1,721,016 research outputs found

    Gli amministratori delle società pubbliche

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    La tesi ha ad oggetto la disciplina degli amministratori delle società pubbliche alla luce delle modifiche normative intervenute a seguito dell’emanazione del Testo Unico sulle società a partecipazione pubblica (d. lgs. n. 175 del 2016). In particolare, il presente lavoro analizza se ed in quale misura il Testo Unico incida sulla normativa “speciale” degli amministratori di tali società, bilanciando, alla luce del principio di proporzionalità espressamente contenuto fra i criteri della Legge delega, le diverse deroghe, previste per la salvaguardia degli interessi pubblici, con le disposizioni in ambito societario contenute nel Codice Civile. Il decreto n. 175, infatti, contiene l’ultima riforma intervenuta, in modo dirompente, in un quadro normativo stratificato, frammentario, complesso ed articolato, con lo scopo di procedere ad una generale riorganizzazione, razionalizzazione ed efficientamento del sistema delle partecipazioni pubbliche, in un’ottica di sistematizzazione organica della materia. La prospettiva di un bilanciamento tra i profili di specialità e la disciplina generale societaria è stata approfondita con riferimento agli aspetti attinenti i requisiti di eleggibilità (nonché la connessa disciplina dell’inconferibilità ed incandidabilità) e le vicende costitutive, modificative ed estintive dell’incarico di amministratore (nomina, revoca, prorogatio e decadenza), avendo riguardo anche alla struttura dell’organo, al sistema dei compensi percepiti e, infine, al regime della responsabilità. Il risultato al quale si è approdati ha mostrato l’esistenza di “aree” caratterizzate dalla permanenza di una disciplina derogatoria, la cui ratio risiede nella tutela di interessi pubblici, e di altre nelle quali vi è una decisa “attrazione” verso il regime di diritto comune societario, alla luce dell’esigenza di eliminare vantaggi artificiosi che finirebbero con il creare ingiustificate distorsioni concorrenziali.La tesi ha ad oggetto la disciplina degli amministratori delle società pubbliche alla luce delle modifiche normative intervenute a seguito dell’emanazione del Testo Unico sulle società a partecipazione pubblica (d. lgs. n. 175 del 2016). In particolare, il presente lavoro analizza se ed in quale misura il Testo Unico incida sulla normativa “speciale” degli amministratori di tali società, bilanciando, alla luce del principio di proporzionalità espressamente contenuto fra i criteri della Legge delega, le diverse deroghe, previste per la salvaguardia degli interessi pubblici, con le disposizioni in ambito societario contenute nel Codice Civile. Il decreto n. 175, infatti, contiene l’ultima riforma intervenuta, in modo dirompente, in un quadro normativo stratificato, frammentario, complesso ed articolato, con lo scopo di procedere ad una generale riorganizzazione, razionalizzazione ed efficientamento del sistema delle partecipazioni pubbliche, in un’ottica di sistematizzazione organica della materia. La prospettiva di un bilanciamento tra i profili di specialità e la disciplina generale societaria è stata approfondita con riferimento agli aspetti attinenti i requisiti di eleggibilità (nonché la connessa disciplina dell’inconferibilità ed incandidabilità) e le vicende costitutive, modificative ed estintive dell’incarico di amministratore (nomina, revoca, prorogatio e decadenza), avendo riguardo anche alla struttura dell’organo, al sistema dei compensi percepiti e, infine, al regime della responsabilità. Il risultato al quale si è approdati ha mostrato l’esistenza di “aree” caratterizzate dalla permanenza di una disciplina derogatoria, la cui ratio risiede nella tutela di interessi pubblici, e di altre nelle quali vi è una decisa “attrazione” verso il regime di diritto comune societario, alla luce dell’esigenza di eliminare vantaggi artificiosi che finirebbero con il creare ingiustificate distorsioni concorrenziali.LUISS PhD Thesi

    Development of a cell motility characterization system for industrial biotechnological applications

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    Cell migration is a very complex mechanism linked to the inflammatory response as well as to several processes of cell biology and development. The movement of cells in response to a chemokine gradient is the most popular form of interaction between cell environment and surface and specific surface receptor triggers an intracellular signaling pathway. This phenomenon is known as chemotaxis and is characteristic of neutrophil movements in response to the chemokine Interleuchin-8 (IL8) in a 3D space. Another paradigm of dynamic interaction between cells is the mechanism underlying the confluency of cells cultured in a Petri dish. This process is particularly studied in growing epithelial cell lines, and is influenced by still undefined external stimuli as well as by cell proliferation and cytoskeleton reorganization, that allow the contact and interaction between cells in 2D space. Chronic inflammation is an ideal condition for the study of cell migration and its de-regulation; understanding the mechanisms involved in cell motility and their putative modulation, is the first step in setting new appropriate models of study. During PhD project, different cellular models have been used: IB3 cell lines belonging to patients with Cystic Fibrosis (caused by mutations of cystic fibrosis transmembrane regulator (CFTR)), and T84 cell lines, a popular model of study of Coeliac Disease, a common intolerance to proteins of wheat. Both disease are characterized by a pro-inflammatory milieu with high level of tissue Transglutaminase (TG2), a multi-functions enzyme with a defined role in several human pathologies. Cystic Fibrosis is the prototype of diseases in which an uncontrolled production of IL8 leads to a dysregulated neutrophil recruitment. The IB3 cell lines have been used to understand a molecular mechanisms of enhanced IL8 production and their modulation. The results evidence i) the role of TG2 as a new pathogenic factor in Cystic Fibrosis; ii) the role of post-translational modifications of TG2 as a link between genetic defect of CFTR ad inflammation iii) the mechanisms of autophagy inhibition via ROS-TG2 axis, in epithelial airway cell line and mice model of CF. The consequence is a fine modulation of IL8 production. The system allows the design of a 3D model to study cell migration under IL8 diffusive flux in qualitative and quantitative ways. Another important pathological system with chronic inflammation is celiac disease and the analysis of interactions of alimentary peptides with the frontline gut epithelium is a useful model of study. The epithelial cells are pivot in the innate immune activation in CD and cytoskeleton rearrangement is the earliest event in such a response to gliadin peptides. The data in T84 cell model show a gliadin peptide-driven pro-inflammatory environment as a consequence of its impaired lysosomal degradation. Moreover, alterations of motility and cytoskeletal reorganization emphasize the “toxic” effect of peptide. Therefore, CD offers an ideal opportunity to set up a 2D model of study of cell motility. Understanding the mechanisms of migration and the identification of appropriate target of modulation of cell recruitment could allow wide industrial applications in biotechnology and will be successful to provide a useful tool to test potential therapeuthic molecules

    Abusi di posizione dominante (anno 2014)

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    Il presente contributo mira a fornire una raccolta dei procedimenti conclusi dall’Autorità nazionale antitrust (di seguito “Autorità”) nell’anno 2014, alla luce della normativa riguardante l’abuso di posizione dominante. Tale periodo di riferimento si caratterizza per una certa esiguità numerica dei procedimenti avviati da parte dell’Autorità — in continuità con quanto evidenziato con riferimento all’anno precedente — a cui corrisponde tuttavia una rilevante eterogeneità quanto agli esiti. Delle quattro decisioni assunte, infatti, si registra un unico caso di chiusura con accettazione di impegni ed un altro di accertamento dell’abuso; negli altri due l’Autorità ha rilevato rispettivamente l’assenza di violazione e la non applicabilità della legge antitrust. Riguardo l’oggetto delle decisioni, si evidenzia come esse riguardino prevalentemente servizi di interesse economico generale (diritti trasmissivi, servizi di trasporto ferroviario, rete idrica e rifiuti urbani a base cellulosica). The paper aims to provide a review of the abuses of dominant position proceedings concluded by the national anti-trust (the “Authority”) in the year 2014. This period is characterised by a small numbers of proceedings initiated by the Authority — in continuity with what has been registered for the past year — which have however a significant heterogeneity as to the outcome. Of the four decisions, in fact, only one case was closed with acceptance of commitments while another one ascertained an abuse of dominant position; in the other two, the Authority established, respectively, the absence of any infringements and the nonapplicability of the antitrust law. Regarding the subject of the decisions, they relate predominantly to services of general economic interest (such as: broadcasting rights, rail transport services, water supply and urban waste management)

    Eosinophilic granulomatosis with polyangiitis (EGPA) and PRES: a case-based review of literature in ANCA-associated vasculitides

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    Eosinophilic granulomatosis with polyangiitis (EGPA) is a small-sized vessel systemic necrotizing vasculitis and belongs to the family of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides. The involvement of central nervous system in this condition is pretty rare. Posterior reversible encephalopathy syndrome (PRES) is a clinical and radiological entity described for the first time by Hinchey et al. (N Engl J Med 334(8):494-500, 1996) and characterized by MRI findings of reversible subcortical vasogenic edema predominantly in the white matter of posterior cerebral lobes. There are few case reports describing the concurrence of PRES with ANCA-associated vasculitides. We describe a case of PRES in a patient with a diagnosis of EGPA with a concise review of the literature. The exact cause of this syndrome is unknown. It has been related to eclampsia, drug-induced hypertension, renal insufficiency and also to rheumatologic diseases. Endothelial injury, hypertension and immunosuppressive medications can compromise the regulation of cerebral blood flow. In ANCA-associated vasculitides, patients presenting with symptoms of PRES represent a challenge to treatment with immunosuppressive medications. However, since an inflammatory process might be implicated, judicious use of these agents along with tight control of blood pressure and a supportive therapy may contribute to the resolution of the encephalopathic syndrome treating at the same time other manifestation related to the rheumatologic disease. Larger clinical studies are warranted to optimize the management of vasculitis-associated PRES

    Towards a rational combination therapy of cystic fibrosis: How cystamine restores the stability of mutant CFTR

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    Cystic fibrosis (CF) is most frequently due to homozygous ΔF508-CFTR mutation. The ΔF508-CFTR protein is unstable in the plasma membrane (PM), even if it is rescued by pharmacological agents that prevent its intracellular retention and degradation. Restoring defective autophagy in CF airways by proteostasis regulators (such as cystamine and its reduced form, cysteamine) can rescue and stabilize ΔF508-CFTR at the PM, thus enabling the action of CFTR potentiators, which are pharmacological agents that stimulate the function of CFTR as an ion channel. The effects of cystamine extend for days (in vitro) and weeks (in vivo) beyond washout, suggesting that once peripheral proteostasis has been re-established, PM-resident ΔF508-CFTR sustains its own stability. We demonstrated that the pharmacological inhibition of wild-type CFTR [cystic fibrosis transmembrane conductance regulator (ATP-binding cassette subfamily C, member 7)], in bronchial epithelial cells decreases the stability of the CFTR protein by inhibiting autophagy, elevating the abundance of SQSTM1/p62 and its interaction with CFTR at the PM, increasing the ubiqutination of CFTR, stimulating the lysosomal degradation of CFTR and avoiding its recycling. All these effects could be inhibited by cystamine. Moreover, CFTR-sufficient epithelia generate permissive conditions for incorporating ΔF508-CFTR into the PM and stabilizing it at this location. These results provide the rationale for a combination therapy of CF in which pretreatment with cystamine or cysteamine enables the later action of CFTR potentiators

    How Effectively Can Oxidative Stress and Inflammation Be Reversed When CFTR Function Is Pharmacologically Improved?

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    A critical challenge in the age of advanced modulator therapies is to understand and determine how effectively chronic oxidative stress and oxidative stress-induced inflammation can be reversed and physiological balance restored when CFTR function is pharmacologically improved. The triple therapy with elexacaftor–tezacaftor–ivacaftor (ETI) suggests that CFTR activity in individuals with at least one F508del mutation can be partially restored to about 50% of normal levels. Although incomplete, the partial recovery of CFTR function has been shown to drastically lower sputum pathogen content, enhance microbiome diversity, and lower inflammation markers within the first year of treatment in adolescents and adults with cystic fibrosis. However, despite these advancements, residual airway infection, oxidative stress and inflammation persist, with levels similar to other chronic lung conditions, like non-CF bronchiectasis. This persistence highlights the necessity for innovative antioxidant and anti-inflammatory treatments, in particular for individuals with advanced lung disease. To address this issue, emerging multi-omics technologies offer valuable tools to investigate the impact of modulator therapies on various molecular pathways. By analyzing changes in gene expression, epigenetic modifications, protein profiles and metabolic processes in airway-derived samples, it could be possible to uncover the mechanisms driving persistent oxidative stress and inflammation. These insights could pave the way for identifying new therapeutic targets to fully restore airway health and overall physiological balance

    Unveiling regional patterns of IgE sensitization to peanut, hazelnut, and walnut in Italy: a nationwide bottom-up molecular survey

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    Background: Tree nut and peanut allergy is increasing in prevalence across Europe, yet the molecular sensitization patterns underlying these allergies remain incompletely defined in Southern Europe, particularly in Italy. Objective: To characterize regional profiles of IgE sensitization to allergenic components of peanut, hazelnut, and walnut across Italy using a bottom-up, molecule-based diagnostic approach. Methods: We retrospectively analyzed data from 1526 patients with suspected nut allergy evaluated in three Italian centers representative of the Northeast, Central, and Southern regions. Specific IgE reactivity to 15 allergenic molecules was assessed using the MADX-ALEX2 multiplex platform. Co-sensitization patterns and regional variations were explored through Euler-Venn analysis. Results: All patients were sensitized to at least one nut allergen, revealing distinct geographic trends. In Northeast Italy, PR-10 proteins predominated (up to 63 %), consistent with birch-related cross-reactivity. In contrast, nsLTP sensitization was highly prevalent in the South (up to 91 %), while Central Italy showed intermediate profiles. Co-sensitization to PR-10 and nsLTPs in the Northeast was not associated with milder reactions. Sensitization to seed storage proteins progressively decreased from North to South. Jug r 1 was the predominant walnut allergen in the Northeast, whereas Jug r 2 and Jug r 3 prevailed in the South. Sensitization to oleosins was rare (<2 %). Conclusion: Italy represents a microcosm of Europe in terms of molecular allergy endotypes, showing a clear North-South gradient in nut allergen sensitization. Multiplex molecular diagnostics unveil region-specific co-sensitizations with potential clinical relevance and support geographically tailored diagnostic and management strategies within a precision allergy framework
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