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Search Results: 1 - 10 of 15888 matches for " Gian Marco Ghiggeri "
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Constitutional Nephrin Deficiency in Conditionally Immortalized Human Podocytes Induced Epithelial-Mesenchymal Transition, Supported by -Catenin/NF-kappa B Activation: A Consequence of Cell Junction Impairment?
Gian Marco Ghiggeri,Maddalena Gigante,Armando Di Donato
International Journal of Nephrology , 2013, DOI: 10.1155/2013/457490
Abstract: The kidney glomerular podocytes are the cellular target of many chronic nephropathies both determined and acquired genetically. Mutations that affected the expression and/or the function of nephrin, a key component of the slit-diaphragm, are often causes of these pathologies. Recent findings showed that murine podocytes could undergo epithelial-mesenchymal transformation (EMT), suggesting new hypotheses about the pathogenesis of glomerular fibrosis. Here, we show that also human podocytes can undergo EMT, but more importantly nephrin ablation itself can trigger this phenotypic transformation. In fact, a model of human podocyte with engineered nephrin deficiency constitutionally expressed high levels of -SMA, vimentin, fibronectin, and other hallmarks of EMT. Since it is known that cell contact abrogation is one of the triggers of EMT, we reasoned that nephrin loss could account for such cell junction disruption and cause the EMT. Therefore, we demonstrated that also normal podocytes could spontaneously undergo EMT if grown in Ca2+-free medium, which is known to impair cell contacts. The analysis of the main intracellular signal transduction pathways evidenced some major anomalies consequent with the nephrin abrogation. The most intriguing was the activation of -catenin pathway, which plays a critical role in podocyte ontogenesis as well as in the nephrin expression and EMT regulation. Also other important signaling proteins, like NF- B, p53, and retinoblastoma protein (RB), showed important activity modifications. Interestingly, most of the above indicated signaling pathway alterations were again reproducible by cell junction rupture, induced by Ca2+ deprivation. Finally, immunofluorescence analysis on kidney sections of patients with NS of Finnish type confirmed the constitutive expression of -SMA. 1. Introduction Epithelial-mesenchymal transition (EMT) and its reverse process (MET) are physiological processes operative since the first days of the embryological development [1, 2]. In adults, this phenotypic transition is often just a physiological response to a call for tissue regeneration, as in the case of normal wounds [3, 4]. In fact, the cells deriving from EMT, the myofibroblasts, smooth muscle cells alike, are specialized fibroblasts highly active in the production of extracellular matrix components (collagens, elastin, fibronectin, metalloproteinase, etc.) [5]. Unfortunately, EMT is often exacerbated during pathological events such as organ fibrosis, where the process occurs out of control and is irreversible. Recently, it has been pointed out
Wolfram Syndrome: New Mutations, Different Phenotype
Concetta Aloi, Alessandro Salina, Lorenzo Pasquali, Francesca Lugani, Katia Perri, Chiara Russo, Ramona Tallone, Gian Marco Ghiggeri, Renata Lorini, Giuseppe d'Annunzio
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0029150
Abstract: Background Wolfram Syndrome (WS) is an autosomal recessive neurodegenerative disorder characterized by Diabetes Insipidus, Diabetes Mellitus, Optic Atrophy, and Deafness identified by the acronym “DIDMOAD”. The WS gene, WFS1, encodes a transmembrane protein called Wolframin, which recent evidence suggests may serve as a novel endoplasmic reticulum calcium channel in pancreatic β-cells and neurons. WS is a rare disease, with an estimated prevalence of 1/550.000 children, with a carrier frequency of 1/354. The aim of our study was to determine the genotype of WS patients in order to establish a genotype/phenotype correlation. Methodology/Principal Findings We clinically evaluated 9 young patients from 9 unrelated families (6 males, 3 females). Basic criteria for WS clinical diagnosis were coexistence of insulin-treated diabetes mellitus and optic atrophy occurring before 15 years of age. Genetic analysis for WFS1 was performed by direct sequencing. Molecular sequencing revealed 5 heterozygous compound and 3 homozygous mutations. All of them were located in exon 8, except one in exon 4. In one proband only an heterozygous mutation (A684V) was found. Two new variants c.2663 C>A and c.1381 A>C were detected. Conclusions/Significance Our study increases the spectrum of WFS1 mutations with two novel variants. The male patient carrying the compound mutation [c.1060_1062delTTC]+[c.2663 C>A] showed the most severe phenotype: diabetes mellitus, optic atrophy (visual acuity 5/10), deafness with deep auditory bilaterally 8000 Hz, diabetes insipidus associated to reduced volume of posterior pituitary and pons. He died in bed at the age of 13 years. The other patient carrying the compound mutation [c.409_424dup16]+[c.1381 A>C] showed a less severe phenotype (DM, OA).
Flexible Strategies for Centralized Public Procurement
Gian Luigi Albano,Marco Sparro
Review of Economics and Institutions , 2010, DOI: 10.5202/rei.v1i2.17
Abstract: When designing a national public procurement system, the degree of centralization (or, equivalently, the degree of demand aggregation) is one of the most crucial as well as puzzling policy choices. Centralized procurement has been traditionally considered as an instrument to reduce public spending. In more recent years, though, and particularly after the 2008 global financial turmoil, a growing interest has arisen among both policy makers and researchers in government procurement as a lever to pursue broader policy goals, such as competitive markets structure, sustainable development and innovation. This paper reviews and discusses several issues related both to the rationales and to the practical implementation of centralized procurement strategies, with a particular focus on the procurement of goods and services.
A Selection Principle for the Sharp Quantitative Isoperimetric Inequality
Marco Cicalese,Gian Paolo Leonardi
Mathematics , 2010,
Abstract: We introduce a new variational method for the study of stability in the isoperimetric inequality. The method is quite general as it relies on a penalization technique combined with the regularity theory for quasiminimizers of the perimeter. Two applications are presented. First we give a new proof of the sharp quantitative isoperimetric inequality in $R^n$. Second we positively answer to a conjecture by Hall concerning the best constant for the quantitative isoperimetric inequality in $R^2$ in the small asymmetry regime.
Best constants for the isoperimetric inequality in quantitative form
Marco Cicalese,Gian Paolo Leonardi
Mathematics , 2010,
Abstract: We prove existence and regularity of minimizers for a class of functionals defined on Borel sets in $R^n$. Combining these results with a refinement of the selection principle introduced by the authors in arXiv:0911.0786, we describe a method suitable for the determination of the best constants in the quantitative isoperimetric inequality with higher order terms. Then, applying Bonnesen's annular symmetrization in a very elementary way, we show that, for $n=2$, the above-mentioned constants can be explicitly computed through a one-parameter family of convex sets known as ovals. This proves a further extension of a conjecture posed by Hall in J. Reine Angew. Math. 428 (1992).
Hierarchical Soft Terms and Flavor Physics
Giudice, Gian F.;Nardecchia, Marco;Romanino, Andrea
High Energy Physics - Phenomenology , 2008, DOI: 10.1016/j.nuclphysb.2008.12.030
Abstract: We study the framework of hierarchical soft terms, in which the first two generations of squarks and sleptons are heavier than the rest of the supersymmetric spectrum. This scheme gives distinctive predictions for the pattern of flavor violations, which we compare to the case of nearly degenerate squarks. Experiments in flavor physics have started to probe the most interesting parameter region, especially in $b\leftrightarrow s$ transitions, where hierarchical soft terms can predict a phase of $B_s$ mixing much larger than in the Standard Model.
Investment Banking Services: Ownership Structures, Financial Advisory and Corporate Governance Models
Renato Giovannini,Vincenzo Capizzi,Gian Marco Chiesi
International Journal of Business Administration , 2010, DOI: 10.5430/ijba.v1n1p49
Abstract: This study is based on the premise that mostly large enterprises require investment banking services, due to their complexity and the difficult scenarios in which they operate. Accordingly, we empirically investigate the hypothesis that both the type of ownership structures and the quality of governance are correlated with the demand for specific investment banking services. The analysis is developed by using a proxy for the propensity of enterprises to demand these services, making reference to an extended definition of investment banking activity. The empirical analysis performed on a sample of 150 enterprises showed that the investment banking propensity indicator is significantly correlated with ownership and governance variables. Next, we verify whether companies characterised by greater probability of access to investment banking services show better income performance. However, no conclusive and univocal conclusions can be drawn yet with regard to the linkage between investment banking propensity and performance.
Sharp stability inequalities for planar double bubbles
Marco Cicalese,Gian Paolo Leonardi,Francesco Maggi
Mathematics , 2012,
Abstract: In this paper we address the global stability problem for double-bubbles in the plane. This is accomplished by combining the "improved convergence theorem" for planar clusters developed in arXiv:1409.6652 with an ad hoc analysis of the problem, which addresses the delicate interaction between the (possible) dislocation of singularities and the multiple-volumes constraint.
Improved convergence theorems for bubble clusters. I. The planar case
Marco Cicalese,Gian Paolo Leonardi,Francesco Maggi
Mathematics , 2014,
Abstract: We describe a quantitative construction of almost-normal diffeomorphisms between embedded orientable manifolds with boundary to be used in the study of geometric variational problems with stratified singular sets. We then apply this construction to isoperimetric problems for planar bubble clusters. In this setting we develop an improved convergence theorem, showing that a sequence of almost-minimizing planar clusters converging in $L^1$ to a limit cluster has actually to converge in a strong $C^{1,\alpha}$-sense. Applications of this improved convergence result to the classification of isoperimetric clusters and the qualitative description of perturbed isoperimetric clusters are also discussed. Analogous results for three-dimensional clusters are presented in part two, while further applications are discussed in some companion papers.
Efficient Implementation of a Demultiplexer Based on a Multirate Filter Bank for the Skyplex Satellites DVB System
Marco Re,Andrea Del Re,Gian Carlo Cardarilli
VLSI Design , 2002, DOI: 10.1080/1065514021000012048
Abstract: In this paper, an extensive comparison among alternative algorithms for the implementation of a digital demultiplexer has been carried out. The computational complexity, the performances and the accuracy with respect to the quantization effects (quantization noise and coefficient quantization) have been evaluated for the different algorithms. The selected digital architecture has been designed to be compliant with the Eutelsat specifications for the Skyplex Digital Video Broadcast (DVB) television system (Re, M., Cardarilli, G.C., Del Re, A. and Lojacono R. (2000) “FPGA Implementation of a Demux based on a multirate filter bank”. International Symposium on Circuits and Systems 2000, 5 (May), 353–356). At present, a more expensive and complex analog structure, based on six Surface Acoustic Wave (SAW) filters, is used. The new digital architecture has been mapped on six Altera Flex 10K-100 devices. The final test bed, that includes a complete interface to the demodulator, has been implemented on a four-layers PCB.
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