Le cancer colorectal est la deuxième cause de mortalité due au cancer en Europe et aux États-Unis. Etant donné l'efficacité limitée et la toxicité élevée des agents de chimiothérapie, de nouvelles approches sont nécessaires. Le flavanolignane silybine représente le principal constituant actif du chardon-marie (Silybum marianum). Les mécanismes moléculaires des propriétés anticancéreuses de la silybine ont été étudiés dans un modèle cellulaire de progression du cancer colorectal humain : les cellules SW480 issues d'un adénocarcinome, et leurs dérivées métastatiques les cellules SW620. Les effets chimiopréventifs de la silybine ont été étudiés dans un modèle de cancérogenèse colique induite par l'azoxyméthane chez le rat. La silybine induit une mort apoptotique avec activation de la caspase-3 dans les deux lignées. L'expression des récepteurs de mort TRAIL est augmentée, et la caspase-8 activée. Le potentiel mitochondrial est perturbé provoquant une libération du cytochrome c et une activation de la caspase-9. En plus de l'activation des voies apoptotiques extrinsèque et intrinsèque la silybine induit une réponse autophagique. La combinaison de la silybine et de TRAIL, un agent anti-cancéreux prometteur, provoque une mort cellulaire synergique dans les deux lignées. Un effet synergique est aussi observé avec la combinaison de la silybine et des inhibiteurs des histones déacétylases (HDAC) : TSA et SAHA. Dans le modèle chez le rat, la silybine réduit de 50% le nombre des lésions prénéoplasiques. En conclusion, la silybine est un agent naturel intéressant pour la prévention du cancer colorectal et dans le cadre d'une combinaison avec TRAIL/des inhibiteurs d'HDACs.

The relation between place attachment and pro-environmental behaviour has not been thoroughly examined. Of the few studies to have investigated this, findings conflict (Uzzell, Pol, & Badenas, 2002; Vaske & Kobrin, 2001). Possibly, these inconsistencies relate to the definition of place attachment. The current study distinguished two dimensions of place attachment: social-symbolic (civic), and physical-natural. Data were collected from 104 community members in two proximate towns. Participants indicated their levels of natural and civic attachment, evaluated the current and future local environmental quality, and reported their pro-environmental behaviours. Greater place attachment was associated with more positive current evaluations in Trail. Surprisingly, environmental evaluations did not predict pro-environmental behaviour in either town. Both types of place attachment predicted pro-environmental behaviour in Nelson, but in Trail, only natural attachment was significant. Thus, for different cities, different types of place attachment will predict pro-environmental behaviour. Implications and directions for further research are discussed.

In the last decades our knowledge concerning cardiovascular risk factors has grown rapidly through results from longitudinal studies. However, despite new treatment, in Western countries coronary heart disease remains the leading cause of death and stroke is still the leading cause of severe disability. The studies reported in these papers examine the relationships between stroke/transient ischaemic attack (TIA) and a number of different factors measured on two different occasions in men born in Uppsala 1920-1924 and are epidemiological in their character. The findings indicate that in addition to already established risk factors, indices of an unhealthy dietary fat intake and high serum lipoprotein(a) are independent predictors of stroke/TIA. Among different glucometabolic variables a low insulin sensitivity index derived from the euglycaemic insulin clamp and proinsulin carries a high predictive value for later stroke, independently of diabetes. Moreover, cognitive test performance measured with Trail Making Test B at age 70 is a strong and independent predictor of brain infarction, indicating that the risk is already increased in the subclinical phase of milder cognitive dysfunction. Performance at a pre-stroke Trail Making Test is also of predictive value for mortality after first-ever stroke/TIA, but none of the studied pre-stroke variables or cognitive tests was found to be related to dependency after an event. In summary these studies provide further knowledge about predictors of stroke and of mortality after first-ever stroke. They also indicate the possible importance of new markers of risk, such as the level of lipoprotein(a), profile of fatty acids in the diet, low insulin sensitivity derived from clamp investigations, level of proinsulin, and cognitive performance measured with Trail Making Tests.

The relation between place attachment and pro-environmental behaviour has not been thoroughly examined. Of the few studies to have investigated this, findings conflict (Uzzell, Pol, & Badenas, 2002; Vaske & Kobrin, 2001). Possibly, these inconsistencies relate to the definition of place attachment. The current study distinguished two dimensions of place attachment: social-symbolic (civic), and physical-natural. Data were collected from 104 community members in two proximate towns. Participants indicated their levels of natural and civic attachment, evaluated the current and future local environmental quality, and reported their pro-environmental behaviours. Greater place attachment was associated with more positive current evaluations in Trail. Surprisingly, environmental evaluations did not predict pro-environmental behaviour in either town. Both types of place attachment predicted pro-environmental behaviour in Nelson, but in Trail, only natural attachment was significant. Thus, for different cities, different types of place attachment will predict pro-environmental behaviour. Implications and directions for further research are discussed.

Le cancer colorectal est la deuxième cause de mortalité due au cancer en Europe et aux États-Unis. Etant donné l’efficacité limitée et la toxicité élevée des agents de chimiothérapie, de nouvelles approches sont nécessaires. Le flavanolignane silybine représente le principal constituant actif du chardon-marie (Silybum marianum). Les mécanismes moléculaires des propriétés anticancéreuses de la silybine ont été étudiés dans un modèle cellulaire de progression du cancer colorectal humain : les cellules SW480 issues d’un adénocarcinome, et leurs dérivées métastatiques les cellules SW620. Les effets chimiopréventifs de la silybine ont été étudiés dans un modèle de cancérogenèse colique induite par l’azoxyméthane chez le rat. La silybine induit une mort apoptotique avec activation de la caspase-3 dans les deux lignées. L’expression des récepteurs de mort TRAIL est augmentée, et la caspase-8 activée. Le potentiel mitochondrial est perturbé provoquant une libération du cytochrome c et une activation de la caspase-9. En plus de l’activation des voies apoptotiques extrinsèque et intrinsèque la silybine induit une réponse autophagique. La combinaison de la silybine et de TRAIL, un agent anti-cancéreux prometteur, provoque une mort cellulaire synergique dans les deux lignées. Un effet synergique est aussi observé avec la combinaison de la silybine et des inhibiteurs des histones déacétylases (HDAC) : TSA et SAHA. Dans le modèle chez le rat, la silybine réduit de 50% le nombre des lésions prénéoplasiques. En conclusion, la silybine est un agent naturel intéressant pour la prévention du cancer colorectal et dans le cadre d’une combinaison avec TRAIL/des inhibiteurs d’HDACs. / Colorectal cancer (CRC) is the second most common cause for cancer-related deaths in Europe and in the USA. Because of the limited efficacy and considerable toxicity of chemotherapeutic agents, new approaches are needed. The hepatoprotective flavonolignan silibinin is the major biologically active compound of the milk thistle (Silybum marianum).The molecular mechanisms of the anticancer properties of silibinin in CRC were studied in an in vitro model of cancer progression consisting of the adenocarcinoma cell line SW480 and its derived metastatic cell line SW620. Its chemopreventive effects were assessed in an in vivo model of azoxymethane-induced colon carcinogenesis in the rat. Silibinin induced apoptotic cell death with activation of caspase-3 in both cell lines. The expression of death receptors was upregulated, and caspase-8 was activated. The potential of the mitochondrial membrane was perturbed permitting the release of cytochrome c and the activation of caspase-9. Besides the activation of the extrinsic and the intrinsic apoptotic pathway, silibinin induced an autophagic response. Combination of silibinin and TRAIL, a promising anticancer agent selectively inducing apoptosis in cancer cells, induced synergistic cell death in both cell lines. Synergy in cell death induction was also observed by the combination of silibinin and the histone deacetylase (HDAC) inhibitors TSA and SAHA. In the preclinical model in the rat, silibinin administration was able to reduce by half the number of preneoplastic lesions present in the colon. In conclusion, silibinin is a promising natural agent for colon cancer chemoprevention and for combination therapy with TRAIL/HDAC inhibitors.

This thesis is focused on explaining the behaviour of population of Aesculapian Snake (Zamenis longissimus) in Poohří region related to a busy road which crosses its area of distribution. To avoid the busy road Aesculapian Snake uses the roads culverts to cross the road safely. Snakes used culverts the most often on July, when their activity culminates. One of the most used culverts was culvert Nr. 2, probably because of its proximity to man-made hatch. Snakes started their activity at 8:00 a.m. and finished at 7:00 p.m. In this study their activity culminates between 4:00 p.m. and 6:00 p.m. and by temperature between 21 - 25°C. None of adults of Aesculapian Snake was detected killed on the road. There were found only juvenile snakes of this species which weren't acquainted yet with local threats.

This study weaves reflections on the Biology teaching on the Atlantic Forest biome and Caatinga through the problem and interpretive trail situations, such as teaching strategies that seek in everyday life situations that facilitate the interpretation of the natural elements, for students realize the potential of plants typical of these biomes. We seek to answer the following question: As students of the 3rd year of high school recognize the characteristics of typical plants of the Indians Palm biomes - AL, from problem situations and interpretive trail? In line with guidelines of Reigota (1995) on environmental issues, the perception is precípua, it helps to understand and interpret what the participants built on the cultural environment in the womb. The objective was to analyze the environmental awareness of students about these biomes and the problem situations and the interpretive trail as teaching strategies to expand perception. Therefore, research on environmental perception of students employed the qualitative approach of a case study, developed in July 2014, with the subject 50 students in two classes of the 3rd year of high school, a public school state of the city of Palmeira dos Indios, the morning and afternoon shifts. Of these, 26 students, the afternoon shift participated in the pedagogical moments with a qualitative approach, as action research, in November and December 2014. The data collection instruments were semi-structured questionnaire, recording video and observation. Responses were grouped into categories based on the content analysis method. The results signaled that these students were unaware of the biomes prevailing in the city, they realized the plants according to the socio-economic utility. In teaching moments didactic strategies with problem situations and interpretive trail, demonstrated significantly contribute to the expansion of environmental awareness. Both strategies were presented fruitful in meeting the objectives of this study, therefore, allowed the interaction among participants, enabling the argument as an organization of thought and opportunity to develop participatory critical skill, on everyday questions giving new meaning to teaching and learning. / O presente estudo tece reflexões a respeito do Ensino de Biologia, sobre os biomas de Mata Atlântica e Caatinga, mediante as situações problema e trilha interpretativa, como estratégias didáticas que buscam no cotidiano, situações que facilitem a interpretação dos elementos naturais, para que os estudantes percebam o potencial das plantas típicas desses biomas. Buscou-se resposta para o seguinte questionamento: Como os estudantes da 3ª série do ensino médio reconhecem as características das plantas típicas dos biomas de Palmeira dos Índios - AL, a partir das situações problema e da trilha interpretativa? Em consonância com orientações de Reigota (1995) quanto às temáticas ambientais, a percepção é precípua, pois ajuda a compreender e interpretar o que os participantes construíram sobre o ambiente no seio cultural. Assim, objetivou-se analisar a percepção ambiental dos estudantes quanto a esses biomas, bem como as situações problema e a trilha interpretativa como estratégias didáticas capazes de ampliar a percepção. Logo, na pesquisa sobre a percepção ambiental dos estudantes utilizou-se da abordagem qualitativa, do tipo estudo de caso, desenvolvida no mês de julho de 2014, tendo como sujeitos cinquenta estudantes de duas turmas da 3ª série do Ensino Médio, de uma escola pública estadual da cidade de Palmeira dos Índios, dos turnos matutino e vespertino. Destes, vinte e seis estudantes, do turno vespertino participaram dos momentos pedagógicos, com abordagem qualitativa, do tipo pesquisa-ação, nos meses de novembro e dezembro de 2014. Os instrumentos de coleta de dados foram o questionário semi-estruturado, a gravação em vídeo e a observação. As respostas foram agrupadas em categorias, com base no método de análise de conteúdo. Os resultados sinalizaram que estes estudantes desconheciam os biomas predominantes no município, percebiam as plantas de acordo com a utilidade socioeconômica. Nos momentos pedagógicos as estratégias didáticas com as situações problema e a trilha interpretativa, demonstraram contribuir significativamente com a ampliação da percepção ambiental. Ambas as estratégias apresentaram-se profícuas em atender aos objetivos desta pesquisa, pois, permitiram a interação entre os participantes, possibilitando a argumentação, como organização do pensamento e oportunidade de desenvolver habilidade crítica participativa, diante das questões do cotidiano ressignificando a o ensino e a aprendizagem.

título de Ingeniería en Biotecnología Molecular / El virus Andes (ANDV) pertenece al género Orthohantavirus (familia Hantaviridae, orden Bunyavirales). En humanos la infección por ANDV produce el síndrome pulmonar asociado a hantavirus, el cual presenta una tasa de mortalidad de alrededor de un 35%. Estos virus se caracterizan por poseer una envoltura lipídica y un genoma de ARN de hebra simple tri-segmentado, de polaridad negativa que codifica para al menos 4 proteínas, entre ellas la proteína de nucleocápside (N) multifuncional y un precursor proteico denominado GPC, que tras ser procesado resulta en las glicoproteínas Gn y Gc que se encuentran ancladas en la envoltura viral. La apoptosis es una respuesta celular común frente a una infección viral. Sin embargo, en el ciclo replicativo de los hantavirus aún es controversial si inducen o inhiben apoptosis. La apoptosis celular puede ser inducida extrínsecamente mediante receptores de muerte específicos, que pueden ser activados por un ligando de la familia del factor de necrosis tumoral, como TRAIL (ligando inductor de apoptosis relacionado al factor de necrosis tumoral, por sus siglas en inglés) a través de una cascada de señalización, mediante un dominio de muerte. En este seminario de título, se buscó determinar si la expresión o localización del receptor de TRAIL, específicamente DR5 (receptor de muerte 5, por sus siglas en inglés) se ve alterada por la expresión de proteínas Gn, Gc y N de ANDV en células humanas, y si una posible variación podría afectar la tasa de apoptosis mediada por TRAIL. En primer lugar, se analizó la expresión de DR5 en distintos tipos celulares, y se determinó que éste receptor se expresa en mayor medida en células A549, por lo que para el resto de los análisis se continuó con esta línea celular. A continuación, se midió la expresión, tanto a nivel transcripcional como traduccional de DR5 en dependencia de ANDV Gn, Gc y N, frente a lo cual, no hubo una variación significativa en la expresión general de este receptor; sin embargo, en donde sí se encontró un incremento significativo fue en la localización de DR5 en la superficie de las células A549 en presencia de ANDV N. De todas formas, no se logró detectar inducción de apoptosis en células humanas transfectadas con ANDV N, lo cual no es posible interpretar debido a la carencia de un control positivo de apoptosis celular. En resumen, estos datos en conjunto muestran que a pesar de que la expresión de ANDV N indujo un aumento en la localización de DR5 en la superficie de células A549, sin embargo, queda por determinar si este aumento podría inducir apoptosis mediada por TRAIL. / Andes virus (ANDV) belongs to the Orthohantavirus genus (Hantaviridae family, Bunyavirales order). In humans ANDV infection causes hantavirus pulmonary syndrome, which has a fatality rate around 35%. These viruses are featured by a lipid envelope and a tri-segmented, single stranded, negative sense RNA genome, that encodes at least four proteins, among them, the multifunctional nucleocapsid protein (N) and a glycoprotein precursor termed GPC, which after being proteolytically cleaved, results in the mature glycoproteins Gn and Gc, which are anchored to the viral envelope. Apoptosis is a common cellular response against a viral infection. However, in the hantavirus replicative cycle, there is still controversy whether these viruses induce or rather block apoptosis. Apoptosis can be triggered extrinsically, through specific death receptors, that can be activated by a ligand belonging to the tumor necrosis factor family, such as TRAIL (tumor necrosis factor–related apoptosis inducing ligand), through a death domain mediated signaling cascade. During this degree seminary, we aimed to determine whether the expression or location of the TRAIL receptor DR5 (death receptor 5), is altered by ANDV Gc, Gn and N expression in human cells, and if any possible variation could affect TRAIL mediated apoptosis. First, we analyzed DR5 expression in different cell types and found that there is a higher extent of DR5 expression in A549 cells, that is why, for the rest of this seminary, we continued the work with this cell line. Next, we measured DR5 expression in these cells at a transcriptional and translational level, after being transfected with plasmids encoding ANDV Gc, Gn or N. We did not find any significant variation in the total amount of DR5 expression; nevertheless, we detected a significant increase in the location of DR5 on the surface of A549 cells in the presence of ANDV N. Although, we were unable to detect apoptosis in human cells transfected with ANDV N due to the lack of a positive control of apoptosis. Finally, all together, our results show that the expression of ANDV N induces an increase in DR5 on the surface of A549 cells, however, it has yet to be determined whether or not, this is enough to induce apoptosis mediated by TRAIL.

The main aim of this diploma thesis is to work out the optimization project proposal of the interpretive trails in the selected area of the Třeboň basin. The result of the optimization is creation of new product in the area of interest. The aim of the project is to contribute to the revival of some places in the nature trail through the innovative product.

The present day world has been experiencing rapid technological advancement on the one hand and increasing number of diseases afflicting the human beings on the other. To deal with the later, medical devices are innovated and introduced in to the market (making use of the technological advancements), on a continuous basis across the world. However, taking an innovated medical device to the market poses innumerable challenges and therefore, these have to be clinically trialled before its launch to ensure safety and efficacy. Of late, India has emerged as one of the preferred destinations to carry out clinical studies due to numerous advantages, primarily its diverse human gene pool and cost-competitiveness. However, there is very little understanding on the landscape of medical devices clinically trialled in India. It is to throw light on this critical issue with respect to the selection of participants in the clinical trial process, selection of locations and determination of trial duration that the present study has been carried out. In addition, the role of patents associated with the introduction of new medical devices in relation to the key challenges is examined. Furthermore, we studied the characteristics of clinical trials by industry and non-industry sponsors and between cardiovascular and other disease related trials. The present study has been carried out based on secondary data covering 108 medical device clinical trial registrations accessed from Clinical Trial Registry of India (CTRI) database pertaining to the period 2008-2014. At the outset, the pattern of trials related to the most prominent diseases such as cardiology and cardiovascular diseases and those which are invasive and non-invasive are examined. Our findings indicate that almost 50% of the trials are related to diseases of cardiology, cardiovascular diseases and those which are invasive in nature. For studying the patenting aspect, we proposed a conceptual grouping of sponsors as Incumbent, Potential Entrant and Supporter, based on their patent holdings in the domestic market and in PCT (Patent Cooperation Treaty) filings. Patents owned by Primary Sponsor (PS) showed significant variations in their clinical trial characteristics particularly the invasiveness of device, disease type, locations and participants. Three quantitative models are developed to identify the factors that influence the selection of number of participants, locations and time taken to execute medical device clinical trials using multivariate statistical techniques. The results of the three conceptual models on number of participants, locations and trial duration showed invasiveness of device and disease type playing significant roles in all the three models. The number of PCTs owned by PS was found to be influential in selecting the number of locations and participants but not the patents owned in IPO (Indian Patent Office). We also observed significant differences between industry and non-industry sponsors in terms of their clinical trial characteristics. The findings of the study formed the basis to understand the medical device clinical trial landscape and other pertinent issues in the Indian context, which enabled us to derive appropriate inferences and policy implications.