Este trabalho busca entender a diversificação craniana dos macacos do Velho Mundo (Catarrhini) integrando duas abordagens para o estudo da evolução de caracteres complexos: a genética quantitativa e a integração morfológica. A investigação tem três objetivos principais: 1) comparar a magnitude e o padrão das relações entre os caracteres cranianos entre todos os Catarrhini; 2) testar a hipótese de que deriva genética é o único agente responsável pela diversificação craniana; 3) explorar as conseqüências evolutivas da associação entre caracteres. De posse de um banco de dados bastante representativo da diversidade dos macacos do Velho Mundo (39 medidas cranianas de cerca de 6.000 crânios de mais de 130 espécies), gerei as matrizes de correlação e de variância/covariância, que resumem as relações entre os caracteres, e comparei-as entre vários grupos. Comparei-as também a expectativas derivadas de modelos teóricos de evolução por deriva genética, além de simular a ação de seleção natural sobre essas matrizes para observar o comportamento evolutivo dos diversos padrões de associação entre caracteres. De maneira geral, o padrão das relações é o mesmo entre todos os Catarrhini, mas a magnitude com que os caracteres estão associados varia bastante. Isso tem conseqüências evolutivas importantíssimas, pois grupos com baixas magnitudes tendem a responder na mesma direção em que a seleção atua (alta flexibilidade evolutiva), enquanto que altas magnitudes estão associadas, independentemente da direção da seleção, a respostas ao longo do eixo de maior variação, que no caso dos Catarrhini corresponde à variação no tamanho (baixa flexibilidade evolutiva). A diversificação inicial do grupo parece ter sido gerada por seleção natural, mas nos níveis de gênero e espécie, deriva genética é o processo predominante; a exceção são os cercopitecíneos, onde há evidência de seleção também nesses níveis. Com base nesses resultados, proponho um modelo que associa a magnitude geral da correlação entre caracteres aos possíveis caminhos evolutivos que uma população pode seguir. Apesar de este trabalho estar empiricamente restrito aos macacos do Velho Mundo, esse modelo é válido para os mamíferos como um todo e pode ser testado em outros grupos, aumentando nossa compreensão de como a associação entre caracteres afeta a evolução dos seres vivos. / This is a study on the cranial diversification of the Catarrhini, a large group of primates that includes all Old World monkeys and apes, bringing together two approaches to investigate the evolution of complex characters: quantitative genetics and morphological integration. It has three main goals: 1) to compare magnitudes and patterns of inter-trait relationships in the skull among catarrhines; 2) to test the null hypothesis that genetic drift is the sole agent responsible for cranial diversification; 3) to explore the evolutionary consequences of inter-trait associations. With a large and representative cranial database of Old World monkeys and apes (39 measurements of around 6,000 skulls from more than 130 species), I generated and compared correlation and variance/covariance matrices, which summarize inter-trait relationships, among several Catarrhini groups. I compared some of those matrices to expectations derived from theoretical models of evolution through genetic drift, and simulated natural selection to observe the evolutionary behavior of each matrix. From a broad perspective, the patterns of relationships are the same among all catarrhines, but the magnitudes are quite variable. This has very important evolutionary consequences, because groups with low overall magnitudes tend to respond in the same direction of selection (high evolutionary flexibility), while higher magnitudes, regardless of the direction of selection, are associated to responses along the axis of highest variation, which in this case corresponds to size variation (low evolutionary flexibility). The initial diversification of catarrhines seems to have been generated by natural selection, but drift probably played a major role at the genus and species level; the exception are the cercopithecines, for which there is evidence for selection also in those levels. Based on these results, I propose a model that links the overall magnitude of inter-trait correlations to the possible evolutionary paths of a given population. This study is empirically restricted to Old World monkeys and apes, but the model has been proved valid to a broader sample of mammals and can be tested for other groups, contributing for our understanding of how complex characters evolve.

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Recent European legislation has enforced a reduction in the use of animal models for safety assessment purposes and carcinogenicity testing. The Syrian hamster embryo cell transformation assay (SHE CTA) has been proposed as a suitable animal alternative, but its implementation into test batteries has been delayed. This is due to concerns regarding the assay’s endpoint subjectivity and, moreover, the model’s relevance to carcinogenicity remains mostly unexplored. Senescence is an essential barrier against uncontrolled cell proliferation and its evasion is necessary for clonal evolution and tumour development. Carcinogenesis can be modelled by reproducing underlying mechanisms leading to senescence bypass. In this project, the SHE CTA was performed using the known mutagen and human carcinogen, benzo(a)pyrene, and the resulting SHE colonies were analysed. It was found that morphological transformation (MT) does not guarantee senescence bypass and cell immortalisation, but increases the likelihood of MT-derived cells subsequently acquiring unlimited growth potential. A limited number (between 10 and 20 %) of MT colonies produced cell clones capable of sustained proliferation and in most cases secondary events were necessary for the evasion of senescence barriers. With regard to mechanisms, p53 point mutations were present in 30 % of immortal B(a)P-induced MT colony-derived cells and located within the protein’s DNA binding domain. No p16 mutations were identified. Expression of p16 mRNA was commonly silenced or markedly reduced by a combination of mechanisms including monoallelic deletion, promoter methylation and BMI-1 overexpression. Taking advantage of the recently available Syrian hamster genomic sequence information generated by the Broad Institute, the coding regions of the Syrian hamster CDKN2A/B locus were shown to have good homology to human nucleotide sequences and confirmed the exonic structures of SH p16, ARF and p15. The findings further implicate the importance of p16 in regulating senescence while providing a molecular evaluation of SHE CTA-derived MT clones.

Whitefish (Coregonus lavaretus) populations diverge into morphs that differ in body size along a benthic-limnetic axis and throughout the depth of the water column. This process is assumedly initiated by the presence of northern pike (Esox lucius) and is followed by morphological adaptations to available food resources. In this study eight populations of whitefish was studied with the purpose of increasing the knowledge about adaptive trait utility in the feeding apparatus of whitefish. This was done by analyzing the mean and absolute maximum and minimum prey size ingested by fish along four morphological trait gradients. The morphological traits was body size, gill raker number and density, and gape size. The results show clear evidence of morphological adaptations in both the benthic and limnetic habitat, furthermore, when comparing the two prey size responses (mean and absolute values) it becomes clear that none of the studied whitefish is physically constrained in terms of the largest prey they can ingest. However, large fish seem to be limited in eating small prey sizes. Interestingly, I also found strong indicators for filter feeding adaptation for one of the studied populations.

Future changes to the pH and temperature of the oceans are predicted to impact the biodiversity of marine ecosystems, particularly those animals that rely on the process of calcification. The marine intertidal gastropod Littorina littorea can be used as a model of intertidal organism for investigating the effects of ocean acidification and high temperature, alone and in combination because its ability to be quickly adapt against environmental stressor. In the first study a single species population of L. littorea was used to test for physiological and biochemical effects underpinning organismal responses to climate change and ocean acidification. Compared with control conditions, snails decreased metabolic rates by 31% in response to elevated pCO2 while by 15% in response to combined pCO2 and temperature. Decreased metabolic rates were associated with metabolic depression, a strategy to match oxygen demand and availability, and an increase in end-product metabolites in the tissue under acidified treatments, indicating an increased reliance on anaerobic metabolism. This study also showed that anthropogenic alteration of CO2 and temperature may also lead to plastic responses, a fundamental mechanism of many marine gastropods to cope environmental variability. At low pH and elevated temperature in isolation or combined showing lower shell growth than individuals kept under control conditions. Percentage change in shell length and thicknesses was also lower under acidified and temperature in isolation or combined than control condition, making shells were more globular and desiccation rates were higher. Further studies to broader latitudinal ranges for six populations of L. littorea showed that shell growth decreased in all six populations under elevated pCO2 compared to control snails particularly those at range edges. Elevated pCO2 also affected to the reduction of shell length and width that causing shell aspect ratio to increase across latitudinal gradients except individuals from Millport, UK. Percentage changes of aperture width and aperture area were also decrease under elevated pCO2 with greater reduction of aperture area were found at populations in the mid-ranges which is assumed this response might be linked to local adaptation of the individual to microclimatic conditions. This study also showed that metabolic rates were negatively affected by high pCO2 and show non-linear trend across latitudinal gradients in compared to individual kept under normal pCO2 conditions. Metabolomic analysis showed that two northern populations of Trondheim and TromsØ were distinct from other populations when exposed to low temperature (15 °C) with elevated pCO2 due to, in part, high concentrations of thymine, uracil, valine and lysine. A similar separation also occurred under medium (25 °C) and high (35 °C) temperature exposure in which one of northern population (Trondheim) was distinct from other populations and had lower concentrations of alanine, betaine and taurine while higher of valine. These results suggest that populations at northern latitudes may apply different ionic transport mechanisms under elevated pCO2 and elevated temperatures and those populations are likely to vary in terms of their physiological responses to this environmental challenge.

An examination of the Desmodium canescens complex (D. canescens; D. tweedyi; D. illinoense) has resulted in the delimitation of a previously unreported alliance between D. canescens and D. tweedyi. The following points support this view: (a) morphological data taken from herbarium and garden specimens indicate that for many characters, the mean values of D. canescens and D. tweedy are not significantly different (b) breeding experiments have shown that artificial interspecific hybridization is possible between D. canescens and D. tweedyi (c) cytological studies have shown that D. canescens and D. tweedyi have a base number of x = 11, while D. illinoense has a base number of x = 10. A new combination is suggested: Desmodium canescens var. tweedyi (Britt.) Williams.

The formation of the myelin sheath is a crucial step during development because it enables fast and efficient propagation of signals within the limited space of the mammalian central nervous system. During the process of myelination, oligodendrocytes actively interact with the extracellular matrix (ECM). These interactions are considered crucial for proper and timely completion of the myelin sheath. However, the exact regulatory circuits involved in the signaling events that occur between the ECM and oligodendrocytes are currently not fully understood. Therefore, in this dissertation we investigated the role of a known integrator of cell-ECM signaling, namely, focal adhesion kinase (FAK), during oligodendrocyte morphological maturation in vivo and in vitro. Conditional and inducible FAK-knockout mice (Fakflox/flox: PLP/CreERT mice) were generated to observe the effect of FAK loss on myelination in vivo. The role of FAK during post-migratory premyelinating oligodendrocyte morphological maturation was explored in vitro using primary rat oligodendrocyte cultures in combination with siRNA or inhibitor treatment. When inducing FAK knockout just prior to and during active myelination in vivo, we observed a significant reduction in the number of myelinated fibers following initial myelination. In addition, our data revealed a decreased number of primary processes extending from oligodendrocyte cell bodies at this stage of development under induction of FAK knockout. In contrast, myelination appeared normal on postnatal day 28. Our in vitro data demonstrated that reduction of FAK expression or activity affected the oligodendrocyte process network maturation in a way that is unique to the ECM substrate present. More specifically, our data suggest that FAK restrains the expansion of the oligodendrocyte process network in the presence of fibronectin and promotes expansion of the oligodendrocyte process network in the presence of laminin-2. We showed that the FAK-mediated restriction of oligodendrocyte morphological maturation is tightly developmentally regulated; being highly active during early stages of post-migratory premyelinating oligodendrocyte morphological maturation but greatly diminished at the later stages of oligodendrocyte development. Thus, our data suggest that FAK controls the efficiency and timing of CNS myelination during its initial stages, at least in part, by regulating oligodendrocyte process network morphological maturation.

This thesis aims to present several combined methods for the morphological processing of Turkic languages, such as Turkish, which pose a specific set of challenges for computational processing, and also aims to make larger data sets publicly available. Because of the highly productive, agglutinative morphology in Turkish, data sparsity---besides the lack of the publicly available large data sets---impose difficulties in natural language processing, especially with regards to relying on purely statistical methods. Therefore, we evaluate a publicly available rule-based morphological analyzer, TRmorph, based on finite state transducers. In order to enhance the efficiency of this analyzer, and to expand its lexicon; we combine statistical and heuristics-based methods for the named entity processing (and construction of gazetteers), morphological disambiguation task and the multiword expression processing. Experiment results obtained so far point out that the use of heuristic-methods provides promising coverage increase for the text being processed by TRmorph, while the statistical approach is used as a back-up for more fine-grained tasks that may not be captured by pattern-based heuristics approach. This way, our proposed combined approach enhances the efficiency of a morphological analyzer based purely on FST...

A new approach to improve the determination of building boundaries through automatic processing of light detection and ranging (LIDAR) data is presented. The LIDAR data is processed and interpolated into a grayscale image of intensity values corresponding to height measurements. Ground measurements are separated from non-ground measurements by using a progressive morphological filter. With these measurements now distinct, further separation of non-ground measurements into building and non-building measurements is performed by growing regions with similar characteristics. These building areas are then refined, resulting in a ground plan representation of building boundaries, known as building footprints. Several algorithms are then implemented to clean these footprints. A new method is developed to analyze actual known satellite imagery in order to confirm identified building footprints.