3 resultados para Intermediation in development

em Universitätsbibliothek Kassel, Universität Kassel, Germany


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The main objective of this PhD research study is to provide a perspective on the urban growth management and sustainable development in Palestine, and more specifically in Hebron district as a case study. Hebron is located 36 km south of Jerusalem, with an overall population size of around 600,000 people living in a total area around1246km2. Hebron is the biggest Palestinian district that has 16 municipalities and 154 localities. The research discusses and analyzes the urban planning system, economical and environmental policies and the solution required to manage and integrate the development elements to develop a sustainable development plan for Hebron. The research provides answers for fundamental questions such as what kind and definition of sustainable development are applicable to the Palestinian case?. What are the sustainability problems there and how the Israeli occupation and unstable political condition affect the sustainable development in Palestine? What are the urban growth management and sustainability policies and actions required from government, public and privets sector in Palestine? The fast urban growth in Palestine is facing many problems and challenges due to the increase in the population size and the resulting impact of this increase including, but not limited to, the demand of new houses, need for more infrastructure services, demands on new industrial, commercial, educational and health projects, which in turn reduces the area of agricultural lands and threatens the natural resources and environment. There are also other associated sustainability problems like the absence of effective plans or regulations that control urban expansion, the absence of sufficient sustainable development plans at the national levels for the district, new job requirements, Israeli restrictions and occupation for more than 60 years, existence of construction factories near residential areas, poor public awareness and poor governmental funds for service projects and development plans. The study consists of nine chapters. Chapter One includes an introduction, study objectives, problems and justifications, while Chapter Two has a theoretical background on sustainability topic and definitions of sustainability. The Palestinian urban planning laws and local government systems are discussed in Chapter Three and the methodology of research is detailed in Chapter Four. As for Chapter Five, it provides a general background on Hebron District including demographical and economical profiles, along with recommendations related to sustainable development for each profile Chapter Six addresses the urban environment, sustainability priorities and policies required. Chapter Seven discusses and analyzes infrastructure services including transportation, water and wastewater. As for Chapter Eight, it addresses the land use, housing and urban expansion beside the cultural heritage, natural heritage with relevant sustainable development polices and recommendations. Finally, Chapter Nine includes a conclusion and comprehensive recommendations integrating all of urban and sustainability event in one map. Hebron has a deep history including a rich cultural heritage aged by thousands of years, with 47% of Hebron district population under 14 years old. Being the biggest Palestinian district, Hebron has thousands of industrial and economical organizations beside a large agricultural sector at Palestine level. This gives Hebron a potential to play major roles in developing a national sustainability plan, as the current urban planning system in Palestine needs urgent reform and development to fulfill the sustainability requirement. The municipalities and ministers should find permanent financial aid for urban planning and development studies so as to face future challenges. The Palestinian government can benefit from available local human resources in development projects; hence Palestinian people have sufficient qualifications in most sectors. The Palestinian people also can invest in the privet sector in Palestine in case businessmen have been encouraged and clear investment laws and plans have been developed. The study provides recommendations associated to the sustainable development in Palestine in general and Hebron, as a case study, in specific. Recommendations include increasing the privet sector as well as the public involvement in urban growth management, and stopping unplanned urban expansion, subjecting granting building permits of new projects to the no-harm environmental impact assessment, increasing the coordination and cooperation between localities and central bodies, protection and renovation of old cites and green areas, increasing the quality and quantity of infrastructure services, establishing district urban planning department to coordinate and organize urban planning and sustainable development activities. Also, among recommendations come dividing Hebron into three planning and administrative areas (north, central and south), and dividing the sustainable development and implementation period (2010 to 2025) into three main phases. Finally, the study strongly recommends benefiting from the same urban development plans in similar districts at national and international levels, also to use new technologies and information systems in urban planning process.

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DNA methyltransferases of type Dnmt2 are a highly conserved protein family with enigmatic function. The aim of this work was to characterize DnmA, the Dnmt2 methyltransferase in Dictyostelium discoideum, and further to investigate its implication in DNA methylation and transcriptional gene silencing. The genome of the social amoeba Dictyostelium encodes DnmA as the sole DNA methyltransferase. The enzyme bears all ten characteristic DNA methyltransferase motifs in its catalytic domain. The DnmA mRNA was found by RT-PCR to be expressed during vegetative growth and down regulated during development. Investigations using fluorescence microscopy showed that both DnmA-myc and DnmA-GFP fusions predominantly localised to the nucleus. The function of DnmA remained initially unclear, but later experiment revealed that the enzyme is an active DNA methyltransferase responsible for all DNA (cytosine) methylation in Dictyostelium. Neither in gel retardation assays, nor by the yeast two hybrid system, clues on the functionality of DnmA could be obtained. However, immunological detection of the methylation mark with an α - 5mC antibody gave initial evidence that the DNA of Dictyostelium was methylated. Furthermore, addition of 5-aza-cytidine as demethylating agent to the Dictyostelium medium and subsequent in vitro incubation of the DNA isolated from these cells with recombinant DnmA showed that the enzyme binds slightly better to this target DNA. In order to investigate further the function of the protein, a gene knock-out for dnmA was generated. The gene was successfully disrupted by homologous recombination, the knock-out strain, however, did not show any obvious phenotype under normal laboratory conditions. To identify specific target sequences for DNA methylation, a microarray analysis was carried out. Setting a threshold of at least 1.5 fold for differences in the strength of gene expression, several such genes in the knock-out strain were chosen for further investigation. Among the up-regulated genes were the ESTs representing the gag and the RT genes respectively of the retrotransposon skipper. In addition Northern blot analysis confirmed the up-regulation of skipper in the DnmA knock-out strain. Bisufite treatment and sequencing of specific DNA stretches from skipper revealed that DnmA is responsible for methylation of mostly asymmetric cytosines. Together with skipper, DIRS-1 retrotransposon was found later also to be methylated but was not present on the microarray. Furthermore, skipper transcription was also up-regulated in strains that had genes disrupted encoding components of the RNA interference pathway. In contrast, DIRS 1 expression was not affected by a loss of DnmA but was strongly increased in the strain that had the RNA directed RNA polymerase gene rrpC disrupted. Strains generated by propagating the usual wild type Ax2 and the DnmA knock-out cells over 16 rounds in development were analyzed for transposon activity. Northern blot analysis revealed activation for skipper expression, but not for DIRS-1. A large number of siRNAs were found to be correspondent to the DIRS-1 sequence, suggesting concerted regulation of DIRS-1 expression by RNAi and DNA methylation. In contrast, no siRNAs corresponding to the standard skipper element were found. The data show that DNA methylation plays a crucial role in epigenetic gene regulation in Dictyostelium and that different, partially overlapping mechanisms control transposon silencing for skipper and DIRS-1. To elucidate the mechanism of targeting the protein to particular genes in the Dictyostelium genome, some more genes which were up-regulated in the DnmA knock-out strain were analyzed by bisulfite sequencing. The chosen genes are involved in the multidrug response in other species, but their function in Dictyostelium is uncertain. Bisulfite data showed that two of these genes were methylated at asymmetrical C-residues in the wild type, but not in DnmA knock-out cells. This suggested that DNA methylation in Dictyostelium is involved not only in transposon regulation but also in transcriptional silencing of specific genes.

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Dictyostelium discoideum is a social amoeba that serves as a model system for RNA interference and related mechanisms. Its position between plants and animals enables evolutionary snapshot of mechanisms and protein machinery involved in investigated subjects. MiRNAs are small regulatory RNAs that are evolutionary conserved and present in animals, plants, viruses and some prokaryotes. They have roles in development, cell growth and differentiation, apoptosis and their miss-regulation is associated with many diseases such as cancer, neurodegenerative disorders and diabetes. Recently, through sequencing of DNA libraries miRNAs have been discovered in D. discoideum. In this work, it has been shown that heterologues miRNA let-7 can be expressed and processed in D. discoideum. Expression of let-7 miRNA in social amoeba resulted in a strong developmental phenotype suggesting an overload of the processing/silencing system or/and endogenous targets. The various effects on prel-7 strain have been observed and characterized, serving as a background for postulation of miRNA roles. An artificial miRNA system has been established and imposed to D. discoideum, showing that miRNAs in Dictyostelium could mediate gene expression on the level of mRNA stability and on the posttranscriptional level. Furthermore, presence of translational inhibition as a type of gene control was shown for the first time in this organism. Due to it new structures representing co-localities of miRNA and target mRNA have been detected. Taken together, this work shows functional artificial miRNA system and postulates roles of endogenous small RNA in social amoeba.