THE TECTONO - STRATIGRAPHIC EVOLUTION OF PINDOS FORELAND EAST OF MESOLONGI

Η ιζηματολογική ανάλυση των υποθαλασσίων ριπιδίων, βόρεια και νότια του ποταμού Εύηνου, ανατολικά της πόλης του Μεσολογγίου, έδειξαν διαφορετικές συνθήκες ιζηματογένεσης. Το νότιο τμήμα που εμφανίζεται μεταξύ των βουνών Κλόκοβα και Βαράσοβα, που επηρεάστηκε από τη δράση της επώθησης της Γαβρόβου, χαρακτηρίζεται από αδρομερείς αποθέσεις εσωτερικού ριπιδίου, τα οποία προέρχονται τόσο από την οροσειρά της Πίνδου όσο και από τα αναδυθέντα όρη της Κλόκοβας και Βαράσοβας. Η επώθηση της Γαβρόβου έλαβε χώρα κατά τη διάρκεια τη ιζηματογένεσης παράγοντας ενδολεκανικά υβώματα τα οποία επηρέασαν τη γεωμετρία της λεκάνης. Στο βόρειο τμήμα, οι αποθέσεις εξωτερικού ριπιδίου περνούν προς τα πάνω σε αποθέσεις εσωτερικού ριπιδίου και δεν παρατηρείται η επώθηση της Γαβρόβου να έχει επηρεάσει το τμήμα αυτό παρά μόνο η επώθηση της Εσωτερικής Ιόνιας ζώνης. Μεταξύ των δύο μελετηθέντων περιοχών, υπάρχει μία έντονα παραμορφωμένη περιοχή, πλάτους περίπου 1km, η οποία εκτείνεται παράλληλα στον ποταμό Εύηνο με μια ΑΒΑ διεύθυνση, δείχνοντας ότι πιθανά ο ποταμός Εύηνος κινείται πάνω σε ένα ρήγμα οριζόντιας μετατόπισης.Sedimetological analysis of submarine fan deposits, both north and south of Evinos River, east of Mesolongi town, showed that there are different sedimentological conditions. The southern part outcropped between Klokova and Varasova Mountains, influenced by Gavrovo thrust activity, is characterized by coarse grained inner fan deposits, and sourced both from Pindos chain and the uplifted Klokova and Varasova Mountains. Gavrovo thrust activity, took place during the sedimentation producing intrabasinal highs, changing basin geometry. In the northern part, where outer fan deposits passes upwards to inner fans, there is no obvious influence of Gavrovo thrust but mostly the influence of internal Ionian Thrust. Between the two studied areas there is a high deformed area, about 1km wide, trending parallel to the Evinos River in a ENE direction, showing that probable Evinos River flows on a strike-slip fault

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

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

Heparan sulfate proteoglycans: structure, protein interactions and cell signaling

Heparan sulfate proteoglycans are ubiquitously found at the cell surface and extracellular matrix in all the animal species. This review will focus on the structural characteristics of the heparan sulfate proteoglycans related to protein interactions leading to cell signaling. The heparan sulfate chains due to their vast structural diversity are able to bind and interact with a wide variety of proteins, such as growth factors, chemokines, morphogens, extracellular matrix components, enzymes, among others. There is a specificity directing the interactions of heparan sulfates and target proteins, regarding both the fine structure of the polysaccharide chain as well precise protein motifs. Heparan sulfates play a role in cellular signaling either as receptor or co-receptor for different ligands, and the activation of downstream pathways is related to phosphorylation of different cytosolic proteins either directly or involving cytoskeleton interactions leading to gene regulation. The role of the heparan sulfate proteoglycans in cellular signaling and endocytic uptake pathways is also discussed.Proteoglicanos de heparam sulfato são encontrados tanto superfície celular quanto na matriz extracelular em todas as espécies animais. Esta revisão tem enfoque nas características estruturais dos proteoglicanos de heparam sulfato e nas interações destes proteoglicanos com proteínas que levam à sinalização celular. As cadeias de heparam sulfato, devido a sua variedade estrutural, são capazes de se ligar e interagir com ampla gama de proteínas, como fatores de crescimento, quimiocinas, morfógenos, componentes da matriz extracelular, enzimas, entreoutros. Existe uma especificidade estrutural que direciona as interações dos heparam sulfatos e proteínas alvo. Esta especificidade está relacionada com a estrutura da cadeia do polissacarídeo e os motivos conservados da cadeia polipeptídica das proteínas envolvidas nesta interação. Os heparam sulfatos possuem papel na sinalização celular como receptores ou coreceptores para diferentes ligantes. Esta ligação dispara vias de sinalização celular levam à fosforilação de diversas proteínas citosólicas ou com ou sem interações diretas com o citoesqueleto, culminando na regulação gênica. O papel dos proteoglicanos de heparam sulfato na sinalização celular e vias de captação endocítica também são discutidas nesta revisão.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Universidade Federal de São Paulo (UNIFESP) Departamento de BioquímicaUniversidade Federal de São Paulo (UNIFESP) Departamento de OftalmologiaUNIFESP, Depto. de BioquímicaUNIFESP, Depto. de OftalmologiaSciEL

Spatial distribution of CD3- and CD8-positive lymphocytes as pretest for POLE wild-type in molecular subgroups of endometrial carcinoma.

INTRODUCTION Over the years, the molecular classification of endometrial carcinoma has evolved significantly. Both POLEmut and MMRdef cases share tumor biological similarities like high tumor mutational burden and induce strong lymphatic reactions. While therefore use case scenarios for pretesting with tumor-infiltrating lymphocytes to replace molecular analysis did not show promising results, such testing may be warranted in cases where an inverse prediction, such as that of POLEwt, is being considered. For that reason we used a spatial digital pathology method to quantitatively examine CD3+ and CD8+ immune infiltrates in comparison to conventional histopathological parameters, prognostics and as potential pretest before molecular analysis. METHODS We applied a four-color multiplex immunofluorescence assay for pan-cytokeratin, CD3, CD8, and DAPI on 252 endometrial carcinomas as testing and compared it to further 213 cases as validation cohort from a similar multiplexing assay. We quantitatively assessed immune infiltrates in microscopic distances within the carcinoma, in a close distance of 50 microns, and in more distant areas. RESULTS Regarding prognostics, high CD3+ and CD8+ densities in intra-tumoral and close subregions pointed toward a favorable outcome. However, TCGA subtyping outperforms prognostication of CD3 and CD8 based parameters. Different CD3+ and CD8+ densities were significantly associated with the TCGA subgroups, but not consistently for histopathological parameter. In the testing cohort, intra-tumoral densities of less than 50 intra-tumoral CD8+ cells/mm2 were the most suitable parameter to assume a POLEwt, irrespective of an MMRdef, NSMP or p53abn background. An application to the validation cohort corroborates these findings with an overall sensitivity of 95.5%. DISCUSSION Molecular confirmation of POLEmut cases remains the gold standard. Even if CD3+ and CD8+ cell densities appeared less prognostic than TCGA, low intra-tumoral CD8+ values predict a POLE wild-type at substantial percentage rates, but not vice versa. This inverse correlation might be useful to increase pretest probabilities in consecutive POLE testing. Molecular subtyping is currently not conducted in one-third of cases deemed low-risk based on conventional clinical and histopathological parameters. However, this percentage could potentially be increased to two-thirds by excluding sequencing of predicted POLE wild-type cases, which could be determined through precise quantification of intra-tumoral CD8+ cells

Designing Building Skins with Biomaterials

This chapter presents several successful examples of biomaterial facade design. It discusses facade function from aesthetical, functional, and safety perspectives. Special focus is directed on novel concepts for adaptation and special functionalities of facades. Analysis of the structure morphologies and aesthetic impressions related to the bio-based building facades is supported with photographs collected by authors in various locations. Finally, particular adaptations and special functionalities of bio-based facades going beyond traditional building envelope concept are supported by selected case studies

CAMEMBERT: A Mini-Neptunes GCM Intercomparison, Protocol Version 1.0. A CUISINES Model Intercomparison Project

With an increased focus on the observing and modelling of mini-Neptunes, there comes a need to better understand the tools we use to model their atmospheres. In this paper, we present the protocol for the CAMEMBERT (Comparing Atmospheric Models of Extrasolar Mini-neptunes Building and Envisioning Retrievals and Transits) project, an intercomparison of general circulation models (GCMs) used by the exoplanetary science community to simulate the atmospheres of mini-Neptunes. We focus on two targets well studied both observationally and theoretically with planned JWST Cycle 1 observations: the warm GJ~1214b and the cooler K2-18b. For each target, we consider a temperature-forced case, a clear sky dual-grey radiative transfer case, and a clear sky multi band radiative transfer case, covering a range of complexities and configurations where we know differences exist between GCMs in the literature. This paper presents all the details necessary to participate in the intercomparison, with the intention of presenting the results in future papers. Currently, there are eight GCMs participating (ExoCAM, Exo-FMS, FMS PCM, Generic PCM, MITgcm, RM-GCM, THOR, and the UM), and membership in the project remains open. Those interested in participating are invited to contact the authors.Comment: Accepted to PS

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

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

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