This thesis describes the development of a synthetic route that encodes a library of compounds containing medium-sized ring systems, with particular emphasis on the use of oxidative fragmentation and rearrangement strategies. Chapter 1 introduces diversity oriented synthesis (DOS) with particular emphasis on medium-sized ring synthesis and fragmentation/rearrangement protocols to achieve diversity. A more detailed discussion of oxidative fragmentation and rearrangement methods is also presented. Chapter 2 describes strategies for the synthesis of a collection of heterocyclic compounds known as diazabenz[e]aceanthrylenes. The scope of the reaction was explored as a function of a range of substituents and of the ring size of the N-aryl lactam that was used. Spectroscopic observations associated with this set of compounds are also discussed. Chapter 3 describes the development of an m-CPBA-mediated oxidative fragmentation of the diazabenz[e]aceanthrylenes. Analysis of the products from these reactions revealed the presence of atropisomerism due to restricted rotation about the N sp²-C(aryl) sp² bond. Chapter 4 focuses on a related example of oxidative fragmentation from the literature. A previously overlooked stereogenic axis is explored in this system using X-ray crystallographic analysis and variable temperature ¹H NMR spectroscopy. Reinterpretation of the reported mechanism-probing experiment led to the isolation of an alternative isomeric product and an improved interpretation for the reaction outcome is presented. Variable temperature ¹H NMR spectroscopic experiments revealed the energy barrier to racemisation in the medium-sized ring-containing analogues and based on this data the mode of ring inversion is discussed. Chapter 5 describes three rearrangements of the medium-sized ring system created in Chapter 3 including the formation of an azepinoindole ring structure, a Favorskii reaction and spiro-oxindole synthesis. A rationalisation for these reaction outcomes is included along with experimental support of mechanistic proposals. The generality and scope of the reactions are demonstrated including a nucleophile screen. Chapter 6 describes the synthesis of a library of 69 compounds consisting of examples of the core structures described in Chapters 2, 3 and 5. A discussion of the selection process and adaption of the protocol to parallel synthesis is presented. This chapter concludes with preliminary screening of the library against a variety of strains of yeasts and bacteria.

Natural environments expose organisms to multifarious selective pressures involving numerous aspects of the overall phenotype, therefore eliciting a response from multiple correlated loci. It has been hypothesized that chromosomal rearrangements can play a role in facilitating local adaptation by establishing new linkage relationships and modifying the recombination patterns between the different chromosomal forms, allowing coordinated adaptation of several loci. The central aim of the work presented here is to test this hypothesis using Drosophila americana as a model system. This species segregates several inversions and an X-4 centromeric fusion which makes it an excellent model to study the role of chromosomal rearrangements on local adaptation. This hypothesis was tested using several approaches. The geographic distribution of the chromosomal rearrangements was determined through sampling of wild populations from a broad geographic range. It was found that several of the chromosomal rearrangements exhibit clinal variation. Furthermore, many of these are found in high linkage disequilibrium. The X-4 fusion is highly associated with inversions on the X and 4th chromosome. Also, two inversions on chromosome 5 are in strong negative linkage disequilibrium. The sequence variation associated with rearrangements of the X was studied using inbred lines. The results show that the inversion and the fusion strongly influence variation on this chromosome. Regions of significant population differentiation and linkage with the rearrangements are found interspersed with loci showing neutral variation indicating that in spite of recombination, allelic associations are maintained on this chromosome. The analysis was also extended to flies directly collected from the wild sampled from a region encompassing a large part of the species' range. Loci throughout chromosome X and 4 were genotyped. Sites in high linkage disequilibrium with the rearrangements and with other assayed sites were found in close proximity with sites that did not show this pattern. In conclusion, the clinal distribution of chromosomal rearrangements and associated genetic variation in conjunction with the detection of islands of linkage disequilibrium among the rearrangements and loci on both chromosomes indicate that chromosomal rearrangements are facilitating local adaptation in D. americana.

Thesis (Ph. D.)--University of Missouri-Columbia, 2003. / Typescript. Vita. Includes bibliographical references (leaves 224-250). Also available on the Internet.

Thesis (Ph. D.)--University of Missouri-Columbia, 2003. / Typescript. Vita. Includes bibliographical references (leaves 224-250). Also available on the Internet.

A central theme in phylogenetics is the reconstruction and analysis of evolutionary trees from a given set of data. To determine the optimal search methods for the reconstruction of trees, it is crucial to understand the size and structure of neighbourhoods of trees under tree rearrangement operations. The diameter and size of the immediate neighbourhood of a tree has been well-studied, however little is known about the number of trees at distance two, three or (more generally) k from a given tree. In this thesis we explore previous results on the size of these neighbourhoods under common tree rearrangement operations (NNI, SPR and TBR). We obtain new results concerning the number of trees at distance k from a given tree under the Robinson-Foulds (RF) metric and the Nearest Neighbour Interchange (NNI) operation, and the number of trees at distance two from a given tree under the Subtree Prune and Regraft (SPR) operation. We also obtain an exact count for the number of pairs of binary phylogenetic trees that share a first RF or NNI neighbour.

Thesis (Ph.D.) -- McMaster University, 1997. / Includes bibliographical references. Also available via World Wide Web.

Thesis (Ph. D.)--McMaster University (Canada), 1990. / Source: Dissertation Abstracts International, Volume: 62-13, Section: A, page: 0000.

Thesis (Ph. D.)--University of Wisconsin--Madison, 1970. / Vita. Typescript. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references.

Submitted by FLAVIA MARCORIN DE OLIVEIRA null (flaviamarcorindeoliveira@gmail.com) on 2016-06-30T18:11:11Z No. of bitstreams: 1 Flávia Marcorin versão final.pdf: 2914788 bytes, checksum: da4eb36add8e9d52d25649b86df175e1 (MD5) / Approved for entry into archive by Ana Paula Grisoto (grisotoana@reitoria.unesp.br) on 2016-07-04T18:08:05Z (GMT) No. of bitstreams: 1 oliveira_fm_me_rcla.pdf: 2914788 bytes, checksum: da4eb36add8e9d52d25649b86df175e1 (MD5) / Made available in DSpace on 2016-07-04T18:08:05Z (GMT). No. of bitstreams: 1 oliveira_fm_me_rcla.pdf: 2914788 bytes, checksum: da4eb36add8e9d52d25649b86df175e1 (MD5) Previous issue date: 2016-06-16 / Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) / A família Loricariidae é uma das mais diversificadas da ordem Siluriformes, com espécies distribuídas entre sete subfamílias: Hypoptopomatinae, Loricariinae, Hypostominae, Neoplecostominae, Lithogeninae, Delturinae e Ancistrinae. As espécies do gênero Ancistrus Kner, 1854, pertencem à subfamília Ancistrinae, têm mostrado grande variação cariotípica, além de características interessantes do ponto de vista citogenético como a presença de cromossomos sexuais e polimorfismos cromossômicos. Desta forma o objetivo do presente trabalho foi caracterizar os cromossomos de quatro espécies do gênero Ancistrus (Ancistrus sp. 1 “cupim”, Ancistrus sp. 2 “cupim”, Ancistrus sp. “mutuca” e Ancistrus sp. “soberbo”) pertencentes à bacia do Paraguai utilizando técnicas de citogenética clássica e molecular para melhor compreensão da evolução cariotípica dessas espécies. As espécies estudadas apresentaram número diploide variando de 2n=42 a 2n=54, NOR localizadas em regiões pericentroméricas e terminais, além de heteromorfismo de tamanho dessas regiões (NOR) em um dos homólogos nas quatro espécies estudadas. O bandamento C mostrou presença de pouca heterocromatina com exceção das espécies Ancistrus sp. 2 “cupim” e Ancistrus sp. “soberbo” que apresentaram dois blocos grandes de heterocromatina em um par de cromossomos, tanto nos machos quanto nas fêmeas. Um exemplar fêmea da espécie Ancistrus sp. 1 “cupim” também apresentou um bloco grande de heterocromatina em um dos homólogos do par 7, sendo esses resultados indicativos de provável relação entre esses blocos de heterocromatina e a diferenciação de cromossomos sexuais. Os resultados obtidos pela técnica de FISH utilizando sondas de DNAr 18S e 5S mostraram que o DNAr 18S está localizado na mesma região da NOR, o DNAr 5S está distribuído em quatro e cinco pares cromossômicos e o double FISH não mostrou co-localização desses genes. No entanto as espécies Ancistrus sp. 2 “cupim” e Ancistrus sp. “soberbo” mostraram variação nos resultados com marcações de DNAr em blocos de heterocromatina. O uso de sonda telomérica mostrou marcações nos telômeros dos cromossomos das quatro espécies estudadas e marcação pericentromérica em um par de cromossomos da espécie Ancistrus sp. 2 “cupim”. Nossos resultados evidenciam possíveis rearranjos cromossômicos do tipo fusão cêntrica, contribuindo com a redução do número diploide e inversões pericêntricas e paracêntricas resultando na localização dos sítios de DNAr. / The Loricariidae family is one of the most diversified of the Siluriformes order, with species distributed in seven subfamilies: Hypoptopomatinae, Loricariinae, Hypostominae, Neoplecostominae, Lithogeninae, Delturinae and Ancistrinae. The species of the genus Ancistrus Kner, 1854, belong to the subfamily Ancistrinae, have shown great karyotype variation, and interesting features of the cytogenetic point of view as the presence of sex chromosomes and chromosome polymorphisms. Thus the aim of this study was to characterize the chromosomes of four species of Ancistrus genus (Ancistrus sp. 1 "cupim", Ancistrus sp. 2 "cupim", Ancistrus sp. "mutuca" and Ancistrus sp. "soberbo") belonging to Paraguay basin using techniques of classical and molecular cytogenetics to better understand the karyotype evolution of these species. The species showed diploid number ranging from 2n = 42 to 2n = 54, NOR located in pericentomeric and terminal regions, and these regions size heteromorphism (NOR) in one of the homologous in the four species. The C-banding showed the presence of few heterochromatin with the exception of species Ancistrus sp. 2 "cupim" and Ancistrus sp. "soberbo" that had two large blocks of heterochromatin in a pair of chromosomes in both males and females. An exemplary female of the species Ancistrus sp. 1 "cupim" also presented a large block of heterochromatin in one of the pair of 7 homologous, and these results indicating probable relationship between these heterochromatin blocks and differentiation of sex chromosomes. The results obtained by FISH technique using probes 18S rDNA and 5S showed that the 18S rDNA is located in the same region of NOR, the 5S rDNA is distributed in four and five chromosome pairs and double FISH showed colocalization of these genes. However of Ancistrus species sp. 2 "cupim" and Ancistrus sp. "soberbo" showed variation in results with rDNA markings in heterochromatin blocks. The use of telomeric probe showed markings on the telomeres of the chromosomes of four species studied and pericentromeric marking on a pair of chromosomes of the species Ancistrus sp. 2 "cupim". Our results indicate possible chromosomal rearrangements type fusion centric, contributing to the reduction of the diploid number and pericentric inversions and paracentric resulting in the location of rDNA sites. / FAPESP: 2015/05993-3

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