The newborn screening for congenital hypothyroidism (CR) started in the West in the sixties. The guidelines for screening were introduced in the majority of western countries some 30 years ago and were adapted in 1997 by the World Health Organization. The United Arab Emirates (UAE) started newborn screening for CH in 1998 and was considered one of the leading countries in the Middle East to apply this programme nationwide. Before newborn screening for CH in the UAE, little was known about the epidemiology of the disease in this part of the world which shares the same epidemiological pattern of the Gulf region and the Middle East This nationwide study investigated the epidemiological pattern of CH in the UAE in terms of assessment of biological and environmental components and their significance in the relatively increased incidence of the disease in this community compared to the worldwide incidence (1:30004000). This study employed radioimmunoassay technique used by the newborn screening programme to measure the capillary Thyroid Stimulating Hormone (TSR) for all newborns at the week of age. In addition, chemical and radiological techniques were employed to screen for positive cases. Firstly, cases detected have been studied in terms of prevalence of the disease in the UAE in relation to other parts of the world and the definition of the epidemiological components and its association to the prevalence of the disease. The study included the investigation of the genotypic pattern of congenital hypothyroidism in the UAE among certain cases with familial dyshormonogesis phenotype. The results show high incidence of the disease compared to the worldwide incidence and also it showed a specific epidemiological pattern. Secondly, the study employed the data obtained in newborn screening for CH in a longitudinal study of TSR pattern of the population and its use to monitor the iodine uptake of this population. This part of study also studied other important implications of the TSR pattern which included the TSR surge and the prevalence of sub clinical cases in which TSH is the main monitor. Thirdly, the study evaluated the controversial issues in the newborn screening programme in the preanalytic and post-analytic phases of the programme. The role of incorporation of the pre and post analytical quality control of the programme in reduction of the morbidity of the disease. Nevertheless, this study provides an overview for the epidemiological pattern of congenital hypothyroidism in the UAE and forms a basic epidemiologic background for further detailed studies that would focus on the clinical aspect and prognostic outcome of the disease. It may be concluded that the clinical picture of congenital hypothyroidism has changed dramatically since newborn screening was instituted in the UAE. Population-based registers and linked-databases can provide very useful information for evaluating screening programmes, and extending current knowledge of the epidemiology of congenital hypothyroidism. This is the first epidemiological study of CH in the UAE in which data from population-based registries were linked, the epidemiologic patterns and associated factors are more representative. The study delineates the significantly increased incidence of congenital hypothyroidism compared to the universal incidence and the clear correlation of this incidence with certain risk factors. Some of these are local which pertain to this area of the world and end in constituting this specific epidemiological pattern.

The susceptibility of human lungs to carcinogens depends on the metabolic balance between activation and detoxification pathways, though for the tumour to develop depcnds on activation of cell immortalisation pathway. The correlation of these pathways has not been reported. The present study described the correlation in transcription of genes of two phases of drug metabolism pathways and immortalisation pathway in four lung cell lines namely; a normal lung cell line (CDD32Lu), alveolar adenocarcinoma (A549), pleural adenocarcinoma (1-1460), and a drug resistance large cell carcinoma (COR-L23/5010). The levels of transcripts of Phase I (CYPL4I, CYPIA2 and CYP2EI), phase II (GSTMJ) and immortalisation (hTERT) genes were investigated. There was evidence suggesting that the transcription of CYPJAI, and CYP/A2 is of cell specific since CYPIAJ transcribed in the A549 eell line only, while CYPIA2 was transcribed in the H460 cell line. The present study validates the ability of CYPIA2 to be expressed in cell line. Moreover, the present study showed abundant expression of CYP2E/ and GSTMJ mRNA in normal and lung cancer cell lines suggesting that these genes may play no active role in lung carcinogenesis. In addition, the transcription level of immortalisation gene (hTERT) and telomerase activity was determined and observed in the A549 cell line only. The novel finding of this research is the cb-transcription of CYPJAJ and JITERT in the A549 cell line. The co-transcription was further analysed by induction of CYPJAJ in all cell lines with the AhR ligands TCDD and 3-MC. The finding reveals the existence of CYPIAI and hTERT co-transcription. Despite the fact that transcription of CYPJAI was observed CYP1A1 activity was not detected even after cell treatment with CYP1A1 inducers. This was possibly due to scarcity of CYP1A! and limited level of haem in the extrahepatic tissue. This study demonstrated a novel basal and induced co-transcription of CYP1AJ and hTERT. The regulation of co transcription was analysed by silencing CYPIAJ using siRNA technology and observing hTERT knockdown. Silencing of CYP1AI was subsequently downregulate hTERT transcription and reduces cells viability. The mechanism of co-transcription was investigated to rule out the involvement of suggested AhR signalling pathway. This was carried out by determining the level of mRNA expression of those genes, which their proteins were involved in the AhR signalling pathway. The results obtained suggest the role of the AhR signalling pathway in the co-transcription of CYPJAJ and hTERT. The data obtained from gene knockdown experiments revealed silencing of CYPJAJ alters hTERT expression and cell proliferation. The present study suggests that siRNA technology can be used as a reliable tool for the validation of co-transcription. Moreover, the concomitant silencing of CYPJAJ and hTERT and inhibition of cells proliferation not only validate the co-transcription but also a valuable finding to be considered as a novel therapeutic target, which may contribute to management of lung cancer. The transcription of CYPIAJ and hTERT has been identified as a cancer risk marker in a diverse range of cancers, the data of the present study suggests the use of CYPJA] 5iRNA as optional gene therapy in cancer management, where CYPJAJ plays a major risk.

This thesis is a continuation of experimental work conducted by Pickup el al. (1997) analysing nickel resistant bacteria isolated from effluent discharged from a sewage outfall in the Lake District, Cumbria. Its aim is to further characterise the nickel resistance determinant ftom Enterobacter cloacae FBA30. FBA30 was found to harbour a 55-60 kb plasmid designated pFBA30 which confers nickel resistance on its host and in laboratory strains of E. coh. pFBA30 is transferable to enteric relatives, but not to non-enteric species and is considered to have a narrow host range. A 10.2kb Sad restriction fi7agment was cloned fi7om pFBA30, which exhibited constitutive nickel resistance both in its original host and in laboratory strains of Eschericia coli. Further work on the 10.2 kb Sacl fragment localised the nickel resistance locus to an internal 2.3 kb PvuII restriction fragment exhibiting extensive homology to the nre determinant of plasmid pTOM9 (Schmidt and Schlegel, 1994). This fragment and a further 1.75 kb Smal fragment derived from it, were used as DNA probes to examine other bacterial strains isolated from the same site. Six strains showing extensive homology were retained for further study (Pickup et al., 1997). The nickel resistance of the six strains appears to be chromosomally encoded. The strains were sorted into groups based upon their sampling date and size of restriction fragment homologous to the probe developed from pFBA30. Group A isolates carry a homologous Null fragment approximately 6.5 kb in size whereas group B isolates carry a 2.5 kb Null fragment. All strains display constitutive nickel resistance and are capable of expressing resistance under both anaerobic and aerobic growth conditions. Furthermore, each strain was discovered to be resistant to a spectrum of heavy metals and antimicrobial agents. Each group consists of a range of enteric bacterial species including Klebsiella, Citrobacter and Enterobacter species.

Multiple sclerosis (MS) is the most common autoimmune inflammatory demyelinating disorder of the human nervous system affecting nearly 1 million people worldwide every year. Current treatments for first-line nontoxic therapy of the relapsing-remitting form of the disease are two forms of recombinant IFN(3, Ia and 1(3 andglatiramèr acetate. The pathogenesis of MS is highlighted by an inflammatory response and myelin destruction. Several recent studies have reported alterations in immune variables such as cytokine concentrations, immune-related molecules such as MHC and adhesion molecules and chemokines; which may contribute to an imbalance between Thi and Th2 T cellmediated immune response. The aims of the present study were to characterize the cytokinetic profile of MS patients through investigating the secretion of the main pro and anti-inflammatory cytokines from peripheral blood mononuclear cells of MS patients compared to controls, and to investigate cytokine receptor expression levels in T and NK cells. In addition, the induction of apoptosis and the involvement of adhesion molecules and metalloproteinases in oligodendrocyte destruction are examined. Finally, the effect of IFN(3 treatment on cytokine secretion levels as well as on the aforementioned immunoregulatory molecules was evaluated. The study population consisted of 60 MS patients (20 untreated, 20 treated with IFNf3-lcz and 20 treated with IFN(3-1(3) in parallel with 25 controls. Serumlplasma samples and peripheral blood mononuclear cells (PBMCs) were isolated from each participant. Using the enzyme linked immunospot (ELISPOT) assay the numbers of cytokine-secreting PBMCs were measured for the following cytokines: IFN-y, TNF-a, IL- 12, IL- 10 and IL-4. The expression levels of the cytokine receptors IL- 1 2R(3 1, IFN-y, IL- 1 OR, TNFaR were estimated in the surface of lymphocytes using flow cytometry and serum levels of soluble CD95, ICAM- 1, VCAM-1, metalloproteinase-9 (MMP-9) and the tissue inhibitor, metalloproteinase-1 (TIMP-1) were evaluated in all samples. The ELISPOT assay proved a very sensitive and valuable tool for characterisation of the cytokine profile of MS patients. Decreased numbers of PBMCs secreting IL-b 0 and IL-4, and increased numbers of PBMCs secreting TNF-a, IL-12 and IFN-y were observed in MS patients compared to healthy controls. Treatment with IFN(3 elevated IL-IO and IL-4 levels, and decreased TNF-a, IL-12 and IFN-y levels in these patients. IFN(3/lci was more efficient in decreasing IL-12 secreting cells and IFN(3/1(3 in decreasing IFN-y, and TNF-a secreting cells and elevating IL-4 and IL- 10 secreting cells Increased expression of IL-12Rj31 and TNF-aR was observed in NK cells and decreased expression of WN-7R and IL-I OR was shown in T cells of MS patients compared to controls. IFNf3 therapy reduced IL-12R(3l levels in I and NK cells (IFNf3-la was more effective), and TNF-uR levels in I cells (IFNj3- 1(3 was more effective), but it increased IFN-1R and IL-1OR in T and NK cells of MS patients. Increased levels of the soluble CD95 apoptosis marker were observed in serum of MS patients compared to controls, which further increased after IFN(3 treatment (IFN(3-10 was more efficient). Increased levels of soluble ICAM-1 and VCAM-1 were observed in serum of MS patients compared to controls, which were further increased after treatment with IFN(3 (IFN-1a was more efficient in increasing sICAM-1 and IFNI3-113 in increasing sVCAM- 1 levels) Increased levels of MMP-9, decreased levels of TIMP- 1, and increased MMP-9ITIMP- I ratio was found in serum of MS patients compared to controls, and treatment with IFN decreased MMP-9 levels, increased TIMP-1 levels and decreased MMP-9/TIMP-1 levels ITCXTII 1.. 4'P + tss i,p s a ,lvaS it"j*.. These results indicate an over expression of Thi type cytokines in MS accompanied by a concomitant suppression of Th2 type immune response as well as by alterations in the expression of cytokine receptors. A consequent activation of other immunoregulatory elements (sCD95, adhesion molecules, metalloproteinases) was also observed which was partly modified by IFNI3 treatment. This study provides important evidence on the role of cytokines and of other inflammatory molecules in MS pathogenesis and highlights possible mechanisms of action of IFNI3 treatment, offering new perspectives for novel, more efficient, diagnostic, and therapeutical approaches for the disease.

abstract: Once considered an abundant species in the eastern United States, local populations of red-shouldered hawks, Buteo lineatus, have declined due to habitat destruction. This destruction has created suitable habitat for red-tailed hawks, Buteo jamaicensis, and therefore increased competition between these two raptor species. Since suitable habitat is the main limiting factor for raptors, a computer model was created to simulate the effect of habitat loss in central Maryland and the impact of increased competition between the more aggressive red-tailed hawk. These simulations showed urban growth contributed to over a 30% increase in red-tailed hawk habitat as red-shouldered hawk habitat decreased 62.5-70.1% without competition and 71.8-76.3% with competition. However there was no significant difference seen between the rate of available habitat decline for current and predicted development growth. / Dissertation/Thesis / M.S. Applied Biological Sciences 2011