Experimental research has revealed components and mechanisms of cellular stress sensing, signalin... more Experimental research has revealed components and mechanisms of cellular stress sensing, signaling, and adaptation. In addition, mathematical modeling has proven to foster the understanding of basic principles of signal transduction and signal processing. In the following, we will give an outline of the modeling process and introduce basic concepts for dynamic model analysis. We briefly review basic dynamic properties of
Antimicrobial peptides (AMPs) may display the ability to penetrate cells, which may be relevant f... more Antimicrobial peptides (AMPs) may display the ability to penetrate cells, which may be relevant for their antibiotic activity. To investigate the relevance of the penetrating activity for the antibiotic activity of AMPs, here we describe a method based on the combined use of confocal microscopy and computational modeling coupled with cell death kinetics.
Progress in Molecular Biology and Translational Science, 2014
Research on the role of mitochondria in aging and disease is rapidly growing. Furthermore, in rec... more Research on the role of mitochondria in aging and disease is rapidly growing. Furthermore, in recent years, it also became clear that mitochondria are dynamic structures undergoing constant and rapid cycles of fusion and fission. The involvement of mitochondria in multiple complex processes makes them a prime target for mathematical and computational modeling. This review consists of two parts. In the first (Section 2), we provide a detailed introduction to the underlying concepts of mathematical modeling to help the reader who is not so familiar with these techniques to judge the requirements and results that can be obtained through modeling. In the second part (Section 3), we review existing mathematical and computational models that investigate mitochondrial dynamics and the role of mitochondria for the aging process.
We studied the dynamics of the proteome of influenza virus A/PR/8/34 (H1N1) infected Madin-Darby ... more We studied the dynamics of the proteome of influenza virus A/PR/8/34 (H1N1) infected Madin-Darby canine kidney cells up to 12 hours post infection by mass spectrometry based quantitative proteomics using the approach of stable isotope labeling by amino acids in cell culture (SILAC). We identified 1311 cell proteins and, apart from the proton channel M2, all major virus proteins. Based on their abundance two groups of virus proteins could be distinguished being in line with the function of the proteins in genesis and formation of new virions. Further, the data indicate a correlation between the amount of proteins synthesized and their previously determined copy number inside the viral particle. We employed bioinformatic approaches such as functional clustering, gene ontology, and pathway (KEGG) enrichment tests to uncover co- regulated cellular protein sets, assigned the individual subsets to their biological function, and determined their interrelation within the progression of vira...
<p>Proteins were selected from the overlap between proteins identified by our approach and ... more <p>Proteins were selected from the overlap between proteins identified by our approach and genes classified as essential for viral reproduction or interacting with viral proteins by Watanabe et al. 2010 <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0094257#pone.0094257-Karlas2" target="_blank">[68]</a>. These proteins were grouped according 453 to their function and put into context by the schematic graphics of the infection cycle.</p
<p>Logarithmic presentation of the protein abundance fold change. For details see <a hre... more <p>Logarithmic presentation of the protein abundance fold change. For details see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0094257#s3" target="_blank">Material and Methods</a>.</p
<p>All normalized time profiles were clustered by a fuzzy clustering algorithm to find modu... more <p>All normalized time profiles were clustered by a fuzzy clustering algorithm to find modules of co-regulated proteins. Enrichment tests for gene ontology terms on each cluster were performed for all proteins with a membership value >0.5 (n = number in brackets). The most significant terms are represented on the right panel (see also <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0094257#pone.0094257.s007" target="_blank">Table S3</a>).</p
<p>The model was used to simulate stepwise thermal transitions from 30°C (the starting cond... more <p>The model was used to simulate stepwise thermal transitions from 30°C (the starting condition) to 37°C, and then from 37°C to 42°C. Outcomes were then tested experimentally by determining Hsf1 phosphorylation levels. (A) Representations of the thermal transitions. (B) Model simulation of Hsf1 phosphorylation during stepwise 30°C–37°C and 37°C–42°C heat shocks. (C) These predictions were tested experimentally by moving exponentially growing cells from 30°C to 37°C for 30 minutes, and then transferring them from 37°C to 42°C for 30 minutes. Proteins were extracted at various time intervals and Hsf1 phosphorylation measured by western blotting. Hsf1 was shown to be transiently induced during the 37°C–42°C transitions. Lambda phosphatase (λ Ppase) controls were included to confirm that Hsf1 phosphorylation had returned to basal levels 30 minutes after a 30°C–37°C heat shock (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0032467#pone-0032467-g002" target="_blank">Figure 2</a>), but that Hsf1 is rapidly phosphorylated following the next 37°C–42°C heat shock. The data reflect the outcomes for at least two independent replicate experiments.</p
Nonalcoholic fatty liver disease (NAFLD) is a common metabolic dysfunction leading to hepatic ste... more Nonalcoholic fatty liver disease (NAFLD) is a common metabolic dysfunction leading to hepatic steatosis. However, NAFLD's global impact on the liver lipidome is poorly understood. Using high-resolution shotgun mass spectrometry, we quantified the molar abundance of 316 species from 22 major lipid classes in liver biopsies of 365 patients, including nonsteatotic patients with normal or excessive weight, patients diagnosed with NAFL (nonalcoholic fatty liver) or NASH (nonalcoholic steatohepatitis), and patients bearing common mutations of NAFLD-related protein factors. We confirmed the progressive accumulation of di- and triacylglycerols and cholesteryl esters in the liver of NAFL and NASH patients, while the bulk composition of glycerophospho- and sphingolipids remained unchanged. Further stratification by biclustering analysis identified sphingomyelin species comprising n24:2 fatty acid moieties as membrane lipid markers of NAFLD. Normalized relative abundance of sphingomyelins SM 43:3;2 and SM 43:1;2 containing n24:2 and n24:0 fatty acid moieties, respectively, showed opposite trends during NAFLD progression and distinguished NAFL and NASH lipidomes from the lipidome of nonsteatotic livers. Together with several glycerophospholipids containing a C22:6 fatty acid moiety, these lipids serve as markers of early and advanced stages of NAFL.
An amendment to this paper has been published and can be accessed via a link at the top of the pa... more An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Experimental research has revealed components and mechanisms of cellular stress sensing, signalin... more Experimental research has revealed components and mechanisms of cellular stress sensing, signaling, and adaptation. In addition, mathematical modeling has proven to foster the understanding of basic principles of signal transduction and signal processing. In the following, we will give an outline of the modeling process and introduce basic concepts for dynamic model analysis. We briefly review basic dynamic properties of
Antimicrobial peptides (AMPs) may display the ability to penetrate cells, which may be relevant f... more Antimicrobial peptides (AMPs) may display the ability to penetrate cells, which may be relevant for their antibiotic activity. To investigate the relevance of the penetrating activity for the antibiotic activity of AMPs, here we describe a method based on the combined use of confocal microscopy and computational modeling coupled with cell death kinetics.
Progress in Molecular Biology and Translational Science, 2014
Research on the role of mitochondria in aging and disease is rapidly growing. Furthermore, in rec... more Research on the role of mitochondria in aging and disease is rapidly growing. Furthermore, in recent years, it also became clear that mitochondria are dynamic structures undergoing constant and rapid cycles of fusion and fission. The involvement of mitochondria in multiple complex processes makes them a prime target for mathematical and computational modeling. This review consists of two parts. In the first (Section 2), we provide a detailed introduction to the underlying concepts of mathematical modeling to help the reader who is not so familiar with these techniques to judge the requirements and results that can be obtained through modeling. In the second part (Section 3), we review existing mathematical and computational models that investigate mitochondrial dynamics and the role of mitochondria for the aging process.
We studied the dynamics of the proteome of influenza virus A/PR/8/34 (H1N1) infected Madin-Darby ... more We studied the dynamics of the proteome of influenza virus A/PR/8/34 (H1N1) infected Madin-Darby canine kidney cells up to 12 hours post infection by mass spectrometry based quantitative proteomics using the approach of stable isotope labeling by amino acids in cell culture (SILAC). We identified 1311 cell proteins and, apart from the proton channel M2, all major virus proteins. Based on their abundance two groups of virus proteins could be distinguished being in line with the function of the proteins in genesis and formation of new virions. Further, the data indicate a correlation between the amount of proteins synthesized and their previously determined copy number inside the viral particle. We employed bioinformatic approaches such as functional clustering, gene ontology, and pathway (KEGG) enrichment tests to uncover co- regulated cellular protein sets, assigned the individual subsets to their biological function, and determined their interrelation within the progression of vira...
<p>Proteins were selected from the overlap between proteins identified by our approach and ... more <p>Proteins were selected from the overlap between proteins identified by our approach and genes classified as essential for viral reproduction or interacting with viral proteins by Watanabe et al. 2010 <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0094257#pone.0094257-Karlas2" target="_blank">[68]</a>. These proteins were grouped according 453 to their function and put into context by the schematic graphics of the infection cycle.</p
<p>Logarithmic presentation of the protein abundance fold change. For details see <a hre... more <p>Logarithmic presentation of the protein abundance fold change. For details see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0094257#s3" target="_blank">Material and Methods</a>.</p
<p>All normalized time profiles were clustered by a fuzzy clustering algorithm to find modu... more <p>All normalized time profiles were clustered by a fuzzy clustering algorithm to find modules of co-regulated proteins. Enrichment tests for gene ontology terms on each cluster were performed for all proteins with a membership value >0.5 (n = number in brackets). The most significant terms are represented on the right panel (see also <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0094257#pone.0094257.s007" target="_blank">Table S3</a>).</p
<p>The model was used to simulate stepwise thermal transitions from 30°C (the starting cond... more <p>The model was used to simulate stepwise thermal transitions from 30°C (the starting condition) to 37°C, and then from 37°C to 42°C. Outcomes were then tested experimentally by determining Hsf1 phosphorylation levels. (A) Representations of the thermal transitions. (B) Model simulation of Hsf1 phosphorylation during stepwise 30°C–37°C and 37°C–42°C heat shocks. (C) These predictions were tested experimentally by moving exponentially growing cells from 30°C to 37°C for 30 minutes, and then transferring them from 37°C to 42°C for 30 minutes. Proteins were extracted at various time intervals and Hsf1 phosphorylation measured by western blotting. Hsf1 was shown to be transiently induced during the 37°C–42°C transitions. Lambda phosphatase (λ Ppase) controls were included to confirm that Hsf1 phosphorylation had returned to basal levels 30 minutes after a 30°C–37°C heat shock (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0032467#pone-0032467-g002" target="_blank">Figure 2</a>), but that Hsf1 is rapidly phosphorylated following the next 37°C–42°C heat shock. The data reflect the outcomes for at least two independent replicate experiments.</p
Nonalcoholic fatty liver disease (NAFLD) is a common metabolic dysfunction leading to hepatic ste... more Nonalcoholic fatty liver disease (NAFLD) is a common metabolic dysfunction leading to hepatic steatosis. However, NAFLD's global impact on the liver lipidome is poorly understood. Using high-resolution shotgun mass spectrometry, we quantified the molar abundance of 316 species from 22 major lipid classes in liver biopsies of 365 patients, including nonsteatotic patients with normal or excessive weight, patients diagnosed with NAFL (nonalcoholic fatty liver) or NASH (nonalcoholic steatohepatitis), and patients bearing common mutations of NAFLD-related protein factors. We confirmed the progressive accumulation of di- and triacylglycerols and cholesteryl esters in the liver of NAFL and NASH patients, while the bulk composition of glycerophospho- and sphingolipids remained unchanged. Further stratification by biclustering analysis identified sphingomyelin species comprising n24:2 fatty acid moieties as membrane lipid markers of NAFLD. Normalized relative abundance of sphingomyelins SM 43:3;2 and SM 43:1;2 containing n24:2 and n24:0 fatty acid moieties, respectively, showed opposite trends during NAFLD progression and distinguished NAFL and NASH lipidomes from the lipidome of nonsteatotic livers. Together with several glycerophospholipids containing a C22:6 fatty acid moiety, these lipids serve as markers of early and advanced stages of NAFL.
An amendment to this paper has been published and can be accessed via a link at the top of the pa... more An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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