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‣ Estudo das bases mecanísticas da diferenciação neuronal mediada pela atividade de Ca2+ através dos receptores purinérgicos e colinérgicos; Study of mechanistic bases of neuronal differentiation mediated by Ca2+ activity through purinergic and cholinergic receptors

Resende, Rodrigo Ribeiro
Fonte: Biblioteca Digitais de Teses e Dissertações da USP Publicador: Biblioteca Digitais de Teses e Dissertações da USP
Tipo: Tese de Doutorado Formato: application/pdf
Publicado em 27/04/2007 Português
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Muitos subtipos de receptores são ativados pelo mesmo ligante, mas estão acoplados a diferentes mensageiros secundários podendo produzir sinalização divergente em uma célula, enquanto receptores ativados por diferentes ligantes, mas que compartilham o mesmo mensageiro secundário, podem produzir sinalização convergente. Para examinar as bases mecanísticas que influenciam a proliferação e a diferenciação celular determinamos as funções de liberação intracelular de Ca2+ e a excitabilidade celular mediada pelos receptores purinérgicos e colinérgicos utilizando imageamento de cálcio por microscopia confocal. Para tanto, caracterizamos a participação dos subtipos P2X1-7 e P2Y1,2,4,6 de receptores purinérgicos aos níveis dos transcritos de mRNA e de expressão protéica, assim como pela atividade de induzir os transientes de [Ca2+]i, aumento na concentração livre de cálcio intracelular, durante a diferenciação neuronal de células P19 de carcinoma embrionário, que foram utilizadas como modelo in vitro para o desenvolvimento neuronal precoce. Em células embriônicas os receptores P2Y1,2, P2X4 ou os heteromultímeros de P2X com farmacologia semelhante ao do receptor P2X4 foram os responsáveis pelos transientes de [Ca2+]i induzidos pelo ATP e seus análogos. Ao término da diferenciação neuronal...

‣ Análise proteômica das diversas fases de diferenciação osteoblástica de células-tronco mesenquimais de medula óssea; Proteomics analysis of the various stages of osteoblastic differentiation of mesenchymal stem cells from bone marrow

Paula, Leonardo Barcelos de
Fonte: Biblioteca Digitais de Teses e Dissertações da USP Publicador: Biblioteca Digitais de Teses e Dissertações da USP
Tipo: Dissertação de Mestrado Formato: application/pdf
Publicado em 13/12/2010 Português
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O crescimento, desenvolvimento e manutenção do tecido ósseo são processos altamente regulados. Diversas proteínas como hormônios, fatores de crescimento e citocinas estão envolvidas nestes processos e exercem atividade direta sobre células osteoblástica e osteoclástica, atuando em sua diferenciação e ativação metabólica. O processo de regeneração óssea é iniciado por fatores estimuladores locais como as proteínas morfogenética óssea (BMP Bone Morphogenetic Proteins). As BMPs são um produto do metabolismo dos osteoblastos, odontoblastos e de várias células tumorais, sendo armazenadas na forma de concentrados no osso, dentina e em células neoplásicas do osteossarcoma e de certos tumores odontogênicos, tais como: fibroma cementificante, cementoblastoma benigno, dentinoma, fibroma odontogênico e odontoma. Esclarecer os mecanismos que controlam a remodelação óssea é uma questão bastante relevante. Nesse sentido, as células-tronco mesenquimais têm despertado grande interesse devido ao seu potencial envolvimento no processo de reparo tissular. A obtenção de osteoblastos funcionais a partir de células-tronco mesenquimais tem sido utilizada na engenharia de tecidos e terapia celular. Desse modo, no presente trabalho foi realizada uma análise proteômica das proteínas envolvidas nas diversas fases de diferenciação osteoblástica de células-tronco mesenquimais de medula óssea de rato Wistar e humana...

‣ Efeitos da fototerapia com laser em baixa intensidade e dos fatores de crescimento PDGF e BMP-2, isolados ou em associação, na diferenciação ósseo/odontogênica de células-tronco de polpa dentária humana; Effects of low intensity laser therapy and growth factors PDGF and BMP-2 on the odontogenic differentiation of dental pulp stem cells

Ferreira, Leila Soares
Fonte: Biblioteca Digitais de Teses e Dissertações da USP Publicador: Biblioteca Digitais de Teses e Dissertações da USP
Tipo: Tese de Doutorado Formato: application/pdf
Publicado em 15/09/2011 Português
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A fototerapia com laser em baixa intensidade (FTLBI) é capaz de aumentar o metabolismo celular, o que poderia influenciar na diferenciação ósseo/odontogênica das células-tronco da polpa dentária humada (hDPSCs). O PDGF e o BMP-2 são fatores de crescimento envolvidos na dentinogênese e na reparação tecidual. O PDGF tem papel importante durante o desenvolvimento embrionário, na proliferação e migração celular e na angiogênese, enquanto o BMP-2 está fortemente associado à diferenciação celular em tecidos mineralizados, como o osso e a dentina. Sendo assim, o objetivo do estudo foi analisar os efeitos da FTLBI e dos fatores de crescimento (PDGF-BB ou BMP-2), isolados ou em associação, na diferenciação ósseo/odontogênica das hDPSCs. Para o estudo hDPSCs foram cultivadas em meio regular (G1) e irradiadas (G2), meio mineralizante (G3) e irradiadas (G4), meio mineralizante contendo PDGF-BB (G5) e irradiadas (G6), meio mineralizante contendo BMP-2 (G7) e irradiadas (G8). Para os grupos irradiados, a FTLBI foi realizada no modo pontual e em contato, com um laser de diodo semi-condutor, com área de feixe de 0,028cm2 e comprimento de onda 660nm (InGaAlP-vermelho), utilizando-se os seguintes parâmetros: potência de 20mW...

‣ Um Modelo para Estudos de Modulação da Pluripotência e Diferenciação Celular em Células-Tronco Pluripotentes; A Model for Studying the Modulation of Pluripotency and Cell Differentiation in Pluripotent Stem Cells

Lima, Ildercílio Mota de Souza
Fonte: Biblioteca Digitais de Teses e Dissertações da USP Publicador: Biblioteca Digitais de Teses e Dissertações da USP
Tipo: Dissertação de Mestrado Formato: application/pdf
Publicado em 07/06/2013 Português
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Células pluripotentes são aquelas que possuem a capacidade de dar origem às células dos três folhetos embrionários (ectoderma, mesoderma e endoderma), bem como também às células germinativas. As células-tronco embrionárias (CTE) são as células pluripotentes mais conhecidas, as quais apresentam uma elevada capacidade de diferenciação celular e autorenovação. Estas propriedades tornam as CTE potenciais ferramentas para a medicina regenerativa, porém seu uso na prática clínica enfrenta várias barreiras. Neste sentido, o acúmulo de conhecimento a respeito dos mecanismos envolvidos na manutenção da pluripotência, levou ao desenvolvimento de técnicas capazes de induzir a pluripotência em células somáticas adultas. Na maioria das abordagens, isto se dá pela expressão ectópica de fatores de transcrição envolvidos na pluripotência (como Oct4 e Nanog). Com isto em vista, torna-se evidente que estudos que levem a um melhor entendimento destas propriedades biológicas, podem levar ao desenvolvimento desta importante área. Apesar destas inovações, os mecanismos responsáveis pela manutenção ou indução da pluripotência e da autorenovação, continuam largamente inexplorados. Neste sentido, o conjunto de técnicas referidas como High Content Screening (HCS) apresenta características fundamentais que permitiriam a interrogação sistemática e em larga-escala de fatores que possam estar influenciando nestes processos. A técnica de HCS se baseia no uso de microscopia de fluorescência em placas de 96 ou mais poços...

‣ Improving murine embryonic stem cell differentiation into cardiomyocytes with neuregulin-1: differential expression of microRNA

Sun, Maoyun; Yan, Xinhua; Bian, Yun; Caggiano, Anthony O.; Morgan, James P.
Fonte: American Physiological Society Publicador: American Physiological Society
Tipo: Artigo de Revista Científica
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Identification of factors that direct embryonic stem (ES) cell (ESC) differentiation into functional cardiomyocytes is essential for successful use of ESC-based therapy for cardiac repair. Neuregulin-1 (NRG1) and microRNA play important roles in the cardiac differentiation of ESCs. Understanding how NRG1 regulates microRNA will provide new mechanistic insights into the role of NRG1 on ESCs. It may also lead to the discovery of novel microRNAs that are important for ESC cardiac differentiation. The objective of this study was to assess the microRNA expression profile during NRG1-induced ESC cardiac differentiation. Murine ESCs were incubated with a recombinant NRG1β or an inhibitor of ErbB2 or ErbB4 during hanging drop-induced cardiac differentiation. The expression of cardiac-specific markers and microRNAs was analyzed by RT-PCR and microRNA array, respectively. We found that the expression of NRG1 and the ErbB receptors was increased during hanging drop-induced cardiac differentiation of ESCs. NRG1 stimulation during a specific developmental window enhanced, while inhibition of the ErbB2 or ErbB4 receptor inhibited, cardiac differentiation of ESCs. NRG1 increased the expression of mmu-miR-296–3p and mmu-miR-200c*, and decreased mmu-miR-465b-5p. Inhibition of mmu-miR-296–3p or mmu-miR-200c* decreased...

‣ Filamin B Regulates Chondrocyte Proliferation and Differentiation through Cdk1 Signaling

Hu, Jianjun; Lu, Jie; Lian, Gewei; Zhang, Jingping; Hecht, Jonathan L.; Sheen, Volney L.
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica
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Humans who harbor loss of function mutations in the actin-associated filamin B (FLNB) gene develop spondylocarpotarsal syndrome (SCT), a disorder characterized by dwarfism (delayed bone formation) and premature fusion of the vertebral, carpal and tarsal bones (premature differentiation). To better understand the cellular and molecular mechanisms governing these seemingly divergent processes, we generated and characterized FlnB knockdown ATDC5 cell lines. We found that FlnB knockdown led to reduced proliferation and enhanced differentiation in chondrocytes. Within the shortened growth plate of postnatal FlnB−/− mice long bone, we observed a similarly progressive decline in the number of rapidly proliferating chondrocytes and premature differentiation characterized by an enlarged prehypertrophic zone, a widened Col2a1+/Col10a1+ overlapping region, but relatively reduced hypertrophic zone length. The reduced chondrocyte proliferation and premature differentiation were, in part, attributable to enhanced G2/M phase progression, where fewer FlnB deficient ATDC5 chondrocytes resided in the G2/M phase of the cell cycle. FlnB loss reduced Cdk1 phosphorylation (an inhibitor of G2/M phase progression) and Cdk1 inhibition in chondrocytes mimicked the null FlnB...

‣ Glutathione homeostasis during terminal human leukemia-60 (HL-60) cell differentiation

Krance, Suzanne M. ; Ballatori, Nazzareno
Fonte: Universidade de Rochester Publicador: Universidade de Rochester
Tipo: Tese de Doutorado Formato: Number of Pages:xvi, 145 leaves
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Thesis (Ph. D.)--University of Rochester. School of Medicine & Dentistry. Dept. of Environmental Medicine, 2008. ; The tripeptide glutathione (L-γ-glutamyl-L-cysteinylglycine; GSH), is the most abundant intracellular thiol and functions as a major regulator of the intracellular redox state. Imbalances in GSH homeostasis are associated with a wide array of disease states, and are implicated in the aging process. For years, research on GSH has focused on its role in detoxification, however a renewed interest in the molecule has focused on its role in major cell processes, including cell differentiation. A number of studies have described GSH status in differentiated cells, however limited information is available concerning GSH status during the process. In addition, many seemingly contradictory reports have been made concerning the effects of altering GSH levels on differentiation outcomes. Studies in this thesis were designed to elucidate GSH status during terminal differentiation, and to determine how altering GSH during the process affects differentiation. It was hypothesized that GSH status is dynamic during terminal differentiation, and that depleting levels of this tripeptide modulates differentiation outcomes. In order to test this hypothesis...

‣ TRANSCRIPTIONAL AND POST-TRANSCRIPTIONAL REGULATION OF ADULT AND FETAL MOUSE NEURAL STEM CELL PROPERTIES: ROLE OF REPRESSOR ELEMENT 1-SILENCING TRANSCRIPTION FACTOR AND MICRORNAS IN NEURONAL AND GLIA DIFFERENTIATION

CARAMANICA, PASQUALE
Fonte: La Sapienza Universidade de Roma Publicador: La Sapienza Universidade de Roma
Tipo: Tese de Doutorado
Português
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Neural stem cells (NSCs) are a self-renewing population of cells that generate the neurons and glia of both the developing and adult central nervous system (CNS). The maintenance versus differentiation of NSCs relies on an intricate network of signalling regulators that finely control gene expression program in a spatial and temporal defined sequence. One factor that has been implicated in neuronal differentiation is the repressor element-1 silencing transcription factor (REST). Recent evidences suggest that REST plays a much broader role that varies according to cell type and developmental stage. In this study, we address the role of REST in regulating the properties of NSCs derived from the mouse adult Subventricular Zone (SVZ). Rest silencing in a transiently or stable transfected adult NSC line (aNSC1) promoted cell differentiation into neurons and glia, despite the presence of growth factors in the culture medium. Interestingly REST silencing did not modify the neurogenic and gliogenic potential of aNSC1 induced to differentiate by growth factors withdrawal. These data suggest that REST is crucial to the maintenance of aNSC1 in an undifferentiated proliferative state but it does not affect their lineage-specific differentiation program. Consistently...

‣ The Role of Ras Oncogene in Differentiation of 3T3-L1 Preadipocytes

Gonzalez, Victor M
Fonte: FIU Digital Commons Publicador: FIU Digital Commons
Tipo: Artigo de Revista Científica Formato: application/pdf
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Ras is a proto-oncogene that codes for a small GTPase and is responsible for linking several extracellular signals to intracellular mechanisms that involve cell growth, differentiation and cell-programmed death in normal and diseased cells. In all these processes, Ras has been extensively investigated. However, the role of Ras GTPases is still poorly understood during the differentiation of 3T3-L1 preadipocytes. In this study I investigated the role of the H-Ras defective mutant, Ras:G12V on the differentiation of 3T3-L1 preadipocytes. Preadipocytes were differentiated in vitro to adipocytes (fat cells) by adding an induction medium containing several factors including glucose and insulin. The formation of fat cells evidenced by the visualization of lipid drops as well as by quantifying the accumulation of Oil red O into lipid drops. To examine the role of Ras:G12V mutant, several selective mutations were introduced in order to determine the signaling transduction pathways (i.e., PI3(K)kinase and MAP(K)Kinase) responsible for the Ras-dependent adipogenesis. Cells expressing Ras:G12V mutant stimulated 3T3-L1 preadipocyte differentiation without he need for induction media, suggesting that Ras activation is an essential factor required for 3T3-L1 preadipocyte differentiation. Introduction of a second mutation on Ras:G12V (i.e....

‣ Novel fibroblast growth factor receptor signalling pathways regulating neuronal differentiation.

Kong, Yang
Fonte: Universidade de Adelaide Publicador: Universidade de Adelaide
Tipo: Tese de Doutorado
Publicado em //2014 Português
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The fibroblast growth factors (FGFs) consist of a family of growth factors that regulate diverse (or pleiotropic) responses, such as cell survival, proliferation, differentiation, and migration in both development and adulthood. The FGFs exert their biological activities through the binding and activation of four structurally related FGF receptors (FGFR1-4). The activation of FGFRs leads to FGFR tyrosine phosphorylation and the recruitment of SH2/PTB-domain signalling proteins, which are essential for initiating the downstream signalling pathways. Although receptor tyrosine phosphorylation is known to be important for cellular responses mediated by FGFRs, the precise mechanisms by which the FGFRs regulate pleiotropic biological responses remain unclear. In addition to receptor tyrosine phosphorylation, previous work in the Cell Growth and Differentiation Laboratory has shown that the FGFR cytoplasmic domain is also phosphorylated on a specific serine residue, Serine 779(S779), which recruits and binds the 14-3-3 family of phosphoserine/threonine-binding adaptor/scaffold proteins. However the precise role of the receptor phosphoserine signalling event in regulating downstream pathways and biological events has remained unclear. Using PC12 pheochromocytoma cells and primary mouse bone marrow stromal cells (BMSCs) as models for growth factor-regulated neuronal differentiation...

‣ Entwicklung und Anwendung neuer Analyseverfahren zur Differenzierung muriner embryonaler Stammzellen; Development and Application of novel Methods for Embryonic Stem Cell Differentiation

Wilhelm, Thomas
Fonte: Universidade de Tubinga Publicador: Universidade de Tubinga
Tipo: Dissertação
Português
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In der vorliegenden Arbeit wurden neuartige Methoden zur Differenzierung muriner embryonaler Stammzellen (ES-Zellen) angewandt und entwickelt, die Analysen früher Differenzierungsprozesse im Modellsystem, sowie die spezifische Differenzierung von Zelltypen ermöglichten. Die Einleitung der Differenzierung embryonaler Stammzellen erfolgte mit einem System (drop arrays) zur Aggregation von ES-Zellen, dessen Design die Erzeugung homogener embryoid bodies (EBs) in Massenkultur (mehrere tausend) ermöglichte. Das vorhandene drop array-System (Kammer, Patent) war Grundlage weiterer EB-Analyse-Verfahren. Mit einem visuellen Aufnahme-System (Live-Imaging-System) konnten frühe hämatopoetische Differenzierungsprozesse während der EB-Entwicklung dokumentiert werden. Die beobachteten hämatopoetischen Vorläufer konnten isoliert und zu hämatopoetischen Zellen der myeloischen Linien, sowie zu Mastzellpopulationen differenziert werden. Im weiteren Verlauf dieser Arbeit wurde der zeit- und konzentrationsabhängige Effekt des Morphogens Retinoinsäure analysiert. Mit einem EB-Dokumentations-System, bei dem die EBs an den arrays automatisiert aufgenommen und gemessen wurden, konnte der antiproliferative Effekt von RA während der EB-Entwicklung dargestellt werden. Unter Verwendung des drop array-Systems konnte die RA-induzierte neuronale Differenzierung für die Entwicklung eines neuen neuronalen Differenzierungsprotokolls genutzt werden...

‣ Kardiomyogene Differenzierungspotenz und Wachstumskinetik von adulten humanen mesenchymalen Stammzellen; Cardiomyogenic differentiation potential and kinetic of growth of adult human mesenchymal stem cells

Wöhrle, Stefanie
Fonte: Universidade de Tubinga Publicador: Universidade de Tubinga
Tipo: Dissertação
Português
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In den Industrienationen sind kardiale Erkrankungen die häufigsten Krankheitsursachen und durch sie und ihre Folgen entstehen jedes Jahr sehr hohe Kosten für das Gesundheitswesen. Durch das entstehende Narbengewebe nach einem Herzmuskelschaden kann die Herzmuskeltätigkeit insuffizient werden. Bislang wurden noch keinen effektiven Methoden zur Regeneration von hypoxisch Herzmuskelschäden etabliert. Tissue engineering und Stammzellforschung könnten viel versprechende Therapieansätze bei nicht regenerierbaren Gewebsdefekten bieten. Im Besonderen könnten hMSCs aus Knochenmark und anderen Geweben aufgrund ihrer relativ einfachen Gewinnung sowie ihrer möglichen Kapazität zur kardiomyogenen Regeneration attraktive Kandidaten darstellen. In einigen Studien wurden zum Teil sehr unterschiedliche Methoden zur kardiomyogenen Differenzierung von hMSC in vivo und in vitro beschrieben. Dabei wurde neben der Transplantation von undifferenzierten hMSC insbesondere auch die kardiomyogene Differenzierung der Zellen in vitro vor der Transplantation untersucht. Insgesamt ist die Datenlage hierzu sehr widersprüchlich: Zum einen zeigen einige Studien klar, dass aus dem Knochenmark gewonnene MSC nicht zu funktionsfähigen Herzmuskelzellen differenzieren...

‣ Diferenciação populacional em genes sob forte seleção balanceadora:um estudo de caso com genes HLA.; Population differentiation at genes under strong balancing selection: a case study on the HLA genes

Brandt, Débora Yoshihara Caldeira
Fonte: Biblioteca Digitais de Teses e Dissertações da USP Publicador: Biblioteca Digitais de Teses e Dissertações da USP
Tipo: Dissertação de Mestrado Formato: application/pdf
Publicado em 22/06/2015 Português
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Seleção balanceadora é definida como aquela que aumenta a variabilidade genética de populações em relação ao esperado sob neutralidade. Uma expectativa sobre seus efeitos é a redução da diferenciação populacional nos genes onde atua. Contudo, regimes que mantêm conjuntos distintos de alelos em diferentes populações poderiam resultar em aumento de diferenciação populacional. Com o objetivo de compreender melhor os efeitos da seleção balanceadora sobre a distribuição da variação genética entre populações, investigamos a diferenciação populacional em genes dos Antígenos Leucocitários Humanos (HLA, do inglês, Human Leukocyte Antigen), que são os genes mais polimórficos do genoma humano e o exemplo mais clássico de seleção balanceadora em humanos. As proteínas HLA são responsáveis pela apresentação de peptídeos aos linfócitos T, mediando uma etapa crítica da resposta imune. A vantagem da manutenção de variação nesses genes está possivelmente associada à capacidade de resposta a uma maior diversidade de patógenos. Neste estudo, analisamos dados do projeto 1000 Genomas (1000G), que sequenciou indivíduos de diferentes populações usando sequenciamento de nova geração (NGS, do inglês...

‣ Durchflusszytometrische Untersuchungen von Oberflächenepitopen von mesenchymalen Stammzellen unter kardiomyogener Differenzierung; Flow cytometric examination of surface epitopes of mesenchymal stem cells under cardiomyogenic differentiation

Nowak, Patrick Wolfgang
Fonte: Universität Tübingen Publicador: Universität Tübingen
Tipo: Dissertation; info:eu-repo/semantics/doctoralThesis
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Bislang muss sich die Therapie des Akuten Koronarsyndroms, insbesondere im Falle eines Myokardinfarktes, auf die Reperfusion des ischämischen Myokardareals beschränken. Eine Restitutio ad integrum ist nicht möglich. Eine vorstellbare therapeutische Alternative könnte die Behandlung mit Kardiomyozyten bzw. mesenchymalen Stammzellen (MSC) darstellen. Dazu ist es Voraussetzung, die Kardiomyozyten bzw. MSCs therapeutisch sicher einsetzen zu können. Hier könnten MSCs aus Knochenmark eine interessante Methode darstellen, da sie einfach zu gewinnen sind und aufgrund ihrer Multipotenz die Fähigkeit zur kardiomyogenen Differenzierung haben. Ziel dieser Arbeit war es, die zahlreichen vorbeschriebenen kardiomygogenen Differenzierungsmedien mittels durchflusszytometrischer Analyse miteinander zu vergleichen. Des Weiteren sollte mit dieser Arbeit untersucht werden, inwiefern sich das Expressionsprofil der Oberflächenepitope im zeitlichen Verlauf und unter zunehmender kardiomyogener Differenzierung veränderte. Mittels Durchflusszytometrie wurden die Oberflächenepitope CD10, CD31, CD45, CD71, CD73, CD90, CD105, CD106, CD117, CD243, CD309 und GD2 untersucht. Die Kriterien der International Society of Cellular Therapy (ISCT) fanden hierbei Anwendung...

‣ Transcriptional regulation of effector CD8+ T cell differentiation and molecular dysfunction during HIV-1 infection

Noto, Alessandra
Fonte: Université de Montréal Publicador: Université de Montréal
Tipo: Thèse ou Mémoire numérique / Electronic Thesis or Dissertation
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Les cellules T CD8+ jouent un rôle primordial dans le contrôle des infections virales en limitant la dissémination des cellules infectées. Lors de l’infection chronique par le virus HIV, les cellules T CD8+ HIV-spécifiques ne se différencient pas en cellules effectrices fonctionnelles capables de tuer les cellules infectées par le virus ; ces cellules ne sont plus capables de proliférer ou de produire l’ IL-2. Ces cellules expriment PD-1 et l’engagement de PD-1, par son ligand, aboutit a plusieurs de ces déficits fonctionnels des cellules T . Le rôle de PD-1 dans la régulation d'évènements transcriptionnels contrôlant la différentiation et l'obtention des fonction effectrices des cellules T CD8+ reste à démontrer. Id2 joue un rôle central dans la différenciation des cellules T CD8+ effectrices. Nous avons émis l’hypothèse que le défaut de maturation observé chez les cellules T CD8+ PD-1 high HIV-spécifiques (CD8+PD-1hi) au cours de l’infection chronique par le virus HIV pouvait être lié à la diminution d’expression du régulateur Id2. Nous avons ainsi démontré que l'engagement de PD-1 contribuait à une diminution d'expression de Id2 et de ses cibles transcriptionnelles. La surexpression de Id2 de ces cellules a permis de restaurer l'expression de marqueurs tels que Granzyme B et Bcl-2 et diminuir l’expression du marqueur de maturation de CD27. La famille des cytokines à chaine gamma joue un rôle clef dans la survie et l’homéostasie des cellules T. Dans ce travail...

‣ Ovarian aromatase and estrogens: A pivotal role for gonadal sex differentiation and sex change in fish

Guiguen, Yann; Fostier, Alexis; Piferrer, Francesc; Chang, Ching-Fong
Fonte: Elsevier Publicador: Elsevier
Tipo: Artículo Formato: 918459 bytes; application/pdf
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15 pages, 6 figures, 1 table.-- Special issue Fish Reproduction; The present review focuses on the roles of estrogens and aromatase (Cyp19a1a), the enzyme needed for their synthesis, in fish gonadal sex differentiation. Based on the recent literature, we extend the already well accepted hypothesis of an implication of estrogens and Cyp19a1a in ovarian differentiation to a broader hypothesis that would place estrogens and Cyp19a1a in a pivotal position to control not only ovarian, but also testicular differentiation, in both gonochoristic and hermaphrodite fish species. This working hypothesis states that cyp19a1a up-regulation is needed not only for triggering but also for maintaining ovarian differentiation and that cyp19a1a down-regulation is the only necessary step for inducing a testicular differentiation pathway. When considering arguments for and against, most of the information available for fish supports this hypothesis since either suppression of cyp19a1a gene expression, inhibition of Cyp19a1a enzymatic activity, or blockage of estrogen receptivity are invariably associated with masculinization. This is also consistent with reports on normal gonadal differentiation, and steroid-modulated masculinization with either androgens...

‣ Sex-related changes in estrogen receptors and aromatase gene expression and enzymatic activity during early development and sex differentiation in the European sea bass (Dicentrarchus labrax)

Blázquez, Mercedes; González Cabeza, Alicia; Papadaki, Maria; Mylonas, Constantinos; Piferrer, Francesc
Fonte: Elsevier Publicador: Elsevier
Tipo: Artículo Formato: 918459 bytes; application/pdf
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7 pages, 2 figures, 1 table.-- PMID: 18573255 [PubMed].-- Printed version published Aug 2008.; The present study addresses the role of aromatase and estrogen receptors in sex differentiation and development. With this purpose, a sea bass female- and a male-dominant group were obtained by successive size gradings since in this species females are already larger than males at the time of sex differentiation. Changes in cyp19a and cyp19b gene expression and enzymatic activity were monitored by a validated real-time PCR and a tritiated water assay, respectively, during early development and sex differentiation. Changes in mRNA expression of estrogen receptors, both erb1 and erb2, were also assessed during this period. Results show clear sex-related differences in cyp19a gene expression and enzymatic activity in gonads, with females exhibiting significantly higher levels than males at 150 days post hatching (DPH), when histological signs of sex differentiation were evident. cyp19b gene expression and activity in brain were detectable during early ontogenesis at 50 DPH but no clear sex-related differences were observed. Both erb1 and erb2 showed higher gene expression levels in testis than in ovaries around 200–250 DPH, corresponding with the time of testicular differentiation and precocious male maturation...

‣ Differentiation of ambisexual gonads and immunohistochemical localization of P450 cholesterol side-chain cleavage enzyme during gonadal sex differentiation in the protandrous anemonefish, Amphiprion clarkii

Miura, Saori; Nakamura, Shigeo; Kobayashi, Yasuhisa; Piferrer, Francesc; Nakamura, Masaru
Fonte: Elsevier Publicador: Elsevier
Tipo: Artículo Formato: 918459 bytes; application/pdf
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9 pages, 4 figures, 2 tables.-- PMID: 17919957 [PubMed].-- Available online Aug 14, 2007.; To clarify the relationship between steroid hormones and sex differentiation of the protandrous anemonefish Amphiprion clarkii, we histologically examined its gonadal differentiation. From hatching to 30 days post hatching (dph), all of the gonads surveyed were sexually undifferentiated. The gonads of all fish first differentiated into ovaries at 60 dph, and the oocytes gradually developed and increased in number as the ovaries grew up until 183 dph. Some cysts of differentiated spermatogenic germ cells appeared in the ovaries at 214 dph, and ambisexual gonads with both ovarian and testicular tissues formed by 273 dph. Using immunohistochemistry, we then investigated the expression of cytochrome P450 cholesterol side-chain cleavage enzyme (P450scc), during gonadal sex differentiation. P450scc-immunopositive reactions first appeared in sexually undifferentiated gonads at 30 dph. Beginning at 60 dph, the number of strongly positive cells increased throughout the differentiation of the ovaries and continued to increase during the testicular differentiation until 210 dph. Immunopositive cells were observed more frequently in ovarian tissue than in testicular tissue in the ambisexual gonads at 270 dph. These results suggest that endogenous steroid hormones are important for the sex differentiation...

‣ Ascl1 phospho-status regulates neuronal differentiation in a Xenopus developmental model of neuroblastoma

Wylie, Luke A.; Hardwick, Laura J. A.; Papkovskaia, Tatiana D.; Thiele, Carol J.; Philpott, Anna
Fonte: The Company of Biologists Publicador: The Company of Biologists
Tipo: Article; published version
Português
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This is the final version of the article. It first appeared from The Company of Biologists via http://dx.doi.org/10.1242/dmm.018630; Neuroblastoma (NB), although rare, accounts for 15% of all paediatric cancer mortality. Unusual among cancers, NBs lack a consistent set of gene mutations and, excluding large-scale chromosomal rearrangements, the genome seems to be largely intact. Indeed, many interesting features of NB suggest that it has little in common with adult solid tumours but instead has characteristics of a developmental disorder. NB arises overwhelmingly in infants under 2?years of age during a specific window of development and, histologically, NB bears striking similarity to undifferentiated neuroblasts of the sympathetic nervous system, its likely cells of origin. Hence, NB could be considered a disease of development arising when neuroblasts of the sympathetic nervous system fail to undergo proper differentiation, but instead are maintained precociously as progenitors with the potential for acquiring further mutations eventually resulting in tumour formation. To explore this possibility, we require a robust and flexible developmental model to investigate the differentiation of NB's presumptive cell of origin. Here, we use Xenopus frog embryos to characterise the differentiation of anteroventral noradrenergic (AVNA) cells...

‣ A reduction in Npas4 expression results in delayed neural differentiation of mouse embryonic stem cells

Klaric, T.S.; Thomas, P.Q.; Dottori, M.; Leong, W.K.; Koblar, S.A.; Lewis, M.D.
Fonte: BioMed Central Publicador: BioMed Central
Tipo: Artigo de Revista Científica
Publicado em //2014 Português
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INTRODUCTION Npas4 is a calcium-dependent transcription factor expressed within neurons of the brain where it regulates the expression of several genes that are important for neuronal survival and synaptic plasticity. It is known that in the adult brain Npas4 plays an important role in several key aspects of neurobiology including inhibitory synapse formation, neuroprotection and memory, yet very little is known about the role of Npas4 during neurodevelopment. The aim of this study was to examine the expression and function of Npas4 during nervous system development by using a combination of in vivo experiments in the developing mouse embryo and neural differentiation of embryonic stem cells (ESCs) as an in vitro model of the early stages of embryogenesis. METHODS Two different neural differentiation paradigms were used to investigate Npas4 expression during neurodevelopment in vitro; adherent monolayer differentiation of mouse ESCs in N2B27 medium and Noggin-induced differentiation of human ESCs. This work was complemented by direct analysis of Npas4 expression in the mouse embryo. The function of Npas4 in the context of neurodevelopment was investigated using loss-of-function experiments in vitro. We created several mouse ESC lines in which Npas4 expression was reduced during neural differentiation through RNA interference and we then analyzed the ability of these Npas4 knockdown mouse ESCs lines to undergo neural differentiation. RESULTS We found that while Npas4 is not expressed in undifferentiated ESCs...