Home About us Contact
|
Home About us Contact | ||
|
|
||
Detailed Mechanisms (detailed + mechanism)
Selected AbstractsSynthesis and Reactivity of 23 - tert -Butyl- and 23 -Phenyltetraarylazuliporphyrins: an Analysis of the Effect of Bulky Substituents on Oxidative Ring Contractions to Benzocarbaporphyrins,EUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 24 2007Jessica A. El-Beck Abstract 6- tert -Butyl- and 6-phenylazulene reacted with pyrrole and benzaldehyde in a molar ratio of 1:3:4 in the presence of BF3·Et2O in chloroform, followed by oxidation with DDQ, to give 23 -substituted tetraphenylazuliporphyrins in 15,20,% yield. Slightly higher yields of the related meso -tetrakis(4-chlorophenyl)azuliporphyrins were obtained using 4-chlorobenzaldehyde. The presence of an electron-donating tert -butyl substituent increased the diatropic character of the azuliporphyrin system as determined by the proton NMR chemical shifts for the internal CH resonance, while intermediary results were noted for 23 -phenylazuliporphyrins. Addition of TFA afforded dications with increased aromatic ring currents, but electron-donating substituents (tBu,>,Ph) again produced a larger upfield shift for the internal CH signal due to stabilization of the tropylium character that is required so that the system can attain carbaporphyrin-type aromaticity. The substituted azuliporphyrins reacted with nickel(II) acetate or palladium(II) acetate to give the corresponding organometallic derivatives. In addition, oxidations with tBuOOH and KOH afforded benzocarbaporphyrin products in approximately 50,% yield. The presence of tert -butyl or phenyl substituents did not block these oxidative ring contraction processes, and the rate of reaction was slightly increased compared to 23 -unsubstituted azuliporphyrins. The major products were 22 - tert -butyl or phenyl-substituted benzocarbaporphyrins and minor products with an additional formyl substituent were also isolated. These products are consistent with an initial nucleophilic addition occurring at the position adjacent to the R group on the azulene ring. Detailed mechanisms are proposed to explain these observations. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007) [source] Recent progress in studies of infantile hemangiomaTHE JOURNAL OF DERMATOLOGY, Issue 4 2010Masatoshi JINNIN Abstract A hallmark of infantile hemangioma, the most common tumor of infancy, is its dramatic growth after birth, by diffuse proliferation of immature endothelial cells, followed by spontaneous regression. The growth and involution of infantile hemangioma is quite different from other vascular anomalies, which do not regress and can occur at any time during life. Some hemangioma lesions can be extremely disfiguring and destructive to normal tissue and may even be life-threatening. Unfortunately, existing therapeutic approaches have limited success and significant adverse effects of some treatment modalities limit their use. Better understanding of the pathogenesis of hemangioma will enable the development of better therapeutic strategies. Here, we review recent studies and new hypotheses on the pathogenesis of the tumor. Detailed mechanisms of activated vascular endothelial growth factor signaling in tumor cells, identification of their origin and characterization of multipotent stem cells that can give rise to infantile hemangioma are shedding new light on this intriguing vascular tumor. [source] Effect of surfactant micelles on the kinetics of oxidation of D -fructose by cerium(IV) in sulfuric acid mediumINTERNATIONAL JOURNAL OF CHEMICAL KINETICS, Issue 1 2006Kabir-ud-Din Kinetics of the oxidation of D -fructose by cerium(IV) has been investigated both in the absence and presence of surfactants (cetyltrimethylammonium bromide, CTAB, and sodium dodecyl sulfate, SDS) in sulfuric acid medium. The reaction exhibits first-order kinetics each in [cerium(IV)] and [D -fructose] and inverse first order in [H2SO4]. The Arrhenius equation is found to be valid for the reaction between 30,50°C. A detailed mechanism with the associated reaction kinetics is presented and discussed. While SDS has no effect, CTAB increases the reaction rate with the same kinetic behavior in its presence. The catalytic role of CTAB micelles is discussed in terms of the pseudophase model proposed by Menger and Portnoy. The association constant Ks that equals to 286 mol,1 dm3 is found for the association of cerium(IV) with the positive head group of CTAB micelles. The effect of inorganic electrolytes (Na2SO4, NaNO3, NaCl) has also been studied and discussed. © 2005 Wiley Periodicals, Inc. Int J Chem Kinet 38: 18,25, 2006 [source] Experimental and modeling study of the oxidation of benzeneINTERNATIONAL JOURNAL OF CHEMICAL KINETICS, Issue 10 2003I. Da Costa This paper describes an experimental and modeling study of the oxidation of benzene. The low-temperature oxidation was studied in a continuous flow stirred tank reactor with carbon-containing products analyzed by gas chromatography. The following experimental conditions were used: 923 K, 1 atm, fuel equivalence ratios from 1.9 to 3.6, concentrations of benzene from 4 to 4.5%, and residence times ranging from 1 to 10 s corresponding to benzene conversion yields from 6 to 45%. The ignition delays of benzene,oxygen,argon mixtures with fuel equivalence ratios from 1 to 3 were measured behind shock waves. Reflected shock waves permitted to obtain temperatures from 1230 to 1970 K and pressures from 6.5 to 9.5 atm. A detailed mechanism has been proposed and allows us to reproduce satisfactorily our experimental results, as well as some data of the literature obtained in other conditions, such as in a plug flow reactor or in a laminar premixed flame. The main reaction paths have been determined for the four series of measurements by sensitivity and flux analyses. © 2003 Wiley Periodicals, Inc. Int J Chem Kinet 35: 503,524, 2003 [source] Laser control of photodissociation process in diatomic moleculeINTERNATIONAL JOURNAL OF QUANTUM CHEMISTRY, Issue 14 2009A. Tawada Abstract In this work, we first aim to realize the complete laser-induced photodissociation of the OH molecule, and then intend to control the wavepacket generated on the continuum state, i.e., to achieve the laser control of the above-threshold dissociation (ATD) spectrum. To numerically solve the Schrödinger equation, we adopt the split operator method (SOM), which conserves the norm of the state vector, and can treat both discrete and continuum states simultaneously and correctly. This photodissociation process induced by the multiphoton absorption involves the ATD spectrum due to the continuum-continuum transition by the intense electric field. First, we investigate the detailed mechanism of the complete photodissociation with the one-color laser pulse by changing the laser parameters. Then, we investigate the control of the ATD spectrum by using the two-color laser field, where we focus on the role of the relative phase and position of two laser pulses. To analyze the population of both discrete and continuum states involved in the resultant wavepacket, we show the effective method by means of the quasicontinuum state on the Morse potential obtained by numerically diagonalizing the Fourier grid Hamiltonian (FGH). © 2009 Wiley Periodicals, Inc. Int J Quantum Chem, 2009 [source] Theoretical study on the partial potential energy surface and formation mechanism of the reactive resonance state of HO + CH4 , H2O + CH3 systemINTERNATIONAL JOURNAL OF QUANTUM CHEMISTRY, Issue 2 2008Xi Lu Abstract In the course of an extensive investigation aimed at understanding the detailed mechanism of a prototypical polyatomic reaction, several remarkable observations were uncovered. To interpret these findings, we surmise the existence of a reactive resonance in this polyatomic reaction. The concerned system is HO + CH4 , H2O + CH3, of which the partial potential energy surface is constructed by the coupling between vibrational models and reactive coordinates. Then we explain the formation mechanism of the reactive resonance state by the partial potential energy surface. Finally, we estimated the lifetime of the resonance state, and it is about 45fs. The study of the reactive resonance in a polyatomic reaction is more than just an extension from a typical atom + diatom reaction. As shown here, it holds great promise to disentangle the elusive intramolecular vibrational dynamics of the transient collision complex in the critical transition-state region. © 2007 Wiley Periodicals, Inc. Int J Quantum Chem, 2008 [source] Protective effect of total flavonoids from Bidens bipinnata L. against carbon tetrachloride-induced liver injury in miceJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 7 2007Ming-mei Zhong Bidens bipinnata L. is well known in China as a traditional Chinese medicine. This study was designed to evaluate the hepatoprotective activity of the total flavonoids of B. bipinnata L. (TFB) against carbon tetrachloride (CCI4)-induced acute liver injury in mice and to determine its mechanism of action. Oral administration of TFB at doses of 50, 100 and 200 mg kg,1 for 7 days significantly reduced the elevated relative values of liver weight, serum transaminases (alanine aminotransferase and aspartate aminotransferase) and the hepatic morphologic changes induced by CCl4 in mice. In addition, TFB markedly inhibited CCl4 -induced lipid peroxidation and enhanced the activity of the antioxidant enzymes superoxide dismutase and glutathione peroxidase. Moreover, pretreatment with TFB suppressed nitric oxide production and nuclear factor- kB activation in CCl4 -treated mice. The results suggest that TFB has significant hepatoprotective activity and its mechanism is related, at least in part, to its antioxidant properties. Further research is required to investigate the detailed mechanism of the protective effect of TFB on acute liver injury. [source] Octanol Modulation of Neuronal Nicotinic Acetylcholine Receptor Single ChannelsALCOHOLISM, Issue 11 2004Yi Zuo Background: We have previously shown that alcohols exert a dual action on neuronal nicotinic acetylcholine receptors (AChRs), with short-chain alcohols potentiating and long-chain alcohols inhibiting acetylcholine (ACh)-induced whole-cell currents. At the single-channel level, ethanol increased the channel open probability and prolonged the channel open time and burst duration. In this study, we examined the detailed mechanism of the inhibitory action of the long-chain alcohol n -octanol on the neuronal nicotinic AChR. Methods: Single-channel currents induced by application of 30 nm ACh were recorded with the patch-clamp technique from human embryonic kidney cells stably expressing the human ,4,2 AChR. Results: Several single-channel parameters were markedly changed by octanol. At least two conductance-state currents were induced by low concentrations of ACh, and octanol increased the proportion of the low-conductance-state current relative to the high-conductance-state current without changing the current amplitude. Major analyses of temporal properties of single-channel currents were performed on the high-conductance-state currents. Octanol decreased the burst duration and duration of openings within burst and prolonged the mean closed time. All of these changes contributed to the decrease in the open probability in a concentration-dependent manner. Conclusions: Several aspects of octanol action on neuronal AChRs at the single-channel level are compatible with an atypical open channel block model reported with muscle nicotinic AChRs. The potentiating action of short-chain alcohols and the inhibitory action of long-chain alcohols on the neuronal nicotinic AChR are mediated through different mechanisms. [source] Cell death: regulation by the Bcl-2 protein familyPSYCHOGERIATRICS, Issue 2006Yoshihide TSUJIMOTO Abstract An increase in mitochondrial membrane permeability is central to cell death including apoptosis and necrosis. During apoptosis, permeabilization of outer mitochondrial membrane leads to the release of several apoptogenic factors, such as cytochrome c and Smac/Diablo, into the cytoplasm that activate downstream death programs, including apoptotic proteases called caspases, although the detailed mechanism of outer mitochondrial membrane permeabilization remains elusive. Although the mitochondrial membrane permeability transition (MPT), resulting in ,, loss, mitochondrial swelling and rupture of the outer membrane has initially been proposed as a general mechanism for apoptotic permeabilization of outer mitochondrial membrane, the recent studies with cyclophilin D-deficient mice indicate that MPT regulates some forms of necrotic death, but not apoptotic death, and that MPT is involved in ischemia,reperfusion injury in heart and brain. Anti-apoptotic proteins, Bcl-2 and Bcl-xL, efficiently block not only apoptotic mitochondrial permeabilization but also MPT. The present paper focuses on the mechanisms by which Bcl-2 family members control the permeability of mitochondrial membrane during apoptosis and necrosis. [source] Influence of Ionization State on the Activation of Temocapril by hCES1: A Molecular-Dynamics StudyCHEMISTRY & BIODIVERSITY, Issue 11 2009Giulio Vistoli Abstract Temocapril is a prodrug whose hydrolysis by carboxylesterase 1 (CES1) yields the active ACE inhibitor temocaprilat. This molecular-dynamics (MD) study uses a resolved structure of the human CES1 (hCES1) to investigate some mechanistic details of temocapril hydrolysis. The ionization constants of temocapril (pK1 and pK3) and temocaprilat (pK1, pK2, and pK3) were determined experimentally and computationally using commercial algorithms. The constants so obtained were in good agreement and revealed that temocapril exists mainly in three ionic forms (a cation, a zwitterion, and an anion), whereas temocaprilat exists in four major ionic forms (a cation, a zwitterion, an anion, and a dianion). All these ionic forms were used as ligands in 5-ns MS simulations. While the cationic and zwitterionic forms of temocapril were involved in an ion-pair bond with Glu255 suggestive of an inhibitor behavior, the anionic form remained in a productive interaction with the catalytic center. As for temocaprilat, its cation appeared trapped by Glu255, while its zwitterion and anion made a slow departure from the catalytic site and a partial egress from the protein. Only its dianion was effectively removed from the catalytic site and attracted to the protein surface by Lys residues. A detailed mechanism of product egress emerges from the simulations. [source] How Does a Membrane Protein Achieve a Vectorial Proton Transfer Via Water Molecules?CHEMPHYSCHEM, Issue 18 2008Steffen Wolf Abstract We present a detailed mechanism for the proton transfer from a protein-bound protonated water cluster to the bulk water directed by protein side chains in the membrane protein bacteriorhodopsin. We use a combined approach of time-resolved Fourier transform infrared spectroscopy, molecular dynamics simulations, and X-ray structure analysis to elucidate the functional role of a hydrogen bond between Ser193 and Glu204. These two residues seal the internal protonated water cluster from the bulk water and the protein surface. During the photocycle of bacteriorhodopsin, a transient protonation of Glu204 leads to a breaking of this hydrogen bond. This breaking opens the gate to the extracellular bulk water, leading to a subsequent proton release from the protonated water cluster. We show in detail how the protein achieves vectorial proton transfer via protonated water clusters in contrast to random proton transfer in liquid water. [source] Delayed genomic and acute nongenomic action of glucocorticosteroids in seasonal allergic rhinitisEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 1 2004H.-C. Tillmann Abstract Background, Glucocorticosteroids are effective in the treatment of allergic rhinitis, a disease characterized by a variety of symptoms, e.g. rhinorrhea and itching. The time course of symptomatic relief for allergic rhinitis by steroids has not been examined in detail to date, although the onset of steroid action is one of the main discriminations between genomic and nongenomic actions of steroids. We therefore investigated the time course of subjective and objective measures of nasal affection after steroid administration in patients with allergic rhinitis following specific allergen challenge. Methods, Six female and 18 male volunteers (median age 26 years) with a history of allergic rhinitis but currently free of symptoms were included in this randomized, placebo-controlled, double-blind, three-period crossover study. A single dose of either betamethasone (60 mg), methylprednisolone (400 mg) or placebo was given intravenously, 5 min after intranasal allergen provocation. After 10, 20, 60, 150 and 240 min, nasal itching and nasal obstruction were assessed using a standardized visual analogue scale. In addition, nasal airflow was measured by anterior rhinomanometry. Results, Nasal itching was markedly reduced following either of the two steroids within 10 min after administration of study drug. Itching was depressed by 38% following betamethasone (P < 0·05) and by 18% following methylprednisolone (P = 0·07) compared with placebo. Nasal airflow and nasal obstruction were not significantly altered by steroids during the first 2 h of the study. However, after 150 min, nasal airflow was 21% rsp. 19% higher after methylprednisolone and betamethasone (P < 0·05) compared with placebo. After 240 min, nasal airflow was increased by 20% following betamethasone (P < 0·05) and by 19% following methylprednisolone. Nasal obstruction was also beneficially affected by both steroids 150 and 240 min after administration compared with placebo (P < 0·05 for both time points following betamethasone). Conclusion, This study for the first time shows rapid in vivo effects of external glucocorticosteroids in humans. Itching, a pathophysiologically complex sensation, is favourably influenced by steroids within 10 min, therefore presumably via nongenomic mechanisms. Though no detailed mechanisms can be derived from this study, steroid interaction with receptors in the central nervous system may play an important role in mediating this effect. [source] PRECLINICAL STUDY: Atypical development of behavioural sensitization to 3,4-methylenedioxymethamphetamine (MDMA, ,Ecstasy') in adolescent rats and its expression in adulthood: role of the MDMA chiralityADDICTION BIOLOGY, Issue 1 2010Nora Von Ameln ABSTRACT Despite the great popularity of 3,4-methylenedioxymethamphetamine (MDMA, Ecstasy) as a drug of abuse, not much is known about the detailed mechanisms of the acute and subchronic effects of the drug. There is especially a lack of information about the distinct behavioural effects of its optical isomers (enantiomers) R- and S-MDMA compared with the racemic RS-MDMA. For this purpose, adolescent rats were repetitively treated during two treatment stages (stage 1: days 1,10; stage 2: days 15, 17, 19) with RS-MDMA (5 or 10 mg/kg) or each of the respective enantiomers (5 mg/kg). The repeated treatment started on postnatal day (PND) 32 and locomotor activity was measured on each day by means of a photobeam-equipped activity box system. RS-MDMA or S-MDMA administration led acutely to massive hyperlocomotion and subchronically, to the development of behavioural sensitization after a short habituation period. R-MDMA was free of hyperactivating effects and even decreased locomotor behaviour upon repeated treatment. Nevertheless, co-administration of R-MDMA increased the hyperactivity of S-MDMA and made the S-MDMA induced behavioural sensitization state-dependent. The animals pre-treated with R-MDMA showed a sensitized response in adulthood when tested with RS-MDMA. Our results indicated that even in the absence of substantial neurotoxicity, both MDMA enantiomers can lead to long-term changes in brain circuitry and concomitant behavioural changes when repeatedly administered in adolescence. The sensitization development was most pronounced in the animals treated with S- and RS-MDMA; the animals with R-MDMA did not develop sensitization under repeated treatment but expressed a sensitized response when challenged with RS-MDMA. [source] In vitro differentiation of lineage-negative bone marrow cells into microglia-like cellsEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 7 2010Daisuke Noto Abstract Microglia are believed to be the only resident immune cells in the CNS, originating from hematopoietic-derived myeloid cells and invading the CNS during development. However, the detailed mechanisms of differentiation and transformation of microglial cells are not fully understood. Here, we demonstrate that murine microglial cells show two morphological forms in vitro, namely, small round cells expressing CD11b, Iba1, triggering receptor expressing on myeloid cells-2 (TREM2), and weakly expressing major histocompatibility complex class II and large flat cells expressing only CD11b and Iba1. Moreover, lineage-negative bone marrow (LN) cells cultured with primary mixed glial culture cells could differentiate into only the small round microglia-like cells, despite the absence of CCR2 and Gr-1 expression. Addition of macrophage colony stimulating factor (M-CSF) to LN cell culture allowed the proliferation and expression of TREM2 in LN cells, and the addition of neutralizing anti-M-CSF antibodies suppressed the proliferation of LN cells despite the expression of TREM2. When LN cells were cultured with M-CSF, the number of small round cells in the culture was considerably low, indicating that the small round morphology of the immature cells is not maintained in the presence of only M-CSF. On the other hand, when LN cells were grown in the presence of astrocytes, the small round cells were maintained at a concentration of approximately 30% of the total population. Therefore, cell,cell contact with glial cells, especially astrocytes, may be necessary to maintain the small round shape of the immature cells expressing TREM2. [source] Material stiffness, branching pattern and soil matric potential affect the pullout resistance of model root systemsEUROPEAN JOURNAL OF SOIL SCIENCE, Issue 6 2007S. B. Mickovski Summary Understanding of the detailed mechanisms of how roots anchor in and reinforce soil is complicated by the variability and complexity of both materials. This study controlled material stiffness and architecture of root analogues, by using rubber and wood, and also employed real willow root segments, to investigate the effect on pullout resistance in wet and air-dry sand. The architecture of model roots included either no laterals (tap-root) or a single pair at two different locations (herringbone and dichotomous). During pullout tests, data on load and displacement were recorded. These studies were combined with Particle Image Velocimetry (PIV) image analysis of the model root-soil system at a transparent interface during pullout to increase understanding of mechanical interactions along the root. Model rubber roots with small stiffness had increasing pullout resistance as the branching and the depth of the lateral roots increased. Similarly, with the stiff wooden root models, the models with lateral roots embedded deeper showed greatest resistance. PIV showed that rubber model roots mobilized their interface shear strength progressively whilst rigid roots mobilized it equally and more rapidly over the whole root length. Soil water suction increased the pullout resistance of the roots by increasing the effective stress and soil strength. Separate pullout tests conducted on willow root samples embedded in sand showed similar behaviour to the rigid model roots. These tests also demonstrated the effect of the root curvature and rough interface on the maximum pullout resistance. [source] Identification of genetic networks involved in the cell growth arrest and differentiation of a rat astrocyte cell line RCG-12,JOURNAL OF CELLULAR BIOCHEMISTRY, Issue 6 2007Ichiro Takasaki Abstract The purpose of the present study is to establish and characterize a conditionally immortalized astrocyte cell line and to clarify the genetic networks responsible for the cell growth arrest and differentiation. A conditionally immortalized astrocyte cell line, RCG-12, was established by infecting primary cultured rat cortical glia cells with a temperature-sensitive simian virus 40 large T-antigen. At a permissive temperature of 33°C, the large T-antigen was expressed and cells grew continuously. On the other hand, the down-regulation of T-antigen at a non-permissive temperature of 39°C led to growth arrest and differentiation. The cells expressed astrocyte-expressed genes such as glial fibrillary acidic protein. Interestingly, the differentiated condition induced by the non-permissive temperature significantly elevated the expression levels of several astrocyte-expressed genes. To identify the detailed mechanisms by which non-permissive temperature-induced cell growth arrest and differentiation, we performed high-density oligonucleotide microarray analysis and found that 556 out of 15,923 probe sets were differentially expressed 2.0-fold. A computational gene network analysis revealed that a genetic network containing up-regulated genes such as RB, NOTCH1, and CDKN1A was associated with the cellular growth and proliferation, and that a genetic network containing down-regulated genes such as MYC, CCNB1, and IGF1 was associated with the cell cycle. The established cell line RCG-12 retains some characteristics of astrocytes and should provide an excellent model for studies of astrocyte biology. The present results will also provide a basis for understanding the detailed molecular mechanisms of the growth arrest and differentiation of astrocytes. J. Cell. Biochem. 102: 1472,1485, 2007. © 2007 Wiley-Liss, Inc. [source] Upregulation of P-cadherin expression in the lesional skin of pemphigus, Hailey-Hailey disease and Darier's diseaseJOURNAL OF CUTANEOUS PATHOLOGY, Issue 6 2001Megumi Hakuno Background: Autoimmune blistering diseases, pemphigus vulgaris (PV) and pemphigus foliaceus (PF), are known to be caused by binding of autoantibodies to the desmosomal cadherins, desmoglein 3 and desmoglein 1, respectively. Recently, mutations in the genes coding Ca2+ pumps leads to inherited blistering diseases, Hailey-Hailey disease (HHD) and Darier's disease (DD). Cadherins are a family of Ca2+ -dependent cell adhesion molecules and P-cadherin is one of the major cadherins expressed in the epidermis. Although detailed mechanisms of acantholysis of these blistering diseases have not been fully clarified, abnormal expression of cadherins caused by altered Ca2+ concentration due to the binding of autoantibodies to cell surface or by mutations in Ca2+ pumps is suggested to be involved in mechanisms of acantholysis of these atuoimmune and inherited blistering diseases. The purpose of the present study was to determine whether altered P-cadherin expression is present in these diseases. Method: Distribution patterns of P-cadherin in skin specimens from patients with PV (n=2), PF (n=2), HHD (n=4) and DD (n=3), were examined with confocal laser scanning microscopy using two anti-P-cadherin antibodies, 6A9 and NCC-CAD-299. Results: In normal control skin, P-cadherin expression was restricted to the basal layer. In contrast, positive immunostaining of P-cadherin was observed not only in the basal cells, but also in the suprabasal cells in lesional skin of all the acantholytic diseases. Conclusions: The present results clearly demonstrated that upregulation of P-cadherin expression occurs in the acantholysis in all the four blistering diseases PV, PF, HHD and DD. Upregulation of P-cadherin may be involved in the pathomechanism of both the autoimmune blistering diseases and the inherited blistering diseases. [source] N-terminal residues regulate proteasomal degradation of AANATJOURNAL OF PINEAL RESEARCH, Issue 3 2010Zheping Huang Abstract:, Serotonin N -acetyltransferase (AANAT) catalyzes the conversion of serotonin to N -acetylserotonin, which is the immediate precursor for formation of melatonin. Although it is known that AANAT is degraded via the proteasomal proteolysis, detailed mechanisms are not defined. In this paper, we tested the in vivo role of proteasome inhibition on AANAT activity and melatonin release and examined the amino acid residues in AANAT that contribute to the proteasome degradation. We have shown that inhibition of proteasome activities in vivo in the intact pineal gland fails to prevent the light-induced suppression of melatonin secretion. Furthermore, in cell lines stably expressing AANAT, inhibition of proteasomal proteolysis, which resulted in a large accumulation of AANAT protein, similarly failed to increase AANAT enzyme activity proportional to the amount of proteins accumulated. Site-directed mutagenesis analysis of AANAT revealed that the AANAT degradation is independent of lysine and the two surface cysteine residues. Deletion analysis of N-terminus identified the second amino acid leucine (L2) as the key residue that contributes to the proteasomal proteolysis of AANAT protein. These results suggest that rat AANAT protein is degraded via the N-end rule pathway of proteasomal proteolysis and the leucine at the N-terminus appears to be the key residue recognized by N-end rule pathway. [source] Pitting corrosion on 316L pipes in terephthalic acid (TA) dryerMATERIALS AND CORROSION/WERKSTOFFE UND KORROSION, Issue 11 2009Y. Gong Abstract Grade 316L is a type of austenitic stainless steel with ultra-low carbon content and it exhibits superior corrosion resistance. However, pitting is always observed in 316L steel when it is exposed to media containing halide ions. In the present study, we found that in the presence of acetate acid (HAc) containing chloride or bromide ions, pitting occurred on the surface of the rotary steam pipes with the matrix material of 316L steel in terephthalic acid (TA) dryer. In order to identify the causes of the failure, metallographic structures and chemical compositions of the matrix material were inspected by an optical microscope (OM) and a photoelectric direct reading spectrometer. Beside these, scanning electron microscopy (SEM) and energy dispersive spectroscopy (EDS) as well as ion chromatography (IC) were used to analyze the micromorphologies of the corrosion pits and the chemical compositions of the corrosion deposits within them. Analysis of the results revealed the sources of halide ions and the factors accelerating the corrosion rate. Beside these, detailed mechanisms of pitting were discussed and six out of all the seven theoretical morphologies of pitting features were obtained in practice. [source] Recombination, repair and replication in the pathogenic Neisseriae: the 3 R,s of molecular genetics of two human-specific bacterial pathogensMOLECULAR MICROBIOLOGY, Issue 1 2003Kimberly A. Kline Summary Most of the detailed mechanisms that have been established for the molecular biological processes that mediate recombination, repair and replication of DNA have come from studies of the Escherichia coli paradigm. The human specific pathogens, Neisseria gonorrhoeae and N. meningitidis, are Gram-negative bacteria that have some molecular processes that are similar to E. coli and others that appear to be divergent. We propose that the pathogenic Neisseriae have evolved a specialized collection of molecular mechanisms to adapt to life limited to human hosts. In this MicroReview, we explore what is known about the basic processes of DNA repair, DNA recombination (genetic exchange and pilin variation) and DNA replication in these human specific pathogens. [source] Structure and function of the Mur enzymes: development of novel inhibitorsMOLECULAR MICROBIOLOGY, Issue 1 2003Ahmed El Zoeiby Summary One of the biggest challenges for recent medical research is the continuous development of new antibiotics interacting with bacterial essential mechanisms. The machinery for peptidoglycan biosynthesis is a rich source of crucial targets for antibacterial chemotherapy. The cytoplasmic steps of the biosynthesis of peptidoglycan precursor, catalysed by a series of Mur enzymes, are excellent candidates for drug development. There has been growing interest in these bacterial enzymes over the last decade. Many studies attempted to understand the detailed mechanisms and structural features of the key enzymes MurA to MurF. Only MurA is inhibited by a known antibiotic, fosfomycin. Several attempts made to develop novel inhibitors of this pathway are discussed in this review. Three novel inhibitors of MurA were identified recently. 4-Thiazolidinone compounds were designed as MurB inhibitors. Many phosphinic acid derivatives and substrate analogues were identified as inhibitors of the MurC to MurF amino acid ligases. [source] Cobalt Coordination and Clustering in ,-Co(OH)2 Revealed by Synchrotron X-ray Total ScatteringCHEMISTRY - A EUROPEAN JOURNAL, Issue 33 2010James Abstract Structures of layered metal hydroxides are not well described by traditional crystallography. Total scattering from a synthesis-controlled subset of these materials, as described here, reveals that different cobalt coordination polyhedra cluster within each layer on short length scales, offering new insights and approaches for understanding the properties of these and related layered materials. Structures related to that of brucite [Mg(OH)2] are ubiquitous in the mineral world and offer a variety of useful functions ranging from catalysis and ion-exchange to sequestration and energy transduction, including applications in batteries. However, it has been difficult to resolve the atomic structure of these layered compounds because interlayer disorder disrupts the long-range periodicity necessary for diffraction-based structure determination. For this reason, traditional unit-cell-based descriptions have remained inaccurate. Here we apply, for the first time to such layered hydroxides, synchrotron X-ray total scattering methods,analyzing both the Bragg and diffuse components,to resolve the intralayer structure of three different ,-cobalt hydroxides, revealing the nature and distribution of metal site coordination. The different compounds with incorporated chloride ions have been prepared with kinetic control of hydrolysis to yield different ratios of octahedrally and tetrahedrally coordinated cobalt ions within the layers, as confirmed by total scattering. Real-space analyses indicate local clustering of polyhedra within the layers, manifested in the weighted average of different ordered phases with fixed fractions of tetrahedrally coordinated cobalt sites. These results, hidden from an averaged unit-cell description, reveal new structural characteristics that are essential to understanding the origin of fundamental material properties such as color, anion exchange capacity, and magnetic behavior. Our results also provide further insights into the detailed mechanisms of aqueous hydrolysis chemistry of hydrated metal salts. We emphasize the power of the methods used here for establishing structure,property correlations in functional materials with related layered structures. [source] | |||||||||||||||||||