Personalized Nutrition

Awareness of the influence of our genetic variation to dietary response (nutrigenetics) and how nutrients may affect gene expression (nutrigenomics) is prompting a revolution in the field of nutrition. Nutrigenetics/Nutrigenomics provide powerful approaches to unravel the complex relationships among nutritional molecules, genetic variants and the biological system. This publication contains selected papers from the ‘3rd Congress of the International Society of Nutrigenetics/Nutrigenomics’ held in Bethesda, Md., in October 2009. The contributions address frontiers in nutrigenetics, nutrigenomics, epigenetics, transcriptomics as well as non-coding RNAs and posttranslational gene regulations in various diseases and conditions. In addition to scientific studies, the challenges and opportunities facing governments, academia and the industry are included

Metagenomic surveillance of viruses at the human-animal interface

Zoonotic viruses are a major contributor to emerging infectious diseases, and continuously burden public health systems. Early detection and effective response to viral emergence require an overview of what viruses are circulating in animal hosts, which of these can and do infect at-risk human populations, and which pose the greatest risk of further spread. However, knowledge of such epidemiological patterns is generally biased towards known pathogens of humans and of economically important livestock species. With metagenomic sequencing, one can begin to address these biases by generating a more representative picture of what viruses are present in different host species living in a shared environment. Vietnam is considered a high-risk setting for the emergence of zoonoses, due to its high population and livestock densities and the prevalence of socio-cultural practices involving frequent close contacts between humans, livestock and wildlife. The Vietnam Initiative on Zoonotic Infections (VIZIONS) was established to improve our understanding of zoonotic emergence in this context. Over 2000 faecal samples and rectal swabs were collected from humans and a variety of farmed animals, and subjected to metagenomic sequencing. In this thesis, I use viral taxonomic classification methods to identify and characterise the viruses present in these samples. I investigate any signals for (putative) zoonotic viruses, and assess whether they could represent emerging public health threats. I also evaluate the roles and challenges of metagenomic surveillance for emerging viruses at the human-animal interface. The first part of this thesis focuses on the development and testing of a viral taxonomic classification pipeline. I describe the basic steps of this pipeline, and the rationale behind the chosen methods. Next, I test the pipeline on a subset of samples and viruses for which diagnostic quantitative PCR (qPCR) data were available for comparison. Receiver operating characteristic (ROC) curve analysis showed that the pipeline accurately distinguishes qPCR positive from qPCR-negative samples, and read pair counts correlate well with qPCR cycle threshold values. Investigation of samples with discordant qPCR and metagenomic results indicated that taxonomic misclassification by the pipeline plays a minor role in these discrepancies. Additionally, I found that, for each of the tested viruses, negative samples have variable read pair counts (“background noise”) that correlate with the total number of read pairs assigned to the virus across all samples of the same sequencing run. I hypothesise that this is due to “index switching”, a form of cross-contamination, and model the association. The findings of these investigations allow me to incorporate additional steps into the pipeline to counteract misclassification, and to use signal thresholds that take into account the effect of index switching cross-contamination. In the second part of this thesis, I focus on the characterisation of viruses identified with the taxonomic classification pipeline. I present an overview of the mammalian viruses found in samples from humans, swine and rats from Dong Thap province. After removing likely contaminants, I categorize the remaining viruses according to their zoonotic potential. Seven of these viruses are known or generally presumed to be zoonotic; three are only found in the animal study populations, but four – Rotavirus A, Picobirnavirus, Human associated cyclovirus 8, and Mammalian orthoreovirus – are shared between human and animal populations. Comparison of signals suggests that viral chatter (Rotavirus A) and cross-species transmission within a more generalist ecology (Picobirnavirus, Human associated cyclovirus 8) are plausible in this setting. Additionally, three putative novel zoonoses are identified, but knowledge gaps hinder extensive interpretation. I evaluate the relevance of these 10 zoonotic and putative novel zoonotic viruses as potential emerging public health threats, and highlight the knowledge gaps that need to be addressed before the risks of these viruses can be properly assessed. Finally, I interpret my findings in the general context of disease emergence, and evaluate the roles and challenges of viral metagenomics as a tool in the surveillance for emerging infectious disease

Going viral : an integrated view on virological data analysis from basic research to clinical applications

Viruses are of considerable interest for several fields of life science research. The genomic richness of these entities, their environmen- tal abundance, as well as their high adaptability and, potentially, pathogenicity make treatment of viral diseases challenging. This thesis proposes three novel contributions to antiviral research that each concern analysis procedures of high-throughput experimen- tal genomics data. First, a sensitive approach for detecting viral genomes and transcripts in sequencing data of human cancers is presented that improves upon prior approaches by allowing de- tection of viral nucleotide sequences that consist of human-viral homologs or are diverged from known reference sequences. Sec- ond, a computational method for inferring physical protein contacts from experimental protein complex purification assays is put for- ward that allows statistically meaningful integration of multiple data sets and is able to infer protein contacts of transiently binding protein classes such as kinases and molecular chaperones. Third, an investigation of minute changes in viral genomic populations upon treatment of patients with the mutagen ribavirin is presented that first characterizes the mutagenic effect of this drug on the hepatitis C virus based on deep sequencing data.Viren sind von beträchtlichem Interesse für die biowissenschaftliche Forschung. Der genetische Reichtum, die hohe Vielfalt, wie auch die Anpassungsfähigkeit und mögliche Pathogenität dieser Organismen erschwert die Behandlung von viralen Erkrankungen. Diese Promotionsschrift enthält drei neuartige Beiträge zur antiviralen Forschung welche die Analyse von experimentellen Hochdurchsatzdaten der Genomik betreffen: erstens, ein sensitiver Ansatz zur Entdeckung viraler Genome und Transkripte in Sequenzdaten humaner Karzinome, der die Identifikation von viralen Nukleotidsequenzen ermöglicht, die von Referenzgenomen ab- weichen oder homolog zu humanen Faktoren sind. Zweitens, eine computergestützte Methode um physische Proteinkontakte von experimentellen Proteinkomplex-Purifikationsdaten abzuleiten welche die statistische Integration von mehreren Datensätzen erlaubt um insbesondere Proteinkontakte von flüchtig interagierenden Proteinklassen wie etwa Kinasen und Chaperonen aus den Daten ableiten zu können. Drittens, eine Untersuchung von kleinsten Änderungen viraler Genompopulationen während der Behandlung von Patienten mit dem Mutagen ribavirin die zum ersten Mal die mutagene Wirkung dieses Medikaments auf das Hepatitis C Virus mittels Tiefensequenzdaten nachweist

Antioxidant effect of Linalool on testicular-injury induced by carbon tetrachloride in male rats

Background: The oxidative stress and generation of free radicals plays an important role in testicular impairment. The aim of this study was to investigate the protective effect of linalool on carbon tetrachloride (CCl4)-induced male reproductive system damage. Methods: In this study, 24 male rats were divided into four groups. Two of the groups were normal control group andCCl4 damage control group which received a daily dose of distilled water for 14 days. Two of the other groups were pretreatment groups; the rats in one of them received a daily dose of 25 mg/kg linalool and those in the other were administered with a daily dose of 100 mg/kg silymarin for 14 days. On the 14th day, the damage control group as well as the pretreatment groups was intraperitoneally injected with 1 ml/kg of the mixture of CCl4and olive oil (1:1). The rats in the normal control group were only administered with olive oil. 48 hours after the injection of CCl4, a part of the testis tissue was separated for conducting antioxidant and malondialdehyde (MDA) tests. Results: The injection of CCl4 into the rats caused a significant increase in the concentration of MDA and insignificant decrease in the level of antioxidants in the testicular lysate as compared to the normal control group (P<0.01). Treatment with linalool improved the level of MDA and enhanced antioxidant as compared to the damage control group (P<0.01). Conclusion: The results of this study indicated that linalool has antioxidant properties and can have a therapeutic effect against CCl4-induced testicular injuries

Urological Cancer 2020

This Urological Cancer 2020 collection contains a set of multidisciplinary contributions to the extraordinary heterogeneity of tumor mechanisms, diagnostic approaches, and therapies of the renal, urinary tract, and prostate cancers, with the intention of offering to interested readers a representative snapshot of the status of urological research

Viral Gene Therapy

The development of technologies that allow targeting of specific cells has progressed substantially in recent years for several types of vectors, particularly viral vectors, which have been used in 70% of gene therapy clinical trials. Particular viruses have been selected as gene delivery vehicles because of their capacities to carry foreign genes and their ability to efficiently deliver these genes associated with efficient gene expression. This book is designed to present the most recent advances in viral gene therap