26 research outputs found
Molecular Signature of Biological Aggressiveness in Clear Cell Sarcoma of the Kidney (CCSK)
: Clear cell sarcoma of the kidney (CCSK) is a rare pediatric renal tumor with a worse prognosis than Wilms' tumor. Although recently, BCOR internal tandem duplication (ITD) has been found as a driver mutation in more than 80% of cases, a deep molecular characterization of this tumor is still lacking, as well as its correlation with the clinical course. The aim of this study was to investigate the differential molecular signature between metastatic and localized BCOR-ITD-positive CCSK at diagnosis. Whole-exome sequencing (WES) and whole-transcriptome sequencing (WTS) were performed on six localized and three metastatic BCOR-ITD-positive CCSKs, confirming that this tumor carries a low mutational burden. No significant recurrences of somatic or germline mutations other than BCOR-ITD were identified among the evaluated samples. Supervised analysis of gene expression data showed enrichment of hundreds of genes, with a significant overrepresentation of the MAPK signaling pathway in metastatic cases (p < 0.0001). Within the molecular signature of metastatic CCSK, five genes were highly and significantly over-expressed: FGF3, VEGFA, SPP1, ADM, and JUND. The role of FGF3 in the acquisition of a more aggressive phenotype was investigated in a cell model system obtained by introducing the ITD into the last exon of BCOR by Crispr/Cas9 gene editing of the HEK-293 cell line. Treatment with FGF3 of BCOR-ITD HEK-293 cell line induced a significant increase in cell migration versus both untreated and scramble cell clone. The identification of over-expressed genes in metastatic CCSKs, with a particular focus on FGF3, could offer new prognostic and therapeutic targets in more aggressive cases
Neuronopathic Gaucher disease models reveal defects in cell growth promoted by Hippo pathway activation
Gaucher Disease (GD), the most common lysosomal disorder, arises from mutations in the GBA1 gene and is characterized by a wide spectrum of phenotypes, ranging from mild hematological and visceral involvement to severe neurological disease. Neuronopathic patients display dramatic neuronal loss and increased neuroinflammation, whose molecular basis are still unclear. Using a combination of Drosophila dGBA1b loss-of-function models and GD patient-derived iPSCs differentiated towards neuronal precursors and mature neurons we showed that different GD- tissues and neuronal cells display an impairment of growth mechanisms with an increased cell death and reduced proliferation. These phenotypes are coupled with the downregulation of several Hippo transcriptional targets, mainly involved in cells and tissue growth, and YAP exclusion from nuclei. Interestingly, Hippo knock-down in the GBA-KO flies rescues the proliferative defect, suggesting that targeting the Hippo pathway can be a promising therapeutic approach to neuronopathic GD.A combination of Drosophila dGBA1b loss-of-function models and Gaucher Disease (GD) patient-derived iPSCs reveals an impairment in GD neuronal cell growth and that Hippo pathway hyperactivation contributes to the impairment
Modeling of clear cell sarcoma of the kidney of the pediatric age
Clear cell sarcoma of the kidney (CCSK) is the second most common pediatric renal tumor, characterized in 90% of cases by the presence of internal tandem duplications (ITDs) localized at the last exon of BCOR gene. BCOR protein constitute a core component of the non-canonical Polycomb Repressive Complex1 (PRC1.1), which performs a fundamental silencing activity.
ITDs in the last BCOR exon at the level of PUFD domain have been identified in many tumor subtypes and could affect PCGF1 binding and the subsequent PRC1.1 activity, although the exact oncogenic mechanism of ITD remains poorly understood.
This project has the objective of investigating the molecular mechanisms underlying the oncogenesis of CCSK, approaching the study with different methodologies. A first model in HEK-293 allowed to obtain important informations about BCOR functionality, suggesting that the presence of ITD generates an altered activity which is very different from a loss-of-function. It has also been observed that BCOR function within the PRC1.1 complex varies with different ITDs. Moreover, it allowed the identification of molecular signatures evoked by the presence of BCOR-ITD, including its role in extracellular matrix interactions and invasiveness promotion.
The parallel analysis of WTS data from 8 CCSK cases permitted the identification of a peculiar signature for metastatic CCSKs, highlighting a 20-fold overexpression of FGF3. This factor promoted a significant increase in invasive ability in the cellular model.
In order to study BCOR-ITD effects over cell stemness and differentiation, an inducible model is being obtained in H1 cells. This way, it will be possible to study the functionality of BCOR-ITD in a context more similar to the origin of CCSKs, evaluating both the specific interactome and phenotypic consequences caused by the mutation
Esperienze di rilevamento fotogrammetrico e multispettrale da APR per la stima dei danni in agricoltura
La sempre maggiore frequenza di eventi metereologici “estremi” pone la necessità di disporre di un metodo di stima dei danni subìti dalle colture in grado di fornire risultati oggettivi, accurati e a costi contenuti allo stesso tempo. L’operazione di stima, infatti, non deve incidere economicamente in modo significativo sull’entità del risarcimento che le compagnie di assicurazione devono corrispondere all’agricoltore assicurato. Il recente sviluppo del cosiddetto telerilevamento di prossimità da APR sembra offrire una soluzione interessante sia dal punto di vista tecnologico che da quello economico.
In questo studio vengono prese in esame due colture estensive e un danno tipico che esse possono subire a causa dell’azione combinata del vento, della pioggia o della grandine: il cosiddetto “allettamento delle piante”. La base per stabilire l’entità economica del danno risiede nella quantificazione della superficie delle zone danneggiate e del livello di allettamento delle piante stesse
UAVs for Structure-From-Motion Coastal Monitoring: A Case Study to Assess the Evolution of Embryo Dunes over a Two-Year Time Frame in the Po River Delta, Italy
Coastal environments are usually characterized by a brittle balance, especially in terms
of sediment transportation. The formation of dunes, as well as their sudden destruction as a result
of violent storms, affects this balance in a significant way. Moreover, the growth of vegetation on
the top of the dunes strongly influences the consequent growth of the dunes themselves. This work
presents the results obtained through a long-term monitoring of a complex dune system by the use
of Unmanned Aerial Vehicles (UAVs). Six different surveys were carried out between November
2015 and December 2017 in the littoral of Rosolina Mare (Italy). Aerial photogrammetric data were
acquired during flight repetitions by using a DJI Phantom 3 Professional with the camera in a
nadiral arrangement. The processing of the captured images consisted of the reconstruction of a
three-dimensional model using the Structure-from-Motion (SfM). Each model was framed in the
European Terrestrial Reference System (ETRS) using GNSS geodetic receivers in Network Real Time
Kinematic (NRTK). Specific data management was necessary due to the vegetation by filtering the
dense cloud. This task was performed by both performing a slope detection and a removal of the
residual outliers. The final products of this approach were thus represented by Digital Elevation
Models (DEMs) of the sandy coastal section. In addition, DEMs of Difference (DoD) were also
computed for the purpose of monitoring over time and detecting variations. The accuracy assessment
of the DEMs was carried out by an elevation comparison through especially GNSS-surveyed points.
Relevant cross sections were also extracted and compared. The use of the Structure-from-Motion
approach by UAVs finally proved to be both reliable and time-saving thanks to quicker in situ
operations for the data acquisition and an accurate reconstruction of high-resolution elevation
models. The low cost of the system and its flexibility represent additional strengths, making this
technique highly competitive with traditional ones
A Low-Cost GNSS Prototype for Tracking Runners in RTK Mode: Comparison with Running Watch Performance
GNSS positioning is widely use in every kind of application. Nowadays, low-cost GNSS modules are becoming available to apply the Real-Time Kinematic mode in those applications in which a centimeter-level accuracy would be appreciated for a precise positioning. In this work, we developed a prototype for collecting data in RTK mode with a single-frequency multi-constellation device during some physical tests performed by a professional runner. Prior to do this, we assessed the accuracy in estimating the distance actually covered during a walking on a signalized line. Also, we verified the capability to detect short sprints of about 12–15 s. Finally, we compared the results of our prototype with a Polar M430 running watch during three Cooper tests and a Kosmin test. The comparison highlighted that the running watch overestimated the total distance systematically and did not describe the performance of the athlete accurately in time. The distance overestimation was +4.7% on average using the running watch, whereas our prototype system exhibited an error level of about 0.1%
Monitoraggio di area lagunare tramite UAVS e telerilevamento multispettrale
Il rilevamento fotogrammetrico basato su sistemi UAV rappresenta da diversi anni una valida alternativa alle tecniche più tradizionali di rilievo terrestre (tramite stazione totale o GNSS), di rilievo fotogrammetrico da aereo o di rilievo satellitare. In particolare, nelle zone difficili da raggiungere, come ad esempio le aree lagunari o deltizie, i vantaggi di un sistema UAV sono soprattutto legati alla velocità di acquisizione del dato, alla precisione ed al grado di dettaglio elevati ed ai costi relativamente limitati. Gli svantaggi si possono sostanzialmente riassumere nel grande numero di immagini rapidamente acquisite e quindi nella grande mole di dati da elaborare; svantaggio che comporta spesso la riduzione delle aree rilevate soprattutto nel caso di rilievo alle grandi e grandissime scale. Nell’esempio del presente lavoro si analizzano tutti questi aspetti in alcuni case studies nella Sacca di Goro – Comacchio (Provincia di Ferrara). Si tratta di un’area lagunare di particolare interesse sia per gli aspetti naturalistici sia per gli aspetti economici (coltivazione di mitili). A causa dei continui apporti di sedimenti da parte della vicina foce del fiume Po, negli ultimi anni, sono stati realizzati numerosi rilievi di monitoraggio di alcune zone della laguna tramite immagini satellitari ad alta risoluzione oltre a rilievi batimetrici e terrestri. Nel caso specifico si sono utilizzati UAVS di tipo commerciale (Phantom 3 – PRO), con camera fotografica standard, nel rilevamento fotogrammetrico di alcune aree della Sacca di Goro che presentano una rapida evoluzione. Il rilievo è stato realizzato anche con UAVS dotato di camera multispettrale (Micasense RedEdge) utilizzata per studiare l’evoluzione della vegetazione di alcune aree interne della Sacca di Goro
Experimental Characterization of a High-Damping Viscoelastic Material Enclosed in Carbon Fiber Reinforced Polymer Components
This work aims to identify the damping properties of a commercial viscoelastic material that can be embedded and cured between the layers of composite laminates. The material may be adopted for reducing the vibration response of composite panels, typically used in automotive and aerospace applications, e.g., as vehicle body shell components. In order to objectively estimate the actual potential to enhance the noise vibration and harshness aspects, the effects of the viscoelastic material on the modal parameters of carbon/epoxy thin panels are quantitatively assessed through experimental modal analysis. Two different experiments are conducted, namely impact hammer tests and shaker excitation measurements. Based on the results of the experimental campaign, the investigated material is confirmed as a promising solution for possibly reducing the severity of vibrations in composite panels, thanks to its high damping properties. Indeed, the presence of just one layer proves to triple the damping properties of a thin panel. An approximate damping model is derived from the measured data in order to effectively simulate the dynamic response of new design solutions, including thin composite panels featuring the viscoelastic material