1,720,960 research outputs found
Tirosin-chinasi Src: studi di regolazione/deregolazione in cellule normali e patologiche
No full textThe Src family of protein kinases (SFKs), plays an important role in regulating the signal transduction by cell surface receptors to the cytoplasmic machinery. SFK enzymes are involved in cell grown, differentiation, migration and survival. SFK activity is regulated in the cell by the phosphorylation state of two tyrosine residues and by the binding of protein-partners, that stabilize the kinases in their active or inactive conformation. In normal cells, the SFK activity is tightly regulated and aberration in its mechanisms of regulation can lead to the constitutive activation, which contributes to several pathologies, including cancer.
The aim of this work was to gain deeper insight into the molecular mechanisms, which give rise to the aberrant regulation of SFK activity in two hematopoietic malignancies. Moreover, we analyzed the signaling of Src-kinase Fyn during muscle differentiation.
B cell chronic lymphocytic leukemia is a pathology caused by the accumulation of slowly proliferating cells with defective apoptosis. Our results indicate that, in these leukemics cells,the Src-kinase Lyn is present in its hyperactive conformation as an integral component of an aberrant cytosolic multiprotein complex of 600 kDa. In this complex, the kinase is physically associated with several proteins, such as Hsp90 through its catalytic domain, and HS1 and SHP-1L through its SH3 domain. Treatment of B-CLL cells with geldanamycin, an Hsp90 inhibitor, abrogates cytosolic Lyn activity, induces the kinase degradation and promotes cellular apoptosis.
In platelets of Philadelphia negative myeloproliferative diseases, that are clonal hematopoietc disordes, our data demonstrate that, at variance with normal cells, Src kinase is not phosphorylated at the C-terminus inactivating tyrosine Y527.
This pre-activated conformation of Src is responsible for the basal hypersensitivity of the pathological platelets, which are greatly activated by low thrombin concentrations, which are ineffective towards normal platelets.
In C2C12 murine muscle cells, we demostrated that, in the early phase of the differentiation process, the Src-kinase Fyn phosphorylates the chaperone Grp94 in the lumen of the endoplasmic reticulum. This event is associated with the release of Tyr-phosphorylated Grp94 from the endoplasmic reticulum chaperone protein Grp94 and the chaperone traslocation to the Golgi apparatus and plasma membrane, where Grp94 has been demonstrated to be required for myotube formation
Immune complexes of glucose-regulated protein94 (Grp94) with IgG, present in the plasma of type 1 diabetic subjects, show strong angiogenic-transforming capacity on HUVECs
No full textCharacterization of immune complexes of idiotypic catalytic and anti-idiotypic inhibitory antibodies in plasma of type 1 diabetic subjects
No full textAn increase in proteolytic activity is an early common feature of diabetes, and is associated with the development of vascular complications. We performed an extensive proteomic investigation on plasma of type 1 diabetic subjects to discover why some of them apparently lacked any measurable proteolytic activity. Activity was found enclosed in immune complexes in which Fab/(Fab)(2) displayed a serine-like catalytic activity. Disaggregation of complexes by means of Protein G affinity chromatography led to the separation of free subunits of Fab, showing a specific amidolytic activity, from Fab that displayed activity on casein and remained closely complexed with whole IgG. On both types of Fab the serine catalytic site appeared to be the same, being located in close vicinity to the antigen-binding site. The distinct substrate specificity was due to the different conformation adopted by the catalytic site depending on the structure of Fab/(Fab)(2), whether in complexes or as free subunits. Catalytic Fab/(Fab)(2) originated from idiotypic antibodies developed against Grp94, identified as the primary antigen covalently complexed with Fab. Whole IgG present in immune complexes were instead mostly formed with anti-idiotypic antibodies developed against the adduct of Fab/(Fab)(2) with Grp94, and were responsible for blocking any catalytic activity. In dot-blot experiments with native Grp94, we confirmed that in any diabetic plasma circulated anti-Grp94, idiotypic, and anti-idiotypic antibodies
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
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
koamabayili/VECTRON-author-checklist: VECTRON author checklist
No full textWe have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
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