323,346 research outputs found

    The role of the proteoglycans OMD and PRELP in the maintenance of brain vasculature

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    OMD and PRELP are proteoglycans belonging to the family of small leucine-rich repeat proteoglycans (SLRPs), whose members have been shown to modulate a variety of cellular processes, including migration, proliferation and differentiation. Abrogated expression of SLRP members has been linked to a multitude of developmental, age-related and inflammatory diseases. Previous work from the Ohnuma lab has shown that OMD and PRELP are strongly expressed in brain vasculature, and in this study, I aim to extend the understanding of OMD and PRELP in the context of vascular homeostasis. The cellular localisation of OMD and PRELP was investigated and I determined that OMD is weakly expressed in neurons, whereas PRELP is expressed in pericytes, vascular smooth muscle cells, microglia and ependymal cells. I have shown that there is vascular dysfunction in PRELP-/- mice. There is increased blood vessel content in the brain, accompanied by blood brain barrier (BBB) breakdown. Analysis of BBB components indicates basement membrane components laminin and perlecan are down-regulated in addition to coverage by pericytes and astrocyte end-feet. PRELP-/- mice also exhibit weakened adherens- and tight-junctions between endothelial cells. I have determined that OMD-/- brain vasculature is comparable to that of wild-type. I propose that PRELP has a role in maintaining vascular function. PRELP may modulate the stability of the BBB by acting as a bridging molecule for basement membrane proteins

    Xenopus NM23-X4 regulates retinal gliogenesis through interaction with p27Xic1

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    Background. In Xenopus retinogenesis, p27Xic1, a Xenopus cyclin dependent kinase inhibitor, functions as a cell fate determinant in both gliogenesis and neurogenesis in a context dependent manner. This activity is essential for co-ordination of determination and cell cycle regulation. However, very little is known about the mechanism regulating the context dependent choice between gliogenesis versus neurogenesis. Results. We have identified NM23-X4, a NM23 family member, as a binding partner of p27Xic1. NM23-X4 is expressed at the periphery of the ciliary marginal zone of the Xenopus retina and the expression overlaps with p27Xic1 at the central side. Our in vivo functional analysis in Xenopus retina has shown that knockdown of NM23-X4 activates gliogenesis. Furthermore, co-overexpression of NM23-X4 with p27Xic1 results in the inhibition of p27Xic1-mediated gliogenesis, through direct interaction of NM23-X4 with the amino-terminal side of p27Xic1. This inhibitory effect on gliogenesis requires serine-150 and histidine-148, which correspond to the important residues for the kinase activities of NM23 family members. Conclusion. This study demonstrates that NM23-X4 functions as an inhibitor of p27Xic1-mediated gliogenesis in Xenopus retina and suggests that this activity contributes to the proper spatio-temporal regulation of gliogenesis

    Diffusive author(s), cohesive author: Analysis of S/N (1994)

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    This study indicates the ways in which various aspects of the author(s) are brought forth in Dumb type’s performance art, the S/N production. Previous research has suggested a non-hierarchical organization of Dumb type and the absence of a “privileged author” in Dumb type’s collaborative work, S/N. However, the results that I have investigated from member’s interviews on the creative process of S/N along with my analysis of the recorded images of S/N, indicate a different aspect of the author(s). First, S/N was created through, so to speak, the collective ideas of the members of Dumb type. Further, S/N has at least nine quotations from previous performances, installations, and printed writings, besides the work-in-progress technique. Explicating one of the “author functions” as given by Michel Foucault, each text has plural subjects of the author. However, it has been revealed from members’ interviews that Teiji Furuhashi had a decision-making role in selecting the members’ ideas within the performance. Since then, S/N has had plural subjects of creation; however, Furuhashi is one of the subjects of creation along with the “privileged author.” S/N has plural authors (diffusive authors) yet at the same time, it has a “privileged author,” Teiji Furuhashi (cohesive author)

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed

    Dispelling the Myths Behind First-author Citation Counts

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    We conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more sophisticated methods

    Tsukushi functions as a Wnt signaling inhibitor by competing with Wnt2b for binding to transmembrane protein Frizzled4

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    The Wnt signaling pathway is essential for the development of diverse tissues during embryogenesis. Signal transduction is activated by the binding of Wnt proteins to the type I receptor low-density lipoprotein receptor-related protein 5/6 and the seven-pass transmembrane protein Frizzled (Fzd), which contains a Wnt-binding site in the form of a cysteine-rich domain. Known extracellular antagonists of the Wnt signaling pathway can be subdivided into two broad classes depending on whether they bind primarily to Wnt or to low-density lipoprotein receptor-related protein 5/6. We show that the secreted protein Tsukushi (TSK) functions as a Wnt signaling inhibitor by binding directly to the cysteine-rich domain of Fzd4 with an affinity of 2.3 x 10(-10) M and competing with Wnt2b. In the developing chick eye, TSK is expressed in the ciliary/iris epithelium, whereas Wnt2b is expressed in the adjacent anterior rim of the optic vesicle, where it controls the differentiation of peripheral eye structures, such as the ciliary body and iris. TSK overexpression effectively antagonizes Wnt2b signaling in chicken embryonic retinal cells both in vivo and in vitro and represses Wnt-dependent specification of peripheral eye fates. Conversely, targeted inactivation of the TSK gene in mice causes expansion of the ciliary body and up-regulation of Wnt2b and Fzd4 expression in the developing peripheral eye. Thus, we uncover a crucial role for TSK as a Wnt signaling inhibitor that regulates peripheral eye formation

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    Can archives of audiovisual TV interviews be used to make authors more visible to students, and thereby reduce the learning gap between native and non-native language speakers in college classes? We examined students in a college course who learned about one scholar's ideas through watching an audiovisual TV interview (i.e., visible author format) and about another scholar's ideas through reading a formal text description (i.e., invisible author format). For the invisible author, native language speakers scored significantly higher than the non-native language speakers on a corresponding exam question (i.e., a cognitive measure), generated more words on the exam question (i.e., a motivational measure), and mentioned the author's name more often in answering the exam question (i.e., an affective measure). For the visible author, the groups did not differ on any of these measures. These findings provide evidence for the idea that making the author visible through audiovisual TV interviews can eliminate the learning gap between native and non-native language speakers. 3 Universities around the world serve students who are non-native speakers of th
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