PPARa: master regulator of lipid metabolism im mouse and human : identification of hepatic PPARa target genes by expression profiling

The peroxisome proliferator activated receptor alpha (PPARα) is a ligand activated tran- scription factor involved in the regulation of a variety of processes, ranging from inflam- mation and immunity to nutrient metabolism and energy homeostasis. PPARα serves as a molecular target for hypolipidemic fibrates drugs which bind the receptor with high affinity. Furthermore, PPARα binds and is activated by numerous fatty acids and fatty acid derived compounds. PPARα governs biological processes by altering the expression of large number of target genes. Although the role of PPARα as a gene regulator in liver has been well estab- lished, a comprehensive overview of its target genes has been missing so far. Additionally, it is not very clear whether PPARα has a similar role in mice and humans and to what extent target genes are shared between the two species. The aim of the research presented in this thesis was to identify PPARα-regulated genes in mouse and human liver and thereby further elucidate hepatic PPARα function. The applied nutrigenomics approaches are mainly expression microarrays combined with knockout mouse models and in vitro cell culture systems. By combining several independent nutrigenomics studies, we generated a comprehensive overview of PPARα-regulated genes in liver with the focus on lipid metabolism. We identi- fied a large number of PPARα target genes involved in different aspects of lipid metabolism. Furthermore, a major role of PPARα in lipogenesis was detected. Our data pointed to several novel putative PPARα target genes. Next, we compared PPARα-regulated genes in primary mouse and human hepatocytes treated with the PPARα agonist Wy14643 and generated an overview of overlapping and species specific PPARα target genes. A large number of genes were found to be regulated by PPARα activation in human primary hepatocytes, which iden- tified a major role for PPARα in human liver. Interestingly, we could characterize mannose binding lectin 2 (Mbl2) as a novel human specific PPARα target gene. Plasma Mbl2 levels were found to be changed in subjects receiving fenofibrate treatment or upon fasting. Regula- tion of Mbl2 by PPARα suggests that it may play a role in regulation of energy metabolism, although additional research is needed. We also compared the PPARα-induced transcriptome in HepG2 cells versus primary human hepatocytes to investigate the suitability of HepG2 cells in PPARα research. The results re- vealed that the HepG2 cell line poorly reflects the established PPARα target genes and func- tion, specifically with respect to lipid metabolism. Finally, we characterized the transcription factors Klf10 and Klf11 as novel PPARα target genes. Our preliminary findings using in vitro transfection assays and in vivo tail vein injection of plasmid DNA suggested a potential metabolic role of Klf10 and Klf11 in liver. In conclusion, this thesis has extended our understanding of PPARα-regulated genes and function in liver, and has specifically highlightened a major role of PPARα in human hepa- tocytes. This research has also given birth to a possible biomarker of hepatic PPARα activity which is of great interest for future studies. Considering the need for proper biomarkers in the field of nutrigenomics and beyond, the properties of Mbl2 as a biomarker should be further investigated. The identification of other novel putative PPARα target genes offers ample op- portunities for continued research

Helminth parasites fauna of the green toad, Bufo variabilis, Laurenti, 1768 (Anura: Bufonidae) from the Fars Province, Iran

The green toad, Bufo variabilis has been a common species of toads in Iran with a wide distribution in most provinces. The main goal of this study was to determine the helminth parasite fauna of B. variabilis in southwest of Iran. Among 30 toads inspected for helminth infection from different sites, 100% harbored one or more parasite species. Some toads were afflicted by intestinal obstruction, due to the infection with a large number of cestodes. Twenty-eight cases (93%) had mixed infection with cestodes (in intestine) and nematodes (in lung). Also, a toad was infected with a single monogenean parasite in its urinary bladder. The identified helminth parasites were monogenean, Polystoma viridis; cestode, Nematotaenia dispar and a species of nematode, Rhabdias ranae. This study reports for the first time the presence of nematode species R. ranae in B. variabilis in Iran

Three Dimensional Seepage Analyses in Mollasadra Dam after Its Impoundments

Mollasadra dam is an earth fill dam with a clayey core and a height of 72 m from river bed, constructed on Kor River. pore water pressure in the dam was investigated following its construction and first and second impoundments. The dam was modeled by a finite element mesh. After the first and second dam impoundments, the overall trend in monitored pore water pressure was well modeled by the transient analysis. The result showed the six month time period between impoundments was long enough for the pore water pressure to reach equilibrium everywhere throughout the core, except where considerable initial constructioninduced pore water pressure was observed. High values of construction-induced pore water pressure at elevation2050 m did not dissipate completely during the 6 month period of almost constant reservoir level (el. 2098.3 m) and the pore pressures were still at the transient state throughout the core. Therefore, it was concluded that porepressures in the core of earth fill dams may not achieve steady state conditions even several months after the dam construction and impoundments

A Qualitative Exploration of On-Campus Experiences of English-Speaking Graduate International Students at a Leading Japanese University

With the rapid expansion of English-medium courses/degree programs at Japanese universities over the past 15 years, a greater number of English-speaking international students from diverse backgrounds are being attracted. However, little research has been conducted to address the needs of this minority group, especially at the graduate level. Employing interpretative phenomenological analysis (IPA), this study explores on-campus satisfaction with life (SWL) of nine graduate international students studying primarily in the Englishmedium regarding the support model of their Japanese university. Four master themes of traditional support, student ideal support, challenges, and best practices are discussed. The results present effective Japanese university support strategies that can promote SWL of English-medium graduate international students

Experimental dataset on water levels, sediment depths and wave front celerity values in the study of multiphase shock wave for different initial up- and down-stream conditions

This data article presents a rich original experimental video sources and wide collections of laboratory data on water levels, sediment depths and wave front celerity values arose from different multiphase dam-break scenarios. The required data of dam-break shock waves in highly silted-up reservoirs with various initial up- and down-stream hydraulic conditions is obtained directly from high-quality videos. The multi-layer shock waves were recorded by three professional cameras mounted along the laboratory channel. The extracted video images were rigorously scrutinized, and the datasets were obtained through the images via image processing method. Different sediment depths in the upstream reservoir and dry- or wet-bed downstream conditions were considered as initial conditions, compromising a total of 32 different scenarios. A total of 198 original experimental videos are made available online in the public repository "Mendeley Data" in 8 groups based on 8 different initial upstream sediment depths [1], [2], [3], [4], [5], [6], [7], [8]. 20 locations along the flume and 15 time snaps after the dam breaks were considered for data collecting. Consequently, a total of 18,000 water level and sediment depth data points were collected to prepare four datasets, which are uploaded in the public repository "Mendeley Data". A total of 9600 water level data points could be accessed in [9], [10], while 8400 sediment depth data points are available online in [11], [12] and could be utilized for validation and practical purposes by other researchers. This data article is related to another research article entitled "Experimental study and numerical verification of silted-up dam-break" [13]

Peroxisome Proliferator-Activated Receptor Alpha Target Genes

The peroxisome proliferator-activated receptor alpha (PPARα) is a ligand-activated transcription factor involved in the regulation of a variety of processes, ranging from inflammation and immunity to nutrient metabolism and energy homeostasis. PPARα serves as a molecular target for hypolipidemic fibrates drugs which bind the receptor with high affinity. Furthermore, PPARα binds and is activated by numerous fatty acids and fatty acid-derived compounds. PPARα governs biological processes by altering the expression of a large number of target genes. Accordingly, the specific role of PPARα is directly related to the biological function of its target genes. Here, we present an overview of the involvement of PPARα in lipid metabolism and other pathways through a detailed analysis of the different known or putative PPARα target genes. The emphasis is on gene regulation by PPARα in liver although many of the results likely apply to other organs and tissues as well

A comprehensive public open space categorization using classification system for sustainable development of public open spaces

Our quality of life significantly depends on open spaces. They offer facility provision for a wide range of social interactions and provide habitats for flora and fauna. A classification of spaces would be useful in preparing public open space policies and fulfilling structure plan. This study aims to propose a comprehensive open space categorization using classification system for Malaysia. A deep investigation in sources in Malaysia reveals that there is lack of comprehensive classification of open spaces and just a hierarchy of open spaces presented. A critical literature review were carried out for this study to understand the approaches of this comprehensive classification and adapted them according to Malaysia context. In order to come up with a comprehensive classification in Malaysia, an analysis of comparison between several cities in different countries was done. The outcomes of the study will provide a systematic classification use for planner and policy makers in preparing open space strategies and in setting development plan policies. It is also useful for designers to obtain the best possible conceptual ideas when designing open spaces