1,721,165 research outputs found
Role of post-translational modifications on cell distribution and FUNCTIONS of protein kinase C theta
No full textThe novel protein kinase C (PKC) theta isozyme has been recently proposed as a drug target
for human leukemias. In single cell types we have identified multiple PKC theta forms,
characterised by differential post-translational modifications. Aim of this work was to
establish if these molecular modifications affect PKC theta intracellular localisation and
catalytic competence.
A critical role in the control of both PKC theta cell distribution and catalytic activity is played
by the phosphorylation state of the kinase activation loop, at the Thr538 residue. PKC theta
molecules showing a Mr of 85 kDa (named theta-85) and dephosphorylated at Thr538 have
been found specifically associated with the Golgi complex and catalytically active. In
contrast, PKC theta molecules with a Mr of 76 kDa (named theta-76), partially
phosphorylated at Thr538, are localised in the detergent-soluble cell fraction. Only theta-76
kinase forms not phosphorylated at Thr538 can undergo conversion to theta-85 by an
autophosphorylation process. Cell treatment with calyculin A, a protein phosphatase 1 and 2A
inhibitor or with LY294002, an inhibitor of Thr538 phosphorylation via PI3K/PDK1, results in
a significant increase in the amount of protein kinase PKC theta associated with the Golgi
complex. Moreover, as demonstrated by the behaviour of Thr538ÆAla and Thr538 ÆGlu PKC
theta mutants, the absence of pThr538 is sufficient for the recruitment of PKC theta to the
Golgi complex. Moreover, the Thr538ÆAla PKC theta mutant also results modified by Nglycosylation.
This kinase form binds wheat germ agglutinin and acquires a lower Mr by
treatment with N-glycosydase F. These findings suggest that different PKC theta forms might
be involved in distinct cell functions. New pharmacological strategies, aimed specifically to
control PKC theta activities that promote malignant cell proliferation, should be designed and
screened on the basis of their effect on individual PKC theta forms
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe 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
Sanguinarine inhibits VEGF-induced Akt phosphorylation.
No full textAngiogenesis is the process of vascular growth by sprouting of preexisting vessels. This process
impacts significantly on many important disease states including cancer, diabetic retinopathy, and
arthritis. Endothelial cells receive multiple information from their environment, which leads them to
progress along all stages of new vessel formation. Vascular endothelial growth factor (VEGF), in
particular appears to be a master regulator of this process. This molecule interacts with cellular
receptors and communicates with cell nucleus through a network of intracellular signaling, most of
all by activating Akt pathway. This activation accounts for many of VEGF effects, including cell
survival, migration, tube formation, and promotion of NO release. Sanguinarine (SA), an alkaloid
isolated from Sanguinaria canadensis, is known for its antiangiogenetic effects by suppressing basal
and VEGF-induced new vessel growth. This article was aimed to evaluate the possible effect of SA
(300 nM) on Akt phosphorylation in a porcine aortic endothelial cell line. The alkaloid significantly
(P < 0.001) inhibited the VEGF-induced Akt increase, thus suggesting that this mode of action
could be responsible, at least partially, for the antiangiogenetic effect of SA
2-Methoxyestradiol inhibits superoxide anion generation while enhances superoxide dismutase activity in swine granulosa cells.
No full text2-Methoxyestradiol (2-ME) is an estradiol metabolite with antiangiogenic properties. It can be produced by granulosa cells and it is present in normal follicle at high concentrations. The identification of reactive oxygen species (ROS) role in the molecular pharmacology of 2-ME is an active area of research. The objective of this article was therefore to evaluate the effect of 2-ME on both superoxide anion (O(2)(-)) production and superoxide dismutase (SOD) activity in swine granulosa cells collected from follicles greater than 5 mm and treated for 48 h with 1 muM 2-ME. 2-ME inhibited (P < 0.001) O(2)(-) generation in swine granulosa cells, while it stimulated (P < 0.05) the SOD activity. We previously demonstrated that a stimulation of O(2)(-) generation triggers angiogenetic response in granulosa cells. Therefore, we argue that the inhibitory effect of 2-ME on O(2)(-) could be responsible for its antiangiogenetic effect
Variations on the Author
Full text link“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
Full text linkWe 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
Dispelling the Myths Behind First-author Citation Counts
Full text linkWe 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
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