The purpose of the present study was to experimentally investigate the effects of interspersing the opportunity to perform a fluent behavior during the acquisition of a new behavior. The experimenter trained left and right paw movements in domestic canines using a multiple treatment design. One paw movement was trained with a typical shaping procedure while the other was trained with an opportunity to perform a fluent behavior, touching the dog’s nose to a plastic disc, following each successive approximation in the shaping procedure. Two extinction phases were implemented during the experiment. The results showed that higher rates of reinforcement were achieved primarily following changes in criteria for reinforcement for the behavior in acquisition. There were no effects on rate of acquisition of the behavior, but adding an alternative fluent behavior may have slowed the differentiation between the reinforced behavior and alternative behaviors for one dog. The behavior trained with the addition of an alternative fluent behavior extinguished more quickly than in the control condition and extinguished at similar rates to the opposite leg movement. This suggests that the technique of offering an alternative fluent behavior may facilitate the chaining of the opposite behavior with the behavior targeted for reinforcement.

Long interspersed nuclear elements-1 (Line-1 or L1) accounts for approximately 17% of the human genome. The majority of L1s are inactive, but ~100 remain retrotransposon competent (RC-L1) and retrotranspose through RNA intermediates to different locations of the genome. It is well established that L1 is involved in both disease initiation and progression via retrotransposition dependent and independent mechanisms. Retrotransposed L1 sequences disrupt loci (e.g. gene structure) in ways that lead to human disease, and activities of L1 si/piRNA, ORF1 and ORF2 proteins are implicated in the etiology and progression of human diseases such as in breast and colon cancer (Miki et al., 1992; Ohms et al., 2014). Despite these implications, very little is known about pharmacological molecules that inhibit and reverse L1’s harmful effects. The clinical utility of L1 as a player in tumorigenesis and as a biomarker for disease initiation and progression is not thoroughly understood. In this review, we analyzed the life cycle of L1, its roles in disease initiation and progression, clinical utilities and potential as a pharmacological target and a biomarker for the diagnosis and treatment of human diseases, such as cancer.

Long interspersed nuclear element-1 (L1) is a genetic element that mobilizes throughout the mammalian genome via retrotransposition and damages host DNA via mutational insertions, chromosomal rearrangements, and reprogramming of gene expression. The cellular mechanisms responsible for aberrant L1 expression during cancer pathogenesis are unclear. Previously, we have shown that L1 reactivation in several human cell lines is dependent upon the activation of aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor member of the PAS superfamily of proteins. We also showed that ectopic expression of L1 reprograms the HepG2 genome leading to epithelial-to-mesenchymal transition (EMT). Here we present evidence that reactivation of L1 and modulation of EMT in HepG2 cells by the AhR ligand benzo(a)pyrene (BaP) is effected through the canonical TGF-β1 signaling pathway. BaP increased TGF-β1 mRNA, SMAD2 phosphorylation and decreased expression of E-Cadherin. The functional relevance of these interactions and the involvement of TGFBR1/ALK5 and SMAD2/3 were confirmed by siRNA interference. Furthermore, expression of L1-encoded ORF1p was positively correlated with the activation of TGF-β1 signaling in human hepatocarcinoma samples at various stages of malignant progression. These results indicate that ligand-mediated AhR activation regulates L1 via canonical TGF-β1 signaling and raise important questions about the molecular etiology of human hepatocarcinomas.

Transposable elements (TEs) are mobile genetic elements capable of replicating and spreading within, and in some cases, between genomes. I describe a whole-genome analysis of DD34E TEs, which belong to the IS630-Tc1-mariner superfamily of DNA transposable elements, in the African malaria mosquito, Anopheles gambiae. Twenty-six new transposons as well as a new family, gambol, were identified. The gambol family shares the DD34E catalytic motif with Tc1-DD34E transposons, but is distinct from these elements in their phylogenetic relationships. Although gambol appears to be related to a few DD34E transposons from cyanobacteria and fungi, no gambol elements have been reported in any other insects or animals thus far. This discovery expands the already expansive diversity of the IS630-Tc1-mariner TEs, and raises interesting questions as to the origin of gambol elements and their apparent diversity in An. gambiae. Several DD34E transposons discovered in An. gambiae possess characteristics that are associated with recent transposition, such as high sequence identity between copies, and intact terminal-inverted repeats and open reading frames. One such element, AgTango, was also found in a distantly related mosquito species, Aedes aegypti, at high amino acid sequence identity (79.9%). It was discovered that Tango transposons have patchy distribution among twelve mosquito species surveyed using PCR as well as genomic searches, suggesting a possible case for horizontal transfer. Additionally, it was discovered that in some mosquito genomes, there are several Tango transposons. These observations suggest differential evolutionary scenarios and/or TE-host interaction of Tango elements between mosquito species. This strengthened the case that AgTango may be a functional transposase, and I sought to test its potential activity in a cell culture-based inter-plasmid transposition assay using the Herves plasmids as a positive control (Arensburger et al., 2005). AgTango constructs were successfully constructed; however, no transposition events were detected for Tango or Herves. Because the positive control failed to work, no assessment can be made concerning Tango's transposase. Possible causes and solutions for these results, alternative means to detect transposition, as well as future directions with Tango are discussed. / Ph. D.

Thèse numérisée par la Direction des bibliothèques de l'Université de Montréal. / Chez l'humain, près de 30% de la masse génomique est constituée de séquences répétées dispersées qui se sont amplifiées par le mécanisme de rétroposition. Ce processus, présent dans tous les génomes eucaryotes, implique la transcription inverse de l'ARN d'un élément répété et l'intégration de l'ADNc qui en résulte dans une nouvelle localisation génomique. Les "Long Interspersed Elements" (LINE) codent pour les activités spécifiques de la rétroposition, telles que la transcriptase inverse et l'endonucléase. A l'inverse les "Short Interspersed Elements" (SINE) ne codent pour aucune activité enzymatique et sont considérés comme des "satellites" des éléments LINE. Nous avons caractérisé 5 nouvelles familles de rétroposon SINE chez les mammifères. Celles-ci font partie des SINE dérivés d'ARNt et ont, comme caractéristique commune, un domaine central nommé "core". Les régions 3 sont distinctes pour chacune des familles, mais fortement identiques aux extrémités 3' de différents LINE. D'autres séquences SINE possédant ces mêmes critères sont présentes dans les génomes d'oiseaux, de reptiles, de poissons et de céphalopodes. Nous avons ainsi identifié une nouvelle "superfamille" de rétroposon appelée CORE-SINE présente chez tous les vertébrés. L'étude du rôle de chaque segment des CORE-SINE ; région dérivée d'ARNt, "core" et région dérivée de LINE, nous a permis de donner de nouveaux éléments de réponse sur l'évolution des rétroposons dans les génomes eucaryotes. Enfin, nous avons décrit la présence d'un nouvel élément LINE dans les génomes de marsupiaux. Celui-ci est fortement identique au rétroposon Bov-B des génomes bovins et reptiles. Sa présence dans ces différents génomes soulève la possibilité d'un transfert horizontal de cet élément. / Almost 30% of the human genome consists of copies of interspersed repeats that amplified by retroposition, a process widely spread among eukaryotic taxa. Retroposition involves reverse transcription of the transcribed copies and reintegration of the resulting cDNAs into the host genome. Retroposition requires specific activities in addition to the enzymatic machinery commonly found in the host cells. The reverse transcriptase as well as the endonuclease involved in the cDNA synthesis and integration, are coded by the actively retroposing long elements such as LINEs. In contrast, short elements (SINEs) do not encode any protein facilitating their proliferation. However, these elements must have used both host-specific and retroposition-specific activities provided in trans to secure their efficient amplification. We have characterised 5 new SINE retroposon families from mammalian genomes. They belong to tRNA-derived SINEs and have also a common central domain called "core". The 3 end regions of all families are distinct but they display high identity with the 3'extremities of different LINEs. Several SINEs with the same characteristics have been found in bird, reptile, fish, and cephalopod genomes. These data point to the existence of a new "super-family" of SINE retroposons, named CORE-SINE, present in all vertebrate genomes. The study of each CORE-SINE segments, i.e. tRNA-derived region, "core" and LINE-derived region, gave new insight into the evolution of retroposon in eukaryotic genomes. Finally, we also described a new LINE element from marsupial genomes. It presents high identity with the Bov-B element from bovine and reptile genomes, which raises the possibility of a horizontal transfer of this element between genomes.

A utilização de resíduos tem se mostrado como uma boa alternativa na redução do impacto causado pelo consumo desordenado de matéria-prima e pela redução das áreas de disposição, em virtude do grande volume de resíduos descartados a cada ano em todo mundo. Neste contexto se inserem os resíduos de pneus provenientes da recauchutagem. Este trabalho foi desenvolvido com o objetivo de estudar algumas propriedades de pavers de concreto, com substituição parcial do agregado por resíduos de pneus. Para a produção dos pavers foram consideradas as faixas de consumo de cimento Portland de 292,84 kg/m³, 323,06 kg/m³ e 347,00 kg/m³, e os níveis de incorporação dos resíduos estudados foram de 8%, 10%, 12%, 15% e 20%, em volume. As propriedades foram: resistência à compressão, absorção de água, resistência ao impacto, resistência à abrasão profunda e expansão por umidade. Os resultados mostram que ocorre queda na resistência à compressão. Na absorção de água, não podemos afirmar que essa propriedade é afetada de maneira negativa. Os pavers demonstraram grande capacidade de absorção de energia (tenacidade). Os resultados de resistência à abrasão mostram-se interessantes para a aplicação em ambientes com baixas solicitações. A expansão por umidade não afetará o intertravamento dos pavers. Dessa forma, os resultados mostraram viabilidade na utilização dos pavers com resíduos de pneus em pavimentação intertravada com solicitações leves. / Concerns regarding the environment and shortage of natural resources have led the way for sustainable alternatives. The recycling process seems to be a suitable alternative to minimize the use of natural resources as well as the lack of proper disposal sites caused by the large amounts of discarded waste worldwide. Within this context, rubber residues from recapped tires are used for insertion. This work was developed with the objective of studying some of the properties of concrete paving, with partial substitution of the aggregate for tire residues. For the production of pavers the bands of Portland cement consumption was considered at 292,84 kg/m³, 323,06 kg/m³ and 347,00 kg/m³, and the levels of residues incorporation at 8%, 10%, 12%, 15% and 20%, in volume. The studied properties were: compressive strength, water absorption, impact resistance, deep abrasion and expansion resistance to humidity. The results show decrease in the compressive strength. The water absorption does not undergo negative influence. Pavers demonstrated substantial capacity for energy absorption (tenacity). The results of abrasion resistance reveal interesting applications for locales with low degree of demands. Expansion by humidity will not affect the interspersing of pavers. However, the results have shown viability in the use of pavers interspersed with tire residues in asphalt with light load demands.

A utilização de resíduos tem se mostrado como uma boa alternativa na redução do impacto causado pelo consumo desordenado de matéria-prima e pela redução das áreas de disposição, em virtude do grande volume de resíduos descartados a cada ano em todo mundo. Neste contexto se inserem os resíduos de pneus provenientes da recauchutagem. Este trabalho foi desenvolvido com o objetivo de estudar algumas propriedades de pavers de concreto, com substituição parcial do agregado por resíduos de pneus. Para a produção dos pavers foram consideradas as faixas de consumo de cimento Portland de 292,84 kg/m³, 323,06 kg/m³ e 347,00 kg/m³, e os níveis de incorporação dos resíduos estudados foram de 8%, 10%, 12%, 15% e 20%, em volume. As propriedades foram: resistência à compressão, absorção de água, resistência ao impacto, resistência à abrasão profunda e expansão por umidade. Os resultados mostram que ocorre queda na resistência à compressão. Na absorção de água, não podemos afirmar que essa propriedade é afetada de maneira negativa. Os pavers demonstraram grande capacidade de absorção de energia (tenacidade). Os resultados de resistência à abrasão mostram-se interessantes para a aplicação em ambientes com baixas solicitações. A expansão por umidade não afetará o intertravamento dos pavers. Dessa forma, os resultados mostraram viabilidade na utilização dos pavers com resíduos de pneus em pavimentação intertravada com solicitações leves. / Concerns regarding the environment and shortage of natural resources have led the way for sustainable alternatives. The recycling process seems to be a suitable alternative to minimize the use of natural resources as well as the lack of proper disposal sites caused by the large amounts of discarded waste worldwide. Within this context, rubber residues from recapped tires are used for insertion. This work was developed with the objective of studying some of the properties of concrete paving, with partial substitution of the aggregate for tire residues. For the production of pavers the bands of Portland cement consumption was considered at 292,84 kg/m³, 323,06 kg/m³ and 347,00 kg/m³, and the levels of residues incorporation at 8%, 10%, 12%, 15% and 20%, in volume. The studied properties were: compressive strength, water absorption, impact resistance, deep abrasion and expansion resistance to humidity. The results show decrease in the compressive strength. The water absorption does not undergo negative influence. Pavers demonstrated substantial capacity for energy absorption (tenacity). The results of abrasion resistance reveal interesting applications for locales with low degree of demands. Expansion by humidity will not affect the interspersing of pavers. However, the results have shown viability in the use of pavers interspersed with tire residues in asphalt with light load demands.

Thesis (Ph.D. in Biophysics & Genetics, Human Medical Genetics Program) -- University of Colorado Denver, 2007. / Typescript. Includes bibliographical references (leaves 123-147). Free to UCD affiliates. Online version available via ProQuest Digital Dissertations;

Made available in DSpace on 2016-06-02T20:30:07Z (GMT). No. of bitstreams: 1 5064.pdf: 2133437 bytes, checksum: 91011d8e6a06f6e7760589cf0b30918d (MD5) Previous issue date: 2013-03-13 / Universidade Federal de Minas Gerais / Studies about the effects of contextual control over equivalence classes have been conducted since the 1980s and a relevant question in this area, both in terms of experimental and applied research, is whether changes in contextual variables could result in changes in classes originally formed under different contextual variables. This research investigated, in four studies, the effects of procedures for establishing the contextual control of conditional relations and equivalence classes. The participants were undergraduate students. The stimuli used as sample and comparison were abstract figures and the contextual stimuli were represented by the colors of the background on which the stimuli were presented. In Study 1, we conducted a procedure for the formation of equivalence classes on backgrounds of red and blue colors. Later we conducted a test that showed the equivalence relations in the presence of contextual stimuli blue, red and green. The results showed that participants had responses consistent with the last equivalence class trained, independent of contextual stimulus. Study 2 replicated the previous study, but tests also showed baseline relations. The results obtained were similar to Study 1. Study 3, initially, partially replicated the procedure of previous studies, only for conditional relations AB and then tested the effects of a conditional discrimination training procedure interspersing the colors of the background. The results revealed that this procedure was most effective in setting the control contextual than those conducted in Studies 1 and 2. Study 4 investigated the effects of a interpersed training procedure for the establishment of the contextual control of recombined conditional relations. The procedure consisted of six phases. Phase1 was conducted a conditional discrimination training interspersing the colors of the background. In Phase 2, we carried out the test of relations trained in Phase1. In Phase 3, tests were conducted in which trials were included with a green background. Phase 4 included the symetry relations. Phase 5 presented the same relations were tested in Step 4, however the configuration of stimulus presentation on the computer screen was different. Finally, in Step 6, a test aimed to verify the abstraction of responding under contextual control, with new stimulus and background colors. The results suggest that the contextual control was established for some of the participants. Investigations about the baseline relations training, specifically the interspersed training , for establishing the contextual control is required to produce more robust results. / Estudos acerca dos efeitos do controle contextual sobre classes de equivalência vêm sendo conduzidos desde a década de 1980 e uma questão relevante nesta área, tanto do ponto de vista experimental quanto aplicado, é se mudanças em variáveis contextuais poderiam resultar em mudanças em classes originalmente formadas sob variáveis contextuais diferentes. A presente pesquisa investigou, em quatro estudos, os efeitos de variáveis de procedimentos para o estabelecimento do controle contextual de relações condicionais e classes de equivalência. Os participantes dos estudos foram estudantes universitários. Os estímulos utilizados como modelo e comparação foram figuras abstratas e os estímulos contextuais foram representados pelas cores do plano de fundo sobre os quais os estímulos eram apresentados. No Estudo 1, foi conduzido um procedimento para a formação de classes de equivalência diferentes na presença das cores azul e vermelha e posteriormente foi conduzido um teste que apresentava as relações de equivalência na presença dos estímulos contextuais azul, vermelho e verde. Os resultados revelaram que os participantes apresentaram respostas consistentes com a última classe de equivalência treinada, independente do estímulo contextual. O Estudo 2 replicou o estudo anterior, incluindo nos testes, além de relações de equivalência, relações de linha de base. Os resultados obtidos foram semelhantes ao do Estudo 1. O Estudo 3, inicialmente, replicou parcialmente o procedimento dos estudos anteriores apenas para relações condicionais AB e, em seguida, testou-se os efeitos de um procedimento de treino de discriminação condicional AB intercalando-se as cores do plano de fundo. Os resultados revelaram que este procedimento foi mais eficaz no estabelecimento do controle contextual que os conduzidos nos Estudos 1 e 2. O Estudo 4 avaliou os efeitos de um procedimento de treino intercalado para o estabelecimento do controle contextual de relações condicionais recombinadas. O procedimento contou com seis etapas, sendo que na Etapa 1 foi conduzido um treino de discriminação condicional intercalando-se as cores do plano de fundo. Na Etapa 2, realizou-se o teste das relações treinadas na Etapa1. Na Etapa 3, foram conduzidos testes nos quais foram incluídas tentativas com um plano de fundo da cor verde. A Etapa 4 incluiu as relações de simetria BA. Na Etapa 5, foram testadas as mesmas relações da Etapa 4, no entanto a configuração de apresentação dos estímulos na tela do computador foi diferente. Finalmente, na Etapa 6, conduziu-se um teste cujo objetivo foi verificar a abstração do responder sob controle contextual, com estímulos e cores do plano de fundo inéditas no experimento. Os resultados sugerem que o controle contextual foi estabelecido para parte dos participantes. Investigações acerca dos treinos das relações de linha de base, especificamente do treino intercalado, para o estabelecimento do controle contextual são necessárias para a produção de resultados mais robustos.

Short interspersed nuclear elements (SINEs) are small non-autonomous and heterogeneous retrotransposons, widespread in animals and plants and usually differentially propagated in related species resulting in genome-specific copy numbers. Within the monocots, the Poaceae (sweet grasses) is the largest and economically most important plant family. The distribution of 24 Poaceae SINE (PoaS) families, five of which showing a subfamily structure, was analyzed in five important cereals (Oryza sativa, Triticum aestivum, Hordeum vulgare, Sorghum bicolor, Zea mays), the energy crop Panicum virgatum and the model grass Brachypodium distachyon. The comparative investigation of SINE abundance and sequence diversity within Poaceae species provides insights into their species‐specific diversification and amplification. The PoaS families and subfamilies fall into two length and structural categories: simple SINEs of up to 180 bp and dimeric SINEs larger than 240 bp. Of 24 PoaS families, 20 are structurally related across species, in particular either in their 5′ or 3′ regions. Hence, reshuffling between SINEs, likely caused by nested insertions of full-lengh and truncated copies, is an important evolutionary mechanism of SINE formation. Most striking, the recently evolved homodimeric SINE family PoaS‐XIV occurs exclusively in wheat (T. aestivum) and consists of two tandemly arranged PoaS‐X.1 copies. Exemplary for deciduous tree species, the evolutionary history of SINE populations was examined in six Salicaceae genomes (Populus deltoides, Populus euphratica, Populus tremula, Populus tremuloides, Populus trichocarpa, Salix purpurea). Four of eleven Salicaceae SINE (SaliS) families exhibit a subfamily organization. The SaliS families consist of two groups, differing in their phylogenetic distribution pattern, sequence similarity and 3’ end structure. These groups probably emerged at different evolutionary periods of time: during the ‘salicoid duplication’ (~ 65 million years ago) in the Salix-Populus progenitor, and during the separation of the genus Salix (~ 45 - 65 million years ago), respectively. Similar to the PoaS families, the majority of the 20 SaliS families and subfamilies share regions of sequence similarity, providing evidence for SINE emergence by reshuffling. Furthermore, they also contain an evolutionarily young dimeric SINE family (SaliS-V), amplified only in two poplar genomes. The special feature of the Salicaceae SINEs is the contrast of the conservation of 5’ start motifs across species and SINE families compared to the high variability of 3’ ends within the SINE families, differing in sequence and length, presumably resulting from mutations in the poly(A) tail as a possible route for SINE elongation. Periods of increased transpositional activity promote the dissemination of novel 3’ ends. Thereby, evolutionarily older motifs are displaced leading to various 3’ end subpopulations within the SaliS families. Opposed to the PoaS families with a largely equal ratio of poly(A) to poly(T) tail SINEs, the SaliS families are exclusively terminated by adenine stretches. Among retrotransposon-based markers, SINEs are highly suitable for the development of molecular markers due to their unidirectional insertion and random distribution mainly in euchromatic genome regions, together with an easy and fast detection of the heterogeneous SINE families. As a prerequisite for the development of SINE-derived inter-SINE amplified polymorphism (ISAP) markers, 13 novel Theaceae SINE families (TheaS-I - TheaS-VII, TheaS-VIII.1 and TheaS-VIII.2, TheaS-IX - TheaS-XIII) were identified in the angiosperm tree species Camellia japonica. Moreover, six Pinaceae SINE families (PinS-I.1 and PinS-I.2, PinS-II – PinS-VI) were detected in the gymnosperm species Larix decidua. Compared to the SaliS and PoaS families, structural relationships are less frequent within the TheaS families and absent in the PinS families. The ISAP analysis revealed the genetic identity of Europe’s oldest historical camellia (C. japonica) trees indicating their vegetative propagation from the same ancestor specimen, which was probably the first living camellia on European ground introduced to England within the 18th century. Historical sources locate the native origin of this ancestral camellia specimen either in the Chinese province Yunnan or at the Japanese Gotō Islands. Comparative ISAPs showed no accordance to the Gotō camellia sample pool and appropriate Chinese reference samples were not available. However, the initial experiments demonstrated the potential of ISAP to resolve variations among natural populations. The ISAP application on angiosperm trees also concerned fast growing Populus clones grown in short rotation coppice plantations for energy production. The species-specific P. tremula ISAP primers might also be applied for the discrimination of hybrid poplar clones involving P. tremuloides genome portions, since SINEs of these two species are highly related. However, due to lineage-specific SINE evolution during speciation, cross-species applications are generally only successful to limited extent. The analysis of poplar hybrids composed of P. maximowiczii with either P. trichocarpa or P. nigra based on P. tremula ISAP primers showed a strongly reduced resolution. In forestry, hybrid larch (e.g. Larix × eurolepis) genotypes have to be selected from the offspring of Japanese (Larix kaempferi) and European larch (Larix decidua) crosses, as they exhibit superior growth rates compared to the parental species. Initial ISAP-based examinations of European larch genotypes provided less polymorphic banding patterns, probably resulting from general high levels of synteny and collinearities reported for gymnosperm species. Hence, the ISAP was combined with the AFLP technique to the novel marker system inter-SINE-restriction site amplified polymorphism (ISRAP). The amplicons originating from genomic regions between SINEs and EcoRI cleavage sites were visualized with the sensitive capillary gel electrophoresis. The ISRAP assays, based on EcoRI adapter primers combined with two different SINE-derived primers, resulted in a sufficient number of polymorphic peaks to distinguish the L. decidua genotypes investigated. Compared to ISAPs, the ISRAP approach provides the required resolution to differentiate highly similar larch genotypes.