Molecular features of colorectal cancer predisposition and progression

Both inherited genetic variations and somatically acquired mutations drive cancer development. The aim of this thesis was to gain insight into the molecular mechanisms underlying colorectal cancer (CRC) predisposition and tumor progression. Whereas one-third of CRC may develop in the context of hereditary predisposition, the known highly penetrant syndromes only explain a small fraction of all cases. Genome-wide association studies have shown that ten common single nucleotide polymorphisms (SNPs) modestly predispose to CRC. Our population-based sample series of around thousand CRC cases and healthy controls was genotyped for these SNPs. Tumors of heterozygous patients were analyzed for allelic imbalance, in an attempt to reveal the role of these SNPs in somatic tumor progression. The risk allele of rs6983267 at 8q24 was favored in the tumors significantly more often than the neutral allele, indicating that this germline variant is somatically selected for. No imbalance targeting the risk allele was observed in the remaining loci, suggesting that most of the low-penetrance CRC SNPs mainly play a role in the early stages of the neoplastic process. The ten SNPs were further analyzed in 788 CRC cases, 97 of which had a family history of CRC, to evaluate their combined contribution. A significant association appeared between the overall number of risk alleles and familial CRC and these ten SNPs seem to explain around 9% of the familial clustering of CRC. Finding more CRC susceptibility alleles may facilitate individualized risk prediction and cancer prevention in the future. Microsatellite instability (MSI), resulting from defective mismatch repair function, is a hallmark of Lynch syndrome and observed in a subset of all CRCs. Our aim was to identify microsatellite frameshift mutations that inactivate tumor suppressor genes in MSI CRCs. By sequencing microsatellite repeats of underexpressed genes we found six novel MSI target genes that were frequently mutated in 100 MSI CRCs: 51% in GLYR1, 47% in ABCC5, 43% in WDTC1, 33% in ROCK1, 30% in OR51E2, and 28% in TCEB3. Immunohistochemical staining of GLYR1 revealed defective protein expression in homozygously mutated tumors, providing further support for the loss of function hypothesis. Another mutation screening effort sought to identify MSI target genes with putative oncogenic functions. Microsatellites were similarly sequenced in genes that were overexpressed and, upon mutation, predicted to avoid nonsense-mediated mRNA decay. The mitotic checkpoint kinase TTK harbored protein-elongating mutations in 59% of MSI CRCs and the mutant protein was detected in heterozygous MSI CRC cells. No checkpoint dysregulation or defective protein localization was observable however, and the biological relevance of this mutation may hence be related to other mechanisms. In conclusion, these two large-scale and unbiased efforts identified frequently mutated genes that are likely to contribute to the development of this cancer type and may be utilized in developing diagnostic and therapeutic applications.

The Distribution of Juvenile Fishes in Maryland Coastal Bays in Relation to Environmental Factors: a Multivariate Analysis

Fish assemblage structure of Maryland's coastal lagoon complex was analyzed for spatial and seasonal patterns for the period 1991-2000. Data was made available by Maryland Department of Natural Resources from their MD Coastal Bays Finfish Survey. Dominant species from separate trawl and wiw surveys included blue crab Callinectes sapidus (erroneously included here as a "fish" due to its dominance and commercial importance), bay anchovy Anchoa mitchilli, spot Leiostomous xanthurus, silver perch Bairdiella ehrysoura, and Atlantic menhaden Brevwrtia tyrannus. Ninety-four fish species were identified in the two surveys, a diversity substantially higher than other survey records for Middle Atlantic Bight estuarine and lagoon systems (richness=26 to 78 species). Total species richness for the trawl survey was highest in Chincoteague and lowest in Assawoman and Sinepuxent. On the other hand, mean richness per tow (-area) and related Shannon Weiner Diversity Index were significantly higher in the northern two bays (Assawoman and Isle of Wight Bays) than in the two southern bays (Chincoteague or Sinepuxent Bays). For the seine survey, effort-adjusted diversity indices were significantly lower for Chincoteague Bay than for the other three bays. Higher relative abundances were observed in the northern bays than in the southern bays. The trawl survey exhibited the lowest catch-per-site in Sinepuxent Bay and the highest in Assawoman Bay. The seine survey had the lowest catch-per-site in Chincoteague Bay while the other three embayments were of similar magnitude. There was clear seasonality in assemblage structure with peak abundance and diversity in the summer compared to other seasons. Blue crabs in particular showed a c. 2-fold decline in relative abundance from early summer to fall, which is likely attributable to harvest removals (i.e., an exploitation rate of c. 50%). Seagrass coverage, although increasing over the course of the 10 year survey, did not have obvious effects on species diversity and abundance across or within the embayments, although it did have positive associations with two important species: bay anchovy and summer flounder Pavalich thys dentatus. Atlantic menhaden were most dominant in Assawoman Bay, which could be related to higher primary production typically observed in this Bay in comparison to the other three. (PDF contains 99 pages)

Gut microbiota promote hematopoiesis to control bacterial infection

The commensal microbiota impacts specific immune cell populations and their functions at peripheral sites, such as gut mucosal tissues. However, it remains unknown whether gut microbiota control immunity through regulation of hematopoiesis at primary immune sites. We reveal that germ-free mice display reduced proportions and differentiation potential of specific myeloid cell progenitors of both yolk sac and bone marrow origin. Homeostatic innate immune defects may lead to impaired early responses to pathogens. Indeed, following systemic infection with Listeria monocytogenes, germ-free and oral antibiotic-treated mice display increased pathogen burden and acute death. Recolonization of germ-free mice with a complex microbiota restores defects in myelopoiesis and resistance to Listeria. These findings reveal that gut bacteria direct innate immune cell development via promoting hematopoiesis, contributing to our appreciation of the deep evolutionary connection between mammals and their microbiota.

Investigations on phytoplankton with special reference to water usage

Experiments and observations on the phytoplankton of certain lakes in the English Lake District were made from early 1973 to the end of March, 1974. They included laboratory and lake bioassays and observations on the quantity and quality of the phytoplankton in six lakes. The introductory sections of the report are about algae, the ecology of phytoplankton and the scope of the contracted work. Laboratory bioassays on water from one lake, Blelham Tarn, showed that phosphorus, silicon (for diatoms) and organic substances forming complexes with iron were the major substances limiting the growth of the algae tested. The growth of the test algae was limited to different degrees by those substances and, to some extent, to a greater or lesser degree at different times of year. It is suggested that a relatively simple form of bioassay could give valuable information to water undertakings. Lake bioassays and other experiments were carried out by using large in situ tubular plastic enclosures. Two such investigations are described. The effects of a change in sewerage in two drainage basins on the phytoplankton of three lakes is described and some data given about changes since 1945 in three other lakes in the same overall drainage basin. These latter lakes have been affected too by changes in sewerage and by increasing inputs of domestic and agricultural wastes. Throughout, the relevance of the work done to practical problems of water usage is kept in mind and discussed. In the last section special reference is made to the largely unpredictable results of water transfers. The report ends with a note on river phytoplankton.

Artes de Exu: intervenções artísticas e representações afro-brasileiras no Rio de Janeiro: Tridente de Ni e Exu dos Ventos

Artes de Exu trata os objetos de arte não só pelos aspectos artísticos e sociológicos, mas também pelos aspectos que ligam as obras a Exu, além do enunciado. Como coisa contida na concepção, na execução e imbricada na própria história da obra. As obras escolhidas são: Tridente de NI (2006) de Alexandre Vogler e Exu dos Ventos (1992), de Mario Cravo Júnior. As obras contêm conflitos que envolvem a mídia, religiosos e políticos. A partir de pesquisas etnográficas é feita uma análise dos olhares que se cruzam na construção dos sentidos na disputa pelo espaço simbólico, considerando ainda o trânsito percorrido pelas obras entre a oficina, o espaço de exposição e a rua. Pertence ainda ao corpo das análises as referências na mídia impressa, forma de veiculação das imagens, apropriações e discursos. As artes de Exu se evidenciam no desenrolar dessas tramas, conforme os objetos artísticos oferecem um lugar para pensar na conciliação entre diferentes: entre a cruz e o tridente, entre Cristo e Exu e entre cristãos e religiões de matriz africana

Female slave narratives: consistency and permanence: a study of two texts from the XIXth and XXth centuries

Esta dissertação tem por objetivo investigar o papel das slave narratives como poderoso gênero literário na denúncia da escravidão africana e na representação do homem negro e da mulher negra nos séculos dezoito e dezenove. Este trabalho também se propõe a investigar o papel das neo-slave narratives no estudo do passado e a representação da identidade negra no século vinte. Ambos os gêneros desafiam seus tempos presentes ao discutirem questões de etnia e subjugação humana, em uma abordagem crítica. Em Incidents in the Life of a Slave Girl (1861), Harriet Jacobs narra sua experiência na escravidão, deixando um importante legado não somente para a História mas também para a Literatura Afro-Americana. Em Dessa Rose (1986), Sherley Anne Williams, revisa o passado para resgatar a memória da escravidão e reescrever a história para examinar seu tempo presente. Além disso, as duas autoras apresentam questões de gênero, levantando questões feministas em suas obras

A voz e a vez de Eva: a nova heroína contemporânea em obras de José Saramago

A proposta deste trabalho é realizar uma análise da figura feminina nos romances Jangada de pedra, História do cerco de Lisboa e Ensaio sobre a cegueira, de José Saramago. Iniciando por uma breve pesquisa da história da mulher como forma de traçar a longa trajetória por que passou até a sua emancipação, o estudo revela, através da análise de diferentes identidades femininas, a abertura de uma nova concepção de mulher na literatura portuguesa.O escritor propõe em sua obra uma reflexão sobre a situação do mundo através do indivíduo e suas atitudes, responsabilidades e anseios. Os ensinamentos que seus romances costumam transmitir aos leitores, na maioria das vezes, partem de personagens femininas. A mulher se completa realizando o papel de mãe, protetora e companheira e, ao mesmo tempo, de amante e guerreira. Considerada pelo presente trabalho uma heroína contemporânea, ela engloba estas duas vertentes que a sociedade por muito tempo insistiu em separar, cuidando da casa e da família ao mesmo tempo em que trabalha e busca seu sustento fora de casa Também é a mulher que, nesta obra, tem o poder da sensibilidade e da compaixão ajudando àqueles que precisam, mesmo quando mal os conhece. E também é ela quem consegue, encantadoramente, metamorfosear-se de menina a mulher, intercalando as imagens de santa e prostituta, sedutora externamente e pura em sua essência.Entretanto, a escrita saramagueana não trata apenas de inibir a matriz patriarcal, ignorando com isso o papel do homem. O que há é o resgate das culturas primitivas matriarcais, com a mulher e o homem governando em igualdade e harmonia. Por este motivo, o homem também é muito importante em seus romances já que, em união com a mulher, incentivado e guiado por ela, partem juntos, através do amor, para uma travessia (humana) existencial, na busca do conhecimento

Ancient DNA from South-East Europe Reveals Different Events during Early and Middle Neolithic Influencing the European Genetic Heritage

The importance of the process of Neolithization for the genetic make-up of European populations has been hotly debated, with shifting hypotheses from a demic diffusion (DD) to a cultural diffusion (CD) model. In this regard, ancient DNA data from the Balkan Peninsula, which is an important source of information to assess the process of Neolithization in Europe, is however missing. In the present study we show genetic information on ancient populations of the South-East of Europe. We assessed mtDNA from ten sites from the current territory of Romania, spanning a time-period from the Early Neolithic to the Late Bronze Age. mtDNA data from Early Neolithic farmers of the Starcevo Cris culture in Romania (Carcea, Gura Baciului and Negrilesti sites), confirm their genetic relationship with those of the LBK culture (Linienbandkeramik Kultur) in Central Europe, and they show little genetic continuity with modern European populations. On the other hand, populations of the Middle-Late Neolithic (Boian, Zau and Gumelnita cultures), supposedly a second wave of Neolithic migration from Anatolia, had a much stronger effect on the genetic heritage of the European populations. In contrast, we find a smaller contribution of Late Bronze Age migrations to the genetic composition of Europeans. Based on these findings, we propose that permeation of mtDNA lineages from a second wave of Middle-Late Neolithic migration from North-West Anatolia into the Balkan Peninsula and Central Europe represent an important contribution to the genetic shift between Early and Late Neolithic populations in Europe, and consequently to the genetic make-up of modern European populations.

As representações da mulher nas letras luso-brasileiras do século XVII

O propósito desta dissertação é estudar as representações femininas nas letras luso-brasileiras do século XVII, sempre levando em conta os pressupostos teóricos formulados pela crítica brasileira atual. Pretende-se examinar as práticas letradas seiscentistas pelo prisma dos critérios retórico-poéticos vigentes na época, em que se destacam a importância dos elementos visuais. O estudo tem como base o contraponto das figuras de Eva e Maria, formando o grande paradigma da dualidade feminina nas letras coloniais; tal construção da imagem da mulher como tentadora e salvadora foi um longo processo desde as letras dos tempos antigos, se intensificando no período medieval até chegar no século XVII. Desse modo, focalizamos as poesias de Gregório de Matos e alguns sermões do padre Antonio Vieira, dialogando com questões históricas, sociais e artísticas no momento de produção das obras para tentar reduzir os riscos de anacronismo, sempre presentes quando abordamos períodos tão distanciados no tempo. Analisamos variadas configurações femininas nas poesias líricas e satíricas de Gregório de Matos; já nos sermões de Vieira, percebemos que o contraponto entre as concepções mariana e eviana fica mais evidente. Mostramos como as figuras femininas examinadas se aproximavam de Eva ou de Maria, levando em conta o contexto sócio-econômico das mesmas. Notamos que o modelo ideal de mulher encarnando na figura de Maria, difundido pela Igreja com o objetivo de alcançar todas as mulheres, não correspondia à realidade das mesmas no sistema colonial e não se adequava as suas necessidades. Examinamos igualmente como tal construção feminina perfeita e submissa circulava nos manuais de boa conduta em que a família patriarcal se encaixava, atendendo às exigências dos modelos propagados pela Igreja Católica na época. Apesar de todos os esforços da Igreja Católica e do homem para domesticar a mulher, tão temida e admirada pelos mesmos, muitas mulheres fugiram aos padrões sociais e foram estigmatizadas, rotuladas, discriminadas, mas acima de tudo foram mulheres que ficaram registradas nas páginas da Inquisição, na história e principalmente, nas letras luso-brasileiras do século XVII, escritas por homens, como o poeta Gregório de Matos e o padre Antonio Vieira

An Historical Review of Sebastes Taxonomy and Systematics

Following the initial description of a species of Sebastes from the Atlantic in the late 1700’s, in the late 1800’s the incredible taxonomic diversity of the genus began to be recognized as more species were discovered in northeast Pacific waters. With over 100 species, most of them from the North Pacific, the genus Sebastes (rockfishes) now presents taxonomic problems at every level. For example, although early efforts to understand relationships among the species resulted in the erection of several subgenera, those and more recent efforts remain largely unsuccessful. Also, the position of the genus within the order Scorpaeniformes, as well as the limits of the genus and the validity of some species are all unresolved. This paper examines the worldwide history and status of taxonomic studies on Sebastes, and reviews the 23 subgenera that have been erected over the years. This review of research, which includes morphological and genetic studies, provides a framework against which to evaluate studies using new genetic techniques.

Caminhos de vida, percursos na educação da infância: um estudo sobre a trajetória profissional da educadora Astrogildes Delgado de Carvalho (anos 1940/1980

A tese aqui apresentada tem como objeto de estudo a trajetória profissional da educadora Astrogildes Delgado de Carvalho, ao longo de um período situado entre as décadas de 1940 a 1980. A educadora em questão, católica militante, praticamente desconhecida no campo educacional, desenvolveu importantes ações tendo como foco, de modo particular, a educação infantil, área ainda pouco valorizada nos primeiros tempos de seu trabalho como educadora. Entre essas ações, situam-se a fundação de duas instituições educacionais que tiveram destaque na cidade de Petrópolis, entre as décadas de 1940 e 1960, a Escola Chapelinho Vermelho e o Externato Delgado de Carvalho, e a atuação na Organização Mundial de Educação Pré-escolar (OMEP), nas décadas de 1970 e 1980, como formadora de educadoras de creches e como responsável pelos Centros de Atendimento ao Pré-Escolar (CAPEs) criados pela instituição, em localidades habitadas por populações menos favorecidas. Este estudo de caráter biográfico pretende lançar luz sobre uma importante figura do campo educacional brasileiro, e contribuir, através da análise de sua trajetória, articulada, por sua vez, à história da OMEP, para a ampliação do conhecimento sobre ações direcionadas à educação infantil e, em particular, a crianças menos favorecidas da sociedade brasileira, nas décadas focalizadas. Na pesquisa, apoiada em uma base documental diversificada, incluindo de modo valorizado o acervo pessoal da educadora, a pretensão foi a de dar destaque a vozes, papeis, memórias vivas e deslindar os fios que foram sendo tecidos ao longo desses anos, valorizando a participação de Astrogildes Delgado de Carvalho na promoção e garantia dos direitos da criança de zero a seis anos.

Evolution of the tectogene concept, 1930-1965

The tectogene, or crustal downbuckle, was proposed in the early 1930s by F.A. Vening Meinesz to explain the unexpected belts of negative gravity anomalies in island arcs. He attributed the isostatic imbalance to a deep sialic root resulting from the action of subcrustal convection currents. Vening Meinesz's model was initially corroborated experimentally by P.H. Kuenen, but additional experiments by D.T. Griggs and geological analysis by H.H. Hess in the late 1930s led to substantial revision in detail. As modified, the tectogene provided a plausible model for the evolution of island arcs into alpine mountain belts for another two decades. Additional revisions became necessary in the early 1950s to accommodate the unexpected absence of sialic crust in the Caribbean and the marginal seas of the western Pacific. By 1960 the cherished analogy between island arcs and alpine mountain belts had collapsed under the weight of the detailed field investigations by Hess and his students in the Caribbean region. Hess then incorporated a highly modified form of the tectogene into his sea-floor spreading hypothesis. Ironically, this final incarnation of the concept preserved some of the weaker aspects of the 1930s original, such as the ad hoc explanation for the regular geometry of island arcs.

Genetic relationship of Chinese and Japanese gamecocks revealed by mtDNA sequence variation

Cockfighting has a very long history dating back to as early as 2500 years ago in China. Cockfighting was intertwined with human cultural traditions, helped disperse chickens across the world, and influenced the subsequent breed selection. Therefore, trac

Independent adaptation to riverine habitats allowed survival of ancient cetacean lineages

The four species of "river dolphins" are associated with six separate great river systems on three subcontinents and have been grouped for more than a century into a single taxon based on their similar appearance. However, several morphologists recently questioned the monophyly of that group. By using phylogenetic analyses of nucleotide sequences from three mitochondrial and two nuclear genes, we demonstrate with statistical significance that extant river dolphins are not monophyletic and suggest that they are relict species whose adaptation to riverine habitats incidentally insured their survival against major environmental changes in the marine ecosystem or the emergence of Delphinidae.