1,721,101 research outputs found
CAR regulate epithelial cell junction stability through control of E-cadherin trafficking
No full textCAR (Coxsackie and Adenovirus Receptor) is the primary docking receptor for typeB coxsackie viruses and subgroup C adenoviruses. CAR is a member of the JAM family of adhesion receptors and is located to both tight and adherens junctions between epithelial cells where it can assemble adhesive contacts through homodimerisation in trans. However, the role of CAR in controlling epithelial junction dynamics remains poorly understood. Here we demonstrate that levels of CAR in human epithelial cells play a key role in determining epithelial cell adhesion through control of E-cadherin stability at cell-cell junctions. Mechanistically, we show that CAR is phosphorylated within the C-terminus by PKCδ and that this in turn controls Src-dependent endocytosis of E-cadherin at cell junctions. This data demonstrates a novel role for CAR in regulating epithelial homeostasis
Introduction to intuitions
Get PDFAvtor se v članku na analitičen način loteva pojma intuicije, obravnava intuicijsko stanje, intuicijsko vsebino, intuicijske zmožnosti, intuicijski proces, matematično intuicijo, moralno intuicijo. Formulira tri teze o intuiciji: o perceptualnem izvoru, kognitivni revščini in bogastvu vsebine in pokaže povezanost teh tez s filozofsko tradicijo (Aristotel, Hume, Parsons, Maddy).The author analyses the notion of intuition, discusses the intuitive state, the content of intuition, intuitive abilities, the intuitive process, mathematical intuition and moral intuition. He formulates three theses about intuition: the thesis of perceptual origin, the thesis of cognitive poverty and the thesis of the richness of content. He also points to the links between these theses and the tradition of philosophy (Aristotle, Hume, Parsons, Maddy)
Talin contains a C-terminal calpain2 cleavage site important in focal adhesion dynamics
Get PDFTalin is a large (~2540 residues) dimeric adaptor protein that associates with the integrin family of cell adhesion molecules in cell-extracellular matrix junctions (focal adhesions; FAs), where it both activates integrins and couples them to the actin cytoskeleton. Calpain2-mediated cleavage of talin between the head and rod domains has previously been shown to be important in FA turnover. Here we identify an additional calpain2-cleavage site that removes the dimerisation domain from the C-terminus of the talin rod, and show that an E2492G mutation inhibits calpain cleavage at this site in vitro, and increases the steady state levels of talin1 in vivo. Expression of a GFP-tagged talin1 E2492G mutant in CHO.K1 cells inhibited FA turnover and the persistence of cell protrusion just as effectively as a L432G mutation that inhibits calpain cleavage between the talin head and rod domains. Moreover, incorporation of both mutations into a single talin molecule had an additive effect clearly demonstrating that calpain cleavage at both the N- and C-terminal regions of talin contribute to the regulation of FA dynamics. However, the N-terminal site was more sensitive to calpain cleavage suggesting that lower levels of calpain are required to liberate the talin head and rod fragments than are needed to clip off the C-terminal dimerisation domain. The talin head and rod liberated by calpain2 cleavage have recently been shown to play roles in an integrin activation cycle important in FA turnover and in FAK-dependent cell cycle progression respectively. The half-life of the talin head is tightly regulated by ubiquitination and we suggest that removal of the C-terminal dimerisation domain from the talin rod may provide a mechanism both for terminating the signalling function of the talin rod and indeed for inactivating full-length talin thereby promoting FA turnover at the rear of the cell
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe 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
Imaging Cells Within 3D Cell-Derived Matrix
No full textMuch of what is known about the mechanisms regulating cell adhesion and migration come from in vitro studies of cells plated on 2-dimensional (2D) extracellular matrix (ECM) proteins. The importance of studying these processes in cells within 3-dimensional (3D) environments is becoming increasingly recognised, as a number of studies have now demonstrated that adhesion formation and migration are markedly different in cells within 3D environments (Cukierman et al. Science 1708-1712, 2001). It is also known that the composition and pliability or density of the ECM are important in regulating cell adhesion and migration (Cukierman et al. Science 1708-1712, 2001). Cell-derived matrices (CDM) are naturally deposited fibrillar ECM from fibroblasts that can be used to study the adhesions and migration of cells in a more physiologically relevant environment
HGF-Induced DU145 Cell Scatter Assay
No full textEpithelial mesenchymal transition (EMT) is a multi-stage process whereby epithelial cells lose their cell:cell adhesions and acquire the capacity to migrate independently. It is a process that is important in normal development and is thought to be adopted by some invasive cancer cells. EMT requires modifications in cell shape and substratum adhesions and these events are dependent on the reorganisation of the actin cytoskeleton. Hepatocyte growth factor (HGF) is a mitogenic growth factor that is well known to induce such a conversion, termed "cell scattering", in Madin Darby canine kidney (MDCK) cells. Recently, we have developed an alternative model of cell scattering using the human prostate cancer cell line, DU145. Like MDCK cells, DU145 cells normally grow as tight colonies with firm cell:cell junctions, but they can be induced to 'scatter' upon HGF stimulation. Here, we describe the optimised protocol for conducting and analysing an HGF-induced DU145 scatter assay. This model is particularly useful for monitoring changes in actin cytoskeletal organisation and dynamics, cell:cell adhesions, and cell migration in human cells that respond to HGF stimulation
Measuring FRET Using Time-Resolved FLIM
No full textCell migration is a process that is controlled by the formation and correct localization of protein complexes and by post-translational modification of individual proteins. Forster or fluorescent resonance energy transfer (FRET) detected using fluorescence lifetime imaging microscopy (FLIM) provides a method by which protein-protein interactions may be detected and spatially localized within a cell. This technique can be used to map protein activation states and the formation and dissolution of protein complexes that control movement of a cell. This chapter describes a protocol for detecting FRET between GFP- and mRFP1-tagged proteins in fixed adherent cells. A background to both FRET and FLIM is provided followed by an overview of the method and a full protocol for sample preparation, data acquisition, and analysis
Variations on the Author
Get PDF“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Get PDFWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
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