Cellular Prion Protein and Caveolin-1 Interaction in a Neuronal Cell Line Precedes Fyn/Erk 1/2 Signal Transduction

It has been reported that cellular prion protein (PrPc) is enriched in caveolae or caveolae-like domains with caveolin-1 (Cav-1) participating to signal transduction events by Fyn kinase recruitment. By using the Glutathione-S-transferase (GST)-fusion proteins assay, we observed that PrPc strongly interacts in vitro with Cav-1. Thus, we ascertained the PrPc caveolar localization in a hypothalamic neuronal cell line (GN11), by confocal microscopy analysis, flotation on density gradient, and coimmunoprecipitation experiments. Following the anti-PrPc antibody-mediated stimulation of live GN11 cells, we observed that PrPc clustered on plasma membrane domains rich in Cav-1 in which Fyn kinase converged to be activated. After these events, a signaling cascade through p42/44 MAP kinase (Erk 1/2) was triggered, suggesting that following translocations from rafts to caveolae or caveolaelike domains PrPc could interact with Cav-1 and induce signal transduction events

Multi-aircraft environmentally-scored weather-resilient optimised 4D-trajectories

Weather phenomena are one of the biggest causes for significant delays and unpredictable disruptions within air traffic management (ATM) network operations. The changing global climate increases the future severity and frequency of these air traffic disturbing weather phenomena. This deteriorates the predictability of 4D trajectory ATM network planning and potentially increases the delays within air traffic operations. Furthermore, aviation itself has a responsibility to mitigate its climate impact to improve the long-term sustainability of the ATM operations and to contribute to the global effort towards the reduction of anthropogenic climate change. The SESAR2020 exploratory research project CREATE (Grant 890898) aims to find answers on how to improve the weather-resilience of ATM-operations and to reduce its climate impact. A concept of operations (ConOps) has been developed which describes an integrated trajectory optimisation framework to tactically define environmentally-scored optimised 4D trajectories, for a multi-aircraft airspace configuration, using advanced numerical weather prediction models, combined with air traffic control (ATC) driven demand-capacity balancing methods. The framework will be applied to an en-route use-case focusing on the unorganised traffic over the North Atlantic, and a Terminal Manoevring Area (TMA) use-case focusing on the Naples Capodichino airspace. The optimised trajectories aim to evade thunderstorms and contrail formation regions, whilst minimising CO2, non-CO2 and local air quality (LAQ) impacts.This project has received funding within the framework of the SESAR Joint Undertaking project “Innovative Operations and Climate and Weather Models to Improve ATM Resilience and Reduce Impacts” (SESARH2020-ER4 CREATE) within the European Union's Horizon 2020 research and innovation programme under grant agreement No 890898. The CREATE consortium is formed by ATM/Meteo/Environmental specialists from the Royal Netherlands Aerospace Centre (NLR), Universitat Politècnica de Catalunya (UPC), Centro Italiano Ricerche Aerospaziali (CIRA), Università degli Studi di Napoli Parthenope (UNIPARTH, project coordinator), ARIANET, Ilmatieteen Laitos (Finnish Meteorological Institute, FMI), and Institute for Sustainable Society and Innovation (ISSNOVA).Peer ReviewedPostprint (published version

Tracing and tracking epiallele families in complex DNA populations

DNA methylation is a stable epigenetic modification, extremely polymorphic and driven by stochastic and deterministic events. Most of the current techniques used to analyse methylated sequences identify methylated cytosines (mCpGs) at a single-nucleotide level and compute the average methylation of CpGs in the population of molecules. Stable epialleles, i.e. CpG strings with the same DNA sequence containing a discrete linear succession of phased methylated/non-methylated CpGs in the same DNA molecule, cannot be identified due to the heterogeneity of the 5′–3′ ends of the molecules. Moreover, these are diluted by random unstable methylated CpGs and escape detection. We present here MethCoresProfiler, an R-based tool that provides a simple method to extract and identify combinations of methylated phased CpGs shared by all components of epiallele families in complex DNA populations. The methylated cores are stable over time, evolve by acquiring or losing new methyl sites and, ultimately, display high information content and low stochasticity. We have validated this method by identifying and tracing rare epialleles and their families in synthetic or in vivo complex cell populations derived from mouse brain areas and cells during postnatal differentiation

What are the implications of the spontaneous spleno-renal shunts in liver cirrhosis?

<p>Abstract</p> <p>Background</p> <p>Although significant advances are expected to be made in the assessment of the portal hypertension-related complications, the prognostic role of spleno-renal shunts has not been fully explored so far. Clarifying this aspect could help tackle the life-treating events occurring in patients suffering from liver cirrhosis. The aim of the study was to analyze the relationships between the spleno-renal shunts presence at doppler ultrasound and the liver cirrhosis complications.</p> <p>Methods</p> <p>Design: eighty one patients out of 129 formed the study population (35 females). Chronic liver damage in these patients was caused by HCV (66), HBV (2), alcohol abuse (2) or unknown etiology, likely non-alcoholic steatohepatitis (11). Setting: two Liver Units of university/primary hospitals in Southern Italy. Main outcome measures: grading of esofageal varices; detection of ascites: assessment of hepatic encephalopathy; evaluation of liver cirrhosis severity; tracking hepatocellular carcinoma; doppler features of spleno-renal shunts and splenic flow velocity; spleen longitudinal diameter at sonography.</p> <p>Results</p> <p>The prevalence of spleno-renal shunts was 18.5%, without no difference concerning the etiology (HCV versus non-HCV, p = 0.870); the prevalence of hepatocellular carcinoma in patients with spleno-renal shunts was superior to that of patients without them (Pearson Chi-square, p = 0.006, power of sample size 74%), also after adjustment for liver decompensation (p = 0.024). The median score of hepatic encephalopathy in patients with and without spleno-renal shunts was similar, i.e., 0 (range, 0-2) versus 0 (0 - 3), p = 0.67. The median splenic vein flow velocity in patients with spleno-renal shunts was significantly inferior to that of patients without them, i.e., 13 cm/sec (95% confidence intervals, 6-18) versus 21 cm/sec (17-24), p < 0.0001. By far the largest percentage of large esophageal varices was in patients without spleno-renal shunts (p = 0.005). In contrast, the frequency of ascites and hepatic encephalopathy severity was overlapping in the two groups. BMI values but not Child-Pugh's classification predicted spleno-renal shunts (Ors = 1.84, 95% confidence intervals = 1.28-2.64, p = 0.001 and 1.145, 95% confidence intervals = 0.77-1.51, p = 0.66).</p> <p>Conclusion</p> <p>Taking into consideration the relatively small sample size, patients with spleno-renal shunts are burdened by an increased incidence of hepatocellular carcinoma. BMI predicted the spleno-renal shunts presence.</p

Research and Development for Near Detector Systems Towards Long Term Evolution of Ultra-precise Long-baseline Neutrino Experiments

With the discovery of non-zero value of $\theta_{13}$ mixing angle, the next generation of long-baseline neutrino (LBN) experiments offers the possibility of obtaining statistically significant samples of muon and electron neutrinos and anti-neutrinos with large oscillation effects. In this document we intend to highlight the importance of Near Detector facilities in LBN experiments to both constrain the systematic uncertainties affecting oscillation analyses but also to perform, thanks to their close location, measurements of broad benefit for LBN physics goals. A strong European contribution to these efforts is possible

Lezioni di Fisica Tecnica

Questo testo, che si prefigge finalità prevalentemente didattiche, rispecchia l'impostazione ed i contenuti che gli Autori hanno dato ai corsi da loro tenuti nelle Facoltà di Ingegneria ed Architettura nell'ambito del cosiddetto Nuovo Ordinamento degli Studi Universitari. Tradizionalmente, lo studio della Fisica Tecnica nei corsi di primo livello si articola nei tre macroargomenti: termodinamica applicata, trasmissione del calore ed impianti termici e di climatizzazione, che costituiscono le parti in cui questo testo si può considerare suddiviso. In particolare, dopo un'introduzione dei concetti fondamentali necessari per affrontare con un approccio ingegneristico le operazioni di calcolo su grandezze fisiche, vengono presentati i bilanci di massa, energia ed entropia per i sistemi chiusi ed aperti e la termodinamica degli stati; a quest'ultimo argomento il testo dedica particolare attenzione, in quanto gli Autori lo ritengono fondamentale per l'applicazione delle leggi della termodinamica ai processi ingegneristici. La trasmissione del calore viene inizialmente illustrata nella sua globalità, per poi passare ad una trattazione più approfondita dei tre meccanismi fondamentali di scambio termico; la necessità di questa impostazione, seguita da quasi tutti i testi di trasmissione del calore, deriva dal fatto che i meccanismi di scambio termico sono quasi sempre contemporaneamente presenti e, quindi, l’assenza di un preliminare studio unitario non permetterebbe di comprendere i casi reali e di risolvere problemi tecnicamente significativi, se non alla fine dell’intera trattazione. A chiusura del capitolo, viene affrontato il dimensionamento degli scambiatori di calore. Gli ultimi capitoli sono poi dedicati agli impianti, sia termici che di climatizzazione. Per quanto riguarda gli impianti termici (motori ed operatori), l'impostazione data all'argomento è tale da poterlo considerare sia un'applicazione dei principi di termodinamica e scambio termico precedentemente trattati, sia un'utile premessa ai successivi corsi di Macchine nell’ambito dell'Ingegneria Industriale; alla stesura di questo capitolo ha collaborato il prof. Renato Della Volpe, docente di Macchine presso la Facoltà di Ingegneria dell'Università di Napoli Federico II, cui va il vivo ringraziamento degli Autori. Lo studio degli impianti di climatizzazione è suddiviso in due capitoli: il primo, propedeutico, che affronta la termodinamica dell'aria umida, ed il secondo che descrive i criteri per il proporzionamento dei suddetti impianti. In questa seconda parte è dato ampio spazio alle tematiche della qualità dell’aria e del comfort termoigrometrico che permettono di specificare le condizioni ambientali che gli impianti di condizionamento devono realizzare