Characterization of the effect of nitrogen deficiency on above-ground plant phenotypes in relation to root complexity in maize

Nitrogen (N) is an essential plant nutrient in maize production, and if considering only natural sources, is often the limiting factor world-wide in terms of a plant’s grain yield. For this reason, many farmers around the world supplement available soil N with synthetic man-made forms. Years of over-application of N fertilizer have led to increased N in groundwater and streams due to leaching and run-off from agricultural sites. In the Midwest Corn Belt much of this excess N eventually makes its way to the Gulf of Mexico leading to eutrophication (increase of phytoplankton) and a hypoxic (reduced oxygen) dead zone. Growing concerns about these types of problems and desire for greater input use efficiency have led to demand for crops with improved N use efficiency (NUE) to allow reduced N fertilizer application rates and subsequently lower N pollution. It is well known that roots are responsible for N uptake by plants, but it is relatively unknown how root architecture affects this ability. This research was conducted to better understand the influence of root complexity (RC) in maize on a plant’s response to N stress as well as the influence of RC on other above-ground plant traits. Thirty-one above-ground plant traits were measured for 64 recombinant inbred lines (RILs) from the intermated B73 & Mo17 (IBM) population and their backcrosses (BCs) to either parent, B73 and Mo17, under normal (182 kg N ha-1) and N deficient (0 kg N ha-1) conditions. The RILs were selected based on results from an earlier experiment by Novais et al. (2011) which screened 232 RILs from the IBM to obtain their root complexity measurements. The 64 selected RILs were comprised of 31 of the lowest complexity RILs (RC1) and 33 of the highest complexity RILs (RC2) in terms of root architecture (characterized as fractal dimensions). The use of the parental BCs classifies the experiment as Design III, an experimental design developed by Comstock and Robinson (1952) which allows for estimation of dominance significance and level. Of the 31 traits measured, 12 were whole plant traits chosen due to their documented response to N stress. The other 19 traits were ear traits commonly measured for their influence on yield. Results showed that genotypes from RC1 and RC2 significantly differ for several above-ground phenotypes. We also observed a difference in the number and magnitude of N treatment responses between the two RC classes. Differences in phenotypic trait correlations and their change in response to N were also observed between the RC classes. RC did not seem to have a strong correlation with calculated NUE (ΔYield/ΔN). Quantitative genetic analysis utilizing the Design III experimental design revealed significant dominance effects acting on several traits as well as changes in significance and dominance level between N treatments. Several QTL were mapped for 26 of the 31 traits and significant N effects were observed across the majority of the genome for some N stress indicative traits (e.g. stay-green). This research and related projects are essential to a better understanding of plant N uptake and metabolism. Understanding these processes is a necessary step in the progress towards the goal of breeding for better NUE crops.

Vitamin D status in the first-trimester: effects of Vitamin D deficiency on pregnancy outcomes.

Objective: To assess serum levels of 25-hydroxyvitamin D [25(OH)D] in the first trimester and to determine the factors affecting deficiency levels and its association with pregnancy outcomes. Methods: Serum 25(OH)D concentrations were measured at 11-14 weeks’ gestation in 229 singleton pregnancies using liquid chromatography-tandem mass spectrometry. Results: The median serum 25(OH)D concentration was 10.8 ng/mL and 45.9% of women had severe vitamin D deficiency with concentrations of <10 ng/mL. Logistic regression analysis revealed that covered dressing style, lack of multivitamin intake, season of blood sampling (November-April) were factors associated with 25(OH)D deficiency. There was a negative correlation between 25(OH)D levels and gestational age at sampling. Low 25(OH)D levels were not associated with adverse pregnancy outcomes. Higher rate of cesarean section (CS) was noted in women with 25(OH)D ≥10 ng/mL compared to those with 25(OH)D < 10mg/ml ( p= 0.01). Conclusion: A high prevalence of vitamin D deficiency was observed in early pregnancy which was related to dress code, use of multi-vitamins and season at sampling. Low 25(OH)D levels were not related with adverse pregnancy outcomes. Women with severe vitamin D deficiency were more likely to deliver vaginally.

Iron deficiency anaemia among apparently healthy pre-school children in Lagos, Nigeria.

Background: Iron deficiency, and specifically iron deficiency anaemia, remains one of the most severe and important nutritional deficiencies in the world today. Objective: To estimate the prevalence and associated factors for iron deficiency anaemia among pre-school children in Lagos. Methodology: The study was conducted from December 2009 to February 2010 at the outpatient clinics of Lagos State University Teaching Hospital, Lagos. Serum iron, total iron binding capacity, transferrin saturation and serum ferritin were assayed in subjects. The primary outcome measured was iron deficiency anaemia established based on the following criteria: hemoglobin <11.0 g/dl1 plus 2 or more of the following: MCV <70fl, transferrin saturation <10% or serum ferritin <15ng/ dL. Statistical analysis included Pearson Chi square analysis and logistic regression analysis. Results: A total of 87 apparently healthy subjects were recruited. Only one subject had iron depletion and this child belonged to the ≤ 2 years age category. None of the recruited subjects had iron deficiency without anaemia. Nine of the study subjects (10.11%) had iron deficiency anaemia. The prevalence of iron deficiency anaemia was significantly higher among younger age group than in the older age group (19.1% Vs 2.1%, p = 0.022). The prevalence of iron deficiency anaemia was significantly higher among subjects with weight-for-age, and weight-for-height Z scores below two standard scores (83.3% and 75.0% respectively, p = <0.001 and 0.001 respectively). Conclusion: The overall prevalence of iron deficiency anaemia among study subjects was 10.11%. Iron deficiency anaemia was more common in children aged two years and below. Weight-for-age and weight-for-height Z scores below minus two standard scores were strongly associated with iron deficiency anaemia.

Prevalence and factors associated with anthropometric failure, vitamin A and iron deficiency among adolescents in a Nigerian urban community.

Background: Under nutrition is a problem of severe magnitude in low income countries like Nigeria. Adolescent school children might also be vulnerable. The dearth of data hinders planning of school health and nutrition programmes for school children. Objective: To determine the prevalence of stunting, thinness; vitamin A and iron deficiencies among adolescent students in Nsukka urban, Nigeria and to determine factors that are associated with these nutritional problems. Methods: A total of 400 participants were randomly selected from 717 students aged 12 – 18 years in 3 randomly selected secondary schools. Questionnaires, anthropometric measurements, and blood analyses were the data collection methods employed. Results: The prevalence of stunting was 33.3% and thinness 31.0%. Neither overweight nor obesity was observed. While 64.0% were anaemic; 44.0% had vitamin A deficiency (VAD). A total of 48.0% had both anaemia and stunting, 42% had VAD + thinness; while 40% had anaemia + VAD. Household income was a predictor of vitamin A status. Children from medium/ high income households had higher odds of having VAD than those from low income households (AOR=0.14; 95% CI=0.031, 0.607; P=0.009). Household income (AOR=0.12; 95% CI=0.021, 0.671; P=0.016), and age (AOR=0.09; 95% CI=0.014, 0.587; P=0.012) were independent determinants of height-for-age status. Conclusion: Among urban adolescent students in Nigeria, stunting, thinness, anaemia and VAD were problems of public health significance. Age and household monthly income played major roles.

PREVALENCE AND PREDICTORS OF VITAMIN A DEFICIENCY AMONG INFANTS IN WESTERN KENYA USING A CROSS-SECTIONAL ANALYSIS

Vitamin A (VA) deficiency (VAD) is a major nutritional public health problem among children under-5-years-old in the developing world including Kenya. A community-based cross-sectional survey among 1,630 children (aged 6-23 mos) was undertaken in Western Kenya. A questionnaire was administered to collect demographic, socio-economic and dietary intake information. Prevalence of low retinol-binding protein (RBP) concentrations was assessed using Dried Blood Spot (DBS) methodology. Analysis of RBP was carried out using rapid enzyme immunoassay (EIA) and C-reactive protein (CRP) was carried out using enzyme linked immunosorbent assay (ELISA) to estimate VA and sub-clinical inflammation statuses, respectively. Values were adjusted for influence of inflammation using CRP (CRP >5 mg/L) and population prevalence of VAD (RBP <0.825 μmol/L, biologically equivalent to 0.70 μmol/L retinol) estimated. Anthropometric data gave three indices: stunting, wasting and underweight—all of which took age and sex into consideration. Mean (geometric± SD) concentration of RBP was adequate (1.56±0.79μmol/L) but the inflammation-adjusted mean (±SE) prevalence of VAD was high (20.1±1.1%) in this population. The level of CRP was within normal range (1.06±4.95 mg/L) whilst 18.4±0.9% of the children had subclinical inflammation (CRP>5 mg/L). Intake of VA capsule (VAC) by a child was a predictor of VAD with children who have not taken VA during the past 1 year prior to the survey having a 30% increased risk of VAD (OR (CI): 1.3 (1.1-1.7); p=0.025. Additionally, age of the child was a predictor with older children (18-23 mos) having a 30 % increased risk of VAD (OR (CI): 1.3 (1.1-1.9); p=0.035); the caretaker’s knowledge on VA and nutrition was also a predictor of VAD with children whose caretaker’s had poor knowledge having a 40 % increased risk of VAD (OR (CI): 1.4 (1.0-1.9); p=0.027. A child’s district of residence was also a significant predictor of VAD. Prevalence of VAD in this sample of infants was high. Predictors of VAD included child intake of VAC in the last 1 year before the survey, older children, children whose caretakers had poor VA and nutritional knowledge and a child’s district of residence. There is a need to improve knowledge on nutrition and VA of caretakers; undertake a targeted VAC distribution, particularly in children older than 1 year and above and use a sustainable food-based intervention in the areas with severe VAD.

PREVALENCE OF IRON DEFICIENCY ANAEMIA AND DIETARY IRON INTAKE AMONG INFANTS AGED SIX TO NINE MONTHS IN KEIYO SOUTH SUB COUNTY, KENYA

The increased prevalence of iron deficiency among infants can be attributed to the consumption of an iron deficient diet or a diet that interferes with iron absorption at the critical time of infancy, among other factors. The gradual shift from breast milk to other foods and liquids is a transition period which greatly contributes to iron deficiency anaemia (IDA). The purpose of this research was to assess iron deficiency anaemia among infants aged six to nine months in Keiyo South Sub County. The specific objectives of this study were: to establish the prevalence of infants with iron deficiency anaemia and dietary iron intake among infants aged 6 to 9 months. The cross sectional study design was adopted in this survey. This study was conducted in three health facilities in Keiyo South Sub County. The infants were selected by use of a two stage cluster sampling procedure. Systematic random sampling was then used to select a total of 244 mothers and their infants. Eighty two (82) infants were selected from Kamwosor sub-district hospital and eighty one (81) from both Nyaru and Chepkorio health facilities. Interview schedules, 24-hour dietary recall and food frequency questionnaires were used for collection of dietary iron intake. Biochemical tests were carried out by use of the Hemo-control photochrometer at the health facilities. Infants whose hemoglobin levels were less than 11g/dl were considered anaemic. Further, peripheral blood smears were conducted to ascertain the type of nutritional anaemia. Data was analyzed using the Statistical Package for Social Sciences (SPSS) computer software version 17, 2009. Dietary iron intake was analyzed using the NutriSurvey 2007 computer software. Results indicated that the mean hemoglobin values were 11.3± 0.84 g/dl. Twenty one percent (21.7%) of the infants had anaemia and further 100% of peripheral blood smears indicated iron deficiency anaemia. Dietary iron intake was a predictor of iron deficiency anaemia in this study (t=-3.138; p=0.01). Iron deficiency anaemia was evident among infants in Keiyo South Sub County. The Ministry of Health should formulate and implement policies on screening for anaemia and ensure intensive nutrition education on iron rich diets during child welfare clinics.

Influence of levels and forms of selenium associated with levels of vitamins C and E on the performance, yield and composition of tilapia fillet

Objetivou-se avaliar a influência da vitamina C (VC), vitamina E (VE) e de duas formas de selênio sobre o desempenho, rendimento e qualidade do filé de tilápia Nilótica. O experimento foi realizado num delineamento inteiramente casualizado composto por seis tratamentos, os quais foram constituídos pela adição de 100, 200 e 400 mg kg-1 das vitaminas C e E, associados com 0,1, 0,2 e 0,4 mg kg-1 de duas formas de selênio. Cada tratamento foi constituído por cinco repetições de 30 peixes cada. A dieta com 200 mg kg-1 de VC e VE + 0,2 mg kg-1 de selênio orgânico proporcionou ganho de peso, comprimento corporal e fator de conversão alimentar semelhantes aos tratamentos com 400 mg kg-1 de VC e VE + 0,4 mg kg-1 de selênio orgânico ou inorgânico. A adição de selênio orgânico à dieta melhorou o ganho de peso e o fator de conversão alimentar em comparação com o selênio inorgânico. A dieta com 0,2 mg kg-1 de selênio orgânico apresentou nível de glutationa peroxidase igual ao da dieta com 0,4 mg kg-1 de selênio inorgânico. Os rendimentos de carcaça e filé não foram influenciados pelos tratamentos, entretanto houve efeito dos tratamentos na composição química do filé.

Abnormal primary and permanent dentitions with ectodermal symptoms predict WNT10A deficiency

BACKGROUND: The WNT10A protein is critical for the development of ectodermal appendages. Variants in the WNT10A gene may be associated with a spectrum of ectodermal abnormalities including extensive tooth agenesis. METHODS: In seven patients with severe tooth agenesis we identified anomalies in primary dentition and additional ectodermal symptoms, and assessed WNT10A mutations by genetic analysis. RESULTS: Investigation of primary dentition revealed peg-shaped crowns of primary mandibular incisors and three individuals had agenesis of at least two primary teeth. The permanent dentition was severely affected in all individuals with a mean of 21 missing teeth. Primary teeth were most often present in positions were succedaneous teeth were missing. Furthermore, most existing molars had taurodontism. Light, brittle or coarse hair was reported in all seven individuals, hyperhidrosis of palms and soles in six individuals and nail anomalies in two individuals. The anomalies in primary dentition preceded most of the additional ectodermal symptoms. Genetic analysis revealed that all seven individuals were homozygous or compound heterozygous for WNT10A mutations resulting in C107X, E222X and F228I. CONCLUSIONS: We conclude that tooth agenesis and/or peg-shaped crowns of primary mandibular incisors, severe oligodontia of permanent dentition as well as ectodermal symptoms of varying severity may be predictors of bi-allelic WNT10A mutations of importance for diagnosis, counselling and follow-up.

Development and application of a selenium speciation method in cattle feed and beef samples using HPLC-ICP-MS: evaluating the selenium metabolic process in cattle.

2016

Investigating the links between muscle strength, sun exposure, dietary vitamin D intake and the vitamin D status of ambulatory older adults in South East Queensland

Vitamin D deficiency and insufficiency are now seen as a contemporary health problem in Australia with possible widespread health effects not limited to bone health1. Despite this, the Vitamin D status (measured as serum 25-hydroxyvitamin D (25(OH)D)) of ambulatory adults has been overlooked in this country. Serum 25(OH)D status is especially important among this group as studies have shown a link between Vitamin D and fall risk in older adults2. Limited data also exists on the contributions of sun exposure via ultraviolet radiation and dietary intake to serum 25(OH)D status in this population. The aims of this project were to assess the serum 25(OH)D status of a group of older ambulatory adults in South East Queensland, to assess the association between their serum 25(OH)D status and functional measures as possible indicators of fall risk, obtain data on the sources of Vitamin D in this population and assess whether this intake was related to serum 25(OH)D status and describe sun protection and exposure behaviors in this group and investigate whether a relationship existed between these and serum 25(OH)D status. The collection of this data assists in addressing key gaps identified in the literature with regard to this population group and their Vitamin D status in Australia. A representative convenience sample of participants (N=47) over 55 years of age was recruited for this cross-sectional, exploratory study which was undertaken in December 2007 in south-east Queensland (Brisbane and Sunshine coast). Participants were required to complete a sun exposure questionnaire in addition to a Calcium and Vitamin D food frequency questionnaire. Timed up and go and handgrip dynamometry tests were used to examine functional capacity. Serum 25(OH)D status and blood measures of Calcium, Phosphorus and Albumin were determined through blood tests. The Mean and Median serum 25-Hydroxyvitamin D (25(OH)D) for all participants in this study was 85.8nmol/L (Standard Deviation 29.7nmol/L) and 81.0nmol/L (Range 22-158nmol/L), respectively. Analysis at the bivariate level revealed a statistically significant relationship between serum 25(OH)D status and location, with participants living on the Sunshine Coast having a mean serum 25(OH)D status 21.3nmol/L higher than participants living in Brisbane (p=0.014). While at the descriptive level there was an apparent trend towards higher outdoor exposure and increasing levels of serum 25(OH)D, no statistically significant associations between the sun measures of outdoor exposure, sun protection behaviors and phenotypic characteristics and serum 25(OH)D status were observed. Intake of both Calcium and Vitamin D was low in this sample with sixty-eight (68%) of participants not meeting the Estimated Average Requirements (EAR) for Calcium (Median=771.0mg; Range=218.0-2616.0mg), while eighty-seven (87%) did not meet the Adequate Intake for Vitamin D (Median=4.46ug; Range=0.13-30.0ug). This raises the question of how realistic meeting the new Adequate Intakes for Vitamin D is, when there is such a low level of Vitamin D fortification in this country. However, participants meeting the Adequate Intake (AI) for Vitamin D were observed to have a significantly higher serum 25(OH)D status compared to those not meeting the AI for Vitamin D (p=0.036), showing that meeting the AI for Vitamin D may play a significant role in determining Vitamin D status in this population. By stratifying our data by categories of outdoor exposure time, a trend was observed between increased importance of Vitamin D dietary intake as a possible determinant of serum 25(OH)D status in participants with lower outdoor exposures. While a trend towards higher Timed Up and Go scores in participants with higher 25(OH) D status was seen, this was only significant for females (p=0.014). Handgrip strength showed statistically significant association with serum 25(OH)D status. The high serum 25(OH)D status in our sample almost certainly explains the limited relationship between functional measures and serum 25(OH)D. However, the observation of an association between slower Time Up and Go speeds, and lower serum 25(OH)D levels, even with a small sample size, is significant as slower Timed Up and Go speeds have been associated with increased fall risk in older adults3. Multivariable regression analysis revealed Location as the only significant determinant of serum 25(OH)D status at p=0.014, with trends (p=>0.1) for higher serum 25(OH)D being shown for participants that met the AI for Vitamin D and rated themselves as having a higher health status. The results of this exploratory study show that 93.6% of participants had adequate 25(OH)D status-possibly due to measurement being taken in the summer season and the convenience nature of the sample. However, many participants do not meet their dietary Calcium and Vitamin D requirements, which may indicate inadequate intake of these nutrients in older Australians and a higher risk of osteoporosis. The relationship between serum 25(OH)D and functional measures in this population also requires further study, especially in older adults displaying Vitamin D insufficiency or deficiency.

Internationalization of Chinese and Korean firms

This article compares and contrasts the growth of Chinese and Korean multinational enterprises (MNEs). The article identifies the similarities and differences between Chinese and Korean MNEs in terms of motivations for internationalization, expansion strategies, and paths. The goal of this article is to contribute to the literature by shifting focus on host-country conditions to home-country conditions in explaining the drivers for firms' internationalization. We conclude that firms are motivated to expand abroad when faced with domestic competitive disadvantages resulting from absence or deficiency of one or more of Porter's Diamond attributes in their domestic market. Implications for further studies are also explored.

Major depressive disorder and nutritional medicine : a review of monotherapies and adjuvant treatments

A literature review was conducted to examine the evidence for nutritional interventions in depression. It revealed a number of significant conclusions. Interestingly, more positive clinical trials were found to support adjuvant, rather than monotherapeutic, use of nutrients to treat depression. Much evidence exists in the area of adjuvant application of folic acid, S-adenosyl-methionine, omega-3, and L-tryptophan with antidepressants. Current evidence does not support omega-3 as an effective monotherapy to treat depression. However, this may be due, at least in part, to olive oil being used as the control intervention, some studies using docosahexaenoic acid alone or a higher docosahexaenoic acid to eicosapentaenoic acid ratio, and significant heterogeneity regarding depressive populations. Nevertheless, adjunctive prescription of omega-3 with antidepressants, or in people with dietary deficiency, may be beneficial. Inositol lacks evidence as an effective antidepressant and cannot be currently recommended. Evidence on the use of L-trytophan for depression is inconclusive and additional studies utilizing a more robust methodology are required.

Biochemical characterization of Aprataxin, the protein deficient in Ataxia with Oculomotor Apraxia type 1

Neurodegenerative disorders are heterogenous in nature and include a range of ataxias with oculomotor apraxia, which are characterised by a wide variety of neurological and ophthalmological features. This family includes recessive and dominant disorders. A subfamily of autosomal recessive cerebellar ataxias are characterised by defects in the cellular response to DNA damage. These include the well characterised disorders Ataxia-Telangiectasia (A-T) and Ataxia-Telangiectasia Like Disorder (A-TLD) as well as the recently identified diseases Spinocerebellar ataxia with axonal neuropathy Type 1 (SCAN1), Ataxia with Oculomotor Apraxia Type 2 (AOA2), as well as the subject of this thesis, Ataxia with Oculomotor Apraxia Type 1 (AOA1). AOA1 is caused by mutations in the APTX gene, which is located at chromosomal locus 9p13. This gene codes for the 342 amino acid protein Aprataxin. Mutations in APTX cause destabilization of Aprataxin, thus AOA1 is a result of Aprataxin deficiency. Aprataxin has three functional domains, an N-terminal Forkhead Associated (FHA) phosphoprotein interaction domain, a central Histidine Triad (HIT) nucleotide hydrolase domain and a C-terminal C2H2 zinc finger. Aprataxins FHA domain has homology to FHA domain of the DNA repair protein 5’ polynucleotide kinase 3’ phosphatase (PNKP). PNKP interacts with a range of DNA repair proteins via its FHA domain and plays a critical role in processing damaged DNA termini. The presence of this domain with a nucleotide hydrolase domain and a DNA binding motif implicated that Aprataxin may be involved in DNA repair and that AOA1 may be caused by a DNA repair deficit. This was substantiated by the interaction of Aprataxin with proteins involved in the repair of both single and double strand DNA breaks (XRay Cross-Complementing 1, XRCC4 and Poly-ADP Ribose Polymerase-1) and the hypersensitivity of AOA1 patient cell lines to single and double strand break inducing agents. At the commencement of this study little was known about the in vitro and in vivo properties of Aprataxin. Initially this study focused on generation of recombinant Aprataxin proteins to facilitate examination of the in vitro properties of Aprataxin. Using recombinant Aprataxin proteins I found that Aprataxin binds to double stranded DNA. Consistent with a role for Aprataxin as a DNA repair enzyme, this binding is not sequence specific. I also report that the HIT domain of Aprataxin hydrolyses adenosine derivatives and interestingly found that this activity is competitively inhibited by DNA. This provided initial evidence that DNA binds to the HIT domain of Aprataxin. The interaction of DNA with the nucleotide hydrolase domain of Aprataxin provided initial evidence that Aprataxin may be a DNA-processing factor. Following these studies, Aprataxin was found to hydrolyse 5’adenylated DNA, which can be generated by unscheduled ligation at DNA breaks with non-standard termini. I found that cell extracts from AOA1 patients do not have DNA-adenylate hydrolase activity indicating that Aprataxin is the only DNA-adenylate hydrolase in mammalian cells. I further characterised this activity by examining the contribution of the zinc finger and FHA domains to DNA-adenylate hydrolysis by the HIT domain. I found that deletion of the zinc finger ablated the activity of the HIT domain against adenylated DNA, indicating that the zinc finger may be required for the formation of a stable enzyme-substrate complex. Deletion of the FHA domain stimulated DNA-adenylate hydrolysis, which indicated that the activity of the HIT domain may be regulated by the FHA domain. Given that the FHA domain is involved in protein-protein interactions I propose that the activity of Aprataxins HIT domain may be regulated by proteins which interact with its FHA domain. We examined this possibility by measuring the DNA-adenylate hydrolase activity of extracts from cells deficient for the Aprataxin-interacting DNA repair proteins XRCC1 and PARP-1. XRCC1 deficiency did not affect Aprataxin activity but I found that Aprataxin is destabilized in the absence of PARP-1, resulting in a deficiency of DNA-adenylate hydrolase activity in PARP-1 knockout cells. This implies a critical role for PARP-1 in the stabilization of Aprataxin. Conversely I found that PARP-1 is destabilized in the absence of Aprataxin. PARP-1 is a central player in a number of DNA repair mechanisms and this implies that not only do AOA1 cells lack Aprataxin, they may also have defects in PARP-1 dependant cellular functions. Based on this I identified a defect in a PARP-1 dependant DNA repair mechanism in AOA1 cells. Additionally, I identified elevated levels of oxidized DNA in AOA1 cells, which is indicative of a defect in Base Excision Repair (BER). I attribute this to the reduced level of the BER protein Apurinic Endonuclease 1 (APE1) I identified in Aprataxin deficient cells. This study has identified and characterised multiple DNA repair defects in AOA1 cells, indicating that Aprataxin deficiency has far-reaching cellular consequences. Consistent with the literature, I show that Aprataxin is a nuclear protein with nucleoplasmic and nucleolar distribution. Previous studies have shown that Aprataxin interacts with the nucleolar rRNA processing factor nucleolin and that AOA1 cells appear to have a mild defect in rRNA synthesis. Given the nucleolar localization of Aprataxin I examined the protein-protein interactions of Aprataxin and found that Aprataxin interacts with a number of rRNA transcription and processing factors. Based on this and the nucleolar localization of Aprataxin I proposed that Aprataxin may have an alternative role in the nucleolus. I therefore examined the transcriptional activity of Aprataxin deficient cells using nucleotide analogue incorporation. I found that AOA1 cells do not display a defect in basal levels of RNA synthesis, however they display defective transcriptional responses to DNA damage. In summary, this thesis demonstrates that Aprataxin is a DNA repair enzyme responsible for the repair of adenylated DNA termini and that it is required for stabilization of at least two other DNA repair proteins. Thus not only do AOA1 cells have no Aprataxin protein or activity, they have additional deficiencies in PolyADP Ribose Polymerase-1 and Apurinic Endonuclease 1 dependant DNA repair mechanisms. I additionally demonstrate DNA-damage inducible transcriptional defects in AOA1 cells, indicating that Aprataxin deficiency confers a broad range of cellular defects and highlighting the complexity of the cellular response to DNA damage and the multiple defects which result from Aprataxin deficiency. My detailed characterization of the cellular consequences of Aprataxin deficiency provides an important contribution to our understanding of interlinking DNA repair processes.