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        Polyphenol-rich blackcurrant extract prevents inflammation in diet-induced obese mice

        Benn, T.,Kim, B.,Park, Y.K.,Wegner, C.J.,Harness, E.,Nam, T.G.,Kim, D.O.,Lee, J.S.,Lee, J.Y. Butterworths ; Elsevier Science Ltd 2014 The Journal of nutritional biochemistry Vol.25 No.10

        Obesity is closely associated with chronic, low-grade inflammation. We investigated if polyphenol-rich blackcurrant extract (BCE) can prevent inflammation in vivo. Male C57BL/6J mice were fed a modified AIN-93M control diet containing high fat/high cholesterol (16% fat, 0.25% cholesterol by weight) or the control diet supplemented with 0.1% BCE (wt/wt) for 12 weeks. In BCE-fed mice, the percentage of body weight and adipocyte size of the epididymal fat were significantly lower than those of control mice. There were fewer crown-like structures (CLS) with concomitant decreases in F4/80, cluster of differentiation 68 and inhibitor of nuclear factor κB kinase ε (IKKε) mRNA in the epididymal adipose of BCE-fed mice. F4/80 and IKKε mRNA levels were positively correlated with CLS number. In the skeletal muscle of mice fed with BCE, mRNA expression of genes involved in energy expenditure and mitochondrial biogenesis, including PPARα, PPARδ, UCP-2, UCP-3 and mitochondrial transcription factor A, were significantly increased. When splenocytes from BCE-fed mice were stimulated by lipopolysaccharides, tumor necrosis factor α and interleukin-1β mRNA were significantly lower than control splenocytes. Together, the results suggest that BCE supplementation decreases obesity-induced inflammation in adipose tissue and splenocytes, at least in part, by modulating energy metabolism in skeletal muscle.

      • Vitamin D: molecular mechanism of action.

        Christakos, Sylvia,Dhawan, Puneet,Benn, Bryan,Porta, Angela,Hediger, Matthias,Oh, Goo T,Jeung, Eui-Bae,Zhong, Yan,Ajibade, Dare,Dhawan, Kopal,Joshi, Sneha New York Academy of Sciences 2007 Annals of the New York Academy of Sciences Vol.1116 No.1

        <P>Vitamin D maintains calcium homeostasis and is required for bone development and maintenance. Recent evidence has indicated an interrelationship between vitamin D and health beyond bone, including effects on cell proliferation and on the immune system. New developments in our lab related to the function and regulation of target proteins have provided novel insights into the mechanisms of vitamin D action. Studies in our lab have shown that the calcium-binding protein, calbindin, which has been reported to be a facilitator of calcium diffusion, also has an important role in protecting against apoptotic cell death in different tissues including protection against cytokine destruction of osteoblastic and pancreatic beta cells. These findings have important implications for the therapeutic intervention of many disorders including diabetes and osteoporosis. Recent studies in our laboratory of intestinal calcium absorption using calbindin-D(9k) null mutant mice as well as mice lacking the 1,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)) inducible epithelial calcium channel, TRPV6, provide evidence for the first time of calbindin-D(9k) and TRPV6 independent regulation of active calcium absorption. Besides calbindin, the other major target of 1,25(OH)(2)D(3) in intestine and kidney is 25(OH)D(3) 24 hydroxylase (24(OH)ase), which is involved in the catabolism of 1,25(OH)(2)D(3). In our laboratory we have identified various factors that cooperate with the vitamin D receptor in regulating 24(OH)ase expression including C/EBP beta, SWI/SNF (complexes that remodel chromatin using the energy of ATP hydrolysis) and the methyltransferases, CARM1 and G9a. Evidence is also presented for C/EBP beta as a nuclear coupling factor that coordinates regulation of osteopontin by 1,25(OH)(2)D(3) and PTH. Our findings define novel mechanisms that may be of fundamental importance in understanding how 1,25(OH)(2)D(3) mediates its multiple biological effects.</P>

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        NMPC of an industrial crystallization process using model-based observers

        Cedric Damour,Lionel Boillereaux,Brigitte Grondin-Perez,Jean-Pierre Chabriat,Michel Benne 한국공업화학회 2010 Journal of Industrial and Engineering Chemistry Vol.16 No.5

        This paper illustrates the benefits of a nonlinear model-based predictive control (NMPC) approach applied to an industrial crystallization process. This relevant approach proposes a setpoint tracking of the crystal mass. The controlled variable, unavailable, is obtained using an extended Luenberger observer. A neural network model is used as internal model to predict process outputs. An optimization problemis solved to compute future control actions taking into account real-time control objectives. The performances of this strategy are demonstrated via simulation in cases of setpoint tracking and disturbance rejection. The results reveal a significant improvement in terms of robustness and energy efficiency. 2010 The Korean Society of Industrial and Engineering Chemistry. Published by Elsevier B.V. All rights reserved.

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        Inclusion of homologous DNA in nuclease-mediated gene targeting facilitates a higher incidence of bi-allelically modified cells

        Beaton, Benjamin P,Kwon, Deug-Nam,Choi, Yun-Jung,Kim, Jae-Hwan,Samuel, Melissa S,Benne, Joshua A,Wells, Kevin D,Lee, Kiho,Kim, Jin-Hoi,Prather, Randall S John WileySons, Ltd 2015 Xenotransplantation Vol.22 No.5

        <P><B>Background</B></P><P>Recent advancements in gene editing techniques have increased in number and utility. These techniques are an attractive alternative to conventional gene targeting methods via homologous recombination due to the ease of use and the high efficiency of gene editing. We have previously produced cytidine monophosphate-N-acetylneuraminic acid hydroxylase (<I>CMAH</I>) knockout (KO) pigs in a Minnesota miniature pig genetic background. These pigs were generated using zinc-finger nucleases (ZFNs) in combination with donor DNA containing a total homology length of 1600 bp (800-bp homology on each arm). Our next aim was to introduce the targeted disruption of alpha-1,3-galactosyltransferase (<I>GGTA1</I>) in the <I>CMAH</I> KO genetic background and evaluate the effect of donor DNA homology length on meganuclease-mediated gene targeting.</P><P><B>Methods</B></P><P>Zinc-finger nucleases from a previous <I>CMAH</I> KO experiment were used as a proof of concept to identify a correlation between the length of donor DNA homology and targeting efficiency. Based on those results, experiments were designed to use transcription activator-like effector nucleases (TALENs) to generate bi-allelically modified <I>GGTA1</I> cells using donor DNAs carrying various lengths of homology. Donor DNA was designed to symmetrically flank the predicted cleavage sites in <I>CMAH</I> and <I>GGTA1</I> for both ZFN and TALEN cleavage sites, respectively. For both genes, the length of total homology ranged from 60 to 1799 bp. Sialyltransferase gene expression profiles were evaluated in <I>CMAH</I> and <I>GGTA1</I> double KO pig cells and were compared to wild-type and <I>CMAH</I> KO cells.</P><P><B>Results</B></P><P>Introduction of donor DNA with ZFNs demonstrated that small amounts of homology (60 bp) could facilitate homology-directed repair during ZFN-mediated targeting of <I>CMAH</I>; however, donor DNA with longer amounts of homology resulted in a higher frequency of homology-directed repair. For the <I>GGTA1</I> KO experiments that used TALENs and donor DNA, donor DNA alone did not result in detectable bi-allelic conversion of <I>GGTA1</I>. As the length of donor DNA increased, the bi-allelic disruption of <I>GGTA1</I> increased from 0.5% (TALENs alone, no donor DNA present) to a maximum of 3% (TALENs and donor DNA with total homology of 1799 bp). Inclusion of homologous donor DNA in TALEN-mediated gene targeting facilitated a higher incidence of bi-allelically modified cells. Using the generated cells, we were able to demonstrate the lack of <I>GGTA1</I> expression and the decrease in gene expression sialyltransferase-related genes.</P><P><B>Conclusions</B></P><P>The approach of using donor DNA in conjunction with a meganuclease can be used to increase the efficiency of gene targeting. The gene editing methods can be applied to other genes as well as other mammalian systems. Additionally, gene expression analysis further confirms that the <I>CMAH</I>/<I>GGTA1</I> double KO pigs can be a valuable source for the study of pig-to-human xenotransplantation.</P>

      • Prevalence of IDH1/2 Mutations in Different Subtypes of Glioma in the North-East Population of Morocco

        Senhaji, Nadia,Louati, Sara,Chbani, Laila,Bardai, Sanae El,Mikou, Karima,MAAROUFI, Mustafa,Benzagmout, Mohammed,Faiz, Mohammed Chaoui El,Marie, Yannick,Mokhtari, Karima,Idbaih, Ahmed,Amarti, Afaf,Benn Asian Pacific Journal of Cancer Prevention 2016 Asian Pacific journal of cancer prevention Vol.17 No.5

        Background: Genetic alterations in gliomas have increasing importance for classification purposes. Thus, we are especially interested in studying IDH mutations which may feature potential roles in diagnosis, prognosis and response to treatment. Our aim was to investigate IDH mutations in diffuse glioma patients diagnosed in university hospital centre of Fez in Morocco. Materials and Methods: IDH1 codon 132 and IDH2 codon 172 were direct-sequenced in 117 diffuse glioma samples diagnosed and treated in University Hospital Hassan II between 2010 and 2014. Results: The R132H IDH1 mutation was identified in 43/117 tumor samples and R172K IDH2 mutation was detected in only one anaplastic oligodendroglioma. IDH mutations were observed in 63.2% of astrocytomas, 73.3% of diffuse oligodendrogliomas and 12.90% of glioblastomas. Conclusions: Our results confirmed other studies published earlier for other populations with some small discrepancies.

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