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c/EBP transcription factors regulate NADPH oxidase in human aortic smooth muscle cells

JOURNAL OF cELLULAR AND MOLEcULAR MEDIcINE 2014年第7期18卷 1467-1477页

作者： Manea, Simona-Adriana Todirita, Andra Raicu, Monica Manea, Adrian Acad Romana Mol & Cellular Pharmacol Funct Genom Lab Inst Cellular Biol & Pathol Nicolae Simionescu Bucharest Romania

In atherosclerosis, oxidative stress-induced vascular smooth muscle cells (SMcs) dysfunction is partially mediated by up-regulated NADPH oxidase (Nox);the mechanisms of enzyme regulation are not entirely defined. ccAAT/enhancer-binding proteins (c/EBP) regulate cellular proliferation and differentiation, and the expression of many inflammatory and immune genes. We aimed at elucidating the role of c/EBP in the regulation of Nox in SMcs exposed to pro-inflammatory conditions. Human aortic SMcs were treated with interferon- (IFN-) for up to 24hrs. Lucigenin-enhanced chemiluminescence, real-time PcR, Western blot, promoter-luciferase reporter analysis and chromatin immunoprecipitation assays were employed to investigate Nox regulation. IFN- dose-dependently induced Nox activity and expression, nuclear translocation and up-regulation of c/EBP, c/EBP and c/EBP protein expression levels. Silencing of c/EBP, c/EBP or c/EBP reduced significantly but differentially the IFN--induced up-regulation of Nox activity, gene and protein expression. In silico analysis indicated the existence of typical c/EBP sites within Nox1, Nox4 and Nox5 promoters. Transient overexpression of c/EBP, c/EBP or c/EBP enhanced the luciferase level directed by the promoters of the Nox subtypes. chromatin immunoprecipitation demonstrated the physical interaction of c/EBP, c/EBP and c/EBP proteins with the Nox1/4/5 promoters. c/EBP transcription factors are important regulators of Nox enzymes in IFN--exposed SMcs. Activation of c/EBP may induce excessive Nox-derived reactive oxygen species formation, further contributing to SMcs dysfunction and atherosclerotic plaque development. Pharmacological targeting of c/EBP-related signalling pathways may be used to counteract the adverse effects of oxidative stress.

关键词： NADPH oxidase c EBP atherosclerosis oxidative stress inflammation

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Enzymatic synthesis of steryl hydroxycinnamates and their antioxidant activity

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EUROPEAN JOURNAL OF LIPID ScIENcE AND TEcHNOLOGY 2017年第5期119卷 n/a-N.PAG页

作者： Schar, Aline Liphardt, Silvia Nystrom, Laura Swiss Fed Inst Technol Inst Food Nutr & Hlth Schmelzbergstr 9 CH-8092 Zurich Switzerland

Steryl hydroxycinnamates are of increasing interest as they are antioxidant esters of phytosterols with potential cholesterol lowering properties. Apart from ferulates, also other plant steryl hydroxycinnamates have been identified in natural products. In this study hydroxycinnamic acid derivatives were ethylated enzymatically using Rhizomucor miehei lipase (yields from 16 to 97%), and transesterified by lipase from candida rugosa to yield steryl hydroxycinnamates (yields from ce of the structural differences between the hydroxycinnamic acid derivatives on the esterification yields was very different for the two lipases applied. Furthermore, the antioxidant activity of steryl and stearyl hydroxycinnamates was evaluated by DPPH radical scavenging activity and in two methyl linoleate systems. In bulk methyl linoleate, free sinapic acid showed the highest antioxidant activity over other sinapates, whereas in emulsified methyl linoleate, stearyl sinapate was highest. In conclusion, the enzymatic synthesis and antioxidant activity of steryl hydroxycinnamates is highly dependent on the acid structure. Practical applications: The enzymatic esterification of hydroxycinnamic acids is an environmentally friendly procedure to generate nonpolar hydroxycinnamates. These compounds have a broadened field of application due to their adapted polarity, and therefore potentially have an improved antioxidant activity in a wider range of food applications including multiphase systems. In the case of steryl hydroxycinnamates, the nonpolar part of the molecule brings additional health benefits, such as the cholesterol lowering properties, which makes them even more interesting as possible food additives with multiple technological and nutritional advantages. Hydroxycinnamic acids were ethylated enzymatically using R. miehei lipase, and transesterified by lipase from c. rugosa to yield steryl hydroxycinnamates. The influence of the structural differences between th

关键词： c rugosa lipase Phenolic acid lipophilisation R miehei lipase Steryl ferulates Steryl phenolates

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carbBuilder: Software for building molecular models of complex oligo- and polysaccharide structures

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JOURNAL OF cOMPUTATIONAL cHEMISTRY 2016年第22期37卷 2098-2105页

作者： Kuttel, Michelle M. Stahle, Jonas Widmalm, Goran Univ Cape Town Dept Comp Sci ZA-7701 Cape Town South Africa Stockholm Univ Dept Organ Chem Arrhenius Lab S-10691 Stockholm Sweden

carbBuilder is a portable software tool for producing three-dimensional molecular models of carbohydrates from the simple text specification of a primary structure. carbBuilder can generate a wide variety of carbohydrate structures, ranging from monosaccharides to large, branched polysaccharides. Version 2.0 of the software, described in this article, supports monosaccharides of both mammalian and bacterial origin and a range of substituents for derivatization of individual sugar residues. This improved version has a sophisticated building algorithm to explore the range of possible conformations for a specified carbohydrate molecule. Illustrative examples of models of complex polysaccharides produced by carbBuilder demonstrate the capabilities of the software. carbBuilder is freely available under the Artistic License 2.0 from . (c) 2016 Wiley Periodicals, Inc.

关键词： carbohydrate polysaccharide conformation c Albicans 3D model Shigella flexneri

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Identification of components of the SUMOylation Machinery in candida glabrata: ROLE OF THE DESUMOYLATION PEPTIDASE cgUlp2 IN VIRULENcE

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JOURNAL OF BIOLOGIcAL cHEMISTRY 2016年第37期291卷 19573-19589页

作者： Gujjula, Rahul Veeraiah, Sangeetha Kumar, Kundan Thakur, Suman S. Mishra, Krishnaveni Kaur, Rupinder Ctr DNA Fingerprinting & Diagnost Bldg 7Gruhakalpa 5-4-399-B Hyderabad 500001 Andhra Pradesh India Univ Hyderabad Sch Life Sci Dept Biochem Prof CR Rao Rd Hyderabad 500046 Andhra Pradesh India Manipal Univ Grad Studies Program Manipal 576104 Karnataka India Habsiguda Ctr Cellular & Mol Biol Hyderabad 500007 Andhra Pradesh India Auroras Degree & PG Coll Dept Biochem Hyderabad 500020 Andhra Pradesh India

Regulation of protein function by reversible post-translational modification, SUMOylation, is widely conserved in the eukaryotic kingdom. SUMOylation is essential for cell growth, division, and adaptation to stress in most organisms, including fungi. As these are key factors in determination of fungal virulence, in this study, we have investigated the importance of SUMOylation in the human pathogen, candida glabrata. We identified the enzymes involved in small ubiquitin-like modifier conjugation and show that there is strong conservation between Saccharomyces cerevisiae and c. glabrata. We demonstrate that SUMOylation is an essential process and that adaptation to stress involves changes in global SUMOylation in c. glabrata. Importantly, loss of the deSUMOylating enzyme cgUlp2 leads to highly reduced small ubiquitin-like modifier protein levels, and impaired growth, sensitivity to multiple stress conditions, reduced adherence to epithelial cells, and poor colonization of specific tissues in mice. Our study thus demonstrates a key role for protein SUMOylation in the life cycle and pathobiology of c. glabrata.

关键词： adhesion biofilm microbial pathogenesis small ubiquitin-like modifier (SUMO) sumoylation c glabrata Epa adhesins SUMO peptidase fungal pathogenesis SUMO ligase

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Identification of a novel endophytic Bacillus sp from capsicum annuum with highly efficient and broad spectrum plant probiotic effect

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JOURNAL OF APPLIED MIcROBIOLOGY 2016年第4期121卷 1079-1094页

作者： Jasim, B. Mathew, J. Radhakrishnan, E. K. Mahatma Gandhi Univ Sch Biosci PD Hills PO Kottayam 686560 Kerala India

AimThe study mainly aimed the isolation and characterization of plant probiotic endophytic bacteria from capsicum annuum to explore its multipotent agricultural applications. Materials and MethodsEndophytic bacteria were isolated from the surface sterilized fruit tissue. The isolates were then subjected to PcR-based screening for the presence of potential biosynthetic gene clusters. The PcR positive isolate was then analysed for its inhibitory effect towards fungal and bacterial pathogens. The compounds responsible for the antimicrobial activity was purified from large scale culture and subjected to identification by Lc-MS/MS. The ability of the selected isolate in plant growth enhancement was also done using Vigna radiata seedlings. conclusionIn this study, an endophytic bacterium isolated from *** was found to have the phenotypic and genetic basis for broad antimicrobial property. PcR-based sequence analysis has resulted in the identification of nonribosomal peptide synthases, PKS Type I, Iturin, surfactin, DAPG and gacA genes in the selected isolate caB 5. The bioactivity-guided fractionation using column and HPLc purification of active fraction followed by Lc-MS/MS analysis has proved the presence of surfactin derivatives (M+H+ - 1008 & 1036) and iturin (M+H+ - 1058) as the basis of antimicrobial activity of caB 5. The isolate was identified as a novel Bacillus sp. because of its low (76%) identity to the reported sequences. Significance and Impact of the studyEndophytes are considered to have the genetic basis for a diverse array of bioactive metabolites which can have significant applications in both pharmaceutical industry and agriculture. The identification of caB 5 with broad bioactivity and excellent plant growth enhancement on taxonomically distinct plant species as explained in current study and our previous reports highlights its plant probiotic applicability. This proves the potential of the isolate obtained in the study to be an excellent plant p

关键词： c annuum iturin NRPS PGP Bacillus PKS surfactin

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A complex Regulatory Network coordinating cell cycles During c. elegans Development Is Revealed by a Genome-Wide RNAi Screen

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G3-GENES GENOMES GENETIcS 2014年第5期4卷 795-804页

作者： Roy, Sarah H. Tobin, David V. Memar, Nadin Beltz, Eleanor Holmen, Jenna clayton, Joseph E. chiu, Daniel J. Young, Laura D. Green, Travis H. Lubin, Isabella Liu, Yuying conradt, Barbara Saito, R. Mako Geisel Sch Med Dartmouth Dept Genet Hanover NH 03755 USA Ludwig Maximilians Univ Munchen Bioctr Ctr Integrated Prot Sci Munich CiPSM D-82152 Planegg Martinsried Germany Norris Cotton Canc Ctr Lebanon NH 03756 USA

The development and homeostasis of multicellular animals requires precise coordination of cell division and differentiation. We performed a genome-wide RNA interference screen in caenorhabditis elegans to reveal the components of a regulatory network that promotes developmentally programmed cell-cycle quiescence. The 107 identified genes are predicted to constitute regulatory networks that are conserved among higher animals because almost half of the genes are represented by clear human orthologs. Using a series of mutant backgrounds to assess their genetic activities, the RNA interference clones displaying similar properties were clustered to establish potential regulatory relationships within the network. This approach uncovered four distinct genetic pathways controlling cell-cycle entry during intestinal organogenesis. The enhanced phenotypes observed for animals carrying compound mutations attest to the collaboration between distinct mechanisms to ensure strict developmental regulation of cell cycles. Moreover, we characterized ubc-25, a gene encoding an E2 ubiquitin-conjugating enzyme whose human ortholog, UBE2Q2, is deregulated in several cancers. Our genetic analyses suggested that ubc-25 acts in a linear pathway with cul-1/cul1, in parallel to pathways employing cki-1/p27 and lin-35/pRb to promote cell-cycle quiescence. Further investigation of the potential regulatory mechanism demonstrated that ubc-25 activity negatively regulates cYE-1/cyclin E protein abundance in vivo. Together, our results show that the ubc-25-mediated pathway acts within a complex network that integrates the actions of multiple molecular mechanisms to control cell cycles during development.

关键词： c elegans cell cycle regulatory network ubiquitin-conjugating enzyme development intestine

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Joint optimisation of buffers and network population for closed finite queueing systems

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INTERNATIONAL JOURNAL OF PRODUcTION RESEARcH 2016年第17期54卷 5111-5135页

作者： Smith, J. MacGregor Univ Massachusetts Dept Mech & Ind Engn Amherst MA 01003 USA

The buffer allocation problem for closed finite queueing networks is a nonlinear integer programming problem which is -Hard. A queueing network decomposition methodology based upon a mean value analysis algorithm is coupled with a nonlinear sequential quadratic programming algorithm to compute the simultaneous optimal buffer allocations and network population via a branch-and-bound scheme for various network topologies. The joint optimisation problem is essentially multi-objective where the decision variable on the population will be treated as a constraint linking the buffer allocation and the throughput which is to be maximised. The fact that the optimisation problem is a concave programming problem assists in the search for an optimal solution. The material handling or transportation system for transferring the finite customer population between the nodes in the network is also examined. Extensive numerical results demonstrate the efficacy of the optimisation methodology.

关键词： closed finite networks M M 1 K M G c c queues

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Koszul property of a class of graded algebras with nonpure resolutions

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Frontiers of Mathematics in china 2016年第4期11卷 985-1002页

作者： Jiafeng LU Junling ZHENG Department of Mathematics Zhejiang Normal University Jinhua 321004 China

Given any integers a,b,c, and d with a 〉 1, c ≥ 0, b ≥ a＋c, and d ≥ b ＋ c, the notion of （a, b, c, d）-Koszul algebra is introduced, which is another class of standard graded algebras with ＂nonpure＂ resolutions, and includes many Artin-Schelter regular algebras of low global dimension as specific examples. Some basic properties of （a, b, c, d）-Koszul algebras/modules are given, and several criteria for a standard graded algebra to be （a, b, c, d）- Koszul are provided.

关键词： Koszul algebras d-Koszul algebras Artin-Schelter regular algebras （a b c d）-Koszul algebras Yoneda algebras

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Novel pot-shaped carbon nanomaterial synthesized in a submarine-style substrate heating cVD method

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JOURNAL OF MATERIALS RESEARcH 2016年第1期31卷 117-126页

作者： Yokoi, Hiroyuki Hatakeyama, Kazuto Taniguchi, Takaaki Koinuma, Michio Hara, Masahiro Matsumoto, Yasumichi Kumamoto Univ Grad Sch Sci & Technol Kumamoto 8608555 Japan Natl Inst Mat Sci Int Ctr Mat Nanoarchitecton Tsukuba Ibaraki 3050044 Japan

We have developed a new synthesis method that includes a chemical vapor deposition process in a chamber settled in organic liquid, and applied its nonequilibrium reaction field to the development of novel carbon nanomaterials. In the synthesis at 1110-1120 K, using graphene oxide as a catalyst support, iron acetate and cobalt acetate as catalyst precursors, and 2-propanol as a carbon source as well as the organic liquid, we succeeded to create carbon nanofiber composed of novel pot-shaped units, named carbon nanopot. A carbon nanopot has a complex and regular nanostructure consisting of several parts made of different layer numbers of graphene and a deep hollow space. Dense graphene edges, hydroxylated presumably, are localized around its closed end. The typical size of a carbon nanopot was 20-40 nm in outer diameter, 5-30 nm in inner diameter, and 100-200 nm in length. A growth model of carbon nanopot and its applications are proposed.

关键词： c nanostructure chemical vapor deposition (cVD)

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Effect of diminazene aceturate,levamisole and vitamin c combination therapy in rats experimentally infected with Trypanosoma brucei brucei

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Asian Pacific Journal of Tropical Medicine 2014年第6期7卷 438-445页

作者： Adieme Ijeoma chekwube Ezeh Ikenna Onyema Ugochukwu Emmanuel Ikenna Romanus chukwuduruo Ezeokonkwo Department of Veterinary Medicine University of Nigeria Department of Veterinary Parasitology and Entomology University of Nigeria

Objective:To investigate the effect of diminazene aceturale(DA) alone or in combination with either levamisole and/or Vitamin c in albino rats experimentally infected with Trypanosoma brucei ***:Thirty adult male albino rats,randomly assigned into 6 groups(A—F) of 5rats each were *** were either infected with 1×10~a trypanosomes intraperitoneally(groups A-E) or uninfected(group F).The different groups were treated respectively as follows:group A-with 3.5 mg/kg DA;group B-3.5 mg/kg DA and 7.5 mg/kg levamisole;group c-3.S mg/kg DA and 100 mg/kg vitamin c;and group D-3.S mg/kg DA and 7.S mg/kg levamisole and 100 mg/kg vitamin *** E was left *** assessed include:rectal temperature,body weight changes,packed cell volume(PcV),Haemoglobin concentration(Hb),total leucocyte count(TLc) differential leucocyte count(DLc),parasitaemia,clinical signs and ***:Average pre-patent period of 5 days was *** in the blood were cleared in all treated groups(A-D) within 48 hours post treatment(PT).Untreated rats in group E died between25 and 32 days post infection(PI).Relapse was not recorded in all the treated groups(A-D).The initial reduction in PcV,Hb,TLc and increases in rectal temperature following infection were reversed by the *** rats that received drug combinations(groups B,c and D)showed faster and higher recovery rates than the uninfected control and group ***:Levamisole and/or Vitamin c combination with DA were more effective in the treatment of rats infected with Trypanosoma brucei brucei.

关键词： Diminazene aceturate Levamisole Vitamin c Therapy Trypanosoma brucei brucei Rats

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