130,576 research outputs found
The vacuolar ATPase is required for physiological as well as pathological activation of the Notch receptor
No full textEvidence indicates that endosomal entry promotes signaling by the Notch receptor, but the mechanisms involved are not clear. In a search for factors that regulate Notch activation in endosomes, we isolated mutants in Drosophila genes that encode subunits of the vacuolar ATPase (V-ATPase) proton pump. Cells lacking V-ATPase function display impaired acidification of the endosomal compartment and a correlated failure to degrade endocytic cargoes. V-ATPase mutant cells internalize Notch and accumulate it in the lysosome, but surprisingly also show a substantial loss of both physiological and ectopic Notch activation in endosomes. V-ATPase activity is required in signal-receiving cells for Notch signaling downstream of ligand activation but upstream of γ-secretase-dependent S3 cleavage. These data indicate that V-ATPase, probably via acidification of early endosomes, promotes not only the degradation of Notch in the lysosome but also the activation of Notch signaling in endosomes. The results also suggest that the ionic properties of the endosomal lumen might regulate Notch cleavage, providing a rationale for physiological as well as pathological endocytic control of Notch activity
3-dimensional polygons determined by permutations
No full textIn this paper we introduce the notion of d-dimensional permupolygons on Z(d), with d >= 2. 2-dimensional permupolygons, also called permutominides, where introduced by Incitti et al. [12]. By using an encoding of permupolygons inspired by the encoding given for convex polyominoes by Bousquet-Melou and Guttmann [6], we easily recover enumerative results about 2-dimensional parallelogram, unimodal, column convex and convex permupolygons. Moreover, we extend these results for dimension d = 3. Finally, we study combinatorial characterizations of permutations defining 3-dimensional permupolygons. We show some necessary and sufficient conditions for a triple of 2-dimensional permutations (pi(1), pi(2), pi(3)) to define a 3-dimensional permupolygon
The vacuolar ATPase is required for physiological as well as pathological activation of the Notch receptor
No full textEvidence indicates that endosomal entry promotes signaling by the Notch receptor, but the mechanisms involved are not clear. Ina search for factors that regulate Notch activation in endosomes, we isolated mutants in Drosophila genes that encode subunitsof the vacuolar ATPase (V-ATPase) proton pump. Cells lacking V-ATPase function display impaired acidification of the endosomalcompartment and a correlated failure to degrade endocytic cargoes. V-ATPase mutant cells internalize Notch and accumulate it inthe lysosome, but surprisingly also show a substantial loss of both physiological and ectopic Notch activation in endosomes. VATPase activity is required in signal-receiving cells for Notch signaling downstream of ligand activation but upstream of -secretase-dependent S3 cleavage. These data indicate that V-ATPase, probably via acidification of early endosomes, promotes notonly the degradation of Notch in the lysosome but also the activation of Notch signaling in endosomes. The results also suggestthat the ionic properties of the endosomal lumen might regulate Notch cleavage, providing a rationale for physiological as wellas pathological endocytic control of Notch activity
THE DROSOPHILA HOMOLOGUE OF THE HUMAN VON HIPPEL-LINDAU TUMOR SUPPRESSOR GENE IS REQUIRED FOR EPITHELIAL INTEGRITY OF FOLLICLE CELLS
No full textThe tumour suppressor gene product pVHL (Von-Hippel Lindau protein) is implicated in a variety of processes including ubiquitination of the alpha subunit of HIF (hypoxia-inducible factor), cell-cycle control, differentiation, extracellular matrix formation and turnover, and angiogenesis. However, the developmental function of VHL gene has not been fully understood. It was shown previously that Drosophila VHL (d-VHL) down-regulates the motility of tubular epithelial cells (tracheal cells). To examine whether d-VHL has a more general role in epithelial morphogenesis, we analyzed the follicle cell phenotype produced by loss-of-function d-VHL mutation. Homozygous d-VHL clones, genetically marked by the absence of GFP, were obtained through somatic recombination using the FLP/FRT system.
Loss of d-VHL function causes a cell autonomous effect on epithelial integrity of the follicle cells, including multilayering and altered cell shape. Strong propidium iodide (nuclear) staining was also observed, indicating possible dysregulation of endocycles. The analysis of epithelial junction protein patterns such as Discs-large, atypical-Protein Kinase C and Crumbs showed that loss of d-VHL function causes altered distribution or absence of these proteins in follicular epithelium. These abnormal epithelial characteristics are associated with detachment from the basement membrane. This is interesting since integrin-mediated basal attachment is presumably the initial step in epithelial morphogenesis. Besides integrin, we have shown that abnormal wing discs (awd) gene, the Drosophila homolog of human nucleotide diphosphate kinase nm23H1, is localized to the basal domain. Interestingly, d-VHL loss of function clones showed strong reduction of awd gene expression. We propose that d-VHL may be a novel epithelial morphogenic factor that promotes the stability of the basal attachment complex
MeSH term explosion and author rank improve expert recommendations
No full textInformation overload is an often-cited phenomenon that reduces the productivity, efficiency and efficacy of scientists. One challenge for scientists is to find appropriate collaborators in their research. The literature describes various solutions to the problem of expertise location, but most current approaches do not appear to be very suitable for expert recommendations in biomedical research. In this study, we present the development and initial evaluation of a vector space model-based algorithm to calculate researcher similarity using four inputs: 1) MeSH terms of publications; 2) MeSH terms and author rank; 3) exploded MeSH terms; and 4) exploded MeSH terms and author rank. We developed and evaluated the algorithm using a data set of 17,525 authors and their 22,542 papers. On average, our algorithms correctly predicted 2.5 of the top 5/10 coauthors of individual scientists. Exploded MeSH and author rank outperformed all other algorithms in accuracy, followed closely by MeSH and author rank. Our results show that the accuracy of MeSH term-based matching can be enhanced with other metadata such as author rank
Going Beyond Counting First Authors in Author Co-citation Analysis
No full textThe 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
Nelle felicissime nozze de serenissimi principi Francesco da Este e d. Lucrezia Barberini, duchi di Modana, &c. : oda /
No full textWoodcut coat of arms on t.p. (d'Este impaling Barberini). Tail-piece, initial.Mode of access: Internet.Binding: modern decorated paper
"Closing the R&D Gap, Evaluating the Sources of R&D Spending"
No full textBoth spending and tax policies have been implemented in the United States with the goal of stimulating private sector research and development (R&D). Karier questions whether current R&D policy, especially the research and experimentation tax credit, can contribute to closing the gap between nondefense expenditures on R&D in the United States and such expenditures in other countries, such as Japan and Germany. He also explores possible changes to our current R&D policy to make it more effective.
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