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    From food to physiology characterization and in vitro digestion of milk products and investigation of postprandial metabolism and inflammation after a high-fat meal intake in a human nutrition intervention study

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    According to the World Health Organization worldwide obesity has more than doubled since 1980. The World health statistics 2012 report shows that one in six adults is obese, one in ten diabetic and one in three has a raised blood pressure. Overweight and obesity are major risk factors for cardiovascular diseases,According to the World Health Organization worldwide obesity has more than doubled since 1980. The World health statistics 2012 report shows that one in six adults is obese, one in ten diabetic and one in three has a raised blood pressure. Overweight and obesity are major risk factors for cardiovascular diseases, diabetes and some cancers. The causes of overweight and obesity are mainly a decrease in physical activity and an increased intake of energy-dense foods leading to a positive energy balance. Not only dietary patterns play a major role in the development of obesity. Food composition also directly impacts on postprandial metabolism and inflammation and, in long term, may contribute to systemic low-grade inflammation, a characteristic associated with the obese state. Thus it is not surprising that there is a growing interest in better understanding the effect of different foods and food compounds on human metabolism and health. The aim of the NutriChip project is to develop a microfluidic chip device to screen foods and their compounds for health promoting, e.g. immune-modulatory, properties. Milk products have been chosen as a food model because their consumption has been shown to be associated with decreased levels of inflammatory markers (1), and also because technological and microbiological transformations allow the realization of various products, such as yoghurt and cheese, having potentially different physiological effects. This thesis covers the biochemical (products characterization and in vitro digestion) and physiological (human nutrition study) aspects of the NutriChip project. Initially, differently heat-treated and fermented milk products were characterized by a proteomic approach. Various fractionation methods were used for selectively enriching minor milk and bacterial proteins in different dairy products. Proteins were separated and identified by two dimensional (2D) gel-electrophoresis and liquid chromatography coupled to mass spectrometry (LC-MS/MS) analysis. All data are collected in an interactive platform, called protein atlas, which is now publicly available on http://www.foodle.ch/de/proteinstart. Currently, the database contains more than 200 different milk proteins and about 250 bacterial proteins. For a better in depth characterization of fermented products, a method for the enrichment of living bacterial cells has been developed. This method allows the investigation of bacterial proteomes under different fermentation conditions. The method was used to monitor the adaption of the yoghurt bacteria Lactobacillus bulgaricus and Streptococcus thermophilus during milk fermentation. Some well-known stress response proteins (chaperone proteins GroEL and DnaK) and various enzymes involved in the glycolysis pathway have been identified as a proof of concept. Another experiment aimed to investigate the bacterial proteome during cheese production with special regards towards the identification of enzymes involved in the formation of the cheese flavor compound 3-methylbutanal. An aminotransferase that catalyzes the first step in the conversion pathway from the amino acid leucine to the flavor compound 3-methylbutanal could be identified. A prerequisite for screening foods for health-modulating activity was the development of a static, three-step in vitro digestion model. The aim was to keep the model as physiological as possible and ideally perform the digestion on a small scale (volume < 15 mL). The digestion model has been thoroughly validated using pasteurized whole milk. The degradation of fat, carbohydrates and proteins into their basic constituents was consistent with human physiological values found in the literature. The system has been used to digest various milk products. With the two proteins α-s1-casein and β-lactoglobulin, a representative of the caseins and whey proteins, respectively, the influence of the fat content, heat treatment and fermentation of the products on their digestibility has been monitored. Particularly we also looked at the generation of bioactive peptides during the digestion process. Towards this aim, the identified peptides in the digestion experiments were compared with bioactive peptide sequences from the literature using the statistic program R. Over 50 milk protein-derived peptides containing bioactive peptide sequences, with e.g. antihypertensive, immune- and cyto-modulatory, opioid functions, could be identified. The next step in simulating the human digestive system is the intestinal transport. Therefore, a cell culture model mimicking the last step of digestion and final absorption of the nutrients, both steps being mediated by intestinal enterocytes, was established. For this aim, Caco-2 cells were used in a Transwell system with an upper and lower compartment containing cell culture medium. Digested milk products were added on top of the Caco-2 cell monolayer and medium was collected from the basolateral chamber for identification of transported, potential bioactive peptides. The final validation of the in vitro models needs the comparison with a human nutrition intervention study. We designed and conducted a dose-response intervention study to determine the caloric dose (500 kcal, 1’000 kcal, 1’500 kcal) of a high-fat meal needed to induce a postprandial metabolic and inflammatory response in normal weight and obese subjects. In our study, we investigated postprandial metabolism and inflammation by measuring classical clinical parameters such as glucose, insulin and triglycerides, as well as the inflammation markers C-reactive protein (CRP), interleukine-6 (IL-6) and endotoxin before and at various time points after the test meals consumption. Our study provided valuable clinical, mechanistic, and methodological insights into the metabolic response of subjects, varying in their metabolic health status, to increasing doses of a high-fat meal. This represents the basis for future studies aiming to investigate health-promoting properties of foods in general, as also their capability in lowering postprandial inflammation, a normal response mechanism after food ingestion. v diabetes and some cancers. The causes of overweight and obesity are mainly a decrease in physical activity and an increased intake of energy-dense foods leading to a positive energy balance. Not only dietary patterns play a major role in the development of obesity. Food composition also directly impacts on postprandial metabolism and inflammation and, in long term, may contribute to systemic low-grade inflammation, a characteristic associated with the obese state. Thus it is not surprising that there is a growing interest in better understanding the effect of different foods and food compounds on human metabolism and health. The aim of the NutriChip project is to develop a microfluidic chip device to screen foods and their compounds for health promoting, e.g. immune-modulatory, properties. Milk products have been chosen as a food model because their consumption has been shown to be associated with decreased levels of inflammatory markers (1), and also because technological and microbiological transformations allow the realization of various products, such as yoghurt and cheese, having potentially different physiological effects. This thesis covers the biochemical (products characterization and in vitro digestion) and physiological (human nutrition study) aspects of the NutriChip project. Initially, differently heat-treated and fermented milk products were characterized by a proteomic approach. Various fractionation methods were used for selectively enriching minor milk and bacterial proteins in different dairy products. Proteins were separated and identified by two dimensional (2D) gel-electrophoresis and liquid chromatography coupled to mass spectrometry (LC-MS/MS) analysis. All data are collected in an interactive platform, called protein atlas, which is now publicly available on http://www.foodle.ch/de/proteinstart. Currently, the database contains more than 200 different milk proteins and about 250 bacterial proteins. For a better in depth characterization of fermented products, a method for the enrichment of living bacterial cells has been developed. This method allows the investigation of bacterial proteomes under different fermentation conditions. The method was used to monitor the adaption of the yoghurt bacteria Lactobacillus bulgaricus and Streptococcus thermophilus during milk fermentation. Some well- known stress response proteins (chaperone proteins GroEL and DnaK) and various enzymes involved in the glycolysis pathway have been identified as a proof of concept. Another experiment aimed to investigate the bacterial proteome during cheese production with special regards towards the identification of enzymes involved in the formation of the cheese flavor compound 3-methylbutanal. An aminotransferase that catalyzes the first step in the conversion pathway from the amino acid leucine to the flavor compound 3-methylbutanal could be identified. v A prerequisite for screening foods for health-modulating activity was the development of a static, three-step in vitro digestion model. The aim was to keep the model as physiological as possible and ideally perform the digestion on a small scale (volume < 15 mL). The digestion model has been thoroughly validated using pasteurized whole milk. The degradation of fat, carbohydrates and proteins into their basic constituents was consistent with human physiological values found in the literature. The system has been used to digest various milk products. With the two proteins α-s1-casein and β-lactoglobulin, a representative of the caseins and whey proteins, respectively, the influence of the fat content, heat treatment and fermentation of the products on their digestibility has been monitored. Particularly we also looked at the generation of bioactive peptides during the digestion process. Towards this aim, the identified peptides in the digestion experiments were compared with bioactive peptide sequences from the literature using the statistic program R. Over 50 milk protein-derived peptides containing bioactive peptide sequences, with e.g. antihypertensive, immune- and cyto-modulatory, opioid functions, could be identified. The next step in simulating the human digestive system is the intestinal transport. Therefore, a cell culture model mimicking the last step of digestion and final absorption of the nutrients, both steps being mediated by intestinal enterocytes, was established. For this aim, Caco-2 cells were used in a Transwell system with an upper and lower compartment containing cell culture medium. Digested milk products were added on top of the Caco-2 cell monolayer and medium was collected from the basolateral chamber for identification of transported, potential bioactive peptides. The final validation of the in vitro models needs the comparison with a human nutrition intervention study. We designed and conducted a dose-response intervention study to determine the caloric dose (500 kcal, 1’000 kcal, 1’500 kcal) of a high-fat meal needed to induce a postprandial metabolic and inflammatory response in normal weight and obese subjects. In our study, we investigated postprandial metabolism and inflammation by measuring classical clinical parameters such as glucose, insulin and triglycerides, as well as the inflammation markers C-reactive protein (CRP), interleukine-6 (IL-6) and endotoxin before and at various time points after the test meals consumption. Our study provided valuable clinical, mechanistic, and methodological insights into the metabolic response of subjects, varying in their metabolic health status, to increasing doses of a high-fat meal. This represents the basis for future studies aiming to investigate health- promoting properties of foods in general, as also their capability in lowering postprandial inflammation, a normal response mechanism after food ingestion.LMIS

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    The 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

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    “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

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    We 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

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    We 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

    Author Index

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    koamabayili/VECTRON-author-checklist: VECTRON author checklist

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    We 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 Under Sail The Imagination of Jack London, 1893-1902

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    In Author Under Sail, Jay Williams offers the first complete literary biography of Jack London as a professional writer engaged in the labor of writing. It examines the authorial imagination in London's work, the use of imagination in both his fiction and nonfiction, and the ways he defined imagination in the creative process in his business dealings with his publishers, editors, and agents. In this first volume of a two-volume biography, Williams traverses the years 1893 to 1902, from London's "Story of a Typhoon" to The People of the Abyss. The Jack London who emerges in the pages of Author Under Sail is a writer whose partnership with publishers, most notably his productive alliance with George Brett of Macmillan, was one of the most formative in American literary history. London pioneered many author models during the heyday of realism and naturalism, blurring the boundaries of these popular genres by focusing on absorption and theatricality and the representation of the seen and unseen. London created an impassioned, sincere, and extremely personal realism unlike that of other American writers of the time. Author Under Sail is a literary tour de force that reveals the full range of London as writer, creative citizen, and entrepreneur at the same time it sheds light on the maverick side of machine-age literature.Intro -- Title Page -- Copyright Page -- Dedication -- Contents -- Acknowledgments -- Introduction -- 1. Spirit Truth -- 2. From Absorption to Theatricality and Back Again -- 3. "I Will Build a New Present" -- 4. Sons as Authors -- 5. Fathers as Publishers -- 6. The Daughter as Author -- 7. Lovers as Authors -- 8. At Sea with the Family -- 9. Yellow News, Yellow Stories -- 10. The Return Home -- Notes -- Bibliography -- Index -- About Jay WilliamsIn Author Under Sail, Jay Williams offers the first complete literary biography of Jack London as a professional writer engaged in the labor of writing. It examines the authorial imagination in London's work, the use of imagination in both his fiction and nonfiction, and the ways he defined imagination in the creative process in his business dealings with his publishers, editors, and agents. In this first volume of a two-volume biography, Williams traverses the years 1893 to 1902, from London's "Story of a Typhoon" to The People of the Abyss. The Jack London who emerges in the pages of Author Under Sail is a writer whose partnership with publishers, most notably his productive alliance with George Brett of Macmillan, was one of the most formative in American literary history. London pioneered many author models during the heyday of realism and naturalism, blurring the boundaries of these popular genres by focusing on absorption and theatricality and the representation of the seen and unseen. London created an impassioned, sincere, and extremely personal realism unlike that of other American writers of the time. Author Under Sail is a literary tour de force that reveals the full range of London as writer, creative citizen, and entrepreneur at the same time it sheds light on the maverick side of machine-age literature.Description based on publisher supplied metadata and other sources.Electronic reproduction. Ann Arbor, Michigan : ProQuest Ebook Central, YYYY. Available via World Wide Web. Access may be limited to ProQuest Ebook Central affiliated libraries
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