Maize Streak Virus: diversity and virulence

Zea mays was first introduced to Africa in Ghana by Portuguese traders in the 16th century. The steady spread of maize cultivation since then has made it the most important cereal crop in Africa today. Whereas improved maize genotypes and agricultural techniques enable yearly yields above 10 tons hectare-1 in the developed world, yearly yields across Africa have remained low at about 1 ton hectare-1 in most countries. Although outmoded agricultural practices are the main reason for poor yields, maize pathogens inflict substantial additional losses. Of the many pathogens currently confronting maize farmers in Africa, Maize streak virus (MSV) is the most significant

Comparative and molecular characterisation of a schizophrenia susceptibility locus

A substantial genetic contribution to the aetiology of schizophrenia and other major mental illnesses has been convincingly and repeatedly established by family, twin and adoption studies. However, phenotypic and genetic heterogeneity have severely hampered linkage and association studies, and consequently the molecular basis of the genetic contribution remains undefined. The use of cytogenetic abnormalities to identify disease loci is a well established technique that overcomes many of the problems of linkage and association studies. A balanced t(l;l I)(q42;q14) translocation segregates in a large Scottish family (LOD = 7.1) with schizophrenia and related psychiatric disorders. At least three independent studies have also identified the 1q42 region of the genome as a susceptibility locus for major mental illness. The chromosome 1 breakpoint region now represents one of the best-supported loci for susceptibility to major mental illness. Two novel genes are directly disrupted by the chromosome 1 breakpoint, Disrupted-In-Schizophrenia 1 and 2 (DISCI and DISC2). The central hypothesis of this work is that genes directly disrupted by, or near to the chromosome 1 breakpoint contribute a significant susceptibility to major mental illness. This thesis set out to characterise DISCI, DISC2 and neighboring genes through comparative sequence analysis. Specifically, the research aimed to better define the locus, the genes, their functions and regulatory sequences, to evaluate the functional consequences of the translocation and how these may relate to the t(1;11) phenotype.Human genomic sequence over the breakpoint region was assembled. The DISCI region of the Fugu rubripes genome was cloned and 45 kb of contiguous genomic sequence generated. The orthologous region of the mouse and chicken genomes was identified and characterised. A pipeline for preliminary genomic annotation and subsequent comparative genomic analysis was developed using the cystic fibrosis locus as a model, and subsequently applied to the DISCI locus. The method of "annotation anchored global sequence alignment" substantially increased the sensitivity in detection of biologically relevant conserved sequence motifs. Comparative genomic analysis, RT-PCR and cDNA clone identification were used to construct a transcriptional map of the Fugu genomic region and refine the human transcription map. Conservation of synteny between 0.7 Mb of the human genome and 45 kb of the Fugu genome was demonstrated, with one boundary of synteny being clearly defined. The region of conserved synteny contained the genes Egg Laying Nine-1 (EGLN1), Translin Associated factor X (TRAX) and DISCI in both species.EGLN1 was found to be a member of a previously undescribed gene family. The mouse and human members were identified and characterised. In addition, evolutionary evidence for a novel mechanism of host - pathogen interactions was discovered. TRAX and its homologue Translin were tentatively identified as members of a nucleic acid helicase family of proteins, providing a mechanistic basis for their known biological roles, and suggesting previously undescribed functional aspects of these proteins. DISCI was found to be rapidly evolving in both genomic structure and protein sequence, although three N-terminal motifs and blocks of coiled coil forming potential in the C-terminal half of the protein are conserved features, suggesting a general structure and function for the protein. Neither the antisense transcript DISC2 nor the intergenic splicing of TRAX to DISCI are conserved in Fugu.The work presented in this thesis has substantially enhanced understanding of the chromosome 1 breakpoint locus both at the genomic and encoded protein level. Two novel gene families have been defined and characterised, allowing a more complete evaluation of their functional candidacy in the aetiology of major mental illness. The sequence and clone resources resulting from this work also form the basis for protein functional studies and future characterisation of the locus in animal models

The creative symbiosis of composer and performer (An examination of collaborative practice in partially improvised works)

This thesis was submitted for the degree of Doctor of Philosophy and awarded by Brunel University.This thesis comprises a portfolio of compositions with supporting commentary in addition to a general commentary on past and contemporary models of performance practice. The compositions all use elements of improvisation and are documented in recorded and score formats. Recordings and discussion of the rehearsal process of these works are also included. The thesis is divided into four parts. The first, entitled ‘Context’, examines issues of performance practice through reference to both historical and contemporary models. In this regard, particular attention is given to the work of Miles Davis and Peter Wiegold. Parts 2, 3 and 4 consist of the portfolio of original compositions with sub-headings as follows: ‘Beginnings’, ‘Transition’ and ‘Current Projects’. As a part of the commentary on the portfolio, the role of the performer as creative artist will also be examined

Advances in honeycomb layered oxides: Part II -- Theoretical advances in the characterisation of honeycomb layered oxides with optimised lattices of cations

The quest for a successful condensed matter theory that incorporates diffusion of cations, whose trajectories are restricted to a honeycomb/hexagonal pattern prevalent in honeycomb layered materials is ongoing, with the recent progress discussed herein focusing on symmetries, topological aspects and phase transition descriptions of the theory. Such a theory is expected to differ both qualitatively and quantitatively from 2D electron theory on static carbon lattices, by virtue of the dynamical nature of diffusing cations within lattices in honeycomb layered materials. Herein, we have focused on recent theoretical progress in the characterisation of pnictogen- and chalcogen-based honeycomb layered oxides with emphasis on hexagonal/honeycomb lattices of cations. Particularly, we discuss the link between Liouville conformal field theory to expected experimental results characterising the optimal nature of the honeycomb/hexagonal lattices in congruent sphere packing problems. The diffusion and topological aspects are captured by an idealised model, which successfully incorporates the duality between the theory of cations and their vacancies. Moreover, the rather intriguing experimental result that a wide class of silver-based layered materials form stable Ag bilayers, each comprising a pair of triangular sub-lattices, suggests a bifurcation mechanism for the Ag triangular sub-lattices, which ultimately requires conformal symmetry breaking within the context of the idealised model, resulting in a cation monolayer-bilayer phase transition. Other relevant experimental, theoretical and computational techniques applicable to the characterisation of honeycomb layered materials have been availed for completeness.Comment: 93 pages, 21 figures, 4 tables, title updated, table of contents adde

Univariate and multivariate statistical approaches for the analyses of omics data: sample classification and two-block integration.

The wealth of information generated by high-throughput omics technologies in the context of large-scale epidemiological studies has made a significant contribution to the identification of factors influencing the onset and progression of common diseases. Advanced computational and statistical modelling techniques are required to manipulate and extract meaningful biological information from these omics data as several layers of complexity are associated with them. Recent research efforts have concentrated in the development of novel statistical and bioinformatic tools; however, studies thoroughly investigating the applicability and suitability of these novel methods in real data have often fallen behind. This thesis focuses in the analyses of proteomics and transcriptomics data from the EnviroGenoMarker project with the purpose of addressing two main research objectives: i) to critically appraise established and recently developed statistical approaches in their ability to appropriately accommodate the inherently complex nature of real-world omics data and ii) to improve the current understanding of a prevalent condition by identifying biological markers predictive of disease as well as possible biological mechanisms leading to its onset. The specific disease endpoint of interest corresponds to B-cell Lymphoma, a common haematological malignancy for which many challenges related to its aetiology remain unanswered. The seven chapters comprising this thesis are structured in the following manner: the first two correspond to introductory chapters where I describe the main omics technologies and statistical methods employed for their analyses. The third chapter provides a description of the epidemiological project giving rise to the study population and the disease outcome of interest. These are followed by three results chapters that address the research aims described above by applying univariate and multivariate statistical approaches for sample classification and data integration purposes. A summary of findings, concluding general remarks and discussion of open problems offering potential avenues for future research are presented in the final chapter.Open Acces