Pleiotropic Phenotypes Associated With PKP2 Variants

Plakophilin-2 (PKP2) is a component of the desmosome complex and known for its role in cell-cell adhesion. Recently, alterations in the Pkp2 gene have been associated with different inherited cardiac conditions including Arrythmogenic Cardiomyopathy (ACM or ARVC), Brugada syndrome (BrS), and idiopathic ventricular fibrillation to name the most relevant. However, the assessment of pathogenicity regarding the genetic variations associated with Pkp2 is still a challenging task: the gene has a positive Residual Variation Intolerance Score and the potential deleterious role of several of its variants has been disputed. Limitations in facilitating interpretation and annotations of these variants are seen in the lack of segregation and clinical data in the control population of reference. In this review, we will provide a summary of all the currently available genetic information related to the Pkp2 gene, including different phenotypes, ClinVar annotations and data from large control database. Our goal is to provide a literature review that could help clinicians and geneticists in interpreting the role of Pkp2 variants in the context of heritable sudden death syndromes. Limitations of current algorithms and data repositories will be discussed

Imaging spectroscopic performances for a Si based detection system

We present the imaging and spectroscopic capabilities of a system based on a single photon counting chip (PCC) bump-bonded on a Si pixel detector. The system measures the energy spectrum and the flux, produced by a standard mammographic tube. We have also made some images of low contrast details, achieving good results

Endogenous glutamine decrease is associated with pancreatic cancer progression

Abstract Pancreatic ductal adenocarcinoma (PDAC) is becoming the second leading cause of cancer-related death in the Western world. The mortality is very high, which emphasizes the need to identify biomarkers for early detection. As glutamine metabolism alteration is a feature of PDAC, its in vivo evaluation may provide a useful tool for biomarker identification. Our aim was to identify a handy method to evaluate blood glutamine consumption in mouse models of PDAC. We quantified the in vitro glutamine uptake by Mass Spectrometry (MS) in tumor cell supernatants and showed that it was higher in PDAC compared to non-PDAC tumor and pancreatic control human cells. The increased glutamine uptake was paralleled by higher activity of most glutamine pathway-related enzymes supporting nucleotide and ATP production. Free glutamine blood levels were evaluated in orthotopic and \u202

82. Cftr Gene Targeting in Murine ES Cells Mediated by the SFHR Technique

Small Fragment Homologous Recombination (SFHR)-mediated targeting is a gene therapy strategy where a specific genomic locus is modified through a target exchange between a small DNA fragment (SDF) and genomic DNA. Here we demonstrate that SFHR can stably introduce a 3-bp deletion (corresponding to |[Delta]|F508) within Cftr (Cystic Fibrosis Transmembrane Conductance Regulator) locus in the genome of mouse embryonic stem (ES) cells. SDFs (about 6.4|[times]|105 molecules per cell) carrying the |[Delta]|F508 mutation were transfected by nucleofection protocol. About 12% of transcript corresponding to deleted allele was detected and about 60% of the electroporated cells no longer had measurable CFTR-dependent chloride efflux. The CFTR activity was also analyzed by measuring the chloride efflux by the fluorescence microscopy-coupled digital video imaging system in each ES cell colony, previously loaded with MQAE, a chloride sensitive dye. An average of 4-6 regions for each cell colony was analysed to verify the genotypic homogeneity of each colony. In fact all regions examined in each colony showed a similar significant chloride efflux after PKA activation. Moreover on twelve electroporated ES colonies analysed, eight were successfully mutated (Cl- efflux not significantly different from zero) while four colonies showed Cl-efflux CFTR-dependent not significantly different from the untreated ones

Semiconductor pixel detectors for digital mammography

Abstract We present some results obtained with silicon and gallium arsenide pixel detectors to be applied in the field of digital mammography. Even though GaAs is suitable for medical imaging applications thanks to its atomic number, which allows a very good detection efficiency, it often contains an high concentrations of traps which decrease the charge collection efficiency (CCE). So we have analysed both electrical and spectroscopic performance of different SI GaAs diodes as a function of concentrations of dopants in the substrate, in order to find a material by which we can obtain a CCE allowing the detection of all the photons that interact in the detector. Nevertheless to be able to detect low contrast details, efficiency and CCE are not the only parameters to be optimized; also the stability of the detection system is fundamental. In the past we have worked with Si pixel detectors; even if its atomic number does not allow a good detection efficiency at standard thickness, it has a very high stability. So keeping in mind the need to increase the Silicon detection efficiency we performed simulations to study the behaviour of the electrical potential in order to find a geometry to avoid the risk of electrical breakdown

Experimental study of Compton scattering reduction in digital mammographic imaging

In mammography, the first cause of image contrast reduction arises from the photons scattered inside the examined organ. The amount of Compton scattering strongly depends on the irradiation area and on the distance between the organ and the X-ray detector. We have experimentally evaluated how these geometrical conditions affect the scattering fraction. Our experimental setup includes a single photon counting device based on a silicon pixel detector as X-ray sensor; a lucite cylinder to simulate the breast tissue, and a lead collimator to define the irradiation area. We have evaluated the contrast and the signal-to-noise ratio for images acquired in different conditions