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Thyroid hormone inhibition of IGF-1-mediated glucose uptake in L-6 myoblasts through intercation with alphaVbeta3 integrin
No full textThe Endocrine Society's 90th Annual MeetingFilename: 851334 Contact Author: Sandra Incerpi Dr. Department/Institution: Biology, University Roma TreAddress: Viale G. Marconi, 446City/State/Zip/Country: Rome, 00146, ItalyPhone: ++39-06-57336335 Fax: ++39-06-57336321 E-mail: [email protected]
NONGENOMIC EFFECTS OF THYROID HORMONE ON THE INTRACELLULAR PH OF L-6 MYOBLASTS: SIGNAL TRANSDUCTION
No full textThyroid hormones activate by a nongenomic mechanism the Na/H exchanger of L-6 cells from rat skeletal muscle, giving rise to an increase of intracellular pH, both at the steady state and under acid load with ammonium chloride (S. Incerpi et al., Endocrinology 140:683-689, 1999). Intracellular pH was measured by the fluorescent indicator 2’,7’bis(carboxyethyl)-5(6)-carboxyfluorescein. The effect was specific as shown by the ineffectiveness of the most common thyroid hormone analogs and by the use of 5-(ethyl-N-isopropyl)amiloride and 4,4’-diisothiocyano-stilbene-2,2’disulfonic acid. The signal transduction appears to be mediated by both intracellular calcium mobilization and protein kinase activity. (S. Incerpi, Curr. Op. Endocrinol. Diab. 9:381-386, 2002). The involvement of intracellular calcium was measured by loading the L-6 myoblasts with the fluorescent probe Fura-2. Thyroid hormone gave rise to a peak after about 90 seconds for L-T3 and 5 min for L-T4, and the thyroid hormone analogs were ineffective. The action of the most common intracellular calcium modulators, such as caffeine and ryanodine was investigated. The effect of thyroid hormone on the intracellular pH appears to be mediated also by protein kinase C, MAP Kinase and Akt activity as assessed by the use of inhibitors and immunoblotting experiments
T3-Agarose: A reliable tool to study nongenomic effects of thyroid hormones
No full textNongenomic effects are nowadays described for most hormones of the nuclear receptor superfamily, such as thyroid hormones (T3, T4). These effects are mainly membrane –located, such as calcium mobilization, glucose uptake, intracellular pH, activation of PKC, and the MAPK pathway; they show a time-course of seconds to minutes. They may be mediated by specific receptors on the plasma membrane of different cells. In these experiments it is important to use agonist hormones conjugated to non-diffusible anchor molecules, such as Agarose. The hormone binds to the membrane and cannot enter the cell: this is an easy way to study membrane effects. T3-Agarose was prepared as reported at the website: www.amershambiosciences.com. T3-Agarose is a membrane-impermeant derivative based on the use of activated CH Sepharose 4BTM, a pre-activated medium for covalent immobilization of either proteins or other ligands containing primary amino groups. The group to be coupled is the amino group (-NH2) and the matrix Agarose (4%), the coupling conditions are pH 5-10, 4-25 °C, 1-4 h. The contamination by free T3 is very low, about 1 mol free T3/10E5 mol T3-Agarose as assessed by RIA. T3-Agarose (1 nM) was able to elicit nongenomic effects of thyroid hormone, in fact it increased intracellular pH and gave rise to an increase in intracellular calcium concentration similar to that obtained with the same concentrations of T3 (1 nM) in L-6 myoblasts. Nuclear responses were not affected by T3-Agarose. The results appear promising and the same technique will be used in the near future also for T4 and analogs that mimic thyroid hormone effects
Thyroid hormone inhibition of IGF-1 mediated glucose uptake in Myoblasts L-6 through interaction with alphaVbeta3 integrin
No full textAim: Thyroid hormone through its membrane receptor, the integrin aVß3, has been reported to be able to modulate the activity of growth factors. We studied glucose uptake in L-6 myoblasts in order to determine whether thyroid hormone modulates the activity of IGF-1, perhaps through crosstalk between the integrin and IGF-1R.Methods: The carrier-mediated hexose uptake (cytochalasin B-inhibitable) was measured for 10 min at 37°C in Hepes-Buffered Saline by 10 μM 2-deoxy-[3H]-D-glucose, after 4 hours of serum depletion. Results: IGF-1 activated glucose uptake in L-6 cells by a PI 3-K-dependent, that is, wortmannin-sensitive, mechanism. Thyroid hormones, 3,5,3'-triiodo-L-thyronine (T3; 1 nM) and L-thyroxine (T4; 100 nM) both stimulated glucose uptake. In the presence of IGF-1, however, T3 and T4 inhibited the IGF-1 effect on glucose uptake by a pathway that was RGD-sensitive, suggesting the involvement of the cell surface receptor for thyroid hormone at the RGD (Arg-Gly-Asp) recognition site on integrin alphaVbeta3 in iodothyronine action on the effect of IGF-1. Echistatin, an RGD-sequence-containing inhibitor of integrins, blocked IGF-1 action on glucose uptake in L6 cells. Conclusions: There are two modes of crosstalk between the integrin receptor for thyroid hormone on integrin alphaVbeta3 and the IGF-1 receptor. One level of crosstalk allows T3 and T4 to modulate IGF-1 action and requires PI 3-K activation. Another mode of crosstalk between the integrin and IGF-1R is thyroid hormone-independent and echistatin-sensitive
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
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