This thesis aims to investigate the extent to which work-related factors contribute to the health inequalities often observed between foreign-origin and native-origin persons in Sweden. Four empirical studies using survey data and population-based registers assessed the health impact of different labor market adversities among groups of foreign-origin persons who were both in and outside the labor market relative to native-origin Swedes. Studies I and II examined associations between different measures of working life quality, including adverse psychosocial and physical working conditions and educational mismatch, and self-reported health among the employed. Adverse psychosocial and physical working conditions minimally contributed to the excess risk of poor health found among workers from low- and middle-income countries. Over-education had a stronger association with increased risk of poor health, most notably among foreign-born workers from countries outside of Western Europe. Under-educated women from these countries also demonstrated an elevated risk of poor health.  There was no association between educational mismatch and poor health among native-born workers.  Studies III and IV focused on the health implications of labor market exclusion, and examined relationships between employment status and risk of all-cause mortality and suicide. The majority of foreign-origin groups that experienced unemployment showed an elevated risk of both mortality and suicide. The magnitude of excess risk varied by generational status and region of origin. Variations in patterns of suicide risk were also evident among migrants by age at arrival and duration of residence. Yet within many foreign-origin groups, health advantages were observed among the employed. The health of migrants is affected by the confluence of several different pre- and post-migration factors.  The extent to which health inequalities are found among persons of foreign-origin in Sweden is influenced by the degree to which they experience labor market adversities, as well as differential vulnerability to the negative effects of these adversities across foreign-origin groups. / <p>At the time of the doctoral defense, the following papers were unpublished and had a status as follows: Paper 3: Manuscript. Paper 4: Manuscript.</p>

Les échanges commerciaux s'intensifient et s'étendent à l'ensemble de la planète. Le consommateur est exigeant et sensible à la qualité et à l'origine des produits alimentaires qu'il achète. Devant la difficulté de mettre en place des systèmes documentaires dans les pays d'Afrique sub-saharienne, des nouvelles stratégies de traçabilité émergent. Parmi les nouveaux moyens de tracer les produits d'origine végétale, l'idée de créer un « code barre biologique » basé sur l'analyse des ADN de microorganismes présents sur les fruits est une piste intéressante. Cette thèse est l'objet d'étude d'un WP dirigé par D. Montet obtenu dans le cadre du projet Inco Innovkar géré par JM Bouvet de l'UR 39. Cette méthode repose sur l'hypothèse que la microflore commensale du fruit de karité est spécifique entre autre d'une zone géographique de production. L'écologie des bactéries, levures et moisissures seront étudiées par le thésard sur le karité et le Physalis, une plante à fruit de la même zone géographique à fort potentiel commercial. L'analyse biochimique des fruits ainsi que l'activité antimicrobienne de certaines molécules sera étudiée (physaline). / Trade intensified and spread to the entire planet. The consumer is demanding and sensitive to the quality and origin of food products they buy. Given the difficulty of setting up documentation systems in countries in sub-Saharan Africa, new strategies are emerging traceability. Among the new means of tracing products of plant origin, the idea of creating a "biological bar code" based on the analysis of DNA of microorganisms on fruit is an interesting idea. This thesis is the subject of a study conducted by D. Montet WP obtained under the Inco project managed by JM Bouvet Innovkar of UR 39. This method assumes that the commensally microflora of the fruit of Shea is among other a specific geographical area of production. The ecology of bacteria, yeasts and molds will be reviewed by the PhD student on Shea butter and Physalis, a plant with fruit of the same geographical area with high commercial potential. Biochemical analysis of fruit and antimic robial activity of certain molecules will be studied (physaline).

No description available.

<p>Brain tumors are an incredibly diverse group of neoplasms, as evidenced by their varied locations in the brain, histological characteristics, and genetic alterations. Brain tumor heterogeneity can be potentially explained by distinct oncogenic events or cells-of-origin, or by region-specific intrinsic or extrinsic factors. Brainstem Glioma (BSG) is a particularly deadly brain tumor, afflicting 200-300 children in the United States each year. High-grade BSG (also known as Diffuse Intrinsic Pontine Glioma, DIPG) cannot be surgically removed, and the standard treatment of radiation therapy provides only temporary relief from symptoms. The past 5 years has witnessed a dramatic increase in knowledge regarding the biological basis of this disease along with the realization that BSG is distinct from other more common types of glioma, such as cerebral cortex glioma (CG). It was the goal of this study to investigate the regional differences in gliomas arising in the brainstem versus the cerebral cortex, using mice as a model system, and to begin to understand the contributions of the various possible sources of heterogeneity.</p><p> </p><p>In doing so, we have uncovered region-specific gene expression patterns in these two types of pediatric gliomas that are apparent even when the initiating genetic alterations and cell-of-origin are kept constant. Focusing on the <italic>paired box 3</italic> (Pax3) gene, which is expressed at higher levels in BSG than CG, we have found that Pax3 expression not only characterizes mouse BSGs driven by PDGF signaling, Ink4aARF-loss, p53-loss, and H3.3-K27M expression, but also identifies a novel subset of human BSGs that are associated with <italic>PDGFRA</italic> alterations and wild type <italic>ACVR1</italic> and that commonly harbor <italic>TP53</italic> alterations and the H3.3-K27M mutation. </p><p>As Pax3 plays a pro-tumorigenic role in other types of cancer, we hypothesized that Pax3 expression contributes to the brainstem gliomagenesis process as well. By utilizing mouse models, we found that Pax3 inhibits apoptosis and promotes proliferation of Nestin-expressing brainstem progenitor cells <italic>in vitro</italic> and enhances PDGF-B-driven BSG <italic>in vivo</italic>. Furthermore, we speculate that Pax3 expression may be a marker for Wnt pathway activation in BSG, which is targetable via pharmacologic agents. Indeed, a subset of Wnt inhibitors tested effectively slowed the growth of BSG cells <italic>in vitro</italic>, however cross talk with the Shh pathway might indicate that dual Wnt and Shh inhibition is necessary.</p><p>In addition, the regional expression pattern of Pax3 in gliomas correlates with its expression in normal murine brain development, leading us to hypothesize that Pax3 progenitor cells in the neonatal brainstem can serve as a cell-of-origin for BSG. We discovered that targeting Pax3 progenitors with PDGF-B overexpression and Ink4aARF- or p53-loss induces high-grade BSG that physiologically resemble the human disease. This novel and distinct model of BSG may be utilized in the future for preclinical studies.</p><p>The identification of Pax3 as a regional marker of mouse and human BSG has led to the discovery of a novel subset of the human disease, the identification of a novel oncogene contributing to pathogenesis, and the characterization of a novel cell-of-origin with the potential to give rise to the disease. This information contributes significantly to the current understanding of the mechanisms and cellular origins of BSG, and will hopefully instruct future investigations into how to better treat this disease.</p> / Dissertation

<p>Soft tissue sarcomas (STSs) are a heterogeneous group of mesenchymal tumors comprised of >70 subtypes. An important question is how the cell of origin and the pathways to tumor development shape the broad array of STS subtypes. By forcing identical tumor-promoting mutations to different cell types in Genetically Engineered Mouse Models (GEMMs) of STS, I have a unique model system to investigate this question. In the process of performing these experiments I observed that genetic mutations are necessary, but not sufficient for rapid sarcoma formation. However, tissue injury dramatically accelerates sarcoma formation in our GEMM of STS. For my thesis, I have worked to understand how cell of origin affects sarcoma subtype and how the microenvironment in our models promotes transformation. I have observed that cell of origin plays an important, but not the only, role in defining STS subtype. Additionally, I have concluded that the microenvironment, and specifically the HGF/c-MET signaling pathway play a crucial role in promoting sarcoma development after acute tissue injury.</p> / Dissertation

L'introduction d'espèces exotiques dans un nouvel environnement constitue l'une des principales causes d'émergence d'agents pathogènes des plantes, à l'origine d'invasions biologiques. C'est le cas de la pourriture brune des cabosses causée par Phytophthora megakarya, à la suite de l'introduction du cacaoyer en Afrique. Cet agent pathogène est endémique à l'Afrique et l'hypothèse la plus probable est celle d'un saut d'hôte à partir d'une plante native africaine. Dans le but de réaliser une étude populationnelle et d'identifier son centre d'origine, nous avons mis au point 12 marqueurs microsatellites. Un total de 727 souches anciennes et récentes, provenant de toute la zone de production cacaoyère en Afrique (Cameroun, Gabon, Sao-Tomé, Nigeria, Togo, Ghana et Côte d'Ivoire) a été analysé. Un mode de reproduction de type clonal a été mis en évidence dans l'ensemble des zones étudiées. Des méthodes de structuration et d'assignation ont permis d'identifier 5 groupes génétiques : 3 groupes Afrique Centrale (AC1, AC2 et AC3), un groupe Afrique de l'Ouest (AO) et un groupe hybride (MC) au Cameroun. Les 5 groupes étaient représentés au Cameroun, suggérant une origine camerounaise de P. megakarya. Au Cameroun, 3 zones géographiques ont montré une forte diversité génétique, mais la zone Ouest qui abrite les zones refuge à Sterculiacées et où ont été implantées les premières cacaoyères serait la zone d'origine et de diversification potentielle de P. megakarya. Le deuxième chapitre de la thèse a porté sur la dynamique spatio-temporelle de P. megakarya en champ, afin d'apporter des informations biologiques complémentaires sur la survie et la dispersion de l'agent pathogène. Une étude épidémiologique a ainsi été menée pendant 2 années consécutives dans 2 zones agroécologiques contrastées au Cameroun (savane et forêt). Les résultats ont montré une diminution significative de l'incidence de la pourriture brune entre les 2 années, en relation certainement avec une variable climatique. Une surdispersion de l'incidence de la maladie a été détectée à la fin de chaque campagne dans les 2 zones, mais l'analyse des semivariogrammes tout au long des 2 campagnes de production a mis en évidence une dépendance spatiale des arbres infectés dans la seule zone forestière. Des foyers d'infection ont été mis en évidence à travers l'analyse de cartes de distribution de la maladie au cours des 2 années successives (GéoStat-R). Nous avons par ailleurs étudié la variabilité génétique entre les souches du sol et celles isolées sur cabosses. Une plus grande diversité génétique a été trouvée dans le sol par rapport aux cabosses infectées, confirmant ainsi que le sol est bien la source d'inoculum primaire de P. megakarya. Mots-clés : Pourriture brune des cabosses, Phytophthora megakarya, émergence, centre d'origine, marqueurs microsatellites, méthodes d'assignation, reproduction clonale, dynamique spatio-temporelle, foyers d'infection. / The introduction of exotic species in a new environment is at the origin of most of the biological invasions. Black pod disease of cacao is an emerging disease caused by Phytophthora megakarya, since the introduction of the cacao in Africa. P. megakarya is endemic in Africa and had most likely emerged on cacao following a host jump from an African native plant. In order to achieve a population study and to identify the center of origin of this pathogen, we selected 12 novel microsatellite markers. A total of 727 strains from all the cacao production zones in Africa (Cameroon, Gabon, Sao-Tomé, Nigeria, Togo, Ghana and Ivory Coast) were analyzed. A clonal mode of reproduction was detected. Structuring and assignment analysis allowed us to identify 5 genetic groups: 3 groups in Central Africa (AC1, AC2 and AC3), one group western Africa (AO) and a hybrid group (MC) in Cameroon. The 5 groups were represented in Cameroon, suggesting a Cameroonian origin of P. megakarya. Three zones in Cameroon showed a strong genetic diversity, but the West would be the potential zone of origin and diversification of P. megakarya. The second chapter of the thesis concerned the spatiotemporal dynamics of P. megakarya in the field, in order to bring additional biological information on the survival and the dispersal of the pathogen. We conducted an epidemiological survey during 2 consecutive years in 2 agroécological zones in Cameroon (savanna and forest). The results showed a significant decrease of the incidence of the desease between 2 years, in relation certainly with a climatic variable. A overdispersion of the incidence of the disease was detected at the end of each campaign in the 2 zones, but the analysis of semivariogrammes throughout 2 production campaigns enlighted a spatial dependence of infected trees in the forest zone only. Infection hot spots were detected through the analysis of disease maps (GéoStat-R). The genetic variability of soil and infected pods isolates was assessed. A higher genetic diversity was found in the soil, suggesting that soil is the primary inoculums sources of P. megakarya. Key-words : Black pod disease, Phytophthora megakarya, emerging disease, center of origin, microsatellite markers, assignation analysis, clonal reproduction, spatiotemporal dynamics, infection hot spots.

La réplication de l'ADN au cours de la phase S est initiée au niveau de sites spécifiques, appelés origines de réplication, qui sont distribués de manière adéquate le long des chromosomes et actifs une seule fois par cycle cellulaire. Les mécanismes qui contrôlent la position des origines de réplication restent énigmatiques chez les mammifères. Les travaux réalisés pendant cette thèse révèlent que la lysine méthyltransférase PR-Set7 humaine, responsable de la mono-méthylation de la lysine 20 de l'histone H4, induit un réarrangement chromatinien au niveau des nombreuses origines de réplication des gènes actifs. Celui-ci est caractérisé par la mono- et tri-méthylation de la lysine 20 de l'histone H4 et la tri-méthylation de la lysine 4 de l'histone H3. Ce profil de méthylation d'histones constituerait un signal épigénétique pour le recrutement sur la chromatine des facteurs nécessaires à la formation des origines de réplication, indépendamment d'un rôle sur la transcription. En effet, la présence d'une forme active de PR-Set7 en amont d'un gène rapporteur est suffisante pour induire cette cascade de méthylation et la formation d'une nouvelle origine de réplication au niveau de ce gène sans en modifier son expression. De la même manière, l'inactivation de l'enzyme dans une cellule conduit à l'inverse à une diminution du nombre total d'origines sans un effet majeur sur l'expression des gènes. Lors de la phase S, PR-Set7 est dégradée via le complexe E3 ligase CRL4Cdt2 et la protéine PCNA. Cette dégradation permet la disparition au niveau de la chromatine du signal de formation des origines, s'assurant ainsi qu'elles sont actives une seule fois par cycle. La mutation du domaine d'interaction avec PCNA est suffisante en effet pour empêcher la dégradation de PR-Set7, entraînant alors la formation et activation répétées des origines pendant la phase S (phénotype de sur-réplication). Ces résultats établissent la cascade de méthylation initiée par PR-Set7 pendant la mitose comme le mécanisme épigénétique contrôlant la mise en place et l'activation d'au moins la moitié des origines de réplication chez les mammifères. / In order to ensure accurate inheritance of genetic information through cell proliferation, chromosomes must be precisely copied once and only once and then correctly distributed to daughter cells. Chromosome replication occurs during the S phase of the cell cycle and is initiated at discrete chromosomal sites called replication origins. However, the ability to activate replication origins occurs during mitosis of the previous cell cycle and continuing into early G1 phase. This crucial step, called DNA replication licensing, consists of the assembly of a multi-protein pre-Replicative Complex (pre-RC) onto origins, making them competent for replication. During S phase, pre-RC are inhibited by different ways, that ensures that origins are activated only once per cycle and prevents DNA rereplication (multiple initiations from the same origin). In metazoans, functional replication origins do not show defined DNA consensus sequences, thus evoking the involvement of chromatin determinants in the selection of these origins.During my thesis, I have discovered that that the onset of licensing in mammalian cells coincides with an increase in histone H4 Lysine 20 monomethylation (H4K20me1) at replication origins by the methyltransferase PR-Set7. By genome mapping of H4-20me1 signals during the cell cycle, we found that nearly half of origins that fire during S phase are associated with H4-K20me1 during mitosis, when the process of replication licensing is activated. This mitotic H4-K20me1 signature is highly significant for origins located near transcription start sites and promoters that are characterized by the presence of CpG islands and H3-K4me3 signals. Furthermore, tethering PR-Set7 methylase activity to an origin-free genomic locus is sufficient to promote a chromatin remodeling follow by a creation of a functional origin of replication and promotes replication initiation. PR-Set7 and H4K20me1 are cell-cycle regulated, with high levels during M and early G1 and very low in S phase. At the onset of S phase, PR-Set7 undergoes an ubiquitin-mediated proteolysis, which depends on its interaction with the sliding-clamp protein PCNA and involves the ubiquitin E3 ligase CRL4-Cdt2. Strikingly, expression of a PR-Set7 mutant insensitive to this degradation causes the maintenance of H4K20me1 and repeated DNA replication at origins. This photolytic regulation controls the initiation of replication origin.This suggests that a cascade of lysine methylation events, initiated by PR-Set7 during mitosis, would define the position of origins in open chromatin structures.

The question to be considered is whether the issue of genetic origin is still present nowadays. I think so, because today, in comparison to the past, there are more children who grow up in single-parent families. In addition there is a significant number of children who are abandoned by their parents and there is also the area of assisted reproduction to be considered which cannot be ignored. These offer possibilities that the previous generations never dreamed of. It is true that nowadays incomplete families no longer mean stigmatization but the awareness of origin for each of us still remains very important. The complete family is not only formally but also an effectively functioning family consisting of the mother, the father and their children, creating the foundation of society. Even though the children have formally both parents, it is also important to know their biological parents in case of that they are not the same as the people who actually take care of them. This comes to the fore especially in connection with the issue of adoption when the bonds of a child with his biological family are replaced with those of "new" parents. In the case of foster care of a child, the real state does not usually get into a conflict with the legal state or more precisely with the formal state because the...

Title: The club development of american football in the Czech Republic In the first part of this thesis American football is introduced, explaining basic game principles and describing the game so that the reader can imagine what the sport is all about. The second part then focuses on examining the emergence of particular American football clubs in the Czech Republic. The whole period is divided into several stages, with a strong focus on finding a common denominator of individual events. The aim is to map American football in the Czech Republic since the establishment of the first club up to the present with emphasis on main themes and key periods. Recording individual events from the perspective of history is an important element for any future research. Keywords: American football, development, club, origin, history, Czech Republic

The Child's Right to Know Their Origin v. Babybox The goal of my Master Thesis is to evaluate the possibility of applying the child's right to know their origin, to find out the relationship between the right and Babybox and objectively compile and assess the existence of Babybox itself. My attention has been focused on other institutes, too, where the right to know one's origin is feasible to achieve as well as on institutes where this right is still being heavily discussed. I concentrated on one part of family law that has to react to the scientific and medical progress and changes in society. The topics I focused on are not unambiguous and it is necessary to deal with them sensitively as it is an issue important for the whole of society. It is clear that every human being wants to know their past and roots for many various reasons. This Thesis is divided into five chapters. The first chapter is dedicated to legal regulations in family law, both international and domestic. The most important international norms and contracts managing children's rights and related questions are included. I found the Convention on the Rights of the Child, where the right to know one's origin is also included, as the most significant norm. Many institutes are in conflict with this Convention. Czech legal framework...