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Sample records for acetyl radicals

  1. Acetyl radical generation in cigarette smoke: Quantification and simulations

    Hu, Na; Green, Sarah A.

    2014-10-01

    Free radicals are present in cigarette smoke and can have a negative effect on human health. However, little is known about their formation mechanisms. Acetyl radicals were quantified in tobacco smoke and mechanisms for their generation were investigated by computer simulations. Acetyl radicals were trapped from the gas phase using 3-amino-2, 2, 5, 5-tetramethyl-proxyl (3AP) on solid support to form stable 3AP adducts for later analysis by high-performance liquid chromatography (HPLC), mass spectrometry/tandem mass spectrometry (MS-MS/MS) and liquid chromatography-mass spectrometry (LC-MS). Simulations were performed using the Master Chemical Mechanism (MCM). A range of 10-150 nmol/cigarette of acetyl radical was measured from gas phase tobacco smoke of both commercial and research cigarettes under several different smoking conditions. More radicals were detected from the puff smoking method compared to continuous flow sampling. Approximately twice as many acetyl radicals were trapped when a glass fiber particle filter (GF/F specifications) was placed before the trapping zone. Simulations showed that NO/NO2 reacts with isoprene, initiating chain reactions to produce hydroxyl radical, which abstracts hydrogen from acetaldehyde to generate acetyl radical. These mechanisms can account for the full amount of acetyl radical detected experimentally from cigarette smoke. Similar mechanisms may generate radicals in second hand smoke.

  2. Generation of acetyl free radicals by radiolysis: comparison of free radicals generated from acetaldehyde and ethylene-glycol

    The optical absorption spectra of the intermediates obtained by pulse radiolysis of N2O-saturated solutions of acetaldehyde or ethylene-glycol and the kinetics of their decays have been investigated. Results suggest that the OH· radical reactions with acetaldehyde or ethylene-glycol produce acetyl and formylmethyl radicals. Besides, these radicals are shown to reduce ferricytochrome c

  3. Structure and Reactivity of the N-Acetyl-Cysteine Radical Cation and Anion: Does Radical Migration Occur?

    Osburn, S.; G. Berden,; Oomens, J.; O' Hair, R. A. J.; Ryzhov, V.

    2011-01-01

    The structure and reactivity of the N-acetyl-cysteine radical cation and anion were studied using ion-molecule reactions, infrared multi-photon dissociation (IRMPD) spectroscopy, and density functional theory (DFT) calculations. The radical cation was generated by first nitrosylating the thiol of N-

  4. Sources, Sinks and Cycling of Acetyl Radicals in Tobacco Smoke: A Model for Biomass Burning Chemistry

    Hu, N.; Green, S. A.

    2012-12-01

    Smoke near the source of biomass burning contains high concentrations of reactive compounds, with NO and CH3CHO concentrations four to six orders of magnitude higher than those in the ambient atmosphere. Tobacco smoke represents a special case of biomass burning that is quite reproducible in the lab and may elucidate early processes in smoke from other sources. The origins, identities, and reactions of radical species in tobacco smoke are not well understood, despite decades of study on the concentrations and toxicities of the relatively stable compounds in smoke. We propose that reactions of NO2 and aldehydes are a primary source for transient free radicals in tobacco smoke, which contrasts with the long-surmised mechanism of reaction between NO2 and dienes. The objective of this study was to investigate the sources, sinks and cycling of acetyl radical in tobacco smoke. Experimentally, the production of acetyl radical was demonstrated both in tobacco smoke and in a simplified mixture of air combined with NO and acetaldehyde, both of which are significant components of smoke. Acetyl radicals were trapped from the gas phase using 3-amino-2, 2, 5, 5-tetramethyl-proxyl (3AP) on solid support to form stable 3AP adducts for later analysis by high performance liquid chromatography (HPLC), mass spectrometry/tandem mass spectrometry (MS-MS/MS) and liquid chromatography-mass spectrometry (LC-MS). The dynamic nature of radical cycling in smoke makes it impossible to define a fixed concentration of radical species; 2.15×e13-3.18×e14 molecules/cm3 of acetyl radicals were measured from different cigarette samples and smoking conditions. Matlab was employed to simulate reactions of NO, NO2, O2, and a simplified set of organic compounds known to be present in smoke, with a special emphasis on acetaldehyde and the acetyl radical. The NO2/acetaldehyde mechanism initiates a cascade of chain reactions, which accounts for the most prevalent known carbon-centered radicals found in

  5. Closing the peroxy acetyl (PA radical budget: observations of acyl peroxy nitrates (PAN, PPN, and MPAN during BEARPEX 2007

    B. W. LaFranchi

    2009-04-01

    Full Text Available Acyl peroxy nitrates (APNs, also known as PANs are formed from the oxidation of aldehydes and other oxygenated VOC (oVOC in the presence of NO2. Formation of APNs suppresses NOx (NOx≡NO+NO2 in urban areas and enhances NOx downwind in urban plumes, increasing the rate of ozone production throughout an urban plume. APNs also redistribute NOx on global scales, enhancing NOx and thus ozone production. There are both anthropogenic and biogenic oVOC precursors to APNs, but a detailed evaluation of their chemistry against observations has proven elusive. Here we describe measurements of PAN, PPN, and MPAN along with the majority of chemicals that participate in their production and loss, including OH, HO2, numerous oVOC, and NO2. Observations were made during the Biosphere Effects on AeRosols and Photochemistry Experiment (BEARPEX 2007 in the outflow of the Sacramento urban plume. These observations are used to evaluate a detailed chemical model of APN ratios and concentrations. We find the ratios of APNs are nearly independent of the loss mechanisms and thus an especially good test of our understanding of their sources. We show that oxidation of methylvinyl ketone, methacrolein, methyl glyoxal, biacetyl and acetaldehyde are all significant sources of the PAN+peroxy acetyl (PA radical reservoir, with methylvinyl ketone (MVK often being the primary non-acetaldehyde source. At high temperatures, oxidation of non-acetaldehyde PA radical sources contributes over 60% to the total PA production rate. An analysis of absolute APN concentrations reveals a missing APN sink that can be resolved by increasing the PA+∑RO2 rate constant by a factor of 3.

  6. Radicals

    Jahn, Ullrich; Cornils, B.

    Weinheim: Wiley-VCH, 2013 - (Cornils, B.; Herrmann, W.; Wong, C.; Zanthoff, H.), s. 1897-1898 ISBN 978-3-527-33307-3 Institutional support: RVO:61388963 Keywords : radicals * enzymatic catalysis * coenzyme B12 * ribonucleotide reductase * mutases Subject RIV: CC - Organic Chemistry

  7. Radical formation of irradiated α-alanine and N-acetyl alanine with heavy ion beams. Effects of the irradiation temperature

    The characteristics of irradiation with C290 MeV/u ion beams were investigated using X-band electron spin resonance (ESR) spectroscopy for a polycrystalline powder of L-α-alanine at from 77K to 310K. The formed main radicals at 190K∼310K were the deamino radical and the decarboxyl radical. Because of the first-derivative ESR, decarboxyl radical showed an expanded spectral width and a lower peak height because of its amino hydrogen and nitrogen than that of the same amount of deamino radical. The ESR of irradiated L-α-alanine predominantly indicates the spectrum of the deamino radical. On the irradiated, L-α-alanine at from 77K to 310K ESR showed 1:4:6:4:1 lines at 220K and at room temperature, which indicate that the methyl group of the radical was rotating. On the other hand, at 77K ESR the spectrum showed nearly 1:5:5:5:1 lines, like the teeth of a saw, on samples irradiated at 270K∼350K (range IV), and 1:4:6:4:1 lines for those irradiated at 180K∼260K (range II and III), respectively. It is considered that the radical conformation of the deamino radical is planar (most stable conformation) on an irradiated sample in range IV, and a pyramidal structure on the irradiated sample in ranges II and III. (author)

  8. Acetylation dynamics and stoichiometry in Saccharomyces cerevisiae

    Weinert, Brian Tate; Iesmantavicius, Vytautas; Moustafa, Tarek; Schölz, Christian; Wagner, Sebastian A; Magnes, Christoph; Zechner, Rudolf; Choudhary, Chuna Ram

    2014-01-01

    Lysine acetylation is a frequently occurring posttranslational modification; however, little is known about the origin and regulation of most sites. Here we used quantitative mass spectrometry to analyze acetylation dynamics and stoichiometry in Saccharomyces cerevisiae. We found that acetylation...

  9. Acetyltransferase and human hemoglobin acetylation

    A minor component of human fetal hemoglobin (Hb F) is acetylated at the amino-terminus of the γ-globin chains. A similar minor component of Hb F is formed during translation of cord blood mRNA in the rabbit reticulocyte lysate system. The acetylation appeared to be enzymatic. This system contains an acetyltransferase capable of acetylating histones and hemoglobins. The enzyme, partially purified by histone-Sepharose affinity chromatography was capable of incorporating labeled acetyl- group from 1-[14C-acetyl]-CoA into both human Hb F0 and HB A0, but at a lower rate than for histones. Characterization of the labeled products indicated that the α-chains of both hemoglobins were being acetylated presumably at a lysyl-residue, but in the case of Hb F0 the amino-terminus of the γ-globin chains was acetylated as well. While histone-Sepharose bound more than 95% of the enzyme, Sepharose linked Hb F0, γ-globin chains, and Hb Bart's bound 14, 5, and 12% of the activity, respectively. Enzyme bound to these resins was not any more active on the hemoglobins than was the enzyme bound to the histone-Sepharose. The histone-Sepharose was also used to detect the enzyme in human cord blood red cells separated by dextran 40 density gradient centrifugation. Activity was found mostly in the young cells, and was directly related to the number of reticulocytes present in any one fraction

  10. Regulation of intermediary metabolism by protein acetylation

    Guan, Kun-Liang; Xiong, Yue

    2010-01-01

    Extensive studies during the past four decades have identified important roles for lysine acetylation in the regulation of nuclear transcription. Recent proteomic analyses on protein acetylation uncovered a large number of acetylated proteins in the cytoplasm and mitochondria, including most enzymes involved in intermediate metabolism. Acetylation regulates metabolic enzymes by multiple mechanisms, including via enzymatic activation or inhibition, and by influencing protein stability. Convers...

  11. Fatal Intoxication with Acetyl Fentanyl.

    Cunningham, Susan M; Haikal, Nabila A; Kraner, James C

    2016-01-01

    Among the new psychoactive substances encountered in forensic investigations is the opioid, acetyl fentanyl. The death of a 28-year-old man from recreational use of this compound is reported. The decedent was found in the bathroom of his residence with a tourniquet secured around his arm and a syringe nearby. Postmortem examination findings included marked pulmonary and cerebral edema and needle track marks. Toxicological analysis revealed acetyl fentanyl in subclavian blood, liver, vitreous fluid, and urine at concentrations of 235 ng/mL, 2400 ng/g, 131 ng/mL, and 234 ng/mL, respectively. Acetyl fentanyl was also detected in the accompanying syringe. Death was attributed to recreational acetyl fentanyl abuse, likely through intravenous administration. The blood acetyl fentanyl concentration is considerably higher than typically found in fatal fentanyl intoxications. Analysis of this case underscores the need for consideration of a wide range of compounds with potential opioid-agonist activity when investigating apparent recreational drug-related deaths. PMID:26389815

  12. Radical Evil

    Carlos Manrique

    2007-12-01

    Full Text Available There is an aporia in Kant’s analysis of evil: he defines radical evilas an invisible disposition of the will, but he also demands an inferential connection between visible evil actions and this invisible disposition. This inference,however, undermines the radical invisibility of radical evil according to Kant’s own definition of the latter. Noting how this invisibility of moral worth is a distinctive feature of Kant’s approach to the moral problem, the paper then asks why, in the Groundwork, he nonetheless forecloses a question about evil that seems to be consistent with this approach. It is argued that to account for this aporia and this foreclosure, one has to interrogate the way in which the category of religion orients Kant’s incipient philosophy of history in Die Religion.

  13. Protein Acetylation in Archaea, Bacteria, and Eukaryotes

    Jörg Soppa

    2010-01-01

    Full Text Available Proteins can be acetylated at the alpha-amino group of the N-terminal amino acid (methionine or the penultimate amino acid after methionine removal or at the epsilon-amino group of internal lysines. In eukaryotes the majority of proteins are N-terminally acetylated, while this is extremely rare in bacteria. A variety of studies about N-terminal acetylation in archaea have been reported recently, and it was revealed that a considerable fraction of proteins is N-terminally acetylated in haloarchaea and Sulfolobus, while this does not seem to apply for methanogenic archaea. Many eukaryotic proteins are modified by differential internal acetylation, which is important for a variety of processes. Until very recently, only two bacterial proteins were known to be acetylation targets, but now 125 acetylation sites are known for E. coli. Knowledge about internal acetylation in archaea is extremely limited; only two target proteins are known, only one of which—Alba—was used to study differential acetylation. However, indications accumulate that the degree of internal acetylation of archaeal proteins might be underestimated, and differential acetylation has been shown to be essential for the viability of haloarchaea. Focused proteomic approaches are needed to get an overview of the extent of internal protein acetylation in archaea.

  14. Acetyl-Phosphate Is a Critical Determinant of Lysine Acetylation in E. coli

    Weinert, Brian T; Iesmantavicius, Vytautas; Wagner, Sebastian A;

    2013-01-01

    Lysine acetylation is a frequently occurring posttranslational modification in bacteria; however, little is known about its origin and regulation. Using the model bacterium Escherichia coli (E. coli), we found that most acetylation occurred at a low level and accumulated in growth-arrested cells in...... acetylate lysine residues in vitro and that AcP levels are correlated with acetylation levels in vivo, suggesting that AcP may acetylate proteins nonenzymatically in cells. These results uncover a critical role for AcP in bacterial acetylation and indicate that most acetylation in E. coli occurs at a low...

  15. Swelling of acetylated wood in organic liquids

    Obataya, E; Obataya, Eiichi; Gril, Joseph

    2005-01-01

    To investigate the affinity of acetylated wood for organic liquids, Yezo spruce wood specimens were acetylated with acetic anhydride, and their swelling in various liquids were compared to those of untreated specimens. The acetylated wood was rapidly and remarkably swollen in aprotic organic liquids such as benzene and toluene in which the untreated wood was swollen only slightly and/or very slowly. On the other hand, the swelling of wood in water, ethylene glycol and alcohols remained unchanged or decreased by the acetylation. Consequently the maximum volume of wood swollen in organic liquids was always larger than that in water. The effect of acetylation on the maximum swollen volume of wood was greater in liquids having smaller solubility parameters. The easier penetration of aprotic organic liquids into the acetylated wood was considered to be due to the scission of hydrogen bonds among the amorphous wood constituents by the substitution of hydroxyl groups with hydrophobic acetyl groups.

  16. Radical Geography

    H. Hataminezhad

    2012-07-01

    Full Text Available Interdisciplinary sciences emerging and specialization were result of historical conditions. Lack of common and grand theories have caused social sciences such as Geography disintegrated to many courses. The Geography science has been divided two main courses, Physical and Human through the time. Every one used another similar science in theoretical principles and methodologies for their domain development and strengthening of their bases. The Human Geography was influenced by Anthropology during nineteenth century and was affected by nineteenth century and dawn twentieth century by Sociology and from mid twentieth century until present time by Biological sciences, Psychology, Political economics and social theories. Radical Geography was one of the Human Geography branches that was influenced by Political economics and left ideology. Radical Geography emphasizes on investigation about quality of life in different spaces and attempts to change socio-economic and spatial relationships, therefore critical Geography is one of its similar approaches.

  17. Histone Acetylation in Drug Addiction

    Renthal, William; Nestler, Eric J.

    2009-01-01

    Regulation of chromatin structure through post-translational modifications of histones (e.g. acetylation) has emerged as an important mechanism to translate a variety of environmental stimuli, including drugs of abuse, into specific changes in gene expression. Since alterations in gene expression are thought to contribute to the development and maintenance of the addicted state, recent efforts are aimed at identifying how drugs of abuse alter chromatin structure and the enzymes which regulate...

  18. Roaming Radicals

    Bowman, Joel M.; Shepler, Benjamin C.

    2011-05-01

    Roaming is a recently verified unusual pathway to molecular products from unimolecular dissociation of an energized molecule. Here we present the evidence for this pathway for H2CO and CH3CHO. Theoretical analysis shows that this path visits the plateau region of the potential energy surface near dissociation to radical products. It is not clear whether roaming is a distinct isolated pathway, in addition to the conventional one via the well-known molecular saddle-point transition state. Evidence is presented to suggest that the two pathways may originate from a single, but highly complicated, dividing surface. Other examples of unusual reaction dynamics are also reviewed.

  19. Analysis of acetylation stoichiometry suggests that SIRT3 repairs nonenzymatic acetylation lesions.

    Weinert, Brian T; Moustafa, Tarek; Iesmantavicius, Vytautas; Zechner, Rudolf; Choudhary, Chunaram

    2015-11-01

    Acetylation is frequently detected on mitochondrial enzymes, and the sirtuin deacetylase SIRT3 is thought to regulate metabolism by deacetylating mitochondrial proteins. However, the stoichiometry of acetylation has not been studied and is important for understanding whether SIRT3 regulates or suppresses acetylation. Using quantitative mass spectrometry, we measured acetylation stoichiometry in mouse liver tissue and found that SIRT3 suppressed acetylation to a very low stoichiometry at its target sites. By examining acetylation changes in the liver, heart, brain, and brown adipose tissue of fasted mice, we found that SIRT3-targeted sites were mostly unaffected by fasting, a dietary manipulation that is thought to regulate metabolism through SIRT3-dependent deacetylation. Globally increased mitochondrial acetylation in fasted liver tissue, higher stoichiometry at mitochondrial acetylation sites, and greater sensitivity of SIRT3-targeted sites to chemical acetylation in vitro and fasting-induced acetylation in vivo, suggest a nonenzymatic mechanism of acetylation. Our data indicate that most mitochondrial acetylation occurs as a low-level nonenzymatic protein lesion and that SIRT3 functions as a protein repair factor that removes acetylation lesions from lysine residues. PMID:26358839

  20. A Method to determine lysine acetylation stoichiometries

    Nakayasu, Ernesto S.; Wu, Si; Sydor, Michael A.; Shukla, Anil K.; Weitz, Karl K.; Moore, Ronald J.; Hixson, Kim K.; Kim, Jong Seo; Petyuk, Vladislav A.; Monroe, Matthew E.; Pasa-Tolic, Ljiljana; Qian, Weijun; Smith, Richard D.; Adkins, Joshua N.; Ansong, Charles

    2014-07-21

    A major bottleneck to fully understanding the functional aspects of lysine acetylation is the lack of stoichiometry information. Here we describe a mass spectrometry method using a combination of isotope labeling and detection of a diagnostic fragment ion to determine the stoichiometry of lysine acetylation on proteins globally. Using this technique, we determined the modification occupancy on hundreds of acetylated peptides from cell lysates and cross-validated the measurements via immunoblotting.

  1. Analysis of acetylation stoichiometry suggests that SIRT3 repairs nonenzymatic acetylation lesions

    Weinert, Brian T; Moustafa, Tarek; Iesmantavicius, Vytautas;

    2015-01-01

    Acetylation is frequently detected on mitochondrial enzymes, and the sirtuin deacetylase SIRT3 is thought to regulate metabolism by deacetylating mitochondrial proteins. However, the stoichiometry of acetylation has not been studied and is important for understanding whether SIRT3 regulates or...... suppresses acetylation. Using quantitative mass spectrometry, we measured acetylation stoichiometry in mouse liver tissue and found that SIRT3 suppressed acetylation to a very low stoichiometry at its target sites. By examining acetylation changes in the liver, heart, brain, and brown adipose tissue of...... fasted mice, we found that SIRT3-targeted sites were mostly unaffected by fasting, a dietary manipulation that is thought to regulate metabolism through SIRT3-dependent deacetylation. Globally increased mitochondrial acetylation in fasted liver tissue, higher stoichiometry at mitochondrial acetylation...

  2. Acetylation of woody lignocellulose: significance and regulation

    Prashant Mohan-Anupama Pawar

    2013-05-01

    Full Text Available Non-cellulosic cell wall polysaccharides constitute approximately one quarter of usable biomass for human exploitation. In contrast to cellulose, these components are usually substituted by O-acetyl groups, which affect their properties and interactions with other polymers, thus affecting their solubility and extractability. However, details of these interactions are still largely obscure. Moreover, polysaccharide hydrolysis to constituent monosaccharides, is hampered by the presence of O-acetyl groups, necessitating either enzymatic (esterase or chemical de-acetylation, increasing the costs and chemical consumption. Reduction of polysaccharide acetyl content in planta is a way to modify lignocellulose towards improved saccharification. In this review we: 1 summarize literature on lignocellulose acetylation in different tree species, 2 present data and current hypotheses concerning the role of O-acetylation in determining woody lignocellulose properties, 3 describe plant proteins involved in lignocellulose O-acetylation, 4 give examples of microbial enzymes capable to de-acetylate lignocellulose, and 5 discuss prospects for exploiting these enzymes in planta to modify xylan acetylation.

  3. Acetylation-Mediated Suppression of Transcription-Independent Memory: Bidirectional Modulation of Memory by Acetylation

    Katja Merschbaecher; Jakob Haettig; Uli Mueller

    2012-01-01

    Learning induced changes in protein acetylation, mediated by histone acetyl transferases (HATs), and the antagonistic histone deacetylases (HDACs) play a critical role in memory formation. The status of histone acetylation affects the interaction between the transcription-complex and DNA and thus regulates transcription-dependent processes required for long-term memory (LTM). While the majority of studies report on the role of elevated acetylation in memory facilitation, we address the impact...

  4. UNIQUE ACETYLATION OF OLIGOSACCHARIDES BY TRICHODERMA REESEI ACETYL ESTERASE IN WATER - VINYL ACETATE MIXTURE

    Purified T. reesei RUT C-30 acetyl esterase catalyzes acetyl transfer to a variety of carbohydrates in water in the presence of vinyl acetate as the acetyl group donor. The degree of conversion and the number of formed acetates depended on the acceptor used. With some acceptors, such as methyl or ...

  5. Acetyl coenzyme A: alpha-glucosaminide N-acetyltransferase. Evidence for a transmembrane acetylation mechanism

    The lysosomal membrane enzyme acetyl-CoA: alpha-glucosaminide N-acetyltransferase catalyzes the transfer of an acetyl group from acetyl-CoA to terminal alpha-linked glucosamine residues of heparan sulfate. The reaction mechanism was examined using highly purified lysosomal membranes from rat liver. The reaction was followed by measuring the acetylation of a monosaccharide acetyl acceptor, glucosamine. The enzyme reaction was optimal above pH 5.5, and a 2-3-fold stimulation of activity was observed when the membranes were assayed in the presence of 0.1% taurodeoxycholate. Double reciprocal analysis and product inhibition studies indicated that the enzyme works by a Di-Iso Ping Pong Bi Bi mechanism. Further evidence to support this mechanism was provided by characterization of the enzyme half-reactions. Membranes incubated with acetyl-CoA and [3H]CoA were found to produce acetyl-[3H]CoA. This exchange was optimal at pH values above 7.0. Treating membranes with [3H] acetyl-CoA resulted in the formation of an acetyl-enzyme intermediate. The acetyl group could then be transferred to glucosamine, forming [3H]N-acetylglucosamine. The transfer of the acetyl group from the enzyme to glucosamine was optimal between pH 4 and 5. The results suggest that acetyl-CoA does not cross the lysosomal membrane. Instead, the enzyme is acetylated on the cytoplasmic side of the lysosome and the acetyl group is then transferred to the inside where it is used to acetylate heparan sulfate

  6. Proteomic profiling of lysine acetylation in Pseudomonas aeruginosa reveals the diversity of acetylated proteins.

    Ouidir, Tassadit; Cosette, Pascal; Jouenne, Thierry; Hardouin, Julie

    2015-07-01

    Protein lysine acetylation is a reversible and highly regulated post-translational modification with the well demonstrated physiological relevance in eukaryotes. Recently, its important role in the regulation of metabolic processes in bacteria was highlighted. Here, we reported the lysine acetylproteome of Pseudomonas aeruginosa using a proteomic approach. We identified 430 unique peptides corresponding to 320 acetylated proteins. In addition to the proteins involved in various metabolic pathways, several enzymes contributing to the lipopolysaccharides biosynthesis were characterized as acetylated. This data set illustrated the abundance and the diversity of acetylated lysine proteins in P. aeruginosa and opens opportunities to explore the role of the acetylation in the bacterial physiology. PMID:25900529

  7. Investigation of acetyl migrations in furanosides

    Migaud ME

    2006-07-01

    Full Text Available Abstract Standard reaction conditions for the desilylation of acetylated furanoside (riboside, arabinoside and xyloside derivatives facilitate acyl migration. Conditions which favour intramolecular and intermolecular mechanisms have been identified with intermolecular transesterifications taking place under mild basic conditions when intramolecular orthoester formations are disfavoured. In acetyl ribosides, acyl migration could be prevented when desilylation was catalysed by cerium ammonium nitrate.

  8. Synthesis of (2-pyridyl)-Acetyl Chitosan and Its Antioxidant Activity

    Li, Rongchun [Dezhou Univ., Dezhou (China)

    2011-10-15

    In this paper, chloracetyl chitosan (CACTS) was prepared at first. In the molecules of CACTS, there are active chlorine groups, which can take part in other reactions. Thus, number of chitosan derivatives will be obtained after chlorine is substituted. Choosing pyridine as the active group, a novel water-soluble chitosan derivative, (2-pyridyl)-acetyl chitosan (PACTS) was obtained and its antioxidant activity against hydroxyl radicals and superoxide radicals was assessed. The results indicated that PACTS had better antioxidant activity than that of chitosan, carboxymethyl chitosan (CMCTS), hydroxypropyl chitosan (HPCTS), and Vitamin C. And the IC{sub 50} values against hydroxyl radicals and superoxide radicals were 0.31 mg/mL and 0.21 mg/mL, respectively.

  9. Synthesis of (2-pyridyl)-Acetyl Chitosan and Its Antioxidant Activity

    In this paper, chloracetyl chitosan (CACTS) was prepared at first. In the molecules of CACTS, there are active chlorine groups, which can take part in other reactions. Thus, number of chitosan derivatives will be obtained after chlorine is substituted. Choosing pyridine as the active group, a novel water-soluble chitosan derivative, (2-pyridyl)-acetyl chitosan (PACTS) was obtained and its antioxidant activity against hydroxyl radicals and superoxide radicals was assessed. The results indicated that PACTS had better antioxidant activity than that of chitosan, carboxymethyl chitosan (CMCTS), hydroxypropyl chitosan (HPCTS), and Vitamin C. And the IC50 values against hydroxyl radicals and superoxide radicals were 0.31 mg/mL and 0.21 mg/mL, respectively

  10. Histone Acetylation in Fungal Pathogens of Plants

    Junhyun Jeon

    2014-03-01

    Full Text Available Acetylation of histone lysine residues occurs in different organisms ranging from yeast to plants and mammals for the regulation of diverse cellular processes. With the identification of enzymes that create or reverse this modification, our understanding on histone acetylation has expanded at an amazing pace during the last two decades. In fungal pathogens of plants, however, the importance of such modification has only just begun to be appreciated in the recent years and there is a dearth of information on how histone acetylation is implicated in fungal pathogenesis. This review covers the current status of research related to histone acetylation in plant pathogenic fungi and considers relevant findings in the interaction between fungal pathogens and host plants. We first describe the families of histone acetyltransferases and deacetylases. Then we provide the cases where histone acetylation was investigated in the context of fungal pathogenesis. Finally, future directions and perspectives in epigenetics of fungal pathogenesis are discussed.

  11. Acetylation-mediated suppression of transcription-independent memory: bidirectional modulation of memory by acetylation.

    Katja Merschbaecher

    Full Text Available Learning induced changes in protein acetylation, mediated by histone acetyl transferases (HATs, and the antagonistic histone deacetylases (HDACs play a critical role in memory formation. The status of histone acetylation affects the interaction between the transcription-complex and DNA and thus regulates transcription-dependent processes required for long-term memory (LTM. While the majority of studies report on the role of elevated acetylation in memory facilitation, we address the impact of both, increased and decreased acetylation on formation of appetitive olfactory memory in honeybees. We show that learning-induced changes in the acetylation of histone H3 at aminoacid-positions H3K9 and H3K18 exhibit distinct and different dynamics depending on the training strength. A strong training that induces LTM leads to an immediate increase in acetylation at H3K18 that stays elevated for hours. A weak training, not sufficient to trigger LTM, causes an initial increase in acetylation at H3K18, followed by a strong reduction in acetylation at H3K18 below the control group level. Acetylation at position H3K9 is not affected by associative conditioning, indicating specific learning-induced actions on the acetylation machinery. Elevating acetylation levels by blocking HDACs after conditioning leads to an improved memory. While memory after strong training is enhanced for at least 2 days, the enhancement after weak training is restricted to 1 day. Reducing acetylation levels by blocking HAT activity after strong training leads to a suppression of transcription-dependent LTM. The memory suppression is also observed in case of weak training, which does not require transcription processes. Thus, our findings demonstrate that acetylation-mediated processes act as bidirectional regulators of memory formation that facilitate or suppress memory independent of its transcription-requirement.

  12. Efficient acetylation of primary amines and amino acids in environmentally benign brine solution using acetyl chloride

    Kaushik Basu; Suchandra Chakraborty; Achintya Kumar Sarkar; Chandan Saha

    2013-05-01

    Acetyl chloride is one of the most commonly available and cheap acylating agent but its high reactivity and concomitant instability in water precludes its use to carry out acetylation in aqueous medium. The present methodology illustrates the efficient acetylation of primary amines and amino acids in brine solution by means of acetyl chloride under weakly basic condition in the presence of sodium acetate and/or triethyl amine followed by trituration with aqueous saturated bicarbonate solution. This effort represents the first efficient use of this most reactive but cheap acetylating agent to acetylate amines in excellent yields in aqueous medium. This is a potentially useful green chemical transformation where reaction takes place in environment-friendly brine solution leading to easy work-up and isolation of the amide derivatives. Mechanistic rationale of this methodology is also important.

  13. Levels of histone acetylation in thyroid tumors.

    Puppin, Cinzia; Passon, Nadia; Lavarone, Elisa; Di Loreto, Carla; Frasca, Francesco; Vella, Veronica; Vigneri, Riccardo; Damante, Giuseppe

    2011-08-12

    Histone acetylation is a major mechanism to regulate gene transcription. This post-translational modification is modified in cancer cells. In various tumor types the levels of acetylation at several histone residues are associated to clinical aggressiveness. By using immunohistochemistry we show that acetylated levels of lysines at positions 9-14 of H3 histone (H3K9-K14ac) are significantly higher in follicular adenomas (FA), papillary thyroid carcinomas (PTC), follicular thyroid carcinomas (FTC) and undifferentiated carcinomas (UC) than in normal tissues (NT). Similar data have been obtained when acetylated levels of lysine 18 of H3 histone (H3K18ac) were evaluated. In this case, however, no difference was observed between NT and UC. When acetylated levels of lysine 12 of H4 histone (H4K12ac) were evaluated, only FA showed significantly higher levels in comparison with NT. These data indicate that modification histone acetylation is an early event along thyroid tumor progression and that H3K18 acetylation is switched off in the transition between differentiated and undifferentiated thyroid tumors. By using rat thyroid cell lines that are stably transfected with doxycyclin-inducible oncogenes, we show that the oncoproteins RET-PTC, RAS and BRAF increase levels of H3K9-K14ac and H3K18ac. In the non-tumorigenic rat thyroid cell line FRTL-5, TSH increases levels of H3K18ac. However, this hormone decreases levels of H3K9-K14ac and H4K12ac. In conclusion, our data indicate that neoplastic transformation and hormonal stimulation can modify levels of histone acetylation in thyroid cells. PMID:21763277

  14. p53 Acetylation: Regulation and Consequences

    Post-translational modifications of p53 are critical in modulating its tumor suppressive functions. Ubiquitylation, for example, plays a major role in dictating p53 stability, subcellular localization and transcriptional vs. non-transcriptional activities. Less is known about p53 acetylation. It has been shown to govern p53 transcriptional activity, selection of growth inhibitory vs. apoptotic gene targets, and biological outcomes in response to diverse cellular insults. Yet recent in vivo evidence from mouse models questions the importance of p53 acetylation (at least at certain sites) as well as canonical p53 functions (cell cycle arrest, senescence and apoptosis) to tumor suppression. This review discusses the cumulative findings regarding p53 acetylation, with a focus on the acetyltransferases that modify p53 and the mechanisms regulating their activity. We also evaluate what is known regarding the influence of other post-translational modifications of p53 on its acetylation, and conclude with the current outlook on how p53 acetylation affects tumor suppression. Due to redundancies in p53 control and growing understanding that individual modifications largely fine-tune p53 activity rather than switch it on or off, many questions still remain about the physiological importance of p53 acetylation to its role in preventing cancer

  15. p53 Acetylation: Regulation and Consequences

    Reed, Sara M. [Department of Pharmacology, The University of Iowa Carver College of Medicine, Iowa City, IA 52242 (United States); Medical Scientist Training Program, The University of Iowa Carver College of Medicine, Iowa City, IA 52242 (United States); Quelle, Dawn E., E-mail: dawn-quelle@uiowa.edu [Department of Pharmacology, The University of Iowa Carver College of Medicine, Iowa City, IA 52242 (United States); Medical Scientist Training Program, The University of Iowa Carver College of Medicine, Iowa City, IA 52242 (United States); Department of Pathology, The University of Iowa Carver College of Medicine, Iowa City, IA 52242 (United States)

    2014-12-23

    Post-translational modifications of p53 are critical in modulating its tumor suppressive functions. Ubiquitylation, for example, plays a major role in dictating p53 stability, subcellular localization and transcriptional vs. non-transcriptional activities. Less is known about p53 acetylation. It has been shown to govern p53 transcriptional activity, selection of growth inhibitory vs. apoptotic gene targets, and biological outcomes in response to diverse cellular insults. Yet recent in vivo evidence from mouse models questions the importance of p53 acetylation (at least at certain sites) as well as canonical p53 functions (cell cycle arrest, senescence and apoptosis) to tumor suppression. This review discusses the cumulative findings regarding p53 acetylation, with a focus on the acetyltransferases that modify p53 and the mechanisms regulating their activity. We also evaluate what is known regarding the influence of other post-translational modifications of p53 on its acetylation, and conclude with the current outlook on how p53 acetylation affects tumor suppression. Due to redundancies in p53 control and growing understanding that individual modifications largely fine-tune p53 activity rather than switch it on or off, many questions still remain about the physiological importance of p53 acetylation to its role in preventing cancer.

  16. p53 Acetylation: Regulation and Consequences

    Sara M. Reed

    2014-12-01

    Full Text Available Post-translational modifications of p53 are critical in modulating its tumor suppressive functions. Ubiquitylation, for example, plays a major role in dictating p53 stability, subcellular localization and transcriptional vs. non-transcriptional activities. Less is known about p53 acetylation. It has been shown to govern p53 transcriptional activity, selection of growth inhibitory vs. apoptotic gene targets, and biological outcomes in response to diverse cellular insults. Yet recent in vivo evidence from mouse models questions the importance of p53 acetylation (at least at certain sites as well as canonical p53 functions (cell cycle arrest, senescence and apoptosis to tumor suppression. This review discusses the cumulative findings regarding p53 acetylation, with a focus on the acetyltransferases that modify p53 and the mechanisms regulating their activity. We also evaluate what is known regarding the influence of other post-translational modifications of p53 on its acetylation, and conclude with the current outlook on how p53 acetylation affects tumor suppression. Due to redundancies in p53 control and growing understanding that individual modifications largely fine-tune p53 activity rather than switch it on or off, many questions still remain about the physiological importance of p53 acetylation to its role in preventing cancer.

  17. Intracellular Acetyl Unit Transport in Fungal Carbon Metabolism

    Strijbis, K.; Distel, B.

    2010-01-01

    Acetyl coenzyme A (acetyl-CoA) is a central metabolite in carbon and energy metabolism. Because of its amphiphilic nature and bulkiness, acetyl-CoA cannot readily traverse biological membranes. In fungi, two systems for acetyl unit transport have been identified: a shuttle dependent on the carrier carnitine and a (peroxisomal) citrate synthase-dependent pathway. In the carnitine-dependent pathway, carnitine acetyltransferases exchange the CoA group of acetyl-CoA for carnitine, thereby forming...

  18. Reversible lysine acetylation controls the activity of the mitochondrial enzyme acetyl-CoA synthetase 2

    Schwer, Bjoern; Bunkenborg, Jakob; Verdin, Regis O; Andersen, Jens S; Verdin, Eric

    2006-01-01

    We report that human acetyl-CoA synthetase 2 (AceCS2) is a mitochondrial matrix protein. AceCS2 is reversibly acetylated at Lys-642 in the active site of the enzyme. The mitochondrial sirtuin SIRT3 interacts with AceCS2 and deacetylates Lys-642 both in vitro and in vivo. Deacetylation of AceCS2 b...

  19. Radical prostatectomy - discharge

    ... prostatectomy - discharge; Laparoscopic radical prostatectomy - discharge; LRP - discharge; Robotic-assisted laparoscopic prostatectomy - discharge ; RALP - discharge; Pelvic lymphadenectomy - ...

  20. Peroxyl radical reactions with carotenoids in microemulsions: Influence of microemulsion composition and the nature of peroxyl radical precursor.

    El-Agamey, Ali; McGarvey, David J

    2016-01-01

    The reactions of acetylperoxyl radicals with different carotenoids (7,7'-dihydro-β-carotene and ζ-carotene) in SDS and CTAC microemulsions of different compositions were investigated using laser flash photolysis (LFP) coupled with kinetic absorption spectroscopy. The primary objective of this study was to explore the influence of microemulsion composition and the type of surfactant used on the yields and kinetics of various transients formed from the reaction of acetylperoxyl radicals with carotenoids. Also, the influence of the site (hydrocarbon phases or aqueous phase) of generation of the peroxyl radical precursor was examined by using 4-acetyl-4-phenylpiperidine hydrochloride (APPHCl) and 1,1-diphenylacetone (11DPA) as water-soluble and lipid-soluble peroxyl radical precursors, respectively. LFP of peroxyl radical precursors with 7,7'-dihydro-β-carotene (77DH) in different microemulsions gives rise to the formation of three distinct transients namely addition radical (λmax=460 nm), near infrared transient1 (NIR, λmax=700 nm) and 7,7'-dihydro-β-carotene radical cation (77DH(•+), λmax=770 nm). In addition, for ζ-carotene (ZETA) two transients (near infrared transient1 (NIR1, λmax=660 nm) and ζ-carotene radical cation (ZETA(•+), λmax=730-740 nm)) are generated following LFP of peroxyl radical precursors in the presence of ζ-carotene (ZETA) in different microemulsions. The results show that the composition of the microemulsion strongly influences the observed yield and kinetics of the transients formed from the reactions of peroxyl radicals (acetylperoxyl radicals) with carotenoids (77DH and ZETA). Also, the type of surfactant used in the microemulsions influences the yield of the transients formed. The dependence of the transient yields and kinetics on microemulsion composition (or the type of surfactant used in the microemulsion) can be attributed to the change of the polarity of the microenvironment of the carotenoid. Furthermore, the nature of

  1. Free radical inactivation of trypsin

    Reactivities of free radical oxidants, radical OH, Br2-anion radical and Cl3COO radical and a reductant, CO2-anion radical, with trypsin and reactive protein components were determined by pulse radiolysis of aqueous solutions at pH 7, 200C. Highly reactive free radicals, radical OH, Br2-anion radical and CO2-anion radical, react with trypsin at diffusion controlled rates. Moderately reactive trichloroperoxy radical, k(Cl3COO radical + trypsin) preferentially oxidizes histidine residues. The efficiency of inactivation of trypsin by free radicals is inversely proportional to their reactivity. The yields of inactivation of trypsin by radical OH, Br2-anion radical and CO2-anion radical are low, G(inactivation) = 0.6-0.8, which corresponds to ∼ 10% of the initially produced radicals. In contrast, Cl3COO radical inactivates trypsin with ∼ 50% efficiency, i.e. G(inactivation) = 3.2. (author)

  2. Antioxidant activity of N-acetyl-glucosamine based thiazolidine derivative

    Li Chunlei; Yang Yan; Han Baoqin; Liu Wanshun

    2007-01-01

    N-acetyl-glucosamine,the monomer of chitin,was cyclo-condensed with L-cysteine to prepare thiazolidine derivative:2-N-acetyl-glucosamine-thiazolidine-4(R)-carboxylic acid(GlcNAcCys).The stability of GlcNAcCys was evaluated by high performance liquid chromatography(HPLC)measurement.The results showed that GlcNAcCys Was more stable than other TCA derivatives,especially in alkaline condition.The direct in vitro antioxidative properties of GlcNAcCys were investigated by using UV radiation-induced lipid peroxidation(LPO)in mitochondria and nuclei and.OH-induced LPO in red blood cell (RBC)ghosts models.UV radiation caused dose-dependent LPO in both mitochondria and nuclei,this effect Was catalvzed by addition of Fd2+ while prevented by co-incubation with GlcNAcCys.When nuclei and mitochondria Was treated with 100μl,300μl,500μl of GlcNAcCys and co-incubated at 37℃ for 30min,LPO was decreased to 96%,72%,68%in nuclei and 95%,72%,68% in mitochondria when compared to the UV radiation group respectively.Hydroxyl radicals(.OH)generated by Fenton reaction induced LPO in RBC ghosts.Pretreatment of RBC ghosts with GlcNAcCys could induce antioxidant RBC ghosts and inhibit concentration-dependent malondialdehyde(MDA)formation in antioxidant RBC ghosts.Its inhibition percent Was 14%,35%,36%,42%at 10,20,30,40ms/ml respectively.In a conclusion,the data suggest that GlcNAcCys has antioxidant ability and can significantly inhibit lipid peroxidation in biological samples tested in vitro.

  3. Radical theory of rings

    Gardner, JW

    2003-01-01

    Radical Theory of Rings distills the most noteworthy present-day theoretical topics, gives a unified account of the classical structure theorems for rings, and deepens understanding of key aspects of ring theory via ring and radical constructions. Assimilating radical theory's evolution in the decades since the last major work on rings and radicals was published, the authors deal with some distinctive features of the radical theory of nonassociative rings, associative rings with involution, and near-rings. Written in clear algebraic terms by globally acknowledged authorities, the presentation

  4. Oxidative Debenzylation and Acetylation of Hexabenzylhexaazaisowutzitane

    2002-01-01

    The oxidative reactivity of hexabenzylhexaazaisowutzitane(HBIW)under different conditions was studied. It was found that the N-benzyl groups were found to form benzoyl group after oxidation. They might also be first debenzylated and then acetylated by potassium permanganate in acetic anhydride/DMF.

  5. Property enhancement of optically transparent bionanofiber composites by acetylation

    Nogi, Masaya; Abe, Kentaro; Handa, Keishin; Nakatsubo, Fumiaki; Ifuku, Shinsuke; Yano, Hiroyuki

    2006-12-01

    The authors studied acetylation of bacterial cellulose (BC) nanofibers to widen the applications of BC nanocomposites in optoelectronic devices. The slight acetylation of BC nanofibers significantly reduces the hygroscopicity of BC nanocomposites, while maintaining their high optical transparency and thermal stability. Furthermore, the degradation in optical transparency at elevated temperature (200°C) was significantly reduced by acetylation treatment. Therefore, the acetylation of bionanofibers has an extraordinary potential as treatment for property enhancement of bionanofiber composites.

  6. Phosphorylation and Acetylation of Acyl-CoA Synthetase- I

    Frahm, Jennifer L; Li, Lei O; Grevengoed, Trisha J;

    2011-01-01

    acetylated amino acids by mass spectrometry. We then compared these results to the post-translational modifications observed in vivo in liver and brown adipose tissue after mice were fasted or exposed to a cold environment. We identified universal N-terminal acetylation, 15 acetylated lysines, and 25...

  7. Laparoscopic Radical Trachelectomy

    Rendón, Gabriel J.; Ramirez, Pedro T.; Frumovitz, Michael; Schmeler, Kathleen M.; Pareja, Rene

    2012-01-01

    Introduction: The standard treatment for patients with early-stage cervical cancer has been radical hysterectomy. However, for women interested in future fertility, radical trachelectomy is now considered a safe and feasible option. The use of minimally invasive surgical techniques to perform this procedure has recently been reported. Case Description: We report the first case of a laparoscopic radical trachelectomy performed in a developing country. The patient is a nulligravid, 30-y-old fem...

  8. Laparoscopic radical cystectomy

    Fergany, Amr

    2012-01-01

    Objective Laparoscopic radical cystectomy (LRC) has emerged as a minimally invasive alternative to open radical cystectomy (ORC). This review focuses on patient selection criteria, technical aspects and postoperative outcomes of LRC. Methods Material for the review was obtained by a PubMed search over the last 10 years, using the keywords ‘laparoscopic radical cystectomy’ and ‘laparoscopic bladder cancer’ in human subjects. Results Twenty-two publications selected for relevance and content we...

  9. Dynamic Protein Acetylation in Plant–Pathogen Interactions

    Song, Gaoyuan; Walley, Justin W.

    2016-01-01

    Pathogen infection triggers complex molecular perturbations within host cells that results in either resistance or susceptibility. Protein acetylation is an emerging biochemical modification that appears to play central roles during host–pathogen interactions. To date, research in this area has focused on two main themes linking protein acetylation to plant immune signaling. Firstly, it has been established that proper gene expression during defense responses requires modulation of histone acetylation within target gene promoter regions. Second, some pathogens can deliver effector molecules that encode acetyltransferases directly within the host cell to modify acetylation of specific host proteins. Collectively these findings suggest that the acetylation level for a range of host proteins may be modulated to alter the outcome of pathogen infection. This review will focus on summarizing our current understanding of the roles of protein acetylation in plant defense and highlight the utility of proteomics approaches to uncover the complete repertoire of acetylation changes triggered by pathogen infection. PMID:27066055

  10. Physiology of free radicals

    Stevanović Jelka

    2011-01-01

    Full Text Available Free radicals imply that every atom, molecule, ion, group of atoms, or molecules with one or several non-paired electrons in outer orbital. Among these are: nitrogenoxide (NO•, superoxide-anion-radical (O2•-, hydroxyl radical (OH•, peroxyl radical (ROO•, alcoxyl radical (RO• and hydroperoxyl radical (HO2•. However, reactive oxygen species also include components without non-paired electrons in outer orbital (so-called reactive non-radical agents, such as: singlet oxygen (1O2, peroxynitrite (ONOO-, hydrogen-peroxide (H2O2, hypochloric acid (eg. HOCl and ozone (O3. High concentrations of free radicals lead to the development of oxidative stress which is a precondition for numerous pathological effects. However, low and moderate concentrations of these matter, which occur quite normally during cell metabolic activity, play multiple significant roles in many reactions. Some of these are: regulation of signal pathways within the cell and between cells, the role of chemoattractors and leukocyte activators, the role in phagocytosis, participation in maintaining, changes in the position and shape of the cell, assisting the cell during adaption and recovery from damage (e.g.caused by physical effort, the role in normal cell growth, programmed cell death (apoptosis and cell ageing, in the synthesis of essential biological compounds and energy production, as well as the contribution to the regulation of the vascular tone, actually, tissue vascularization.

  11. VUV photoionization and dissociative photoionization of the prebiotic molecule acetyl cyanide: Theory and experiment

    The present combined theoretical and experimental investigation concerns the single photoionization of gas-phase acetyl cyanide and the fragmentation pathways of the resulting cation. Acetyl cyanide (AC) is inspired from both the chemistry of cyanoacetylene and the Strecker reaction which are thought to be at the origin of medium sized prebiotic molecules in the interstellar medium. AC can be formed by reaction from cyanoacetylene and water but also from acetaldehyde and HCN or the corresponding radicals. In view of the interpretation of vacuum ultraviolet (VUV) experimental data obtained using synchrotron radiation, we explored the ground potential energy surface (PES) of acetyl cyanide and of its cation using standard and recently implemented explicitly correlated methodologies. Our PES covers the regions of tautomerism (between keto and enol forms) and of the lowest fragmentation channels. This allowed us to deduce accurate thermochemical data for this astrobiologically relevant molecule. Unimolecular decomposition of the AC cation turns out to be very complex. The implications for the evolution of prebiotic molecules under VUV irradiation are discussed

  12. VUV photoionization and dissociative photoionization of the prebiotic molecule acetyl cyanide: Theory and experiment

    Bellili, A.; Hochlaf, M., E-mail: hochlaf@univ-mlv.fr, E-mail: martin.schwell@lisa.u-pec.fr [Laboratoire Modélisation et Simulation Multi Echelle, MSME UMR 8208 CNRS, Université Paris-Est, 5 bd Descartes, 77454 Marne-la-Vallée (France); Schwell, M., E-mail: hochlaf@univ-mlv.fr, E-mail: martin.schwell@lisa.u-pec.fr; Bénilan, Y.; Fray, N.; Gazeau, M.-C. [Laboratoire Interuniversitaire des Systèmes Atmosphériques (LISA), UMR 7583 CNRS, Institut Pierre et Simon Laplace, Universités Paris-Est Créteil et Paris Diderot, 61 Avenue du Général de Gaulle, 94010 Créteil (France); Mogren Al-Mogren, M. [Chemistry Department, Faculty of Science, King Saud University, P.O. Box 2455, Riyadh 11451 (Saudi Arabia); Guillemin, J.-C. [Institut des Sciences Chimiques de Rennes, Ecole Nationale Supérieure de Chimie de Rennes, CNRS, UMR 6226, Allée de Beaulieu, CS 50837, 35708 Rennes Cedex 7 (France); Poisson, L. [Laboratoire Francis Perrin, CNRS URA 2453, CEA, IRAMIS, Laboratoire Interactions Dynamique et Lasers, Bât 522, F-91191 Gif/Yvette (France)

    2014-10-07

    The present combined theoretical and experimental investigation concerns the single photoionization of gas-phase acetyl cyanide and the fragmentation pathways of the resulting cation. Acetyl cyanide (AC) is inspired from both the chemistry of cyanoacetylene and the Strecker reaction which are thought to be at the origin of medium sized prebiotic molecules in the interstellar medium. AC can be formed by reaction from cyanoacetylene and water but also from acetaldehyde and HCN or the corresponding radicals. In view of the interpretation of vacuum ultraviolet (VUV) experimental data obtained using synchrotron radiation, we explored the ground potential energy surface (PES) of acetyl cyanide and of its cation using standard and recently implemented explicitly correlated methodologies. Our PES covers the regions of tautomerism (between keto and enol forms) and of the lowest fragmentation channels. This allowed us to deduce accurate thermochemical data for this astrobiologically relevant molecule. Unimolecular decomposition of the AC cation turns out to be very complex. The implications for the evolution of prebiotic molecules under VUV irradiation are discussed.

  13. Acetylation Is Indispensable for p53 Activation

    Tang, Yi; Zhao, Wenhui; Chen, Yue; Zhao, Yingming; Gu, Wei

    2008-01-01

    The activation of the tumor suppressor p53 facilitates the cellular response to genotoxic stress; however, the p53 response can only be executed if its interaction with its inhibitor Mdm2 is abolished. There have been conflicting reports on the question of whether p53 posttranslational modifications, such as phosphorylation or acetylation, are essential or only play a subtle, fine-tuning role in the p53 response. Thus, it remains unclear whether p53 modification is absolutely required for its...

  14. p53 Acetylation: Regulation and Consequences

    Reed, Sara M.; Quelle, Dawn E.

    2014-01-01

    Post-translational modifications of p53 are critical in modulating its tumor suppressive functions. Ubiquitylation, for example, plays a major role in dictating p53 stability, subcellular localization and transcriptional vs. non-transcriptional activities. Less is known about p53 acetylation. It has been shown to govern p53 transcriptional activity, selection of growth inhibitory vs. apoptotic gene targets, and biological outcomes in response to diverse cellular insults. Yet recent in vivo ev...

  15. The neurobiology of acetyl-L-carnitine.

    Traina, Giovanna

    2016-01-01

    A large body of evidence points to the positive effects of dietary supplementation of acetyl-L-carnitine (ALC). Its use has shown health benefits in neuroinflammation, which is a common denominator in a host of neurodegenerative diseases. ALC is the principal acetyl ester of L-Carnitine (LC), and it plays an essential role in intermediary metabolism, acting as a donor of acetyl groups and facilitating the transfer of fatty acids from cytosol to mitochondria during beta-oxidation. Dietary supplementation of ALC exerts neuroprotective, neurotrophic, antidepressive and analgesic effects in painful neuropathies. ALC also has antioxidant and anti-apoptotic activity. Moreover, ALC exhibits positive effects on mitochondrial metabolism, and shows promise in the treatment of aging and neurodegenerative pathologies by slowing the progression of mental deterioration. In addition, ALC plays neuromodulatory effects on both synaptic morphology and synaptic transmission. These effects are likely due to affects of ALC through modulation of gene expression on several targets in the central nervous system. Here, we review the current state of knowledge on effects of ALC in the nervous system. PMID:27100509

  16. Fragrance material review on acetyl cedrene.

    Scognamiglio, J; Letizia, C S; Politano, V T; Api, A M

    2013-12-01

    A toxicologic and dermatologic review of acetyl cedrene when used as a fragrance ingredient is presented. Acetyl cedrene is a member of the fragrance structural group Alkyl Cyclic Ketones. The generic formula for this group can be represented as (R1)(R2)CO. These fragrances can be described as being composed of an alkyl, R1, and various substituted and bicyclic saturated or unsaturated cyclic hydrocarbons, R2, in which one of the rings may include up to 12 carbons. Alternatively, R2 may be a carbon bridge of C2-C4 carbon chain length between the ketone and cyclic hydrocarbon. This review contains a detailed summary of all available toxicology and dermatology papers that are related to this individual fragrance ingredient and is not intended as a stand-alone document. Available data for acetyl cedrene were evaluated then summarized and includes physical properties, acute toxicity, skin irritation, mucous membrane (eye) irritation, skin sensitization, elicitation, phototoxicity, photoallergy, toxicokinetics, repeated dose, reproductive toxicity, and genotoxicity data. A safety assessment of the entire Alkyl Cyclic Ketones will be published simultaneously with this document; please refer to Belsito et al. (2013) (Belsito, D., Bickers, D., Bruze, M., Calow, P., Dagli, M., Fryer, A.D., Greim, H., Miyachi, Y., Saurat, J.H., Sipes, I.G., 2013. A Toxicologic and Dermatologic Assessment of Alkyl Cyclic Ketones When Used as Fragrance Ingredients. Submitted with this manuscript.) for an overall assessment of the safe use of this material and all Alkyl Cyclic Ketones in fragrances. PMID:23907023

  17. Biosynthesis and turnover of O-acetyl and N-acetyl groups in the gangliosides of human melanoma cells

    We and others previously described the melanoma-associated oncofetal glycosphingolipid antigen 9-O-acetyl-GD3, a disialoganglioside O-acetylated at the 9-position of the outer sialic acid residue. We have now developed methods to examine the biosynthesis and turnover of disialogangliosides in cultured melanoma cells and in Golgi-enriched vesicles from these cells. O-Acetylation was selectively expressed on di- and trisialogangliosides, but not on monosialogangliosides, nor on glycoprotein-bound sialic acids. Double-labeling of cells with [3H]acetate and [14C]glucosamine introduced easily detectable labels into each of the components of the ganglioside molecules. Pulse-chase studies of such doubly labeled molecules indicated that the O-acetyl groups turn over faster than the parent molecule. When Golgi-enriched vesicles from these cells were incubated with [acetyl-3H]acetyl-coenzyme A, the major labeled products were disialogangliosides. [Acetyl-3H]O-acetyl groups were found at both the 7- and the 9-positions, indicating that both 7-O-acetyl GD3 and 9-O-acetyl GD3 were synthesized by the action of O-acetyltransferase(s) on endogenous GD3. Analysis of the metabolically labeled molecules confirmed the existence of both 7- and 9-O-acetylated GD3 in the intact cells. Surprisingly, the major 3H-labeled product of the in vitro labeling reaction was not O-acetyl-GD3, but GD3, with the label exclusively in the sialic acid residues. Fragmentation of the labeled sialic acids by enzymatic and chemical methods showed that the 3H-label was exclusively in [3H]N-acetyl groups. Analyses of the double-labeled sialic acids from intact cells also showed that the 3H-label from [3H]acetate was exclusively in the form of [3H]N-acetyl groups, whereas the 14C-label was at the 4-position

  18. Acetylation phenotype variation in pediatric patients with atopic dermatitis

    Rafi A Majeed Al-Razzuqi

    2011-01-01

    Full Text Available Background: Few studies have been done on the relation between acetylator status and allergic diseases. Aim: To determine any possible association between acetylating phenotype in pediatric patients with atopic dermatitis (AD and the disease prognosis. Patients and Methods: Thirty-six pediatric patients and forty two healthy children as a control group were participated in the study. All participants received a single oral dose of dapsone of 1.54 mg/kg body weight, after an overnight fast. Using high performance liquid chromatography (HPLC, plasma concentrations of dapsone and its metabolite (monoacetyldapsone were estimated to phenotype the participants as slow and rapid acetylators according to their acetylation ratio (ratio of monoacetyldapsone to dapsone. Results: 72.2% of pediatric patients with AD showed slow acetylating status as compared to 69.4% of control individuals. Also, 73% of AD patients with slow acetylating phenotype had familial history of allergy. The severity of AD occurred only in slow acetylator patients. The eczematous lesions in slow acetylators presented mainly in the limbs, while in rapid acetylators, they were found mostly in face and neck. Conclusion: This study shows an association between the N-acetylation phenotype variation and clinical aspects of AD.

  19. Amino acid peroxyl radicals. Formation and reaction with ascorbate

    Complete text of publication follows. Proteins are significant targets for partly reduced oxygen species in vivo. This results in random formation of radicals on the amino acid residues (AA·) of the protein, which in turn, in the presence of oxygen, can yield the corresponding peroxyl radicals (AAOO·). Both radical types can cause further biological damage. We studied the N-acetylamide derivatives of the amino acids glycine, alanine and proline as models of these residues in proteins. We generated the amino acid radicals specifically by reaction with hydroxyl radicals produced in solutions irradiated with 2 MeV electrons in the presence of N2O. In the absence of oxygen the amino acid radicals decayed with rate constants in the narrow range (0.9-1.3) x 109 M-1s-1, while in the presence of oxygen they were converted very rapidly to the corresponding peroxyl radicals with rate constants that vary between 6.3 x 108 and 5.5 x 109 M-1s-1, depending on the amino acid. The corresponding N-acetylated amino acids were also studied and showed similar behaviour but with slightly smaller rate constants. Antioxidants are able to repair tyrosyl and tryptophanyl radicals in various proteins in vitro. For ascorbate, the principal endogenous biological antioxidant, we have measured rate constants in the range 105-108 M-1s-1. The peroxyl radicals of all amino acids studied here were reduced by oxidizing ascorbate to the ascorbyl radical. The reaction was followed at 360 nm, where ascorbyl radical has an absorption coefficient of 3300 M-1cm-1, and the derived rate constants were all close to 107 M-1s-1. However, the spontaneous decay of peroxyl radicals is also fast and competes with the reaction with ascorbate. It is to be stressed that reaction of AAOO· and ascorbate gives rise to hydroperoxides (AAOOH) that are also reactive molecules. Our study suggests that reaction with protein radicals may be responsible for the ascorbate loss reported in organisms exposed to oxidative

  20. Radical chemistry of artemisinin

    Denisov, Evgenii T; Solodova, S L; Denisova, Taisa G [Institute of Problems of Chemical Physics, Russian Academy of Sciences, Chernogolovka, Moscow Region (Russian Federation)

    2010-12-29

    The review summarizes physicochemical characteristics of the natural sesquiterpene peroxide artemisinin. The kinetic schemes of transformations of artemisinin radicals under anaerobic conditions are presented and analyzed. The sequence of radical reactions of artemisinin in the presence of oxygen is considered in detail. Special emphasis is given to the intramolecular chain oxidation resulting in the transformation of artemisinin into polyatomic hydroperoxide. The kinetic characteristics of elementary reaction steps involving alkyl, alkoxyl, and peroxyl radicals generated from artemisinin are discussed. The results of testing of artemisinin and its derivatives for the antimalarial activity and the scheme of the biochemical synthesis of artemisinin in nature are considered.

  1. Acetylation and characterization of spruce (Picea abies) galactoglucomannans.

    Xu, Chunlin; Leppänen, Ann-Sofie; Eklund, Patrik; Holmlund, Peter; Sjöholm, Rainer; Sundberg, Kenneth; Willför, Stefan

    2010-04-19

    Acetylated galactoglucomannans (GGMs) are the main hemicellulose type in most softwood species and can be utilized as, for example, bioactive polymers, hydrocolloids, papermaking chemicals, or coating polymers. Acetylation of spruce GGM using acetic anhydride with pyridine as catalyst under different conditions was conducted to obtain different degrees of acetylation on a laboratory scale, whereas, as a classic method, it can be potentially transferred to the industrial scale. The effects of the amount of catalyst and acetic anhydride, reaction time, temperature and pretreatment by acetic acid were investigated. A fully acetylated product was obtained by refluxing GGM for two hours. The structures of the acetylated GGMs were determined by SEC-MALLS/RI, (1)H and (13)C NMR and FTIR spectroscopy. NMR studies also indicated migration of acetyl groups from O-2 or O-3 to O-6 after a heating treatment in a water bath. The thermal stability of the products was investigated by DSC-TGA. PMID:20144827

  2. Preparation, physicochemical characterization and application of acetylated lotus rhizome starches.

    Sun, Suling; Zhang, Ganwei; Ma, Chaoyang

    2016-01-01

    Acetylated lotus rhizome starches were prepared, physicochemically characterized and used as food additives in puddings. The percentage content of the acetyl groups and degree of substitution increased linearly with the amount of acetic anhydride used. The introduction of acetyl groups was confirmed via Fourier transform infrared (FT-IR) spectroscopy. The values of the pasting parameters were lower for acetylated starch than for native starch. Acetylation was found to increase the light transmittance (%), the freeze-thaw stability, the swelling power and the solubility of the starch. Sensorial scores for puddings prepared using native and acetylated lotus rhizome starches as food additives indicated that puddings produced from the modified starches with superior properties over those prepared from native starch. PMID:26453845

  3. Radical cystectomy in eldery

    Bančević Vladimir; Aleksić Predrag; Milović Novak; Spasić Aleksandar; Kovačević Božidar; Toševski Perica; Čampara Zoran; Milošević Radovan; Cerović Snežana

    2015-01-01

    Background/Aim. Radical cystectomy is the method of choice for the treatment of muscle invasive bladder cancer. This major surgery is associated with many complications, especially in older patients. The aim of this study was to analyze preoperative comorbidity, and intraoperative and postoperative complicatons in patients older than 75 years. Methods. This clinical, retrospective study included 46 patients over 75 years, who underwent radical cystectomy. I...

  4. Acetylation of Tau Inhibits Its Degradation and Contributes to Tauopathy

    Min, Sang-Won; Cho, Seo-Hyun; Zhou, Yungui; Schroeder, Sebastian; Haroutunian, Vahram; Seeley, William W.; Huang, Eric J.; Shen, Yong; Masliah, Eliezer; Mukherjee, Chandrani; Meyers, David; Cole, Philip A.; Ott, Melanie; Gan, Li

    2010-01-01

    Neurodegenerative tauopathies characterized by hyperphosphorylated tau include frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17) and Alzheimer's disease (AD). Reducing tau levels improves cognitive function in mouse models of AD and FTDP-17, but the mechanisms regulating the turnover of pathogenic tau are unknown. We found that tau is acetylated and that tau acetylation prevents degradation of phosphorylated tau (p-tau). Using two antibodies specific for acetylated ta...

  5. Getting a Knack for NAC: N-Acetyl-Cysteine

    Sansone, Randy A.; Sansone, Lori A.

    2011-01-01

    N-acetyl-cysteine, N-acetylcysteine, N-acetyl cysteine, and N-acetyl-L-cysteine are all designations for the same compound, which is abbreviated as NAC. NAC is a precursor to the amino acid cysteine, which ultimately plays two key metabolic roles. Through its metabolic contribution to glutathione production, cysteine participates in the general antioxidant activities of the body. Through its role as a modulator of the glutamatergic system, cysteine influences the reward-reinforcement pathway....

  6. Obesity, cancer, and acetyl-CoA metabolism

    Lee, Joyce V.; Shah, Supriya A.; Wellen, Kathryn E.

    2013-01-01

    As rates of obesity soar in the Unites States and around the world, cancer attributed to obesity has emerged as major threat to public health. The link between obesity and cancer can be attributed in part to the state of chronic inflammation that develops in obesity. Acetyl-CoA production and protein acetylation patterns are highly sensitive to metabolic state and are significantly altered in obesity. In this article, we explore the potential role of nutrient-sensitive lysine acetylation in r...

  7. Determination of amphetamine by HPLC after acetylation.

    Veress, T

    2000-01-01

    An analytical procedure has been developed for the HPLC determination of amphetamine by off-line pre-column derivatization. The proposed procedure consists of sample preparation by acetylation of amphetamine with acetic anhydride and a subsequent reversed-phase HPLC separation on an octadecyl silica stationary phase with salt-free mobile phase (tetrahydrofuran, acetonitrile, 0.1% triethylamine in water, 15:15:70 v/v) applying UV-detection. The applicability of the elaborated procedure is demonstrated with results obtained by analysis of real samples seized in the Hungarian black market. PMID:10641931

  8. Lipase-catalyzed synthesis of acetylated EGCG and antioxidant properties of the acetylated derivatives

    (-)-Epigallocatechin-3-O-gallate (EGCG) acetylated derivatives were prepared by lipase catalyzed acylation of EGCG with vinyl acetate to improve its lipophilicity and expand its application in lipophilic media. The immobilized lipase, Lipozyme RM IM, was found to be the optimum catalyst. The optimiz...

  9. Protein lysine acetylation in bacteria: Current state of the art.

    Ouidir, Tassadit; Kentache, Takfarinas; Hardouin, Julie

    2016-01-01

    Post-translational modifications of proteins are key events in cellular metabolism and physiology regulation. Lysine acetylation is one of the best studied protein modifications in eukaryotes, but, until recently, ignored in bacteria. However, proteomic advances have highlighted the diversity of bacterial lysine-acetylated proteins. The current data support the implication of lysine acetylation in various metabolic pathways, adaptation and virulence. In this review, we present a broad overview of the current knowledge of lysine acetylation in bacteria. We emphasize particularly the significant contribution of proteomics in this field. PMID:26390373

  10. Differential patterns of histone acetylation in inflammatory bowel diseases

    Adcock Ian M

    2011-01-01

    Full Text Available Abstract Post-translational modifications of histones, particularly acetylation, are associated with the regulation of inflammatory gene expression. We used two animal models of inflammation of the bowel and biopsy samples from patients with Crohn's disease (CD to study the expression of acetylated histones (H 3 and 4 in inflamed mucosa. Acetylation of histone H4 was significantly elevated in the inflamed mucosa in the trinitrobenzene sulfonic acid model of colitis particularly on lysine residues (K 8 and 12 in contrast to non-inflamed tissue. In addition, acetylated H4 was localised to inflamed tissue and to Peyer's patches (PP in dextran sulfate sodium (DSS-treated rat models. Within the PP, H3 acetylation was detected in the mantle zone whereas H4 acetylation was seen in both the periphery and the germinal centre. Finally, acetylation of H4 was significantly upregulated in inflamed biopsies and PP from patients with CD. Enhanced acetylation of H4K5 and K16 was seen in the PP. These results demonstrate that histone acetylation is associated with inflammation and may provide a novel therapeutic target for mucosal inflammation.

  11. Probing the acetylation code of histone H4.

    Lang, Diana; Schümann, Michael; Gelato, Kathy; Fischle, Wolfgang; Schwarzer, Dirk; Krause, Eberhard

    2013-10-01

    Histone modifications play crucial roles in genome regulation with lysine acetylation being implicated in transcriptional control. Here we report a proteome-wide investigation of the acetylation-dependent protein-protein interactions of the N-terminal tail of histone H4. Quantitative peptide-based affinity MS experiments using the SILAC approach determined the interactomes of H4 tails monoacetylated at the four known acetylation sites K5, K8, K12, and K16, bis-acetylated at K5/K12, triple-acetylated at K8/12/16 and fully tetra-acetylated. A set of 29 proteins was found enriched on the fully acetylated H4 tail while specific binders of the mono and bis-acetylated tails were barely detectable. These observations are in good agreement with earlier reports indicating that the H4 acetylation state establishes its regulatory effects in a cumulative manner rather than via site-specific recruitment of regulatory proteins. PMID:23970329

  12. Probing the acetylation code of histone H4.

    Lang, D; Schümann, M; Gelato, K.; Fischle, W; Schwarzer, D; Krause, E.

    2013-01-01

    Histone modifications play crucial roles in genome regulation with lysine acetylation being implicated in transcriptional control. Here we report a proteome-wide investigation of the acetylation-dependent protein–protein interactions of the N-terminal tail of histone H4. Quantitative peptide-based affinity MS experiments using the SILAC approach determined the interactomes of H4 tails monoacetylated at the four known acetylation sites K5, K8, K12, and K16, bis-acetylated at K5/K12, triple-ace...

  13. Reduced Wall Acetylation Proteins Play Vital and Distinct Roles in Cell Wall O-Acetylation in Arabidopsis

    Manabe, Yuzuki; Verhertbruggen, Yves; Gille, Sascha;

    2013-01-01

    The Reduced Wall Acetylation (RWA) proteins are involved in cell wall acetylation in plants. Previously, we described a single mutant, rwa2, which has about 20% lower level of O-acetylation in leaf cell walls and no obvious growth or developmental phenotype. In this study, we generated double...... quadruple rwa mutant can be completely complemented with the RWA2 protein expressed under 35S promoter, indicating the functional redundancy of the RWA proteins. Nevertheless, the degree of acetylation of xylan, (gluco) mannan, and xyloglucan as well as overall cell wall acetylation is affected differently...... in different combinations of triple mutants, suggesting their diversity in substrate preference. The overall degree of wall acetylation in the rwa quadruple mutant was reduced by 63% compared with the wild type, and histochemical analysis of the rwa quadruple mutant stem indicates defects in cell...

  14. Free Radical Reactions in Food.

    Taub, Irwin A.

    1984-01-01

    Discusses reactions of free radicals that determine the chemistry of many fresh, processed, and stored foods. Focuses on reactions involving ascorbic acid, myoglobin, and palmitate radicals as representative radicals derived from a vitamin, metallo-protein, and saturated lipid. Basic concepts related to free radical structure, formation, and…

  15. Gangs, Terrorism, and Radicalization

    Scott Decker

    2011-01-01

    Full Text Available What can street gangs tell us about radicalization and extremist groups? At first glance, these two groups seem to push the boundaries of comparison. In this article, we examine the important similarities and differences across criminal, deviant, and extremist groups. Drawing from research on street gangs, this article explores issues such as levels of explanation,organizational structure, group process, and the increasingly important role of technology and the Internet in the context of radicalization. There are points of convergence across these groups, but it is important to understand the differences between these groups. This review finds little evidence to support the contention that American street gangs are becoming increasingly radicalized. This conclusion is based largely on organizational differences between gangs and terror groups.

  16. Sexuality Following Radical Prostatectomy

    Fode, Mikkel; Serefoglu, Ege C; Albersen, Maarten;

    2016-01-01

    INTRODUCTION: Radical prostatectomies can result in urinary incontinence and sexual dysfunction. Traditionally, these issues have been studied separately, and the sexual problem that has received the most focus has been erectile dysfunction. AIM: To summarize the literature on sexually related side...... effects and their consequences after radical prostatectomy and focus on the occurrence and management of problems beyond erectile dysfunction. METHODS: The literature on sexuality after radical prostatectomy was reviewed through a Medline search. Original research using quantitative and qualitative...... methodologies was considered. Priority was given to studies exploring aspects of sexuality other than erectile function. MAIN OUTCOME MEASURES: The prevalence, predictive factors, and management of post-prostatectomy sexual problems beyond erectile dysfunction. RESULTS: Most patients will develop urinary...

  17. Emerging Functions for N-Terminal Protein Acetylation in Plants

    Gibbs, Daniel J.

    2015-01-01

    N-terminal (Nt-) acetylation is a widespread but poorly understood co-translational protein modification. Two reports now shed light onto the proteome-wide dynamics and protein-specific consequences of Nt-acetylation in relation to plant development, stress-response, and protein stability, identifying this modification as a key regulator of diverse aspects of plant growth and behaviour.

  18. Medial temporal N-acetyl-aspartate in pediatric major depression.

    MacMaster, Frank P; Moore, Gregory J; Russell, Aileen; Mirza, Yousha; Taormina, S Preeya; Buhagiar, Christian; Rosenberg, David R

    2008-10-30

    The medial temporal cortex (MTC) has been implicated in the pathogenesis of pediatric major depressive disorder (MDD). Eleven MDD case-control pairs underwent proton magnetic resonance spectroscopic imaging. N-acetyl-aspartate was lower in the left MTC (27%) in MDD patients versus controls. Lower N-acetyl-aspartate concentrations in MDD patients may reflect reduced neuronal viability. PMID:18703320

  19. Medial temporal N-acetyl aspartate in pediatric major depression

    MacMaster, Frank P.; Moore, Gregory J; Russell, Aileen; Mirza, Yousha; Taormina, S. Preeya; Buhagiar, Christian; Rosenberg, David R.

    2008-01-01

    The medial temporal cortex (MTC) has been implicated in the pathogenesis of pediatric major depressive disorder (MDD). Eleven MDD-case control pairs underwent proton magnetic resonance spectroscopic imaging. N-acetyl-aspartate was lower in left MTC (27%) in MDD patients versus controls. Lower N-acetyl-aspartate concentrations in MDD patients may reflect reduced neuronal viability. PMID:18703320

  20. Homegrown religious radicalization

    Khawaja, Iram

    and their families. Existing literature and ways of thinking about the social psychological process of radicalization will be reviewed, such as social identity theory and transformative learning theory, and a theoretical framework based on a focus on belonging, recognition and the sense of community......It has been reported that a growing number of youngsters from Western Europe are engaging in conflicts motivated by religious and political conflicts in the Middle East. This paper aims at exploring the reasons behind this seemingly religious radicalization from the point of view of the youngsters...

  1. The Protective and Therapeutic Roles of Hexamethylenetetramine and N-Acetyl-Cysteine on Sulfur Mustard-Induced Oxidative Stress in Rat Serum

    Jafari, M; SH Sadraie; GR Kaka; Z Abdi; R. Rezaie; M Salehi

    2016-01-01

    Introduction: Sulfur mustard(SM) is a strong alkylating agent that increases the formation of free radicals. Therefore, this study aimed to evaluate the protective and therapeutic roles of hexamethylenetetramine (HMT) and N-acetyl-cysteine(NAC) in reduction of SM-induced oxidative stress in rat serum. Methods: In the present experimental study, male Wistar rats were randomly divided into eight groups including: control group, SM group (an endotracheal injection of SM 0.5%/kg only once), HM...

  2. Antemortem stress regulates protein acetylation and glycolysis in postmortem muscle.

    Li, Zhongwen; Li, Xin; Wang, Zhenyu; Shen, Qingwu W; Zhang, Dequan

    2016-07-01

    Although exhaustive research has established that preslaughter stress is a major factor contributing to pale, soft, exudative (PSE) meat, questions remain regarding the biochemistry of postmortem glycolysis. In this study, the influence of preslaughter stress on protein acetylation in relationship to glycolysis was studied. The data show that antemortem swimming significantly enhanced glycolysis and the total acetylated proteins in postmortem longissimus dorsi (LD) muscle of mice. Inhibition of protein acetylation by histone acetyltransferase (HAT) inhibitors eliminated stress induced increase in glycolysis. Inversely, antemortem injection of histone deacetylase (HDAC) inhibitors, trichostatin A (TSA) and nicotinamide (NAM), further increased protein acetylation early postmortem and the glycolysis. These data provide new insight into the biochemistry of postmortem glycolysis by showing that protein acetylation regulates glycolysis, which may participate in the regulation of preslaughter stress on glycolysis in postmortem muscle. PMID:26920270

  3. Unchanged acetylation of isoniazid by alcohol intake

    Wilcke, J T R; Døssing, M; Angelo, H R;

    2004-01-01

    SETTING: In 10 healthy subjects, the influence of acute alcohol intake on the pharmacokinetics of isoniazid (INH) was studied. OBJECTIVE: To test the hypothesis that alcohol increases the conversion of INH by acetylation into its metabolite acetylisoniazid. DESIGN: In a crossover design, an oral...... dose of 300 mg INH was administered on 2 separate days, 14 days apart, with or without alcohol to a serum alcohol of about 21 mmol/l (1 g/l) maintained for 12 h. RESULTS: Neither the metabolism of INH nor that of acetylisoniazid was changed by acute alcohol intake. CONCLUSION: Acute alcohol intake has...... no impact on the conversion of INH to its metabolite acetylisoniazid, which is catalysed by the enzyme N-acetyltranferase. Accordingly, a metabolic effect of acute alcohol intake on INH metabolism probably contributes little to the therapeutic failure of anti-tuberculosis treatment among alcoholics....

  4. Role of acetyl CoA

    Existence of an acetyltransferase, which catalizes acetylation of deacetylcephalosporin C to cephalosporin C, was demonstrated for the first time in cell-free extracts of Cephalosporium acremonium. The pH optimum of the enzyme appeared to be 7.0 to 7.5 and the enzyme required essentially Mg2+ as a cofactor for its reaction. The activity of this enzyme was not observed in the cell-free extracts of deacetylcephalosporin C-producing mutants Nos. 20, 29, 36 and 40, but was recovered in a revertant obtained from the mutant No. 40. These results indicate that deacetylcephalosporin C accumulation by these mutants was due to the lack of the acetyltransferase and made it reasonable that the terminal reaction of cephalosporin C biosynthesis in Cephalosporium acremonium proceeded by the catalytic action of acetyltransferase. (auth.)

  5. The biology of lysine acetylation integrates transcriptional programming and metabolism

    Mujtaba Shiraz

    2011-03-01

    Full Text Available Abstract The biochemical landscape of lysine acetylation has expanded from a small number of proteins in the nucleus to a multitude of proteins in the cytoplasm. Since the first report confirming acetylation of the tumor suppressor protein p53 by a lysine acetyltransferase (KAT, there has been a surge in the identification of new, non-histone targets of KATs. Added to the known substrates of KATs are metabolic enzymes, cytoskeletal proteins, molecular chaperones, ribosomal proteins and nuclear import factors. Emerging studies demonstrate that no fewer than 2000 proteins in any particular cell type may undergo lysine acetylation. As described in this review, our analyses of cellular acetylated proteins using DAVID 6.7 bioinformatics resources have facilitated organization of acetylated proteins into functional clusters integral to cell signaling, the stress response, proteolysis, apoptosis, metabolism, and neuronal development. In addition, these clusters also depict association of acetylated proteins with human diseases. These findings not only support lysine acetylation as a widespread cellular phenomenon, but also impel questions to clarify the underlying molecular and cellular mechanisms governing target selectivity by KATs. Present challenges are to understand the molecular basis for the overlapping roles of KAT-containing co-activators, to differentiate between global versus dynamic acetylation marks, and to elucidate the physiological roles of acetylated proteins in biochemical pathways. In addition to discussing the cellular 'acetylome', a focus of this work is to present the widespread and dynamic nature of lysine acetylation and highlight the nexus that exists between epigenetic-directed transcriptional regulation and metabolism.

  6. Trichoderma reesei CE16 acetyl esterase and its role in enzymatic degradation of acetylated hemicellulose

    Biely, Peter; Cziszarava, Maria; Agger, Jane W.;

    2014-01-01

    Results The combined action of GH10 xylanase and acetylxylan esterases (AcXEs) leads to formation of neutral and acidic xylooligosaccharides with a few resistant acetyl groups mainly at their non-reducing ends. We show here that these acetyl groups serve as targets for TrCE16 AcE. The most promin...

  7. Acetylation/deacetylation reactions of T-2, acetyl T-2, HT-2, and acetyl HT-2 toxins in bovine rumen fluid in vitro

    Munger, C.E.; Ivie, G.W.; Christopher, R.J.; Hammock, B.D.; Phillips, T.D.

    A tritiated preparation of the trichothecene mycotoxin, T-2 toxin, underwent both acetylation and deacetylation reactions when incubated with bovine rumen fluid in vitro. Products from incubations of T-2 in rumen fluid included acetyl T-2, HT-2, and acetyl HT-2. Direct studies with tritiated samples of each of these metabolites confirmed their relatively facile interconversion in the rumen. Studies with (/sup 3/H)HT-2 under conditions of inhibited esterase activity (added diisopropyl fluorophosphate) showed that acetylation is preferred at C-3 vs. C-4. Studies with (/sup 3/H)acetyl T-2 indicated that deacetylation similarly occurs with greater rapidity at C-3. There were no indications that ester hydrolysis of these trichothecenes occurred at C-8 or C-15 or that they were subjected to epoxide reduction reactions. These data suggest that acetylation of T-2 and other trichothecenes in the rumen in situ may ultimately result in the absorption of more lipophilic metabolites whose toxicological and residual properties are at present unknown.

  8. Acetylation/deacetylation reactions of T-2, acetyl T-2, HT-2, and acetyl HT-2 toxins in bovine rumen fluid in vitro

    A tritiated preparation of the trichothecene mycotoxin, T-2 toxin, underwent both acetylation and deacetylation reactions when incubated with bovine rumen fluid in vitro. Products from incubations of T-2 in rumen fluid included acetyl T-2, HT-2, and acetyl HT-2. Direct studies with tritiated samples of each of these metabolites confirmed their relatively facile interconversion in the rumen. Studies with [3H]HT-2 under conditions of inhibited esterase activity (added diisopropyl fluorophosphate) showed that acetylation is preferred at C-3 vs. C-4. Studies with [3H]acetyl T-2 indicated that deacetylation similarly occurs with greater rapidity at C-3. There were no indications that ester hydrolysis of these trichothecenes occurred at C-8 or C-15 or that they were subjected to epoxide reduction reactions. These data suggest that acetylation of T-2 and other trichothecenes in the rumen in situ may ultimately result in the absorption of more lipophilic metabolites whose toxicological and residual properties are at present unknown

  9. Violent Radicalization in Europe

    Dalgaard-Nielsen, Anja

    2010-01-01

    When, why, and how do people living in a democracy become radicalized to the point of being willing to use or directly support the use of terrorist violence against fellow citizens? This question has been at the center of academic and public debate over the past years as terrorist attacks...

  10. Radical School Reform.

    Gross, Beatrice, Ed.; Gross, Ronald, Ed.

    This book provides a comprehensive examination of the nature of the school crisis and the ways in which radical thinkers and educators are dealing with it. Excerpts from the writings of Jonathan Kozol, John Holt, Kenneth Clark, and others are concerned with the realities of education in ghettos and suburbs. Paul Goodman, Marshall McLuhan, Sylvia…

  11. Radical Financial Innovation

    Robert J. Shiller

    2004-01-01

    Radical financial innovation is the development of new institutions and methods that permit risk management to be extended far beyond its former realm, covering important new classes of risks. This paper compares past such innovation with potential future innovation, looking at the process that produced past success and the possibilities for future financial innovation.

  12. Radically enhanced molecular recognition

    Trabolsi, Ali

    2009-12-17

    The tendency for viologen radical cations to dimerize has been harnessed to establish a recognition motif based on their ability to form extremely strong inclusion complexes with cyclobis(paraquat-p-phenylene) in its diradical dicationic redox state. This previously unreported complex involving three bipyridinium cation radicals increases the versatility of host-guest chemistry, extending its practice beyond the traditional reliance on neutral and charged guests and hosts. In particular, transporting the concept of radical dimerization into the field of mechanically interlocked molecules introduces a higher level of control within molecular switches and machines. Herein, we report that bistable and tristable [2]rotaxanes can be switched by altering electrochemical potentials. In a tristable [2]rotaxane composed of a cyclobis(paraquat-p-phenylene) ring and a dumbbell with tetrathiafulvalene, dioxynaphthalene and bipyridinium recognition sites, the position of the ring can be switched. On oxidation, it moves from the tetrathiafulvalene to the dioxynaphthalene, and on reduction, to the bipyridinium radical cation, provided the ring is also reduced simultaneously to the diradical dication. © 2010 Macmillan Publishers Limited. All rights reserved.

  13. On Radical Feminism

    翟良锴

    2015-01-01

    <正>All men are created equal.For centuries,human have been struggling for their rights.Women,as a special social force,are fighting vigorously for their equal rights with men.According to an introduction to feminism,there are three main types of feminism:socialist,reformist and radical(Feminism 101).In order

  14. OH radicals in the troposphere

    OH radicals are radicals which determine the photochemistry of the troposphere. The reactivity of OH radicals to organic substances is one of the fundamental criteria for the evaluation of abiotic decomposition. Details are given about the photochemical formation and reaction of OH radicals, the decomposition reactions of organic compounds in the gaseous phase, the determination of the specific rates of OH radical decomposition reactions, measuring methods for the determination of OH radical concentrations in the troposphere, selected results, OH concentration distributions obtained from model calculations, and the influence of trace gases on OH concentrations. A summary, conclusions, and research proposals are attached. (orig./BBR)

  15. Free radical transfer in polymers

    For the present study of free-radical transfer in polymers pulse radiolysis and product studies have been carried out in aqueous solutions using thus far only the water-soluble polymers polyacrylic acid, polymethacrylic acid and polyvinyl alcohol. When OH radicals, generated in the radiolysis of N2O-saturated aqueous solutions, react with polymers the lifetime of the polymer radical thus created very much depends on the number of radicals per polymer chain. When there are a large number of radicals per chain their bimolecular decay may be faster than the corresponding (diffusion controlled) decay of monomeric radicals, but when the macromolecule contains only few or even just one radical their lifetime is considerably prolonged. Highly charged polymers such as polyacrylic acid at high pH attain a rod-like conformation which again favors a long lifetime of the radicals. Under such conditions, radical transfer reactions can occur. For example, in polyacrylic acid OH radicals generate two kinds of radicals side by side. The radical in β-position to the carboxylate group converts into the thermodynamically more stable α-radicals by an H-transfer reaction as can be followed by spectrophotometry. Besides radical transfer reactions β-fragmentation reactions occur causing chain scission. Such reactions can be followed in a pulse radiolysis experiment by conductometry, because counter ions are released upon chain scission. Such a process is especially effective in the case of polymethacrylic acid, where it results in a chain depolymerization. An intramolecular H-abstraction is also observed in the γ-radiolysis of polyacrylic acid with the corresponding peroxyl radicals. This causes a chain reaction to occur. The resulting hydroperoxides are unstable and decarboxylate given rise to acetylacetone-like products. In polyvinyl alcohol the peroxyl radicals in α-position to the alcohol function undergo HO2-elimination. This prevents a scission of the polymer chain in the

  16. Role of Histone Acetylation in Cell Cycle Regulation.

    Koprinarova, Miglena; Schnekenburger, Michael; Diederich, Marc

    2016-01-01

    Core histone acetylation is a key prerequisite for chromatin decondensation and plays a pivotal role in regulation of chromatin structure, function and dynamics. The addition of acetyl groups disturbs histone/DNA interactions in the nucleosome and alters histone/histone interactions in the same or adjacent nucleosomes. Acetyl groups can also provide binding sites for recruitment of bromodomain (BRD)-containing non-histone readers and regulatory complexes to chromatin allowing them to perform distinct downstream functions. The presence of a particular acetylation pattern influences appearance of other histone modifications in the immediate vicinity forming the "histone code". Although the roles of the acetylation of particular lysine residues for the ongoing chromatin functions is largely studied, the epigenetic inheritance of histone acetylation is a debated issue. The dynamics of local or global histone acetylation is associated with fundamental cellular processes such as gene transcription, DNA replication, DNA repair or chromatin condensation. Therefore, it is an essential part of the epigenetic cell response to processes related to internal and external signals. PMID:26303420

  17. Toward Radicalizing Community Service Learning

    Sheffield, Eric C.

    2015-01-01

    This article advocates a radicalized theoretical construction of community service learning. To accomplish this radicalization, I initially take up a discussion of traditional understandings of CSL rooted in pragmatic/progressive thought. I then suggest that this traditional structural foundation can be radicalized by incorporating Deborah…

  18. Synthesis and in Vitro Antioxidant Activity Evaluation of 3-Carboxycoumarin Derivatives and QSAR Study of Their DPPH• Radical Scavenging Activity

    Maria Teresa Sumaya-Martínez; Zeferino Gómez-Sandoval; Daniel Jaramillo Cano; Manuel Villanueva-García; Francisco J. Martínez-Martínez; Rodrigo Said Razo-Hernández; Ana Lilia Peraza-Campos

    2012-01-01

    The in vitro antioxidant activities of eight 3-carboxycoumarin derivatives were assayed by the quantitative 1,1-diphenyl-2-picrylhydrazil (DPPH•) radical scavenging activity method. 3-Acetyl-6-hydroxy-2H-1-benzopyran-2-one (C1) and ethyl 6-hydroxy-2-oxo-2H-1-benzopyran-3-carboxylate (C2) presented the best radical-scavenging activity. A quantitative structure-activity relationship (QSAR) study was performed and correlated with the experimental DPPH• scavenging data. We use...

  19. Oligorotaxane Radicals under Orders

    WANG, YUPING; Frasconi, Marco; Liu, Wei-Guang; Sun, Junling; Wu, Yilei; Nassar, Majed S.; Botros, Youssry Y.; Goddard, William A.; Wasielewski, Michael R.; Stoddart, J. Fraser

    2016-01-01

    A strategy for creating foldameric oligorotaxanes composed of only positively charged components is reported. Threadlike components—namely oligoviologens—in which different numbers of 4,4′-bipyridinium (BIPY2+) subunits are linked by p-xylylene bridges, are shown to be capable of being threaded by cyclobis(paraquat-p-phenylene) (CBPQT4+) rings following the introduction of radical-pairing interactions under reducing conditions. UV/vis/NIR spectroscopic and electrochemical investigations sugge...

  20. Oligorotaxane Radicals under Orders

    WANG, YUPING; Frasconi, Marco; Liu, Wei-Guang; Sun, Junling; Wu, Yilei; Nassar, Majed S.; Botros, Youssry Y.; Goddard, William A.; Wasielewski, Michael R.; Stoddart, J. Fraser

    2016-01-01

    A strategy for creating foldameric oligorotaxanes composed of only positively charged components is reported. Threadlike components—namely oligoviologens—in which different numbers of 4,4′-bipyridinium (BIPY^(2+)) subunits are linked by p-xylylene bridges, are shown to be capable of being threaded by cyclobis(paraquat-p-phenylene) (CBPQT^(4+)) rings following the introduction of radical-pairing interactions under reducing conditions. UV/vis/NIR spectroscopic and electrochemical investigations...

  1. Acetylation of C/EBPα inhibits its granulopoietic function.

    Bararia, Deepak; Kwok, Hui Si; Welner, Robert S; Numata, Akihiko; Sárosi, Menyhárt B; Yang, Henry; Wee, Sheena; Tschuri, Sebastian; Ray, Debleena; Weigert, Oliver; Levantini, Elena; Ebralidze, Alexander K; Gunaratne, Jayantha; Tenen, Daniel G

    2016-01-01

    CCAAT/enhancer-binding protein alpha (C/EBPα) is an essential transcription factor for myeloid lineage commitment. Here we demonstrate that acetylation of C/EBPα at lysine residues K298 and K302, mediated at least in part by general control non-derepressible 5 (GCN5), impairs C/EBPα DNA-binding ability and modulates C/EBPα transcriptional activity. Acetylated C/EBPα is enriched in human myeloid leukaemia cell lines and acute myeloid leukaemia (AML) samples, and downregulated upon granulocyte-colony stimulating factor (G-CSF)- mediated granulocytic differentiation of 32Dcl3 cells. C/EBPα mutants that mimic acetylation failed to induce granulocytic differentiation in C/EBPα-dependent assays, in both cell lines and in primary hematopoietic cells. Our data uncover GCN5 as a negative regulator of C/EBPα and demonstrate the importance of C/EBPα acetylation in myeloid differentiation. PMID:27005833

  2. Partially Acetylated Sugarcane Bagasse For Wicking Oil From Contaminated Wetlands

    Sugarcane bagasse was partially acetylated to enhance its oil-wicking ability in saturated environments while holding moisture for hydrocarbon biodegradation. The water sorption capacity of raw bagasse was reduced fourfold after treatment, which indicated considerably increased ...

  3. Function-structure relationships of acetylated pea starches

    J. Huang

    2006-01-01

    Cowpea, chickpea and yellow pea starches were studied and the results showed that their properties were strongly related to the chemical fine structures of the starches. Furthermore, granular starches were modified using two types of chemical acetylation reagents and then separated into different size fractions. The amount of introduced acetyl groups was found to depend on the size of the granules for the reaction with rapidly reacting reagent acetic acid anhydride, whereas the amount of intr...

  4. Site-specific acetylation of ISWI by GCN5

    Chioda Mariacristina

    2007-08-01

    Full Text Available Abstract Background The tight organisation of eukaryotic genomes as chromatin hinders the interaction of many DNA-binding regulators. The local accessibility of DNA is regulated by many chromatin modifying enzymes, among them the nucleosome remodelling factors. These enzymes couple the hydrolysis of ATP to disruption of histone-DNA interactions, which may lead to partial or complete disassembly of nucleosomes or their sliding on DNA. The diversity of nucleosome remodelling factors is reflected by a multitude of ATPase complexes with distinct subunit composition. Results We found further diversification of remodelling factors by posttranslational modification. The histone acetyltransferase GCN5 can acetylate the Drosophila remodelling ATPase ISWI at a single, conserved lysine, K753, in vivo and in vitro. The target sequence is strikingly similar to the N-terminus of histone H3, where the corresponding lysine, H3K14, can also be acetylated by GCN5. The acetylated form of ISWI represents a minor species presumably associated with the nucleosome remodelling factor NURF. Conclusion Acetylation of histone H3 and ISWI by GCN5 is explained by the sequence similarity between the histone and ISWI around the acetylation site. The common motif RKT/SxGx(KacxPR/K differs from the previously suggested GCN5/PCAF recognition motif GKxxP. This raises the possibility of co-regulation of a nucleosome remodelling factor and its nucleosome substrate through acetylation of related epitopes and suggests a direct crosstalk between two distinct nucleosome modification principles.

  5. A dysregulated acetyl/SUMO switch of FXR promotes hepatic inflammation in obesity

    Kim, Dong-Hyun; Xiao, Zhen; Kwon, Sanghoon; Sun, Xiaoxiao; Ryerson, Daniel; Tkac, David; Ma, Ping; Wu, Shwu-Yuan; Chiang, Cheng-Ming; Zhou, Edward; Xu, H. Eric; Palvimo, Jorma J; Chen, Lin-Feng; Kemper, Byron; Kemper, Jongsook Kim

    2014-01-01

    Acetylation of transcriptional regulators is normally dynamically regulated by nutrient status but is often persistently elevated in nutrient-excessive obesity conditions. We investigated the functional consequences of such aberrantly elevated acetylation of the nuclear receptor FXR as a model. Proteomic studies identified K217 as the FXR acetylation site in diet-induced obese mice. In vivo studies utilizing acetylation-mimic and acetylation-defective K217 mutants and gene expression profilin...

  6. A radical publishing collective: the Journal of Radical Librarianship

    Simon Barron

    2015-01-01

    The Journal of Radical Librarianship is a new open-access journal publishing scholarly work in the field of radical librarianship. The focus on critical approaches to librarianship and anti-marketisation of information is reflected not only in our subject matter but in our publishing model, our licensing model, and our organisational practices. We hope to foster open and engaging discussions about radical approaches to librarianship and information studies.

  7. Purification and properties of an O-acetyl-transferase from Escherichia coli that can O-acetylate polysialic acid sequences

    Certain strains of bacteria synthesize an outer polysialic acid (K1) capsule. Some strains of K1+ E.coli are also capable of adding O-acetyl-esters to the exocyclic hydroxyl groups of the sialic acid residues. Both the capsule and the O-acetyl modification have been correlated with differences in antigenicity and pathogenicity. The authors have developed an assay for an O-acetyl-transferase in E.coli that transfers O-[3H]acetyl groups from [3H]acetyl-Coenzyme A to colominic acid (fragments of the polysialic acid capsule). Using this assay, the enzyme was solubilized, and purified ∼ 600-fold using a single affinity chromatography step with Procion Red-A Agarose. The enzyme also binds to Coenzyme A Sepharose, and can be eluted with high salt or Coenzyme A. The partially purified enzyme has a pH optimum of 7.0 - 7.5, is unaffected by divalent cations, is inhibited by high salt concentrations, is inhibited by Coenzyme A (50% inhibition at 100 μM), and shows an apparent Km for colominic acid of 3.7 mM (sialic acid concentration). This enzyme could be involved in the O-acetyl +/- form variation seen in some strains of K1+ E.coli

  8. N-Acetyl Cysteine Inhibits Endothelin-1-Induced ROS Dependent Cardiac Hypertrophy through Superoxide Dismutase Regulation

    Sobia Mushtaq

    2015-07-01

    Full Text Available Objective: Oxidative stress down regulates antioxidant enzymes including superoxide dismutase (SOD and contributes to the development of cardiac hypertrophy. N-Acetyl cysteine (NAC can enhance the SOD activity, so the aim of this study is to highlight the inhibitory role of NAC against endothelin-1 (ET-1-induced cardiac hypertrophy. Materials and Methods: In this experimental study at QAU from January, 2013 to March, 2013. ET-1 (50 μg/kg and NAC (50 mg/kg were given intraperitoneally to 6-day old neonatal rats in combination or alone. All rats were sacrificed 15 days after the final injection. Histological analysis was carried out to observe the effects caused by both drugs. Reactive oxygen species (ROS analysis and SOD assay were also carried out. Expression level of hypertrophic marker, brain natriuretic peptide (BNP, was detected by western blotting. Results: Our findings showed that ET-1-induced cardiac hypertrophy leading towards heart failure was due to the imbalance of different parameters including free radical-induced oxidative stress and antioxidative enzymes such as SOD. Furthermore NAC acted as an antioxidant and played inhibitory role against ROS-dependent hypertrophy via regulatory role of SOD as a result of oxidative response associated with hypertrophy. Conclusion: ET-1-induced hypertrophic response is associated with increased ROS production and decreased SOD level, while NAC plays a role against free radicals-induced oxidative stress via SOD regulation.

  9. Oligorotaxane Radicals under Orders.

    Wang, Yuping; Frasconi, Marco; Liu, Wei-Guang; Sun, Junling; Wu, Yilei; Nassar, Majed S; Botros, Youssry Y; Goddard, William A; Wasielewski, Michael R; Stoddart, J Fraser

    2016-02-24

    A strategy for creating foldameric oligorotaxanes composed of only positively charged components is reported. Threadlike components-namely oligoviologens-in which different numbers of 4,4'-bipyridinium (BIPY(2+)) subunits are linked by p-xylylene bridges, are shown to be capable of being threaded by cyclobis(paraquat-p-phenylene) (CBPQT(4+)) rings following the introduction of radical-pairing interactions under reducing conditions. UV/vis/NIR spectroscopic and electrochemical investigations suggest that the reduced oligopseudorotaxanes fold into highly ordered secondary structures as a result of the formation of BIPY(•+) radical cation pairs. Furthermore, by installing bulky stoppers at each end of the oligopseudorotaxanes by means of Cu-free alkyne-azide cycloadditions, their analogous oligorotaxanes, which retain the same stoichiometries as their progenitors, can be prepared. Solution-state studies of the oligorotaxanes indicate that their mechanically interlocked structures lead to the enforced interactions between the dumbbell and ring components, allowing them to fold (contract) in their reduced states and unfold (expand) in their fully oxidized states as a result of Coulombic repulsions. This electrochemically controlled reversible folding and unfolding process, during which the oligorotaxanes experience length contractions and expansions, is reminiscent of the mechanisms of actuation associated with muscle fibers. PMID:27163033

  10. Bursectomy at radical gastrectomy

    Cuneyt; Kayaalp

    2015-01-01

    Radical gastrectomy with extended lymph node dissec tion and prophylactic resection of the omentum, peri toneum over the posterior lesser sac, pancreas and/o spleen was advocated at the beginning of the 1960 s in Japan. In time, prophylactic routine resections of the pancreas and/or spleen were abandoned because of the high incidence of postoperative complications. However omentectomy and bursectomy continued to be standard parts of traditional radical gastrectomy. The bursaomentalis was thought to be a natural barrier against invasion of cancer cells into the posterior part of the stomach. The theoretical rationale for bursectomy was to reduce the risk of peritoneal recurrences by eliminating the peritoneum over the lesser sac, which might include free cancer cells or micrometastases. Over time, the indication for bursectomy was gradually reduced to only patients with posterior gastric wall tumors penetrating the serosa. Despite its theoretical advantages, its benefit for recurrence or survival has not been proven yet. The possible reasons for this inconsistency are discussed in this review. In conclusion, the value of bursectomy in the treatment of gastric cancer is still under debate and large-scale randomized studies are necessary. Until clear evidence of patient benefit is obtained, its routine use cannot be recommended.

  11. Histones of Chlamydomonas reinhardtii. Synthesis, acetylation, and methylation

    Histones of the green alga Chlamydomonas reinhardtii were prepared by a new method and fractionated by reversed-phase high-performance liquid chromatography. Acid-urea-Triton gel analysis and tritiated acetate labeling demonstrated high levels of steady-state acetylation for the single histone H3 protein, in contrast to low levels on histones H4 and H2B. Twenty percent of histone H3 is subject to dynamic acetylation with, on average, three acetylated lysine residues per protein molecule. Histone synthesis in light-dark-synchronized cultures was biphasic with pattern differences between two histone H1 variants, between two H2A variants, and between H2B and ubiquitinated H2B. Automated protein sequence analysis of histone H3 demonstrated a site-specific pattern of steady-state acetylation between 7 and 17% at five of the six amino-terminal lysines and of monomethylation between 5 and 81% at five of the eight amino-terminal lysines in a pattern that may limit dynamic acetylation. An algal histone H3 sequence was confirmed by protein sequencing with a since threonine as residue 28 instead of the serine(28)-alanine(29) sequence, present in all other known plant and animal H3 histones

  12. Curcumin-induced Histone Acetylation in Malignant Hematologic Cells

    Junbin HU; Yan WANG; Yan CHEN

    2009-01-01

    This study investigated the inhibitory effects of curcumin on proliferation of hemato-logical malignant cells in vitro and the anti-tumor mechanism at histone acetylation/histone deacety-lation levels.The effects of curcumin and histone deacetylase inhibitor trichostatin A (TSA) on the growth of Raji cells were tested by MTT assay.The expression of acetylated histone-3 (H3) in Raji,HL60 and K562 cells,and peripheral blood mononuclear cells (PBMCs) treated with curcumin or TSA was detected by immunohistochemistry and FACS.The results showed curcumin inhibited pro-liferation of Raji cells significantly in a time- and dose-dependent fashion,while exhibited low toxic-ity in PBMCs.Curcumin induced up-regulation of the expression of acetylated H3 dose-dependently in all malignant cell lines tested.In conclusion,curcumin inhibited proliferation of Raji cells selec-tively,enhanced the level of acetylated H3 in Raji,HL60,and K562 cells,which acted as a histone deacetylase inhibitor like TSA.Furthermore,up-regulation of H3 acetylation may play an important role in regulating the proliferation of Raji cells.

  13. Olig1 Acetylation and Nuclear Export Mediate Oligodendrocyte Development.

    Dai, Jinxiang; Bercury, Kathryn K; Jin, Weilin; Macklin, Wendy B

    2015-12-01

    The oligodendrocyte transcription factor Olig1 is critical for both oligodendrocyte development and remyelination in mice. Nuclear to cytoplasmic translocation of Olig1 protein occurs during brain development and in multiple sclerosis, but the detailed molecular mechanism of this translocation remains elusive. Here, we report that Olig1 acetylation and deacetylation drive its active translocation between the nucleus and the cytoplasm in both mouse and rat oligodendrocytes. We identified three functional nuclear export sequences (NES) localized in the basic helix-loop-helix domain and one specific acetylation site at Lys 150 (human Olig1) in NES1. Olig1 acetylation and deacetylation are regulated by the acetyltransferase CREB-binding protein and the histone deacetylases HDAC1, HDAC3, and HDAC10. Acetylation of Olig1 decreased its chromatin association, increased its interaction with inhibitor of DNA binding 2 and facilitated its retention in the cytoplasm of mature oligodendrocytes. These studies establish that acetylation of Olig1 regulates its chromatin dissociation and subsequent translocation to the cytoplasm and is required for its function in oligodendrocyte maturation. PMID:26631469

  14. Radical cystectomy in eldery

    Bančević Vladimir

    2015-01-01

    Full Text Available Background/Aim. Radical cystectomy is the method of choice for the treatment of muscle invasive bladder cancer. This major surgery is associated with many complications, especially in older patients. The aim of this study was to analyze preoperative comorbidity, and intraoperative and postoperative complicatons in patients older than 75 years. Methods. This clinical, retrospective study included 46 patients over 75 years, who underwent radical cystectomy. Indications for surgery, and complications during and after the surgery were followed up. Results. Preoperatively, anemia caused by hematuria was registered in 76% of the patients. In 52% of the patients urine derivation was performed by ileal conduit, in 35% by ureterocutaneostomy and in 13% orthotopic ileal neobladder was created. The average duration of surgery was 190 (120-300 min. A total of 76% of the patients were treated by blood supstitution intraoperatively, average 630 (310-1230 mL. Concerning pathological stage of transitional cell carcinoma of urinary bladder, 26% of the patients had T2, 4% T3a, 52% T3b, and 14% T4a stage. In one case, planocellular carcinoma was diagnosed by patohistological examination, and in 2 cases prostate carcinoma was incidentally found. The average duration of hospitalization was 16 (8-35 days. Conclusion. The main reason for cystectomy in patients over 70 and 80 years was gross hematuria caused by bladder cancer, with consecutive anemia which could not be solved using endoscopic treatment or blood supstitution. As expected, a prolonged stay in hospital after cystectomy, and a higher rate of complications were recorded in this population.

  15. H4K44 Acetylation Facilitates Chromatin Accessibility during Meiosis

    Jialei Hu

    2015-12-01

    Full Text Available Meiotic recombination hotspots are associated with histone post-translational modifications and open chromatin. However, it remains unclear how histone modifications and chromatin structure regulate meiotic recombination. Here, we identify acetylation of histone H4 at Lys44 (H4K44ac occurring on the nucleosomal lateral surface. We show that H4K44 is acetylated at pre-meiosis and meiosis and displays genome-wide enrichment at recombination hotspots in meiosis. Acetylation at H4K44 is required for normal meiotic recombination, normal levels of double-strand breaks (DSBs during meiosis, and optimal sporulation. Non-modifiable H4K44R results in increased nucleosomal occupancy around DSB hotspots. Our results indicate that H4K44ac functions to facilitate chromatin accessibility favorable for normal DSB formation and meiotic recombination.

  16. Recycling and Reuse of Ionic Liquid in Homogeneous Cellulose Acetylation

    HUANG Kelin; WU Rui; CAO Yan; LI Huiquan; WANG Jinshu

    2013-01-01

    Molecular distillation was used to recover ionic liquid (IL) 1-allyl-3-methylimidazolium chloride (AmimC1) in homogeneous cellulose acetylation.The five factors that affect the separation efficiency of molecular distillation,namely,feed flow rate,distillation temperature,feed temperature,wiper rotating speed,and distillation pressure,are discussed.The optimal recovery condition was determined via orthogonal experiments using an OA9(34) design.The IL was recycled and reused 5 times in the homogeneous cellulose acetylation system under optimal conditions.The purity of recycled IL the 5th time reached 99.56%.FT-IR (Fourier transform infrared spectroscopy) and 1H NMR (nuclear magnetic resonance) spectroscopy showed that the structure of the recovered IL is not changed.This work proves that AmirnCl has excellent reusability,and that molecular distillation is an effective method for recovering IL in homogeneous cellulose acetylation.

  17. Study on Reactions of 2-Acetyl-7-methylaminotropone with Pyridinecarboxyaldehydes

    GAO Wen-Tao; ZHENG Zhuo

    2003-01-01

    @@ Cinnamoyl group is a versatile constituent because of bearing active carbonyl group and α, β-unsaturated car bon-carbon double bond. A wide variety of heterocycle-fused troponoid compounds have been derived from cinnamoyl-substituted tropones. For examples, the 3-(4-aryl-3-cyano-2- methoxypyridin-6-yl)tropones were synthesized by the reactions of 2-acetyl-7-methylaminotropone with malononitrile via michael addition and cyclization. [1] There have been some reports about the synthesis of 2-cinnamoyl-7-methylaminotropone, [2,3] herein we further report the synthesis of this kind of compounds by the reactions of 2-acetyl-7-methylaminotropone with pyridinecarboxyaldehydes.

  18. Acetylation site specificities of lysine deacetylase inhibitors in human cells

    Schölz, Christian; Weinert, Brian Tate; Wagner, Sebastian A;

    2015-01-01

    Lysine deacetylases inhibitors (KDACIs) are used in basic research, and many are being investigated in clinical trials for treatment of cancer and other diseases. However, their specificities in cells are incompletely characterized. Here we used quantitative mass spectrometry (MS) to obtain...... acetylation signatures for 19 different KDACIs, covering all 18 human lysine deacetylases. Most KDACIs increased acetylation of a small, specific subset of the acetylome, including sites on histones and other chromatin-associated proteins. Inhibitor treatment combined with genetic deletion showed that the...

  19. Studies of radiation-produced radicals and radical ions

    The radiolytic oxidation of anti-5-methylbicyclo[2.1.0]pentane gives the 1-methylcyclopentene radical cation as the sole rearrangement product H migration whereas oxidation of its syn isomer results in the highly selective formation of the 3-methylcyclopentene radical cation by methyl group migration. Since exactly the same stereoselectivity of olefin formation was observed in corresponding PET (photosensitized electron transfer) studies in the liquid phase, it is concluded that the rearrangement in this case also occurs through the intermediacy of radical cations. Clearly, the radical cation rearrangement must occur very rapidly (10-8--10-9s) under liquid-phase conditions at room temperature to compete with back electron transfer, and therefore the hydrogen (or methyl) migration is a fast process under these conditions. An intramolecular cycloaddition reaction was demonstrated in the radical cation rearrangement of 4-vinylcyclohexene to bicyclo[3.2.1]oct-2-ene. ESR studies show that the radiolytic oxidation of quadricyclane in Freon matrices under conditions of high substrate dilution leads to the bicyclo[3.2.0]hepta-2,6-diene radical cation as well as the previously reported norbornadiene radical cation, the former species predominating at sufficiently low concentrations

  20. Photofragment translational spectroscopy of three body dissociations and free radicals

    North, S.W.

    1995-04-01

    This dissertation describes several three-body dissociations and the photodissociation of methyl radicals studied using photofragment translational spectroscopy. The first chapter provides an introduction to three body dissociation, examines current experimental methodology, and includes a discussion on the treatment of photofragment translational spectroscopy data arising from three-body fragmentation. The ultraviolet photodissociation of azomethane into two methyl radicals and nitrogen is discussed in chapter 2. Chapter 3 describes the photodissociation of acetone at 248 nm and 193 nm. At 248 nm the translational energy release from the initial C-C bond cleavage matches the exit barrier height and a comparison with results at 266 nm suggests that is invariant to the available energy. A fraction of the nascent CH{sub 3}CO radicals spontaneously dissociate following rotational averaging. The for the second C-C bond cleavage also matches the exit barrier height. At 193 nm the experimental data can be successfully fit assuming that the dynamics are analogous to those at 248 nm. A simplified model of energy partitioning which adequately describes the experimental results is discussed. Experiments on acetyl halides provide additional evidence to support the proposed acetone dissociation mechanism. A value of 17.0{+-}1.0 kcal/mole for the barrier height, CH{sub 3}CO decomposition has been determined. The photodissociation of methyl radical at 193 nm and 212.8 nm is discussed in the chapter 5. The formation of CH{sub 2} ({sup 1}A{sub l}) and H ({sup 2}S) was the only single photon dissociation pathway observed at both wavelengths.

  1. New lysine-acetylated proteins screened by immunoaffinity and liquid chromatography-mass spectrometry

    2010-01-01

    The lack of selective extraction specific for lysine-acetylated proteins has been a major problem in the field of acetylation biology,though acetylation plays a key role in many biological processes.In this paper,we report for the first time the proteomic screening of lysine-acetylated proteins from a mouse liver tissue,by a new approach of immunoaffinity purification of lysine-acetylated peptides combined with nano-HPLC/MS/MS analysis.We have found 20 lysine-acetylated proteins with 21 lysine-acetylated sites,among which 12 lysine-acetylated proteins and 16 lysine-acetylated sites have never been reported before.Notably,three acetyltransferases harboring in mitochondrion are newly discovered acetyltransferases responsible for the acetylation of nonhistone proteins.We have explored the significant patterns of residue preference by the hierarchical clustering analysis of amino acid residues surrounding acetylation sites,which could be helpful to the prediction of new sites of lysine acetylation.Our findings provide more candidates for studying the important roles played by acetylation in diverse cellular pathways and related human diseases.

  2. Expression of Genes Related to Oxidative Stress in Yeast Treated with Ionizing Radiation and N-acetyl -L-cysteine

    Park, Ji Young; Kim, Jin Kyu [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of); Nili, Mohammad [Dawnesh Radiation Research Institute, Barcelona (Spain)

    2010-10-15

    Ionizing radiation (IR) induces water radiolysis, which generates highly reactive hydroxyl radicals. Reactive oxygen species (ROS) cause apoptosis and cell damage including DNA strand breaks (DSBs), base damage, protein damage and lipid-hydroperoxide. Detoxifying enzymes are immediately triggered for ROS scavenging. Yeast contains two forms of superoxide dismutase (SOD). SOD1 as a cytosolic copper-zinc superoxide dismutase is located in the cytoplasm and cytosol. SOD2 as a manganese containing enzyme is act in mitochondria matrix and mitochondrion. These enzymes scavenge superoxide radicals by catalyzing the conversion of two of these radicals into hydrogen peroxide and molecular oxygen. The hydrogen peroxide formed by superoxide dismutase and by other processes is scavenged by catalase, a ubiquitous heme protein that catalyzes the dismutation of hydrogen peroxide into water and molecular oxygen. Yeast contains two catalases. Catalase A (CTA1) and Cytosolic catalase T (CTT1) is located in peroxisome and cytoplasm, respectively. Yeast has two glutathione (GSH) peroxidases, which are GPX1 and GPX2. GPX1 and GPX2 are component of cellular component and cytoplasm, respectively. The biochemical function of GSH peroxidase is to reduce lipid-hydroperoxides to their corresponding alcohols and to reduce free hydrogen peroxide to water. Otherwise, chemicals and materials help ROS detoxification against oxidative damage. N-acetyl-Lcysteine (NAC) having a thiol, a precursor for glutathione (GSH), is known as one of the antioxidants. In this study, we examined the effect of NAC through gene expressions related to protective enzyme against oxidative stress in yeast

  3. Expression of Genes Related to Oxidative Stress in Yeast Treated with Ionizing Radiation and N-acetyl -L-cysteine

    Ionizing radiation (IR) induces water radiolysis, which generates highly reactive hydroxyl radicals. Reactive oxygen species (ROS) cause apoptosis and cell damage including DNA strand breaks (DSBs), base damage, protein damage and lipid-hydroperoxide. Detoxifying enzymes are immediately triggered for ROS scavenging. Yeast contains two forms of superoxide dismutase (SOD). SOD1 as a cytosolic copper-zinc superoxide dismutase is located in the cytoplasm and cytosol. SOD2 as a manganese containing enzyme is act in mitochondria matrix and mitochondrion. These enzymes scavenge superoxide radicals by catalyzing the conversion of two of these radicals into hydrogen peroxide and molecular oxygen. The hydrogen peroxide formed by superoxide dismutase and by other processes is scavenged by catalase, a ubiquitous heme protein that catalyzes the dismutation of hydrogen peroxide into water and molecular oxygen. Yeast contains two catalases. Catalase A (CTA1) and Cytosolic catalase T (CTT1) is located in peroxisome and cytoplasm, respectively. Yeast has two glutathione (GSH) peroxidases, which are GPX1 and GPX2. GPX1 and GPX2 are component of cellular component and cytoplasm, respectively. The biochemical function of GSH peroxidase is to reduce lipid-hydroperoxides to their corresponding alcohols and to reduce free hydrogen peroxide to water. Otherwise, chemicals and materials help ROS detoxification against oxidative damage. N-acetyl-Lcysteine (NAC) having a thiol, a precursor for glutathione (GSH), is known as one of the antioxidants. In this study, we examined the effect of NAC through gene expressions related to protective enzyme against oxidative stress in yeast

  4. Radical production in biological systems

    This paper describes our effort to develop a metric for radiation exposure that is more fundamental than adsorbed dose and upon which a metric for exposure to chemicals could be based. This metric is based on the production of radicals by the two agents. Radicals produced by radiation in biological systems commonly assumed to be the same as those produced in water despite the presence of a variety of complex molecules. This may explain why the extensive efforts to describe the relationship between energy deposition (track structure) and molecular damage to DNA, based on the spectrum of radicals produced, have not been successful in explaining simple biological effects such as cell killing. Current models assume that DNA and its basic elements are immersed in water-like media and only model the production and diffusion of water-based radicals and their interaction with DNA structures; these models lack the cross sections associated with each macro-component of DNA and only treat water-based radicals. It has been found that such models are not realistic because DNA is not immersed in pure water. A computer code capable of simulating electron tracks, low-energy electrons, energy deposition in small molecules, and radical production and diffusion in water like media has been developed. This code is still in at a primitive stage and development is continuing. It is being used to study radical production by radiation, and radical diffusion and interactions in simple molecular systems following their production. We are extending the code to radical production by chemicals to complement our PBPK modeling efforts. It therefore has been developed primarily for use with radionuclides that are in biological materials, and not for radiation fields

  5. Guest Editorial: Processes of Radicalization and De-Radicalization

    Donatella Della Porta

    2012-05-01

    Full Text Available The study of radicalization and de-radicalization, understood as processes leading towards the increased or decreased use of political violence, is central to the question of how political violence emerges, how it can be prevented, and how it can be contained. The focus section of this issue of the International Journal of Conflict and Violence addresses radicalization and de-radicalization, seeking to develop a more comprehensive understanding of the processes, dynamics, and mechanisms involved and taking an interdisciplinary approach to overcome the fragmentation into separate disciplines and focus areas. Contributions by Pénélope Larzillière, Felix Heiduk, Bill Kissane, Hank Johnston, Christian Davenport and Cyanne Loyle, Veronique Dudouet, and Lasse Lindekilde address repressive settings, legitimacy, institutional aspects, organizational outcomes, and dynamics in Europe, Asia, Africa, and North and South America.

  6. Tubulin acetylation: responsible enzymes, biological functions and human diseases.

    Li, Lin; Yang, Xiang-Jiao

    2015-11-01

    Microtubules have important functions ranging from maintenance of cell morphology to subcellular transport, cellular signaling, cell migration, and formation of cell polarity. At the organismal level, microtubules are crucial for various biological processes, such as viral entry, inflammation, immunity, learning and memory in mammals. Microtubules are subject to various covalent modifications. One such modification is tubulin acetylation, which is associated with stable microtubules and conserved from protists to humans. In the past three decades, this reversible modification has been studied extensively. In mammals, its level is mainly governed by opposing actions of α-tubulin acetyltransferase 1 (ATAT1) and histone deacetylase 6 (HDAC6). Knockout studies of the mouse enzymes have yielded new insights into biological functions of tubulin acetylation. Abnormal levels of this modification are linked to neurological disorders, cancer, heart diseases and other pathological conditions, thereby yielding important therapeutic implications. This review summarizes related studies and concludes that tubulin acetylation is important for regulating microtubule architecture and maintaining microtubule integrity. Together with detyrosination, glutamylation and other modifications, tubulin acetylation may form a unique 'language' to regulate microtubule structure and function. PMID:26227334

  7. Acetylation regulates DNA repair mechanisms in human cells.

    Piekna-Przybylska, Dorota; Bambara, Robert A; Balakrishnan, Lata

    2016-06-01

    The p300-mediated acetylation of enzymes involved in DNA repair and replication has been previously shown to stimulate or inhibit their activities in reconstituted systems. To explore the role of acetylation on DNA repair in cells we constructed plasmid substrates carrying inactivating damages in the EGFP reporter gene, which should be repaired in cells through DNA mismatch repair (MMR) or base excision repair (BER) mechanisms. We analyzed efficiency of repair within these plasmid substrates in cells exposed to deacetylase and acetyltransferase inhibitors, and also in cells deficient in p300 acetyltransferase. Our results indicate that protein acetylation improves DNA mismatch repair in MMR-proficient HeLa cells and also in MMR-deficient HCT116 cells. Moreover, results suggest that stimulated repair of mismatches in MMR-deficient HCT116 cells is done though a strand-displacement synthesis mechanism described previously for Okazaki fragments maturation and also for the EXOI-independent pathway of MMR. Loss of p300 reduced repair of mismatches in MMR-deficient cells, but did not have evident effects on BER mechanisms, including the long patch BER pathway. Hypoacetylation of the cells in the presence of acetyltransferase inhibitor, garcinol generally reduced efficiency of BER of 8-oxoG damage, indicating that some steps in the pathway are stimulated by acetylation. PMID:27104361

  8. Surface effects in the acetylation of granular potato starch

    Steeneken, P.A.M.; Woortman, A.J.J.

    2008-01-01

    The occurrence of surface effects in the acetylation of granular potato starch with acetic anhydride to degrees of substitution 0.04-0.2 was studied by two different approaches. The first approach involved the fractionation of granular starch acetates into five different size classes and analysis of

  9. Predicting post-translational lysine acetylation using support vector machines

    Gnad, Florian; Ren, Shubin; Choudhary, Chunaram;

    2010-01-01

    spectrometry to identify 3600 lysine acetylation sites on 1750 human proteins covering most of the previously annotated sites and providing the most comprehensive acetylome so far. This dataset should provide an excellent source to train support vector machines (SVMs) allowing the high accuracy in silico...

  10. The potential role of wood acetylation in climate change mitigation

    Van der Lugt, P.; Vogtländer, J.G.; Alexander, J.; Bongers, F.; Stebbins, H.

    2014-01-01

    In a carbon footprint assessment, the greenhouse gas emissions during the life cycle of a material can be measured, and compared to alternative products in terms of kg CO2 equivalent. If applied correctly, wood acetylation opens up a range of new innovative applications in which high performance yet

  11. Protein Acetylation Is Involved in Salmonella enterica Serovar Typhimurium Virulence.

    Sang, Yu; Ren, Jie; Ni, Jinjing; Tao, Jing; Lu, Jie; Yao, Yu-Feng

    2016-06-01

    Salmonella causes a range of diseases in different hosts, including enterocolitis and systemic infection. Lysine acetylation regulates many eukaryotic cellular processes, but its function in bacteria is largely unexplored. The acetyltransferase Pat and NAD(+)-dependent deacetylase CobB are involved in the reversible protein acetylation in Salmonella Typhimurium. Here, we used cell and animal models to evaluate the virulence of pat and cobB deletion mutants in S. Typhimurium and found that pat is critical for bacterial intestinal colonization and systemic infection. Next, to understand the underlying mechanism, genome-wide transcriptome was analyzed. RNA sequencing data showed that the expression of Salmonella pathogenicity island 1 (SPI-1) is partially dependent on pat In addition, we found that HilD, a key transcriptional regulator of SPI-1, is a substrate of Pat. The acetylation of HilD by Pat maintained HilD stability and was essential for the transcriptional activation of HilA. Taken together, these results suggest that a protein acetylation system regulates SPI-1 expression by controlling HilD in a posttranslational manner to mediate S. Typhimurium virulence. PMID:26810370

  12. Enzymatic synthesis of carbon-11 N-acetyl-D-glucosamine

    An enzymatic synthesis of [11C] N-acetyl-D-glucosamine is described. 11CO2 is reacted with methylmagnesium bromide to form [1-11C]acetate. The latter is converted to [11C]acetylcoenzyme A by passage over an enzyme reactor containing immobilized acetylcoenzyme A synthetase, and to the title compound after purification. (author)

  13. SCANDIUM TRIFLATE CATALYZED ACETYLATION OF STARCH UNDER MILD CONDITIONS

    Scandium (III) trifluoromethan sulfonate (Sc(OTf)3) was investigated as a catalyst for the acetylation of starch in order to determine the potential for preparing new types of starch esters under mild conditions. At room temperature, dry granular corn starch reacts with acetic anhydride in the pres...

  14. Redox Properties of Free Radicals.

    Neta, P.

    1981-01-01

    Describes pulse radiolysis as a useful means in studing one-electron redox potentials. This method allows the production of radicals and the determination of their concentration and rates of reaction. (CS)

  15. DMPD: Acetylation of MKP-1 and the control of inflammation. [Dynamic Macrophage Pathway CSML Database

    Full Text Available 18922786 Acetylation of MKP-1 and the control of inflammation. Chi H, Flavell RA. S...ci Signal. 2008 Oct 14;1(41):pe44. (.png) (.svg) (.html) (.csml) Show Acetylation of MKP-1 and the control of inflammation.... PubmedID 18922786 Title Acetylation of MKP-1 and the control of inflammation. Authors Chi H,

  16. The Acetyl Group Buffering Action of Carnitine Acetyltransferase Offsets Macronutrient-Induced Lysine Acetylation of Mitochondrial Proteins

    Michael N. Davies

    2016-01-01

    Full Text Available Lysine acetylation (AcK, a posttranslational modification wherein a two-carbon acetyl group binds covalently to a lysine residue, occurs prominently on mitochondrial proteins and has been linked to metabolic dysfunction. An emergent theory suggests mitochondrial AcK occurs via mass action rather than targeted catalysis. To test this hypothesis, we performed mass spectrometry-based acetylproteomic analyses of quadriceps muscles from mice with skeletal muscle-specific deficiency of carnitine acetyltransferase (CrAT, an enzyme that buffers the mitochondrial acetyl-CoA pool by converting short-chain acyl-CoAs to their membrane permeant acylcarnitine counterparts. CrAT deficiency increased tissue acetyl-CoA levels and susceptibility to diet-induced AcK of broad-ranging mitochondrial proteins, coincident with diminished whole body glucose control. Sub-compartment acetylproteome analyses of muscles from obese mice and humans showed remarkable overrepresentation of mitochondrial matrix proteins. These findings reveal roles for CrAT and L-carnitine in modulating the muscle acetylproteome and provide strong experimental evidence favoring the nonenzymatic carbon pressure model of mitochondrial AcK.

  17. The Acetyl Group Buffering Action of Carnitine Acetyltransferase Offsets Macronutrient-Induced Lysine Acetylation of Mitochondrial Proteins.

    Davies, Michael N; Kjalarsdottir, Lilja; Thompson, J Will; Dubois, Laura G; Stevens, Robert D; Ilkayeva, Olga R; Brosnan, M Julia; Rolph, Timothy P; Grimsrud, Paul A; Muoio, Deborah M

    2016-01-12

    Lysine acetylation (AcK), a posttranslational modification wherein a two-carbon acetyl group binds covalently to a lysine residue, occurs prominently on mitochondrial proteins and has been linked to metabolic dysfunction. An emergent theory suggests mitochondrial AcK occurs via mass action rather than targeted catalysis. To test this hypothesis, we performed mass spectrometry-based acetylproteomic analyses of quadriceps muscles from mice with skeletal muscle-specific deficiency of carnitine acetyltransferase (CrAT), an enzyme that buffers the mitochondrial acetyl-CoA pool by converting short-chain acyl-CoAs to their membrane permeant acylcarnitine counterparts. CrAT deficiency increased tissue acetyl-CoA levels and susceptibility to diet-induced AcK of broad-ranging mitochondrial proteins, coincident with diminished whole body glucose control. Sub-compartment acetylproteome analyses of muscles from obese mice and humans showed remarkable overrepresentation of mitochondrial matrix proteins. These findings reveal roles for CrAT and L-carnitine in modulating the muscle acetylproteome and provide strong experimental evidence favoring the nonenzymatic carbon pressure model of mitochondrial AcK. PMID:26748706

  18. Radical polymerization of monoethyl itaconate

    Katsikas Lynne; Nišević Nataša; Ignjatović Milka; Adamović Vladimir; Đakov Tatjana A.; Popović Ivanka G.

    2003-01-01

    The radical polymerization of monoethyl itaconate (MEI) was investigated in bulk and in solution at 60°C using a,a'-azobisisobutyronitrile as initiator. It was established that the obtained polymer poly(monoethyl itaconate) was insoluble in its monomer, implying that the bulk polymerization of MEI was a precipitation polymerization. The polymerization kinetics of MEI were discussed and compared to the polymerization kinetics of structurally similar alkyl itaconates. The homogeneous radical po...

  19. Ecoporn, Irrationalities and Radical Environmentalism

    Măntescu, Liviu

    2016-01-01

    This study explores the ‘irrationalities’ of deep ecology activism in the context of radical environmentalism by using the empirical example of ecoporn. Fuck For Forest is an environmental Non-Governmental Organisation which undertakes fund-raising for re-forestation and forest protection by means of pornography. Following twelve months of ethnographic fieldwork, this study presents first research results on a radical environmental project which does not promote democratic and established pro...

  20. N-acetyl Cysteine Reduced Oxidative Damages in Guinea Pigs Exposed to Cigarette Smoke and / or Gamma Radiation

    The objective of this study was to evaluate the role of n-acetyl cysteine (NAC) supplementation on oxidative cigarette smoke induced-oxidative damage in irradiated guinea pigs. N-acetyl cysteine was injected (i.p) to guinea pigs at a dose of 150 mg/kg b. w/day pre-exposure to cigarette smoke for one hour daily for 30 successive days. Animals were submitted to fractionate whole body gamma radiation (2 Gy installment every two weeks up to 4 Gy total dose started on the 2nd week of the experiment). Animals were sacrificed during the first hours from the last treatment of cigarette smoke. The results obtained showed significant increase in malondialdehyde (MDA) content associated with decreased superoxide dismutase (SOD) activity and glutathione (GSH) concentration in cardiac and pulmonary tissues as compared with their equivalent in control animals. The activities of lactate dehydrogenase (LDH), creatine phosphokinase (CPK), aspartate transaminase (AST), concentration of nitric oxide (NO), total cholesterol, Triacylglycerol, LDL-cholesterol were significant increased in plasma associated with significant decreased HDL-cholesterol. The administration of NAC has significantly attenuated the cigarette smoke and/or irradiation-induced changes in all the studied parameters. It could be concluded that NAC reduced cigarette smoke and radiation hazards via neutralized their capability to generate excessive reactive oxygen species (ROS) and free radicals in the biological systems

  1. Affinity Separation of Lectins Using Porous Membranes Immobilized with Glycopolymer Brushes Containing Mannose or N-Acetyl-D-Glucosamine

    Yoshiko Miura

    2013-07-01

    Full Text Available Porous membranes with glycopolymer brushes were prepared as biomaterials for affinity separation. Glycopolymer brushes contained acrylic acid and D-mannose or N-acetyl-D-glucosamine, and were formed on substrates by surface-initiated atom transfer radical polymerization. The presence of glycopolymer brush was confirmed by X-ray photoelectron spectroscopy, contact angle, and ellipsometry measurements. The interaction between lectin and the glycopolymer immobilized on glass slides was confirmed using fluorescent-labeled proteins. Glycopolymer-immobilized surfaces exhibited specific adsorption of the corresponding lectin, compared with bovine serum albumin. Lectins were continuously rejected by the glycopolymer-immobilized membranes. When the protein solution was permeated through the glycopolymer-immobilized membrane, bovine serum albumin was not adsorbed on the membrane surface. In contrast, concanavalin A and wheat germ agglutinin were rejected by membranes incorporating D-mannose or N-acetyl-D-glucosamine, respectively. The amounts of adsorbed concanavalin A and wheat germ agglutinin was increased five- and two-fold that of adsorbed bovine serum albumin, respectively.

  2. 2-Acetylthiamin pyrophosphate (acetyl-TPP) pH-rate profile for hydrolysis of acetyl-TPP and isolation of acetyl-TPP as a transient species in pyruvate dehydrogenase catalyzed reactions

    Rate constants for the hydrolysis of acetyl-TPP were measured pH values of 2.5 and 7.5 and plotted as log kobs versus pH. The pH-rate profile defined two legs, each with a slope of +1 but separated by a region of decreased slope between pH 4 and pH 6. The rates were insensitive to buffer concentrations. Each leg of the profile reflected specific-base-catalyzed hydrolysis of acetyl-TPP, analogous to the hydrolysis of 2-acetyl-3,4-dimethylthiazolium ion. The separation of the two legs of this profile has been shown to be caused by the ionization of a group exhibiting a pKa of 4.73 within acetyl-TPP that is remote from the acetyl group, the aminopyrimidine ring, which is promoted below pH 4.73. The protonation level of this ring has been shown to control the equilibrium partitioning of acetyl-TPP among its carbinolamine, keto, and hydrate forms. The differential partitioning of these species is a major factor causing the separation between the two legs of the pH-rate profile. The characteristic pH-rate profile and the availability of synthetic acetyl-TPP have facilitated the isolation and identification of [1-14C]acetyl-TPP from acid-quenched enymatic reaction mixtures at steady states. [1-14C]Acetyl-TPP was identified as a transient species in reactions catalyzed by the PDH complex or the pyruvate dehydrogenase component of the complex (E1). The pH-rate profile for hydrolysis of [1-14C]-acetyl-TPP, isolated from enzymatic reactions was found to be indistinguishable from that for authentic acetyl-TPP, which constituted positive identification of the 14C-labeled enzymic species

  3. Histone H3 acetylation in the postmortem Parkinson's disease primary motor cortex.

    Gebremedhin, Kibrom G; Rademacher, David J

    2016-08-01

    Although the role of epigenetics in Parkinson's disease (PD) has not been extensively studied, α-synuclein, the main component of Lewy bodies, decreased histone H3 acetylation. Here, we determined if there were histone acetylation changes in the primary motor cortex which, according to the Braak model, is one of the last brain regions affected in PD. Net histone H3 acetylation, histone H3 lysine 9 (H3K9), histone H3 lysine 14 (H3K14), histone H3 lysine 18 (H3K18), and histone H3 lysine 23 (H3K23) acetylation was assessed in the primary motor cortex of those affected and unaffected by PD. There was net increase in histone H3 acetylation due to increased H3K14 and H3K18 acetylation. There was a decrease in H3K9 acetylation. No between-groups difference was detected in H3K23 acetylation. Relationships between Unified Lewy Body Staging scores and histone H3 acetylation and substantia nigra depigmentation scores and histone H3 acetylation were observed. No relationships were detected between postmortem interval and histone H3 acetylation and expired age and histone H3 acetylation. These correlational data support the notion that the histone H3 acetylation changes observed here are not due to the postmortem interval or aging. Instead, they are due to PD and/or factors that covary with PD. The data suggest enhanced gene transcription in the primary motor cortex of the PD brain due to increase H3K14 and H3K18 acetylation. This effect is partially offset by a decreased H3K9 acetylation, which might repress gene transcription. PMID:27241718

  4. Altered acetylation and succinylation profiles in Corynebacterium glutamicum in response to conditions inducing glutamate overproduction.

    Mizuno, Yuta; Nagano-Shoji, Megumi; Kubo, Shosei; Kawamura, Yumi; Yoshida, Ayako; Kawasaki, Hisashi; Nishiyama, Makoto; Yoshida, Minoru; Kosono, Saori

    2016-02-01

    The bacterium Corynebacterium glutamicum is utilized during industrial fermentation to produce amino acids such as l-glutamate. During l-glutamate fermentation, C. glutamicum changes the flux of central carbon metabolism to favor l-glutamate production, but the molecular mechanisms that explain these flux changes remain largely unknown. Here, we found that the profiles of two major lysine acyl modifications were significantly altered upon glutamate overproduction in C. glutamicum; acetylation decreased, whereas succinylation increased. A label-free semi-quantitative proteomic analysis identified 604 acetylated proteins with 1328 unique acetylation sites and 288 succinylated proteins with 651 unique succinylation sites. Acetylation and succinylation targeted enzymes in central carbon metabolic pathways that are directly related to glutamate production, including the 2-oxoglutarate dehydrogenase complex (ODHC), a key enzyme regulating glutamate overproduction. Structural mapping revealed that several critical lysine residues in the ODHC components were susceptible to acetylation and succinylation. Furthermore, induction of glutamate production was associated with changes in the extent of acetylation and succinylation of lysine, suggesting that these modifications may affect the activity of enzymes involved in glutamate production. Deletion of phosphotransacetylase decreased the extent of protein acetylation in nonproducing condition, suggesting that acetyl phosphate-dependent acetylation is active in C. glutamicum. However, no effect was observed on the profiles of acetylation and succinylation in glutamate-producing condition upon disruption of acetyl phosphate metabolism or deacetylase homologs. It was considered likely that the reduced acetylation in glutamate-producing condition may reflect metabolic states where the flux through acid-producing pathways is very low, and substrates for acetylation do not accumulate in the cell. Succinylation would occur more

  5. Specificity of antibodies to O-acetyl-positive and O-acetyl-negative group C meningococcal polysaccharides in sera from vaccinees and carriers.

    Arakere, G; Frasch, C E

    1991-01-01

    Most group C Neisseria meningitidis strains produce an O-acetyl-positive polysaccharide, a homopolymer of alpha-2----9-linked N-acetylneuraminic acid with O-acetyl groups at the C-7 and C-8 of its sialic acid residues. The majority of disease isolates have been reported to contain this polysaccharide. Some strains produce group C polysaccharide lacking O-acetyl groups. The licensed vaccine contains the O-acetyl-positive polysaccharide. We have measured the antibody specificities to the two po...

  6. The games radicals play : special issue on free radicals and radical ions

    Walton, John C; Ffrancon Williams

    2015-01-01

    Chemistry and Physics have aptly been described as “most excellent children of Intellect and Art” [1]. Both these “children” engage with many playthings, and molecules rank as one of their first favorites, especially radicals, which are amongst the most lively and exciting. Checking out radicals dancing to the music of entropy round their potential energy ballrooms is surely both entertaining and enlightening. Radicals’ old favorite convolutions are noteworthy, but the new styles, modes and a...

  7. The growing landscape of lysine acetylation links metabolism and cell signalling

    Choudhary, Chuna Ram; Weinert, Brian Tate; Nishida, Yuya;

    2014-01-01

    Lysine acetylation is a conserved protein post-translational modification that links acetyl-coenzyme A metabolism and cellular signalling. Recent advances in the identification and quantification of lysine acetylation by mass spectrometry have increased our understanding of lysine acetylation......, implicating it in many biological processes through the regulation of protein interactions, activity and localization. In addition, proteins are frequently modified by other types of acylations, such as formylation, butyrylation, propionylation, succinylation, malonylation, myristoylation, glutarylation and...... deacylating enzymes and also highlight the mechanisms by which acetylation regulates various cellular processes....

  8. Proteomic analysis of lysine acetylation sites in rat tissues reveals organ specificity and subcellular patterns

    Lundby, Alicia; Hansen, Kasper Lage; Weinert, Brian Tate; Breinholt Bekker-Jensen, Dorte; Secher, Anna; Skovgaard, Tine; Kelstrup, Christian; Dmytriyev, Anatoliy; Choudhary, Chuna Ram; Lundby, Carsten; Olsen, Jesper Velgaard

    2012-01-01

    Lysine acetylation is a major posttranslational modification involved in a broad array of physiological functions. Here, we provide an organ-wide map of lysine acetylation sites from 16 rat tissues analyzed by high-resolution tandem mass spectrometry. We quantify 15,474 modification sites on 4...... subcellular acetylation distribution is tissue-type dependent and that acetylation targets tissue-specific pathways involved in fundamental physiological processes. We compare lysine acetylation patterns for rat as well as human skeletal muscle biopsies and demonstrate its general involvement in muscle...

  9. Crystalline bipyridinium radical complexes and uses thereof

    Fahrenbach, Albert C.; Barnes, Jonathan C.; Li, Hao; Stoddart, J. Fraser; Basuray, Ashish Neil; Sampath, Srinivasan

    2015-09-01

    Described herein are methods of generating 4,4'-bipyridinium radical cations (BIPY.sup..cndot.+), and methods for utilizing the radical-radical interactions between two or more BIPY.sup..cndot.+ radical cations that ensue for the creation of novel materials for applications in nanotechnology. Synthetic methodologies, crystallographic engineering techniques, methods of physical characterization, and end uses are described.

  10. Crystalline bipyridinium radical complexes and uses thereof

    Fahrenbach, Albert C.; Barnes, Jonathan C.; Li, Hao; Stoddart, J. Fraser; Basuray, Ashish Neil; Sampath, Srinivasan

    2015-09-01

    Described herein are methods of generating 4,4'-bipyridinium radical cations (BIPY.sup..cndot.+), and methods for utilizing the radical-radical interactions between two or more BIPY.sup..cndot.+ radical cations that ensue for the creation of novel materials for applications in nanotechnology. Synthetic methodologies, crystallographic engineering techniques, methods of physical characterization, and end uses are described.

  11. Ubiquitination of Notch1 is regulated by MAML1-mediated p300 acetylation of Notch1

    Popko-Scibor, Anita E.; Lindberg, Mikael J.; Hansson, Magnus L.; Holmlund, Teresa [Division of Molecular Toxicology, Institute of Environmental Medicine, Karolinska Institutet, 171 77 Stockholm (Sweden); Wallberg, Annika E., E-mail: Annika.Wallberg@ki.se [Division of Molecular Toxicology, Institute of Environmental Medicine, Karolinska Institutet, 171 77 Stockholm (Sweden)

    2011-12-16

    Highlights: Black-Right-Pointing-Pointer p300 acetylates conserved lysines within Notch1 C-terminal nuclear localization signal. Black-Right-Pointing-Pointer MAML1 and CSL, components of Notch transcription complex, increase Notch acetylation. Black-Right-Pointing-Pointer MAML1-dependent acetylation of Notch1 by p300 decreases the ubiquitination of Notch1. Black-Right-Pointing-Pointer CDK8 inhibits Notch acetylation and Notch transcription enhanced by p300. -- Abstract: Earlier studies demonstrated the involvement of the p300 histone acetyltransferase in Notch signaling but the precise mechanisms by which p300 might modulate Notch function remains to be investigated. In this study, we show that p300 acetylates Notch1 ICD in cell culture assay and in vitro, and conserved lysines located within the Notch C-terminal nuclear localization signal are essential for Notch acetylation. MAML1 and CSL, which are components of the Notch transcription complex, enhance Notch acetylation and we suggest that MAML1 increases Notch acetylation by potentiating p300 autoacetylation. Furthermore, MAML1-dependent acetylation of Notch1 ICD by p300 decreases the ubiquitination of Notch1 ICD in cellular assays. CDK8 has been shown to target Notch1 for ubiquitination and proteosomal degradation. We show that CDK8 inhibits Notch acetylation and Notch transcription enhanced by p300. Therefore, we speculate that acetylation of Notch1 might be a mechanism to regulate Notch activity by interfering with ubiquitin-dependent pathways.

  12. N-Acetyltransferase 2 (NAT2) in Tunisian Population: Correlation Between Acetylation Phenotype and Genotype

    One hundred tuberculous patients were studied during 2004-2005 to determine acetylation phenotype, frequent mutations of NAT2 gene and to compare acetylation phenotype with NAT2 genotype in Tunisian population. Acetylation phenotype was determined by determination of acetylation index. Five mutations of NAT2 gene were evaluated by PCR/RFLP. Results show bimodal distribution of acetylation SA and RA phenotype, 75% and 25% and genotype 56% and 44%, respectively. Ten NAT2 alleles were found, NAT2*4 being the major one. Thirty-two different genotypes were found (9 RA and 23 SA). The major one was NAT2*6 B/NAT2*4. The concordance value was 79%. A good sensibility (98, 2%) of acetylation test for SA detection was found. Thus, acetylation phenotype in SA is predicted with poor error risk. (author)

  13. Lysine acetylation targets protein complexes and co-regulates major cellular functions

    Choudhary, Chuna Ram; Kumar, Chanchal; Gnad, Florian; Nielsen, Michael L; Rehman, Michael; Walther, Tobias C; Olsen, Jesper V; Mann, Matthias

    2009-01-01

    Lysine acetylation is a reversible posttranslational modification of proteins and plays a key role in regulating gene expression. Technological limitations have so far prevented a global analysis of lysine acetylation's cellular roles. We used high-resolution mass spectrometry to identify 3600...... lysine acetylation sites on 1750 proteins and quantified acetylation changes in response to the deacetylase inhibitors suberoylanilide hydroxamic acid and MS-275. Lysine acetylation preferentially targets large macromolecular complexes involved in diverse cellular processes, such as chromatin remodeling......, cell cycle, splicing, nuclear transport, and actin nucleation. Acetylation impaired phosphorylation-dependent interactions of 14-3-3 and regulated the yeast cyclin-dependent kinase Cdc28. Our data demonstrate that the regulatory scope of lysine acetylation is broad and comparable with that of other...

  14. Peroxy radical partitioning during the AMMA radical intercomparison exercise

    M. D. Andrés-Hernández

    2010-04-01

    Full Text Available Peroxy radicals were measured onboard two scientific aircrafts during the AMMA (African Monsoon Multidisciplinary Analysis campaign in summer 2006. This paper reports results from the flight on 16 August 2006 during which measurements of HO2 by laser induced fluorescence spectroscopy at low pressure (LIF-FAGE and total peroxy radicals (RO2*=HO2+ΣRO2, R= organic chain by two similar instruments based on the peroxy radical chemical amplification (PerCA technique were subject of a blind intercomparison. The German DLR-Falcon and the British FAAM-BAe-146 flew wing tip to wing tip for about 30 min making concurrent measurements on 2 horizontal level runs at 697 and 485 hPa over the same geographical area in Burkina Faso. A full set of supporting measurements comprising photolysis frequencies, and relevant trace gases like CO, NO, NO2, NOy, O3 and a wider range of VOCs were collected simultaneously.

    Results are discussed on the basis of the characteristics and limitations of the different instruments used. Generally, no data bias are identified and the RO2* data available agree quite reasonably within the instrumental errors. The [RO2*]/[HO2] ratios, which vary between 1:1 and 3:1, as well as the peroxy radical variability, concur with variations in photolysis rates and in other potential radical precursors. Model results provide additional information about dominant radical formation and loss processes.

  15. Peroxy radical partitioning during the AMMA radical intercomparison exercise

    M. D. Andrés-Hernández

    2010-11-01

    Full Text Available Peroxy radicals were measured onboard two scientific aircrafts during the AMMA (African Monsoon Multidisciplinary Analysis campaign in summer 2006. This paper reports results from the flight on 16 August 2006 during which measurements of HO2 by laser induced fluorescence spectroscopy at low pressure (LIF-FAGE and total peroxy radicals (RO2* = HO2+ΣRO2, R = organic chain by two similar instruments based on the peroxy radical chemical amplification (PeRCA technique were subject of a blind intercomparison. The German DLR-Falcon and the British FAAM-BAe-146 flew wing tip to wing tip for about 30 min making concurrent measurements on 2 horizontal level runs at 697 and 485 hPa over the same geographical area in Burkina Faso. A full set of supporting measurements comprising photolysis frequencies, and relevant trace gases like CO, NO, NO2, NOy, O3 and a wider range of VOCs were collected simultaneously.

    Results are discussed on the basis of the characteristics and limitations of the different instruments used. Generally, no data bias are identified and the RO2* data available agree quite reasonably within the instrumental errors. The [RO2*]/[HO2] ratios, which vary between 1:1 and 3:1, as well as the peroxy radical variability, concur with variations in photolysis rates and in other potential radical precursors. Model results provide additional information about dominant radical formation and loss processes.

  16. Chemical Genetics of Acetyl-CoA Carboxylases

    Xuyu Zu

    2013-01-01

    Full Text Available Chemical genetic studies on acetyl-CoA carboxylases (ACCs, rate-limiting enzymes in long chain fatty acid biosynthesis, have greatly advanced the understanding of their biochemistry and molecular biology and promoted the use of ACCs as targets for herbicides in agriculture and for development of drugs for diabetes, obesity and cancers. In mammals, ACCs have both biotin carboxylase (BC and carboxyltransferase (CT activity, catalyzing carboxylation of acetyl-CoA to malonyl-CoA. Several classes of small chemicals modulate ACC activity, including cellular metabolites, natural compounds, and chemically synthesized products. This article reviews chemical genetic studies of ACCs and the use of ACCs for targeted therapy of cancers.

  17. Standard Electrode Potentials Involving Radicals in Aqueous Solution: Inorganic Radicals

    Armstrong, David A.; Huie, Robert E.; Koppenol, Willem H.; Lymar, Sergei V.; Merenyi, Gabor; Neta, Pedatsur; Ruscic, Branko; Stanbury, David M.; Steenken, Steen; Wardman, Peter

    2015-12-01

    Recommendations are made for standard potentials involving select inorganic radicals in aqueous solution at 25 °C. These recommendations are based on a critical and thorough literature review and also by performing derivations from various literature reports. The recommended data are summarized in tables of standard potentials, Gibbs energies of formation, radical pKa’s, and hemicolligation equilibrium constants. In all cases, current best estimates of the uncertainties are provided. An extensive set of Data Sheets is appended that provide original literature references, summarize the experimental results, and describe the decisions and procedures leading to each of the recommendations

  18. Radical-Enhanced Chinese Character Embedding

    Sun, Yaming; Lin, Lei; Tang, Duyu; Yang, Nan; Ji, Zhenzhou; Wang, Xiaolong

    2014-01-01

    We present a method to leverage radical for learning Chinese character embedding. Radical is a semantic and phonetic component of Chinese character. It plays an important role as characters with the same radical usually have similar semantic meaning and grammatical usage. However, existing Chinese processing algorithms typically regard word or character as the basic unit but ignore the crucial radical information. In this paper, we fill this gap by leveraging radical for learning continuous r...

  19. Use of Intravenous N-Acetyl Systein in Paracetamol Intoxication

    Latif Duran; Bülent Şişman; Canan Doğruel; Türker Yardan; Ahmet Baydın; Yücel Yavuz

    2011-01-01

    Objective: In this study, we aimed to present our clinical experiences of intravenous (IV) N-Acetyl cystein administration in patients admitted to our emergency department with paracetamol intoxication.Material and Methods: This study was conducted between January 2007 and December 2009, in the Ondokuz Mayis University Medical Faculty Hospital, Emergency Service, and the hospital records of adult patients admitted with paracetamol poisoning were examined retrospectively. Fifty three patients ...

  20. The potential role of wood acetylation in climate change mitigation

    Van der Lugt, P.; Vogtländer, J.G.; J. Alexander; Bongers, F.; Stebbins, H.

    2014-01-01

    In a carbon footprint assessment, the greenhouse gas emissions during the life cycle of a material can be measured, and compared to alternative products in terms of kg CO2 equivalent. If applied correctly, wood acetylation opens up a range of new innovative applications in which high performance yet carbon intensive non-renewable materials such as metals, plastics and concrete may be replaced by abundantly available nondurable wood species. To better understand the difference in greenhouse ga...

  1. Histone acetylation regulates osteodifferentiation of hDPSCs via DSPP.

    Gu, Shensheng; Liang, Jingping; Wang, Jia; Liu, Bin

    2013-01-01

    Dental pulp stem cells (DPSCs) are a unique population of precursor cells isolated from postnatal human dental pulp, with the ability to regenerate a reparative dentin-like complex. We examined the regulation of odontoblast-like differentiation of DPSCs by histone acetylation. Western blot analysis showed that histone H3 acetylation was strongly induced in osteodifferentiation medium. Inhibition of histone acetyltransferase by garcinol reversed osteodifferentiation and mineral formation. Real-time polymerase chain reaction assay indicated that the dentin sialophosphoprotein (DSPP) gene, which is mainly expressed in odontoblasts and preameloblasts in teeth and plays an important role in tooth function, was also down-regulated in garcinol-treated cells. Moreover, lentivirus-mediated knockdown of DSPP in human DPSCs was associated with significant inhibition of mineral formation, but not osteoblast differentiation. In conclusion, the results of this study suggest that DSPP positively affects mineral formation, and that odontoblast-like differentiation and maturation of DPSCs can be regulated by histone acetylation of the DSPP gene. PMID:23747867

  2. Acetylation modification regulates GRP78 secretion in colon cancer cells.

    Li, Zongwei; Zhuang, Ming; Zhang, Lichao; Zheng, Xingnan; Yang, Peng; Li, Zhuoyu

    2016-01-01

    High glucose-regulated protein 78 (GRP78) expression contributes to the acquisition of a wide range of phenotypic cancer hallmarks, and the pleiotropic oncogenic functions of GRP78 may result from its diverse subcellular distribution. Interestingly, GRP78 has been reported to be secreted from solid tumour cells, participating in cell-cell communication in the tumour microenvironment. However, the mechanism underlying this secretion remains elusive. Here, we report that GRP78 is secreted from colon cancer cells via exosomes. Histone deacetylase (HDAC) inhibitors blocked GRP78 release by inducing its aggregation in the ER. Mechanistically, HDAC inhibitor treatment suppressed HDAC6 activity and led to increased GRP78 acetylation; acetylated GRP78 then bound to VPS34, a class III phosphoinositide-3 kinase, consequently preventing the sorting of GRP78 into multivesicular bodies (MVBs). Of note, we found that mimicking GRP78 acetylation by substituting the lysine at residue 633, one of the deacetylated sites of HDAC6, with a glutamine resulted in decreased GRP78 secretion and impaired tumour cell growth in vitro. Our study thus reveals a hitherto-unknown mechanism of GRP78 secretion and may also provide implications for the therapeutic use of HDAC inhibitors. PMID:27460191

  3. Acetylation modification regulates GRP78 secretion in colon cancer cells

    Li, Zongwei; Zhuang, Ming; Zhang, Lichao; Zheng, Xingnan; Yang, Peng; Li, Zhuoyu

    2016-01-01

    High glucose-regulated protein 78 (GRP78) expression contributes to the acquisition of a wide range of phenotypic cancer hallmarks, and the pleiotropic oncogenic functions of GRP78 may result from its diverse subcellular distribution. Interestingly, GRP78 has been reported to be secreted from solid tumour cells, participating in cell-cell communication in the tumour microenvironment. However, the mechanism underlying this secretion remains elusive. Here, we report that GRP78 is secreted from colon cancer cells via exosomes. Histone deacetylase (HDAC) inhibitors blocked GRP78 release by inducing its aggregation in the ER. Mechanistically, HDAC inhibitor treatment suppressed HDAC6 activity and led to increased GRP78 acetylation; acetylated GRP78 then bound to VPS34, a class III phosphoinositide-3 kinase, consequently preventing the sorting of GRP78 into multivesicular bodies (MVBs). Of note, we found that mimicking GRP78 acetylation by substituting the lysine at residue 633, one of the deacetylated sites of HDAC6, with a glutamine resulted in decreased GRP78 secretion and impaired tumour cell growth in vitro. Our study thus reveals a hitherto-unknown mechanism of GRP78 secretion and may also provide implications for the therapeutic use of HDAC inhibitors. PMID:27460191

  4. Astrocyte Reactivity Following Blast Exposure Involves Aberrant Histone Acetylation

    Bailey, Zachary S.; Grinter, Michael B.; VandeVord, Pamela J.

    2016-01-01

    Blast induced neurotrauma (BINT) is a prevalent injury within military and civilian populations. The injury is characterized by persistent inflammation at the cellular level which manifests as a multitude of cognitive and functional impairments. Epigenetic regulation of transcription offers an important control mechanism for gene expression and cellular function which may underlie chronic inflammation and result in neurodegeneration. We hypothesize that altered histone acetylation patterns may be involved in blast induced inflammation and the chronic activation of glial cells. This study aimed to elucidate changes to histone acetylation occurring following injury and the roles these changes may have within the pathology. Sprague Dawley rats were subjected to either a 10 or 17 psi blast overpressure within an Advanced Blast Simulator (ABS). Sham animals underwent the same procedures without blast exposure. Memory impairments were measured using the Novel Object Recognition (NOR) test at 2 and 7 days post-injury. Tissues were collected at 7 days for Western blot and immunohistochemistry (IHC) analysis. Sham animals showed intact memory at each time point. The novel object discrimination decreased significantly between two and 7 days for each injury group (p processes. We have shown aberrant histone acetylation patterns involved in blast induced astrogliosis and cognitive impairments. Further understanding of their role in the injury progression may lead to novel therapeutic targets. PMID:27551260

  5. Selective cleavage enhanced by acetylating the side chain of lysine.

    Fu, Leixiaomeng; Chen, Tingting; Xue, Gaiqing; Zu, Lily; Fang, Weihai

    2013-01-01

    Selective cleavage is of great interest in mass spectrometry studies as it can help sequence identification by promoting simple fragmentation pattern of peptides and proteins. In this work, the collision-induced dissociation of peptides containing internal lysine and acetylated lysine residues were studied. The experimental and computational results revealed that multiple fragmentation pathways coexisted when the lysine residue was two amino acid residues away from N-terminal of the peptide. After acetylation of the lysine side-chain, b(n)+ ions were the most abundant primary fragment products and the Lys(Ac)-Gly amide bond became the dominant cleavage site via an oxazolone pathway. Acetylating the side-chain of lysine promoted the selective cleavage of Lys-Xxx amide bond and generated much more information of the peptide backbone sequence. The results re-evaluate the selective cleavage due to the lysine basic side-chain and provide information for studying the post-translational modification of proteins and other bio-molecules containing Lys residues. PMID:23303756

  6. Hepatoprotective effect of N-acetyl -L-cysteine on Cl4 - induced liver damage in rats under oxidative stress of radiation exposure

    Hepato protective properties of N-acetyl-L-cysteine (NAC) were investigated in rats under stress of radiation exposure in case of liver cirrhosis injury induced by carbon tetrachloride (CCl4) (tetrachloromethane). N-acetyl-L-cysteine treatment showed regression of cirrhosis in the liver tissue with significant inhibition of the increased liver malondialdehyde, triacylglycerols and cholesterol. Simultaneously, N-acetyl-L-cysteine suppressed the increase in plasma activities of aminotransferases (ALT, AST), alkaline phosphatase and billirubin, which are considered as markers of liver functional state. Status of oxidative/anti oxidative profile was the mechanistic approach to the nature of protection by N-acetyl-L-cysteine. Results revealed amelioration to a great extent in blood glutathione (GSH), glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), glucose-6-phosphate dehydrogenase (G6PDH) and catalase. Whole body exposure of rats to gamma-rays (four doses each of 4 Gy/dose/week) caused increases in lipid peroxides accompanied by depression of reduced glutathione (GSH). This decrease is probably due to the damages produced by the lipid peroxides. The activities of antioxidant enzymes; superoxide dismutase (SOD), catalase and glutathione peroxidase (GPx) were inhibited, which might be due to the increase of the superoxide radical and H2O2 and were accompanied also by a fall in glucose-6-phosphate dehydrogenase (G6PHD) activity. The excessive production of free radicals and lipid peroxides might cause leakage of cytosolic enzymes such as aminotransferases (AST and ALT) and alkaline phosphatase. Pretreatment with NAC (150 mg/kg) in saline for 7 days prevented the radiation-induced damage to an appreciable extent. From the results, it may be concluded that NAC is effective in protecting from the damages caused by gamma radiations in case of cirrhotic liver and its prospects as an adjuvant to radiotherapy should be considered. The anti fibrotic effect recorded in

  7. Laparoscopic radical and partial cystectomy

    Challacombe Ben

    2005-01-01

    Full Text Available Radical cystectomy remains the standard treatment for muscle invasive organ confined bladder carcinoma. Laparoscopic radical cystoprostatectomy (LRC is an advanced laparoscopic procedure that places significant demands on the patient and the surgeon alike. It is a prolonged procedure which includes several technical steps and requires highly developed laparoscopic skills including intra-corporeal suturing. Here we review the development of the technique, the indications, complications and outcomes. We also examine the potential benefits of robotic-assisted LRC and explore the indications and technique of laparoscopic partial cystectomy.

  8. Radical democratic politics and feminism

    Martínez Labrin, Soledad

    2006-05-01

    Full Text Available In the article I present a reflection around the radical democratic project proposed by Chantal Mouffe and Ernesto Laclau. Specifically, I examine the application of the project in the context of the “new social movements” and especially, of feminist movement. I state the need of drawing attention to universalism and essentialism as the main obstacles to generate a collective proposal without margins. Nevertheless, doubts remind about the possibility of building up a feminism tailored by the radical democratic project, in a stage in which the political action of such a movement is characterized by categories that are closed and crystallized

  9. Quantification of a radical beam source for methyl radicals

    A radical beam source for methyl radicals (CH3) was characterized applying ionization-threshold mass spectrometry. The beam source is based on thermal dissociation of methane (CH4) or azomethane (N2(CH3)2) in a heated tungsten capillary. A flux of (3±1)x1013 cm-2 s-1 CH3 radicals is produced using methane as precursor gas and a capillary temperature of 1650 K. Alternatively, a flux of (3±1)x1014 cm-2 s-1 CH3 is produced using azomethane as precursor gas and a capillary temperature of 1150 K. The dominant production of methyl from the precursor methane occurs due to reaction 2 CH4+M→2 CH3+H2+M at the hot tungsten surface. The dominant production of methyl from azomethane occurs due to the reaction N2(CH3)2→2 CH3+N2. Besides methyl radicals, only stable molecules contribute to the emitted flux; within the detection limit, no atomic hydrogen is observed. From the comparison of ionization-threshold mass spectrometry and standard mass spectrometry, it is concluded that the cracking pattern of methane varies with the methane gas temperature. This is explained by the vibrational assisted dissociation of methane

  10. Acetylator genotype-dependent formation of 2-aminofluorene-hemoglobin adducts in rapid and slow acetylator Syrian hamsters congenic at the NAT2 locus.

    Feng, Y; Rustan, T D; Ferguson, R J; Doll, M A; Hein, D W

    1994-01-01

    Arylamine-hemoglobin adducts are a valuable dosimeter for assessing arylamine exposures and carcinogenic risk. The effects of age, sex, time-course, dose, and acetylator genotype on levels of 2-aminofluorene-hemoglobin adducts were investigated in homozygous rapid (Bio. 82.73/H-Patr) and slow (Bio. 82.73/H-Pats) acetylator hamsters congenic at the polymorphic (NAT2) acetylator locus. Following administration of a single ip dose of [3H]2-aminofluorene, peak 2-aminofluorene-hemoglobin adduct levels were achieved at 12-18 hr and retained a plateau up to 72 hr postinjection in both rapid and slow acetylator congenic hamsters. 2-Aminofluorene-hemoglobin adduct levels did not differ significantly between young (5-6 weeks) and old (32-49 weeks) hamsters or between male and female hamsters within either acetylator genotype. 2-Aminofluorene-hemoglobin adduct levels increased in a dose-dependent manner (r = 0.95, p = 0.0001) and were consistently higher in slow versus rapid acetylator congenic hamsters in studies of both time-course and dose-effect. The magnitude of the acetylator genotype-dependent difference was a function of dose; 2-aminofluorene-hemoglobin adduct levels were 1.5-fold higher in slow acetylator congenic hamsters following a 60 mg/kg 2-aminofluorene dose (p = 0.0013) but 2-fold higher following a 100 mg/kg 2-aminofluorene dose (p < 0.0001). These results show a specific and significant role for NAT2 acetylator genotype in formation of arylamine-hemoglobin adducts, which may reflect the relationship between acetylator genotype and the incidence of different cancers from arylamine exposures. PMID:8291051

  11. Exploring the Theories of Radicalization

    Maskaliūnaitė Asta

    2015-12-01

    Full Text Available After the London bombings in July 2005, the concern of terrorism scholars and policy makers has turned to “home-grown” terrorism and potential for political violence from within the states. “Radicalization” became a new buzz word. This article follows a number of reviews of the literature on radicalization and offers another angle for looking at this research. First, it discusses the term “radicalization” and suggests the use of the following definition of radicalization as a process by which a person adopts belief systems which justify the use of violence to effect social change and comes to actively support as well as employ violent means for political purposes. Next, it proposes to see the theories of radicalization focusing on the individual and the two dimensions of his/her motivation: whether that motivation is internal or external and whether it is due to personal choice or either internal (due to some psychological traits or external compulsion. Though not all theories fall neatly within these categories, they make it possible to make comparisons of contributions from a variety of different areas thus reflecting on the interdisciplinary nature of the study of terrorism in general and radicalization as a part of it.

  12. Detecting Social Polarization and Radicalization

    Qureshi, Pir Abdul Rasool; Memon, Nasrullah; Wiil, Uffe Kock;

    2011-01-01

    This paper proposes a novel system to detect social polarization and to estimate the chances of violent radicalization associated with it. The required processes for such a system are indicated; it is also analyzed how existing technologies can be integrated into the proposed system to fulfill the...

  13. Kinetics of nitroxyl radical reactions

    Absolute rate-constants for the reaction of the nitroxyl free radicals TAN and TMPN with radiation-chemically-formed radicals and ions have been determined. k(TAN + X) (in M-1 sec-1) = 4.0 x 109 (for X =OH), 2.9 x 1010(esub(aq)-), 8.0 x 109 (H), 7.2 x 108 (CH2OH), 4.0 x 108 (CH3CHOH), 4.3 x 108 ((CH3)2COH), 2.8 x 108 (CH2(CH3)2COH), 5.9 x 107 (glucose radical), 4.0 x 108 (c-C5H9), and k(TMPN + X) = 3.4 x 109 (OH), 7.8 x 109 (esub(aq)-), 4.9 x 109 (H), 4.4 x 108 (CH2OH), 4.9 x 108 (CH3CHOH), 3.6 x 108 ((CH3)2COH), 1.5 x 108 (CH2(CH3)2COH), 4.9 x 107 (glucose radical), 4.3 x 108 (c-C5H9). Direct measurements by means of a pulse-radiolysis conductivity technique were based on the formation and destruction of charged species in these reactions within certain pH ranges. It is indicated that the radiosensitizing nitroxyles undergo both redox and addition reactions. (author)

  14. Reaction between protein radicals and other biomolecules

    Østdal, Henrik; Davies, Michael Jonathan; Andersen, Henrik J

    2002-01-01

    The present study investigates the reactivity of bovine serum albumin (BSA) radicals towards different biomolecules (urate, linoleic acid, and a polypeptide, poly(Glu-Ala-Tyr)). The BSA radical was formed at room temperature through a direct protein-to-protein radical transfer from H(2)O(2....... Subsequent analysis showed a decrease in the concentration of urate upon reaction with the BSA radical, while the BSA radical in the presence of poly(Glu-Ala-Tyr) resulted in increased formation of the characteristic protein oxidation product, dityrosine. Reaction between the BSA radical and a linoleic acid...

  15. From Radical Translation to Radical Interpretation and Back

    António Zilhão

    2003-12-01

    Full Text Available Both Quine and Davidson put forth programs of empirical semantics satisfying the conditions that characterize the so-called “standpoint of interpretation.” Quine’s less ambitious program of radical translation rests upon two buttresses: causality and empathy. Davidson’s more ambitious program of radical interpretation replaces causality with truth and empathy with rationality. Although the replacement of causality with intersubjective truth seems to me to be a fully justified move, I nevertheless contend that it is more realistic to develop the work of interpretation drawing upon Quine’s less ambitious requirement of empathy than upon Davidson’s view of human agency as rational agency. In order to substantiate this contention, I present an argument to the effect that Davidson’s characterization of human agency as rational is not compatible with his other requirement that truth should pro-vide the essential link connecting speech with environment and action.

  16. Acetylated starch nanocrystals: Preparation and antitumor drug delivery study.

    Xiao, Huaxi; Yang, Tao; Lin, Qinlu; Liu, Gao-Qiang; Zhang, Lin; Yu, Fengxiang; Chen, Yuejiao

    2016-08-01

    In this study, we developed a new nanoparticulate system for acetylated starch nanocrystals (ASN) using broken rice. ASN with different degrees of substitution (DS) of 0.04, 0.08 and 0.14 were prepared using acetic anhydride as acetylating agent through reaction with starch nanocrystals (SN). The resulting ASN were investigated for the capability to load and release doxorubicin hydrochloride (DOX), and the antitumor activities of DOX-loaded SN and DOX-loaded ASN were evaluated as potential drug delivery systems for cancer therapy. Cellular uptake and cytotoxicity of nanocrystals and the DOX-loaded nanocrystals were investigated using fluorescence microscopy and a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) (MTT) assay. Compared with acetylated starches (AS) and native starches (NS), ASN with DS 0.14 loaded up to 6.07% of DOX with a higher loading efficiency of 91.1% and had steadier drug-release rates. Toxicity analysis using the rat hepatocytes model suggested that ASN was biocompatible and could be used for drug delivery. Furthermore, ASN were taken up by cancer cells in vitro and significantly enhanced the cytotoxicity of DOX against HeLa human cervical carcinoma cells. The IC50 value of DOX-loaded ASN-DS 0.14 was 3.8μg/mL for 24h of treatment, which was significantly lower than that of free DOX (21μg/mL). These results indicate that the prepared ASN using broken rice is a promising vehicle for the controlled delivery of DOX for cancer therapy. PMID:27156696

  17. Autoimmune regulator is acetylated by transcription coactivator CBP/p300

    Saare, Mario, E-mail: mario.saare@ut.ee [Molecular Pathology, Institute of General and Molecular Pathology, University of Tartu, 19th Ravila Str, Tartu (Estonia); Rebane, Ana [Molecular Pathology, Institute of General and Molecular Pathology, University of Tartu, 19th Ravila Str, Tartu (Estonia); SIAF, Swiss Institute of Allergy and Asthma Research, University of Zuerich, Davos (Switzerland); Rajashekar, Balaji; Vilo, Jaak [BIIT, Bioinformatics, Algorithmics and Data Mining group, Institute of Computer Science, University of Tartu, Tartu (Estonia); Peterson, Paert [Molecular Pathology, Institute of General and Molecular Pathology, University of Tartu, 19th Ravila Str, Tartu (Estonia)

    2012-08-15

    The Autoimmune Regulator (AIRE) is a regulator of transcription in the thymic medulla, where it controls the expression of a large set of peripheral-tissue specific genes. AIRE interacts with the transcriptional coactivator and acetyltransferase CBP and synergistically cooperates with it in transcriptional activation. Here, we aimed to study a possible role of AIRE acetylation in the modulation of its activity. We found that AIRE is acetylated in tissue culture cells and this acetylation is enhanced by overexpression of CBP and the CBP paralog p300. The acetylated lysines were located within nuclear localization signal and SAND domain. AIRE with mutations that mimicked acetylated K243 and K253 in the SAND domain had reduced transactivation activity and accumulated into fewer and larger nuclear bodies, whereas mutations that mimicked the unacetylated lysines were functionally similar to wild-type AIRE. Analogously to CBP, p300 localized to AIRE-containing nuclear bodies, however, the overexpression of p300 did not enhance the transcriptional activation of AIRE-regulated genes. Further studies showed that overexpression of p300 stabilized the AIRE protein. Interestingly, gene expression profiling revealed that AIRE, with mutations mimicking K243/K253 acetylation in SAND, was able to activate gene expression, although the affected genes were different and the activation level was lower from those regulated by wild-type AIRE. Our results suggest that the AIRE acetylation can influence the selection of AIRE activated genes. -- Highlights: Black-Right-Pointing-Pointer AIRE is acetylated by the acetyltransferases p300 and CBP. Black-Right-Pointing-Pointer Acetylation occurs between CARD and SAND domains and within the SAND domain. Black-Right-Pointing-Pointer Acetylation increases the size of AIRE nuclear dots. Black-Right-Pointing-Pointer Acetylation increases AIRE protein stability. Black-Right-Pointing-Pointer AIRE acetylation mimic regulates a different set of AIRE

  18. Targeted Quantitation of Acetylated Lysine Peptides by Selected Reaction Monitoring Mass Spectrometry

    Rardin, Matthew J.; Held, Jason M.; Gibson, Bradford W.

    2013-01-01

    Mass spectrometry (MS) allows for the large-scale identification of multiple peptide analytes in complex mixtures. However, the low abundance of acetylated peptides in the overall mixture requires an enrichment step. After enrichment, the resulting acetylated peptides of interest can be quantitated using selected reaction monitoring (SRM)-MS with stable isotope dilution. Here, we describe the enrichment of lysine acetylated peptides from typsin digested mouse liver mitochondria, and the targe...

  19. Production and characterization of a monoclonal antibody to the O-acetylated peptidoglycan of Proteus mirabilis.

    Gyorffy, S; Clarke, A J

    1992-01-01

    A monoclonal antibody (PmPG5-3) specific for the O-acetylated peptidoglycan of Proteus mirabilis 19 was produced by an NS-1 myeloma cell line and purified from ascites fluid by a combination of ammonium sulfate precipitation and affinity chromatography. The monoclonal antibody (an immunoglobulin M) was characterized by a competition enzyme-linked immunosorbent assay to be equally specific for both insoluble and soluble O-acetylated peptidoglycan but weakly recognized chemically de-O-acetylate...

  20. Acetyl hexapeptide-3 in a cosmetic formulation acts on skin mechanical properties - clinical study

    Kassandra Azevedo Tadini; Daiane Garcia Mercurio; Patrícia Maria Berardo Gonçalves Maia Campos

    2015-01-01

    abstract Acetyl hexapeptide-3 has been used in anti-aging topical formulations aimed at improving skin appearance. However, few basic studies address its effects on epidermis and dermis, when vehiculated in topical formulations. Thus, the objective of this study was to determine the clinical efficacy of acetyl hexapeptide-3 using biophysical techniques. For this purpose, formulations with and without acetyl hexapeptide-3 were applied to the ventral forearm and the face area of forty female vo...

  1. Production of N α -acetylated thymosin α1 in Escherichia coli

    Ren, Yuantao; Yao, Xueqin; Dai, Hongmei; Li, Shulong; Fang, Hongqing; Chen, Huipeng; Zhou, Changlin

    2011-01-01

    Background Thymosin α1 (Tα1), a 28-amino acid N α -acetylated peptide, has a powerful general immunostimulating activity. Although biosynthesis is an attractive means of large-scale manufacture, to date, Tα1 can only be chemosynthesized because of two obstacles to its biosynthesis: the difficulties in expressing small peptides and obtaining N α -acetylation. In this study, we describe a novel production process for N α -acetylated Tα1 in Escherichia coli. Results To obtain recombinant N α -ac...

  2. Efficacy of N-Acetyl Cysteine in Traumatic Brain Injury

    Eakin, Katharine; Baratz-Goldstein, Renana; Pick, Chiam G.; Zindel, Ofra; Balaban, Carey D; Hoffer, Michael E.; Lockwood, Megan; Miller, Jonathan; Hoffer, Barry J.

    2014-01-01

    In this study, using two different injury models in two different species, we found that early post-injury treatment with N-Acetyl Cysteine (NAC) reversed the behavioral deficits associated with the TBI. These data suggest generalization of a protocol similar to our recent clinical trial with NAC in blast-induced mTBI in a battlefield setting [1], to mild concussion from blunt trauma. This study used both weight drop in mice and fluid percussion injury in rats. These were chosen to simulate e...

  3. Electron attachment to fluorocarbon radicals

    Shuman, Nicholas

    2014-10-01

    Most plasma environments contain populations of short-lived species such as radicals, the chemistry of which can have significant effects on the overall chemistry of the system. However, few experimental measurements of the kinetics of electron attachment to radicals exist due to the inherent difficulties of working with transient species. Calculations from first principles have been attempted, but are arduous and, because electron attachment is so sensitive to the specifics of the potential surface, their accuracy has not been established. Electron attachment to small fluorocarbon radicals is particularly important, as the data are needed for predictive modeling of plasma etching of semiconductor materials, a key process in the industrial fabrication of microelectronics. We have recently developed a novel flowing afterglow technique to measure several types of otherwise difficult to study plasma processes, including thermal electron attachment to radicals. Variable Electron and Neutral Density Attachment Mass Spectrometry (VENDAMS) exploits dissociative electron attachment in a weakly ionized plasma as a radical source. Here, we apply VENDAMS to a series of halofluorocarbon precursors in order to measure the kinetics of thermal electron attachment to fluorocarbon radicals. Results are presented for CF2, CF3, C2F5,C2F3,1-C3F7, 2-C3F7, and C3F5 from 300 K to 900 K. Both the magnitude and the temperature dependences of rate coefficients as well as product branching between associative and dissociative attachment are highly system specific; however, thermal attachment to all species is inefficient, never exceeding 5% of the collision rate. The data are analyzed using a recently developed kinetic modeling approach, which uses extended Vogt-Wannier theory as a starting point, accounts for dynamic effects such as coupling between the electron and nuclear motions through empirically validated functional forms, and finally uses statistical theory to determine the fate of

  4. Aspirin acetylates wild type and mutant p53 in colon cancer cells: identification of aspirin acetylated sites on recombinant p53.

    Ai, Guoqiang; Dachineni, Rakesh; Kumar, D Ramesh; Marimuthu, Srinivasan; Alfonso, Lloyd F; Bhat, G Jayarama

    2016-05-01

    Aspirin's ability to inhibit cell proliferation and induce apoptosis in cancer cell lines is considered to be an important mechanism for its anti-cancer effects. We previously demonstrated that aspirin acetylated the tumor suppressor protein p53 at lysine 382 in MDA-MB-231 human breast cancer cells. Here, we extended these observations to human colon cancer cells, HCT 116 harboring wild type p53, and HT-29 containing mutant p53. We demonstrate that aspirin induced acetylation of p53 in both cell lines in a concentration-dependent manner. Aspirin-acetylated p53 was localized to the nucleus. In both cell lines, aspirin induced p21(CIP1). Aspirin also acetylated recombinant p53 (rp53) in vitro suggesting that it occurs through a non-enzymatic chemical reaction. Mass spectrometry analysis and immunoblotting identified 10 acetylated lysines on rp53, and molecular modeling showed that all lysines targeted by aspirin are surface exposed. Five of these lysines are localized to the DNA-binding domain, four to the nuclear localization signal domain, and one to the C-terminal regulatory domain. Our results suggest that aspirin's anti-cancer effect may involve acetylation and activation of wild type and mutant p53 and induction of target gene expression. This is the first report attempting to characterize p53 acetylation sites targeted by aspirin. PMID:26596838

  5. Ionizing radiation induces immediate protein acetylation changes in human cardiac microvascular endothelial cells

    Reversible lysine acetylation is a highly regulated post-translational protein modification that is known to regulate several signaling pathways. However, little is known about the radiation-induced changes in the acetylome. In this study, we analyzed the acute post-translational acetylation changes in primary human cardiac microvascular endothelial cells 4 h after a gamma radiation dose of 2 Gy. The acetylated peptides were enriched using anti-acetyl conjugated agarose beads. A total of 54 proteins were found to be altered in their acetylation status, 23 of which were deacetylated and 31 acetylated. Pathway analyses showed three protein categories particularly affected by radiation-induced changes in the acetylation status: the proteins involved in the translation process, the proteins of stress response, and mitochondrial proteins. The activation of the canonical and non-canonical Wnt signaling pathways affecting actin cytoskeleton signaling and cell cycle progression was predicted. The protein expression levels of two nicotinamide adenine dinucleotide (NAD+)-dependent deacetylases, sirtuin 1 and sirtuin 3, were significantly but transiently upregulated 4 but not 24 h after irradiation. The status of the p53 protein, a target of sirtuin 1, was found to be rapidly stabilized by acetylation after radiation exposure. These findings indicate that post-translational modification of proteins by acetylation and deacetylation is essentially affecting the radiation response of the endothelium. (author)

  6. Effect of acetylation on arthropathic activity of group A streptococcal peptidoglycan-polysaccharide fragments.

    Stimpson, S. A.; Lerch, R A; Cleland, D R; Yarnall, D P; Clark, R L; Cromartie, W. J.; Schwab, J. H.

    1987-01-01

    Purified group A streptococcal peptidoglycan-polysaccharide (PG-PS) fragments were either de-O-acylated, or acetylated and then de-O-acylated to yield N-acetylated PG-PS. Native PG-PS was poorly degraded, N-acetylated PG-PS was extensively degraded, and de-O-acylated PG-PS was only slightly degraded by hen egg white lysozyme. N-acetylated PG-PS was also extensively degraded by human lysozyme and partially degraded by rat serum or rat liver extract. After a single intraperitoneal injection of ...

  7. Sirtuin-dependent reversible lysine acetylation of glutamine synthetases reveals an autofeedback loop in nitrogen metabolism.

    You, Di; Yin, Bin-Cheng; Li, Zhi-Hai; Zhou, Ying; Yu, Wen-Bang; Zuo, Peng; Ye, Bang-Ce

    2016-06-14

    In cells of all domains of life, reversible lysine acetylation modulates the function of proteins involved in central cellular processes such as metabolism. In this study, we demonstrate that the nitrogen regulator GlnR of the actinomycete Saccharopolyspora erythraea directly regulates transcription of the acuA gene (SACE_5148), which encodes a Gcn5-type lysine acetyltransferase. We found that AcuA acetylates two glutamine synthetases (GlnA1 and GlnA4) and that this lysine acetylation inactivated GlnA4 (GSII) but had no significant effect on GlnA1 (GSI-β) activity under the conditions tested. Instead, acetylation of GlnA1 led to a gain-of-function that modulated its interaction with the GlnR regulator and enhanced GlnR-DNA binding. It was observed that this regulatory function of acetylated GSI-β enzymes is highly conserved across actinomycetes. In turn, GlnR controls the catalytic and regulatory activities (intracellular acetylation levels) of glutamine synthetases at the transcriptional and posttranslational levels, indicating an autofeedback loop that regulates nitrogen metabolism in response to environmental change. Thus, this GlnR-mediated acetylation pathway provides a signaling cascade that acts from nutrient sensing to acetylation of proteins to feedback regulation. This work presents significant new insights at the molecular level into the mechanisms underlying the regulation of protein acetylation and nitrogen metabolism in actinomycetes. PMID:27247389

  8. p53 targets simian virus 40 large T antigen for acetylation by CBP.

    Poulin, Danielle L; Kung, Andrew L; DeCaprio, James A

    2004-08-01

    Simian virus 40 (SV40) large T antigen (T Ag) interacts with the tumor suppressor p53 and the transcriptional coactivators CBP and p300. Binding of these cellular proteins in a ternary complex has been implicated in T Ag-mediated transformation. It has been suggested that the ability of CBP/p300 to modulate p53 function underlies p53's regulation of cell proliferation and tumorigenesis. In this study, we provide further evidence that CBP activity may be mediated through its synergistic action with p53. We demonstrate that SV40 T Ag is acetylated in vivo in a p53-dependent manner and T Ag acetylation is largely mediated by CBP. The acetylation of T Ag is dependent on its interaction with p53 and on p53's interaction with CBP. We have mapped the site of acetylation on T Ag to the C-terminal lysine residue 697. This acetylation site is conserved between the T antigens of the human polyomaviruses JC and BK, which are also known to interact with p53. We show that both JC and BK T antigens are also acetylated at corresponding sites in vivo. While other proteins are known to be acetylated by CBP/p300, none are known to depend on p53 for acetylation. T Ag acetylation may provide a regulatory mechanism for T Ag binding to a cellular factor or play a role in another aspect of T Ag function. PMID:15254196

  9. Acetylation of cyclin-dependent kinase 5 is mediated by GCN5

    Lee, Juhyung; Yun, Nuri; Kim, Chiho [Department of Systems Biology, Yonsei University College of Life Science and Biotechnology, Seoul 120-749 (Korea, Republic of); Song, Min-Young; Park, Kang-Sik [Department of Physiology and Biomedical Science Institute, Kyung Hee University School of Medicine, Seoul 130-701 (Korea, Republic of); Oh, Young J., E-mail: yjoh@yonsei.ac.kr [Department of Systems Biology, Yonsei University College of Life Science and Biotechnology, Seoul 120-749 (Korea, Republic of)

    2014-04-25

    Highlights: • Cyclin-dependent kinase 5 (CDK5) is present as an acetylated form. • CDK5 is acetylated by GCN5. • CDK5’s acetylation site is mapped at Lys33. • Its acetylation may affect CDK5’s kinase activity. - Abstract: Cyclin-dependent kinase 5 (CDK5), a member of atypical serine/threonine cyclin-dependent kinase family, plays a crucial role in pathophysiology of neurodegenerative disorders. Its kinase activity and substrate specificity are regulated by several independent pathways including binding with its activator, phosphorylation and S-nitrosylation. In the present study, we report that acetylation of CDK5 comprises an additional posttranslational modification within the cells. Among many candidates, we confirmed that its acetylation is enhanced by GCN5, a member of the GCN5-related N-acetyl-transferase family of histone acetyltransferase. Co-immunoprecipitation assay and fluorescent localization study indicated that GCN5 physically interacts with CDK5 and they are co-localized at the specific nuclear foci. Furthermore, liquid chromatography in conjunction with a mass spectrometry indicated that CDK5 is acetylated at Lys33 residue of ATP binding domain. Considering this lysine site is conserved among a wide range of species and other related cyclin-dependent kinases, therefore, we speculate that acetylation may alter the kinase activity of CDK5 via affecting efficacy of ATP coordination.

  10. Preparation of radioactive acetyl-l-carnitine by an enzymatic exchange reaction

    A rapid method for the preparation of [1-14C]acetyl-L-carnitine is described. The method involves exchange of [1-14C]acetic acid into a pool of unlabeled acetyl-L-carnitine using the enzymes acetyl-CoA synthetase and carnitine acetyltransferase. After isotopic equilibrium is attained, radioactive acetylcarnitine is separated from the other reaction components by chromatography on Dowex 1 (C1-) anion exchange resin. One of the procedures used to verify the product [1-14C]acetyl-L-carnitine can be used to synthesize (3S)-[5-14C]citric acid

  11. Preparation of radioactive acetyl-l-carnitine by an enzymatic exchange reaction

    Emaus, R.; Bieber, L.L.

    1982-01-15

    A rapid method for the preparation of (1-/sup 14/C)acetyl-L-carnitine is described. The method involves exchange of (1-/sup 14/C)acetic acid into a pool of unlabeled acetyl-L-carnitine using the enzymes acetyl-CoA synthetase and carnitine acetyltransferase. After isotopic equilibrium is attained, radioactive acetylcarnitine is separated from the other reaction components by chromatography on Dowex 1 (C1/sup -/) anion exchange resin. One of the procedures used to verify the product (1-/sup 14/C)acetyl-L-carnitine can be used to synthesize (3S)-(5-/sup 14/C)citric acid.

  12. Synthesis of Andrographolide Glucopyranoside and Selective Cleavage of O-acetyl Groups in Sugar Moiety

    WANG Shao-Min; LIU Hong-Min

    2008-01-01

    Andrographolide glucopyranosides were synthesized from andrographolide and tetra-O-acetyl-β-D-glucopyranosyl bromide via a Koenigs-Knorr reaction and deacetylation with a moderate deacetylation reagent dibutyltin oxide in methanol for the first time.The structures of the andrographolide derivatives were confirmed by IR, NMR,and HRMS.Deprotection of the acetylated andrographolide glucopyranoside with dibutyltin oxide in methanol selectively removed all acetyl groups of the sugar moiety, whereas the acetyl group of the andrographolide part and the base- or acid-sensitive functional groups were retained.

  13. Meat consumption, N-acetyl transferase 1 and 2 polymorphism and risk of breast cancer, in Danish postmenopausal women

    Egeberg, Rikke; Olsen, Anja; Autrup, Herman;

    2008-01-01

    total meat intake and red meat intake and breast cancer risk were confined to intermediate/fast N-acetyl transferase 2 acetylators (P-interaction=0.03 and 0.04). Our findings support an association between meat consumption and breast cancer risk and that N-acetyl transferase 2 polymorphism has a......The aim of this study was to investigate whether polymorphisms in N-acetyl transferase 1 and 2 modify the association between meat consumption and risk of breast cancer. A nested case-control study was conducted among 24697 postmenopausal women included in the 'Diet, Cancer and Health' cohort study...... increment in intake. Compared with slow acetylators, the IRR (95% confidence interval) among fast N-acetyl transferase 1 acetylators was 1.43 (1.03-1.99) and 1.13 (0.83-1.54) among intermediate/fast N-acetyl transferase 2 acetylators. Interaction analyses revealed that the positive associations between...

  14. EPR spin trapping of protein radicals

    Davies, Michael Jonathan; Hawkins, Clare L

    2004-01-01

    Electron paramagnetic resonance (EPR) spin trapping was originally developed to aid the detection of low-molecular-mass radicals formed in chemical systems. It has subsequently found widespread use in biology and medicine for the direct detection of radical species formed during oxidative stress...... selected examples of radical formation on proteins....

  15. Radical carbonylations using a continuous microflow system

    Takahide Fukuyama

    2009-07-01

    Full Text Available Radical-based carbonylation reactions of alkyl halides were conducted in a microflow reactor under pressurized carbon monoxide gas. Good to excellent yields of carbonylated products were obtained via radical formylation, carbonylative cyclization and three-component coupling reactions, using tributyltin hydride or TTMSS as a radical mediator.

  16. Comparative analysis of pharmacological treatments with N-acetyl-dl-leucine (Tanganil) and its two isomers (N-acetyl-L-leucine and N-acetyl-D-leucine) on vestibular compensation: Behavioral investigation in the cat.

    Tighilet, Brahim; Leonard, Jacques; Bernard-Demanze, Laurence; Lacour, Michel

    2015-12-15

    Head roll tilt, postural imbalance and spontaneous nystagmus are the main static vestibular deficits observed after an acute unilateral vestibular loss (UVL). In the UVL cat model, these deficits are fully compensated over 6 weeks as the result of central vestibular compensation. N-Acetyl-dl-leucine is a drug prescribed in clinical practice for the symptomatic treatment of acute UVL patients. The present study investigated the effects of N-acetyl-dl-leucine on the behavioral recovery after unilateral vestibular neurectomy (UVN) in the cat, and compared the effects of each of its two isomers N-acetyl-L-leucine and N-acetyl-D-leucine. Efficacy of these three drug treatments has been evaluated with respect to a placebo group (UVN+saline water) on the global sensorimotor activity (observation grids), the posture control (support surface measurement), the locomotor balance (maximum performance at the rotating beam test), and the spontaneous vestibular nystagmus (recorded in the light). Whatever the parameters tested, the behavioral recovery was strongly and significantly accelerated under pharmacological treatments with N-acetyl-dl-leucine and N-acetyl-L-leucine. In contrast, the N-acetyl-D-leucine isomer had no effect at all on the behavioral recovery, and animals of this group showed the same recovery profile as those receiving a placebo. It is concluded that the N-acetyl-L-leucine isomer is the active part of the racemate component since it induces a significant acceleration of the vestibular compensation process similar (and even better) to that observed under treatment with the racemate component only. PMID:26607469

  17. Free radicals and Dupuytren's contracture.

    Murrell, G. A.; Francis, M. J.; Bromley, L.

    1987-01-01

    The concentration of substrate expressed as hypoxanthine capable of reacting with xanthine oxidase to release superoxide free radicals (O2-) was measured in control and Dupuytren's contracture palmar fascia. In Dupuytren's contracture palmar fascia the concentration of hypoxanthine was six times that of control and was greatest in "nodular" areas. Xanthine oxidase activity was also detected in Dupuytren's contracture palmar fascia. These results suggest a greater potential for hypoxanthine-xa...

  18. The Metabolic Fate of Deoxynivalenol and Its Acetylated Derivatives in a Wheat Suspension Culture: Identification and Detection of DON-15-O-Glucoside, 15-Acetyl-DON-3-O-Glucoside and 15-Acetyl-DON-3-Sulfate

    Clemens Schmeitzl

    2015-08-01

    Full Text Available Deoxynivalenol (DON is a protein synthesis inhibitor produced by the Fusarium species, which frequently contaminates grains used for human or animal consumption. We treated a wheat suspension culture with DON or one of its acetylated derivatives, 3-acetyl-DON (3-ADON, 15-acetyl-DON (15-ADON and 3,15-diacetyl-DON (3,15-diADON, and monitored the metabolization over a course of 96 h. Supernatant and cell extract samples were analyzed using a tailored LC-MS/MS method for the quantification of DON metabolites. We report the formation of tentatively identified DON-15-O-β-D-glucoside (D15G and of 15-acetyl-DON-3-sulfate (15-ADON3S as novel deoxynivalenol metabolites in wheat. Furthermore, we found that the recently identified 15-acetyl-DON-3-O-β-D-glucoside (15-ADON3G is the major metabolite produced after 15-ADON challenge. 3-ADON treatment led to a higher intracellular content of toxic metabolites after six hours compared to all other treatments. 3-ADON was exclusively metabolized into DON before phase II reactions occurred. In contrast, we found that 15-ADON was directly converted into 15-ADON3G and 15-ADON3S in addition to metabolization into deoxynivalenol-3-O-β-D-glucoside (D3G. This study highlights significant differences in the metabolization of DON and its acetylated derivatives.

  19. Autotrophic acetyl coenzyme A biosynthesis in Methanococcus maripaludis

    To detect autotrophic CO2 assimilation in cell extracts of Methanococcus maripaludis, lactate dehydrogenase and NADH were added to convert pyruvate formed from autotropically synthesized acetyl coenzyme A to lactate. The lactate produced was determined spectrophotometrically. When CO2 fixation was pulled in the direction of lactate synthesis, CO2 reduction to methane was inhibited. Bromoethanesulfonate (BES), a potent inhibitor of methanogenesis, enhanced lactate synthesis, and methyl coenzyme M inhibited it in the absence of BES. Lactate synthesis was dependent on CO2 and H2, but H2 + CO2-independent synthesis was also observed. In cell extracts, the rate of lactate synthesis was about 1.2 nmol min-1 mg of protein-1. When BES was added, the rate of lactate synthesis increased to 2.1 nmol min-1 mg of protein-1. Because acetyl coenzyme A did not stimulate lactate synthesis, pyruvate synthase may have been the limiting activity in these assays. Radiolabel from 14CO2 was incorporated into lactate. The percentages of radiolabel in the C-1, C-2, and C-3 positions of lactate were 73, 33, and 11%, respectively. Both carbon monoxide and formaldehyde stimulated lactate synthesis. 14CH2O was specifically incorporated into the C-3 of lactate, and 14CO was incorporated into the C-1 and C-2 positions. Low concentrations of cyanide also inhibited autotrophic growth, CO dehydrogenase activity, and autotrophic lactate synthesis. These observations are in agreement with the acetogenic pathway of autotrophic CO2 assimilation

  20. The dynamic organization of fungal acetyl-CoA carboxylase

    Hunkeler, Moritz; Stuttfeld, Edward; Hagmann, Anna; Imseng, Stefan; Maier, Timm

    2016-04-01

    Acetyl-CoA carboxylases (ACCs) catalyse the committed step in fatty-acid biosynthesis: the ATP-dependent carboxylation of acetyl-CoA to malonyl-CoA. They are important regulatory hubs for metabolic control and relevant drug targets for the treatment of the metabolic syndrome and cancer. Eukaryotic ACCs are single-chain multienzymes characterized by a large, non-catalytic central domain (CD), whose role in ACC regulation remains poorly characterized. Here we report the crystal structure of the yeast ACC CD, revealing a unique four-domain organization. A regulatory loop, which is phosphorylated at the key functional phosphorylation site of fungal ACC, wedges into a crevice between two domains of CD. Combining the yeast CD structure with intermediate and low-resolution data of larger fragments up to intact ACCs provides a comprehensive characterization of the dynamic fungal ACC architecture. In contrast to related carboxylases, large-scale conformational changes are required for substrate turnover, and are mediated by the CD under phosphorylation control.

  1. A Preliminary Study: N-acetyl-L-cysteine Improves Semen Quality following Varicocelectomy

    Foroogh Barekat

    2016-05-01

    Full Text Available Background: Surgery is considered the primary treatment for male infertility from clinical varicocele. One of the main events associated with varicocele is excessive production of reactive oxygen species (ROS. N-acetyl-L-cysteine (NAC, an antioxidant that scavenges free radicals, is considered a supplement to alleviate glutathione (GSH depletion during oxidative stress. Despite beneficial effects of NAC in other pathological events, there is no report on the effect of NAC in individuals with varicocele. Therefore, the aim of this study is to evaluate the outcome of NAC on semen quality, protamine content, DNA damage, oxidative stress and fertility following varicocelectomy. Materials and Methods: This prospective clinical trial included 35 infertile men with varicocele randomly divided into control (n=20 and NAC (n=15 groups. We assessed semen parameters, protamine content [chromomycin A3 (CMA3], DNA integrity [terminal deoxynucleotidyltransferase-mediated dUTP nick-end labeling (TUNEL] and oxidative stress [2', 7'-dichlorodihydrofluorescein-diacetate (DCFH-DA] before and three months after varicocelectomy. Results: Percentage of abnormal semen parameters, protamine deficiency, DNA fragmentation and oxidative stress were significantly decreased in both groups compared to before surgery. We calculated the percentage of improvement in these parameters compared to before surgery for each group, then compared the results between the groups. Only percentage of protamine deficiency and DNA fragmentation significantly differed between the NAC and control groups. Conclusion: The results of this study, for the first time, revealed that NAC improved chromatin integrity and pregnancy rate when administered as adjunct therapy post-varicocelectomy (Registeration Number: IRCT201508177223N5.

  2. Can N-acetyl-L-cysteine affect zinc metabolism when used as a paracetamol antidote?

    Brumas, V; Hacht, B; Filella, M; Berthon, G

    1992-07-01

    N-Acetyl-L-cysteine (NAC) has long been used in the treatment of chronic lung diseases. Inhalation and oral administration of the drug are both effective in reducing mucus viscosity. In addition, NAC oral therapy allows to restore normal mucoprotein secretion in the long term. Although displaying heavy metal-complexing potential, NAC exerts no detectable influence on the metabolism of essential trace metals when used in the above context (i.e. at doses near 600 mg day-1). However, this may no longer be the case when NAC is used as an oxygen radical scavenger, like in the treatment of paracetamol poisoning. In the latter case, intravenous doses as high as 20 g day-1 are administered, which may induce excessive zinc urinary excretion. In order to allow a better appreciation of the risk of zinc depletion during NAC therapy, the present work addresses the role of this drug towards zinc metabolism at the molecular level. First, formation constants for zinc-NAC complexes have been determined under physiological conditions. Then, computer simulations for blood plasma and gastrointestinal fluid have been run to assess the influence of NAC and its metabolites (e.g. cysteine and glutathione) on zinc excretion and absorption. Blood plasma simulations reveal that NAC can effectively mobilise an important fraction of zinc into urinary excretable complexes as from concentrations of 10(-3) mol dm-3 (which corresponds to a dose of about 800 mg). This effect can still be enhanced by the action of NAC metabolites, among which cysteine is the most powerful zinc sequestering agent. In contrast, simulations relative to gastrointestinal conditions suggest that NAC should tend to increase zinc absorption, regardless of its dose. PMID:1529808

  3. Acetyl L-Carnitine Modulating Irradiation Induced Cardio-Pulmonary Toxicity in Rats

    In The Present study male adult Wister albino rats were irradiated at 4 Gy whole body gamma irradiation and Acetyl L-carnitine (ALC) was evaluated as a potential radio-protector under conditions that would model the oxidative stress syndrome. ALC protect the heart and lung from the depletion of SOD, GSHPx activities and GSH content followed radiation exposure. Protection from the increase of malonaldehyde (MDA) in heart and lung tissues as well as serum creatine phosphokinase (CPK), AST and LDH has been observed. These results imply that ALC can act as a radio-protector against many aspects of oxidative damage. ALC is an ester of the tri methylated amino acid L-carnitine, and is synthesized endogenously in the human brain, liver and kidney by the enzyme ALC transferase or obtained from dietary sources (Goa and Brogden, 1987). L carnitine and short chain derivatives are essential cofactors for mitochondrial transport and oxidation of long chain fatty acid and act also as scavengers of oxygen free radicals in mammalian tissue (Izgut-Uysal et al., 2001). The transport of ALC and PLC occurs more easily than L-carnitine through the lipid component of the intestinal barrier suggesting possible better oral bioavailability of the esters than L-carnitine (Marciniani et al., 1991). ALC has antioxidant activity towards oxidative stress via an inhibition of the increase in lipid hydro peroxidation (Yasui et al., 2002). ALC significantly enhances the regenerative capacity of neurons that survive peripheral nerve trauma (Marciniani et al., 1991) and has also shown neuro-protective effect in rats (Bigini et al., 2002)

  4. The Antioxidant Role of Glutathione and N-Acetyl-Cysteine Supplements and Exercise-Induced Oxidative Stress

    Willoughby Darryn

    2005-12-01

    Full Text Available Abstract An increase in exercise intensity is one of the many ways in which oxidative stress and free radical production has been shown to increase inside our cells. Effective regulation of the cellular balance between oxidation and antioxidation is important when considering cellular function and DNA integrity as well as the signal transduction of gene expression. Many pathological states, such as cancer, Parkinson's disease, and Alzheimer's disease have been shown to be related to the redox state of cells. In an attempt to minimize the onset of oxidative stress, supplementation with various known antioxidants has been suggested. Glutathione and N-acetyl-cysteine (NAC are antioxidants which are quite popular for their ability to minimize oxidative stress and the downstream negative effects thought to be associated with oxidative stress. Glutathione is largely known to minimize the lipid peroxidation of cellular membranes and other such targets that is known to occur with oxidative stress. N-acetyl-cysteine is a by-product of glutathione and is popular due to its cysteine residues and the role it has on glutathione maintenance and metabolism. The process of oxidative stress is a complicated, inter-twined series of events which quite possibly is related to many other cellular processes. Exercise enthusiasts and researchers have become interested in recent years to identify any means to help minimize the detrimental effects of oxidative stress that are commonly associated with intense and unaccustomed exercise. It is possible that a decrease in the amount of oxidative stress a cell is exposed to could increase health and performance.

  5. Chemical repair of trypsin-histidinyl radical

    Oxyl radicals, such as hydroxyl, alkoxyl and peroxyl, react with biomolecules to produce bioradicals. Unless chemically repaired by suitable antioxidants, these bioradicals form stable products. This leads to loss of biological function of parent biomolecules with deleterious biological results, such as mutagenesis and cancer. Consequently, the understanding of the mechanisms of oxyl radical damage to biomolecules and chemical repair of such damage is crucial for the development of strategies for anticarcinogenesis and radioprotection. In this study the chemical repair of the histidinyl radical generated upon the trichloromethylperoxyl radical reaction with trypsin vas investigated by gamma radiolysis. The trypsin histidinyl radical is a resonance-stabilized heterocyclic free radical which was found to be unreactive with oxygen. The efficacy of the chemical repair of the trypsin-histidinyl radical by endogenous antioxidants which are electron donors (e.g. 5-hydroxytryptophan, uric acid) is compared to that of antioxidants which are H-atom donors (e. g. glutathione). 9 refs., 2 figs., 1 tab

  6. Polymorphic acetylation of the antibacterials, sulfamethazine and dapsone, in South Indian subjects.

    Peters, J H; Gordon, G R; Karat, A B

    1975-07-01

    A group of South Indian subjects was studied for their capacities to acetylate sulfamethazine (SMZ) and dapsone (DDS) and to clear DDS from the circulation. An apparent trimodal distribution of acetylator phenotypes was found in 49 subjects (51% slow, 12% intermediate, and 37% rapid acetylators) from measurements of the percentage acetylation of SMZ in 6-hour plasma samples after administration of 10 mg SMZ/kg. The intermediate phenotype was not discernible from either the percentage acetylation of SMZ in urine (collected concurrently with the plasma after SMZ) or that of DDS in plasma after the ingestion of 50 mg DDS by the same subjects. The latter two measurements yielded a bimodal distribution of 59% slow and 41% rapid acetylators, nearly identical to earlier reported distributions of isoniazid inactivator phenotypes in larger numbers of South Indian tuberculosis patients. In the current group, acetylation of DDS and SMZ was positively correlated. The half-time of disappearance (T 1/2) of DDS, an expression of the rate of clearance from the plasma, ranged from 13 to 40 hours. No correlation was found between the subject's capacity to acetylate DDS and the T 1/2 value for DDS. These results were generally consistent with earlier observations made during similar studies of American and Filipino subjects. PMID:1155699

  7. chiral Synthesis of 13-Acetyl-12-hydroxy-podocarpane-8, 11,13-triene-7-one

    2001-01-01

    An enantioselective synthetic route to (+)-13-acetyl-12-hydroxy-podocarpane-8,11,13-triene-7-one 1a and (-)-13-acetyl-12-hydroxy-podocarpane-8,11,13-triene-7-one 1b was developed from (S)-(-)-a -cyclocitral 8a and (R)-(+)-a -cyclocitral 8b.

  8. The Effect of Acetyl-L-Carnitine Administration on Persons with Down Syndrome

    Pueschel, Siegfried M.

    2006-01-01

    Since previous investigations reported improvements in cognition of patients with dementia after acetyl-L-carnitine therapy and since there is an increased risk for persons with Down syndrome to develop Alzheimer disease, this study was designed to investigate the effect of acetyl-L-carnitine administration on neurological, intellectual, and…

  9. Acetylation of Starch with Vinyl Acetate in Imidazolium Ionic Liquids and Characterization of Acetate Distribution

    Starch was acetylated with vinyl acetate in different 1-butyl-3-methylimidazolium (BMIM) salts as solvent in effort to produce starches with different acetylation patterns. Overall degree of substitution was much higher for basic anions such as acetate and dicyanimide (dca) than for neutral anions ...

  10. A dysregulated acetyl/SUMO switch of FXR promotes hepatic inflammation in obesity.

    Kim, Dong-Hyun; Xiao, Zhen; Kwon, Sanghoon; Sun, Xiaoxiao; Ryerson, Daniel; Tkac, David; Ma, Ping; Wu, Shwu-Yuan; Chiang, Cheng-Ming; Zhou, Edward; Xu, H Eric; Palvimo, Jorma J; Chen, Lin-Feng; Kemper, Byron; Kemper, Jongsook Kim

    2015-01-13

    Acetylation of transcriptional regulators is normally dynamically regulated by nutrient status but is often persistently elevated in nutrient-excessive obesity conditions. We investigated the functional consequences of such aberrantly elevated acetylation of the nuclear receptor FXR as a model. Proteomic studies identified K217 as the FXR acetylation site in diet-induced obese mice. In vivo studies utilizing acetylation-mimic and acetylation-defective K217 mutants and gene expression profiling revealed that FXR acetylation increased proinflammatory gene expression, macrophage infiltration, and liver cytokine and triglyceride levels, impaired insulin signaling, and increased glucose intolerance. Mechanistically, acetylation of FXR blocked its interaction with the SUMO ligase PIASy and inhibited SUMO2 modification at K277, resulting in activation of inflammatory genes. SUMOylation of agonist-activated FXR increased its interaction with NF-κB but blocked that with RXRα, so that SUMO2-modified FXR was selectively recruited to and trans-repressed inflammatory genes without affecting FXR/RXRα target genes. A dysregulated acetyl/SUMO switch of FXR in obesity may serve as a general mechanism for diminished anti-inflammatory response of other transcriptional regulators and provide potential therapeutic and diagnostic targets for obesity-related metabolic disorders. PMID:25425577

  11. Effects of acetylation on the emulsifying properties of Artemisia sphaerocephala Krasch. polysaccharide.

    Li, Junjun; Hu, Xinzhong; Li, Xiaoping; Ma, Zhen

    2016-06-25

    In the present study, polysaccharides extracted from Artemisia sphaerocephala Krasch. seeds (ASKP) were acetylated to improve the emulsifying properties of the macromolecules. Several methods were applied for the acetylation purpose, among which the acetic anhydride-pyridine method with formamide as solvent was found to be the most effective one. Acetylated ASKPs with various degree of substitution (DS) were successfully produced and structurally characterized using HPSEC-MALS, FTIR and (1)H NMR techniques in this study. Results showed that acetylation treatment could cause the degradation of ASKP. Moreover, with the increase of DS, both the molecular weight and radius of gyration increased, as well as the molecular conformation trended to be more compact. Low DS (DS: 0.04 and 0.13) conferred acetylated ASKP a lower viscosity than that of ASKP. With the increase of DS, the viscosity of acetylated ASKPs increased and exceeded that of ASKP. Compared with ASKP, acetylated ASKPs could reduce the surface tension to a greater extent and demonstrated a much smaller droplet size (ZD) in an oil/water emulsion system. Acetylated ASKPs were capable of stabilizing the oil/water emulsion for 3 days at 60°C, whose performance was as good as that of gum acacia. In conclusion, such a hydrophobic modification on ASKP conferred it better emulsifying properties. PMID:27083845

  12. Effect of Acetyl Group on Mechanical Properties of Chitin/Chitosan Nanocrystal: A Molecular Dynamics Study

    Cui, Junhe; Yu, Zechuan; Lau, Denvid

    2016-01-01

    Chitin fiber is the load-bearing component in natural chitin-based materials. In these materials, chitin is always partially deacetylated to different levels, leading to diverse material properties. In order to understand how the acetyl group enhances the fracture resistance capability of chitin fiber, we constructed atomistic models of chitin with varied acetylation degree and analyzed the hydrogen bonding pattern, fracture, and stress-strain behavior of these models. We notice that the acetyl group can contribute to the formation of hydrogen bonds that can stabilize the crystalline structure. In addition, it is found that the specimen with a higher acetylation degree presents a greater resistance against fracture. This study describes the role of the functional group, acetyl groups, in crystalline chitin. Such information could provide preliminary understanding of nanomaterials when similar functional groups are encountered. PMID:26742033

  13. Effects of Partially N-acetylated Chitosans to Elicit Resistance Reaction on Brassica napus L.

    ZHANG Xue-kun; TANG Zhang-lin; CHEN Li; GUO Yi-hong; CHEN Yun-ping; LI Jia-na

    2002-01-01

    The effects to elicit resistance reaction on oilseed rape (Brassica napus L. cv Xinongchangjiao )by four partially N-acetylated chitosan 7B, 8B, 9B and 10B (Degree of acetylation (D. A. ) is 30%, 20%,10%, 0%, respectively) and Glycol chitosan (GC, D.A. is 0%) were investigated and compared. Results showed that chitosan were similar to salicylic acid (SA), and could induce resistance reaction, but the reaction was influenced by the degree of acetylation of chitosan. Fully deacetylated chitosans, 10B and GC, elicited chitinase activity, but partially acetylated chitosan, 7B, 8B and 9B, inhibited chitinase activity. Phenyalanine ammonia-lyase (PAL) was also elicited. Elicitor activity increased with on increasing degree of acetylation, 7B induced highest PAL activity among all chitosans. All chitosans induced peroxidase (POD) in a similar level.After elicited by glycol chitosan, like SA treatment, the seedlings increased disease resistance to Sclerotinia sclerotiorum significantly.

  14. Acetylation dynamics of human nuclear proteins during the ionizing radiation-induced DNA damage response

    Bennetzen, Martin; Andersen, J.S.; Lasen, D.H.;

    2013-01-01

    -dependent posttranslational modifications (PT Ms). To complement our previous analysis of IR-induced temporal dynamics of nuclear phosphoproteome, we now identify a range of human nuclear proteins that are dynamically regulated by acetylation, and predominantly deacetylation, during IR-induced DDR by using mass spectrometry......-based proteomic approaches. Apart from cataloging acetylation sites through SILAC proteomic analyses before IR and at 5 and 60 min after IR exposure of U2OS cells, we report that: (1) key components of the transcriptional machinery, such as EP 300 and CREBBP, are dynamically acetylated; (2) that nuclear...... to assess lysine acetylation status and thereby validate the mass spectrometry data. We thus present evidence that nuclear proteins, including those known to regulate cellular functions via epigenetic modifications of histones, are regulated by (de)acetylation in a timely manner upon cell's exposure...

  15. Effect of Acetyl Group on Mechanical Properties of Chitin/Chitosan Nanocrystal: A Molecular Dynamics Study

    Junhe Cui

    2016-01-01

    Full Text Available Chitin fiber is the load-bearing component in natural chitin-based materials. In these materials, chitin is always partially deacetylated to different levels, leading to diverse material properties. In order to understand how the acetyl group enhances the fracture resistance capability of chitin fiber, we constructed atomistic models of chitin with varied acetylation degree and analyzed the hydrogen bonding pattern, fracture, and stress-strain behavior of these models. We notice that the acetyl group can contribute to the formation of hydrogen bonds that can stabilize the crystalline structure. In addition, it is found that the specimen with a higher acetylation degree presents a greater resistance against fracture. This study describes the role of the functional group, acetyl groups, in crystalline chitin. Such information could provide preliminary understanding of nanomaterials when similar functional groups are encountered.

  16. Aromatic-radical oxidation chemistry

    Glassman, I.; Brezinsky, K. [Princeton Univ., NJ (United States)

    1993-12-01

    The research effort has focussed on discovering an explanation for the anomalously high CO{sub 2} concentrations observed early in the reaction sequence of the oxidation of cyclopentadiene. To explain this observation, a number of plausible mechanisms have been developed which now await experimental verification. One experimental technique for verifying mechanisms is to probe the reacting system by perturbing the radical concentrations. Two forms of chemical perturbation of the oxidation of cyclopentadiene were begun during this past year--the addition of NO{sub 2} and CO to the reacting mixture.

  17. Laser spectroscopy of hydrocarbon radicals

    Chen, P. [Harvard Univ., Cambridge, MA (United States)

    1993-12-01

    The author reports the application of supersonic jet flash pyrolysis to the specific preparation of a range of organic radicals, biradicals, and carbenes in a skimmed molecular beam. Each species was produced cleanly and specifically, with little or no secondary reactions by the thermal dissociation of appropriately designed and synthesized organic precursors. Photoelectron spectra of the three isomeric C{sub 3}H{sub 2} carbenes, ortho-benzyne, and the {alpha},3-dehydrotoluene biradical, were used to establish adiabatic ionization potentials for use in thermochemical determinations.

  18. Iron and iron derived radicals

    We have discussed some reactions of iron and iron-derived oxygen radicals that may be important in the production or treatment of tissue injury. Our conclusions challenge, to some extent, the usual lines of thought in this field of research. Insofar as they are born out by subsequent developments, the lessons they teach are two: Think fast! Think small! In other words, think of the many fast reactions that can rapidly alter the production and fate of highly reactive intermediates, and when considering the impact of competitive reactions on such species, think how they affect the microenvironment (on the molecular scale) ''seen'' by each reactive molecule. 21 refs., 3 figs., 1 tab

  19. Detection of a secondary muoniated radical

    McCollum, Brett M.; Brodovitch, Jean-Claude [TRIUMF and Department of Chemistry, Simon Fraser University, Burnaby, BC, V5A 1S6 (Canada); Clyburne, Jason A.C. [Department of Chemistry, Saint Mary' s University, Halifax, NS, B3H 3C3 (Canada); Percival, Paul W., E-mail: percival@sfu.c [TRIUMF and Department of Chemistry, Simon Fraser University, Burnaby, BC, V5A 1S6 (Canada); West, Robert [Organosilicon Research Center, University of Wisconsin, Madison, WI 53706 (United States)

    2009-04-15

    Muoniated free radicals are formed by addition of muonium to unsaturated molecules. Successful detection by transverse-field muon spin rotation (muSR) usually requires pure or highly concentrated samples and a muonium reaction rate in excess of 10{sup 9} M{sup -1}s{sup -1} to ensure that the muon spin polarization is coherently transferred to the radical. For this reason muoniated radicals reported to date are all the primary radical products of Mu reaction. Thus, it was expected that Mu addition to a silylene would result in detection of a silyl radical. However, the muon hyperfine constant determined by experiment is much smaller than the value predicted by density functional calculations. Instead, it is consistent with a disilanyl radical, the secondary radical formed by reaction of the initially formed silyl radical with a second silylene molecule. From an analysis of the signal amplitude it was deduced that the second-order rate constant for reaction of the muoniated silyl radical with the parent silylene is 5.7x10{sup 8} M{sup -1}s{sup -1}. This work represents the first example of direct detection of a secondary radical product by transverse-field muSR.

  20. H3K9 acetylation and radial chromatin positioning

    Strašák, Luděk; Bártová, Eva; Harničarová, Andrea; Galiová-Šustáčková, Gabriela; Krejčí, Jana; Kozubek, Stanislav

    2009-01-01

    Roč. 220, č. 1 (2009), s. 91-101. ISSN 0021-9541 R&D Projects: GA MŠk(CZ) LC06027; GA MŠk(CZ) LC535; GA AV ČR(CZ) 1QS500040508; GA AV ČR(CZ) IAA5004306; GA ČR(CZ) GA204/06/0978 Grant ostatní: GA ČR(CZ) GP310/07/P480 Institutional research plan: CEZ:AV0Z50040507; CEZ:AV0Z50040702 Keywords : chromatin structure * RIDGE and anti-RIDGE regions * H3K9 acetylation Subject RIV: BO - Biophysics Impact factor: 4.586, year: 2009

  1. Ach1 is involved in shuttling mitochondrial acetyl units for cytosolic C2 provision in Saccharomyces cerevisiae lacking pyruvate decarboxylase

    Chen, Yun; Zhang, Yiming; Siewers, Verena;

    2015-01-01

    Saccharomyces cerevisiae, acetyl-CoA is compartmentalized in the cytosol, mitochondrion, peroxisome and nucleus, and cannot be directly transported between these compartments. With the acetyl-carnitine or glyoxylate shuttle, acetyl-CoA produced in peroxisomes or the cytoplasm can be transported into the......-fermentative yeast strain. We found that mitochondrial Ach1 can convert acetyl-CoA in this compartment into acetate, which crosses the mitochondrial membrane before being converted into acetyl-CoA in the cytosol. Based on our finding we propose a model in which acetate can be used to exchange acetyl units between...... mitochondria and the cytosol. These results will increase our fundamental understanding of intracellular transport of acetyl units, and also help to develop microbial cell factories for many kinds of acetyl-CoA derived products....

  2. Mechanism of the lysosomal membrane enzyme acetyl coenzyme A: alpha-glucosaminide N-acetyltransferase

    Acetyl-CoA:α-glucosaminide N-acetyltransferase is a lysosomal membrane enzyme, deficient in the genetic disease Sanfilippo C syndrome. The enzyme catalyzes the transfer of an acetyl group from cytoplasmic acetyl-CoA to terminal α-glucosamine residues of heparan sulfate within the organelle. The reaction mechanism was examined using high purified lysosomal membranes from rat liver and human fibroblasts. The N-acetyltransferase reaction is optimal above pH 5.5 and a 2-3 fold stimulation of activity is observed in the presence of 0.1% taurodeoxycholate. Double reciprocal analysis and product inhibition studies indicate that the enzyme works by a Di-Iso Ping Pong Bi Bi mechanism. The binding of acetyl-CoA to the enzyme is measured by exchange label from [3H]CoA to acetyl-CoA, and is optimal at pH's above 7.0. The acetyl-enzyme intermediate is formed by incubating membranes with [3H]acetyl-CoA. The acetyl group can be transferred to glucosamine, forming [3H]N-acetylglucosamine; the transfer is optimal between pH 4 and 5. Lysosomal membranes from Sanfilippo C fibroblasts confirm that these half reactions carried out by the N-acetyltransferase. The enzyme is inactivated by N-bromosuccinimide and diethylpyrocarbonate, indicating that a histidine is involved in the reaction. These results suggest that the histidine residue is at the active site of the enzyme. The properties of the N-acetyltransferase in the membrane, the characterization of the enzyme kinetics, the chemistry of a histidine mediated acetylation and the pH difference across the lysosomal membrane all support a transmembrane acetylation mechanism

  3. Hair Analysis for Determination of Isoniazid Concentrations and Acetylator Phenotype during Antituberculous Treatment

    Michael Eisenhut

    2012-01-01

    Full Text Available Background. Analysis of isoniazid (INH uptake has been based on measurement of plasma concentrations providing a short-term and potentially biased view. Objectives. To establish hair analysis as a tool to measure long-term uptake of INH and to assess whether acetylator phenotype in hair reflects N-acetyltransferase-2 (NAT2 genotype. Design and Methods. INH and acetyl-INH concentrations in hair were determined in patients on INH treatment for M. tuberculosis infection using high pressure liquid chromatography/mass spectrometry. Acetyl-INH/INH ratios were correlated with NAT-2 genotype. Results. Hair concentrations of INH, determined in 40 patients, were not dependent on ethnic group or body mass index and were significantly higher in male compared to female patients (median (range 2.37 ng/mg (0.76–4.9 versus 1.11 ng/mg (0.02–7.20 (P=0.02. Acetyl-INH/INH ratios were a median of 15.2% (14.5 to 31.7 in homozygous rapid acetylator NAT-2 genotype and 37.3% (1.73 to 51.2 in the heterozygous rapid acetylator NAT-2 genotype and both significantly higher than in the slow acetylator NAT-2 genotype with 5.8% (0.53 to 14.4 (P<0.05. Conclusions. Results of hair analysis for INH showed lower concentrations in females. Acetyl-INH/INH ratios were significantly lower in patients with slow acetylator versus rapid acetylator genotypes.

  4. Free radicals and lipid peroxidation mediated injury in burn trauma: the role of antioxidant therapy

    (ascorbic acid, glutathione, N-acetyl-L-cysteine, or vitamins A, E, and C alone or in combination) have been shown to reduce burn and burn/sepsis mediated mortality, to attenuate changes in cellular energetics, to protect microvascular circulation, reduce tissue lipid peroxidation, improve cardiac output, and to reduce the volume of required fluid resuscitation. Antioxidant vitamin therapy with fluid resuscitation has also been shown to prevent burn related cardiac NF-κB nuclear migration, to inhibit cardiomyocyte secretion of TNF-α, IL-1β, and IL-6, and to improve cardiac contractile function. These data collectively support the hypothesis that cellular oxidative stress is a critical step in burn-mediated injury, and suggest that antioxidant strategies designed to either inhibit free radical formation or to scavage free radicals may provide organ protection in patients with burn injury

  5. System-wide Studies of N-Lysine Acetylation in Rhodopseudomonas palustris Reveals Substrate Specificity of Protein Acetyltransferases

    Crosby, Heidi A [University of Wisconsin, Madison; Pelletier, Dale A [ORNL; Hurst, Gregory {Greg} B [ORNL; Escalante-Semerena, Jorge C [University of Wisconsin, Madison

    2012-01-01

    Background: Protein acetylation is widespread in prokaryotes. Results: Six new acyl-CoA synthetases whose activities are controlled by acetylation were identified, and their substrate preference established. A new protein acetyltransferase was also identified and its substrate specificity determined. Conclusion: Protein acetyltransferases acetylate a conserved lysine residue in protein substrates. Significance: The R. palustris Pat enzyme specifically acetylates AMP-forming acyl-CoA synthetases and regulates fatty acid metabolism.

  6. Three novel acetylation sites in the Foxp3 transcription factor regulate the suppressive activity of regulatory T cells

    Kwon, Hye-Sook; Lim, Hyung W; Wu, Jessica; Schnoelzer, Martina; Verdin, Eric; Ott, Melanie

    2012-01-01

    The Foxp3 transcription factor is the master regulator of regulatory T cell (Treg) differentiation and function. Its activity is regulated by reversible acetylation. Using mass spectrometry of immunoprecipitated proteins, we identify three novel acetylation sites in murine Foxp3 (K31, K262, and K267) and the corresponding sites in human FoxP3 proteins. Newly raised modification-specific antibodies against acetylated K31 and K267 confirm acetylation of these residues in murine Tregs. Mutant Fo...

  7. 40 CFR 180.1089 - Poly-N-acetyl-D-glucosamine; exemption from the requirement of tolerance.

    2010-07-01

    ... 40 Protection of Environment 23 2010-07-01 2010-07-01 false Poly-N-acetyl-D-glucosamine; exemption... FOOD Exemptions From Tolerances § 180.1089 Poly-N-acetyl-D-glucosamine; exemption from the requirement... biochemical nematicide poly-N-acetyl-D-glucosamine on a variety of agricultural crops....

  8. A Radically Configurable Six-State Compound

    Barnes, Jonathan C.; Fahrenbach, Albert C.; Cao, Dennis; Dyar, Scott M.; Frasconi, Marco; Giesener, Marc A.; Benítez, Diego; Tkatchouk, Ekaterina; Chernyashevskyy, Oleksandr; Shin, Weon Ho; Li, Hao; Sampath, Srinivasan; Stern, Charlotte L.; Sarjeant, Amy A.; Hartlieb, Karel J.

    2013-01-01

    Most organic radicals possess short lifetimes and quickly undergo dimerization or oxidation. Here, we report on the synthesis by radical templation of a class of air- and water-stable organic radicals, trapped within a homo[2]catenane composed of two rigid and fixed cyclobis (paraquat-p-phenylene) rings. The highly energetic octacationic homo[2]catenane, which is capable of accepting up to eight electrons, can be configured reversibly, both chemically and electrochemically, bet...

  9. Quantitative determination of atmospheric hydroperoxyl radical

    Springston, Stephen R. (Upton, NY); Lloyd, Judith (Westbury, NY); Zheng, Jun (Stony Brook, NY)

    2007-10-23

    A method for the quantitative determination of atmospheric hydroperoxyl radical comprising: (a) contacting a liquid phase atmospheric sample with a chemiluminescent compound which luminesces on contact with hydroperoxyl radical; (b) determining luminescence intensity from the liquid phase atmospheric sample; and (c) comparing said luminescence intensity from the liquid phase atmospheric sample to a standard luminescence intensity for hydroperoxyl radical. An apparatus for automating the method is also included.

  10. Photodynamically generated bovine serum albumin radicals

    Silvester, J A; Timmins, G S; Davies, Michael Jonathan

    1998-01-01

    Porphyrin-sensitized photoxidation of bovine serum albumin (BSA) results in oxidation of the protein at (at least) two different, specific sites: the Cys-34 residue giving rise to a thiyl radical (RS.); and one or both of the tryptophan residues (Trp-134 and Trp-214) resulting in the formation of...... by a range of proteases. The generation of protein-derived radicals also results in an enhancement of photobleaching of the porphyrin, suggesting that protein radical generation is linked to porphyrin photooxidation....

  11. Involvement of free radicals in breast cancer

    Ríos-Arrabal, Sandra; Artacho-Cordón, Francisco; León, Josefa; Román-Marinetto, Elisa; del Mar Salinas-Asensio, María; Calvente, Irene; Núñez, Maria Isabel

    2013-01-01

    Researchers have recently shown an increased interest in free radicals and their role in the tumor microenvironment. Free radicals are molecules with high instability and reactivity due to the presence of an odd number of electrons in the outermost orbit of their atoms. Free radicals include reactive oxygen and nitrogen species, which are key players in the initiation and progression of tumor cells and enhance their metastatic potential. In fact, they are now considered a hallmark of cancer. ...

  12. A reactivity-selectivity study of the Friedel-Crafts acetylation of 3,3′-dimethylbiphenyl and the oxidation of the acetyl derivatives

    Titinchi Salam JJ

    2012-06-01

    Full Text Available Abstract Background Friedel-Crafts acetylation is an important route to aromatic ketones, in research laboratories and in industry. The acetyl derivatives of 3,3′-dimethylbiphenyl (3,3′-dmbp have applications in the field of liquid crystals and polymers and may be oxidized to the dicarboxylic acids and derivatives that are of interest in cancer treatment. Findings The effect of solvent and temperature on the selectivity of monoacetylation of 3,3’-dmbp by the Perrier addition procedure was studied using stoichiometric amounts of reagents. 4-Ac-3,3′-dmbp was formed almost quantitatively in boiling 1,2-dichloroethane and this is almost twice the yield hitherto reported. Using instead a molar ratio of substrate:AcCl:AlCl3 equal to 1:4:4 or 1:6:6 in boiling 1,2-dichloroethane, acetylation afforded 4,4′- and 4,6′-diacetyl-3,3′-dmbp in a total yield close to 100%. The acetyl derivatives were subsequently converted to the carboxylic acids by hypochlorite oxidation. The relative stabilities of the isomeric products and the corresponding σ-complexes were studied by DFT calculations and the data indicated that mono- and diacetylation followed different mechanisms. Conclusions Friedel-Crafts acetylation of 3,3′-dmbp using the Perrier addition procedure in boiling 1,2-dichloroethane was found to be superior to other recipes. The discrimination against the 6-acetyl derivative during monoacetylation seems to reflect a mechanism including an AcCl:AlCl3 complex or larger agglomerates as the electrophile, whereas the less selective diacetylations of the deactivated 4-Ac-3,3′-dmbp are suggested to include the acetyl cation as the electrophile. The DFT data also showed that complexation of intermediates and products with AlCl3 does not seem to be important in determining the mechanism.

  13. Dynamics of Radical-Mediated Enzyme Catalyses

    Warncke, Kurt

    1997-11-01

    An emergent class of enzymes harnesses the extreme reactivity of electron-deficient free radical species to perform some of the most difficult reactions in biology. The regio- and stereo-selectivity achieved by these enzymes defies long-held ideas that radical reactions are non-specific. The common primary step in these catalyses is metal- or metallocenter-assisted generation of an electron-deficient organic "initiator radical". The initiator radical abstracts a hydrogen atom from the substrate, opening a new reaction channel for rearrangement to the product. Our aim is to elucidate the detailed molecular mechanisms of the radical pair separation and radical rearrangement steps. Radical pair separation and substrate radical rearrangement are tracked by using time-resolved (10-7 to 10-3 s) techniques of pulsed-electron paramagnetic resonance spectroscopy (FT-EPR, ESEEM). Synchronous time-evolution of the reactions is attained by triggering with a visible laser pulse. Transient non-Boltzmann population of the states of the spin-coupled systems, and resultant electron spin polarization, facilitates study at or near room temperature under conditions where the enzymes are operative. The systems examined include ethanolamine deaminase, a vitamin B12 coenzyme-dependent enzyme, ribonucleotide reductase and photosynthetic reaction centers. The electronic and nuclear structural and kinetic information obtained from the pulsed-EPR studies is used to address how the initiator radicals are stabilized against deleterious recombination with the metal, and to distinguish the participation of concerted versus sequential rearrangement pathways.

  14. Optimal pain management for radical prostatectomy surgery

    Joshi, Grish P; Jaschinski, Thomas; Bonnet, Francis; Kehlet, Henrik

    2015-01-01

    evidence to develop an optimal pain management protocol in patients undergoing radical prostatectomy. Most studies assessed unimodal analgesic approaches rather than a multimodal technique. There is a need for more procedure-specific studies comparing pain and analgesic requirements for open and minimally...... invasive surgical procedures. Finally, while we wait for appropriate procedure specific evidence from publication of adequate studies assessing optimal pain management after radical prostatectomy, we propose a basic analgesic guideline.......BACKGROUND: Increase in the diagnosis of prostate cancer has increased the incidence of radical prostatectomy. However, the literature assessing pain therapy for this procedure has not been systematically evaluated. Thus, optimal pain therapy for patients undergoing radical prostatectomy remains...

  15. Near-Ring Radicals and Class Pairs

    L.Godloza; N.J.Groenewald; W.A.Olivier

    2005-01-01

    For near-ring ideal mappings p1 and p2, we investigate radical theoretical properties of and the relationship among the class pairs (p1: p2), (Sp2: Sp1) and (Rp2:Rp1). Conditions on p1 and p2 are given for a general class pair to form a radical class of various types. These types include the Plotkin and KA-radical varieties. A number of examples are shown to motivate the suitability of the theory of Hoehnke-radicals over KA-radicals when radical pairs of near-rings are studied. In particular, it is shown that (pc: P3) forms a KA-radical class, where Pc denotes the class of completely prime nearrings and P3 the class of 3-prime near-rings. This gives another near-ring generalization of the 2-primal ring concept. The theory of radical pairs are also used to show that in general the class of 3-semiprime near-rings is not the semisimple class of the 3-prime radical.

  16. The Games Radicals Play: Special Issue on Free Radicals and Radical Ions

    John C. Walton

    2015-02-01

    Full Text Available Chemistry and Physics have aptly been described as “most excellent children of Intellect and Art” [1]. Both these “children” engage with many playthings, and molecules rank as one of their first favorites, especially radicals, which are amongst the most lively and exciting. Checking out radicals dancing to the music of entropy round their potential energy ballrooms is surely both entertaining and enlightening. Radicals’ old favorite convolutions are noteworthy, but the new styles, modes and arrangements appearing on the scene are even more interesting. Some of these are ephemeral and enjoy only a brief appearance, others are retro-types reappearing in new guises, still others are genuinely new and “go viral” in the scientific world. This Special Issue of Molecules contains the observations and reflections of a select group of chemists and physicists fascinated by this spectacle. It contains an eclectic mix reflecting on new modes and advances as well as on permutations and combinations that revive mature themes. [...

  17. Aberrant histone H4 acetylation in dead somatic cell-cloned calves

    Lei Zhang; Shaohua Wang; Qiang Li; Xiangdong Ding; Yunping Dai; Ning Li

    2008-01-01

    In somatic cell-cloned animals, inefficient epigenetic reprogramming can result in an inappropriate gene expression and histone H4 acetylation is one of the key epigenetic modifications regulating gene expression. In this study, we investigated the levels of histone H4 acetylation of 11 development-related genes and expression levels of 19 genes in lungs of three normal control calves and nine aber-rant somatic cell-cloned calves. The results showed that nine studied genes had decreased acetylation levels in aberrant clones (p 0.05). Whereas 13 genes had significantly decreased expression (p 0.05), and only one gene had higher expression level in clones (p < 0.05). Furthermore, FGFR, GHR, HGFR and IGF1 genes showed lowered levels of both histone H4 acetylation and expression in aberrant clones than in controls, and the level of histone H4 acetylation was even more lowered in aberrant clones than those in controls. It was suggested that the lower levels of histone H4 acetylation in aberrant clones caused by the previous memory of cell differentiation might not support enough chromatin reprogramming, thus affecting appropriate gene expressions, and growth and development of the cloned calves. To our knowledge, this is the first study on how histone H4 acetylation affects gene expression in organs of somatic cell-cloned calves.

  18. Profiling of cytosolic and peroxisomal acetyl-CoA metabolism in Saccharomyces cerevisiae.

    Yun Chen

    Full Text Available As a key intracellular metabolite, acetyl-coenzyme A (acetyl-CoA plays a major role in various metabolic pathways that link anabolism and catabolism. In the yeast Saccharomyces cerevisiae, acetyl-CoA involving metabolism is compartmentalized, and may vary with the nutrient supply of a cell. Membranes separating intracellular compartments are impermeable to acetyl-CoA and no direct transport between the compartments occurs. Thus, without carnitine supply the glyoxylate shunt is the sole possible route for transferring acetyl-CoA from the cytosol or the peroxisomes into the mitochondria. Here, we investigate the physiological profiling of different deletion mutants of ACS1, ACS2, CIT2 and MLS1 individually or in combination under alternative carbon sources, and study how various mutations alter carbon distribution. Based on our results a detailed model of carbon distribution about cytosolic and peroxisomal acetyl-CoA metabolism in yeast is suggested. This will be useful to further develop yeast as a cell factory for the biosynthesis of acetyl-CoA-derived products.

  19. Improved Species-Specific Lysine Acetylation Site Prediction Based on a Large Variety of Features Set.

    Wuyun, Qiqige; Zheng, Wei; Zhang, Yanping; Ruan, Jishou; Hu, Gang

    2016-01-01

    Lysine acetylation is a major post-translational modification. It plays a vital role in numerous essential biological processes, such as gene expression and metabolism, and is related to some human diseases. To fully understand the regulatory mechanism of acetylation, identification of acetylation sites is first and most important. However, experimental identification of protein acetylation sites is often time consuming and expensive. Therefore, the alternative computational methods are necessary. Here, we developed a novel tool, KA-predictor, to predict species-specific lysine acetylation sites based on support vector machine (SVM) classifier. We incorporated different types of features and employed an efficient feature selection on each type to form the final optimal feature set for model learning. And our predictor was highly competitive for the majority of species when compared with other methods. Feature contribution analysis indicated that HSE features, which were firstly introduced for lysine acetylation prediction, significantly improved the predictive performance. Particularly, we constructed a high-accurate structure dataset of H.sapiens from PDB to analyze the structural properties around lysine acetylation sites. Our datasets and a user-friendly local tool of KA-predictor can be freely available at http://sourceforge.net/p/ka-predictor. PMID:27183223

  20. Proteomic Analysis of Lysine Acetylation Sites in Rat Tissues Reveals Organ Specificity and Subcellular Patterns

    Alicia Lundby

    2012-08-01

    Full Text Available Lysine acetylation is a major posttranslational modification involved in a broad array of physiological functions. Here, we provide an organ-wide map of lysine acetylation sites from 16 rat tissues analyzed by high-resolution tandem mass spectrometry. We quantify 15,474 modification sites on 4,541 proteins and provide the data set as a web-based database. We demonstrate that lysine acetylation displays site-specific sequence motifs that diverge between cellular compartments, with a significant fraction of nuclear sites conforming to the consensus motifs G-AcK and AcK-P. Our data set reveals that the subcellular acetylation distribution is tissue-type dependent and that acetylation targets tissue-specific pathways involved in fundamental physiological processes. We compare lysine acetylation patterns for rat as well as human skeletal muscle biopsies and demonstrate its general involvement in muscle contraction. Furthermore, we illustrate that acetylation of fructose-bisphosphate aldolase and glycerol-3-phosphate dehydrogenase serves as a cellular mechanism to switch off enzymatic activity.

  1. Proteomic investigations of lysine acetylation identify diverse substrates of mitochondrial deacetylase sirt3.

    Eri Maria Sol

    Full Text Available Lysine acetylation is a posttranslational modification that is dynamically regulated by the activity of acetyltransferases and deacetylases. The human and mouse genomes encode 18 different lysine deacetylases (KDACs which are key regulators of many cellular processes. Identifying substrates of KDACs and pinpointing the regulated acetylation sites on target proteins may provide important information about the molecular basis of their functions. Here we apply quantitative proteomics to identify endogenous substrates of the mitochondrial deacetylase Sirtuin 3 (Sirt3 by comparing site-specific acetylation in wild-type murine embryonic fibroblasts to Sirt3 knockout cells. We confirm Sirt3-regulated acetylation of several mitochondrial proteins in human cells by comparing acetylation in U2OS cells overexpressing Sirt3 to U2OS cells in which Sirt3 expression was reduced by shRNA. Our data demonstrate that ablation of Sirt3 significantly increases acetylation at dozens of sites on mitochondrial proteins. Substrates of Sirt3 are implicated in various metabolic pathways, including fatty acid metabolism and the tricarboxylic acid cycle. These results imply broader regulatory roles of Sirt3 in the mitochondria by modulating acetylation on diverse substrates. The experimental strategy described here is generic and can be applied to identify endogenous substrates of other lysine deacetylases.

  2. Radical surgery in septic abortion.

    Chatterjee, P; Ghosh, M; Ghosh, S

    1979-08-01

    At R.G. Kar Medical College Hospital, Calcutta, 10 cases of septic abortion from 1975-1977 were studied. Hysterectomies were preformed on 4 cases due to emergency situations including traumatised uterine fundus and perforated cervix, and on 6 cases after conservative treatment. Upon performing laparotomy in 9 cases, a uterine rent was detected; in 1 case there was a perforation in the posterior wall of the cervix, and in 5 cases mechanical obstructions due to internal adhesions to the uterine rent were found. 4 patients died primarily because of the patients seeking help too late. It is suggested that under high risk circumstances, laparotomy is advantageous to conservative medical management since bowel injuries and mechanical obstructions can only be detected by laparotomy. Radical surgery, however, should be undertaken before the patients general condition deteriorates to the point that the patient cannot tolerate surgical intervention. PMID:12336028

  3. Students' Ideas and Radical Constructivism

    Sánchez Gómez, Pedro J.

    2016-08-01

    In this article, I study, from the point of view of the analytic philosophy of mind, the compatibility of students' ideas studies (SIS) with radical constructivism (RC). I demonstrate that RC is based on a psychology of narrow mental states; that is, the idea that the mental content of an individual can be fully characterised without any reference external to her or him. I show that this fact imposes some severe restrictions to SIS to be incorporated into RC. In particular, I argue that only qualitative studies can comply with the requirement of narrowness. Nevertheless, I propose that quantitative works can be employed as sources of types in order to study token actual students. I use this type-token dichotomy to put forward an outline of a theory of the relation between school contents and mental contents. In this view, token mental contents regarding a given topic can be defined, and probed, only by resorting to typical school contents.

  4. Photoionisation of the tropyl radical

    Kathrin H. Fischer

    2013-04-01

    Full Text Available We present a study on the photoionisation of the cycloheptatrienyl (tropyl radical, C7H7, using tunable vacuum ultraviolet synchrotron radiation. Tropyl is generated by flash pyrolysis from bitropyl. Ions and electrons are detected in coincidence, permitting us to record mass-selected photoelectron spectra. The threshold photoelectron spectrum of tropyl, corresponding to the X+ 1A1’ ← X 2E2” transition, reveals an ionisation energy of 6.23 ± 0.02 eV, in good agreement with Rydberg extrapolations, but slightly lower than the value derived from earlier photoelectron spectra. Several vibrations can be resolved and are reassigned to the C–C stretch mode ν16+ and to a combination of ν16+ with the ring breathing mode ν2+. Above 10.55 eV dissociative photoionisation of tropyl is observed, leading to the formation of C5H5+ and C2H2.

  5. Students' Ideas and Radical Constructivism

    Sánchez Gómez, Pedro J.

    2016-04-01

    In this article, I study, from the point of view of the analytic philosophy of mind, the compatibility of students' ideas studies (SIS) with radical constructivism (RC). I demonstrate that RC is based on a psychology of narrow mental states; that is, the idea that the mental content of an individual can be fully characterised without any reference external to her or him. I show that this fact imposes some severe restrictions to SIS to be incorporated into RC. In particular, I argue that only qualitative studies can comply with the requirement of narrowness. Nevertheless, I propose that quantitative works can be employed as sources of types in order to study token actual students. I use this type-token dichotomy to put forward an outline of a theory of the relation between school contents and mental contents. In this view, token mental contents regarding a given topic can be defined, and probed, only by resorting to typical school contents.

  6. Iron and iron derived radicals

    Borg, D.C.; Schaich, K.M.

    1987-04-01

    We have discussed some reactions of iron and iron-derived oxygen radicals that may be important in the production or treatment of tissue injury. Our conclusions challenge, to some extent, the usual lines of thought in this field of research. Insofar as they are born out by subsequent developments, the lessons they teach are two: Think fastexclamation Think smallexclamation In other words, think of the many fast reactions that can rapidly alter the production and fate of highly reactive intermediates, and when considering the impact of competitive reactions on such species, think how they affect the microenvironment (on the molecular scale) ''seen'' by each reactive molecule. 21 refs., 3 figs., 1 tab.

  7. Transport and metabolism of indole-3-acetyl-myo-inositol-galactoside in seedlings of Zea mays

    Komoszynski, M.; Bandurski, R. S.

    1986-01-01

    Indole-3-acetyl-myo-inositol galactoside labeled with 3H in the indole and 14C in the galactose moieties was applied to kernels of 5 day old germinating seedlings of Zea mays. Indole-3-acetyl-myo-inositol galactoside was not transported into either the shoot or root tissue as the intact molecule but was instead hydrolyzed to yield [3H]indole-3-acetyl-myo-inositol and [3H]indole-3-acetic acid which were then transported to the shoot with little radioactivity going to the root. With certain assumption concerning the equilibration of applied [3H]indole-3-acetyl-myo-inositol-[U-14C]galactose with the endogenous pool, it may be concluded that indole-3-acetyl-myo-inositol galactoside in the endosperm supplies about 2 picomoles per plant per hour of indole-3-acetyl-myo-inositol and 1 picomole per plant per hour of indole-3-acetic acid to the shoot and thus is comparable to indole-3-acetyl-myo-inositol as a source of indole-acetic acid for the shoot. Quantitative estimates of the amount of galactose in the kernels suggest that [3H]indole-3-acetyl-myo-inositol-[14C]galactose is hydrolyzed after the compound leaves the endosperm but before it reaches the shoot. In addition, [3H]indole-3-acetyl-myo-inositol-[14C]galactose supplies appreciable amounts of 14C to the shoot and both 14C and 3H to an uncharacterized insoluble fraction of the endosperm.

  8. Inhibitory effects of chitosan on superoxide anion radicals and lipid free radicals

    2002-01-01

    With the electron spin resonance (ESR) technique, the inhibitory effects of chitosan on superoxide anion radicals and linoleic acid lipid radicals were found. The inhibitory ratio E for these two kinds of radicals is in proportion to the concentration of chitosan. It was also observed that E for linoleic acid lipid radicals increased with the increase of the degree of deacetylation and decreased with the increase of the molecular weight of chitosan.

  9. The small delta antigen of hepatitis delta virus is an acetylated protein and acetylation of lysine 72 may influence its cellular localization and viral RNA synthesis

    Hepatitis delta virus (HDV) is a single-stranded RNA virus that encodes two viral nucleocapsid proteins named small and large form hepatitis delta antigen (S-HDAg and L-HDAg). The S-HDAg is essential for viral RNA replication while the L-HDAg is required for viral assembly. In this study, we demonstrated that HDAg are acetylated proteins. Metabolic labeling with [3H]acetate revealed that both forms of HDAg could be acetylated in vivo. The histone acetyltransferase (HAT) domain of cellular acetyltransferase p300 could acetylate the full-length and the N-terminal 88 amino acids of S-HDAg in vitro. By mass spectrometric analysis of the modified protein, Lys-72 of S-HDAg was identified as one of the acetylation sites. Substitution of Lys-72 to Arg caused the mutant S-HDAg to redistribute from the nucleus to the cytoplasm. The mutant reduced viral RNA accumulation and resulted in the earlier appearance of L-HDAg. These results demonstrated that HDAg is an acetylated protein and mutation of HDAg at Lys-72 modulates HDAg subcellular localization and may participate in viral RNA nucleocytoplasmic shuttling and replication

  10. Genome-wide analysis of H4K5 acetylation associated with fear memory in mice

    Park, C. Sehwan; Rehrauer, Hubert; Mansuy, Isabelle M.

    2013-01-01

    Background Histone acetylation has been implicated in learning and memory in the brain, however, its function at the level of the genome and at individual genetic loci remains poorly investigated. This study examines a key acetylation mark, histone H4 lysine 5 acetylation (H4K5ac), genome-wide and its role in activity-dependent gene transcription in the adult mouse hippocampus following contextual fear conditioning. Results Using ChIP-Seq, we identified 23,235 genes in which H4K5ac correlates...