1,721,090 research outputs found
Thyroid Phylogeny: from seaweeds to man
No full textIodine uptake and production of iodine-aminoacids are evolutionarily very old phenomena. Seaweed are the first eukaryotic organism presenting these functions; they are rich in iodine and are at basis of the food chain. The monoiodotirosines, precursors of thyroxine, have been identified in a wide variety of invertebrates, such as Gorgonians and Tunicates. The structure of the thyroid appears for the first time in Cyclostomes adults (Lamprey), while in Tunicates (Ciona intestinalis) and Amphioxus is present a similar structure, the endostyle, which is an invagination of the ventral wall of the pharynx containing glandular cells that are able to concentrate iodine. This is not a true endocrine gland because the secretion is poured into the alimentary canal. In the larva of Lamprey (Ammocoetes) during the metamorphosis some of the epithelial cells persist and transform in the follicles. The cyclostomes, therefore, represent a link between the endostyle of protochordates and the thyroid gland of higher chordates. This hypothesis is confirmed by molecular genetic studies which have demonstrated the expression of Thyroid Transcription Factor (TTF-1) in the endostyle of Ciona, Lamprey and Amphioxus. The TTF-1 is an ancestral transcription factor which controls the survival of thyroid follicular cells at the beginning of organogenesis and regulates the expression of thyroid-specific genes in adult life. Clin Ter 2012; 163(2):e73-7
STRUCTURE AND STABILITY OF THE NON COVALENT SWAPPED DIMER OF BOVINE SEMINAL RIBONUCLEASE
No full textA growing number of pancreatic-type ribonucleases (RNases) present cytotoxic activity against malignant cells. The cytoxicity of these enzymes is related to their resistance to the ribonuclease protein inhibitor (RI). In particular, bovine seminal ribonuclease (BS-RNase) is toxic to tumor cells both in vitro and in vivo. BS-RNase is a covalent dimer with two intersubunit disulfide bridges between Cys31 of one chain and Cys32 of the second and vice versa. The native enzyme is an equilibrium mixture of two isomers, MxM and MM. In the former the two subunits swap their N-terminal helices. The cytotoxic action is a peculiar property of MxM. In the reducing environment of cytosol, MM dissociates into monomers, which are strongly inhibited by RI, whereas MxM remains as a non-covalent dimer (NCD), which evades RI. We have solved the crystal structure of NCD, carboxyamidomethylated at residues Cys31 and Cys32 (NCD-CAM), in a complex with 2-deoxycitidylyl( 3-5)-2-deoxyadenosine. The molecule reveals a quaternary structural organization much closer to MxM than to other N-terminal-swapped non-covalent dimeric forms of RNases. Model building of the complexes between these non-covalent dimers and RI reveals that NCD-CAM is the only dimer equipped with a quaternary organization capable of interfering seriously with the binding of the inhibitor. Moreover, a detailed comparative structural analysis of the dimers has highlighted the residues, which are mostly important in driving the quaternary structure toward that found in NCD-CA
THE UNSWAPPED CHAIN OF BOVINE SEMINAL RIBONUCLEASE: CRYSTAL STRUCTURE OF THE FREE AND LIGANDED MONOMERIC DERIVATIVE
No full textDIMERO NON COVALENTE DELLA RIBONUCLEASI BOVINA SEMINALE CON SCAMBIO DEI DOMINI N-TERMINALI: STRUTTURA E STABILITÀ
No full textEFFECT OF POINT MUTATIONS ON THE HIGHLY RIGID STRUCTURE OF ONCONASE, A CANCER CHEMOTHERAPEUTIC
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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
Regioselective Synthesis of 4,5-Diaryl-1-methyl-1H-imidazoles Including Highly Cytotoxic Derivatives by Pd-Catalyzed Direct C-5 Arylation of 1-Methyl-1H-imidazole with Aryl Bromides
No full textA general and efficient three-step procedure for the highly regioselective synthesis of 1-methyl-1H-imidazoles possessing electron-rich, electron-neutral, and/or electron-deficient aryl moieties at their 4- and 5-positions is described. The first step involves the Pd-catalyzed direct C-5 arylation of commercially available 1-methyl-1H-imidazole with aryl bromides, and the second and third steps of the sequence involve the selective C-4 bromination of the resulting 5-aryl-1-methyl-1H-imidazoles with NBS, followed by a PdCl(2)(dppf)-catalyzed Suzuki-type reaction between 5-aryl-4-bromo-1-methyl-1H-imidazoles and arylboronic acids under phase-transfer conditions. Two 4,5-diaryl-1-methyl-1H-imidazoles so prepared, which can be regarded as Z-restricted analogues of naturally occurring combretastatin A-4 (CA-4), proved to be highly cytotoxic against a variety of human tumor cell lines, and one of these derivatives has been shown to be more cytotoxic than CA-4 and all of the imidazole derivatives investigated in the literature thus far. ( (C) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008
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