100 research outputs found

    Drosophila TIEG Is a Modulator of Different Signalling Pathways Involved in Wing Patterning and Cell Proliferation

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    Acquisition of a final shape and size during organ development requires a regulated program of growth and patterning controlled by a complex genetic network of signalling molecules that must be coordinated to provide positional information to each cell within the corresponding organ or tissue. The mechanism by which all these signals are coordinated to yield a final response is not well understood. Here, I have characterized the Drosophila ortholog of the human TGF-β Inducible Early Gene 1 (dTIEG). TIEG are zinc-finger proteins that belong to the Krüppel-like factor (KLF) family and were initially identified in human osteoblasts and pancreatic tumor cells for the ability to enhance TGF-β response. Using the developing wing of Drosophila as “in vivo” model, the dTIEG function has been studied in the control of cell proliferation and patterning. These results show that dTIEG can modulate Dpp signalling. Furthermore, dTIEG also regulates the activity of JAK/STAT pathway suggesting a conserved role of TIEG proteins as positive regulators of TGF-β signalling and as mediators of the crosstalk between signalling pathways acting in a same cellular context

    Tumor-specific expression of αvβ3 integrin promotes spontaneous metastasis of breast cancer to bone

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    INTRODUCTION: Studies in xenograft models and experimental models of metastasis have implicated several β3 integrin-expressing cell populations, including endothelium, platelets and osteoclasts, in breast tumor progression. Since orthotopic human xenograft models of breast cancer are poorly metastatic to bone and experimental models bypass the formation of a primary tumor, however, the precise contribution of tumor-specific αvβ3 to the spontaneous metastasis of breast tumors from the mammary gland to bone remains unclear. METHODS: We used a syngeneic orthotopic model of spontaneous breast cancer metastasis to test whether exogenous expression of αvβ3 in a mammary carcinoma line (66cl4) that metastasizes to the lung, but not to bone, was sufficient to promote its spontaneous metastasis to bone from the mammary gland. The tumor burden in the spine and the lung following inoculation of αvβ3-expressing 66cl4 (66cl4beta3) tumor cells or control 66cl4pBabe into the mammary gland was analyzed by real-time quantitative PCR. The ability of these cells to grow and form osteolytic lesions in bone was determined by histology and tartrate-resistant acid phosphatase staining of bone sections following intratibial injection of tumor cells. The adhesive, migratory and invasive properties of 66cl4pBabe and 66cl4beta3 cells were evaluated in standard in vitro assays. RESULTS: The 66cl4beta3 tumors showed a 20-fold increase in metastatic burden in the spine compared with 66cl4pBabe. A similar trend in lung metastasis was observed. αvβ3 did not increase the proliferation of 66cl4 cells in vitro or in the mammary gland in vivo. Similarly, αvβ3 is not required for the proliferation of 66cl4 cells in bone as both 66cl4pBabe and 66cl4beta3 proliferated to the same extent when injected directly into the tibia. 66cl4beta3 tumor growth in the tibia, however, increased osteoclast recruitment and bone resorption compared with 66cl4 tumors. Moreover, αvβ3 increased 66cl4 tumor cell adhesion and αvβ3-dependent haptotactic migration towards bone matrix proteins, as well as their chemotactic response to bone-derived soluble factors in vitro. CONCLUSION: These results demonstrate for the first time that tumor-specific αvβ3 contributes to spontaneous metastasis of breast tumors to bone and suggest a critical role for this receptor in mediating chemotactic and haptotactic migration towards bone factors

    Current challenges facing the assessment of the allergenic capacity of food allergens in animal models

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    Food allergy is a major health problem of increasing concern. The insufficiency of protein sources for human nutrition in a world with a growing population is also a significant problem. The introduction of new protein sources into the diet, such as newly developed innovative foods or foods produced using new technologies and production processes, insects, algae, duckweed, or agricultural products from third countries, creates the opportunity for development of new food allergies, and this in turn has driven the need to develop test methods capable of characterizing the allergenic potential of novel food proteins. There is no doubt that robust and reliable animal models for the identification and characterization of food allergens would be valuable tools for safety assessment. However, although various animal models have been proposed for this purpose, to date, none have been formally validated as predictive and none are currently suitable to test the allergenic potential of new foods. Here, the design of various animal models are reviewed, including among others considerations of species and strain, diet, route of administration, dose and formulation of the test protein, relevant controls and endpoints measured

    Transcriptional Activity and Nuclear Localization of Cabut, the Drosophila Ortholog of Vertebrate TGF-β-Inducible Early-Response Gene (TIEG) Proteins

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    BackgroundCabut (Cbt) is a C2H2-class zinc finger transcription factor involved in embryonic dorsal closure, epithelial regeneration and other developmental processes in Drosophila melanogaster. Cbt orthologs have been identified in other Drosophila species and insects as well as in vertebrates. Indeed, Cbt is the Drosophila ortholog of the group of vertebrate proteins encoded by the TGF-ß-inducible early-response genes (TIEGs), which belong to Sp1-like/Krüppel-like family of transcription factors. Several functional domains involved in transcriptional control and subcellular localization have been identified in the vertebrate TIEGs. However, little is known of whether these domains and functions are also conserved in the Cbt protein.Methodology/Principal FindingsTo determine the transcriptional regulatory activity of the Drosophila Cbt protein, we performed Gal4-based luciferase assays in S2 cells and showed that Cbt is a transcriptional repressor and able to regulate its own expression. Truncated forms of Cbt were then generated to identify its functional domains. This analysis revealed a sequence similar to the mSin3A-interacting repressor domain found in vertebrate TIEGs, although located in a different part of the Cbt protein. Using β-Galactosidase and eGFP fusion proteins, we also showed that Cbt contains the bipartite nuclear localization signal (NLS) previously identified in TIEG proteins, although it is non-functional in insect cells. Instead, a monopartite NLS, located at the amino terminus of the protein and conserved across insects, is functional in Drosophila S2 and Spodoptera exigua Sec301 cells. Last but not least, genetic interaction and immunohistochemical assays suggested that Cbt nuclear import is mediated by Importin-α2.Conclusions/SignificanceOur results constitute the first characterization of the molecular mechanisms of Cbt-mediated transcriptional control as well as of Cbt nuclear import, and demonstrate the existence of similarities and differences in both aspects of Cbt function between the insect and the vertebrate TIEG proteins

    Diversity and distribution of oribatid mites (Acari:Oribatida) in a lowland rain forest in Peru and in several environments of the Brazilians states of Amazonas, Rondônia, Roraima and Pará

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    We are summarizing the current state of knowledge of the diversity and distribution of oribatid mites in 26 environments in northern Brazil and of a rain forest in Peru. The published studies were mostly concentrated in Central Amazon. Only one report is a result from an agricultural polyculture. We are providing the first lists of species for savannas and for the Brazilian states of Roraima and Pará. Up to date, 146 species are definitively identified from a total of 444 taxa with 188 known genera, reinforcing the notion of a rich biodiverse area. The high number of 298 non-described species (morphospecies) clearly shows the inadequacy of the current taxonomic knowledge for the region. Most of the registers are from forest environments. In the soil from primary forests, we registered the highest diversity (54-155 species/morphospecies). Eighty-nine species were unique to primary forests, followed by 34 for savannas, 32 in trees, 10 in "igapó", 4 in caatinga, 3 in secondary forests, two in "varzea" and one in polyculture. Twenty genera were the most speciose. The species with the largest home ranges were Rostrozetes foveolatus, Scheloribates sp. A, and Galumna sp. A. Our numbers reflect the lack of taxonomists and show that the taxonomic knowledge must be improved for the region or we will continue to work with taxonomic resolution of Order or Family and a high percentage of morphospecies, which will probably be appropriate to the question being asked in each study, but not for a comparison among environments

    Consensus Conference on Clinical Management of pediatric Atopic Dermatitis

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    SOL-NUTRI 1.0

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    SOL-NUTRI è un software freeware per sistemi operativi Microsoft Windows per il calcolo delle soluzioni nutritive da utilizzarsi per le coltivazioni fuori suolo ed in vaso

    Geomorphological evidence from the MAPPA-Web-GIS: explanatory notes

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    Detecting landforms in floodplains is perhaps the most challenging activity for a geomorphologist (Castiglioni 2001). In fact the natural evolution of a floodplain tends to cancel landforms soon after they are no longer active. The Pisa Plain, in particular, was formed in sea-level rise conditions, and thus its evolution was accompanied by a constant rise of base-level. Aggradation was then combined with progradation, resulting in a progressive burial of landforms. Nevertheless those landforms that were buried by more recent alluvium, such as stream channels or marshes, leave a fingerprint which may be visible on modern topography in the form of weak undulations in the ground floor. These are normally undetectable in the field and need an extremely detailed micro-relief representation to be highlighted. Such “inherited” landforms, even if recognized, are then difficult to classify and constrain chronologically. Finally their mutual relationships are hard to assess. Long-aged settlement contributes to modify past fluvial landforms in floodplains, creating an artificial drainage network and enhancing natural topographic highs building artificial ground levels. Specific great-scale surveys are necessary to investigate floodplains geomorphological setting, and a cross-disciplinary approach is in most cases indispensable (Piovan et alii 2006). A Digital Terrain Model reproducing the topography of investigated area with a very high spatial resolution becomes fundamental for studying some landscapes of difficult interpretation as the floodplains where the original morphologies can be lost or modified by the natural environmental changes or by the human activity (Ninfo et alii 2011). Mapping landforms is the first step to perform landscape interpretation. The representation code used by Italian scholars (Servizio Geologico Nazionale, 1994) is a powerful tool that provides all the necessary information to genetically constrain landforms and to assess their mutual relationship in time and space. In this work, though, we preferred not to use this type of representation. In fact in the MAPPA Project all data (archaeological, geological and geomorphological) are included in a digital mapping instrument (the MAPPA web-GIS) which provides access to all the project results for a wide community of end-users, such as researchers, professionals, operators of local public institutions, dealing with archaeological heritage protection, environmental management, natural hazard mitigation. This tool must be simple to consult and must enable real-time queries of data. For this reason a specific legend has been worked out for the MAPPA Web GIS geomorphological map. The milestone of geomorphological maps of the Pisa Plain (Mazzanti 1994) was actually based on cross-checking information on surface lithology with evidence from aerial photography and hystoricalarchaeological data. More recent documents (e.g. Provincia di Pisa http://sit.provincia.pisa.it), improved the resolution of the data but with limited accuracy due to the lack of a suitable topographic base. In the framework of the MAPPA Project new geomorphological evidence was collected thanks to the availability of a Lidar survey and new detailed remote sensing analyses (Bini et alii 2012). The Airborne Lidar Scanning (ALS), acquiring spatially dense altimetry data set over short periods of time, allows the production of very detailed Digital Terrain Models (DTM) even in areas strongly urbanized or covered by dense vegetation. Remote sensing enables to map those features that are hardly detectable in the field due to their scarce relief energy. The nature of surface fingerprints of buried landforms could be verified thanks to the project data base. These new data were represented according to a special code worked out in order to incorporate our data in the MAPPA-Web-GIS; this code will be illustrated in the following, together with the criteria used for landforms detection.Published295-3005.10. TTC - Sistema webN/A or not JCRrestricte

    Fluvial origin of the valley system in northern Victoria Land (Antarctica) from quantitative geomorphic analysis.

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    A network of sinuous valleys with typical dendritic pattern characterizes northern Victoria Land (NVL) in Antarctica. Subparallel to parallel and angular to rectangular patterns are also present. Quantitative geomorphic analysis of the valley network has been carried out utilizing GIS spatial analysis. While drainage densities and drainage frequencies show low values, segments of the NVL valley network are substantially well organized, as indicated by bifurcation ratio (Rb) and direct bifurcation ratio (Rbd) parameters. All basins faithfully adhere to Horton's laws of drainage network composition. Quantitative geomorphic analysis suggests that the valley system can be ascribed to fluvial origin and that consequently, a morphoclimatic system completely different from that of present day must have driven its carving. The resulting data provide indications about the origin of the valley network and this invaluable information can be used for the reconstruction of earlier phases of glacial history and climatic and tectonic evolution of this significant Antarctic region. Fluvial erosion enhanced the denudation of the Transantarctic Mountains from at least 55 Ma to at least the Eocene-Oligocene boundary (ca 34 Ma). Fluvial basins adapted to the tectonic structure, following the main regional fault systems. A well-developed alpine topography postdates the fluvial morphology. Temperate glaciers were responsible for denudation until the Late Miocene. Parasitic glaciers presently mantle the previously sculpted topography. Present-day glacial erosion is negligible and denudation has been exceedingly slow since 7.5 Ma
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