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        Rapid, Dynamic Activation of Müller Glial Stem Cell Responses in Zebrafish

        Sifuentes, Christopher J.,Kim, Jung-Woong,Swaroop, Anand,Raymond, Pamela A. The Association for Research in Vision and Ophthal 2016 Investigative Ophthalmology & Visual Science Vol.57 No.13

        <P><B>Purpose</B></P><P>Zebrafish neurons regenerate from Müller glia following retinal lesions. Genes and signaling pathways important for retinal regeneration in zebrafish have been described, but our understanding of how Müller glial stem cell properties are regulated is incomplete. Mammalian Müller glia possess a latent neurogenic capacity that might be enhanced in regenerative therapies to treat degenerative retinal diseases.</P><P><B>Methods</B></P><P>To identify transcriptional changes associated with stem cell properties in zebrafish Müller glia, we performed a comparative transcriptome analysis from isolated cells at 8 and 16 hours following an acute photic lesion, prior to the asymmetric division that produces retinal progenitors.</P><P><B>Results</B></P><P>We report a rapid, dynamic response of zebrafish Müller glia, characterized by activation of pathways related to stress, nuclear factor–κB (NF-κB) signaling, cytokine signaling, immunity, prostaglandin metabolism, circadian rhythm, and pluripotency, and an initial repression of Wnt signaling. When we compared publicly available transcriptomes of isolated mouse Müller glia from two retinal degeneration models, we found that mouse Müller glia showed evidence of oxidative stress, variable responses associated with immune regulation, and repression of pathways associated with pluripotency, development, and proliferation.</P><P><B>Conclusions</B></P><P>Categories of biological processes/pathways activated following photoreceptor loss in regeneration-competent zebrafish Müller glia, which distinguished them from mouse Müller glia in retinal degeneration models, included cytokine signaling (notably NF-κB), prostaglandin E2 synthesis, expression of core clock genes, and pathways/metabolic states associated with pluripotency. These regulatory mechanisms are relatively unexplored as potential mediators of stem cell properties likely to be important in Müller glial cells for successful retinal regeneration.</P>

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        Regulation of Noncoding Transcriptome in Developing Photoreceptors by Rod Differentiation Factor NRL

        Zelinger, Lina,Karakü,lah, Gö,khan,Chaitankar, Vijender,Kim, Jung-Woong,Yang, Hyun-Jin,Brooks, Matthew J.,Swaroop, Anand The Association for Research in Vision and Ophthal 2017 Investigative Ophthalmology & Visual Science Vol.58 No.11

        <P><B>Purpose</B></P><P>Transcriptome analysis by next generation sequencing allows qualitative and quantitative profiling of expression patterns associated with development and disease. However, most transcribed sequences do not encode proteins, and little is known about the functional relevance of noncoding (nc) transcriptome in neuronal subtypes. The goal of this study was to perform a comprehensive analysis of long noncoding (lncRNAs) and antisense (asRNAs) RNAs expressed in mouse retinal photoreceptors.</P><P><B>Methods</B></P><P>Transcriptomic profiles were generated at six developmental time points from flow-sorted <I>Nrl</I>p-GFP (rods) and <I>Nrl</I>p-GFP;<I>Nrl</I><SUP>−/−</SUP> (S-cone like) mouse photoreceptors. Bioinformatic analysis was performed to identify novel noncoding transcripts and assess their regulation by rod differentiation factor neural retina leucine zipper (NRL). In situ hybridization (ISH) was used for validation and cellular localization.</P><P><B>Results</B></P><P>NcRNA profiles demonstrated dynamic yet specific expression signature and coexpression clusters during rod development. In addition to currently annotated 586 lncRNAs and 454 asRNAs, we identified 1037 lncRNAs and 243 asRNAs by de novo assembly. Of these, 119 lncRNAs showed altered expression in the absence of NRL and included NRL binding sites in their promoter/enhancer regions. ISH studies validated the expression of 24 lncRNAs (including 12 previously unannotated) and 4 asRNAs in photoreceptors. Coexpression analysis demonstrated 63 functional modules and 209 significant antisense-gene correlations, allowing us to predict possible role of these lncRNAs in rods.</P><P><B>Conclusions</B></P><P>Our studies reveal coregulation of coding and noncoding transcripts in rod photoreceptors by NRL and establish the framework for deciphering the function of ncRNAs during retinal development.</P>

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        Radioprotective and Antioxidant Activity of Fractionated Extracts of Berries of Hippophae rhamnoides

        Rakesh Kumar Sharma,Raman Chawla,Rajesh Arora,Shikha Singh,Ravinder Kumar Sagar,Raj Kumar,Ashok Sharma,Manju L. Gupta,Surender Singh,Jagdish Prasad,Haider A. Khan,Anand Swaroop,A.K. Sinha,A.K. Gupta,R 한국식품영양과학회 2007 Journal of medicinal food Vol.10 No.1

        Plants are an abundant source of medicinal compounds, some of which are useful in combating free radical-1002 (flavonoid-poor fraction) of Hippophae rhamnoideswere screened on the basis of their reducing power in the aqueousphase. REC-1001 was selected for further study, since it exhibited 27.38 times higher antioxidant activity than REC-1002.REC-1001 also showed significant (P. .05) membrane protection potential at 50 .g/mL, which was attributed to its abilityto scavenge peroxyl radicals (64.82. 1.25% scavenging within 1,440 min). A significant (P. .05) difference of 67.02% infree radical scavenging activity at 1,000 ng/mL between REC-1001 and vitamin E demonstrated the extract fraction’s worthc-tion. Further, REC-1001 was found to be nontoxic up to 200 mg/kg of body weight. This research suggests that the REC-1001 fraction of H. rhamnoidesextract is a safe and effective antioxidant nutraceutical product.

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