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abstract: This research addresses human adaptive decisions made at the Pleistocene-Holocene transition - the transition from the Last Glacial Maximum (LGM) to the climate regime in which humankind now lives - in the Mediterranean region of southeast Spain. Although on a geological time scale the Pleistocene-Holocene transition is the latest in a series of widespread environmental transformations due to glacial-interglacial cycles, it is the only one for which we have a record of the response by modern humans. Mediterranean Spain lay outside the refugium areas of late Pleistocene Europe, in which advancing ice sheets limited the land available for subsistence and caused relative demographic packing of hunter-gatherers. Therefore, the archaeological records of Mediterranean Spain contain more generally applicable states of the Pleistocene-Holocene transition, making it a natural laboratory for research on human adaptation to an environmental transformation. Foragers in Mediterranean Spain appear to have primarily adapted to macroclimatic change by extending their social networks to access new subsistence resources and by changing the mix of traditional relationships. Comparing faunal records from two cave sites near the Mediterranean coast with Geographic Information System (GIS) reconstructions of the coastal littoral plain from the LGM to the Holocene indicates the loss of the large ungulate species (mainly Bos primigenius and Equus) at one site coincided with the associated littoral disappearing due to sea level rise in the late Upper Paleolithic. Farther north, where portions of the associated littoral remained due to a larger initial mass and a more favorable topography, the species represented in the faunal record were constant through time. Social boundary defense definitions of territory require arranging social relationships in order to access even this lightly populated new hunting area on the interior plain. That the values of the least-cost-paths fit the parameters of two models equating varying degrees of social alliance with direct travel distances also helps support the hypothesis that foragers in Mediterranean Spain adapted to the consequences of macroclimatic change by extending their social networks to gain access to new subsistence resources Keeping these relationships stable and reliable was a mitigating factor in the mobility patterns of foragers during this period from direct travel to more distant down-the-line exchange. Information about changing conditions and new circumstances flowed along these same networks of social relationships. The consequences of climate-induced environmental changes are already a concern in the world, and human decisions in regard to future conditions are built upon past precedents. As the response to environmental risk centers on increasing the resilience of vulnerable smallholders, archaeology has an opportunity to apply its long-term perspective in the search for answers / Dissertation/Thesis / Ph.D. Anthropology 2013

A Caderina-E està intimamente relacionada com a transiÃÃo epitelial-mesenquimal e com a progressÃo tumoral em muitos tipos de cÃncer, inclusive no cÃncer colorretal. O objetivo deste trabalho foi avaliar a imunoexpressÃo de Caderina-E no cÃncer colorretal primÃrio e nas respectivas metÃstases linfonodais, na mucosa colÃnica normal, e investigar possÃveis correlaÃÃes desta expressÃo com parÃmetros clÃnicopatolÃgicos. Setenta e sete casos de colectomias por carcinoma colorretal e dez casos de linfonodos metastÃticos, dos arquivos do Departamento de Patologia e Medicina Legal/Universidade Federal do CearÃ, foram utilizados. Realizou-se o Tissue Microarray e imunohistoquÃmica, com anticorpo monoclonal anti-Caderina-E. Foram avaliados os seguintes escores: 0 = ausÃncia de expressÃo; 1 = expressÃo citoplasmÃtica; 2 = expressÃo mista (citoplasmÃtica e membranar); 3 = expressÃo membranar pura. Foi utilizada tanto a classificaÃÃo proposta por Jawhari et al., agrupando os casos em expressÃo anormal (escores 0, 1 e 2) e expressÃo normal (escore 3), como os critÃrios propostos por Almeida et al., agrupando os casos como expressÃo nÃo-membranar (escores 0 e 1) e expressÃo membranar (escores 2 e 3). Os tumores primÃrios tiveram mais casos de expressÃo de Caderina-E anormal em comparaÃÃo com a mucosa normal (p < 0.0001). NÃo houve diferenÃa significante entre expressÃo de Caderina-E no tumor intestinal e em metÃstases linfonodais, embora nestas a expressÃo membranar tenha sido mais freqÃente do que no sÃtio primÃrio. Tumores de cÃlulas agrupadas apresentaram maior expressÃo de Caderina-E membranar do que os de cÃlulas isoladas, tanto utilizando a classificaÃÃo de Jawhari et al. (p = 0.0230), como os critÃrios propostos por Almeida et al. (p = 0.0043). Em conclusÃo, a expressÃo anormal de Caderina-E no tumor primÃrio, com persistÃncia freqÃente da imunomarcaÃÃo membranar associada à marcaÃÃo citoplasmÃtica (marcaÃÃo anormal heterogÃnea ou mista), reforÃa as evidÃncias de que esta alteraÃÃo no cÃncer à mais qualitativa do que propriamente quantitativa. O predomÃnio da expressÃo membranar no sÃtio primÃrio da neoplasia e na metÃstase, com ou sem expressÃo citoplasmÃtica associada, principalmente em tumores de cÃlulas agrupadas, sugere que a presenÃa da Caderina-E à essencial para a invasÃo local e progressÃo tumoral, em oposiÃÃo ao clÃssico paradigma de que a progressÃo tumoral se exacerba com a perda desta molÃcula de adesÃo. / E-cadherin is closely related to epitelial-mesenchymal transition and tumor progression in many cancers, including colorectal cancer. The aim of this study is to evaluate the expression of E-cadherin in primary colorectal cancer as well as in lymph node metastasis, establishing also a comparison with the expression of E-cadherin in normal colonic mucosa. We utilized 77 cases of colectomies for colorectal carcinoma and 10 cases of metastatic lymph nodes from the files of the Department of Pathology and Forensic Medicine/Federal University of Ceara. Tissue microarray and immunohistochemistry were performed with monoclonal anti-E-cadherin, evaluated using the following scores: 0 = no staining; 1 = cytoplasmic staining; 2 = mixed staining (cytoplasmic and membranous); 3 = membranous staining. It was used the classification proposed by Jawahri et al. which includes cases of abnormal expression (0, 1 and 2 scores) and cases of normal expression (3 score), and was also used the classification proposed by Almeida et al. which includes cases of non-membranous expression (0 and 1 scores) and membranous expression (2 and 3 scores). Primary tumors presented more cases of abnormal E-cadherin expression in comparison to normal colonic mucosa (p < 0.0001). There were no differences between E-cadherin expression in the primary tumor in comparison to lymph node metastasis. The grouped cell tumors showed increased expression of E-cadherin in comparison to isolated cell tumors, either using the classification proposed by Jawhari et al. (p = 0.0230) and the classification proposed by Almeida et al. (p = 0.0043). In conclusion, abnormal expression of E-cadherin in the primary tumor, with frequent membranar immunostaining associated with the cytoplasmic marking (abnormal heterogeneous or mixed staining), reinforces the evidence that E-cadherin expression change in cancer is more qualitative than quantitative. The predominance of membranar expression in primary tumor and lymph node metastasis, with or without associated cytoplasmatic expression, particularly in cell-grouped tumors, suggests that E-cadherin presence is essential for local invasion and tumor progression, as opposed to the classical paradigm that tumor progression is exacerbated by the loss of this adhesion molecule.

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