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Μηχανισμοί αλληλεπίδρασης του α αδρενεργικού συστήματος με το σύστημα της θυρεοειδικής ορμόνης - θυρεοειδικών υποδοχέων σε μοντέλο απομονωθέντων νεογνικών καρδιομυοκυττάρων
Thyroid hormone receptor alpha1 (TR alpha 1) is predominantly expressed in the myocardium but its biological function under physiological or pathological conditions remains largely unknown. The present study investigated possible interactions between alpha1 adrenergic and thyroid hormone signaling at the level of TR alpha 1, potential underlying mechanisms and physiological consequences, as well as the role of TR alpha 1 in cell differentiation. This may be of physiological relevance since both thyroid hormone and adrenergic signalling are implicated in the pathophysiology of cardiac remodelling. Neonatal cardiomyocytes obtained from newborn rats (0-72 hours) were exposed to 20μΜ phenylephrine (PE, an alpha1 adrenergic agonist) for 8 min., 60 min. and 5 days, in the absence or excess of Τ₃ in the culture medium. PE administration, in the absence of Τ₃, resulted in disoriented, dense myofibrils and undefined shape. This response was accompanied by an increase in phospho-p44 (20.0 fold in 8 min., 3.0 fold in 60 min.), phospho-p42 (16.0 fold in 8 min., 4.0 fold in 60 min.), phospho-Akt (1.5 fold in 8 min.), in phospho-JNK (3.0 fold in 8 min.) and phospho-p38MAPK (2.2 fold in 8 min.), p<0.05. Furthermore, a 5.0 fold increase in TR alpha 1 expression in nucleus and 2.0 fold decrease in TR alpha 1 expression in cytosol, p<0.05 were observed. As a result, a fetal pattern of myosin isoform expression with marked expression of beta-MHC was observed in PE treated vs the untreated cells, p<0.05. PD98059 (an ERK signaling inhibitor) abrogated this response. Rapamycine (an m-TOR inhibitor) abrogated the response, without affecting the myosin isoform expression, while the inhibition of either JNK or p38MAPK signaling caused no changes. In the presence of 100nM Τ₃ in the culture medium, the cardiomyocytes had an elongated shape with a filamentous actin pattern organized into orderly arrays. This response was accompanied by a 1.6 fold increase in TR alpha 1 expression in nucleus and 2.0 fold in cytosol in PE-Τ₃ vs PE treated cells, p<0.05, and the fetal pattern of myosin isoform expression was prevented. In conclusion, in neonatal cardiomyocytes, nuclear TR alpha 1 is overexpressed after prolonged activation of the alpha 1- adrenergic signalling by PE. This response seems to be an ERK kinase and/or m-TOR dependent process. Over-expression of TR alpha 1 may lead to fetal cardiac phenotype in the absence of thyroid hormone availability.Ο θυρεοειδικός υποδοχέας α1 (TRa1) εκφράζεται κυρίως στο μυοκάρδιο, αλλά η βιολογική του λειτουργία υπό φυσιολογικές ή παθολογικές καταστάσεις παραμένει σε μεγάλο βαθμό άγνωστη. Η μελέτη αυτή πραγματεύεται τις πιθανές αλληλεπιδράσεις μεταξύ της σηματοδοτικής οδού των α1 αδρενεργικών υποδοχέων και της θυρεοειδικής ορμόνης στο επίπεδο του TRa1 τους πιθανούς μηχανισμούς και τις φυσιολογικές συνέπειες. Αυτό μπορεί να έχει θεραπευτική σημασία, δεδομένου ότι τόσο η θυρεοειδική ορμόνη όσο και οι αδρενεργικοί υποδοχείς εμπλέκονται στην παθοφυσιολογία της καρδιακής αναδιαμόρφωσης. Νεογνικά καρδιομυοκύτταρα απομονώθηκαν από επίμυες 0-72 ωρών και εκτέθηκαν σε 20μΜ φαινυλεφρίνης (ΡΕ, ένας α1 αδρενεργικός αγωνιστής) για 8 λεπτά, 60 λεπτά και 5 ήμερες, με παρουσία ή μη τριιωδοθυρονίνης (Τ₃) στο καλλιεργητικό μέσο. Η χορήγηση ΡΕ, απουσία Τ₃, αποδιοργάνωσε τα κύτταρα προσδίδοντάς τους ακανόνιστο σχήμα. Αυτή η απόκριση συνοδεύτηκε από αύξηση των φωσφο-p44 (20 φορές στα 8 και 3 φορές στα 60 λεπτά), φωσφο-p42 (16 φορές στα 8 και 4 φορές στα 60 λεπτά), φωσφο-Akt (1.5 φορές στα 8 λεπτά), φωσφο-JNK (3 φορές στα 8 λεπτά) και φωσφο-p38ΜΑΡΚ (2.2 φορές στα 8 λεπτά), p<0.05. Επιπρόσθετα, παρατηρήθηκε αύξηση της έκφρασης του TRa1 κατά 5 φορές στον πυρήνα και μείωση του κατά 2 φορές στο κυτταρόπλασμα, p<0.05. Συνεπώς, παρατηρήθηκε ένα εμβρυϊκό πρότυπο έκφρασης των ισόμορφων της μυοσίνης με σημαντική αύξηση της έκφρασης της β-MHC στην ομάδα ΡΕ σε σχέση με την ομάδα CONT. Το PD98059 (ένας αναστολέας της ERK σηματοδοτικής οδού) ανέστειλε αυτή την απόκριση. Η ραπαμυκίνη (ένας αναστολέας του m-TOR) ανέστειλε επίσης αυτή την απόκριση, χωρίς να επηρεάσει την έκφραση των ισομορφών της μυοσίνης. Η αναστολή των σηματοδοτικών μονοπατιών των JNK και p38ΜΑΡΚ δεν προκάλεσε καμία αλλαγή. Τα κύτταρα απέκτησαν επίμηκες σχήμα με καλά οργανωμένο κυτταροσκελετό, παρουσία 100nM Τ₃ στο θρεπτικό μέσο. Αυτή η απόκριση συνοδεύτηκε από αύξηση της έκφρασης του TRa1 κατά 1.6 φορές στον πυρήνα και 2 φορές στο κυτταρόπλασμα στην ομάδα ΡΕ-Τ₃ συγκρινόμενη με την ομάδα ΡΕ, p<0.05 και κατάργηση του εμβρυϊκού προτύπου έκφρασης των ισομορφών της μυοσίνης. Εν κατακλείδι, ο πυρηνικός υποδοχέας TRa1 υπερεκφράζεται σε νεογνικά καρδιομυοκύτταρα μετά από διέγερση της αδρενεργικής σηματοδότησης από την ΡΕ. Αυτή η απόκριση φαίνεται να εξαρτάται από τα σηματοδοτικά μονοπάτια των κινασών ERK ή/και m-TOR. Η υπερέκφραση του TRa1 ίσως οδηγεί στον εμβρυϊκό καρδιακό φαινότυπο απουσία θυρεοειδικής ορμόνης
Going Beyond Counting First Authors in Author Co-citation Analysis
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
Variations on the Author
“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
We 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
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
koamabayili/VECTRON-author-checklist: VECTRON author checklist
We 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
Author-wise bibliometric analysis based on entropy.
Author-wise bibliometric analysis based on entropy.</p
Author Under Sail The Imagination of Jack London, 1893-1902
In Author Under Sail, Jay Williams offers the first complete literary biography of Jack London as a professional writer engaged in the labor of writing. It examines the authorial imagination in London's work, the use of imagination in both his fiction and nonfiction, and the ways he defined imagination in the creative process in his business dealings with his publishers, editors, and agents. In this first volume of a two-volume biography, Williams traverses the years 1893 to 1902, from London's "Story of a Typhoon" to The People of the Abyss. The Jack London who emerges in the pages of Author Under Sail is a writer whose partnership with publishers, most notably his productive alliance with George Brett of Macmillan, was one of the most formative in American literary history. London pioneered many author models during the heyday of realism and naturalism, blurring the boundaries of these popular genres by focusing on absorption and theatricality and the representation of the seen and unseen. London created an impassioned, sincere, and extremely personal realism unlike that of other American writers of the time. Author Under Sail is a literary tour de force that reveals the full range of London as writer, creative citizen, and entrepreneur at the same time it sheds light on the maverick side of machine-age literature.Intro -- Title Page -- Copyright Page -- Dedication -- Contents -- Acknowledgments -- Introduction -- 1. Spirit Truth -- 2. From Absorption to Theatricality and Back Again -- 3. "I Will Build a New Present" -- 4. Sons as Authors -- 5. Fathers as Publishers -- 6. The Daughter as Author -- 7. Lovers as Authors -- 8. At Sea with the Family -- 9. Yellow News, Yellow Stories -- 10. The Return Home -- Notes -- Bibliography -- Index -- About Jay WilliamsIn Author Under Sail, Jay Williams offers the first complete literary biography of Jack London as a professional writer engaged in the labor of writing. It examines the authorial imagination in London's work, the use of imagination in both his fiction and nonfiction, and the ways he defined imagination in the creative process in his business dealings with his publishers, editors, and agents. In this first volume of a two-volume biography, Williams traverses the years 1893 to 1902, from London's "Story of a Typhoon" to The People of the Abyss. The Jack London who emerges in the pages of Author Under Sail is a writer whose partnership with publishers, most notably his productive alliance with George Brett of Macmillan, was one of the most formative in American literary history. London pioneered many author models during the heyday of realism and naturalism, blurring the boundaries of these popular genres by focusing on absorption and theatricality and the representation of the seen and unseen. London created an impassioned, sincere, and extremely personal realism unlike that of other American writers of the time. Author Under Sail is a literary tour de force that reveals the full range of London as writer, creative citizen, and entrepreneur at the same time it sheds light on the maverick side of machine-age literature.Description based on publisher supplied metadata and other sources.Electronic reproduction. Ann Arbor, Michigan : ProQuest Ebook Central, YYYY. Available via World Wide Web. Access may be limited to ProQuest Ebook Central affiliated libraries
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