Exploring the Interior: Essays on Literary and Cultural History

In this fascinating collection of essays Harvard Emeritus Professor Karl S. Guthke examines the ways in which, for European scholars and writers of the eighteenth and early nineteenth century, world-wide geographical exploration led to an exploration of the self. Guthke explains how in the age of Enlightenment and beyond intellectual developments were fuelled by excitement about what Ulrich Im Hof called "the grand opening-up of the wide world”, especially of the interior of the non-European continents. This outward turn was complemented by a fascination with "the world within” as anthropology and ethnology focused on the humanity of the indigenous populations of far-away lands – an interest in human nature that suggested a way for Europeans to understand themselves, encapsulated in Gauguin’s Tahitian rumination "What are we?” The essays in the first half of the book discuss first- or second-hand, physical or mental encounters with the exotic lands and populations beyond the supposed cradle of civilisation. The works of literature and documents of cultural life featured in these essays bear testimony to the crossing not only of geographical, ethnological, and cultural borders but also of borders of a variety of intellectual activities and interests. The second section examines the growing interest in astronomy and the engagement with imagined worlds in the universe, again with a view to understanding homo sapiens, as compared now to the extra-terrestrials that were confidently assumed to exist. The final group of essays focuses on the exploration of the landscape of what was called "the universe within”; featuring, among a variety of other texts, Schiller’s plays The Maid of Orleans and William Tell, these essays observe and analyse what Erich Heller termed "The Artist’s Journey into the Interior.” This collection, which travels from the interior of continents to the interior of the mind, is itself a set of explorations that revel in the discovery of what was half-hidden in language. Written by a scholar of international repute, it is eye-opening reading for all those with an interest in the literary and cultural history of (and since) the Enlightenment

Exploring the Interior

"In this fascinating collection of essays Harvard Emeritus Professor Karl S. Guthke examines the ways in which, for European scholars and writers of the eighteenth and early nineteenth century, world-wide geographical exploration led to an exploration of the self. Guthke explains how in the age of Enlightenment and beyond intellectual developments were fuelled by excitement about what Ulrich Im Hof called ""the grand opening-up of the wide world”, especially of the interior of the non-European continents. This outward turn was complemented by a fascination with ""the world within” as anthropology and ethnology focused on the humanity of the indigenous populations of far-away lands – an interest in human nature that suggested a way for Europeans to understand themselves, encapsulated in Gauguin’s Tahitian rumination ""What are we?” The essays in the first half of the book discuss first- or second-hand, physical or mental encounters with the exotic lands and populations beyond the supposed cradle of civilisation. The works of literature and documents of cultural life featured in these essays bear testimony to the crossing not only of geographical, ethnological, and cultural borders but also of borders of a variety of intellectual activities and interests. The second section examines the growing interest in astronomy and the engagement with imagined worlds in the universe, again with a view to understanding homo sapiens, as compared now to the extra-terrestrials that were confidently assumed to exist. The final group of essays focuses on the exploration of the landscape of what was called ""the universe within”; featuring, among a variety of other texts, Schiller’s plays The Maid of Orleans and William Tell, these essays observe and analyse what Erich Heller termed ""The Artist’s Journey into the Interior.” This collection, which travels from the interior of continents to the interior of the mind, is itself a set of explorations that revel in the discovery of what was half-hidden in language. Written by a scholar of international repute, it is eye-opening reading for all those with an interest in the literary and cultural history of (and since) the Enlightenment.

Use of systems biology to decipher host–pathogen interaction networks and predict biomarkers

AbstractIn systems biology, researchers aim to understand complex biological systems as a whole, which is often achieved by mathematical modelling and the analyses of high-throughput data. In this review, we give an overview of medical applications of systems biology approaches with special focus on host–pathogen interactions. After introducing general ideas of systems biology, we focus on (1) the detection of putative biomarkers for improved diagnosis and support of therapeutic decisions, (2) network modelling for the identification of regulatory interactions between cellular molecules to reveal putative drug targets and (3) module discovery for the detection of phenotype-specific modules in molecular interaction networks. Biomarker detection applies supervised machine learning methods utilizing high-throughput data (e.g. single nucleotide polymorphism (SNP) detection, RNA-seq, proteomics) and clinical data. We demonstrate structural analysis of molecular networks, especially by identification of disease modules as a novel strategy, and discuss possible applications to host–pathogen interactions. Pioneering work was done to predict molecular host–pathogen interactions networks based on dual RNA-seq data. However, currently this network modelling is restricted to a small number of genes. With increasing number and quality of databases and data repositories, the prediction of large-scale networks will also be feasible that can used for multidimensional diagnosis and decision support for prevention and therapy of diseases. Finally, we outline further perspective issues such as support of personalized medicine with high-throughput data and generation of multiscale host–pathogen interaction models

How to Predict Molecular Interactions between Species?

Organisms constantly interact with other species through physical contact which leads to chan-ges on the molecular level, for example the transcriptome. These changes can be monitored forall genes, with the help of high-throughput experiments such as RNA-seq or microarrays. Theadaptation of the gene expression to environmental changes within cells is mediated throughcomplex gene regulatory networks. Often, our knowledge of these networks is incomplete. Netw-ork inference predicts gene regulatory interactions based on transcriptome data. An emergingapplication of high-throughput transcriptome studies are dual transcriptomics experiments. Here,the transcriptome of two or more interacting species is measured simultaneously. Based ona dual RNA-seq data set of murine dendritic cells infected with the fungal pathogen Candidaalbicans, the software tool NetGenerator was applied to predict an inter-species gene regulatorynetwork. To promote further investigations of molecular inter-species interactions, we recentlydiscussed dual RNA-seq experiments for host-pathogen interactions and extended the appliedtool NetGenerator (Schulze et al., 2015). The updated version of NetGenerator makes use ofmeasurement variances in the algorithmic procedure and accepts gene expression time seriesdata with missing values. Additionally, we tested multiple modeling scenarios regarding the stimulifunctions of the gene regulatory network. Here, we summarize the work by Schulze et al. (2015)and put it into a broader context. We review various studies making use of the dual transcriptomicsapproach to investigate the molecular basis of interacting species. Besides the application tohost-pathogen interactions, dual transcriptomics data are also utilized to study mutualistic andcommensalistic interactions. Furthermore, we give a short introduction into additional approachesfor the prediction of gene regulatory networks and discuss their application to dual transcriptomicsdata. We conclude that the application of network inference on dual-transcriptomics data is apromising approach to predict molecular inter-species interactions

Integrative analysis of the heat shock response in Aspergillus fumigatus

<p>Abstract</p> <p>Background</p> <p><it>Aspergillus fumigatus </it>is a thermotolerant human-pathogenic mold and the most common cause of invasive aspergillosis (IA) in immunocompromised patients. Its predominance is based on several factors most of which are still unknown. The thermotolerance of <it>A. fumigatus </it>is one of the traits which have been assigned to pathogenicity. It allows the fungus to grow at temperatures up to and above that of a fevered human host. To elucidate the mechanisms of heat resistance, we analyzed the change of the <it>A. fumigatus </it>proteome during a temperature shift from 30°C to 48°C by 2D-fluorescence difference gel electrophoresis (DIGE). To improve 2D gel image analysis results, protein spot quantitation was optimized by missing value imputation and normalization. Differentially regulated proteins were compared to previously published transcriptome data of <it>A. fumigatus</it>. The study was augmented by bioinformatical analysis of transcription factor binding sites (TFBSs) in the promoter region of genes whose corresponding proteins were differentially regulated upon heat shock.</p> <p>Results</p> <p>91 differentially regulated protein spots, representing 64 different proteins, were identified by mass spectrometry (MS). They showed a continuous up-, down- or an oscillating regulation. Many of the identified proteins were involved in protein folding (chaperones), oxidative stress response, signal transduction, transcription, translation, carbohydrate and nitrogen metabolism. A correlation between alteration of transcript levels and corresponding proteins was detected for half of the differentially regulated proteins. Interestingly, some previously undescribed putative targets for the heat shock regulator Hsf1 were identified. This provides evidence for Hsf1-dependent regulation of mannitol biosynthesis, translation, cytoskeletal dynamics and cell division in <it>A. fumigatus</it>. Furthermore, computational analysis of promoters revealed putative binding sites for an AP-2alpha-like transcription factor upstream of some heat shock induced genes. Until now, this factor has only been found in vertebrates.</p> <p>Conclusions</p> <p>Our newly established DIGE data analysis workflow yields improved data quality and is widely applicable for other DIGE datasets. Our findings suggest that the heat shock response in <it>A. fumigatus </it>differs from already well-studied yeasts and other filamentous fungi.</p

Effect of L-carnitine on the hepatic transcript profile in piglets as animal model

<p>Abstract</p> <p>Background</p> <p>Carnitine has attracted scientific interest due to several health-related effects, like protection against neurodegeneration, mitochondrial decay, and oxidative stress as well as improvement of glucose tolerance and insulin sensitivity. The mechanisms underlying most of the health-related effects of carnitine are largely unknown.</p> <p>Methods</p> <p>To gain insight into mechanisms through which carnitine exerts its beneficial metabolic effects, we fed piglets either a control or a carnitine supplemented diet, and analysed the transcriptome in the liver.</p> <p>Results</p> <p>Transcript profiling revealed 563 genes to be differentially expressed in liver by carnitine supplementation. Clustering analysis of the identified genes revealed that most of the top-ranked annotation term clusters were dealing with metabolic processes. Representative genes of these clusters which were significantly up-regulated by carnitine were involved in cellular fatty acid uptake, fatty acid activation, fatty acid β-oxidation, glucose uptake, and glycolysis. In contrast, genes involved in gluconeogenesis were down-regulated by carnitine. Moreover, clustering analysis identified genes involved in the insulin signaling cascade to be significantly associated with carnitine supplementation. Furthermore, clustering analysis revealed that biological processes dealing with posttranscriptional RNA processing were significantly associated with carnitine supplementation.</p> <p>Conclusion</p> <p>The data suggest that carnitine supplementation has beneficial effects on lipid and glucose homeostasis by inducing genes involved in fatty acid catabolism and glycolysis and repressing genes involved in gluconeogenesis.</p