1,720,968 research outputs found
Nutrigenomics in human peripheral blood mononuclear cells : the effects of fatty acids on gene expression profiles of human circulating cells as assessed in human intervention studies
No full textResearch on the effects of nutrition on the function and health of organs in the human body, such as liver and intestine, is difficult, because for this research organ tissue is needed. Since nutrition research is usually performed in healthy volunteers, this tissue is difficult to obtain. However, to find out what happens on cellular level we do need human cells. Because blood cells are transported through the entire body and are relatively easy to obtain, these cells are ideal to study the effect of nutrition on cellular level. For this research we used the latest molecular genomics techniques to study the activity (on/off switching, increase/decrease) of all our genes at once. We found that consumption of different types of fat, both directly after consumption and after continued intake, changed the activity of specific groups of genes in these cells. With this research we have shown that the subtle effects of nutrition can be studied using nutrigenomics techniques in humans by using blood cells
High fat challenges and detection of early perturbations in endothelial health : the use of a comprehensive phenotyping approach
No full text Background:Cardiovascular disease (CVD) is one of the leading causes of morbidity and mortality worldwide. One of the pathophysiology’s that play a pivotal role in the development and progression of CVD is a dysfunctional endothelium. An important lifestyle risk factor for endothelial dysfunction is the diet and several nutrients have been classified to be either beneficial or harmful for the endothelium. Although CVD usually affects middle-aged or older adults, the onset of endothelial dysfunction begins in early life, emphasising the need for primary prevention. We therefore aimed to identify markers of early perturbations in endothelial health by using dietary stressors, e.g. high fat (HF) challenge test. Thereafter we aimed to evaluate if the potential early markers are reversible and can be improved after an intervention with a dietary anti-stressor. Methods:First we validated the HF challenge test as a tool to trigger the endothelial response capacity. For that purpose, we compared the postprandial response after a HF shake with an average breakfast shake in young healthy men by assessing several plasma markers and functional measures of endothelial function. To identify new markers for early perturbations in endothelial health and to optimized the HF challenge test we applied three HF challenges differing in fatty acid type in two populations of middle-aged men, i.e. one at high- and one at low risk for developing CVD and characterized the postprandial response by applying high-throughput metabolomic and transcriptomic tools next to an extensive phenotyping of vascular function and vascular health parameters. Lastly, we evaluated if the, in the studies above, identified potential early biomarker profile is reversible and can be improved after an intervention with a dietary anti-stressor by means of a high flavanol chocolate intervention. Results:In young men, we observed that a HF challenge decreased flow mediated dilation (FMD), but this decrease was also found after the consumption of an average breakfast shake. IL-8 concentrations were more pronouncedly increased after HF shake consumption compared to an average breakfast control shake. In middle-aged men, a HF challenge decreased the augmentation index (AIX) and elicited an activated state of cellular adherence in the circulation as determined by increased plasma soluble adhesion molecules, increased leukocyte cell surface integrin and selectin expression and increased number of leukocytes. A challenge high in mono-unsaturated fatty acids (MUFAs) elicited the highest postprandial triglyceride (TG) concentrations and the most pronounced effects on AIX. By applying high-throughput metabolomic tools, we observed that oxylipin profiles were affected by the HF challenge and that these changes were depended on dietary fatty acid composition. Application of transcriptome profiling revealed that changes in peripheral blood mononuclear cell (PBMC) gene expression profiles after a HF challenge test were different between lean and obese subjects, with the most deviating effect after MUFA intake. The saturated fatty acid (SFA) shake decreased the expression of genes involved in cholesterol uptake and cholesterol biosynthesis and increased expression of genes involved in cholesterol efflux. MUFA increased expression of inflammatory genes and of peroxisome proliferator-activated receptor α (PPARα) target genes involved in β-oxidation. 4-week daily intake of a dietary anti-stressor, e.g. dark chocolate, increased fasting FMD and decreased AIX, and elicited a less activated state of cellular adherence, as determined by a decrease in plasma soluble adhesion molecules, a decrease in leukocyte cell surface integrin and selectin expression and a decrease in the number of leukocytes. Conclusions:In this thesis we extensively characterized the postprandial response to a HF challenge in human subjects with different disease risk profiles and optimized the HF challenge test. We identified MUFAs as most potent fatty acids to trigger the vascular and cellular response capacity, which makes it the optimal fatty acid type to use in a HF challenge test. We demonstrated that besides functional measures of vascular function, also plasma and cellular factors involved in leukocyte adhesion to the endothelium are adversely affected by dietary stressors and are beneficially affected by a dietary anti-stressor. Therefore, we conclude that endothelial health can be more comprehensively measured by means of a biomarker profile consisting not only of the vascular function measures FMD and AIX, but also of a subset of soluble adhesion molecules in the plasma, leukocyte counts and cell surface integrin and selectin expression. To identify potential new leads for biomarkers, we applied whole genome gene expression profiling, combined with the HF challenge test which enabled us to detect small differences in health status. Furthermore, we identified metabolic and inflammatory pathways that are specifically affected by either MUFAs or SFAs. These findings increased our understanding on how a SFA or MUFA challenge exert their distinct effects on stress related and metabolic compensatory cellular processes and provided us with new potential leads to detect early perturbations in endothelial health.</p
The transcriptome as early marker of diet-related health : evidence in energy restriction studies in humans
No full textBackground: Nutrition research is facing several challenges with respect to finding diet related health effects. The effects of nutrition on health are subtle, show high interindividual variations in response, and can take long before they become visual. Recently, the definition of health has been redefined as an organism’s ability to adapt to challenges and ‘this definition’ can be extended to metabolic health. In the metabolic context the ability to adapt has been named ‘phenotypic flexibility’. A potential new tool to magnify the effects of diet on health is the application of challenge tests. Combined with a comprehensive tool such as transcriptomics, the study of challenge tests before and after an intervention might be able to test a change in phenotypic flexibility. A dietary intervention well-known to improve health through weight loss is energy restriction (ER). ER can be used as a model to examine the potential of challenge tests in combination with transcriptomics to magnify diet-induced effects on health. As opposed to ER, caloric restriction (CR) is a reduction in energy intake aimed at improving health and life span in non-obese subjects and not directly aimed at weight loss. In this thesis, we aimed to investigate the use of the transcriptome as an early and sensitive marker of diet-related health.Methods: First we studied the consequences of age on the effects of CR on the peripheral blood mononuclear cells (PBMCs) transcriptome. For that purpose, we compared the changes in gene expression in PBMCs from old men with the changes in gene expression in PBMCs from young men upon three weeks of 30% CR. To study the effect of a change in dietary composition during ER, we compared the changes in gene expression upon a 12 weeks high protein 25% ER diet with the changes in gene expression upon a 12 weeks normal protein 25% ER diet in white adipose tissue (WAT). Next, we investigated the added value of measuring the PBMC transcriptome during challenge tests compared to measuring the PBMC transcriptome in the fasted state to magnify the effects of ER on health. This was investigated by measuring the changes in gene expression upon an oral glucose tolerance test (OGTT) and upon a mixed meal test (MMT), both before and after 12 weeks of 20% ER. Finally, we determined the differences between a challenge test consisting of glucose alone, the OGTT, or consisting of glucose plus other macronutrients, the MMT, on the PBMC transcriptome in diet-related health.Results: We observed that the transcriptome of PBMCs of healthy young men had a higher responsiveness in immune response pathways compared to the transcriptome of PBMCs of aged men upon CR (chapter 2). Also, we showed that upon a normal protein-ER diet the transcriptome of WAT showed a decrease in pathways involved in immune response and inflammasome, whereas no such effect was found upon a high protein-ER diet. These effect were observed while parameters such as weight loss, glucose, and waist circumference did not change due to the different protein quantities (chapter 3). 12 weeks of 20% ER was shown to increase phenotypic flexibility as reflected by a faster and more pronounced downregulation of OXPHOS, cell adhesion, and DNA replication during the OGTT compared to the control diet (chapter 4). Finally, two challenge tests consisting of either glucose (OGTT) or glucose plus fat and protein (MMT), were shown to result in a larger overlap than difference in the changes in gene expression of PBMCs (chapter 5).Conclusions: Based on the differential changes in gene expression upon CR at different ages, we concluded that age is an important modulator in the response to CR. As a high protein ER diet induced transcriptional changes seemed to reflect less beneficial health effects than a normal protein ER diet we concluded that the diet composition is important in the health-effect of ER as measured by the transcriptome. Based on the faster PBMCs changes in gene expression during an OGTT upon 12 weeks of 20% ER, we concluded that the PBMC transcriptome combined with a challenge test can reflect changes in phenotypic flexibility. This makes challenge tests a suitable tool to study diet-related health effects. Finally, based on the changes in gene expression of the MMT and OGTT, we conclude that glucose in a challenge test is the main denominator of the postprandial changes in gene expression in the first two hours. Overall, these results lead to the conclusion that the transcriptome, especially in combination with challenges test, can be used as an early marker of diet-related health. The direct relation to health still needs to be investigated, but the possibility to use the transcriptome as an early marker of diet-related health gives rise to a better understanding of the effects of nutrition on health
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
Dispelling the Myths Behind First-author Citation Counts
Full text linkWe 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
Prostate cancer risk and recurrence: the role of nutrition and clinical aspects
No full text Background Prostate cancer is the most common cancer among men in Western countries. Knowledge on prostate cancer aetiology is required for identification of high-risk groups, optimization of treatment strategies, and development of prevention programs. The aim of this thesis was toobtain insight into nutritional and clinical factors relevant to different stages of prostate cancer. Methods and results First, an inventory of potential risk factors for prostate cancer was made by asking 956 patients with prostate cancer about perceived causes of their disease. Among the 143 patients who provided self-reported causes, heredity, specific environmental factors, nutrition or lifestyle, and stress were most frequently reported. Second, two potential risk factors, i.e. blood lipid levels and a previous cancer diagnosis, for incident prostate cancer were evaluated. Higher levels of total and LDL cholesterol were significantly associated with an increased risk of (aggressive) prostate cancer after 6.5 years of follow-up in a population-based cohort of 2,118 men (43 cases). Analyses from another population-based cohort among 551,553 men (9,243 cases) showed that cancer survivors diagnosed with a first cancer (other than prostate cancer) between 1989 and 2008 had an overall increased risk of prostate cancer in the first year after their first cancer diagnosis. This increased prostate cancer risk is most likely the result of active screening or incidental detection, because the effects disappeared after one year of follow-up for most of the specific first cancer sites. Third, the effect of body mass index (BMI) on risk of biochemical recurrence was studied in two cohorts of 493 patients (142 cases) and 1,302 patients (297 cases) treated with radical prostatectomy for prostate cancer. BMI was not associated with risk of biochemical recurrence in these patients. Finally, the effects of selenium, a suggested candidate for prostate cancer chemoprevention, on gene expression profiles in the prostate were examined in a randomized and placebo-controlled intervention trial with 15 participants (n=8 selenium, n=7 placebo). Selenium (300 µg/day as selenized yeast) affected the expression of genes towards an anti-inflammatory gene expression profile. Furthermore, we were able to detect expression changes in genes implicated in the epithelial-to-mesenchymal transition. Conclusion The results of this thesis show that specific nutritional and clinical factors might influence risk of prostate cancer or have an effect on gene expression in the prostate. A future challenge is the confirmation and 'translation' of these findings into the development and implementation of effective treatment and prevention strategies for prostate cancer.</p
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