Tissue-resident macrophages (MΦ) such as microglia, Kupffer and Langerhans cells derive from Myb-independent yolk sac (YS) progenitors generated before the emergence of hematopoietic stem cells (HSCs). Myb-independent YS-derived resident MΦ self-renew locally, independently of circulating adult monocytes and HSCs. In contrast, adult blood monocytes as well as infiltrating, gut and dermal MΦ derive from Myb-dependent HSCs and are less proliferative. These findings are derived from the mouse, using gene knock-outs and lineage tracing, but their applicability to human development has not been formally demonstrated. Here I use a human pluripotent stem cell (hPSC) differentiation model of hematopoiesis, capable of monocyte/MΦ production over prolonged periods of time, as a tool to investigate human mononuclear phagocyte ontogeny. Using a transcriptomic approach I showed that hiPSC-derived monocytes/MΦ (iPS-Mo/MΦ) produced early in differentiation (first weeks) are more proliferative and less immunologically mature than iPS-Mo/MΦ produced at a later time point. I therefore hypothesised either that iPS-Mo/MΦ only become fully mature after several weeks of differentiation or that there are two developmentally distinct waves of MΦ produced over time. By comparing the transcription profile of iPS-Mo/MΦs to that of primary adult blood monocytes and fetal microglia I then showed that early and late iPS-Mo/MΦs were transcriptionally closer to fetal microglia than to adult blood monocytes. To further investigate if iPS-Mo/MΦs are indeed of the same developmental origin as MYB-independent MΦ such as microglia, I used a CRISPR-Cas9 knock-out strategy to show for the first time, that human iPS-Mo/MΦs develop in a MYB-independent, RUNX1 and SPI1 (PU.1)-dependent fashion. This result makes human iPS-Mo/MΦs developmentally related to, and a good model for, MYB-independent tissue-resident \Macros such as alveolar and kidney MΦs, microglia, Kupffer and Langerhans cells. Interestingly, while MYB was not required for the generation of iPS-Mo/MΦs, its knock-out resulted in an increase in iPS-Mo/MΦ production. To investigate this increase I developed two methods for quantifying the differentiation bottleneck occurring during hiPSC differentiation to iPS-Mo/MΦs. Those techniques highlighted a potential increase in progenitor cell generation in MYB KO cells and thus lay foundation to improve our technical understanding of EB differentiation and will enable enhanced manipulation of the EB model.

Primitive neuroectodermal tumor (PNET) is part of the Ewing sarcoma family of tumors. The present case reports a primitive neuroectodermal tumor (PNET) of rare location in the bladder in a newborn. It was evaluated with prenatal ultrasound and postnatal tomography that revealed a mass in the posterior wall of the bladder. The patient underwent partial cystectomy with subsequent analysis of the surgical piece removed, the histopathological study indicated a tumor of mesenchymal origin, and immunohistochemical staining confirmed the diagnosis of PNET of the bladder. Satisfactory result and short-term follow-up. / Revisión por pares

Abstract Not Provided / Thesis / Master of Science (MSc)

No description available.

Early embryogenesis is highlighted by the emergence of several embryonic end extraembryonic lineages. One such lineage is the primitive endoderm, which will eventually give rise to the yolk sac. Once believed to be a vestigial structure, the yolk sac is now believed to play a more prominent role in embryogenesis as it provides nutrients to the preimplantation embryo. The endoderm may also interact with the trophectoderm lineage, as they develop in close contact within the embryo. The efficiency of developing primitive endoderm in vitro is considerably low, leading to a lapse in our understanding of its development and function in cattle and other ruminants. The goal of the first study was to establish a protocol for developing primitive endoderm cultures and characterizing these cells. Bovine embryos were produced in vitro, and primitive endoderm outgrowths were created with fibroblast growth factor 2 (FGF2) supplementation. These cells can be produced in culture with 80.3 5.6% efficiency. Furthermore, outgrowths can be maintained in culture for 6-8 weeks before reaching a quiescent state. A true bovine primitive endoderm cell line does not currently exist, however, these cells hold potential in improving the current understanding of early lineage specification in cattle. A second set of studies was performed to examine the effects of maternal obesity on the preimplantation conceptus and endometrium. Exposure to maternal obesity in utero affects offspring development at the postnatal, adolescent, and adult stages of development; however, its impacts on early embryogenesis are not well studied. This work utilized an obese ewe model. Once the obese phenotype was established, ewes were bred. Conceptus and endometrial tissue were collected at D 14 of pregnancy, and samples were processed for RNA-sequencing analysis. There were no differences in pregnancy rate, ovulation rate, or pregnancies/ovulation between obese and lean animals. At an RPKM threshold of 0.2, fold-change 2, and FDR 0.05, 669 and 21 differentially expressed genes (DEGs) were identified between obese- and lean-derived endometrial samples and conceptus samples, respectively. Likewise, 137 DEGs were identified between male and female conceptuses. The PANTHER GO-Slim Biological Process system identified several biological processes affected by obesity in both the endometrium and conceptus tissue. GO terms do not currently exist for "placenta" and "trophoblast", so a literature search was conducted to identify DEGs involved in implantation and placentation. This revealed 125 placentation DEGs in the endometrium, and 4 DEGs in conceptuses between obese and lean groups. A follow-up study was conducted to examine the abundance of transcripts with regulatory roles in embryogenesis. Conceptuses exhibited differential expression of DNA methyltransferase 1 (DNMT1) based on obesity exposure, fibroblast growth factor receptor 2 (FGFR2) in a sex*obesity interaction, and peroxisome proliferator-activated receptor gamma (PPARG) and prostaglandin-endoperoxide synthase 2 (PTGS2) in a sex-specific manner. Collectively these results identify the preimplantation period as a susceptible time to maternal obesity in both conceptus and endometrial tissue. Together, these studies aim to provide a better understanding of the events controlling early embryogenesis, and insight into the implication of insults during this time. These findings will prove to be beneficial in establishing the link between maternal health, endometrial function, and subsequent offspring outcomes, with the hope of promoting a more viable embryo and thus healthier offspring. / Ph. D. / Early embryogenesis in cattle is afflicted with high embryonic loss, costing the dairy and beef industries a fair portion of their profits. The mechanisms behind these losses are not well understood, however, cellular miscommunications during lineage specification are likely to blame. Of particular interest is the endoderm lineage, which gives rise to the embryonic yolk sac. Initially believed to be a transient structure, we now believe the yolk sac is indispensable in embryogenesis as it provides nutrients to the preimplantation embryo. Our current understanding of primitive endoderm and the resulting yolk sac in cattle is severely lacking because few primitive endoderm in vitro models exist. A portion of the following work is focused on developing a protocol for producing primitive endoderm cell lines in vitro. This work improved the rate of producing primitive endoderm cells in vitro and characterized those cells. These cells will be used as a tool to better understand the mechanisms involved in early embryogenesis. Furthermore, they may help identify targets for manipulating early development to lessen the high rate of embryonic loss in cattle. The stage of early embryogenesis may also be particularly susceptible to intrauterine stressors, such as maternal obesity, because of the lineage segregation events occurring at this time. Insults to the earliest lineages can have lasting developmental effects, as these cell types will give rise to the embryo proper, yolk sac, and placenta. The effects of maternal obesity have been extensively studied in the postnatal, adolescent, and adult stages of development, however, insights into the effects on early embryogenesis are missing. The final studies of the following work are focused on the effects of maternal obesity on the preimplantation ovine conceptus and endometrium. This work utilized RNA-sequencing technology as well a qRT-PCR to identify differential gene and transcript expression in conceptus and endometrial samples collected from lean and obese ewes. Following analysis, we identified several crucial biological processes affected by maternal obesity. Of particular interest were those involved in implantation and placentation, indicating developmental programming events during early embryogenesis may be at fault for the abnormal offspring outcomes observed in previous studies. This work highlights the susceptibility of the preimplantation conceptus to maternal obesity and identifies the endometrium as a mediator between maternal nutrition and conceptus development. Additionally, this work identifies alterations in genes involved in placentation in both the conceptus and endometrium, indicating developmental programing events have occurred. As a whole, this work developed a new tool for examining early embryogenesis and the specification events that occur during that time. It also examines the embryonic impacts of maternal obesity during that critical window of development. These findings will prove to be invaluable in factors involved in early embryo development and function in ruminant species.

La population au Rmi rencontrée dans notre pratique va être le support de ce travail.Nous examinerons à travers cinq cas cliniques les points de similitude afin de comprendre leurs dépendances à l’allocation du revenu minimum. Il s’agira de se saisir de quel investissement psychique est alors pourvu l’argent et en quoi cet investissement rend inopérant l’échange avec l’institution sociale car il ne représente plus cet équivalent universel. Nous constaterons alors que la violence de l’échange provient de cette rencontre impossible entre le sujet et l’institution sociale. Nous remarquerons le type de lien qui unit le sujet à l’institution et de quelle fonction psychique celle-ci est investie. Nous observerons le déplacement de certains processus psychiques inconscients sur la scène sociale, déplacement qui nécessite la construction du champ de ce que nous avons appelé : la clinique du social. Nous considèrerons que la réflexion sur les dispositifs cliniciens nécessite de penser la question du lien et en particulier l’analyse du lien inter-partenarial dans la chaîne des dispositifs d’insertion. Nous proposerons des pistes de réflexion sur la notion d’échange comme objet de connaissance psychanalytique. / Our study group will comprised of population receiving the Rmi (French minimum revenue subsidy for the unemployed) that we encountered in our practice.Five clinical cases will enable us to examine common points in order to understand their shared dependency on minimum revenue subsidy.Our objective will be to question money as psychic investment and how this investment renders exchange with the social institution inoperative, money no longer representing this universal equivalent. Violence in exchanges will then observed due to this impossible encounter between the subject and the social institution. We will note the type of link uniting the subject to the institution and the type of psychic function of which it is invested. We observe the displacement of certain unconscious psychic processes upon the social scene, this displacement requiring the construction of a field which we have named: clinical field of the social.We will consider that reflections concerning clinical set-ups require thinking the question of the link and in particular the analysis of the inter partner link along the chain of unemployment offices. We will propose that our study lead up to the notion of exchange as object of psychoanalytical knowledge.

Thesis (M.A.)--Université catholique de Louvain, 1950. / Includes bibliographical references (p. [763]-850).

Thesis (L.L.D. (Faculty of Law))--University of the Western Cape, 2008. / Includes bibliographical references (leaves 415-452)

Les découvertes de systèmes hydrothermaux marins ont permis de dire qu'ils réunissaient les conditions favorables à l'apparition des premières formes de vie car des concentrations appréciables en N2, CO2, H2S, CH4, C2H6 et C3H8 ainsi que des quantités détectables (10-9 mol) de n-alcanes de poids moléculaire élevé (C16-C29) ont été mesurées dans les fluides hydrothermaux de la ride médio-Atlantique. Les premières formes de vie étaient sans doute des êtres microbiens simples et unicellulaires qui ont pu trouver dans les composés organiques l'énergie nécessaire à leur évolution. Les systèmes hydrothermaux marins peuvent avoir constitués un environnement favorable à l'apparition de la vie car ces systèmes sont caractérisés par des fumeurs noirs et des fumeurs blancs avec un écosystème indépendant de l'énergie solaire où vivent les organismes les plus primitifs trouvés dans les environnements actuels, les hyperthermophiles. Ces arguments sont très importants en ce qui concerne les conditions qui régnaient à l'Archéen. Les systèmes hydrothermaux Archéens sont les seuls environnements où la vie primitive a pu être protégée des impacts des météorites et de la vaporisation partielle de l'océan. Ces systèmes sont compatibles avec l'origine et l'évolution de la vie. Les études expérimentales, sur la synthèse et la stabilité des composés prébiotiques dans des conditions hydrothermales sont couplées aux études théoriques en thermodynamique permises par les travaux de mesure expérimentales. L'origine abiogéniques des composés organiques azotés dans les conditions hydrothermales est primordiale dans l'histoire de la Terre / Hydrothermal Systems discovery involve it gather favorable conditions to act for the appearing of the first living shape, because significant concentrations in N2, CO2, H2S, CH4, C2H6 and C3H8 and detectable quantities (10-9 mol) of heavy weights n-alcanes (C19-C29) were measured in hydrothermal fluids of the mid-Atlantic ridge. The first living shape were without no doubt simple or unicellular microbes being which finding in organic compounds the satisfying energize for their evolution. Hydrothermal systems could have constitute a favorable environment for the appearing of life because these systems are characterized by black smokers and white smokers with an ecosystems independent of solar energize where the most primitives organisms live, found in actual environments, the hyperthermophiles. These arguments are very important concerning the conditions ruling in Archean. The hydrothermal systems of Archean were the only environment where the primitive life was protect of meteoritic impact and partial vaporization of the ocean. These systems are compatible with origin and evolution of life. The experimental study, on the synthesis and stability of prebiotic compounds in hydrothermal conditions are gathered with thermodynamic studies permit by the works of experimental measures. Abiogenic origin of nitrogen organic compounds in hydrothermal conditions is primordial in the history of the Earth

De récentes études ont démontré que la danse était une approche efficace pour améliorer les symptômes moteurs et non-moteurs ainsi que la qualité de vie chez les patients atteints de la maladie de Parkinson (MP). Nous supposons que la Danse-Thérapie à Expression Primitive (DTEP) est une méthode plus adaptée que les approches à médiations corporelles actuellement proposées et qu’elle pourrait véhiculer des bénéfices plus importants. L'hypothèse principale est que la DTEP aura des effets bénéfiques sur la marche et sur l’équilibre, ainsi que sur le plan psychique, qu’elle améliorera la qualité de vie et le lien social, et qu’elle pourrait constituer une composante importante d'une approche multidisciplinaire de la gestion à long terme de la MP.La première étude, en partenariat avec l’hôpital Bellan et d'une durée de deux ans, a permis d’élaborer, d’observer et d’adapter un dispositif de DTEP afin de développer un dispositif type et de pouvoir proposer une prise en charge novatrice. La seconde étude, en partenariat avec l’hôpital Pitié-Salpêtrière et d’une durée de sept mois, a permis de tester la faisabilité d'une telle étude, d'expérimenter le critère principal que constitue la marche et de mesurer les effets de la DTEP avec les outils d'évaluation qui, après avoir passé en revue les études sur le sujet, nous sont apparus comme les plus pertinents et reconnus dans le milieu médical et auprès de cette population.Le développement d’une approche originale entre Sciences Humaines et Sociales et médecine pourra servir à nourrir les pratiques et la prise en charge des patients en apportant des éléments utiles à la formation des professionnels et à l’organisation des soins. La réflexion qui a fondé la méthodologie des études développées contribuera quant à elle à alimenter la recherche et à mettre en place de nouvelles études. / Recent studies have shown that dance may be an appropriate and effective strategy for improving motor and non-motor symptoms, as well as quality of life on individuals with Parkinson’s Disease (PD). Dance-Therapy through primitive expression (DTPE), as a mind-body therapy, may convey superior benefits, not only on physical areas but also on psychological and social ones. The main hypothesis is that Dance-Therapy will lead to greater gait and balance ability, an improved quality of life, will have psychological and social benefits and is an important component of a multidisciplinary approach to long-term management of PD.The first study, which lasted for two years, consisted of elaborating, observing and modifying the DTPE proposals in order to adapt them to the requirements of Parkinson's disease and to develop protocols of sessions in order to propose an innovative management of the disease.The second study, developed after a thorough literature review and which lasted seven months, made it possible to test the feasibility of such a study, to test a first main outcome (gait) and to evaluate the effects of the DTPE with the scales, which, after reviewing the studies on the subject, appeared to us to be the most relevant and well recognized in the medical community.The development of an original approach between Human and Social Sciences and Medicine can be used to feed the practices and care of patients by providing useful elements for the training of professionals and the organization of care. The thinking that has grounded the methodology of the studies developed in this thesis will contribute to fueling research and setting up new studies.