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      • Genome-wide association study in a Chinese population identifies a susceptibility locus for type 2 diabetes at 7q32 near <i>PAX4</i>

        Ma, R. C. W.,Hu, C.,Tam, C. H.,Zhang, R.,Kwan, P.,Leung, T. F.,Thomas, G. N.,Go, M. J.,Hara, K.,Sim, X.,Ho, J. S. K.,Wang, C.,Li, H.,Lu, L.,Wang, Y.,Li, J. W.,Wang, Y.,Lam, V. K. L.,Wang, J.,Yu, W.,Ki Springer-Verlag 2013 Diabetologia Vol.56 No.6

        <P><B>Aims/hypothesis</B></P><P>Most genetic variants identified for type 2 diabetes have been discovered in European populations. We performed genome-wide association studies (GWAS) in a Chinese population with the aim of identifying novel variants for type 2 diabetes in Asians.</P><P><B>Methods</B></P><P>We performed a meta-analysis of three GWAS comprising 684 patients with type 2 diabetes and 955 controls of Southern Han Chinese descent. We followed up the top signals in two independent Southern Han Chinese cohorts (totalling 10,383 cases and 6,974 controls), and performed in silico replication in multiple populations.</P><P><B>Results</B></P><P>We identified <I>CDKN2A/B</I> and four novel type 2 diabetes association signals with <I>p</I> < 1 × 10<SUP>−5</SUP> from the meta-analysis. Thirteen variants within these four loci were followed up in two independent Chinese cohorts, and rs10229583 at 7q32 was found to be associated with type 2 diabetes in a combined analysis of 11,067 cases and 7,929 controls (<I>p</I><SUB>meta</SUB> = 2.6 × 10<SUP>−8</SUP>; OR [95% CI] 1.18 [1.11, 1.25]). In silico replication revealed consistent associations across multiethnic groups, including five East Asian populations (<I>p</I><SUB>meta</SUB> = 2.3 × 10<SUP>−10</SUP>) and a population of European descent (<I>p</I> = 8.6 × 10<SUP>−3</SUP>). The rs10229583 risk variant was associated with elevated fasting plasma glucose, impaired beta cell function in controls, and an earlier age at diagnosis for the cases. The novel variant lies within an islet-selective cluster of open regulatory elements. There was significant heterogeneity of effect between Han Chinese and individuals of European descent, Malaysians and Indians.</P><P><B>Conclusions/interpretation</B></P><P>Our study identifies rs10229583 near <I>PAX4</I> as a novel locus for type 2 diabetes in Chinese and other populations and provides new insights into the pathogenesis of type 2 diabetes.</P><P><B>Electronic supplementary material</B></P><P>The online version of this article (doi:10.1007/s00125-013-2874-4) contains peer-reviewed but unedited supplementary material, which is available to authorised users.</P>

      • SCIESCOPUSKCI등재

        Investigation of the Insulin-like Growth Factor System in Breast Muscle during Embryonic and Postnatal Development in Langshan and Arbor Acres Chickens Subjected to Different Feeding Regimens

        Lu, F.Z.,Chen, J.,Wang, X.X.,Liu, Honglin Asian Australasian Association of Animal Productio 2009 Animal Bioscience Vol.22 No.4

        Nutrient availability may control muscle growth directly and indirectly through its influence on regulatory factors. We analyzed the effects of nutrient availability on the breast muscle insulin-like growth factor system. Real time RT-PCR was used to quantify the level of transcription in breast muscle from Langshan (LS) layer and Arbor Acres (AA) broiler chickens subjected to different feeding regimens during embryonic and postnatal development. The AA chickens were fed AA diet (AA, control group) while the LS chickens were either fed LS diet (LL) or AA diet (LA). According to our results, insulin-like growth factor (IGF)-II (embryonic day 16 (E16) - postnatal day 42 (P42)), IGF-I receptor (IGF-IR, E18-P42), and IGF binding protein (IGFBP)-2 (E18-P42), -5 (E16-P14), -7 (E12-P0), and -3 (E12-P0) were positively correlated with IGF-I, while IGFBP-3 (P0-P28) was negatively correlated with IGF-I. In comparison, IGF-IR (E18-P42), IGFBP-2 (E18-P42), IGFBP-5 (E14-P0), and IGFBP-3 (E16-P0) were positively correlated with IGF-II, while IGF-IR (E10-E16) and IGFBP-3 (P0-P28) were negatively correlated with IGF-II. Moreover, IGFBP-2 (E16-P42), -7 (E10-E16), and -3 (E10-E16) were positively correlated with IGF-IR, while IGFBP-3 (P0-P28) was negatively correlated with IGF-IR. Finally, IGFBP-7 (E12-P0) was positively correlated with IGFBP-3, while IGFBP-2 (P0-P28) and -7 (P0-P42) were negatively correlated with IGFBP-3. Overall, the AA chickens exhibited higher levels of IGF-I, IGF-IR, and IGFBP-2 mRNA expression than the LL chickens, while the opposite was true for IGFBP-7. No strain differences in IGF-I, IGF-IR, and IGFBP-7 mRNA expression were detected between LA and AA chickens; however, a strain difference was observed for IGFBP-2. LA chickens exhibited higher levels of IGFBP-2 than LL chickens, while the opposite was true for IGFBP-7. Our data show the first evidence that certain genes may be correlated during specific developmental periods and that strain differences in the expression of those genes in LS and AA chickens are due to differential responses to the same diet.

      • SCISCIESCOPUS

        Novel architecture of carbon nanotube decorated poly(methyl methacrylate) microbead vapour sensors assembled by spray layer by layer

        Feller, J. F.,Lu, J.,Zhang, K.,Kumar, B.,Castro, M.,Gatt, N.,Choi, H. J. Royal Society of Chemistry 2011 Journal of materials chemistry Vol.21 No.12

        <P>For the first time vapour sensors were made by assembling multi-wall carbon nanotube (CNT) decorated poly(methyl methacrylate) microbeads (PMMAµB) by spray layer by layer (sLbL). This combination of materials and technique resulted in an original hierarchical architecture with a segregated network of CNT bridging PMMAµB. The chemo-resistive behaviour of these conductive polymer nanocomposite (CPC) sensors was studied in terms of sensitivity and selectivity towards standard volatile organic compounds (VOC), as well as quantitativity and reproducibility of responses <I>A</I><SUB>r</SUB> to methanol, water, toluene and chloroform. Results show that 3D sLbL assembly allows boosting CNT network sensitivity by a factor 2 and selectivity for methanol vapour by a factor of 5. Additionally CNT-PMMAµB sensors gave responses proportional to vapour molecules content that could easily be fitted by the Langmuir–Henry-clustering model. Such sensors are thus expected to be good candidates for implementation in electronic noses.</P> <P>Graphic Abstract</P><P>Vapour sensors with original hierarchical 3D conducting architecture from CNT decorated PMMAµ beads spraying layer by layer. <IMG SRC='http://pubs.rsc.org/services/images/RSCpubs.ePlatform.Service.FreeContent.ImageService.svc/ImageService/image/GA?id=c0jm03779f'> </P>

      • SCISCIESCOPUS

        Variable number of tandem repeats of 9 Plasmodium vivax genes among Southeast Asian isolates

        Wang, B.,Nyunt, M.H.,Yun, S.G.,Lu, F.,Cheng, Y.,Han, J.H.,Ha, K.S.,Park, W.S.,Hong, S.H.,Lim, C.S.,Cao, J.,Sattabongkot, J.,Kyaw, M.P.,Cui, L.,Han, E.T. Verlag fur Recht und Gesellschaft 2017 Acta tropica Vol.170 No.-

        <P>The variable number of tandem repeats (VNTRs) provides valuable information about both the functional and evolutionary aspects of genetic diversity. Comparative analysis of 3 Plasmodium falciparum genomes has shown that more than 9% of its open reading frames (ORFs) harbor VNTRs. Although microsatellites and VNTR genes of P. vivax were reported, the VNTR polymorphism of genes has not been examined widely. In this study, 230 P. vivax genes were analyzed for VNTRs by SERV, and 33 kinds of TR deletions or insertions from 29P. vivax genes (12.6%) were found. Of these, 9 VNTR fragments from 8 P. vivax genes were used for PCR amplification and sequence analysis to examine the genetic diversity among 134 isolates from four Southeast Asian countries (China, Republic of Korea, Thailand, and Myanmar) with different malaria endemicity. We confirmed the existence of extensive polymorphism of VNTR fragments in field isolates. This detection provides several suitable markers for analysis of the molecular epidemiology of P. vivax field isolates. (C) 2017 Elsevier B.V. All rights reserved.</P>

      • SCISCIESCOPUS

        Genetic polymorphism in pvmdr1 and pvcrt-o genes in relation to in vitro drug susceptibility of Plasmodium vivax isolates from malaria-endemic countries

        Lu, F.,Lim, C.S.,Nam, D.H.,Kim, K.,Lin, K.,Kim, T.S.,Lee, H.W.,Chen, J.H.,Wang, Y.,Sattabongkot, J.,Han, E.T. Verlag für Recht und Gesellschaft ; Elsevier 2011 Acta Tropica Vol.117 No.2

        Treatment failure of chloroquine for Plasmodium vivax infection has increased in endemic countries. However, the molecular mechanisms for resistance and in vitro susceptibility of P. vivax to chloroquine remain elusive. We investigated the prevalence of mutations in the pvmdr1 and pvcrt-o genes, and the copy number of the pvmdr1 gene in isolates from the Republic of Korea (ROK), Thailand, the Union of Myanmar (Myanmar), and Papua New Guinea (PNG). We also measured in vitro susceptibility of Korean isolates to antimalarial drugs. The pvmdr1 analysis showed that mutations at amino acid position Y976F of pvmdr1 were found in isolates from Thailand (17.9%), Myanmar (13.3%), and PNG (100%), but none from the ROK, and mutation at position F1076L was present in isolates from the ROK (100%), Thailand (60.7%), and Myanmar (46.7%). One copy of the pvmdr1 gene was observed in most isolates and double copy numbers of the gene were observed in two Thai isolates. In the exons of the pvcrt-o gene that were sequenced, a K10 insertion was present in isolates from Thailand (56.0%) and Myanmar (46.2%), and the wild type was found in all Korean isolates. The results suggest that gene polymorphisms and copy number variation was observed in isolates of P. vivax from Southeast Asian countries. In Korean isolates polymorphism as limited to the F1076L variant, and no isolates with high level of resistance were found by in vitro susceptibility determinations. Moreover, our results provide a baseline for future prospective drug studies in malaria-endemic areas.

      • Molecular and structural characteristics of multidrug resistance-associated protein 7 in Chinese liver fluke Clonorchis sinensis

        Dai, F.,Yoo, W. G.,Lee, J. Y.,Lu, Y.,Pak, J. H.,Sohn, W. M.,Hong, S. J. Springer Science + Business Media 2017 Parasitology research Vol.116 No.3

        <P>Multidrug resistance-associated protein 7 (MRP7, ABCC10) is a C subfamily member of the ATP-binding cassette (ABC) superfamily. MRP7 is a lipophilic anion transporter that pumps endogenous and xenobiotic substrates from the cytoplasm to the extracellular milieu. Here, we cloned and characterized CsMRP7 as a novel ABC transporter from the Chinese liver fluke, Clonorchis sinensis. Full-length cDNA of CsMRP7 was 5174 nt, encoded 1636 amino acids (aa), and harbored a 147-bp 5'-untranslated region (5'-UTR) and 116-bp 3'-UTR. Phylogenetic analysis confirmed that CsMRP7 was closer to the ABCC subfamily than the ABCB subfamily. Tertiary structures of the N-terminal region (1-322 aa) and core region (323-1621 aa) of CsMRP7 were generated by homology modeling using glucagon receptor (PDB ID: 5ee7_A) and P-glycoprotein (PDB ID: 4f4c_A) as templates, respectively. CsMRP7 nucleotide-binding domain 2 (NBD2) was conserved more than NBD1, which was the sites of ATP binding and hydrolysis. Like typical long MRPs, CsMRP7 has an additional membrane-spanning domain 0 (MSD0) and cytoplasmic loop, along with a common structural fold consisting of MSD1-NBD1-MSD2-NBD2 as a single polypeptide assembly. MSD0, MSD1, and MSD2 consisted of TM1-7, TM8-13, and TM14-19, respectively. The CsMRP7 transcript was more abundant in the metacercariae than in the adult worms. Truncated NBD1 (39 kDa) and NBD2 (44 kDa) were produced in bacteria and mouse immune sera were raised. CsMRP7 was localized in the apical side of the intestinal epithelium, sperm in the testes and seminal receptacle, receptacle membrane, and mesenchymal tissue around intestine in the adult worm. These results provide molecular information and insights into structural and functional characteristics of CsMRP7 and homologs of flukes.</P>

      • SCISCIESCOPUS

        Peroxisome proliferator-activated receptor δ improves porcine blastocyst hatching via the regulation of fatty acid oxidation

        Guo, J.,Lu, W.F.,Liang, S.,Choi, J.W.,Kim, N.H.,Cui, X.S. Butterworths, etc ; Elsevier Science Ltd 2017 Theriogenology Vol.90 No.-

        Peroxisome proliferator-activated receptor δ (Pparδ) is a nuclear receptor that plays critical roles in lipid metabolism, glucose metabolism, and cell growth and differentiation. Several recent studies have shown that Pparδ promotes blastocyst hatching in vitro. However, the mechanism by which it promotes preimplantation embryonic development in vitro remains unclear. In this study, oocytes and parthenotes were treated with a specific agonist of PPARδ, GW501516. The activation of PPARδ had no effect on oocyte maturation for 1 μM and 10 μM GW501516 compared with the control group. Additionally, the PPARδ agonist did not affect blastocyst formation (77.79 +/- 3.59% [10 μM], 79.00 +/- 5.53% [50 μM], and 79.64 +/- 6.00% [100 μM] vs. 81.69 +/- 2.61% [control]). However, the blastocyst hatching rate was significantly greater for parthenotes treated with 10 and 50 μM agonist, and did not differ between those treated with 100 μM agonist and the control group (61.80 +/- 3.03% [10 μM], 65.10 +/- 5.25% [50 μM], and 38.85 +/- 7.45% [100 μM] vs. 41.77 +/- 10.88% [0 μM]). Activation of PPARδ also increased blastocyst quality and cell number, as well as ATP production. There were no clear differences in mitochondrial membrane potential, mitochondrion copy number, or glucose consumption between the treatment and control groups. However, PPARδ activation enhanced lipid accumulation via Fabp3 and Fabp5. Fatty acid oxidation also increased in response to treatment with the agonist via the rate-limiting gene Cpt2. Reactive oxygen species were modified and REDOX maintenance-related gene expression increased significantly in GW501516-exposed blastocysts. In addition, the activation of PPARδ resulted in changes in miRNA content. After treatment with the PPARδ agonist, miR-99 increased and miR-32 decreased. These data showed that PPARδ has a positive impact on blastocyst hatching via the regulation of lipid metabolism.

      • KCI등재

        Evaluation of mango saponin in broilers: effects on growth performance, carcass characteristics, meat quality and plasma biochemical indices

        Y.N. Zhang,J. Wang,B. Qi,S.G. Wu,H.R. Chen,H.Y. Luo,D.J. Yin,F.J. Lu,H.J. Zhang,G.H. Qi 아세아·태평양축산학회 2017 Animal Bioscience Vol.30 No.8

        Objective: The objective of the present study was to determine whether mango saponin (MS) could be used as a feed additive in broiler chicks by evaluating growth performance, carcass characteristics, meat quality, and plasma biochemical indices. Methods: A total of 216 1-d-old Arbor Acres male broiler chicks were randomly assigned into three dietary treatments supplemented with 0 (control), 0.14% (MS 0.14%), or 0.28% (MS 0.28%) MS. Each treatment had six replicates (cages) with 12 chicks each. The feeding trial lasted for six weeks. Results: Compared with the control, dietary supplemented with 0.14% or 0.28% MS increased average daily weight gain of chicks in the grower (22 to 42 d) and the whole (1 to 42 d) phases, and the final body weight of chicks on d 42 was higher in MS supplemented groups (p<0.05). Lower L45 min* (lightness) and L24 h* values, lower b24 h* (yellowness) value, and higher a45 min* (redness) and a24 h* values of the breast muscle were observed in chicks fed with 0.28% MS on d 42 (p<0.05). The total antioxidant capacity in plasma increased in MS 0.14% group on d 21 (p<0.001). Lower contents of plasma total cholesterol and triglyceride were observed in chicks fed with 0.28% MS on d 21 and d 42, whereas the group supplemented with 0.14% MS only decreased plasma triglyceride content on d 21 (p<0.05). The glucose content in plasma decreased in MS 0.28% group on d 42 (p<0.001). Conclusion: Overall, MS could be used as a feed additive in broiler chicks, and the supplemental level of 0.28% MS in diet could improve growth performance, meat quality, and plasma lipid metabolism in broiler chicks.

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