La prévalence du syndrome métabolique (MetS) est en constante augmentation dans les pays industrialisés. La stéatose hépatique, caractérisée par une accumulation massive de lipides dans les hépatocytes est une des manifestations du MetS. Parmi les SNP (Single Nucleotide Polymorphism) associés au MetS et à la stéatose hépatique, le SNP I148M de l'adiponutrine/PNPLA3 (Patatin-like Phospholipase Domain-Containing) est décrit comme un nouveau marqueur de la stéatose et également de la sévérité des différentes atteintes hépatiques des NAFLD (Non-alcoholic Fatty Liver diseases). L'objectif de ma thèse a été de déterminer le rôle de l'adiponutrine dans le foie, d'une part, en étudiant sa régulation transcriptionnelle par les facteurs de transcription SREBP1c (Sterol Responive Element Binding Protein) et ChREBP (Carbohydrate Responsive Element Binding Protein) en réponse à l'insuline et au glucose et d'autre part, en étudiant l'impact de sa surexpression sur le métabolisme glucido-lipidique dans le foie de souris. L'adiponutrine est régulée de façon semblable aux enzymes lipogéniques et semble avoir un impact sur le métabolisme lipidique dans le foie. Comme l'adiponutrine, différents SNP des médiateurs de la voie Wnt/β-caténine sont également associés au syndrome métabolique et au diabète. La voie Wnt/β-caténine joue un rôle déterminant dans la zonation du lobule hépatique. Nous nous sommes intéressés à la régulation de cette voie par les conditions nutritionnelles et dans un contexte physiopathologique de stéatose et de résistance à l'insuline. Nos résultats montrent la régulation de cette voie par les hormones pancréatiques (insuline et glucagon) dans le foie favorisant ainsi l'orientation métabolique des hépatocytes en fonction des besoins. De plus, cette voie est dérégulée dans le foie d'animaux résistants à l'insuline, suggérant qu'elle pourrait avoir une fonction dans ce désordre métabolique.

As preocupações com a integridade e o equilíbrio ambiental das regiões costeiras decorrem do fato de serem as mais ameaçadas do planeta, justamente por representarem para as sociedades humanas um elo de ligação e de intensa troca de mercadorias entre si, com a exploração desordenada e muitas vezes predatória de seus recursos naturais, tornado-se, já na era industrial o principal local de lazer, turismo ou moradia de grandes massas de populações urbanos. A vocação de uso de determinada paisagem esta relacionada às funções que a mesma desempenha. O que ocorre é que o padrão de desenvolvimento adotado e a atual configuração sócio-econômica determinam usos que nem sempre coincidem com a sua melhor utilização. A fim de subsidiar futuros planos de uso e ocupação racional do solo das áreas naturais adjacentes ao Balneário Cassino (Rio Grande, RS), de acordo com os preceitos do Gerenciamento Costeiro Integrado, desenvolveu-se um Dianóstico Sócio-Ambiental da área dentro de abordagem sistêmica. Foram considerados principais componentes e processos urbanos e ambientais, definidos a partir da interpretação de aerofotografias, levantamentos de campo quali-quantitativos e informações bibliográficas. Os resultados são apresentados na forma de tabelas, quadros, levantamentos fotográficos, modelos diagramáticos conceituais, e mapas temáticos, que permitiram entender a organização estrutural e funcional da paisagem, e fundamentar uma ordenação espacial dos usos desta área, de modo a adequá-los às suas especificidades ambientais, histórico-culturais, sócio-econômicas e legais. / The integrity and the environmental equilibrium of coastal zones are increasingly becoming a concern to environmental scientists. Coastal environments are one of the most threatened in the world. Besides, they represent, to the human societies, a link of connection and intense exchange of merchandise amongst each other, with disordered and, at many times, predatory exploration, becoming, already at the industrial age, a main site of leisure, tourism and habitation of large masses of urban population. The vocation of a determined landscape is related to the functions and roles it plays. What actually occurs is that the development pattern adopted and the actual socio-economics determine the uses, which not always coincide with its best utilization. In order to assist future plans of rational use and occupation of natural areas adjacent to Cassino's Bathing Resort (Rio Grande, RS), in agreement with the Integrated Coastal Zone Management, a social-environmental diagnosis of the study site was developed using the systemic approach. The main environmental and urban processes and components were considered. They were defined based on aerophotos interpretation, quail-quantitative field survey and bibliographic information. The results, presented in the form of tables, photographic surveys, conceptual diagrammatic models and thematic maps, allowed to understand the structural and functional organization of the landscape and to establish a spatial ordering of land use to adequate them to their environmental, historic-social, socioeconomics and legal specificities.

As preocupações com a integridade e o equilíbrio ambiental das regiões costeiras decorrem do fato de serem as mais ameaçadas do planeta, justamente por representarem para as sociedades humanas um elo de ligação e de intensa troca de mercadorias entre si, com a exploração desordenada e muitas vezes predatória de seus recursos naturais, tornado-se, já na era industrial o principal local de lazer, turismo ou moradia de grandes massas de populações urbanos. A vocação de uso de determinada paisagem esta relacionada às funções que a mesma desempenha. O que ocorre é que o padrão de desenvolvimento adotado e a atual configuração sócio-econômica determinam usos que nem sempre coincidem com a sua melhor utilização. A fim de subsidiar futuros planos de uso e ocupação racional do solo das áreas naturais adjacentes ao Balneário Cassino (Rio Grande, RS), de acordo com os preceitos do Gerenciamento Costeiro Integrado, desenvolveu-se um Dianóstico Sócio-Ambiental da área dentro de abordagem sistêmica. Foram considerados principais componentes e processos urbanos e ambientais, definidos a partir da interpretação de aerofotografias, levantamentos de campo quali-quantitativos e informações bibliográficas. Os resultados são apresentados na forma de tabelas, quadros, levantamentos fotográficos, modelos diagramáticos conceituais, e mapas temáticos, que permitiram entender a organização estrutural e funcional da paisagem, e fundamentar uma ordenação espacial dos usos desta área, de modo a adequá-los às suas especificidades ambientais, histórico-culturais, sócio-econômicas e legais. / The integrity and the environmental equilibrium of coastal zones are increasingly becoming a concern to environmental scientists. Coastal environments are one of the most threatened in the world. Besides, they represent, to the human societies, a link of connection and intense exchange of merchandise amongst each other, with disordered and, at many times, predatory exploration, becoming, already at the industrial age, a main site of leisure, tourism and habitation of large masses of urban population. The vocation of a determined landscape is related to the functions and roles it plays. What actually occurs is that the development pattern adopted and the actual socio-economics determine the uses, which not always coincide with its best utilization. In order to assist future plans of rational use and occupation of natural areas adjacent to Cassino's Bathing Resort (Rio Grande, RS), in agreement with the Integrated Coastal Zone Management, a social-environmental diagnosis of the study site was developed using the systemic approach. The main environmental and urban processes and components were considered. They were defined based on aerophotos interpretation, quail-quantitative field survey and bibliographic information. The results, presented in the form of tables, photographic surveys, conceptual diagrammatic models and thematic maps, allowed to understand the structural and functional organization of the landscape and to establish a spatial ordering of land use to adequate them to their environmental, historic-social, socioeconomics and legal specificities.

Made available in DSpace on 2015-05-07T14:49:21Z (GMT). No. of bitstreams: 0 Previous issue date: 2005-02-28 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES / In the present work a study on environmental impacts caused by agricultural activities and the identification of potentially degraded or degraded areas resulting from such activities was performed. The study areas selected were the municipality of Conde, located on the south littoral of the State of Paraíba, Northeast Brazil, whose geographical coordinates are lat 07°15 3 S and long 34° 54 27 W, totalling an area of 16,477.3 ha; and the rural settlement of Barra de Gramame, in the north of that municipality, whose geographical coordinates are between lat 7o14 06 and 7o15 32 S, and between long 34o48 37 and 34o51 11 W, totalling an area of 772.17 ha. This work was carried out in two stages: firstly, the most susceptible areas to degradation and the areas unduly exploited were mapped by using topographic charts on the scale of 1:100,000 and by using maps and images from satellite LANDSAT TM-7 scene 214/065, Channels 1, 2, 3, 4, 5, and 7, resolution at 30 m, from August 2001; in the second stage a study on the impact of agricultural practices in the rural settlement was performed and the mapping and evaluation of environmental impact levels were carried out by using topographic chart on the scale of 1:10,000 and images from the satellite SPOT, Channel 4, resolution at 10 m, from August 2001. During both stages, some field visits were carried out, where it was used a GPS (global positioning system) equipment and through a GIS (geographic information system) maps and images were overlaid. The second stage, concerning the rural settlement, was performed in more detail than the first stage. The rural settlement of Barra de Gramame is a representative area of the municipality of Conde, whose results obtained from the second stage contribute to a better knowledge on environmental degradation processes in the whole municipality and also in similar areas on the Brazilian northeastern littoral / Neste trabalho realizou-se um estudo dos impactos ambientais causados pelas atividades agrícolas e identificação das áreas potencialmente degradadas ou degradadas por esta atividade. As áreas selecionadas para desenvolver este estudo foram: o município do Conde localizado no litoral sul do Estado da Paraíba Brasil, entre as coordenadas geográficas de 07° 15 3 de latitude sul e 34° 54 27 de longitude oeste, ocupando uma área de 16.477,3 ha.; e o assentamento rural de Barra de Gramame, localizado no norte daquele município, cujas coordenadas são 7o14 06 e 7o15 32 de Latitude Sul e 34o48 37 e 34o51 11 de Longitude Oeste, ocupando uma área de 772,17ha. O trabalho foi desenvolvido em duas etapas: primeiramente mapearam-se as áreas do município mais susceptíveis à degradação e as que estão sendo indevidamente exploradas, nesta etapa foram utilizadas cartas topográficas na escala de 1:100.000, mapas e imagens de satélite LANDSAT TM-7 cena 214/065, Bandas 1, 2, 3, 4, 5, e 7, resolução 30 metros de agosto de 2001; na segunda etapa fez-se o estudo do impacto das práticas agrícolas no assentamento rural e o mapeamento e avaliação dos níveis de impacto ambiental, foram utilizadas cartas topográficas na escala de 1:10.000 e imagens do satélite SPOT, Banda 4, resolução de 10 metros de agosto 2001. Nas duas etapas realizaramse visitas de campo onde foi utilizado um equipamento de GPS e através de um SIG realizouse a sobreposição dos mapas e imagens. A segunda etapa, referente ao assentamento rural, foi desenvolvida em um nível de detalhamento maior do que a primeira etapa. O assentamento rural de Barra de Gramame é uma área representativa do município do Conde e por isso, os resultados obtidos da segunda etapa contribuem para o melhor conhecimento dos processos de degradação ambiental em todo o município e em áreas semelhantes do litoral do Nordeste brasileiro

La chaîne du Mayombe constitue la portion congolaise du système orogénique « Araçuaï-West Congo » qui se répartit entre la marge orientale du Brésil et la marge occidentale de l’Afrique centrale. Elle s’allonge parallèlement au littoral atlantique suivant la direction NW-SE. En tenant compte des données géochronologiques, elle se subdivise en deux domaines lithostratigraphiques : (i) le domaine paléoprotérozoïque et (ii) le domaine néoprotérozoïque. Le domaine paléoprotérozoique de la chaîne du Mayombe correspond à la partie interne de la chaîne et se caractérise par la co-existence des roches d’origine sédimentaire et magmatique déformées et métamorphisées à des degrés variés. Ces roches se répartissent en trois principaux groupes lithologiques : (i) le Groupe de la Loémé, (ii) le Groupe de la Loukoula et (iii) le Groupe de la Bikossi. L’analyse structurale des Groupes de la Loémé et de la Loukoula montre que ceux-ci sont plissés et fracturés. Dans le Groupe de la Loémé les plis présentent des axes qui s’orientent dans les directions NE-SW, NNE-SSW et N-S tandis que dans le Groupe de la Loukoula, le plissement se fait suivant la direction NE-SW. Le Groupe de la Bikossi se caractérise par des plis qui s’orientent dans les directions identifiées dans les précédants Groupes. L’étude géochimique réalisée sur les échantillons provenant du domaine paléoprotérozoïque de la chaîne du Mayombe montre que ce dernier est hétérogénique c’est-à-dire qu’il implique des terrains d’origine et de lithologie variées. La caractérisation pétrologique des ensembles lithologiques des groupes de la Loémé et de la Loukoula montre que ceux-ci sont affectés par au moins deux événements métamorphiques distincts qui se superposent. Le premier événement se traduit par des paragenèses à grenat-biotite-oligoclase dans les métapélites et par le développement de la hornblende brune dans les métabasites permettant ainsi de situer le contexte d’évolution dans le faciès des amphibolites. Le second événement s’enregistre de façon différente dans le Groupe de la Loémé et dans le Groupe de la Loukoula. Il se traduit respectivement par des assemblages à grenat-biotite-oligoclase dans les formtaions du Groupe de la Loémé et par une paragenèse à chlorite-albite-épidote dans le Groupe de la Loukoula. Les échantillons rattachés au Groupe de la Bikossi ne présentent que les traces d’un seul événement métamorphique marqué par les paragenèses à grenat-biotite-muscovite et grenat-chloritoïde-chlorite avec une température oscillant entre 510-568°C pour une pression d’environ 8 kbar. La datation U-Pb sur zircons a permis de : (i) définir les sources des matériaux détritiques ayant constitué les bassins évoluant de l’Archéen au Protérozoïque (3300-1500) ; (ii) de confirmer l’âge paléoprotérozoïque (2070-2040 Ma) du magmatisme éburnéen ainsi que l’âge néoprotérozoïque (925 Ma) des granites de type Mfoubou et Mont Kanda et (iii) mettre en évidence des perturbations du système isotopique U-Pb des zircons à 642 ± 36 Ma et 539 ± 18 Ma. Les analyses 40Ar-39Ar sur biotite, muscovite et amphibole des échantillons du domaine occidental de la chaîne du Mayombe ont fourni des âges qui situent l’événement tectono-thermique pan-africain entre 615 Ma et 496 Ma. / The Mayombe belt is the congolese part of the Araçuaï-West Congo belt system which extend from eastern margin of Brazil to western margin of central Africa. It runs parallel to the Atlantic coastline with NW-SE trend. Considering geochronological data, it is subdivided into two lithostratigraphic domains : (i) the Paleoproterozoic domain and (ii) the Neoproterozoic domain. The Paleoproterozoic domain of the Mayombe range corresponds to the inner part of the belt and is characterized by the coexistence of para and orthoderived rocks deformed and metamorphosed to varying degrees. These rocks are distributed among the three main lithological Groups : (i) the Loémé Group, (ii) the Loukoula Group and (iii) the Bikossi Group. Structural analysis of Loémé and Loukoula Groups shows folded and fractured stuctures. In the Loémé Group, folds trend NE-SW, NNE-SSW and N-S while in the Loukoula Group, the main shortening trends NE-SW. The Bikossi Group is characterized by folds oriented in the directions identified in the preceding Groups. The geochemical study carried out on samples from the Paleoproterozoic domain of the Mayombe belt shows that the latter is heterogeneous, by involving rocks of various origin and lithology. The petrological characterization of Loémé and Loukoula Groups shows that they are affected by at least two distinct metamorphic events that overlap. The first event is characterized by garnet-biotite-oligoclase parageneses in metapelites and by the development of brown hornblende in metabasites, thus allowing the evolution context to be situated in the amphibolite facies. The second event is recorded differently in Loémé Group and Loukoula Group. It consits respectively in garnet-biotite-oligoclase assemblages in the Loemé Group and in chlorite-albite-epidote paragenesis in the Loukoula Group. Samples from Bikossi Group present only traces of a single metamorphic event marked by garnet-biotite-muscovite and garnet-chloritoid-chlorite parageneses whose temperature is estimated at 510-568°C for 8 kbar of pressure. U-Pb dating of zircons allows to : (i) define the Archean-Paleoproterozoic (3300-1500Ma) sources of metasedimentary rocks (ii) confirm Paleoproterozoic (2070-2040 Ma) age of Eburnean magmatism and Neoproterozoic (925 Ma) Mfoubou and Mont Kanda type magmatism and (iii) to highlight the perturbations of zircons U-Pb isotopic system at 642 ± 36 Ma and 539 ± 18 Ma. The 40Ar-39Ar analyzes on biotite, muscovite and amphibole from samples of the western domain of Mayombe betl provided since the age range of Pan-African tectono-thermal event at 615-496 Ma.

A radiometric survey of the zoned 21 Ma, A-type Sheeprock granite, western Utah, combined with measurements of magnetic susceptibility and field observations were analyzed using a geographic information system. The intrusion spans 25 square km and is roughly eliptical in shape with its long axis trending northwest. Concentration maps (composed of more than 500 survey stations) of eU, eTh, texture, magnetic susceptibility, color, and joint density help to constrain magmatic and post-magmatic processes related to its chemical and physical zonation. Uranium ranges from 3.9 to 26.9 ppm (mean 12.7) and thorium from 1.7 to 125.7 ppm (mean 45.5). Similarities in spatial patterns and near normal distributions of U and Th imply minimal remobilization and secondary equilibrium of U. Relatively high magnetic susceptibility (6 to 12*10^-3 SI units), low eU and eTh, and limited whole rock chemical anayses show the southeastern part of the pluton is more mafic and most likely formed as an early cumulate. Dominant textures are porphyritic with a fine-grained matrix along the northeastern margin, coarsening to a medium-grained matrix along the southwestern margin. This transition from fine to medium-grained matrix textures is believed to be a preserved solidification front that had migrated from the roof and walls inward during cooling. Late stage magma mixing is evidenced by a string of mafic enclaves along the axis of the pluton near this solidification front. eU and eTh generally increase toward the finer-grained northeastern margin of the pluton. This has been interpreted to be the primary result of fractionation of U and Th into monazite and thorite. As mafic cumulates formed along the northeastern margin residual liquids were displaced inward. This depleted the more evolved parts of the pluton in U and Th. Beryl, a distinquishing characteristic of the most evolved portions of the pluton, is concentrated in two areas along the central axis of the intrusion. The intrusion is a cumulative of three magmatic phases, the second of which crystallized from the margins inward. Joint spacing is a major factor in controlling post-magmatic processes. The pluton has a higher density of joints (10 cm apart) near the upper margins, and fewer joints (> 1 meter apart) at lower elevations. Differential cooling and magma pressures are believed to have controlled the varying joint densities. Increased alteration, oxidation, and red-staining are more prevalent in areas of higher joint density. Magnetic susceptibility is bimodal. The high mode (5.4*10^-3 SI) is on the low end of magnetite-series granites and occurs most often in the white granite. The low mode (0.07*10^-3 SI) implies significant post-magmatic oxidation and the destruction of magnetite and correlates to the red granite. Truncated chemical and textural patterns along the pluton's northwestern margin support evidence for range front normal faulting.

Sessile invertebrates in the rocky intertidal experience intermittent periods of air exposure due to tidal flux, presenting risks of temperature extremes, hypoxia, nutrient limitation, and most dangerously, desiccation. Microscale variation in severity and frequency of these risks is widely dependent on vertical position within the intertidal zone. Common acorn barnacles (Balanus glandula) have a wide vertical distribution in the intertidal, creating large differences in microhabitat between the highest and lowest individuals in the population. This study set out to explore whether tidal position dependent differences exist in the response to oxygen and desiccation stress in B. glandula. We hypothesized that B. glandula from relatively high tidal heights, which are exposed to the air for a greater duration, will be better suited to tolerate anoxic and desiccation stress than conspecifics from lower tidal heights. To explore this, we compared responses of B. glandula collected from high and low intertidal positions to A) anoxia (0 mg O2/L) and hypoxia (≤ 2 mg O2/L) on survival, behavior (closed opercular plates, cirral beating, pneumostome formation), enzyme activity (lactate dehydrogenase (LDH), superoxide dismutase (SOD)), and tissue-lactate accumulation, in addition to B) the effects of humid (98% RH) and dry (32% RH) air emersion (at 17˚C) on survival, opercular behavior (open/closed), evaporative water loss (EWL) rates, and tissue-lactate accumulation. Relative to barnacles from the low intertidal, we found that barnacles from the high intertidal survive longer during anoxia and air emersion stress, close their operculum sooner in dry air, lose more water during air exposure at any humidity level, and tend to accumulate less D-lactate. We suspect that high intertidal B. glandula can survive desiccation longer by ejecting stores of mantle cavity fluid, thereby creating a moist lung-like, air-filled internal environment, then remaining largely closed and metabolically inactive when in air to avoid drying out and becoming anoxic. These differences may reflect plasticity or selective pressure in response to environmental stress during development and highlight the potential importance of microscale stress heterogeneity in influencing species climate change tolerance and potential distribution patterns.

Made available in DSpace on 2014-07-29T16:21:19Z (GMT). No. of bitstreams: 1 Faleiro Frederico Dissertacao.pdf: 1687158 bytes, checksum: e1a8a44e89beea38d1a839934c890e56 (MD5) Previous issue date: 2012-03-28 / The human actions has triggered many threats to biodiversity like land-use and climate changes, overexploitation, pollution, and introduction of invasive species, which can affect organisms both at local and global scale. The science of spatial conservation prioritization emerged as a quantitative approach to support the spatial decisions in face of these threats, while minimizing the socioeconomic and political conflicts. Here we developed spatial solutions to the conservation of non-flying mammals from Brazilian Cerrado considering the socioeconomic costs and the opportunities of environmental governance (first objective). Further, we generated solutions to face the land-use and climate change taking into account the dispersal abilities of species and uncertainties in the species distribution modeling (SDM) process (second objective). We considered the current network of reserves of the Cerrado in both objectives. We built SDMs for 154 species combining model projections weighted by their statistical fit to produce consensus maps of species distribution grouped in three distinct types of models (envelope, statistical and machine-learning models), for both current future scenarios of climate (used only in the last aim). For the first goal, we used the current predicted distribution to run spatial prioritization analyses indicating the best sites for the conservation investment considering human population density, land cost, anthropogenic land use, level of environmental governance, and the distribution of species in trade-off analyses. For the second goal, we used both current and future predicted distribution to run optimization procedures and propose priority sites for conservation, while minimizing species climate-forced dispersal distance , the mean uncertainty associated to the SDM process, and taking into account the future changes in the landscape (by our land use model). SDMs indicated that species-rich sites converge to regions with high population density, high land cost, high anthropogenic land use, and with diverse levels of environmental governance. There was a significant change in spatial priorities when socioeconomic and political dimensions were included in analyses: top priority sites moved towards the north. This spatial change reduced by 68% the potential conservation conflicts with human population, by 72% the likely conflicts arising from land cost and by 68% anthropogenic land use. It also increased by 51% the beneficial effect of environmental governance. Including land-use changes and the modeling uncertainty in the conservation planning process changed significantly the spatial distribution of priority sites in the region. While the inclusion of land-use models altered the spatial location of priority sites at the regional scale, the effects of climate change tended to take place at the local scale. Note that, our solutions already include possible dispersal corridors linking current and future priority sites for mammal conservation, as well as a formal risk analysis based on planning uncertainties. Our results allowed dealing with both complex nature of conflicts among socioeconomic and political dimensions, and the dynamic problem imposed mainly by land-use and climate change. Thus, our analyses figure as a methodological prospect supporting the decision-make process and the consequent translation of conservation planning outcomes into conservations actions / As ações humanas têm desencadeado diversas ameaças a biodiversidade como as mudanças de uso do solo e do clima, sobre-exploração, poluição e introdução de espécies invasoras, que afetas os organismos da escala local até a global. A ciência da conservação espacial para conservação emergiu como uma abordagem quantitativa que tem o objetivo de auxiliar escolhas espaciais que lidem com essas ameaças enquanto minimizam conflitos socioeconômicos e políticos. Aqui nós desenvolvemos soluções espaciais para conservação de mamíferos não voadores do Cerrado considerando os custos socioeconômicos e as oportunidades vindas da governança ambiental (primeiro objetivo). Além disso, nós geramos soluções espaciais que lidem com as mudanças do uso do solo e climáticas levando em consideração as capacidades de dispersão das espécies e as incertezas associadas ao processo de modelagem de distribuição de espécies (MDE) (segundo objetivo). Em ambos objetivos nós consideramos a atual rede de reservas do Cerrado. Nós modelamos a distribuição de 154 espécies combinando as projeções dos modelos e pesado pelo ajuste estatístico para produzir os mapas consenso de distribuição das espécies, agrupados em três distintos tipos de modelos (modelos de envelope, estatísticos e de inteligência artificial), para a atualidade e projetados para o futuro (usado apenas no último objetivo). Para o primeiro objetivo, nós usamos as predições da atual distribuição das espécies para realizar as análises de priorização espacial, indicando os melhores locais para investimento considerando a densidade humana, custo da terra, uso do solo antropogênico, nível de governança ambiental e a distribuição das espécies na perspectiva da análise de demandas conflitantes. Para o segundo objetivo, nós usamos a distribuição atual e futura das espécies para realizar o procedimento de otimização e propor locais para conservação que minimizem os efeitos da dispersão induzida pelas mudanças climáticas, incertezas associadas ao processo MDE e considerando as futuras mudanças na paisagem (através do nosso modelo de uso do solo). A MDE indicou que locais ricos em espécies convergem para locais com alta densidade populacional, alto custo de terra, alta proporção de uso do solo voltado para atividades humanas e diversos níveis de governança ambiental. Houve significativas mudanças nas prioridades espaciais quando as dimensões socioeconômicas e políticas foram incluídas nas análises, fazendo que os locais prioritários mudassem para o norte. Essa mudança espacial reduziu em 68% de potenciais conflitos com população humana, em 72% de conflitos de custo da terra, em 68% de conflitos com o uso do solo antropogênico e 51% de aumento dos possíveis benefícios da governança ambiental. Quando incluímos as mudanças de uso de solo e a incerteza da modelagem no processo de planejamento, os locais prioritários mudaram significativamente na região. Enquanto a inclusão das mudanças no uso do solo alterou a localização espacial dos locais prioritários em escala regional, os efeitos da mudança climática tenderam a ocorrem em escala local. Note que nossas soluções já incluíram possíveis corredores de dispersão para ligação entre as atuais áreas prioritárias com aquelas importantes no futuro, tão bem quanto a análise de risco baseado nas incertezas do planejamento. Nossos resultados permitiram lidar tanto com a complexa natureza dos conflitos entre dimensões socioeconômicas e políticas quanto com problema dinâmico imposto principalmente pelas mudanças do uso do solo e climáticas. Assim, nossas análises auxiliam metodologicamente a dar suporte no processo de tomada de decisão e a consequente tradução dos resultados de planejamentos de conservação em ações de conservação

Over the last decade a huge amount of experimental data on biological systems has been generated by modern high-throughput methods. Aided by bioinformatics, the '-omics' (genomics, transcriptomics, proteomics, metabolomics and interactomics) have listed, quantif ed and analyzed molecular components and interactions on all levels of cellular regulation. However, a comprehensive framework, that does not only list, but links all those components, is still largely missing. The biology-based but highly interdisciplinary field of systems biology aims at such a holistic understanding of complex biological systems covering the length scales from molecules to whole organisms. Spanning the length scales, it has to integrate the data from very different fields and to bring together scientists from those fields. For linking experiments and theory, hypothesis-driven research is an indispensable concept, formulating a cycle of experiment, modeling, model predictions for new experiments and, fi nally, their experimental validation as the start of the new iteration. On the hierarchy of length scales certain unique entities can be identi fied. At the nanometer scale such functional entities are molecules and at the micrometer level these are the cells. Cells can be studied in vitro as independent individuals isolated from an organism, but their interplay and communication in vivo is crucial for tissue function. Control over such regulation mechanisms is therefore a main goal of medical research. The requirements for understanding cellular interplay also illustrate the interdisciplinarity of systems biology, because chemical, physical and biological knowledge is needed simultaneously. Following the notion of cells as the basic units of life, the focus of this thesis are mathematical multi-scale models of multi-cellular systems employing the concept of individual (or agent) based modeling (IBM). This concept accounts for the entity cell and their individuality in function and space. Motivated by experimental observations, cells are represented as elastic and adhesive spheres. Their interaction is given by a model for elastic homogeneous spheres, which has been established for analysis of the elastic response of cells, plus an adhesion term. Cell movement is modeled by an equation of motion for each cell which is based on the balance of interaction, friction and active forces on the respective cell. As a fi rst step the model was carefully examined with regard to the model assumptions, namely, spherical shape, homogeneous isotropic elastic body and apriori undirected movement. The model examination included simulations of cell sorting and compression of multicellular spheroids. Cell sorting could not be achieved with only short range adhesion. However, it sorting completed with long range interactions for small cell numbers, but failed for larger aggregates. Compression dynamics of multi-cellular spheroids was apparently reproduced qualitatively by the model. But in a more detailed survey neither the time scales nor the rounding after compression could be reproduced. Based on these results, the applications consistent with the assumed simpli cations are discussed. One already established application is colony growth in two-dimensional cell cultures. In order to model cell growth and division, a two-phase model of the cell cycle was established. In a growth phase the cell doubles its volume by stochastic increments, and in a mitotic phase it divides into two daughter cells of equal volume. Additionally, control of the cell cycle by contact inhibition is included in the model. After examination of its applicability, the presented model is used for simulations of in vitro growth of mesenchymal stem cells (MSC) and subsequent cartilage formation in multi-cellular spheroids. A main factor for both processes is the oxygen concentration. Experimental results have shown, that i) MSC grow much better in vitro at low than at high oxygen concentrations and ii) the MSC progeny harvested from low oxygen culture produce higher amounts of the cartilage components aggrecan and collagen II in multicellular spheroids than the ones from high oxygen culture. In order to model these processes, IBM was extended by a stochastic model for cellular differentiation. In this model cellular differentiation is captured phenomenologically by two additional individual properties, the degree of differentiation and the lineage or cell type, which are subject to fl uctuations, that are state and environment dependent. After fitting the model parameters to the experimental results on MSC growth in monoclonal expansion cultures at low and high oxygen concentrations, the resulting simulated cell populations were used for initialization of the simulations of cartilage formation in multi-cellular spheroids. The model nicely reproduced the experimental results on growth dynamics and the observed number of functional cells in the spheroids and suggests the following explanation for the difference between the two expansion cultures: due to the stronger pre-differentiation found after expansion in high oxygen, the plasticity of these cells is smaller and less cell adopt the chondrogenic phenotype and start to produce cartilage. Moreover, the model predicts an optimal oxygen concentration for cartilage formation independent of expansion culture and a de-differentiating effect of low oxygen culture within 24h. Because all simulations comply with the concept of hypothesis-driven research and follow closely the experimental protocols, they can easily be tested and are currently used for optimization of a bioreactor for cartilage production. Cell populations are composed of individual cells and regulation of population properties is performed by individual cell, but knowledge about individual cell fates is largely missing due to the problem of single cell tracking. The IBM modeling approach used for modeling MSC growth and differentiation generically includes information of each individual cell and is therefore perfectly suited for tackling this question. Based on the validated parameter set, the model was used to generate predictions on plasticity of single cells and related population dynamics. Single cell plasticity was quantifi ed by calculating transition times into stem cell and differentiated cell states at high and low oxygen concentrations. At low oxygen the results predict a frequent exchange between all subpopulations, while at high oxygen a quasi-deterministic differentiation is found. After quantifying the plasticity of single cells at low and high oxygen concentration, the plasticity of a cell population is addressed in a simulation closely following a regeneration experiment of populations of hematopoietic progenitor cells. In the simulation the regeneration of the distribution of differentiation states in the population is monitored after selection of subpopulations of stem cells and differentiated cells. Simulated regeneration occurs on the time scales estimated from the single cell transition times except the unexpectedly fast regeneration from differentiated cells in the high oxygen environment, which favors differentiation. The latter case emphasizes the importance of single outlier cells in such system, which in this case repopulate less differentiated states with their progeny. In general, cell proliferation and regeneration behavior are in uenced by biomechanical and geometrical properties of the environment e.g. matrix stiffness or cell density. Because in the model cells are represented as physical objects, a variation of friction is linked to cell motility. The cultures of less motile cells become denser at the same size and the effects of contact inhibition of growth more pronounced. This variation of friction coe fficients allows the comparison of cultures with varying degrees of contact inhibition regarding their differentiation structure and the results suggest, that stalled proliferation is su fficient to explain the well-known differentiation effects in confl uent colonies. In addition, the composition of the simulated stem cell pool was analyzed regarding differentiation. In contrast to the established pedigree models, where stem cell can only be produced by asymmetric division, this model predicts that most of the cells in stem cell states descend from progenitor cells of intermediate differentiation states. A more detailed analysis of single cell derived clones revealed properties that could not be described by the model so far. First, a differentiation gradient was observed in larger colonies, that was the opposite of the one predicted by the model. Second, the proliferative activity turned out to depend not only on oxygen, but also to be a property of individual clones persisting over many generations. Because the relation slow growth/pre-differentiation also holds for single cell derived clones, the general model of differentiation is extended by another heritable individual property. Motivated by the decline of proliferation and differentiation in culture and the high metabolic and epigenetic activity during cell division, each division event is assumed to de-stabilize stem cell states. Consequently, in the model the cells age in terms of cell divisions determines the fl uctuations in stem cell states and the environment the mean fl uctuation strength. Including this novel concept, that links aging to growth and differentiation dynamics, into the model reproduces the experimental results regarding differentiation gradient and persistent clonal heterogeneity. The spatial differentiation pattern can largely be explained by the spatio-temporal growth pattern of the mono-clonal cell assembly: cells close to the border of the cell assembly have undergone more cell divisions than those in the interior and therefore their stem cell states are less stable. Heterogeneity of single-cell derived clones depends on the age of the first cell in the clone. When the stem cell fluctuations equal the mean fl uctuations strength, the proliferative activity passes a maximum at a certain age due to the destabilization of stem cell states. Thereafter the proliferative activity decreases, because more time is spent in non-proliferative differentiated states. Considering the number of divisions the cells have already undergone in vivo and after the initial expansion in vitro, it can be assumed that all cells have already passed this maximum. Interestingly, the model also predicts an optimal age for directed differentiation, when cells stably differentiate, but have not lost the required plasticity. According to the model, this clonal heterogeneity may be caused purely in vitro, but hypothetical simulation of in vivo aging yielded results consistent with experiments on MSC from rats of varying age. Finally, the detailed molecular regulation mechanisms in a multi-scale tissue model of liver zonation was studied, in which the key molecular components were explicitly modeled. Hence, this model resolved the intracellular regulation in higher resolution than the above considered differentiation models which had summarized the intracellular control and differentiation mechanisms by a few phenomenological, dynamical variables. The metabolic zonation of the liver is essential for many of the complex liver functions. One of the vitally important enzymes, glutamine synthetase, (GS) is only synthesized in a strictly defi ned pattern. Experimental evidence has shown that a particular pathway, the canonical wnt pathway, controls expression of the gene for GS. A model for transport, receptor dynamics and intracellular regulation mechanism has been set up for modeling the spatio-temporal formation of this pattern. It includes membrane-bound transport of the morphogen and an enzyme kinetics approach to fibeta-catenin-regulation in the interior of the cell. As an IBM this model reproduces the results of co-culture experiments in which two-dimensional arrangements of liver cells and an epithelial liver cell line give rise to different patterns of GS synthesis. The two main predictions of the model are: First, GS-synthesis requires a certain local cell number of wnt releasing cells. And second, a simple inversion of geometry explains the difference between the specifi c GS pattern found in the liver and in the co-culture experiments. Summarizing the results presented in this thesis, it can be concluded that properties such as the occurrence of memory effects and single cells pursuing fates far off the population average could be essential for biological function. Considering the role of single cells in many tissues, the use of individual based methods, that are able to take such effects into account, can be expected to be a very valuable tool for the problems of systems biology.

Made available in DSpace on 2017-07-10T18:13:14Z (GMT). No. of bitstreams: 1 Tiago Debona.pdf: 762754 bytes, checksum: 84144469bdb5ba849d0c3229b1d70835 (MD5) Previous issue date: 2012-08-24 / This study evaluated the hypothesis that the fish assemblage on reservoir of Hydropower Plant Governador Pedro Viriato Parigot de Souza (Capivari) is structured along its longitudinal axis, forming two or three distinct zones, which is influenced by environmental variables. For this, samples of fishes and abiotic variables were carried out quarterly between January 2004 and October 2008, in three sites (dam, intermediate and backwater) along the longitudinal gradient of the reservoir. The major variation gradients of assemblage structure (pure) were summarized with the non-metric multidimensional scaling (NMS) and compared longitudinal with the multi-response permutation procedure (MRPP). Further, it was examined the existence of indicator species at each site. In sequence, the variation gradients of assemblage structure related with abiotic variables (restricted) were extracted under the linear constraints imposed by these variables on canonical correspondence analysis (CCA). The congruence between the pure and restricted gradients was then evaluated with the Mantel test. We captured 30.085 individuals of which the fluvial local had greater richness. Ordination of NMS and MRPP test showed that the gradients of the pure structure of the fish assemblage were differentiated on longitudinal axis of reservoir, and identified differences in fluvial site from others, found greater preference of species for this site. The ordering of the CCA had a greater influence of water transparency, followed by pH and dissolved oxygen, which was consistent with the ordering of the NMS by Mantel test. Thus, we can conclude that the structure of the fish assemblage in Capivari Reservoir presented zonation pattern, with two distinct zones in a longitudinal gradient, which found greater preference of the species by fluvial area, being mainly influenced by lower values water transparency and higher levels of pH and dissolved oxygen in this site. / O presente estudo teve por avaliar a hipótese de que a assembleia de peixes do reservatório da Usina Hidrelétrica Governador Pedro Viriato Parigot de Souza (Capivari) se apresenta estruturada longitudinalmente, formando duas ou três zonas distintas, sendo estas influenciadas por variáveis ambientais. Para isso foram realizadas coletas de peixes e variáveis abióticas trimestralmente entre janeiro de 2004 e outubro de 2008 em três locais (barragem, intermediário e remanso) ao longo do gradiente longitudinal do reservatório. Os maiores gradientes de variação da estrutura da assembleia (puros) foram sumarizados com o escalonamento multidimensional não-métrico (NMS) e comparados longitudinalmente com o procedimento permutacional de multiresposta (MRPP). Adicionalmente analisou-se a ocorrência de espécies com distribuições preferenciais em cada local. Na sequência, os gradientes de variação da estrutura da assembleia associada às variáveis abióticas (restritos) foram extraídos sob a restrição linear imposta pelas mesmas através da análise de correspondência canônica (ACC). A congruência entre os gradientes puros e restritos foi então avaliada com o teste de Mantel. Em todo o período foram capturados 38.085 indivíduos sendo que o local remanso teve maior riqueza. A ordenação da NMS e o teste da MRPP mostraram que os gradientes puros da estrutura da assembleia de peixes foram diferenciados longitudinalmente, identificando diferença do local remanso dos demais, sendo verificada maior preferência de espécies por este local. A ordenação da ACC demonstrou maior influência da transparência da água, seguida de pH e do oxigênio dissolvido, sendo esta congruente com a ordenação da NMS. Assim, pode-se concluir que a estrutura da assembleia de peixes no reservatório de Capivari apresentou um padrão de zonação formando duas zonas distintas em um gradiente longitudinal, onde foi verificado maior preferência das espécies pela zona fluvial (local remanso), sendo influenciado principalmente por esta apresentar menores valores de transparência da água e maiores índices de pH e oxigênio dissolvido.