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Synthesis of Neoglycoproteins as Potential Biomarkers for Chagas Disease and Cutaneous Leishmaniasis Caused by Leishmania (Viannia) Braziliensis
No full textProtozoan parasites are responsible for causing numerous diseases in humans and mammals worldwide. Among them are Chagas disease (CD), caused by the parasite Trypanosoma cruzi (T. cruzi), and tegumentary leishmaniasis (TL), caused by the parasite Leishmania (Viannia). Both diseases coexist in many regions of Latin America, and current hurdles to differentiallydiagnose them and determine chemotherapy success need to be overcome. CD can be diagnosed by traditional serological tests and polymerase chain reaction (PCR), but disadvantages of thesemethods are that they may produce false negatives because the antigens used in commercial CD kits are not conserved across all T.cruzi genotypes. Additionally, to determine the treatment efficacy by conventional serology would have to rely on negative antibody seroconversion, which takes 10-20 years. On the other hand, PCR might not detect the parasite when its concentration in the blood circulation is below ~0.3-0.5 parasite equivalent/ mL of blood. For CL, traditional diagnostic methods, like microscopy, parasite culture, or PCR, have limitations due to the irregular distribution of parasites in biopsy samples. However, even when parasitemia is low, antibody levels in CD and CL patients remain high, with the CD or CL-specific anti-a-Gal antibodies being universally present. The infective form of T. cruzi expresses glycosylphosphatidylinositol (GPI)-anchored mucins (tGPI mucins) with unusual immunogenic glycans having terminal nonreducing a-Galp residues. Besides, another immunogenic moiety, b-galactofuranose (bGalf), is believed to be contained in the (GPI)-anchor. Most of those oligosaccharides are branched and their precise structures remain unknown. The CD-specific anti-a-Gal Abs show a rapid seroconversion within 2-3 years or less, following chemotherapy, making them potential candidates for diagnosis and monitoring post-chemotherapy using serological assays. Similarly, L. (V.) braziliensis expresses a family of low-molecular mass glycoinositolphospholipids (GIPLs), containing terminal a-Galpresidues. So far, the exact structures of the immunodominant glycotopes responsible for eliciting IgG antibodies in CL patients have not been determined. However, neoglycoprotein NGP28b, composed of the trisaccharide Galpa1,6Galpb1,3Galfb derived from the type-2 (GIPL)-3 of Leishmania major and linked to bovine serum albumin (BSA), acts as a reliable serological BMK for L. (V.) braziliensis infection in Brazil. This suggests the existence of GIPL-3 or an analogous structure within this parasite, with its terminal trisaccharide either acting as or constituting an immunodominant glycotope. Given these findings, we investigate specific parasite-derived serological BMKs for CD and CL infection in certain New World regions utilizing chemiluminescent enzyme-linked immunosorbent assay (cELISA). Chapter 1 briefly introduces the hypothesis and specific aims of this study. Chapter 2 demonstrates the background and significance of performing this research in diagnosing and following up CD and CL. Chapter 3 describes the synthesis, optimization steps, and serological evaluation of two b-Galf-containing neoglycoproteins, NGP29b and NGP32b, believed to exist in the GPI anchor of T.cruzi using chronic CD (CCD) patient sera from endemic areas. The biological data obtained suggest that both NGPs are suitable as diagnostic biomarkers for CCD and that the branched tetrasaccharide Galfb1,3Manpa1,2[Galfb1,3]Manpa present in NGP32b is an immunodominant glycotope. In chapter 4, we studied two a-Galp-containing neoglycoproteins, NGP33b and NGP34b, that contain trisaccharide glycans believed to exist in the tGPI mucins of T. cruzi. We present their synthesis and serological evaluation using CD and CL patient sera from endemic areas. Surprisingly, the biological data indicate that the Galpα1,6 containing NGP33b is not suitable for diagnosing CD, but reacts strongly with sera of CL patients, suggesting that the Galp1,6 moiety is an immunodominant glycotope in L.braziliensis. Also described is the partial synthesis of tetrasaccharide G38SH, another glycan structure potentially present in the T. cruzi tGPI mucins, as suggested by glycomics data. Finally, chapter 5 discusses the synthesis of aGalα1,6Galα1,3Galfβ1,3Manα-containing NGP, NGP31b, as a synthetic biomarker for L. (V.) braziliensis CL in comparison to NGP28b. Included is also a study of the glycotope size requirement. In the future, the promising new NGPs should be more deeply studied as diagnostic and/or prognostic BMKs with a larger number of patient samples. If confirmed as BMKs these NGPs could have a substantial impact on public health as they could be used for disease diagnosis and determination of treatment efficacy. One can also envision the development of an affordable lateral flow assay for point-of-care testing in developing countries where access to ELISA technologies is limited
Synthesis Of Neoglycoproteins As Potential Biomarkers For Chagas Disease And Cutaneous Leishmaniasis Caused By Leishmania (viannia) Braziliensis
Get PDFProtozoan parasites are responsible for causing numerous diseases in humans and mammals worldwide. Among them are Chagas disease (CD), caused by the parasite Trypanosoma cruzi (T. cruzi), and tegumentary leishmaniasis (TL), caused by the parasite Leishmania (Viannia). Both diseases coexist in many regions of Latin America, and current hurdles to differentially diagnose them and determine chemotherapy success need to be overcome. CD can be diagnosed by traditional serological tests and polymerase chain reaction (PCR), but disadvantages of these methods are that they may produce false negatives because the antigens used in commercial CD kits are not conserved across all T.cruzi genotypes. Additionally, to determine the treatment efficacy by conventional serology would have to rely on negative antibody seroconversion, which takes 10-20 years. On the other hand, PCR might not detect the parasite when its concentration in the blood circulation is below ~0.3-0.5 parasite equivalent/ mL of blood. For CL, traditional diagnostic methods, like microscopy, parasite culture, or PCR, have limitations due to the irregular distribution of parasites in biopsy samples. However, even when parasitemia is low, antibody levels in CD and CL patients remain high, with the CD or CL-specific anti-a-Gal antibodies being universally present. The infective form of T. cruzi expresses glycosylphosphatidylinositol (GPI)- anchored mucins (tGPI mucins) with unusual immunogenic glycans having terminal nonreducing a-Galp residues. Besides, another immunogenic moiety, b-galactofuranose (bGalf), is believed to be contained in the (GPI)-anchor. Most of those oligosaccharides are branched and their precise structures remain unknown. The CD-specific anti-a-Gal Abs show a rapid seroconversion within 2-3 years or less, following chemotherapy, making them potential candidates for diagnosis and monitoring post-chemotherapy using serological assays. Similarly, L. (V.) braziliensis expresses a family of low-molecular mass glycoinositolphospholipids (GIPLs), containing terminal a-Galp residues. So far, the exact structures of the immunodominant glycotopes responsible for eliciting IgG antibodies in CL patients have not been determined. However, neoglycoprotein NGP28b, composed of the trisaccharide Galpa1,6Galpb1,3Galfb derived from the type-2 (GIPL)-3 of Leishmania major and linked to bovine serum albumin (BSA), acts as a reliable serological BMK for L. (V.) braziliensis infection in Brazil. This suggests the existence of GIPL-3 or an analogous structure within this parasite, with its terminal trisaccharide either acting as or constituting an immunodominant glycotope. Given these findings, we investigate specific parasite-derived serological BMKs for CD and CL infection in certain New World regions utilizing chemiluminescent enzyme-linked immunosorbent assay (cELISA). Chapter 1 briefly introduces the hypothesis and specific aims of this study. Chapter 2 demonstrates the background and significance of performing this research in diagnosing and following up CD and CL. Chapter 3 describes the synthesis, optimization steps, and serological evaluation of two b-Galf-containing neoglycoproteins, NGP29b and NGP32b, believed to exist in the GPI anchor of T.cruzi using chronic CD (CCD) patient sera from endemic areas. The biological data obtained suggest that both NGPs are suitable as diagnostic biomarkers for CCD and that the branched tetrasaccharide Galfb1,3Manpa1,2[Galfb1,3]Manpa present in NGP32b is an immunodominant glycotope. In chapter 4, we studied two a-Galp-containing neoglycoproteins, NGP33b and NGP34b, that contain trisaccharide glycans believed to exist in the tGPI mucins of T. cruzi. We present their synthesis and serological evaluation using CD and CL patient sera from endemic areas. Surprisingly, the biological data indicate that the Galpα1,6 containing NGP33b is not suitable for diagnosing CD, but reacts strongly with sera of CL patients, suggesting that the Galp�1,6 moiety is an immunodominant glycotope in L.braziliensis. Also described is the partial synthesis of tetrasaccharide G38SH, another glycan structure potentially present in the T. cruzi tGPI mucins, as suggested by glycomics data. Finally, chapter 5 discusses the synthesis of a Galα1,6Galα1,3Galfβ1,3Manα-containing NGP, NGP31b, as a synthetic biomarker for L. (V.) braziliensis CL in comparison to NGP28b. Included is also a study of the glycotope size requirement. In the future, the promising new NGPs should be more deeply studied as diagnostic and/or prognostic BMKs with a larger number of patient samples. If confirmed as BMKs these NGPs could have a substantial impact on public health as they could be used for disease diagnosis and determination of treatment efficacy. One can also envision the development of an affordable lateral flow assay for point-of-care testing in developing countries where access to ELISA technologies is limited
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
Author-wise bibliometric analysis based on entropy.
No full textAuthor-wise bibliometric analysis based on entropy.</p
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