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Developing immune-regulatory materials using immobilized monosaccharides with immune-instructive properties
No full textDataset contains raw and processed data used for the creation of figures in publication "Developing immune-regulatory materials using immobilized monosaccharides with immune-instructive properties
Discovering novel immune-modulatory monosaccharides using high-throughput screening strategies
Get PDFIntroduction: New strategies for immunomodulation and immunotherapy to fight infections, allergic diseases and cancer have shown real promise in recent years. Dendritic cells (DCs) are considered gatekeepers of the immune system and act as a bridge between innate and adaptive immune systems. Upon antigen uptake in peripheral tissues, DCs migrate to the lymph nodes and interact with T cells where they guide T cell polarisation towards distinct inflammatory or regulatory phenotypes. Their ability in shaping adaptive immune responses makes DCs ideal targets for immune modulation. The immune-instructive properties of DCs upon encountering T cells are dependent on their cytokine profile and the co-stimulatory molecules expressed. In this project, I used a high throughput screening strategy to investigate immune modulatory properties of a combinatorial library of immobilised synthetic monosaccharides with a particular focus on their ability to modulate key phenotypic and functional properties of human DCs. I also investigated the modulatory properties of these monosaccharides in particulate form, using gold nanoparticles (AuNPs) coated with monosaccharides, and studied their impact on DCs phenotype and function as well as identifying sugar moieties that enhance uptake of the AuNPs.
Results: A selection of immobilised carbohydrates including 100%1-amino-1-deoxy--Dgalactose (Gal1), 100%2-amino-2-deoxy--D-galactose (Gal2), 90%2-amino-2-deoxy--Dgalactose+10%1-amino-1-deoxy--D-mannose (Gal2-Man1), 2-amino-2-deoxy--Dgalactose+10%2-amino-2-deoxy--D-mannose (Gal2-Man2), 40%1-amino-1-deoxy--Dmannose + 60%2-amino-2-deoxy--D-mannose (Man1-Man2) and 50%1-amino-1-deoxy-- D-galactose +50%2-amino-2-deoxy--D-galactose (Gal1-Gal2), significantly downregulated LPS induced CD40 expression, compared to LPS alone, upregulated CD274 but had no significant changes in the expression of CD86 compared to unconditioned LPS stimulated controls. This was accompanied by a significant decrease in the activity of key immune regulatory enzyme 2,3 indoleamine dioxygenase (IDO) and production of interleukin (IL)-12, a signature pro-inflammatory cytokine. Furthermore, DCs stimulated with the same combinations of carbohydrates showed a significant increase in production of prototypic regulatory cytokine IL-10. Collectively these data suggest an anti-inflammatory/regulatory phenotype for DCs treated with these carbohydrates. Furthermore, DCs conditioned with a selection of anti-inflammatory carbohydrates (Gal1-Gal2 and Gal1) induced naïve T cell polarisation towards regulatory phenotype while other carbohydrate combinations shown to increase IL-12 production (Man1-Man2, Gal2-Man1 and Gal2-Man2) induced T-helper 1 phenotype confirming the anti and prof inflammatory DC phenotypes respectively. Moreover, an increase in IL-17 and RORγt expression confirmed presence of TH17 in conditions treated with Gal1 and Gal1-Gal2 while a decrease in the latter was noted in Man1-Gal2. This was also confirmatory in the allergy module where Gal1-Gal2 maintained production of IL-17 and Man1-Gal2 had significant reduction in IL-17 clearly showing the carbohydrates potential in immunomodulation. Carbohydrate coated AuNPs showed differential uptake by DCs where 100%fucose, 100%mannose, 90%mannose+10%Galactose and 80%mannose+20%Galactose coated AuNPs had highest internalization. Flow cytometry showed increased lysosomal and endosomal localisation for AuNPs coated with 100%fucose over the other conditions compared to uncoated AuNPs. Investigations of the fate of the particles showed significant increased co-localization of AuNPs with lysosomes for 100%fucose, 80%fucose+20%galactose and 70%galactose+20%mannose compared to other conditions. On the other hand, co-localization of AuNPs with endosomes for 100%mannose was significantly higher than other conditions. An understanding of receptor mediated endocytosis (active uptake) and micropinocytosis (passive uptake) mechanisms was assessed using Methyl-β-cyclodextrins where there was a significant reduction of uptake between Methyl-β-cyclodextrins treated and untreated conditions suggesting the predominant mechanism of internalization of the AuNPs is active uptake. Conclusions: Collectively these observations show the potential immunomodulatory effects of immobilised monosaccharides in priming DCs and skewing immune responses towards different functional pro- or anti-inflammatory/regulatory phenotypes. It also provides insights into using monosaccharides to optimize cellular uptake of nanoparticles as well as guiding trafficking towards different intracellular compartments. This understanding could pave the way for utilising simple monosaccharides in the development of anti-inflammatory coatings for graft implants and reduction of chronic inflammatory and autoimmune responses as well as potent drug delivery platforms guided towards antigen delivery and RNA silencing therapies
Discovering novel immune-modulatory monosaccharides using high-throughput screening strategies
Get PDFIntroduction: New strategies for immunomodulation and immunotherapy to fight infections, allergic diseases and cancer have shown real promise in recent years. Dendritic cells (DCs) are considered gatekeepers of the immune system and act as a bridge between innate and adaptive immune systems. Upon antigen uptake in peripheral tissues, DCs migrate to the lymph nodes and interact with T cells where they guide T cell polarisation towards distinct inflammatory or regulatory phenotypes. Their ability in shaping adaptive immune responses makes DCs ideal targets for immune modulation. The immune-instructive properties of DCs upon encountering T cells are dependent on their cytokine profile and the co-stimulatory molecules expressed. In this project, I used a high throughput screening strategy to investigate immune modulatory properties of a combinatorial library of immobilised synthetic monosaccharides with a particular focus on their ability to modulate key phenotypic and functional properties of human DCs. I also investigated the modulatory properties of these monosaccharides in particulate form, using gold nanoparticles (AuNPs) coated with monosaccharides, and studied their impact on DCs phenotype and function as well as identifying sugar moieties that enhance uptake of the AuNPs.
Results: A selection of immobilised carbohydrates including 100%1-amino-1-deoxy--Dgalactose (Gal1), 100%2-amino-2-deoxy--D-galactose (Gal2), 90%2-amino-2-deoxy--Dgalactose+10%1-amino-1-deoxy--D-mannose (Gal2-Man1), 2-amino-2-deoxy--Dgalactose+10%2-amino-2-deoxy--D-mannose (Gal2-Man2), 40%1-amino-1-deoxy--Dmannose + 60%2-amino-2-deoxy--D-mannose (Man1-Man2) and 50%1-amino-1-deoxy-- D-galactose +50%2-amino-2-deoxy--D-galactose (Gal1-Gal2), significantly downregulated LPS induced CD40 expression, compared to LPS alone, upregulated CD274 but had no significant changes in the expression of CD86 compared to unconditioned LPS stimulated controls. This was accompanied by a significant decrease in the activity of key immune regulatory enzyme 2,3 indoleamine dioxygenase (IDO) and production of interleukin (IL)-12, a signature pro-inflammatory cytokine. Furthermore, DCs stimulated with the same combinations of carbohydrates showed a significant increase in production of prototypic regulatory cytokine IL-10. Collectively these data suggest an anti-inflammatory/regulatory phenotype for DCs treated with these carbohydrates. Furthermore, DCs conditioned with a selection of anti-inflammatory carbohydrates (Gal1-Gal2 and Gal1) induced naïve T cell polarisation towards regulatory phenotype while other carbohydrate combinations shown to increase IL-12 production (Man1-Man2, Gal2-Man1 and Gal2-Man2) induced T-helper 1 phenotype confirming the anti and prof inflammatory DC phenotypes respectively. Moreover, an increase in IL-17 and RORγt expression confirmed presence of TH17 in conditions treated with Gal1 and Gal1-Gal2 while a decrease in the latter was noted in Man1-Gal2. This was also confirmatory in the allergy module where Gal1-Gal2 maintained production of IL-17 and Man1-Gal2 had significant reduction in IL-17 clearly showing the carbohydrates potential in immunomodulation. Carbohydrate coated AuNPs showed differential uptake by DCs where 100%fucose, 100%mannose, 90%mannose+10%Galactose and 80%mannose+20%Galactose coated AuNPs had highest internalization. Flow cytometry showed increased lysosomal and endosomal localisation for AuNPs coated with 100%fucose over the other conditions compared to uncoated AuNPs. Investigations of the fate of the particles showed significant increased co-localization of AuNPs with lysosomes for 100%fucose, 80%fucose+20%galactose and 70%galactose+20%mannose compared to other conditions. On the other hand, co-localization of AuNPs with endosomes for 100%mannose was significantly higher than other conditions. An understanding of receptor mediated endocytosis (active uptake) and micropinocytosis (passive uptake) mechanisms was assessed using Methyl-β-cyclodextrins where there was a significant reduction of uptake between Methyl-β-cyclodextrins treated and untreated conditions suggesting the predominant mechanism of internalization of the AuNPs is active uptake. Conclusions: Collectively these observations show the potential immunomodulatory effects of immobilised monosaccharides in priming DCs and skewing immune responses towards different functional pro- or anti-inflammatory/regulatory phenotypes. It also provides insights into using monosaccharides to optimize cellular uptake of nanoparticles as well as guiding trafficking towards different intracellular compartments. This understanding could pave the way for utilising simple monosaccharides in the development of anti-inflammatory coatings for graft implants and reduction of chronic inflammatory and autoimmune responses as well as potent drug delivery platforms guided towards antigen delivery and RNA silencing therapies
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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