1,721,438 research outputs found
El tiempo y la naturaleza en la obra de Ricardo E. Molinari
Full text linkEn 1975 la editorial El Mangrullo publicó en Buenos Aires la obra poética de Ricardo E. Molinari titulada Las sombras del pájaro tostado, obra poética (1923-1973), compilada por Federico Vogelius. Por circunstancias extraliterarias, la obra no circuló en Buenos Aires. Lo importante de su publicación consiste no sólo en un homenaje al autor, sino que contiene casi todas las plaquettes que se editaron y que son de difícil obtención, por haberse impreso en tirajes muy reducidos. El propósito de este trabajo es el de realizar un análisis de la obra de Ricardo E. Molinari tratando de esclarecer los códigos de naturaleza y temporalidad que en ella se encuentran.Tesis digitalizada en SEDICI en colaboración con la Biblioteca de Humanidades "Prof. Guillermo Obiols" (FAHCE-UNLP).Doctor en LetrasUniversidad Nacional de La PlataFacultad de Humanidades y Ciencias de la Educació
UNRAVELLING THE MOLECULAR MECHANISMS OF IMPAIRED LIMB DEVELOPMENT: ROLE OF DNP63A IN SPLIT-HAND/FOOT MALFORMATION TYPE 4 AND IN THALIDOMIDE TERATOGENICITY
Full text linkThe p63 transcription factor, homolog to the p53 tumour suppressor, plays a key role in limb, epithelial and cranio-facial development. p63 activity and stability are tightly modulated to guarantee correct development of such structures and an impairment of this regulative mechanism can result in severe malformations. The control of p63 function is achieved not only through the regulation of its gene expression but also through a complex network of post-translational modifications. Acetylation, phosphorylation and ubiquitination affect p63 half-life, the specificity and efficiency of protein-protein interactions and overall modulate the transcriptional activity of the protein.
Here we describe two pathways that, by post-translationally modifying ΔNp63α protein, modulate its stability and function.
One such pathway involves FGF8, c-Abl and p300 which cooperate in controlling the stability and function of ΔNp63α protein by leading to its acetylation on lysine 193 (K193). Interestingly, K193 is mutated into glutamic acid (K193E) in patients affected by Split Hand/Foot Malformation (SHFM) type 4. c-Abl kinase activity is required to transduce the signal induced by FGF8 leading to ΔNp63α stabilization and transcriptional activation, through its acetylation mediated by p300. The ΔNp63α-K193E mutant, which cannot be acetylated by this pathway, displays promoter-specific loss of DNA binding activity and consequent altered expression of development-associated ΔNp63α target genes. Our results, elucidating an important regulatory pathway activated by FGF8 and essential for ΔNp63α activation and stabilization, shed new light on the molecular mechanism that could be at the basis of the SHFM4 pathogenesis.
The other pathway that we here present is a degradative pathway promoted by the teratogenic drug thalidomide that leads to proteasome-mediated degradation of ΔNp63α, resulting in a lack of activation of ΔNp63α development-related target genes. In cell lines, thalidomide treatment induces a downregulation of ΔNp63α protein via the action of GSK3 kinase and FBWX7 ubiquitin ligase. Upon thalidomide treatment, GSK3 kinase is required to phosphorylate ΔNp63α on the residues serine 383 and threonine 397. This phosphorylation is recognized as a signal by FBWX7 which in turn ubiquitinates ΔNp63α, leading to its proteasome-mediated degradation. Thalidomide treatment induces a downregulation of ΔNp63α protein levels also in vivo in zebrafish embryos, where it results in a phenotypical and molecular impairment of fin development. Importantly, the microinjection of zp63-mRNA into zebrafish embryos treated with thalidomide rescues both the phenotypical and molecular defects induced by the drug, indicating that the downregulation of ΔNp63α is, at least in part, at the bases of thalidomide-induced malformations. Our results, by demonstrating that ΔNp63α is a molecular target of thalidomide teratogenicity, provide a fundamental missing piece in the description of the drug molecular mechanism of action. Thalidomide is now used for the treatment of multiple myeloma and leprosy: a better understanding of its mechanism of action might pave the way for the design of related compounds with equal therapeutic properties but devoid of teratogenic activity
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
Carta de E. Molinari elogiando a Almafuerte y solicitándole material inédito para publicar en <i>La Verdad</i>
No full textCarta sin fecha escrita en Avellaneda en la que E. Molinari le comenta a Palacios que publicarán un número especial de La Verdad donde publicarán "La Inmortal" completa y todas sus poesías, y le solicita si puede enviarle alguna producción inédita para dicha publicación.Biblioteca Pública de la Universidad Nacional de La Plat
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
Impianti elettrici e compatibilità ambientale nel Nuovo Polo Espositivo della Fiera di Milano
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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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