Cellular responses to zinc involving the transcription factor ZNF658 and its target genes

PhD ThesisZinc is an essential trace element that plays a crucial role in catalytic, structural and regulatory functions of many proteins including enzymes and transcription factors; thus maintenance of zinc balance is critical for normal cellular function. Cellular mechanisms that maintain zinc balance include the regulation of genes coding for proteins that play vital roles in zinc homeostasis. These proteins include zinc transporters belonging to the ZIP (SLC39A) and ZnT (SLC30A) families as well as the zinc-binding metallothionein proteins. In contrast to bacterial and yeast systems, a transcription factor responsible for mediating transcriptional repression of a suite of genes in response to elevated zinc levels in mammals has hitherto not been identified. Using Caco-2 cells as a model of human intestinal epithelial cells and detection of protein binding by electrophoretic mobility shift analysis, we show that zinc finger protein ZNF658 binds specifically to the zinc transcriptional regulatory element (ZTRE), previously demonstrated to mediate this response in a panel of three genes: SLC30A5 (ZnT5 zinc transporter), SLC30A10 (ZnT10 zinc transporter) and CBWD (whose prokaryotic homologs are emerging players in metal biology). We also demonstrate that siRNA-driven reduction of ZNF658 attenuated or abrogated transcriptional repression in response to elevated zinc levels of these same genes by measuring transcript abundance using RT-qPCR and using promoter-reporter gene constructs. In addition, the region of ZNF658 responsible for binding to the ZTRE was identified (the C-terminal zinc finger domain) and the requirement for both sides of the palindromic ZTRE sequence for function was demonstrated. This study therefore identifies the first metazoan transcription factor that plays a pivotal role in the orchestrated cellular response to increased zinc levels to restore cellular zinc balance necessary to achieve a broad spectrum of zinc-dependent functions and begins to probe its molecular action. We also report an important role for the mammalian CBWD gene product in protection of cells from either depleted or excess zinc by virtue of the fact that overexpression of recombinant CBWD protein altered cellular tolerance to both elevated and depleted levels of zinc consistent with a homeostatic function. In addition, we present preliminary evidence that changes in the expression of ZNF658 and its target genes, in particular SLC30A10 (ZnT10), may be related to cell senescence, suggesting that changes in zinc homeostasis are components of this process. Overall, the work presented contributes to understanding zinc regulated gene expression and cellular zinc homeostasis.Tertiary Education Trust Fund (TETFund) through the Benue State University (BSU) Makurd

Role of Media Publics in the Implementation Of New Technologies

The use of media publics is an ideal tool for the successful marketing of a technological enterprise. A public can be described as any group or community that affects the level of impact of an organization (Mules, 1998). Media publics plays a major role in creating a perception on how consumers receive a product. Furthermore, the use of media publics give technology firms a platform to reach its intended target. The aim of this poster is to explore the role of the media publics and how it also affects the implementation of new technologies

Feminine Identity Confined: The Archaeology of Japanese Women at Amache, a WWII Internment Camp

In 1942, approximately 120,000 people of Japanese ancestry were evacuated from the West Coast to ten different internment camps in the interior of the United States. One of these camps was the Granada Relocation Center, otherwise known as Amache, located in southeastern Colorado. Through the analysis of archaeological material, archival documents, and oral histories, this thesis explores the experiences of Japanese American women interned at Amache. Feminine identity was greatly changed and redefined during confinement. These changes in feminine identity are examined in the public and private arenas of daily life within confinement. The construction of new and altered individual and community identities are also explored. By examining how feminine identity was both changed as well as maintained during confinement, many differences between generations of Japanese women are exposed. Commonalities and similarities are also revealed that ultimately highlight the great adaptability, resilience, and perseverance of Japanese women in confinement

Corrosion and hydrate formation in natural gas pipelines

Gas industry annually invests millions of dollars on corrosion inhibitors in order to minimize corrosion implications on flow assurance; however, attention has never been focused on possibilities of these chemicals to promote hydrate formation along deepwater pipelines, which would equally result in another flow assurance problem of high magnitude. This study investigated the possibilities of corrosion inhibitors to aid the formation of gas hydrate along offshore (or underwater) pipeline systems; developed a predictive model on corrosion rate for natural gas pipelines with gas hydrates as the corroding agent and finally investigated the ability of pure N2 and H2 gases to inhibit the formation of gas hydrates.All experiments in this thesis were conducted by forming various water-gas systems in a cylindrical cryogenic sapphire cell. The first investigative work on hydrate-corrosion relationship was conducted by allowing contacts between an industrial grade natural gas (with 20% CO2 content) and five different corrosion inhibitors that are commonly used at offshore fields. The equipment, consisting of several fittings could operate at a temperature range of -160oC – 60oC (with accuracy of ± 0.10oC) and pressure range of 1bar to 500bar (with accuracy of ± 0.5bar). Using the ‗Temperature Search‘ method, the hydrate formation temperature point for each inhibitor was located at 500ppm and 100bar and the result compared with that of control experiment. Due to observed significant influence, further investigations were conducted on Dodecylpyridinium Chloride (DPC) at various concentrations and pressures. The corrosion model was developed based on hydrate‘s thermodynamic properties such as the operating temperature, pressure, fluid fugacity, wall shear stress, superficial velocity, enthalpy, entropy and activity coefficient amongst others, and a Matlab computer code was written to simulate the generated solution algorithm. Finally, components interaction study was conducted on various gas mixtures inside the sapphire cell to investigate the ability of pure N2 and H2 gases to inhibit the formation of gas hydrates.The obtained results established that all corrosion inhibitors aid hydrate promotion; this was attributed to their surfactant and hydrogen bonding properties which were essential for hydrate formation. The five investigated inhibitors showed different promotional rates with DPC having the highest promotional ability. The different promotional rate is due to their different sizes and structures, active functional groups and affinity for water molecules which determine the type(s) of hydrogen bonding exhibited by each inhibitor while in solution. The significant performance of DPC compared to other inhibitors was justified by the specific available active functional group which obeys electronegativity trend of periodic table to determine whether the resulting bond type will be polar covalent, ionic or ionic with some covalent characteristic in nature. Also, DPC hydrates revealed strong influence of the chemical‘s surfactant properties at all pressures and concentrations while its Critical Micelle Concentration (CMC) was believed to be 5000ppm due to the various anomaly behaviors exhibited at this particular concentration.The developed mathematical model adequately predicted corrosion rates with gas hydrate as the corroding agent and its effectiveness was confirmed by the level of agreement between its generated results and existing literatures. The resulting corrosion rate from hydrates could be as high as 174mm/yr (0.48mm/day). This is extremely alarming compared to the industry‘s aim to operate below 2mm/yr. At this rate, an underwater pipeline would be subjected to full bore rupture within some days if corrective measures are not quickly taken.Furthermore, the components interaction study revealed that CH4 played key roles on hydrate formation patterns during natural gas transportation through offshore pipeline system; the higher a natural gas CH4 content, the higher the risk of hydrates promotion. It also showed that when alone, CO2 does not form hydrate at low concentrations but showed a remarkable ability to aid hydrate formation when mixed with CH4. This is not surprising since it is also a former with ability to form Type I hydrate due to its very small size. Again, the ability of pure N2 and pure H2 gases to inhibit the formation of gas hydrate was confirmed but with H2 showing more significant effects. This was ascribed to their individual pressure condition to form hydrate. Though, N2 gas with small molecules forms Type II hydrate at a relatively higher pressure above the investigated pressures, it still forms hydrate within higher operating pressures practiced at gas fields during the transportation. However, H2 gas can never form hydrate at any natural gas transportation conditions. H2 gas only forms hydrates at extremely high pressure of about 2000bar because its molecules are too small and usually leaked out of hydrate cage, thus, reducing the amount that could be stored. By extension, these individual properties affect their interactions with natural gas during the hydrate formation process.Conclusively, this study has essentially revealed a new hydrate-corrosion relationship and established the need for comprehensive investigations in this research area. At all the investigated pressures, it was realized that DPC prolonged the complete blockage of the glass orifice at 10000ppm. This special characteristic may suggest the potential in applying the chemical as an additive for natural gas transportation and storage in slurry forms. Finally, the use of pure N2 or H2 as hydrate inhibitor in the offshore pipeline would be very cost effective to the industry. However, extreme care should be taken during the selection process since there are needs to further investigate the safety factors, material availability, cost implication and recovery from the main gas stream in order to choose the better option

Phylogenetic Evidence of the Public and Veterinary Health Threat of Dog Rabies in Nigeria

Molecular phylogenetics has been utilised to trace spillovers of rabies infection from reservoir host species to dead-end non-reservoirs including humans and other susceptible mammalian species. In this study we demonstrate phylogenetic evidence of the transmission of rabies virus infection from a reservoir host to humans and other animals. Here, we analysed phylogenetically a partial region of the nucleoprotein gene of 33 representative Nigerian rabies viruses predominantly recovered fromdogs. The analyses revealed monophyletic group with 2 subclusters according to geographical locality of origin of the viruses. Furthermore, a correlation between humandependent activities such as movement was observed. The data indicated that the virus isolates analysed here together with sequence obtained from Genbank of a human (Nigerian) formed one dominant group. This finding could be attributable to migration and translocation of animals infected with these rabies strains across the country. These molecular epidemiological data further contribute to depicting the public and veterinary health threat that rabies still poses in Nigeria and its implication to food security in this developing economy

Role of Nigerian libraries for sustainable educational system,information literacy and national development

There is a growing concern in the minds of people on the relevance of the library in the 21st century. This paper critically addresses some of the key functions of the library in supporting education and improving information literacy of the people for national development in Nigeria. It further reiterates the importance of the library in the Nigerian educational system and concludes that a nation may not be developed without a sustainable educational system and well-stocked libraries to support information literacy, learning, teaching and research activities of the people