1,721,025 research outputs found
At the crossroads of polarity, proliferation and apoptosis : The use of Drosophila to unravel the multifaceted role of endocytosis in tumor suppression
Full text linkEndocytosis is an important regulator of cell-cell signaling and endocytic trafficking has been increasingly implicated in control of tumor suppression. Recent insights from Drosophila indicate that impairment of multiple trafficking steps which lead to receptor degradation can cause tumor formation in epithelial organs. These tumors are characterized by sustained activation of a number of mitogenic signaling pathways, and by subversion of epithelial polarity and the apoptotic response. Cooperation between such alterations, as well as tumor-host interactions, is also observed. The recapitulation of several hallmarks of human cancers in fly tumors provides a framework to understand the role of defective endocytosis in cancer. © 2009 Federation of European Biochemical Societies
Alarming shift away from sharing results
No full textWe discuss the issue of the scientific method starting from what is happening in the scientific communit
Modulating the WNT pathway in Drosophila models of Cornelia de Lange Syndrome
Full text linkCornelia de Lange syndrome (CdLS) is a rare genetic disorder affecting neurodevelopment and the gastrointestinal and musculoskeletal systems. CdLS is caused by mutations within NIPBL, SMC1A, SMC3, RAD21, HDAC8 and BRD4 genes. These genes codify for the cohesin complex (or associated proteins), a multiprotein structure playing a role in chromatid adhesion, DNA repair and gene expression regulation. Our laboratory has shown that a strong correlation exists between cohesin complex function and WNT signalling, an intracellular pathway involved in regulation of expression of several genes controlling cell division and embryonic development. Recently, it has been observed that in nipblb- and smc1a-loss-of-function zebrafish embryos, in NIPBL- and SMC1A- mutated patient fibroblasts and in CdLS murine neural stem cells (NSCs) similar patterns of canonical WNT pathway alterations and cyclinD1 downregulation are present. Indeed, zebrafish embryos adverse phenotype was rescued by chemical activation of the WNT pathway. Drosophila melanogaster is an inexpensive model to study CdLS and to screen in vivo for therapeutic compounds. Therefore, we have used flies’ strains mutated in nipped-B and hdac3 genes (respectively NIPBL and HDAC8 in humans) for assessing the existing correlation between cohesin complex and WNT pathway. Moreover, we have selected D. melanogaster mutants to screen for chemicals that revert the CdLS associated-phenotypes efficiently. In particular, we have tested WNT activators in order to investigate which effects they have on the mutated flies, assessing body weight and changes in brain structures (i.e. mushroom bodies) and possibly select compounds to test on vertebrate models. Funding: This work has been supported by Fondazione Cariplo, grant 2015-0783 to Valentina Massa
Shaping development with ESCRTs
No full textOriginally identified for their involvement in endosomal sorting and multivesicular endosome (MVE) biogenesis, components of the endosomal sorting complex required for transport (ESCRT) are now known to control additional cellular functions such as receptor signalling, cytokinesis, autophagy, polarity, migration, miRNA activity and mRNA transport. The diverse cell biological functions of ESCRT proteins are translated into a pleiotropic set of developmental trajectories that reflect the wide repertoire of these evolutionarily conserved proteins
The Drosophila Tumor Suppressor vps25 Prevents Nonautonomous Overproliferation by Regulating Notch Trafficking
No full textSummaryCell-cell signaling coordinates proliferation of metazoan tissues during development, and its alteration can induce malignant transformation. Endocytosis regulates signaling by controlling the levels and activity of transmembrane receptors, both prior to and following ligand engagement. Here, we identify Vps25, a component of the ESCRT machinery that regulates endocytic sorting of signaling receptors, as an unconventional type of Drosophila tumor suppressor. vps25 mutant cells undergo autonomous neoplastic-like transformation, but they also stimulate nonautonomous cell proliferation. Endocytic trafficking defects in vps25 cells cause endosomal accumulation of the signaling receptor Notch and enhanced Notch signaling. Increased Notch activity leads to ectopic production of the mitogenic JAK-STAT pathway ligand Unpaired, which is secreted from mutant cells to induce overproliferation of the surrounding epithelium. Our data show that defects in endocytic sorting can both transform cells and, through heterotypic signaling, alter the behavior of neighboring wild-type tissue
When membranes need an ESCRT : endosomal sorting and membrane remodelling in health and disease
Full text linkOriginally discovered as regulators of cargo sorting during endosomal trafficking, ESCRT (endosomal sorting complexes required for transport) proteins are emerging as flexible machines that shape the behaviour of membranes throughout the cell. Deregulation of ESCRT activity is observed in neuro-degenerative diseases, virus infection and cancer. However, the mechanisms of pathogenesis involving ESCRTs have not yet fully come into focus. Here, we review the current knowledge of ESCRT function in health and disease and provide educated guesses for future research and focused therapeutic intervention
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
The Fusome and Microtubules Enrich Par-1 in the Oocyte, Where It Effects Polarization in Conjunction with Par-3, BicD, Egl, and Dynein
No full textAbstractAfter its specification, the Drosophila oocyte undergoes a critical polarization event that involves a reorganization of the microtubules (MT) and relocalization of the determinant Orb within the oocyte. This polarization requires Par-1 kinase and the PDZ-containing Par-3 homolog, Bazooka (Baz). Par-1 has been observed on the fusome, which degenerates before the onset of oocyte polarization. How Par-1 acts to polarize the oocyte has been unclear. Here we show that Par-1 becomes restricted to the oocyte in a MT-dependent fashion after disappearance of the fusome. At the time of polarization, the kinase itself and the determinant BicaudalD (BicD) are relocalized from the anterior to the posterior of the oocyte. Par-1 and BicD are interdependent and require MT and the minus end-directed motor Dynein for their relocalization. We show that baz is required for Par-1 relocalization within the oocyte and that the distributions of Baz and Par-1 in the Drosophila oocyte are complementary and strikingly reminiscent of the two PAR proteins in the C. elegans embryo. We propose that, through the combined actions of the fusome, MT, and Baz, Par-1 is selectively enriched and localized within the oocyte, where, in conjunction with BicD, Egalitarian (Egl), and Dynein, it acts on the MT cytoskeleton to effect polarization
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
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