La protéine GPR50, qui fait partie de la famille des récepteurs de la mélatonine, est classée, avec une centaine d’autres protéines à sept domaines transmembranaires (7TM), dans la catégorie des récepteurs couplés aux protéines G hétérotrimériques (RCPG) orphelins, c’est-à-dire pour lesquels aucun ligand n’a pu être identifié. De plus en plus d’études montrent que les 7TM peuvent avoir des fonctions indépendantes d’un ligand. C’est le cas de GPR50 qui inhibe les fonctions du récepteur de la mélatonine MT1 en interagissant directement avec lui. Nous avons cherché à identifier d’autres partenaires associés à GPR50 en appliquant la technique de purification par affinité en tandem et avons mis en évidence son interaction avec un récepteur du facteur de croissance Transforming Growth Factor ß (TGFβ), le récepteur de type I (TβRI).Nous décrivons ici la formation d’un complexe entre GPR50 et le récepteur TβRI au niveau de la membrane plasmique, avec pour conséquence l’induction d’une activité constitutive du récepteur et des voies de signalisation en aval en l’absence de TGFβ, mais également en l’absence du récepteur TßRII qui est habituellement indispensable pour l’activation de TβRI par phosphorylation. Cette activité constitutive se traduit par la phosphorylation des protéines Smad2 et Smad3, leur intégration dans un complexe avec Smad4, la translocation du complexe dans le noyau et finalement l’activation de la transcription de leurs gènes-cibles. Nous avons décrypté les mécanismes moléculaires de cette activation constitutive en montrant que GPR50 entre en compétition, pour l’interaction avec TβRI, avec le régulateur négatif FKBP12, une protéine inhibitrice de l’activité basale du récepteur en l’absence de ligand. Nous avons identifié dans la queue intracytoplasmique de GPR50 un motif répétitif similaire à la séquence de FKBP12 impliquée dans son interaction avec TβRI , motif qui constitue la base moléculaire de cette compétition.Nous avons étudié les conséquences fonctionnelles de cette activation en surexprimant GPR50 de manière stable dans la lignée cellulaire MDA-MB-231, dérivée d’un cancer de sein. Nous avons observé dans ces cellules des effets pro-migratoires et anti-prolifératifs similaires à ceux causés par l’administration de TGFβ.En conclusion, ce travail décrit un nouveau mode d’activation du récepteur TβRI en l’absence de ligand, mais identifie également une nouvelle fonction indépendante d’un ligand pour le RCPG orphelin GPR50. En perspective de ce travail, nous allons essayer d’identifier des conditions biologiques où cette interaction pourrait prendre place afin de confirmer ces résultats dans un contexte plus physiologique. / During the last years, it became more and more accepted, that orphan G Protein coupled receptors (GPCRs) with a transmembrane spanning heptahelical core (7TM) can have ligand-independent functions. One of those 100 orphan GPCRs is GPR50, a 7TM protein with a long cytosolic domain. Recently, studies revealed ligand-independent functions for GPR50, where it has the capacity to modulate the activity of other proteins upon complex formation. By applying a tandem affinity purification approach we sought to identify further putative interacting partners of GPR50. One of the identified binding partners is the transforming growth factor β (TGFβ) receptor type I (TβRI).The TGFβ-dependent signal transduction pathway of serine/threonine kinases is a pathway with direct signal flow from ligand over the receptor to its substrates, the Smads which translocate into nucleus where they bind DNA and regulate gene expression. An important question concerns the generation of specificity and fine-tuning of TGFβ-dependent signaling. Throughout the years, an important number of proteins which regulate the activity of the TGFβ signal transduction pathway in a positive or negative manner have been identified. Most of them act in a cell-context-dependent manner, allowing the regulation of TGFβ signaling adapted to the particular circumstances.We report here the complex formation of GPR50 and TβRI on the plasma membrane. The consequence of this interaction is the GPR50-mediated induction of a constitutive activation of the TβRI and its downstream signaling in a TGFβ ligand-independent manner. This has been monitored by Smad2/3 phosphorylation, Smad2/3-Smad4 complex formation and their subsequent translocation into the nucleus, where they activate Smad-dependent gene expression. In order to decipher the molecular mechanism that allows this activation, we showed that GPR50 competes with the negative regulator, that prevents leaky TGFβ signaling, the gatekeeping molecule FKBP12, for binding to the TβRI. We identified a motif in FKBP12 involved in the interaction with TβRI with similarities to a motif in GPR50, providing a molecular basis for the replacement of FKBP12 by GPR50 in the TβRI complex. We showed that GPR50 is capable of activating the TβRI even in the absence of the TβRII, which normally is required for activating the TβRI by phosphorylation. This reveals a previously unknown mode of activation of the TβRI in absence of the TGFβ ligand and TβRII. In order to identify the functional consequences of this crosstalk, we studied migration and growth of MDA-MB-231 breast cancer cells stably overexpressing GPR50. In these cells, TGFβ-like pro-migratory and anti-proliferative effects have been observed.Future research will help to identify tissues and biological circumstances, where this crosstalk could take place for putting this novel mode of regulation of TGFβ signaling pathway into a context-dependent-manner. Additionally our work established another ligand-independent task for the orphan 7TM protein GPR50, consolidating its function as binding partner and activity modulator.

Esta pesquisa tem como objeto Os Entes Silenciosos da Sociedade Israelita segundo o Deuteronômio. E com quê esse objeto tem a ver? A pesquisa será desenvolvida a partir do livro de Deuteronômio e mirará àqueles que estão em silêncio dentro do livro. São eles: o pobre, a viúva, o órfão, o estrangeiro, o levita, o escravo e a escrava. No desenvolvimento da pesquisa, notou-se que todos eles poderiam ser colocados sob a nomenclatura de pobre. E, de fato, todos eles são pobres. Mas o redator emprega as palavras para pobre para designar um homem que, mesmo que estando em situação econômica degradada, ele ainda é livre, e, em determinado momento de sua vida, pode até optar por se tornar um escravo de um irmão. Também, percebeu-se que há quatro personagens que, quase sempre, aparecem juntos. Esses são aqueles que são chamados pelas palavras: viúva, órfão, estrangeiro e levita. Diante disso, a pesquisa foi desenvolvida da seguinte forma: o capítulo inicial, onde se faz o levantamento das palavras que ocorrem dentro do Deuteronômio, e no qual se faz algumas observações iniciais. O segundo capítulo buscará entender as palavras para pobre que ocorrem dentro do Deuteronômio. Notar-se-á aqui que elas apontam para um irmão israelita e que legislação será feita para que o tu/vós, a quem se dirige o redator do livro, aja em obediência a fala de seu Deus e seja benigno com o seu irmão empobrecido. O capítulo termina com um tratamento de Moisés como um personagem que foi identificado com os Entes Silenciosos do Israel antigo. O terceiro capítulo será desenvolvido com os Entes Silenciosos que aparecem, comumente, juntos. Eles são considerados estrangeiros por sua condição de desarraigamento. Eles não possuem propriedade. Mas existem dentro da propriedade do tu/vós. A pesquisa também desenvolverá um entendimento do dízimo do terceiro ano. O quarto capítulo trata dos escravos e escravas. A legislação deuteronômica fará uma distinção entre os escravos e escravas que são de Israel e os que não o são. O ano da libertação dos empobrecidos e dos escravizados será tratado, em sua segunda parte, pois, a primeira fora tratada no capítulo 2. / This research has the object \"The Silent Beings of Israeli society according to Deuteronomy.\" And what this object has to do? The research will be developed from the book of Deuteronomy and will target those who are silent inside the book. They are: the poor, the widow, the orphan, the stranger, the Levite, the male and female slaves. In developing the survey, it was noted that all of them could be placed under the nomenclature of \"poor.\" And indeed, they are all poor. But the writer uses the words to \"poor\" to mean a \"man\" that even being in degraded economic situation, he is still free, and at one point in your life, he can even chooses to become a slave of a brother. Also, it was noted that there are four personages that almost always appear together. These are those who are called by the words: widow, orphan, the stranger, and Levite. Therefore, the research was carried out as follows: the first chapter, where it is the lifting of words that occur within the Deuteronomy, and which makes some opening remarks. The second chapter will seek to understand the words to poor occurring within the Deuteronomy. It will be noted here that they point to an Israeli brother and that legislation will be made so that the \"thou / you\", to whom is the book\'s editor, act in obedience to the speech of their God and be charitable with your impoverished brother. The chapter concludes with a treatment of Moses as a man who was identified with the Silent Beings of ancient Israel. The third chapter will be developed with the Silent Beings that appear commonly together. They are considered \"foreign\" by their uprooting condition. They have no property. But they are within the grounds of \"thou / you.\" The research also develop an understanding of the tithe of the third year. The fourth chapter deals with the male and female slaves. The Deuteronomic legislation will make a distinction between male and female slaves who are of Israel and those who are not. The year of the liberation of impoverished and enslaved will be treated in its second part, because the first had been treated in Chapter 2.

Xiao, Lijia. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2013. / Includes bibliographical references (leaves 139-158). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese.

L'incidence des maladies hépatiques est en augmentation, ce qui rend urgente la recherche de systèmes de vectorisation d'agents thérapeutiques vers le foie. La maladie sur laquelle porte notre étude est la maladie orpheline de Wilson. Elle induit une accumulation de cuivre (Cu) principalement dans les hépatocytes et les chélateurs de Cu systémiques utilisés à ce jour pour la traiter présentent de nombreux effets secondaires. C'est dans ce contexte que nous proposons une stratégie innovante qui consiste à piéger sélectivement le cuivre en excès dans les cellules hépatiques. Des chélateurs sélectifs du Cu(I), degré d'oxydation du Cu disponible intracellulaire, ont été conçus. Afin de cibler ces derniers vers les cellules hépatiques, nous avons focalisé notre intérêt sur le récepteur aux asialoglycoprotéines (ASGP-R), une lectine abondamment et presque exclusivement exprimée à la membrane des hépatocytes.Deux familles de glycoconjugués contenant une unité de ciblage associée à une unité de vectorisation des hépatocytes ont été développées : l'une possède une plateforme cyclodécapeptidique et l'autre une plateforme pseudopeptidique d'architecture tripodale. Les unités de ciblage sont composées de N-acétylgalactosamines présentés de manière multivalente, permettant une reconnaissance et une endocytose sélective des glycoconjugués dans les hépatocytes par l'intermédiaire de la lectine ASGP R. Les deux familles de composés ont montré leur capacité à entrer dans les cellules hépatiques et à faire diminuer le taux de Cu intracellulaire disponible.L'objectif de ce travail de thèse est l'étude et l'optimisation du système de ciblage. Les efficacités d'internalisation des deux familles de glycoconjugués dans les hépatocytes sont pour cela comparée. En outre, l'influence de la structure moléculaire des glycoconjugués sur l'efficacité de ciblage est étudiée. Plusieurs glycoconjugués appartenant à chacune des deux familles de composés ont donc été synthétisés, et leur propriétés d'internalisation dans les hépatocytes humains analysée par cytométrie en flux. / Regarding the increasing incidence of liver diseases in the past decades, the discovery of drug delivery systems is becoming a major research area. In particular, the Wilson disease is a liver dysfunction, which needs more specific treatments than those available nowadays. This genetic disorder induces a toxic copper overload in the hepatocytes. Because current copper chelating therapies present many side effects due to their lack of specificity, we propose an innovative strategy that would selectively detoxify copper in liver cells. Since excess intracellular Cu is in the +I oxidation state, we figured that a chelator that would enter the hepatocytes and be specific for Cu(I) could represent an efficient strategy. To selectively target the hepatic cells, we focus our interest on a lectin, which is highly and exclusively expressed in the membrane of the hepatocytes: the asialoglycoprotein receptor (ASGP-R).Two different kinds of glycoconjugates that contain a Cu(I) chelating unit associated to liver targeting systems have been obtained : one has a cyclodecapeptide scaffold and the other a tripodal pseudopeptide core. The targeting units are composed of N-acetylgalactosamine (GalNAc) residues multivalently presented, allowing the selective recognition and endocytosis of the glyconconjugates thanks to ASGP-R. These two families of molecules were demonstrated to enter hepatocytes and to chelate intracellular copper.The aim of the present work is to study and optimise the targeting system. We have compared the efficiency of the targeting systems of the two families of molecules. Moreover the influence of several structural parameters on the internalisation efficiency was determined. Several compounds belonging to cyclodecapeptide and tripode families have been synthesised, and their ability to enter in human hepatocytes has been analysed by flow cytometry.

Les récepteurs nucléaires régulent l’expression des gènes importants pour le développement et l’homéostasie des cellules eucaryotes. Si certains d’entre eux sont activés par la liaison d’un ligand naturel, d’autres, comme le récepteur ERR, sont orphelins et ne possèdent pas de ligand naturel connu à ce jour. ERR se lie via son domaine DBD sur un élément de réponse ERRE au niveau des régions promotrices des gènes et son activité peut être modulée par la liaison de ligands synthétiques antagonistes. Par une approche de biologie structurale intégrative combinant biochimie, biophysique et cristallographie aux rayons-X, mon travail de thèse consistait en l’étude de l’organisation structurale d’ERR pour comprendre les mécanismes d’antagonisme induits par le ligand agoniste inverse XCT-790, et la topologie qu’il adopte en interagissant avec l’ADN. Mon projet était axé sur l’étude des domaines modulaires DBD et LBD en complexe avec ADN et ligand transposée à l’étude fonctionnelle du récepteur entier. Par un important travail biochimique, j’ai mis en place les protocoles de purification de ces protéines et caractérisé biophysiquement la stabilité et la stœchiométrie des complexes avec ADN et ligand. J’ai mis en évidence que le ligand XCT-790 se lie sur chacun des monomères de LBD avec une forte affinité et que le DBD interagit avec un ERRE sous la forme d’un monomère. De multiples essais de cristallisation ont abouti à l’obtention de cristaux pour les complexes avec le LBD et le DBD ayant diffracté respectivement jusqu’à 3,5 Å et 7 Å de résolution sans néanmoins pouvoir en déterminer les structures. L’ensemble de ces résultats permettent de conclure que le DBD est monomérique sur les ERRE et IR3 et semble être dimérique sur l’élément de réponse combiné ERRE/ERE. La topologie qu’adopte ERR sur l’ADN est dictée par la liaison de ligand et serait la conséquence d’une communication allostérique entre les domaines modulaires. Ces connaissances acquises faciliteront la détermination structurale d’ERR entier par cristallographie aux rayons-X ou par cryo-microscopie électronique. / Nuclear receptors regulate expression of important genes involved in development and homeostasis in eukaryotic cells. While some of them are regulated by the binding of a natural ligand, others, like ERR, are orphan and don’t have any natural ligand identified up to now. ERR binds to ERRE response elements through its DBD on promoter regions of genes and its activity can be modulated by the binding of synthetic antagonist ligands. By an integrative structural biology approach, my thesis work consisted in the study of the structural organization of ERR to understand the antagonism mechanisms induced by the inverse agonist XCT-790, and the adopted topology upon binding to DNA. My project focused on the study of the modular domains DBD and LBD complexes with DNA and ligand and extended to the functional study of the whole receptor. Thanks to significant biochemical work, I set up the purification protocols for these proteins and characterized by biophysics the stability and stoichiometry of the DNA and ligand complexes. This work revealed that XCT-790 binds on each LBD monomer with high affinity and that the DBD interacts to an ERRE as a monomer. Many crystallization trials led to crystals for the LBD and DBD complexes that diffracted respectively up to 3.5 Å and 7 Å of resolution but no structure could be determined. These results allow to conclude that the DBD is monomeric on the ERRE and IR3 and appears to be dimeric on the combined response element ERRE/ERE. The topology adopted by ERR on DNA is guided by the ligand binding and might be the consequence for an allosteric communication between the modular domains. These results provide the basis for a future structure determination of the full ERR by X-ray crystallography and cryo electron microscopy.

Esta pesquisa tem como objeto Os Entes Silenciosos da Sociedade Israelita segundo o Deuteronômio. E com quê esse objeto tem a ver? A pesquisa será desenvolvida a partir do livro de Deuteronômio e mirará àqueles que estão em silêncio dentro do livro. São eles: o pobre, a viúva, o órfão, o estrangeiro, o levita, o escravo e a escrava. No desenvolvimento da pesquisa, notou-se que todos eles poderiam ser colocados sob a nomenclatura de pobre. E, de fato, todos eles são pobres. Mas o redator emprega as palavras para pobre para designar um homem que, mesmo que estando em situação econômica degradada, ele ainda é livre, e, em determinado momento de sua vida, pode até optar por se tornar um escravo de um irmão. Também, percebeu-se que há quatro personagens que, quase sempre, aparecem juntos. Esses são aqueles que são chamados pelas palavras: viúva, órfão, estrangeiro e levita. Diante disso, a pesquisa foi desenvolvida da seguinte forma: o capítulo inicial, onde se faz o levantamento das palavras que ocorrem dentro do Deuteronômio, e no qual se faz algumas observações iniciais. O segundo capítulo buscará entender as palavras para pobre que ocorrem dentro do Deuteronômio. Notar-se-á aqui que elas apontam para um irmão israelita e que legislação será feita para que o tu/vós, a quem se dirige o redator do livro, aja em obediência a fala de seu Deus e seja benigno com o seu irmão empobrecido. O capítulo termina com um tratamento de Moisés como um personagem que foi identificado com os Entes Silenciosos do Israel antigo. O terceiro capítulo será desenvolvido com os Entes Silenciosos que aparecem, comumente, juntos. Eles são considerados estrangeiros por sua condição de desarraigamento. Eles não possuem propriedade. Mas existem dentro da propriedade do tu/vós. A pesquisa também desenvolverá um entendimento do dízimo do terceiro ano. O quarto capítulo trata dos escravos e escravas. A legislação deuteronômica fará uma distinção entre os escravos e escravas que são de Israel e os que não o são. O ano da libertação dos empobrecidos e dos escravizados será tratado, em sua segunda parte, pois, a primeira fora tratada no capítulo 2. / This research has the object \"The Silent Beings of Israeli society according to Deuteronomy.\" And what this object has to do? The research will be developed from the book of Deuteronomy and will target those who are silent inside the book. They are: the poor, the widow, the orphan, the stranger, the Levite, the male and female slaves. In developing the survey, it was noted that all of them could be placed under the nomenclature of \"poor.\" And indeed, they are all poor. But the writer uses the words to \"poor\" to mean a \"man\" that even being in degraded economic situation, he is still free, and at one point in your life, he can even chooses to become a slave of a brother. Also, it was noted that there are four personages that almost always appear together. These are those who are called by the words: widow, orphan, the stranger, and Levite. Therefore, the research was carried out as follows: the first chapter, where it is the lifting of words that occur within the Deuteronomy, and which makes some opening remarks. The second chapter will seek to understand the words to poor occurring within the Deuteronomy. It will be noted here that they point to an Israeli brother and that legislation will be made so that the \"thou / you\", to whom is the book\'s editor, act in obedience to the speech of their God and be charitable with your impoverished brother. The chapter concludes with a treatment of Moses as a man who was identified with the Silent Beings of ancient Israel. The third chapter will be developed with the Silent Beings that appear commonly together. They are considered \"foreign\" by their uprooting condition. They have no property. But they are within the grounds of \"thou / you.\" The research also develop an understanding of the tithe of the third year. The fourth chapter deals with the male and female slaves. The Deuteronomic legislation will make a distinction between male and female slaves who are of Israel and those who are not. The year of the liberation of impoverished and enslaved will be treated in its second part, because the first had been treated in Chapter 2.

<p>The objective of the study was to explore the conditions of every day life of child-headed households in South Africa. Following research questions were developed:</p><p>• How do South African children who are the head of the household perceive his or her life situation and the role as the household-head?</p><p>• How are the relations with siblings and other relatives?</p><p>• What kind of support do they need?</p><p>In order to fulfil the objective an interview study with the design as a case study was con-ducted. Seven children and young adults who had been heading household since under the age of 18 were found to be interviewed about their conditions of life. The result is presented as six case studies and is then discussed in the light of earlier knowledge on the subject as well as focusing on unique and mutual experienced of the informants. The results strongly support results in earlier research on life conditions for Child-headed households (CHH). Children living in CHHs face immense challenges and difficulties in their every day life and the sup-port given is not enough. Conclusions that are made include that improving assistance must be offered both in the dimensions of prevention of children living alone and immediate support to children already living in CHHs.</p>

<p>G protein-coupled receptors (GPCRs) are signal mediators that have a prominent role in the regulation of physiological processes and they make up the targets for 30-45% of all drugs. </p><p>Papers I and II describe the discovery of new human GPCRs belonging to the Rhodopsin family, a family which contains many common drug targets. The new receptors have only weak relationships to previously known GPCRs. However, they have been evolutionary conserved in several species and most of them display distinct expression patterns.</p><p>In paper III we identified new human GPCRs belonging to the Adhesion family, which is characterised by very long N-termini containing conserved domains. The different compositions of conserved domains as well as the expression patterns suggest that the Adhesions can have several different functions.</p><p>In paper IV we revealed remarkable species variations in the repertoires of Trace Amine-Associated Receptors (TAARs), which are relatives of the biogenic amine receptors. The human, mouse and rat TAAR genes are located in only one locus and are therefore most likely the result of gene tandem duplications. 47 of the 57 zebrafish TAARs were mapped to nine different loci on six chromosomes containing from 1 to 27 genes each. This study suggests that the TAARs arose through several different mechanisms involving tetraploidisation, block duplications, and local duplication events. </p><p>Papers V and VI are overall analyses of the repertoires of GPCRs in humans, mice and rats; which contain approximately 800, 1800 and 1900 members, respectively. The repertoires were compared to distinguish between species-specific and common (orthologous) members, something which is important for example when predicting drug effects from experiments in rodents. The Glutamate, Adhesion, Frizzled and Secretin families show no or very little variation between human and rodents, whereas the repertoires of olfactory, vomeronasal and Taste2 receptors display large differences between all three species. </p>

The objective of the study was to explore the conditions of every day life of child-headed households in South Africa. Following research questions were developed: • How do South African children who are the head of the household perceive his or her life situation and the role as the household-head? • How are the relations with siblings and other relatives? • What kind of support do they need? In order to fulfil the objective an interview study with the design as a case study was con-ducted. Seven children and young adults who had been heading household since under the age of 18 were found to be interviewed about their conditions of life. The result is presented as six case studies and is then discussed in the light of earlier knowledge on the subject as well as focusing on unique and mutual experienced of the informants. The results strongly support results in earlier research on life conditions for Child-headed households (CHH). Children living in CHHs face immense challenges and difficulties in their every day life and the sup-port given is not enough. Conclusions that are made include that improving assistance must be offered both in the dimensions of prevention of children living alone and immediate support to children already living in CHHs.

The overall aim of this study is to investigate the perception of support provided to orphan children in foster care placement in terms of education, care and support as well as protection by orphan children themselves, foster parents and social workers. Due to HIV/AIDS many children are being orphaned and are left behind without any visible means of support. HIV/AIDS remains undoubtedly one of the greatest challenges of the world today, as there is no part of the world that has not felt the devastating impact of the pandemic. This is already evidenced by the increase in number of orphans, child headed households and other vulnerable children affected by HIV/AIDS and the inability of the extended family system to provide such children with basic requirements such as shelter, food, medical care, education, love and support. The first chapter is focusing on the Magnitude of OVC in general and Namibia in particular. According to the National Plan of Action for OVC in Namibia, the total number of orphans and vulnerable children was estimated at 128 000 in 2007 (MGECW, 2007). According to 2001 Population and Housing Census the whole Khomas region had 6674 OVC, while Khomas urban had 5708 OVC, which means that in the Khomas region more OVC in an Urban areas while rural areas had less number which was 389 OVC (NPC, 2005). Chapter two presents a literature review and focuses on the phenomena of foster care placement. It includes the definition of terms such as an orphan child, a vulnerable child and foster care placement. It gives background details of foster care placement in general and foster care placement in the Namibia context. Also the support (care and support, education and protection) being offered to children in foster care placement are discussed. Chapter three focuses on the research methods and data collection of this study. The following elements are described in this chapter: Setting and samples, procedure, methods and methodological consideration, the role of the researcher, the limitations of the study and the ethnographic situation. Chapter four is devoted to the foster care placement legal framework in Namibia where the current foster care placement processes to access government grant to support foster families are discussed as well as foster care placement policy implications in Namibia. The conclusion of the findings on foster care placement processes is included. Chapter five consists of the analysis of the study. It provides the background information of the samples, questions, responses and interpretations of the main views of the respondents on the support provided to children in foster care placement in terms of care and support, education, protection as well as foster care placement process are provided in this chapter. Chapter six is focuses on discussions and conclusion. It includes major views of the respondents and the understanding of different voices of orphan children in foster care placement, foster parents and social workers who are professionals in this matter.