1,720,956 research outputs found
Molecular basis of the interaction between glycosaminoglycans, mimetics and proteins
Get PDFHeparin (H) and heparan sulfate (HS) are polysaccharides belonging to the glycosaminoglycan (GAG) family. As a proteoglycan, HS is present either in the outer face of the cell membrane or in the extra cellular matrix (ECM). HS is involved in the modulation of the communication between cells and cell-ECM. Like polyanionic molecules, H/HS are involved in a great number of GAG-protein interactions and biological activities such as blood coagulation, lipid metabolism, cell adhesion and growth factor regulation (Ori, A., 2008; Capila, I., 2002). Recently, it has been shown an increasing in H/HS-protein complexes structural studies. This lead to an improved understanding of H/HS-protein interactions. Does H/HS interaction network represent the crossroad of the cell-ECM molecular net? The aim of the present study is oriented to clarify some H/HS network aspects, for instance the H/HS-fibroblast growth factor (FGF) family interactions, the H/HS-βamyloid (βA) and the H/HS-antithrombin III (AT) interactions. Different methods were applied to elucidate biochemical and structural data: Nuclear Magnetic Resonance (NMR), Dynamic Light Scattering (DLS) and Surface Plasmon Resonance (SPR). Literature results showed as oligosaccharides derived from H (H oligosaccharides) are able to mimic H/HS effects in H/HS-protein binding and biological activity (Linhardt, R. J., 1999; Yates, E. A., 2004; Guerrini M., 2002). According to H oligosaccharides properties, we decide to use H oligosaccharides having different sulfation pattern and derived by partial depolimerization of beef lung and pig mucosal heparin. NMR and DLS data confirm the great importance of βA folding for the chemo-physical environment as previously reported (Zagorski M. G., 1992; Mandal P. K., 2004; Valerio M., 2008). Preliminary NMR results of βAs (βA (1-40), βA (1-28) and βA (25-35))/H oligosaccharides in solution suggest a critical role in βAs stability. 1H-15N heteronuclear correlation spectroscopy (HSQC) spectra acquired before and after H tetrasaccharide and AGA*IA (see methods) addition show some interesting differences, showing the influence of sulfation and length of the chains in the aggregation phenomena. SPR results confirm the importance of sulfation pattern and monosaccharides sequence in FGF/H oligosaccharides interactions. Changing in sulfation pattern (6-O desulfation or 2-O desulfation) strongly affects FGF-1/H oligosaccharides-binding mechanisms
ADDRESSING THE MOLECULAR BASIS OF THE INTERACTION BETWEEN GLYCOSAMYNOGLYCAN, MIMETICS AND PROTEINS
Get PDFGlycosaminoglycans (GAGs) are some of the most relevant biological molecules, involved in important biological, physiological activities and also used as pharmaceutical agents. GAG research activities oriented to understand their nature, molecular population composition, characterisation, protein-GAG interaction network and putative pharmaceutical properties are essential to develop new drug with a more controlled and described activity. Recently experimental and clinical informations had increased the attention over heparan sulfate (HS)/ heparin (Hep) coagulant and not coagulant activity opening new fields of research oriented to develop new therapeutical strategy involving heparin usage. Hep mimetics/dericvatives can be extremely helpful from this perspective, due to their controlled nature, molecular features and structure, thus they can be employed as performance drugs. My Ph.D. thesis deals with statistical characterisation of commercial and not commercial pharmaceutical heparin, composition and structural characterisation of heparin mimetics and characterisation of protein-heparin interaction for drug design strategy. Thesis focus was oriented on three different subject: 1) build a library of accepted and well charaterised heparins, set up a statistical analysis based on a principal component analysis (PCA) approach to statistically define heparin molecular nature and to develop a new heparin quality control procedure. 2) 1D/2D NMR interaction studies (1H, TOCSY, NOESY, ROESY, trNOE and STD) to understand the importance of heparin antithrombin (AT) binding domain (AT-bd, the pentasaccharide β-D-N-acetylated,6-O-sulfated glucosamine -α(1->4)-D-glucuronic acid -β(1->4)-D-N-sulfated,3,6-O-sulfated glucosamine -α(1->4)-D-2-O-sulfated iduronic acid -α(1->4)-D-N-sulfated,6-O-sulfated glucosamine, also abbreviated as AGA*IA) flanking residues over AT activation on octasaccharides bearing the pentasaccharide sequence with normal or modified reducent residue in complex with AT. 3) dynamic light scattering (DLS) studies on amyloid beta 1-40 (Aβ1-40)-heparin or heparin mimetics/derivatives as a new strategy to counter act Aβ aggregation progression involved in Alzheimer disease (AD) and better understand the deep relationship between Aβ peptide and GAGs
Backbone and side-chain (1)H, (15)N, (13)C assignment and secondary structure of BPSL1445 from Burkholderia pseudomallei
No full textBPSL1445 is a lipoprotein produced by the Gram-negative bacterium Burkholderia pseudomallei (B.pseudomallei), the etiological agent of melioidosis. Immunodetection assays against sera patients using protein microarray suggest BPSL1445 involvement in melioidosis. Herein we report backbone, side chain NMR assignment and secondary structure for the recombinant protein
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe 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
Get PDF“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
Get PDFWe 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
Get PDFWe 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
No full textWe 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
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