Proefschrift--Rijksuniversiteit te Groningen. / "Stellingen" [2] p. inserted. Includes bibliographical references.

Thesis (Ph. D.)--University of Wisconsin--Madison, 1966. / Abstracted in Dissertations abstracts, v.27 (1966) no. 6, p. 2189-B. Typescript. Vita. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references.

Thesis (M.S.) -- Worcester Polytechnic Institute. / Keywords: DNA; hybridization; microfluidics; kinetics. Includes bibliographical references (leaves 145-148).

Resumo: O presente trabalho teve como objetivo o planejamento e síntese de novas substâncias inibidoras da acetilcolinesterase, enzima cuja modulação está associada ao tratamento de diversas patologias, entre elas a doença de Alzheimer. Para isto foi utilizada a técnica de docking molecular visando o reconhecimento dos sítios de interação da enzima que possibilitaram a modelagem de novos compostos híbridos. O modelo de docking foi criado utilizando a enzima de Torpedo californica, muito semelhante à acetilcolinesterase humana, complexada com a tacrina, donepezil e (-)-huperzina A que foi validado por cross-docking. Em seguida, a (-)-3-O-acetil-espectalina (32), (-)-3-O-acetil-cassina (36) e derivados virtualmente planejados foram ancorados na enzima e a partir de sobreposições destes alcalóides com os inibidores de acetilcolinesterase comerciais foram planejados diversos híbridos que apresentaram interações mais efetivas com a proteína que os modelos originais. Além disto, foram realizados estudos sobre o modo de inibição de 32, que corroboraram os resultados obtidos in vivo, apresentando inibição não-competitiva. A análise por docking e dinâmica molecular sugeriu que 32 e 36 apresentam diferentes interações com a enzima, sendo 36 potencialmente mais ativo que 32. O híbrido planejado por docking que apresentou melhor interação com a AChE, além de maior viabilidade sintética foi selecionado e por análise retrossintética foram escolhidas a 3-hidroxi-2-hidrometil-piridina (38) e a 4-bromoquinolina (42) como materiais de partida para uma rota convergente. Os estudos sintéticos levaram a obtenção de intermediários piridínicos sendo que numa das etapas da rota proposta, onde o objetivo era a proteção seletiva da hidroxila piridínica de 38, foi observada a proteção da hidroxila metil-piridínica o que sugere a migração dos grupos acetil... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: The goal of this research deals with the design and synthesis of new acetylcholinesterase inhibitor molecules. This enzyme is associated to the treatment of several pathologies including Alzheimer's disease and thus the importance of studying molecules that may interact with it. To fulfill this task we used molecular docking aiming to recognize the enzyme's interaction sites allowing us to design new hybrid compounds. The docking model was created using Torpedo californica's enzyme, very similar to human acetylcholinesterase, complexed with tacrine, donepezil and (-)-huperzine A, all validated by cross-docking. Furthermore, (-)-3-O-acetyl-espectaline (32), (-)-3-O-acetyl-cassine (36) and virtually designed derivatives, were docked into the enzyme through geometric comparisons of known commercially available acetylcholinesterase inhibitors, allowing us to produce a series of enzyme effective molecular hybrids when compared to the original ones. Additionally, we studied the inhibition mode of action of 32 that confirmed the in vivo results showing a non-competitive inhibition. Docking and molecular dynamics of 32 and 36 revealed that they showed different enzyme interactions and that the latter compound was potentially more active than 32. The hybrid molecule planned by docking that showed a better interaction with AChE and, with the best synthetic viability was selected showing 3-hydroxy-2-hydromethyl-pyridine (38) and 4-bromoquinoline (42) as the starting materials of a convergent route. The synthesis studies lead us to the production of pyridine intermediaries and, in one of the stages where the main goal was the selective protection of a pyridine hydroxyl group; we observed instead, the protection of the methyl pyridine hydroxyl moiety suggesting the migration of the acetyl and benzoyl groups. We used several coupling methods for the pyridine and quinoline nuclei... (Complete abstract click electronic access below) / Orientador: Vanderlan da Silva Bolzani / Coorientador: Carlos Alberto Mansour Fraga / Banca: Ângela Regina Araújo / Banca: Luiz Carlos Dias / Banca: Maria Helena Sarragiotto / Banca: Nelilma Correia Romeiro / Doutor

1. Serial cytological observations were made on one abnormal seedling from the thornless segregants of the F2 progeny from crossing two tetraploid (2n=28) Rubus species. The number of root tip chromosomes was found to vary from 9 to 48 per cells, with the mode always at 35. The wide variation in chromosome number decreased with time, until at one point there was almost stability at 2n=35. 2. The number of satellites per cell was proportional to the number of nuoleoli per cell. Evidence from the number of satellites per cell suggests that different chromosomes were being involved in the different complements. 3. There was a correlation between the chromosome number and corresponding cell sizes within the aneuploid series. 4. Virus infection was not responsible for the variation of somatic chromosome numbers from cell to cell. 'The cause of the instability was not definitely located but it is suggested that its initiation arose from the egg sell as Rubus pollen is sensitive to chromosome unbalance. 5. Chromosome number instability of this plant is discussed in relation to other examples from the same and different genera.

By the end of 1972, a total of thirteen rabbits had been injected. One serum was raised to Brassica oleracea S23S23 kale pollen proteins, but no s-antibody was stimulated. All the others were raised to stigma proteins. A range of s-alleles and varieties of B.oleracea was used including S23S23, S16S16 kale, S2S2, S45S45 and S5S5 brussels sprout and S15S15 cabbage. S15 and S5 were of low dominance, S2 and S45 of intermediate dominance and S23, S14 and S16 of high dominance. S-antibodies were raised to S23 and S16 in kale, and S2 and S45 in brussels sprout. Only the S16-antibody had a high titre of 1/16, the other were 1/4 or less. In two of the cases , booster injections stimulated the S-antibody response where the first course of injections stimulated the S-antibody response where the first course of injections stimulated the S-antibody response where the first course of injections had failed. Relatively dilute stigma extracts of 250 stigmas/ml stimulated most s-antibodies. An injection schedule of more than two months produced cross-reactions or new specificities. Extract which had been frozen or treated with formalin gave a poorer antibody response than freshly-prepared extract. No S-antibodies were stimulated by these treatments. In its present form, the technique was unsuitable for routine S-allele diagnosis in B.oleracea because of the low rate of successful sera and the low titres stimulated. Improvements to the technique are suggested. Between 35 and 40% of the total protein content was lost when a stigma extract was frozen, but the S-protein was not lost. B.oleracea pollen germinated on an agar and sucrose medium. Germination was stimulated by 0.0005% queroetin, but tube growth was not. Querotin was detected as glycosides in the pollen and stigma tissue of B.oleracea. It was not involved in the incompatibility reaction of the stigma.

Made available in DSpace on 2014-06-11T19:35:09Z (GMT). No. of bitstreams: 0 Previous issue date: 2010-08-13Bitstream added on 2014-06-13T19:45:05Z : No. of bitstreams: 1 danuello_ac_dr_araiq.pdf: 2901494 bytes, checksum: 00bdc27de65694c0e80f9d4ed89c46a3 (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / O presente trabalho teve como objetivo o planejamento e síntese de novas substâncias inibidoras da acetilcolinesterase, enzima cuja modulação está associada ao tratamento de diversas patologias, entre elas a doença de Alzheimer. Para isto foi utilizada a técnica de docking molecular visando o reconhecimento dos sítios de interação da enzima que possibilitaram a modelagem de novos compostos híbridos. O modelo de docking foi criado utilizando a enzima de Torpedo californica, muito semelhante à acetilcolinesterase humana, complexada com a tacrina, donepezil e (–)-huperzina A que foi validado por cross-docking. Em seguida, a (–)-3-O-acetil-espectalina (32), (–)-3-O-acetil-cassina (36) e derivados virtualmente planejados foram ancorados na enzima e a partir de sobreposições destes alcalóides com os inibidores de acetilcolinesterase comerciais foram planejados diversos híbridos que apresentaram interações mais efetivas com a proteína que os modelos originais. Além disto, foram realizados estudos sobre o modo de inibição de 32, que corroboraram os resultados obtidos in vivo, apresentando inibição não-competitiva. A análise por docking e dinâmica molecular sugeriu que 32 e 36 apresentam diferentes interações com a enzima, sendo 36 potencialmente mais ativo que 32. O híbrido planejado por docking que apresentou melhor interação com a AChE, além de maior viabilidade sintética foi selecionado e por análise retrossintética foram escolhidas a 3-hidroxi-2-hidrometil-piridina (38) e a 4-bromoquinolina (42) como materiais de partida para uma rota convergente. Os estudos sintéticos levaram a obtenção de intermediários piridínicos sendo que numa das etapas da rota proposta, onde o objetivo era a proteção seletiva da hidroxila piridínica de 38, foi observada a proteção da hidroxila metil-piridínica o que sugere a migração dos grupos acetil... / The goal of this research deals with the design and synthesis of new acetylcholinesterase inhibitor molecules. This enzyme is associated to the treatment of several pathologies including Alzheimer’s disease and thus the importance of studying molecules that may interact with it. To fulfill this task we used molecular docking aiming to recognize the enzyme’s interaction sites allowing us to design new hybrid compounds. The docking model was created using Torpedo californica’s enzyme, very similar to human acetylcholinesterase, complexed with tacrine, donepezil and (–)-huperzine A, all validated by cross-docking. Furthermore, (–)-3-O-acetyl-espectaline (32), (–)-3-O-acetyl-cassine (36) and virtually designed derivatives, were docked into the enzyme through geometric comparisons of known commercially available acetylcholinesterase inhibitors, allowing us to produce a series of enzyme effective molecular hybrids when compared to the original ones. Additionally, we studied the inhibition mode of action of 32 that confirmed the in vivo results showing a non-competitive inhibition. Docking and molecular dynamics of 32 and 36 revealed that they showed different enzyme interactions and that the latter compound was potentially more active than 32. The hybrid molecule planned by docking that showed a better interaction with AChE and, with the best synthetic viability was selected showing 3-hydroxy-2-hydromethyl-pyridine (38) and 4-bromoquinoline (42) as the starting materials of a convergent route. The synthesis studies lead us to the production of pyridine intermediaries and, in one of the stages where the main goal was the selective protection of a pyridine hydroxyl group; we observed instead, the protection of the methyl pyridine hydroxyl moiety suggesting the migration of the acetyl and benzoyl groups. We used several coupling methods for the pyridine and quinoline nuclei... (Complete abstract click electronic access below)

No description available.

Diversity is perhaps , the most outstanding feature of the living world. Traditionally, biological diversity was thought to arise mainly through de nova mutations that increase in frequency through natural selection or genetic drift. However, it is now recognized that hybridization between already divergent populations constitutes another important source of genetic and phenotypic variation, upon which natural and/or sexual selection can operate. Hence, the idea that hybridization can actually promote diversification is becoming increasingly supported. In this thesis work, I explore the role of hybridization in the origin of biological diversity. In particular, I have studied the structure of two overlapping hybrid zones between races of two mimetic species of Heliconius butterflies: Heliconius melpomene and H. erato, in Eastern Ecuador, South America. This thesis work is composed of four empirical studies: 1) a characterization of the phenotypic effects caused by the major wing colour-pattern loci that segregate in the studied hybrid zones, 2) a characterization of the hybrid zones in the field, 3) a field experiment to test whether frequency-dependent selection is maintaining the distinctiveness of the hybridizing races in spite of gene flow, and whether it explains the high abundance of one particular H. erato hybrid form, and 4) a quantification of continuous colour-pattern variation using a novel morphometric technique, which was then used for a preliminary QTL mapping analysis of colour-pattern at the chromosome level. The most outstanding finding of this thesis was the fact that the allele frequency dines for the two major colour-pattern loci segregating in the hybrid zone (D and Ac/ScfJ are significantly displaced from each other in both studied species. This dine displacement is associated with the high abundance of one particular hybrid form of H. erato. This hybrid phenotype is one of the possible homozygote hybrids (i.e. homozygote for the allele from one of the parental populations at one locus, but homozygote for the allele of the other parental population at the other locus). As a result, this hybrid breeds true when mated to its own kind, and could potentially form a self-sustaining population. It was hypothesised then that this particularly abundant hybrid phenotype might constitute a diverging hybrid form (i.e. a sort of incipient race). The implications of this hypothesis led to the field � � . experiment aimed at testing whether frequency-dependent selection was favouring the highly abundant hybri'd phenotype in the zone of cline mismatch. The results of this experiment were mixed but enlightening: even though I could not detect differences in attack rates associated with colour-pattern, I found that all tested colour morphs were significantly more attacked in the hybrid zone than in the parental .zones. This finding suggested that predation against all colour morphs is stronger in t~e hy�b�nd ~one. The implications of all these results for the role of hybridization in biological d1vers1f1cat10n are discussed extensively in this thesis. By studying the genetic bases of colour-pattern as well as the dynamics of hybridization in the wild, this thesis work is making important contributions to the understanding of the role of hybridization in biological diversification including thee reconstructin of a possible route through which novel hybrid phenotypes could be established in nature.

No description available.