1,720,956 research outputs found
Could Iron Overload Impair the Migratory Ability of Neurons? Evidence from a Cell-Based Model
No full textBackground: Iron is essential for proper brain development in the fetal and early neonatal period. Iron represents a micronutrient for cellular metabolism and aerobic respiration, but cellular iron overload produces toxic build-up in many organs
(including brain) via free radical formation. In thalassaemic patients with pubertal failure, iron overload is the most important factor afflicting the hypothalamic-pituitary axis, leading to hypogonadotrophic hypogonadism and growth failure. Methods: Mouse GN-11 cells (immature GnRH neurons with migratory ability) were used.
Hepcidin, ferritin and transferrin receptor gene expression was evaluated by PCR. GN-11 chemotaxis was assessed by Boyden chamber assay. Activation of
chemomigration-related cell signaling (extracellular signal-regulated kinase (ERK), 5' adenosine monophosphate-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC)) was evaluated by Western blot analysis. Results: GN-11 cells
express hepcidin, ferritin and transferrin receptor genes. 150 μM ferric ammoniumcitrate (FAC) treatment inhibited (-35%, P < 0.05) FBS-induced chemo-migration of GN-11 cells, which was rescued by pre-treatment with 100 μM deferoxamine, a
specific iron chelator. Time-course experiments showed that 150 μM FAC was able to phosphorylate both ERK and AMPK after 10 min treatment. Specific ERK and AMPK inhibitors, U0126 and Compound C, respectively, abolished FAC-mediated signaling. Moreover, U0126 and Compound C (both 10 μM) counteracted FAC-driven phosphorylation of ACC, an AMPK downstream protein. Conclusions: The present data show that iron negatively affects neuron migration via ERK and AMPK. Among the consequences of this event, iron overload may impair migration of GnRH neurons from the olfactory placode into forebrain and hypothalamus, where they
promote reproductive competence
Iron overload impairs the migratory ability of a model of immature and migratory GnRH neurons
No full textIron represents a micronutrient for cellular metabolism and aerobic respiration, and is essential for proper brain development in the fetal and early neonatal period. However, excess iron produces toxic build-up via free radical formation. In thalassaemic and juvenile hemochromatosis patients with pubertal failure, iron overload interferes with the correct function of the hypothalamic–pituitary axis, leading to hypogonadotrophic hypogonadism and growth failure, but the mechanisms are still unclear. Aim of this study was to investigate the mechanisms of iron toxicity in vitro in GN-11 cells, a model of immature and migratory GnRH neurons. Gene expression analysis by semi-quantitative PCR showed that GN-11 express the iron proteins ferritin (a primary intracellular iron-storage protein) and transferrin (iron-binding extracellular glycoprotein that controls the level of free Fe and deliver iron to cells), as well as hepcidin (an iron regulatory hormone). Exposure of GN11 cells to 150 μM ferric ammonium citrate (FAC) resulted in the inhibition (−35%, P<0.05) of fetal bovine serum (FBS)-induced chemo-migration, assessed by Boyden chamber assay. Pre-treatment with 100 μM deferoxamine, a specific iron chelator, reverted the above reported effect. Time-course experiments showed that 150 μM FAC was associated with induction of phosphorylation of both extracellular signal-regulated kinase (ERK) and 5′ adenosine monophosphate-activated protein kinase (AMPK) after 10 min treatment, as evaluated by Western blotting. Specific ERK and AMPK inhibitors, U0126 and Compound C, respectively, abolished FAC-mediated signaling. Moreover, U0126 and Compound C (both 10 μM) counteracted FAC-driven phosphorylation of acetyl-CoA carboxylase, an AMPK downstream protein. In conclusion, the present data, though preliminary, show that acute iron treatment negatively affects the migration of GN-11 neurons in vitro, and is associated with the activatio of ERK and AMPK signaling pathways. We hypothesize that iron overload may impair migration of GnRH neurons from the olfactory placode into forebrain and hypothalamus, where they promote reproductive competence
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
Effects of somatostatin analogs on cell proliferation of DU-145 and PC-3 human androgen-indipendent prostate cancer cell lines.
No full text
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
- …
