THE DUAL ROLE OF YAP IN DRIVING TGFß-MEDIATED ENDMT

Endothelial-to-mesenchymal transition (EndMT) is a biological process that allows the transdifferentiation of endothelial cells into mesenchymal cells, thus originating cells capable of novel functions necessary for the surrounding environment. EndMT regulates endocardial cushion formation during embryo development, and it is stimulated by the TGF\u3b2/BMP family of ligands. In adults, EndMT is activated upon an injury event or during pathological conditions like organ fibrosis, cerebral cavernous malformation, cancer-associated fibroblast generation, and others. Hence, it is necessary to better characterize the molecular regulators cooperating with TGF\u3b2 signaling in driving EndMT, to possibly provide novel therapeutic targets to treat these pathological conditions. Here we studied YAP, a co-transcriptional regulator involved in several cell biology processes, among which epithelial-to-mesenchymal transition (EMT). Since EndMT is considered a \u201cspecialized\u201d form of EMT, and since YAP and TGF\u3b2 signaling were shown to cross-talk in other contexts, we hypothesized that YAP contributes to EndMT by modulating TGF\u3b2 signaling, and characterized the underlying molecular mechanism. Results here presented demonstrate that YAP is required for a complete TGF\u3b2-mediated EndMT response in vitro, and that YAP contributes specifically to SMAD3-, but not SMAD1-, driven EndMT gene transcription. We provide novel evidence that YAP positively regulates EndMT playing the twofold role of acting as SMAD3 co-transcriptional factor on the promoter of EndMT target genes and, in parallel, preventing SMAD3 from degradation. YAP is therefore emerging as a possible candidate target to inhibit pathological TGF\u3b2-driven EndMT

Fused Adjacency Matrices to enhance information extraction: the beer benchmark

Multivariate exploratory data analysis allows revealing patterns and extracting information from complex multivariate data sets. However, highly complex data may not show evident groupings or trends in the principal component space, e.g. because the variation of the variables are not grouped but rather continuous. In these cases, classical exploratory methods may not provide satisfactory results when the aim is to find distinct groupings in the data. To enhance information extraction in such situations, we propose a novel approach inspired by the concept of combining weak classifiers, but in the unsupervised context. The approach is based on the fusion of several adjacency matrices obtained by different distance measures on data from different analytical platforms. This paper is intended to present and discuss the potential of the approach through a benchmark data set of beer samples. The beer data were acquired using three spectroscopic techniques: Visible, near-Infrared and Nuclear Magnetic Resonance. The results of fusing the three data sets via the proposed approach are compared with those from the single data blocks (Visible, NIR and NMR) and from a standard mid-level data fusion methodology. It is shown that, with the suggested approach, groupings related to beer style and other features are efficiently recovered, and generally more evident

Il Valore dell'esperienza nei progetti di Alternanza Scuola Lavoro. Le testimonianze di giovani studentesse e studenti delle Scuole Secondarie di Secondo Grado del territorio di Cesena e Forlì

La tematica dell’avvicendamento dei giovani verso il mondo del lavoro in Italia è, da molto decenni, una tra le maggiori problematiche che definisce il grave tasso di disoccupazione dei i giovani adulti e che persuade le Istituzioni ad attivarsi in numerosi tentativi che mirano alla sua risoluzione. La Scuola e il mondo del lavoro hanno tentato e, tutt’ora, stanno tendando, di ridurre questo divario attraverso la realizzazione di progetti che possano, da un lato aiutare la Scuola a tramutare i saperi in competenze e, dall’altro, di avvicinare sempre più il mondo del lavoro ai nuovi giovani e alle loro realtà. L’alternanza scuola-lavoro e, i più attuali progetti per le competenze trasversali e l’orientamento PCTO, vogliono essere il mezzo attraverso il quale correggere questa distanza e collegare queste due realtà. Si avvia così un dialogo tra scuola e mondo del lavoro definito da una proposta educativo-didattica che si allarga al mondo delle imprese, delle aziende, degli enti e delle istituzioni con l’obiettivo di offrire agli studenti la possibilità di interfacciarsi a nuove realtà. L’elaborato prende in considerazione la tematica dal punto di vista esperienziale di giovani studentesse e giovani studenti delle Scuole Secondarie Superiori del territorio di Cesena e Forlì che, attraverso le loro dirette testimonianze raccontano l’esperienza vissuta. Le testimonianze, rilevate attraverso un’intervista qualitativa, hanno come obiettivo quello di cogliere le percezioni degli intervistati in relazione ai significati attribuiti all’esperienza vissuta. In particolare l’intervista mira ad indagare le dimensioni psicologiche e più nello specifico, quelle emotive, relative alla soddisfazione della esperienza, alla valutazione di coerenza tra le aspettative e la realtà incontrata, alla valutazione dell’impatto sul percorso scolastico e sulle scelte future – di formazione e/o professionali - e di come l’esperienza abbia o meno contribuito a mondificare e migliorare queste dimensioni

A Metabolomic Approach to Beer Characterization

The consumers’ interest towards beer consumption has been on the rise during the past decade: new approaches and ingredients get tested, expanding the traditional recipe for brewing beer. As a consequence, the field of “beeromics” has also been constantly growing, as well as the demand for quick and exhaustive analytical methods. In this study, we propose a combination of nuclear magnetic resonance (NMR) spectroscopy and chemometrics to characterize beer. 1H-NMR spectra were collected and then analyzed using chemometric tools. An interval-based approach was applied to extract chemical features from the spectra to build a dataset of resolved relative concentrations. One aim of this work was to compare the results obtained using the full spectrum and the resolved approach: with a reasonable amount of time needed to obtain the resolved dataset, we show that the resolved information is comparable with the full spectrum information, but interpretability is greatly improved

Determination of the geographical origin of green coffee beans using NIR spectroscopy and multivariate data analysis

In this work, near infrared (NIR) spectroscopy and multivariate data analysis were investigated as a fast and non disruptive method to classify green coffee beans on continents and countries bases. FT-NIR spectra of 191 coffee samples, origin from 2 continents and 9 countries, were acquired by two different laboratories. Laboratory-independent Partial Least Square-Discriminant Analysis and interval PIS-DA models were developed by following a hierarchical approach, i.e. considering at first the continent and then the country of origin as discrimination rule. The best continent-based classification model was able to identify correctly more than 98% in prediction, whereas 100% of them were correctly predicted by the best country-based classification model. The inter-laboratory reliability of the proposed method was confirmed by McNemar test, since no significant differences (P > 0.05) were found. Furthermore, a validation was performed predicting the spectral test set of a laboratory using the model developed by the other one

High throughput prediction of chylomicron triglycerides in human plasma by nuclear magnetic resonance and chemometrics

<p>Abstract</p> <p>Background</p> <p>The lipid content of the chylomicrons is a key biomarker and risk factor of cardiovascular diseases and for the understanding of obesity. A high throughput determination of chylomicrons in human blood plasma is outlined.</p> <p>Methods</p> <p>The new method, which uses a combination of Nuclear Magnetic Resonance (NMR) analysis and multivariate calibration analysis (chemometrics), is based on a correlation analysis towards the established standard method (ultracentrifugation and colorimetric test kit) and enables extraordinarily fast, inexpensive, and robust prediction of triglyceride (TG) content in chylomicrons. It is the position and shape of the complex lipid methylene resonance band that determines the chylomicron TG status and this information is extracted by the multivariate regression method.</p> <p>Results</p> <p>The resulting method is a relatively simple multivariate model that facilitates parsimonious and accurate prediction of chylomicron lipids from NMR spectra of blood. The chemometric model predicts the chylomicron TG content with a correlation coefficient (R) of 0.96 when plotted against density gradient ultracentrifugation data.</p> <p>Conclusions</p> <p>The new rapid method facilitates large scale clinical and nutritional trials with inclusion of diagnostics of chylomicron status and thus creates new opportunities for research in lifestyle diseases and obesity.</p

Metabolomics as a Powerful Tool for Molecular Quality Assessment of the Fish Sparus aurata

The molecular profiles of perchloric acid solutions extracted from the flesh of Sparus aurata fish specimens, produced according to different aquaculture systems, have been investigated. The 1H-NMR spectra of aqueous extracts are indicative of differences in the metabolite content of fish reared under different conditions that are already distinguishable at their capture, and substantially maintain the same differences in their molecular profiles after sixteen days of storage under ice. The fish metabolic profiles are studied by top-down chemometric analysis. The results of this exploratory investigation show that the fish metabolome accurately reflects the rearing conditions. The level of many metabolites co-vary with the rearing conditions and a few metabolites are quantified including glycogen (stress indicator), histidine, alanine and glycine which all display significant changes dependent on the aquaculture system and on the storage times