficiency is a cause of vigabatrin-induced retinal phototoxicity,ANNALS OF NEUROLOGY, Issue 1 2009Firas Jammoul MD Objective Although vigabatrin irreversibly constricts the visual field, it remains a potent therapy for infantile spasms and a third-line drug for refractory epilepsies. In albino animals, this drug induces a reduction in retinal cell function, retinal disorganization, and cone photoreceptor damage. The objective of this study was to investigate the light dependence of the vigabatrin-elicited retinal toxicity and to screen for molecules preventing this secondary effect of vigabatrin. Methods Rats and mice were treated daily with 40 and 3mg vigabatrin, respectively. Retinal cell lesions were demonstrated by assessing cell function with electroretinogram measurements, and quantifying retinal disorganization, gliosis, and cone cell densities. Results Vigabatrin-elicited retinal lesions were prevented by maintaining animals in darkness during treatment. Different mechanisms including taurine deficiency were reported to produce such phototoxicity; we therefore measured amino acid plasma levels in vigabatrin-treated animals. Taurine levels were 67% lower in vigabatrin-treated animals than in control animals. Taurine supplementation reduced all components of retinal lesions in both rats and mice. Among six vigabatrin-treated infants, the taurine plasma level was found to be below normal in three patients and undetectable in two patients. Interpretation These results indicate that vigabatrin generates a taurine deficiency responsible for its retinal phototoxicity. Future studies will investigate whether cotreatment with taurine and vigabatrin can limit epileptic seizures without inducing the constriction of the visual field. Patients taking vigabatrin could gain immediate benefit from reduced light exposures and dietetic advice on taurine-rich foods. Ann Neurol 2009;65:98,107 [source] Preparation, Characterization and Electrocatalytic Studies on Copper Complex Dye Film Modified ElectrodesELECTROANALYSIS, Issue 13 2007Shen-Ming Chen Abstract Copper complex dye (C.I. Direct Blue 200) film modified electrodes have been prepared by multiple scan cyclic voltammetry. The effect of solution pH and nature of electrode material on film formation was investigated. The optimum pH for copper complex film formation on glassy carbon was found to be 1.5. The mechanism of film formation on ITO seems to be similar to that on GC surface but completely different mechanism followed with gold electrode. Cyclic voltammetric features of our modified electrodes are in consistent with a surface-confined redox process. The voltammetric response of modified electrode was found to be depending on pH of the contacting solution. UV-visible spectra show that the nature of copper complex dye is identical in both solution phase and after forming film on electrode. The electrocatalytic behavior of copper complex dye film modified electrode towards oxidation of dopamine, ascorbic acid and reduction of SO52, was investigated. The oxidation of dopamine and ascorbic acid occurred at less positive potential on film electrode compared to bare glassy carbon electrode. Feasibility of utilizing our modified electrode in analytical estimation of dopamine, ascorbic acid was also demonstrated. [source] Investigation of the stereodynamics of tris-(, -diimine),transition metal complexes by enantioselective dynamic MEKCELECTROPHORESIS, Issue 2 2009Sabrina Bremer Abstract Enantiomerization of octahedral tris(, -diimine),transition metal complexes was investigated by enantioselective dynamic MEKC. Varying both the transition metal ion (Fe2+, Fe3+, and Ni2+) and the bidentate diimine ligand (1,10-phenanthroline and 2,2,-bipyridyl), the enantiomer separations were performed either in a 100,mM sodium tetraborate buffer (pH 9.3) or in a 100,mM sodium tetraborate/sodium dihydrogenphosphate buffer (pH 8.0) both containing sodium cholate as chiral surfactant. The unified equation of dynamic chromatography was employed to determine apparent reaction rate constants from the electropherograms showing distinct plateau formation. Apparent activation parameters ,H, and ,S, were calculated from temperature-dependent measurements between 10.0 and 35.0°C in 2.5,K steps. It was found that the nature of the central metal ion and the ligand strongly influence the enantiomerization barrier. Surprisingly, complexes containing the 2,2,-bipyridyl ligand show highly negative activation entropies between ,103 and ,116,J (K,mol),1 while the activation entropy of tris(1,10-phenanthroline) complexes is positive indicating a different mechanism of interconversion. Furthermore, it was found that the Ni2+ complexes are stereostable under the conditions investigated here making them a lucent target as enantioselective catalysts. [source] Characterization by NMR Spectroscopy, X-ray Analysis and Cytotoxic Activity of the Ruthenium(II) Compounds [RuL3](PF6)2(L = 2-Phenylazopyridine or o -Tolylazopyridine) and [RuL'2L"](PF6)2(L', L" = 2-Phenylazopyridine, 2,2'-Bipyridine)EUROPEAN JOURNAL OF INORGANIC CHEMISTRY, Issue 13 2005Anna C. G. Hotze Abstract Tris(ligand) complexes [RuL3](PF6)2 (L = 2-phenylazopyridine or o -tolylazopyridine) and mixed ligand [RuL'2L"](PF6)2 (L' and L" are 2-phenylazopyridine or 2,2'-bipyridine) have been synthesized, structurally characterized and investigated for cytotoxic activity. These complexes are important to study the hypothesis that the compound ,-[Ru(azpy)2Cl2] (azpy = 2-phenylazopyridine) exhibits a high cytotoxicity due to its two cis chloride ligands, which might be exchanged for biological targets as DNA. Molecular structures of mer -[Ru(azpy)3](PF6)2 (1) and mer -[Ru(tazpy)3](PF6)2 (5) (tazpy = o -tolylazopyridine) have been determined by X-ray diffraction. Series of complexes [RuL3](PF6)2 and [RuL'2L"](PF6)2 show interesting NMR spectroscopic data; e.g. the spectrum of mer -[Ru(azpy)3](PF6)2 (1) shows extremely broadened resonances at room temp. but sharpened resonances at low temperature. In the 1H NMR spectra of compounds [Ru(azpy)2(bpy)]2+ and [Ru(bpy)2(azpy)]2+ (bpy = 2,2-bipyridine), respectively, less broadened (room temp.) or completely sharp resonances (room temp.) occur in comparison to 1 (under same conditions). By selecting the right temperature and/or concentration, NMR spectra of these series of compounds have been resolved using 2D COSY and NOESY NMR spectroscopy. Remarkably, the cytotoxicity data against a series of human tumor cell lines (A498, EVSA-T, H226, IGROV, M19, MCF-7 and WIDR) show a moderate cytotoxicity for these series of tris(ligand) complexes. So, even though no chloride ligands are present in these tris(ligand) complexes, a considerable cytotoxic activity is observed. This would imply that the 2-phenylazopyridine ruthenium(II) complexes act by a completely different mechanism than the well-known cisplatin. This finding is important, because an anticancer compound acting via a different mechanism is a prerequisite in designing new anticancer drugs. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005) [source] The crystal structure of phenylpyruvate decarboxylase from Azospirillum brasilense at 1.5 Å resolutionFEBS JOURNAL, Issue 9 2007Implications for its catalytic, regulatory mechanism Phenylpyruvate decarboxylase (PPDC) of Azospirillum brasilense, involved in the biosynthesis of the plant hormone indole-3-acetic acid and the antimicrobial compound phenylacetic acid, is a thiamine diphosphate-dependent enzyme that catalyses the nonoxidative decarboxylation of indole- and phenylpyruvate. Analogous to yeast pyruvate decarboxylases, PPDC is subject to allosteric substrate activation, showing sigmoidal v versus [S] plots. The present paper reports the crystal structure of this enzyme determined at 1.5 Å resolution. The subunit architecture of PPDC is characteristic for other members of the pyruvate oxidase family, with each subunit consisting of three domains with an open ,/, topology. An active site loop, bearing the catalytic residues His112 and His113, could not be modelled due to flexibility. The biological tetramer is best described as an asymmetric dimer of dimers. A cysteine residue that has been suggested as the site for regulatory substrate binding in yeast pyruvate decarboxylase is not conserved, requiring a different mechanism for allosteric substrate activation in PPDC. Only minor changes occur in the interactions with the cofactors, thiamine diphosphate and Mg2+, compared to pyruvate decarboxylase. A greater diversity is observed in the substrate binding pocket accounting for the difference in substrate specificity. Moreover, a catalytically important glutamate residue conserved in nearly all decarboxylases is replaced by a leucine in PPDC. The consequences of these differences in terms of the catalytic and regulatory mechanism of PPDC are discussed. [source] Fibrate induction of the adrenoleukodystrophy-related gene (ABCD2)FEBS JOURNAL, Issue 12 2001Promoter analysis, role of the peroxisome proliferator-activated receptor PPAR X-linked adrenoleukodystrophy (X-ALD) is a neurodegenerative disease due to a defect in the ABCD1 (ALD) gene. ABCD1, and the two close homologues ABCD2 (ALDR) and ABCD3 (PMP70), are genes encoding ATP-binding cassette half-transporters of the peroxisomal membrane. As overexpression of the ABCD2 or ABCD3 gene can reverse the biochemical phenotype of X-ALD (reduced ,-oxidation of very-long-chain fatty acids), pharmacological induction of these partially redundant genes may represent a therapeutic approach to X-ALD. We previously reported that the ABCD2 and ABCD3 genes could be strongly induced by fibrates, which are hypolipidaemic drugs and peroxisome-proliferators in rodents. We provide evidence that the induction is dependent on peroxisome proliferator-activated receptor (PPAR,) as both genes were not induced in fenofibrate-treated PPAR,,/, knock-out mice. To further characterize the PPAR, pathway, we cloned and analysed the promoter of the ABCD2 gene, the closest homologue of the ABCD1 gene. The proximal region (2 kb) of the rat promoter displayed a high conservation with the human and mouse cognate sequences suggesting an important role of the region in regulation of the ABCD2 gene. Classically, fibrate-induction involves interaction of PPAR, with a response element (PPRE) characterized by a direct repeat of the AGGTCA-like motif. Putative PPRE motifs of the rat ABCD2 promoter were studied in the isolated form or in their promoter context by gel-shift assay and transfection of COS-7 cells. We failed to characterize a functional PPRE, suggesting a different mechanism for the PPAR,-dependent regulation of the ABCD2 gene. [source] A cryptic lysis gene near the start of the Q, replicase gene in the +1 frameGENES TO CELLS, Issue 10 2004Tohru Nishihara The maturation/lysis (A2) protein encoded by the group B single-stranded RNA bacteriophage Q, mediates lysis of host Escherichia coli cells. We found a frameshift mutation in the replicase (,-subunit) gene of Q, cDNA causes cell lysis. The mutant has a single base deletion 73 nucleotides (nt) 3, from the start of the replicase gene with consequent translation termination at a stop codon 129,131 nt further 3,. The 43-amino acid C-terminal part of the 67-amino acid product encoded by what in WT (wild-type) is the +1 frame, is rich in basic amino acids This 67-aa protein can mediate cell lysis whose characteristics indicate that the protein may cause lysis by a different mechanism and via a different target, than that caused by the A2 maturation/lysis protein. Synthesis of a counterpart of the newly discovered lysis product in wild-type phage infection would require a hypothetical ribosomal frameshifting event. The lysis gene of group A RNA phages is also short, 75 codons in MS2, and partially overlaps the first part of their equivalently located replicase gene, raising significant evolutionary implications for the present finding. [source] Synthesis of polyetherols with isocyanuric ring.INTERNATIONAL JOURNAL OF CHEMICAL KINETICS, Issue 8 2009Kinetics, mechanisms of reactions, part 2: Consecutive reaction of ethylene carbonate with isocyanuric acid The kinetics and mechanism of the reaction between isocyanuric acid and ethylene carbonate was studied. The multistep reaction in the presence of potassium carbonate as catalyst leads to polyetherols. The imide and hydroxyl groups of intermediates react with ethylene carbonate by slightly different mechanism and kinetics. The rate constants for these elementary processes were established, and based on these experimental data the mechanism of reaction was proposed. Using the isocyanuric acid and 1,3,5-tris(2-hydroxyethyl)isocyanurate, it has been found that the reaction of ethylene carbonate with intermediates occurs via a mixed mechanism. © 2009 Wiley Periodicals, Inc. Int J Chem Kinet 41: 523,531, 2009 [source] Evolving Treatment Options for Prevention of Cardiovascular Events in High-Risk Hypertensive PatientsJOURNAL OF CLINICAL HYPERTENSION, Issue 11 2007Prakash Deedwania MD The identification and treatment of high-risk patients for cardiovascular disease reduces the risk of morbidity and mortality. Significant risk factors for cardiovascular events in hypertensive patients over and above dyslipidemia, smoking, and obesity include coronary heart disease, peripheral arterial disease, cerebrovascular/carotid artery disease, and diabetes. Treatment options for the reduction of cardiovascular events in hypertensive patients include diuretics, ,-blockers, ,-blockers, calcium channel blockers, angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), and aldosterone antagonists. All of these agents, in various combinations, have been found to reduce the risk of cardiovascular events, even in high-risk patients. The use of ACE inhibitors or ARBs (usually in combination with a diuretic) has proven especially effective in reducing cardiovascular events in diabetes and, although both classes of drugs target the renin-angiotensin-aldosterone system, each has a different mechanism of action. Some investigators believe that combination therapy with an ACE inhibitor and ARB, usually given with other medications, may be more effective than either agent alone with other drugs. The Ongoing Telmisartan Alone and in Combination With Ramipril Global Endpoint Trial (ONTARGET) is evaluating the cardioprotective effect of an ACE inhibitor (ramipril) plus an ARB (telmisartan) in high-risk patients. [source] Analysis of interactions responsible for vasopressin binding to human neurohypophyseal hormone receptors,molecular dynamics study of the activated receptor,vasopressin,G, systemsJOURNAL OF PEPTIDE SCIENCE, Issue 3 2006Magdalena J., lusarz Abstract Vasopressin (CYFQNCPRG-NH2, AVP) is a semicyclic endogenous peptide, which exerts a variety of biological effects in mammals. The main physiological roles of AVP are the regulation of water balance and the control of blood pressure and adrenocorticotropin hormone (ACTH) secretion, mediated via three different subtypes of vasopressin receptors: V1a, V1b and V2 receptors (V1aR, V1bR and V2R, respectively). They are the members of the class A, G-protein-coupled receptors (GPCRs). AVP also modulates several behavioral and social functions. In this study, the interactions responsible for AVP binding to vasopressin V1a and V2 receptors versus the closely related oxytocin ([I3,L8]AVP, OT) receptor (OTR) have been investigated. Three-dimensional models of the activated receptors were constructed using multiple sequence alignment, followed by homology modeling using the complex of activated rhodopsin with Gt,C -terminal peptide of transducin MII-Gt(338-350) prototype as a template. AVP was docked into the receptor-G, systems. The three lowest-energy pairs of receptor-AVP-G, (two complexes per each receptor) were selected. The 1-ns unconstrained molecular dynamics (MD) of complexes embedded into the fully hydrated 1-palmitoyl-2-oleoyl- sn -glycero-3-phosphatidylcholine (POPC) lipid bilayer was conducted in the AMBER 7.0 force field. Six relaxed receptor-AVP-G, models were obtained. The residues responsible for AVP binding to vasopressin receptors have been identified and a different mechanism of AVP binding to V2R than to V1aR has been proposed. Copyright © 2005 European Peptide Society and John Wiley & Sons, Ltd. [source] A Variant of Des-,-Carboxy Prothrombin Was Increased in Alcoholic Liver Disease Without Hepatocellular CarcinomaALCOHOLISM, Issue 2001Motoyuki Ohhira Serum variants of des-,-carboxy prothrombin (DCP) recognized by two different monoclonal antibodies, 19B7 and MU-3, were measured in patients with alcoholic liver disease (ALD), and the values were compared with those of viral liver disease (VLD) and hepatocellular carcinoma (HCC). In the assay that used 19B7 antibody, DCP levels in ALD and HCC were significantly higher than that of VLD, although there was no significant difference in the values between ALD and HCC. In the assay that used MU-3 antibody, DCP level of HCC was significantly higher than those of ALD and VLD, although there was no significant difference in values between ALD and VLD. The ratio of 19B7/MU-3 assay values was significantly higher for ALD than the ratios for VLD and HCC. It is suggested that ALD has a different DCP variant pattern compared with VLD and HCC, which suggests that ALD has a different mechanism of DCP production. [source] Polygonal impact craters in Argyre region, Mars: Implications for geology and cratering mechanicsMETEORITICS & PLANETARY SCIENCE, Issue 10 2008T. ÖHMAN Such polygonal impact craters (PICs) are controlled by pre-existing target structures, mainly faults or other similar planes of weakness. In the Argyre region, Mars, PICs comprise , 17% of the total impact crater population (>7 km in diameter), and PICs are relatively more common in older geologic units. Their formation is mainly controlled by radial fractures induced by the Argyre and Ladon impact basins, and to a lesser extent by the basin-concentric fractures. Also basin-induced conjugate shear fractures may play a role. Unlike the PICs, ridges and graben in the Argyre region are mostly controlled by Tharsis-induced tectonism, with the ridges being concentric and graben radial to Tharsis. Therefore, the PICs primarily reflect an old impact basin-centered tectonic pattern, whereas Tharsis-centered tectonism responsible for the graben and the ridges has only minor influence on the PIC rim orientations. According to current models of PIC formation, complex PICs should form through a different mechanism than simple PICs, leading to different orientations of straight rim segments. However, when simple and complex PICs from same areas are studied, no statistically significant difference can be observed. Hence, in addition to enhanced excavation parallel to the strike of fractures (simple craters) and slumping along the fracture planes (complex craters), we propose a third mechanism involving thrusting along the fracture planes. This model is applicable to both simple and small complex craters in targets with some dominating orientations of structural weakness. [source] Toxicity Mode-of-action: Discrimination via Infrared Spectra And Eigenvalues of the Modified Adjacency MatrixMOLECULAR INFORMATICS, Issue 2 2003Anna Pino Abstract Aquatic toxicity can be partitioned into a number of mechanisms of action, the allocation of a given chemical to its particular mode being of fundamental importance for the toxicological risk assessment. We investigated the possibility to automatically allocate each chemical to its putative aquatic toxicity mode-of-action on the basis of the sole chemical physical information. In this paper, we refer to the four mode-of-action classes defined in Hermens' laboratory [1, 2]; the chemical descriptors used were the Infrared spectra and the Burden's Modified Adjacency Matrix Eigenvalues. At odds with Infrared spectrum, the Eigenvalues were able to allocate the chemicals into the different mechanism of action classes via a nonlinear discrimination method (K-nearest neighbours classifier). [source] Control of nitrogen metabolism by Bacillus subtilis glutamine synthetaseMOLECULAR MICROBIOLOGY, Issue 2 2008Abraham L. Sonenshein Summary Two recent papers describe the molecular mechanism by which the activity of GlnR, the repressor of the glutamine synthetase operon in Bacillus subtilis, is stimulated by glutamine-bound (i.e. feedback-inhibited) glutamine synthetase (FBI-GS). Remarkably, FBI-GS acts as a molecular chaperone to stabilize the association of GlnR dimers with their DNA binding sites. This mechanism allows the cell to shut off synthesis of GS, and hence of glutamine, when both the enzyme and its product are in excess. FBI-GS also regulates the activity of TnrA, the global regulator of nitrogen metabolism genes, but by a very different mechanism. Thus, the same enzyme,metabolite complex has two different roles in transcriptional regulation. [source] VIMOS-VLT spectroscopy of the giant Ly, nebulae associated with three z, 2.5 radio galaxies,MONTHLY NOTICES OF THE ROYAL ASTRONOMICAL SOCIETY, Issue 2 2007M. Villar-Martín ABSTRACT The morphological and spectroscopic properties of the giant (>60 kpc) Ly, nebulae associated with three radio galaxies at z, 2.5 (MRC 1558,003, 2025,218 and 0140,257) have been investigated using integral field spectroscopic data obtained with the Visible Multi-Object Spectrograph (VIMOS) on VLT. The morphologies are varied. The nebula of one source has a centrally peaked, rounded appearance. In the other two objects, it consists of two spatial components. The three nebulae are aligned with the radio axis within ,30°. The total Ly, luminosities are in the range (0.3,3.4) × 1044 erg s,1. The Ly, spectral profile shows strong variation through the nebulae, with full width at half-maximum (FWHM) values in the range ,400,1500 km s,1 and velocity shifts Voffset, 120,600 km s,1. We present an infall model that can successfully explain the morphology, size, surface brightness distribution and the velocity field of the Ly, nebula associated with MRC 1558,003. It can also explain why Ly, is redshifted relative to other emission lines and the FWHM values of the non-resonant He ii line. This adds further support to our previous conclusion that the quiescent giant nebulae associated with this and other high-redshift powerful radio galaxies are in infall. A problem for this model is the difficulty to reproduce the large Ly, FWHM values, which might be the consequence of a different mechanism. We have discovered a giant (,85 kpc) Ly, nebula associated with the radio galaxy MRC 0140,257 at z= 2.64. It shows strikingly relaxed kinematics (FWHM < 300 km s,1 and Voffset, 120 km s,1), unique among high- z (,2) radio galaxies. [source] Review Article: Review: Endothelial-myofibroblast transition, a new player in diabetic renal fibrosisNEPHROLOGY, Issue 5 2010JINHUA LI ABSTRACT Diabetic nephropathy (DN) is the most common cause of chronic kidney failure and end-stage renal disease in the Western world. Studies from diabetic animal models and clinical trials have shown that inhibition of the renin-angiotensin system delays the progression of advanced DN. However, a recent large-scale clinical trial has revealed that inhibition of renin-angiotensin system in early phases of DN does not slow the decline of renal function or the development of morphological lesions, suggesting that different mechanism(s) may be involved in the different stages of DN. The role of epithelial-mesenchymal transition in renal fibrosis has been intensively investigated. Recently, endothelial-mesenchymal transition, or endothelial-myofibroblast transition (EndoMT) has emerged as another mechanism involved in both developmental and pathological processes. The essential role of EndoMT in cardiac development has been thoroughly studied. EndoMT also exists and contributes to the development and progression of cardiac fibrosis, lung fibrosis, liver fibrosis and corneal fibrosis. EndoMT is a specific form of epithelial-mesenchymal transition. During EndoMT, endothelial cells lose endothelial markers and obtain mesenchymal markers. Recent evidence from our laboratory and others suggests that EndoMT plays an important role in the development of renal fibrosis in several pathological settings, including experimental DN. This review considers the evidence supporting the occurrence of EndoMT in normal development and in pathology, as well as the latest findings suggesting EndoMT contributes to fibrosis in DN. Whether experimental findings of EndoMT will be reproduced in human studies remains to be determined. [source] Differential expression of specific microRNA and their targets in acute myeloid leukemia,AMERICAN JOURNAL OF HEMATOLOGY, Issue 5 2010Giuseppe Cammarata Acute myeloid leukemia (AML) the most common acute leukemia in adults is characterized by various cytogenetic and molecular abnormalities. However, the genetic etiology of the disease is not yet fully understood. MicroRNAs (miRNA) are small noncoding RNAs which regulate the expression of target mRNAs both at transcriptional and translational level. In recent years, miRNAs have been identified as a novel mechanism in gene regulation, which show variable expression during myeloid differentiation. We studied miRNA expression of leukemic blasts of 29 cases of newly diagnosed and genetically defined AML using quantitative reverse transcription polymerase chain reaction (RT-PCR) for 365 human miRNA. We showed that miRNA expression profiling reveals distinctive miRNA signatures that correlate with cytogenetic and molecular subtypes of AML. Specific miRNAs with consolidated role on cell proliferation and differentiation such as miR-155, miR-221, let-7, miR-126 and miR-196b appear to be associated with particular subtypes. We observed a significant differentially expressed miRNA profile that characterizes two subgroups of AML with different mechanism of leukemogenesis: core binding factor (CBF) and cytogenetically normal AML with mutations in the genes of NPM1 and FLT3- ITD. We demonstrated, for the first time, the inverse correlation of expression levels between miRNA and their targets in specific AML genetic groups. We suggest that miRNA deregulation may act as complementary hit in the multisteps mechanism of leukemogenesis offering new therapeutic strategies. Am. J. Hematol. 2010. © 2010 Wiley-Liss, Inc. [source] Affinity cleavage at the divalent metal site of porcine NAD-specific isocitrate dehydrogenasePROTEIN SCIENCE, Issue 1 2000Yu-Chu Huang Abstract A divalent metal ion, such as Mn2+, is required for the catalytic reaction and allosteric regulation of pig heart NAD-dependent isocitrate dehydrogenase. The enzyme is irreversibly inactivated and cleaved by Fe2+ in the presence of O2 and ascorbate at pH 7.0. Mn2+ prevents both inactivation and cleavage. Nucleotide ligands, such as NAD, NADPH, and ADP, neither prevent nor promote inactivation or cleavage of the enzyme by Fe2+. The NAD-specific isocitrate dehydrogenase is composed of three distinct subunits in the ratio 2,:1 ,:1 ,. The results indicate that the oxidative inactivation and cleavage are specific and involve the 40 kDa , subunit of the enzyme. A pair of major peptides is generated during Fe2+ inactivation: 29.5 + 10.5 kDa, as determined by SDS-PAGE. Amino-terminal sequencing reveals that these peptides arise by cleavage of the Val262-His263 bond of the , subunit. No fragments are produced when enzyme is incubated with Fe2+ and ascorbate under denaturing conditions in the presence of 6 M urea, indicating that the native structure is required for the specific cleavage. These results suggest that His263 of the , subunit may be a ligand of the divalent metal ion needed for the reaction catalyzed by isocitrate dehydrogenase. Isocitrate enhances the inactivation of enzyme caused by Fe2+ in the presence of oxygen, but prevents the cleavage, suggesting that inactivation occurs by a different mechanism when metal ion is bound to the enzyme in the presence of isocitrate: oxidation of cysteine may be responsible for the rapid inactivation in this case. Affinity cleavage caused by Fe2+ implicates , as the catalytic subunit of the multisubunit porcine NAD-dependent isocitrate dehydrogenase. [source] Obesity, Smoking, and Frontal Brain DysfunctionTHE AMERICAN JOURNAL ON ADDICTIONS, Issue 5 2010Lance Bauer PhD Obesity, smoking, and conduct problems have all been associated with decrements in brain function. However, their additive and interactive effects have rarely been examined. To address the deficiency, we studied P300a and P300b electroencephalographic potentials in 218 women grouped by the presence versus absence of: (1) a BMI , 30 kg/m2; (2) recent smoking; and (3) , 2 childhood conduct problems. Analyses revealed smaller P300a and P300b amplitudes over the posterior scalp among recent smokers versus nonsmokers. No corresponding group differences were found in P300 latencies or frontal scalp amplitudes. The most interesting analysis result was an interaction between conduct problems and obesity limited to the frontally generated P300a component: its latency was significantly greater in women with both attributes than in those with either or neither attribute. An exploratory ANOVA, substituting the genotype of a GABRA2 SNP for conduct problems, also demonstrated an interaction with obesity affecting P300a latency. It is hypothesized that conduct problems, and a conduct-problem-associated GABRA2 genotype, decrease the age-of-onset and/or increase the lifetime duration of obesity. As a result, they may potentiate the adverse effects of obesity on frontal white matter and thereby increase P300a latency. Smoking may affect brain function by a different mechanism to reduce posterior scalp P300a and P300b amplitudes while preserving frontal scalp P300a latency and amplitude.,(Am J Addict 2010;00:1,10) [source] | ||||||||||||||||||||||||||||||||||||||||||||||||||||