661 |
Understanding Epigenetic Controllers of Stem Cell Fate and FunctionFactor, Daniel C. 02 February 2018 (has links)
No description available.
|
662 |
New Insights into the Biochemistry and Cell Biology of RNA RecappingTrotman, Jackson B. 25 July 2018 (has links)
No description available.
|
663 |
BIOGENESIS AND FUNCTIONAL APPLICATIONS OF PIWI INTERACTING RNAs (piRNAs)Balaratnam, Sumirtha 25 July 2018 (has links)
No description available.
|
664 |
From NF-κB to FACT: Mechanisms and Translational Applications of EGFR-mediated NF-κB RegulationDermawan, Josephine Kam Tai 03 September 2015 (has links)
No description available.
|
665 |
Identifying Novel In Vivo Epigenetic Dependencies in GlioblastomaMiller, Tyler Eugene 13 September 2016 (has links)
No description available.
|
666 |
Translational control of mRNAs transcribed from HIV-1 provirus and HIV-1 based lentiviral vectorsYilmaz, Alper 19 September 2007 (has links)
No description available.
|
667 |
Multiple Mechanisms Contribute to Regulation of Gene Expression in the <i>C. elegans</i> Excretory SystemArmstrong, Kristin R. 08 September 2008 (has links)
No description available.
|
668 |
Molecular genetic characterization of SMAD signaling molecules in pulmonary arterial hypertensionNasim, Md. Talat, Ogo, T., Ahmed, Mohammed I., Randall, R., Chowdhury, H.M., Snape, K.M., Bradshaw, T.Y., Southgate, L., Lee, G.J., Jackson, I., Lord, G.M., Gibbs, J.S., Wilkins, M.R., Ohta-Ogo, K., Nakamura, K., Girerd, B., Coulet, F., Soubrier, F., Humbert, M., Morrell, N.W., Trembath, R.C., Machado, R.D. January 2011 (has links)
Yes / Heterozygous germline mutations of BMPR2 contribute to familial clustering of pulmonary arterial hypertension (PAH). To further explore the genetic basis of PAH in isolated cases, we undertook a candidate gene analysis to identify potentially deleterious variation. Members of the bone morphogenetic protein (BMP) pathway, namely SMAD1, SMAD4, SMAD5, and SMAD9, were screened by direct sequencing for gene defects. Four variants were identified in SMADs 1, 4, and 9 among a cohort of 324 PAH cases, each not detected in a substantial control population. Of three amino acid substitutions identified, two demonstrated reduced signaling activity in vitro. A putative splice site mutation in SMAD4 resulted in moderate transcript loss due to compromised splicing efficiency. These results demonstrate the role of BMPR2 mutation in the pathogenesis of PAH and indicate that variation within the SMAD family represents an infrequent cause of the disease.
|
669 |
Long-term culture-expanded alveolar macrophages restore their full epigenetic identity after transfer in vivoSubramanian, Sethuraman, Busch, Clara Jana-Lui, Molawi, Kaaweh, Geirsdottir, Laufey, Maurizio, Julien, Vargas Aguilar, Stephanie, Belahbib, Hassiba, Gimenez, Gregor, Yuda, Ridzky Anis Advent, Burkon, Michaela, Favret, Jérémy, Najjar, Sara Gholamhosseinian, de Laval, Berengère, Kandalla, Prashanth Kumar, Sarrazin, Sandrine Sarrazin Zentrum für Regenerative, Alexopoulou, Lena, Siewake, Michael H. 26 August 2022 (has links)
Alveolar macrophages (AMs) are lung tissue-resident macrophages that can be expanded in culture, but it is unknown to what extent culture affects their in vivo identity. Here we show that mouse long-term ex vivo expanded AMs (exAMs) maintained a core AM gene expression program, but showed culture adaptations related to adhesion, metabolism and proliferation. Upon transplantation into the lung, exAMs reacquired full transcriptional and epigenetic AM identity, even after several months in culture and could self-maintain long-term in the alveolar niche. Changes in open chromatin regions observed in culture were fully reversible in transplanted exAMs and resulted in a gene expression profile indistinguishable from resident AMs. Our results indicate that long-term proliferation of AMs in culture did not compromise cellular identity in vivo. The robustness of exAM identity provides new opportunities for mechanistic analysis and highlights the therapeutic potential of exAMs.
|
670 |
Identification of transcriptional regulators functions in the human fungal pathogen Candida albicans using functional genomicsKhayat, Aline 01 1900 (has links)
Candida albicans, une levure pathogène de l’humain, cause des infections envahissantes chez les individus immunodéprimés. C. albicans peut changer sa morphologie entre les formes levures et filamenteuses, un déterminant de virulence considérable qui est influencé par plusieurs facteurs environnementaux comme le pH, le sérum, les nutriments, et le farnesol, une molécule de la détection du quorum. Le génome de C. albicans a été séquencé et à date, plusieurs gènes codant des régulateurs de transcription (RT) restent incaracterisés. Basé sur des criblages à grande-échelle, il a été possible d’attribuer des phénotypes à certains des RT incaractérisés, cependant, leurs cibles traduisant ces phénotypes restent inconnues. Le but de cette thèse était d’étudier les fonctions biologiques de RT sélectionnés et d’établir des réseaux transcriptionnels chez C. albicans. J’ai utilisé des approches génétiques et génomiques afin d’identifier et de caractériser le regulon de ces RT, ce qui a permis de déterminer leur fonctions biologiques. Notre groupe avait identifié Fcr1p, un RT dont la délétion augmente la filamentation et la tolérance à plusieurs antifongiques. Cependant, le mécanisme sous-jacent reste inconnu. Dans le Chapitre 2, j’ai identifié le régulon d’Fcr1p et j’ai trouvé qu’il régule ses cibles de façon complexe étant en même temps un activateur et un répresseur d’expression de gènes. J’ai démontré que Fcr1p agit comme répresseur direct des gènes de l’assimilation et du métabolisme de l’azote. L’expression de plusieurs de ces cibles était dépendante d’Fcr1p en conditions d’épuisement d’azote. J’ai montrés que Fcr1p agit aussi comme répresseur indirect de gènes hyphe-spécifiques ainsi qu’un activateur indirect de transport et de métabolisme du carbone et de gènes levure-spécifiques. De plus, la suréxpression d’Fcr1p abolit la filamentation sur le milieu Spider, confirmant que c’est un répresseur de filamentation. Dans le Chapitre 3, j’ai décris un crible génétique basé sur un principe de co-culture pour identifier des mutants de RT défectueux en production de farnesol. Conséquemment, les RT Ada2p, Cas5p, Fgr15p, Cas1p, et Rlm1p, impliqués dans le maintien de la paroi cellulaire, ont été identifiés. La quantification du farnesol intracellulaire de ces mutants a confirmé que le défaut observé peut être attribué à un défaut de la biosynthèse de farnesol plutôt qu’à un défaut de sécrétion de celui-ci. Pour comprendre le mécanisme responsable de ce défaut, nous avons commencé par caractériser le régulon de Cas5p par des analyses de profilages d’expression et de localisation. J’ai montré que Cas5p se lie à des gènes impliqués dans le catabolisme des hydrocarbures et la production d’énergie. Cas5p induit aussi des gènes impliqués dans le catabolisme des hydrocarbures et des lipides et réprime des gènes impliqués dans le métabolisme primaire, montrant que Cas5p régule plusieurs voies métaboliques, notamment celle du carbone. En plus des fonctions d’Ada2p et Rlm1p dans la liaison et/ou la régulation de gènes du catabolisme des hydrocarbures, nos résultats appuient avec la proposition que le farnesol constitue une traduction du métabolisme du carbone cellulaire. Dans l’ensemble, ces résultats ont aidé à élucider le rôle d’Fcr1p ainsi que 5 autres RT dans la régulation de voies métaboliques fondamentales influençant le dimorphisme, un attribut crucial de la virulence chez C. albicans. / Candida albicans, an important human fungal pathogen, causes life-threatening invasive infections in immuno-compromised individuals. It switches between yeast and filamentous forms. This dimorphism is a considerable virulence attribute and one that is influenced by many environmental factors, such as pH, serum, nutrients and farnesol, a quorum sensing molecule. The genome of C. albicans has been sequenced and to date, many of the genes encoding transcriptional regulators (TRs) remain uncharacterized. Based on large-scale screens, it was possible to assign phenotypes to some of the uncharacterized TRs, however the targets of these TRs that mediate these phenotypes remain to be identified. The aim of this thesis work was to understand the normal biological function of selected TRs and construct transcriptional networks in C. albicans. I used genetic and genomic approaches to identify and characterize the regulon of these TRs, which helped to define their biological functions. Our group has previously identified Fcr1p, a zinc cluster TR whose deletion increases cell tolerance to multiple drugs and enhances filamentation. However, the mechanism by which it mediates these phenotypes is still unknown. In Chapter 2, I identified the regulon of Fcr1p and found that it regulates its targets in a complex manner since it can act both as an activator and as a repressor of gene expression. I have shown that Fcr1p acts as a direct negative regulator of genes involved in nitrogen source assimilation and metabolism. The Fcr1p-dependent expression of a number of its targets also occurs under nitrogen starvation conditions. Results also showed that Fcr1p is an indirect negative regulator of hyphal-specific genes, and an indirect positive regulator of carbon source transport and metabolism, as well as yeast-specific genes. Furthermore, Fcr1p overexpression abrogates filamentation on Spider medium confirming that it is a negative regulator of filamentation. In Chapter 3, I describe a genetic screen based on a co-culture assay with A. nidulans to identify TR mutants defective in farnesol production. Our results identified Ada2p, Cas5p, Fgr15p, Cas1p, and Rlm1p, five TRs involved in cell wall integrity. Intracellular farnesol quantification in these mutants confirmed that the observed defect in farnesol production could be attributed to impairment in farnesol biosynthesis rather than export of this molecule. To get an insight into the molecular mechanism responsible for this defect, we started by identifying the regulon of Cas5p using expression and location profiling. Results showed that Cas5p binds genes involved in carbohydrate catabolism and energy production. Cas5p also upregulates genes involved in carbohydrate and lipid catabolism and downregulates genes involved in primary metabolism, indicating that Cas5p is involved in the regulation of many pathways, with a clear involvement in carbon metabolism. Coupled to the known function of Ada2p and Rlm1p in binding and/or regulating genes involved in carbohydrate catabolism, our results support the proposition that farnesol is a metabolic read-out of the cell carbon metabolic activity. Taken together, these results helped elucidate the role of Fcr1p as well as five other TRs in the regulation of central metabolic pathways that influence morphological switching, a crucial attribute of C.albicans virulence.
|
Page generated in 0.0722 seconds