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Molecular Mechanisms of Cilia Related Diseases
Eukaryotic cilia are evolutionarily conserved microtubule-based structures that protrude from the cell surface. In vertebrates, multiple motile and primary (immotile) cilia fulfill sensory and motility functions that are critical for embryonic development and the homeostasis of adult tissues. Cilia malfunction has been shown to cause a growing number of diseases presenting phenotypes such as brain and skeletal developmental problems, intellectual disability, blindness, infertility, obesity, and kidney cysts. Despite their clinical relevance, we are still far from fully understanding the basic biology of these multiple cilia types. For example, we do not know the molecular compositions of all...
Tuning the 3D Microenvironment of Reprogrammed Tubule Cells Enhances Biomimetic Modeling of Polycystic Kidney Disease
Abstract: Renal tubular cells frequently lose differentiation markers and physiological properties when propagated in conventional cell culture conditions. Embedding cells in 3D microenvironments or controlling their 3D assembly by bioprinting can enhance their physiological properties, which is beneficial for modeling diseases in vitro. A potential cellular source for modeling renal tubular physiology and kidney diseases in vitro are directly reprogrammed induced renal tubular epithelial cells (iRECs). iRECs were cultured in various biomaterials and as bioprinted tubular structures. They showed high compatibility with the embedding substrates and dispensing methods. The morphology of multic...
Cilia-localized LKB1 Regulates Chemokine Signaling, Macrophage Recruitment, and Tissue Homeostasis in the Kidney
Abstract: Polycystic kidney disease (PKD) and other renal ciliopathies are characterized by cysts, inflammation, and fibrosis. Cilia function as signaling centers, but a molecular link to inflammation in the kidney has not been established. Here, we show that cilia in renal epithelia activate chemokine signaling to recruit inflammatory cells. We identify a complex of the ciliary kinase LKB1 and several ciliopathy-related proteins including NPHP1 and PKD1. At homeostasis, this ciliary module suppresses expression of the chemokine CCL2 in tubular epithelial cells. Deletion of LKB1 or PKD1 in mouse renal tubules elevates CCL2 expression in a cell-autonomous manner and results in peritubular accumulation of CCR2+ mononuclear phagocytes, promoting a ciliopathy phenotype. Our findings establish an epithelial organelle, the cilium, as a gatekeeper of tissue immune cell numbers. This represents an unexpected disease mechanism for renal ciliopathies and establishes a new model for how epithelial cells regulate immune cells to affect tissue homeostasis
Efficient Genome Editing of Differentiated Renal Epithelial Cells
Abstract: Recent advances in genome editing technologies have enabled the rapid and precise manipulation of genomes, including the targeted introduction, alteration, and removal of genomic sequences. However, respective methods have been described mainly in non-differentiated or haploid cell types. Genome editing of well-differentiated renal epithelial cells has been hampered by a range of technological issues, including optimal design, efficient expression of multiple genome editing constructs, attainable mutation rates, and best screening strategies. Here, we present an easily implementable workflow for the rapid generation of targeted heterozygous and homozygous genomic sequence alteratio...
Lipocaline 2 Et Néphropathies Chroniques
viter ou retarder la survenue de l'insuffisance r nale chronique est en enjeu majeur en n phrologie. En effet, les seuls traitements disponibles ce jour (dialyse et/ou transplantation r nale) restent lourds de risques et de complications pour les patients et constituent un r el probl me de sant publique. Pour proposer des traitements th rapeutiques capables de freiner la progression de l'insuffisance r nale chronique, il est imp ratif de comprendre les m canismes mol culaires mis en jeu lors de ce processus. En combinant des mod les exp rimentaux des souris g n tiquement modifi es, nous avons d couvert une nouvelle fonction de la lipocaline 2 et d montr son r le crucial dans la pathog n se de la progression des l sions r nales. Ces travaux sont la premi re d monstration in vivo que la lipocaline 2 agit comme facteur de croissance en m diant l'effet mitog ne de l'EGFR (Epidermal Growth Factor Receptor). De plus, nous avons montr que la lipocaline 2 semble pr dire l' volution des n phropathies chroniques et pourrait donc tre la fois un biomarqueur et une nouvelle cible th rapeutique sur laquelle agir pour freiner la progression des maladies r nales chroniques chez l'homme.
L'Emoi de l'histoire
None
2012
Particularly in the humanities and social sciences, festschrifts are a popular forum for discussion. The IJBF provides quick and easy general access to these important resources for scholars and students. The festschrifts are located in state and regional libraries and their bibliographic details are recorded. Since 1983, more than 659,000 articles from more than 30,500 festschrifts, published between 1977 and 2011, have been catalogued.
L'épicerie Sansoucy 03 : La maison des soupirs
Les ambitieux projets que l'entêté épicier Théodore Sansoucy caressait ne se sont pas concrétisés comme il l'entendait. Pour l'instant, dans le petit logement à l'étage supérieur de son magasin, les choses se compliquent. Placide habite la résidence familiale malgré les réticences de son père. Irène, sans emploi, devient postulante chez les soeurs de La Providence. Héloïse étouffe dans la maisonnée et Colombine est enceinte malgré sa volonté de ne pas devenir mère. Léandre trempe dans les loteries illégales pour se faire de l'argent rapidement, au grand regret de Paulette, la migraineuse en voie d'adopter un enfant. Simone, pour sa part, désespère de rester encabané...
