<b>Copyright information:</b>Taken from "Dissecting complex transcriptional resp... more <b>Copyright information:</b>Taken from "Dissecting complex transcriptional responses using pathway-level scores based on prior information"http://www.biomedcentral.com/1471-2105/8/S6/S6BMC Bioinformatics 2007;8(Suppl 6):S6-S6.Published online 27 Sep 2007PMCID:PMC1995543.in as measured by Hughes et al. [27]. The two-sample t-test reveals that the mean expression level of genes in the GO category "ergosterol biosynthesis" is significantly higher than expected (dotted line; = 7.4; = 1.1·10). Fisher's exact test can be used to score over-representation of the same GO category in the set of most induced genes. However, this requires one to first define a threshold for the expression fold-change of individual genes. The solid line shows how the P-value from Fisher's exact test depends on this threshold.
Background Conventional clinical trials are essential for generating high-quality evidence by mea... more Background Conventional clinical trials are essential for generating high-quality evidence by measuring the efficacy of interventions in rigorously controlled clinical environments. However, their execution can be expensive and time-consuming. In addition, clinical trials face several logistical challenges regarding the identification, recruitment, and retention of participants; consistent data collection during trials; and adequate patient follow-up. This might lead to inefficient resource utilization. In order to partially address the current problems with conventional clinical trials, there exists the need for innovations. One such innovation is the virtual clinical trial (VCT). VCTs allow for the collection and integration of diverse data from multiple information sources, such as electronic health records, clinical and demographic data, patient-reported outcomes, anthropometric and activity measurements, and data collected by digital biomarkers or (small) samples that participa...
Type 2 Diabetes (T2D) is a chronic disease diagnosed based on fasting plasma glucose (FPG). A FPG... more Type 2 Diabetes (T2D) is a chronic disease diagnosed based on fasting plasma glucose (FPG). A FPG > 6.9 mmol/L may result in the diagnosis of T2D by the general physician (GP) and result in general lifestyle advice to eat less and be more physically active. Because T2D can have different causes by the failure of one or multiple organs (especially pancreas, liver and muscle), it is of importance to determine this for a patient. Each specific organ failure will result in another lifestyle advice (diet, exercise or the combination). The aim of the present study was to examine whether this T2D subtyping resulted in a higher efficacy of the assigned lifestyle interventions as compared to general lifestyle advice.118 newly diagnosed T2D subjects of multiple primary care practices in Hillegom, The Netherlands, participated. 60 subjects underwent a lifestyle treatment, coached by a dietitian and physiotherapist, based on the outcome of an Oral Glucose Tolerance Test (OGTT) at baseline. B...
Citrate uptake in Bacillus subtilis is mediated by a secondary transporter that transports the co... more Citrate uptake in Bacillus subtilis is mediated by a secondary transporter that transports the complex of citrate and divalent metal ions. The gene coding for the transporter termed CitM was cloned, sequenced, and functionally expressed in Escherichia coli. Translation of the base sequence to the primary sequence revealed a transporter that is not homologous to any known secondary transporter. However, CitM shares 60% sequence identity with the gene product of open reading frame N15CR that is on the genome of B. subtilis and for which no function is known. The hydropathy profiles of the primary sequences of CitM and the unknown gene product are very similar, and secondary structure prediction algorithms predict 12 transmembrane-spanning segments for both proteins. Open reading frame N15CR was cloned and expressed in E. coli and was shown to be a citrate transporter as well. The transporter is termed CitH. A remarkable difference between the two transporters is that citrate uptake by...
Personalized nutrition is fast becoming a reality due to a number of technological, scientific, a... more Personalized nutrition is fast becoming a reality due to a number of technological, scientific, and societal developments that complement and extend current public health nutrition recommendations. Personalized nutrition tailors dietary recommendations to specific biological requirements on the basis of a person's health status and goals. The biology underpinning these recommendations is complex, and thus any recommendations must account for multiple biological processes and subprocesses occurring in various tissues and must be formed with an appreciation for how these processes interact with dietary nutrients and environmental factors. Therefore, a systems biology-based approach that considers the most relevant interacting biological mechanisms is necessary to formulate the best recommendations to help people meet their wellness goals. Here, the concept of "systems flexibility" is introduced to personalized nutrition biology. Systems flexibility allows the real-time evaluation of metabolism and other processes that maintain homeostasis following an environmental challenge, thereby enabling the formulation of personalized recommendations. Examples in the area of macro-and micronutrients are reviewed. Genetic variations and performance goals are integrated into this systems approach to provide a strategy for a balanced evaluation and an introduction to personalized nutrition. Finally, modeling approaches that combine personalized diagnosis and nutritional intervention into practice are reviewed.
In another project, protein localization was studied by tagging Green Fluorescent Protein (GFP) t... more In another project, protein localization was studied by tagging Green Fluorescent Protein (GFP) to individual proteins . Protein localization within a cell often correlates with, and indicates, function. The subcellular localization of 2,744 proteins was determined, of which 1,000 proteins with an unknown function. (4) The same approach of proteins tagged with a reporter, was used to determine the abundance of proteins in the cell by using GFP fluorescence as a measure for the amount of pro- SAGA and TFIID are involved in gene regulation in a general way; the regulation of more specific gene groups is carried out by specialized transcription factors (TFs). These transcription factors, which should not be confused with the general transcription factors (GTFs), can be Yap1p from the nucleus to the cytoplasm. Under oxidative-stress-inducing conditions, the interaction between Yap1 and Crm1 is inhibited and Yap1 is accumulating in the nucleus, leading to elevated expression of its target genes. Yap1p binds to the 5ʼ-TTASTAA-3ʼ sequence in the promoter region of its target genes. Several of the genes regulated by Yap1p are involved in glutathione metabolism, such as the genes encoding the glutathione-synthesizing enzymes, GSH1 and GSH2. Furthermore, Yap1p regulates the glutathione-dependent antioxidant genes GPX2 and GLR1. In general, Yap1p targets are involved in the detoxification of ROS. In yeast, intracellular Ca 2+ signaling is mediated by the Ca 2+ /calmodulin-dependent phos-Chapter
Transcriptomics in combination with in vitro cell systems is a powerful approach to unravel modes... more Transcriptomics in combination with in vitro cell systems is a powerful approach to unravel modes of action of toxicants. An important question is to which extent the modes of action as revealed by transcriptomics depend on cell type, species and study type (in vitro or in vivo). To acquire more insight into this, we assessed the transcriptomic effects of the immunosuppressive drug cyclosporine A (CsA) upon 6 h of exposure of the mouse cytotoxic T cell line CTLL-2, the thymoma EL-4 and primary splenocytes and compared these to the effects in spleens of mice orally treated with CsA for 7 days. EL-4 and CTLL-2 cells showed the highest similarities in response. CsA affected many genes in primary splenocytes that were not affected in EL-4 or CTLL-2. Pathway analysis demonstrated that CsA upregulated the unfolded protein response, endoplasmic reticulum stress and NRF2 activation in EL-4 cells, CTLL-2 cells and primary mouse splenocytes but not in mouse spleen in vivo. As expected, CsA downregulated cell cycle and immune response in splenocytes in vitro, spleens in vivo as well as CTLL-2 in vitro. Genes up- and downregulated in human Jurkat, HepG2 and renal proximal tubular cells were similarly affected in CTLL-2, EL-4 and primary splenocytes in vitro. In conclusion, of the models tested in this study, the known mechanism of immunotoxicity of CsA is best represented in the mouse cytotoxic T cell line CTLL-2. This is likely due to the fact that this cell line is cultured in the presence of a T cell activation stimulant (IL-2) making it more suitable to detect inhibitory effects on T cell activation.
ABSTRACT This chapter concerns the application of bioinformatics methods to the analysis of toxic... more ABSTRACT This chapter concerns the application of bioinformatics methods to the analysis of toxicogenomics data. The chapter starts with an introduction covering how bioinformatics has been applied in toxicogenomics data analysis, and continues with a description of the foundations of a specific bioinformatics method called text-mining. Next, the integration of text-mining with toxicogenomics data analysis methods is described. Four different areas in toxicogenomics where conventional bioinformatics solutions can be assisted by text-mining are described: class discovery and separation, connectivity mapping, mechanistic analysis, and identification of early predictors of toxicity.
ABSTRACT Food processing is concerned with the proper conversion of raw materials to value added ... more ABSTRACT Food processing is concerned with the proper conversion of raw materials to value added end products fit for consumption. During the process, microbiological contamination of raw materials has to be inactivated and re-contamination during processing or upon product storage has to be prevented. In this chapter, we stress the need for active research and surveillance of the ecology and molecular biology of food spoilage yeasts. We briefly highlight the main developments in the area. Subsequently, the research geared to identifying new anti-yeast targets and the understanding of stress resistance using classical approaches is discussed. Most important is the discussion of sorbic acid resistance, the weak-organic acid food preservative used in the majority of cases. We discuss the evidente in favour of an involvement of ATP driven acid and anion extrusion Pumps in resistance development, but we also highlight the incompleteness of the current model. Modern approaches using genome-wide screening of stress responses offer new tools for an assessment of the full picture of stress reactions. We indicate examples of this and discuss the bioinformatics methods that go with genomics experiments in Order to extract the appropriate knowledge from the data. Yeast stress physiology, genetics and `functional genomics&#39;, is put in a perspective of future research and challenges.
<b>Copyright information:</b>Taken from "Dissecting complex transcriptional resp... more <b>Copyright information:</b>Taken from "Dissecting complex transcriptional responses using pathway-level scores based on prior information"http://www.biomedcentral.com/1471-2105/8/S6/S6BMC Bioinformatics 2007;8(Suppl 6):S6-S6.Published online 27 Sep 2007PMCID:PMC1995543.in as measured by Hughes et al. [27]. The two-sample t-test reveals that the mean expression level of genes in the GO category "ergosterol biosynthesis" is significantly higher than expected (dotted line; = 7.4; = 1.1·10). Fisher's exact test can be used to score over-representation of the same GO category in the set of most induced genes. However, this requires one to first define a threshold for the expression fold-change of individual genes. The solid line shows how the P-value from Fisher's exact test depends on this threshold.
Background Conventional clinical trials are essential for generating high-quality evidence by mea... more Background Conventional clinical trials are essential for generating high-quality evidence by measuring the efficacy of interventions in rigorously controlled clinical environments. However, their execution can be expensive and time-consuming. In addition, clinical trials face several logistical challenges regarding the identification, recruitment, and retention of participants; consistent data collection during trials; and adequate patient follow-up. This might lead to inefficient resource utilization. In order to partially address the current problems with conventional clinical trials, there exists the need for innovations. One such innovation is the virtual clinical trial (VCT). VCTs allow for the collection and integration of diverse data from multiple information sources, such as electronic health records, clinical and demographic data, patient-reported outcomes, anthropometric and activity measurements, and data collected by digital biomarkers or (small) samples that participa...
Type 2 Diabetes (T2D) is a chronic disease diagnosed based on fasting plasma glucose (FPG). A FPG... more Type 2 Diabetes (T2D) is a chronic disease diagnosed based on fasting plasma glucose (FPG). A FPG > 6.9 mmol/L may result in the diagnosis of T2D by the general physician (GP) and result in general lifestyle advice to eat less and be more physically active. Because T2D can have different causes by the failure of one or multiple organs (especially pancreas, liver and muscle), it is of importance to determine this for a patient. Each specific organ failure will result in another lifestyle advice (diet, exercise or the combination). The aim of the present study was to examine whether this T2D subtyping resulted in a higher efficacy of the assigned lifestyle interventions as compared to general lifestyle advice.118 newly diagnosed T2D subjects of multiple primary care practices in Hillegom, The Netherlands, participated. 60 subjects underwent a lifestyle treatment, coached by a dietitian and physiotherapist, based on the outcome of an Oral Glucose Tolerance Test (OGTT) at baseline. B...
Citrate uptake in Bacillus subtilis is mediated by a secondary transporter that transports the co... more Citrate uptake in Bacillus subtilis is mediated by a secondary transporter that transports the complex of citrate and divalent metal ions. The gene coding for the transporter termed CitM was cloned, sequenced, and functionally expressed in Escherichia coli. Translation of the base sequence to the primary sequence revealed a transporter that is not homologous to any known secondary transporter. However, CitM shares 60% sequence identity with the gene product of open reading frame N15CR that is on the genome of B. subtilis and for which no function is known. The hydropathy profiles of the primary sequences of CitM and the unknown gene product are very similar, and secondary structure prediction algorithms predict 12 transmembrane-spanning segments for both proteins. Open reading frame N15CR was cloned and expressed in E. coli and was shown to be a citrate transporter as well. The transporter is termed CitH. A remarkable difference between the two transporters is that citrate uptake by...
Personalized nutrition is fast becoming a reality due to a number of technological, scientific, a... more Personalized nutrition is fast becoming a reality due to a number of technological, scientific, and societal developments that complement and extend current public health nutrition recommendations. Personalized nutrition tailors dietary recommendations to specific biological requirements on the basis of a person's health status and goals. The biology underpinning these recommendations is complex, and thus any recommendations must account for multiple biological processes and subprocesses occurring in various tissues and must be formed with an appreciation for how these processes interact with dietary nutrients and environmental factors. Therefore, a systems biology-based approach that considers the most relevant interacting biological mechanisms is necessary to formulate the best recommendations to help people meet their wellness goals. Here, the concept of "systems flexibility" is introduced to personalized nutrition biology. Systems flexibility allows the real-time evaluation of metabolism and other processes that maintain homeostasis following an environmental challenge, thereby enabling the formulation of personalized recommendations. Examples in the area of macro-and micronutrients are reviewed. Genetic variations and performance goals are integrated into this systems approach to provide a strategy for a balanced evaluation and an introduction to personalized nutrition. Finally, modeling approaches that combine personalized diagnosis and nutritional intervention into practice are reviewed.
In another project, protein localization was studied by tagging Green Fluorescent Protein (GFP) t... more In another project, protein localization was studied by tagging Green Fluorescent Protein (GFP) to individual proteins . Protein localization within a cell often correlates with, and indicates, function. The subcellular localization of 2,744 proteins was determined, of which 1,000 proteins with an unknown function. (4) The same approach of proteins tagged with a reporter, was used to determine the abundance of proteins in the cell by using GFP fluorescence as a measure for the amount of pro- SAGA and TFIID are involved in gene regulation in a general way; the regulation of more specific gene groups is carried out by specialized transcription factors (TFs). These transcription factors, which should not be confused with the general transcription factors (GTFs), can be Yap1p from the nucleus to the cytoplasm. Under oxidative-stress-inducing conditions, the interaction between Yap1 and Crm1 is inhibited and Yap1 is accumulating in the nucleus, leading to elevated expression of its target genes. Yap1p binds to the 5ʼ-TTASTAA-3ʼ sequence in the promoter region of its target genes. Several of the genes regulated by Yap1p are involved in glutathione metabolism, such as the genes encoding the glutathione-synthesizing enzymes, GSH1 and GSH2. Furthermore, Yap1p regulates the glutathione-dependent antioxidant genes GPX2 and GLR1. In general, Yap1p targets are involved in the detoxification of ROS. In yeast, intracellular Ca 2+ signaling is mediated by the Ca 2+ /calmodulin-dependent phos-Chapter
Transcriptomics in combination with in vitro cell systems is a powerful approach to unravel modes... more Transcriptomics in combination with in vitro cell systems is a powerful approach to unravel modes of action of toxicants. An important question is to which extent the modes of action as revealed by transcriptomics depend on cell type, species and study type (in vitro or in vivo). To acquire more insight into this, we assessed the transcriptomic effects of the immunosuppressive drug cyclosporine A (CsA) upon 6 h of exposure of the mouse cytotoxic T cell line CTLL-2, the thymoma EL-4 and primary splenocytes and compared these to the effects in spleens of mice orally treated with CsA for 7 days. EL-4 and CTLL-2 cells showed the highest similarities in response. CsA affected many genes in primary splenocytes that were not affected in EL-4 or CTLL-2. Pathway analysis demonstrated that CsA upregulated the unfolded protein response, endoplasmic reticulum stress and NRF2 activation in EL-4 cells, CTLL-2 cells and primary mouse splenocytes but not in mouse spleen in vivo. As expected, CsA downregulated cell cycle and immune response in splenocytes in vitro, spleens in vivo as well as CTLL-2 in vitro. Genes up- and downregulated in human Jurkat, HepG2 and renal proximal tubular cells were similarly affected in CTLL-2, EL-4 and primary splenocytes in vitro. In conclusion, of the models tested in this study, the known mechanism of immunotoxicity of CsA is best represented in the mouse cytotoxic T cell line CTLL-2. This is likely due to the fact that this cell line is cultured in the presence of a T cell activation stimulant (IL-2) making it more suitable to detect inhibitory effects on T cell activation.
ABSTRACT This chapter concerns the application of bioinformatics methods to the analysis of toxic... more ABSTRACT This chapter concerns the application of bioinformatics methods to the analysis of toxicogenomics data. The chapter starts with an introduction covering how bioinformatics has been applied in toxicogenomics data analysis, and continues with a description of the foundations of a specific bioinformatics method called text-mining. Next, the integration of text-mining with toxicogenomics data analysis methods is described. Four different areas in toxicogenomics where conventional bioinformatics solutions can be assisted by text-mining are described: class discovery and separation, connectivity mapping, mechanistic analysis, and identification of early predictors of toxicity.
ABSTRACT Food processing is concerned with the proper conversion of raw materials to value added ... more ABSTRACT Food processing is concerned with the proper conversion of raw materials to value added end products fit for consumption. During the process, microbiological contamination of raw materials has to be inactivated and re-contamination during processing or upon product storage has to be prevented. In this chapter, we stress the need for active research and surveillance of the ecology and molecular biology of food spoilage yeasts. We briefly highlight the main developments in the area. Subsequently, the research geared to identifying new anti-yeast targets and the understanding of stress resistance using classical approaches is discussed. Most important is the discussion of sorbic acid resistance, the weak-organic acid food preservative used in the majority of cases. We discuss the evidente in favour of an involvement of ATP driven acid and anion extrusion Pumps in resistance development, but we also highlight the incompleteness of the current model. Modern approaches using genome-wide screening of stress responses offer new tools for an assessment of the full picture of stress reactions. We indicate examples of this and discuss the bioinformatics methods that go with genomics experiments in Order to extract the appropriate knowledge from the data. Yeast stress physiology, genetics and `functional genomics&#39;, is put in a perspective of future research and challenges.
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Papers by André Boorsma