La normativa anticorruzione nei gruppi societari in pubblico comando

Il presente elaborato si è posto l’obiettivo di compiere una indagine su di una normativa che disciplina un fenomeno rappresentante da sempre un grave problema per il nostro Paese e l’intero contesto europeo: la corruzione. In modo particolare si è focalizzata l’attenzione sull’applicazione della normativa anticorruzione , e degli strumenti preventivi che la caratterizzano, nelle società in pubblico comando. La presente tesi parte proprio da una disamina generale di quella che è la corruzione nella pubblica amministrazione e delle ragioni che hanno spinto il legislatore ad “occuparsi” di tale problema, ma visto che la complessità del fenomeno corruttivo richiede forme di contrasto giuridico differenziate, in tale prima parte dell’ elaborato sono state analizzate in primis l’organizzazione amministrativa (ANAC, Dipartimento della funzione pubblica, Comitato interministeriale) atta a predisporre ed aggiornare i vari strumenti di prevenzione; per poi focalizzare l’attenzione su alcuni di questi strumenti, senza dimenticare che questi rimedi adottati dall’ordinamento italiano costituiscono solo una parte della necessaria disciplina anticorruzione: la trasparenza amministrativa, disciplinata dal d.lgs. n. 33/2013, da tempo considerata un potente strumento di lotta alla corruzione perché consente l’emersione dei fenomeni corruttivi e mantiene la giusta “pressione” dei cittadini, singoli o organizzati, titolari di un potere di controllo diffuso sul corretto e imparziale svolgimento dell’azione amministrativa; ed i Piani per la prevenzione della corruzione (il Piano Nazionale Anticorruzione a livello nazionale ed il Piano Triennale di Prevenzione della corruzione a livello decentrato) funzionali al monitoraggio delle attività più esposte al rischio della corruzione ed alla pianificazione di interventi mirati a disincentivare l’illegalità delle condotte, prevedendo, evitando e combattendo i fatti corruttivi prima che vengano commessi. In ultima analisi l’attenzione si è spostata sul soggetto a cui sono attribuite le iniziative e su cui ricadono le responsabilità per il funzionamento dell’intero meccanismo preventivo in campo pubblico, il Responsabile della prevenzione della corruzione, fondamentale nel creare una rete di protezione, preventiva, dell’immagine e della funzionalità della Pubblica Amministrazione. La legge n. 190/2012 ha quali destinatari le Pubbliche Amministrazioni, tuttavia, l’articolo 1, comma 34 estende alle società partecipate pubbliche l’assoggettamento, senza limitazione alcuna, dell’ampio spettro degli obblighi corruttivi, al pari delle Amministrazioni propriamente pubbliche. È questa la parte più “delicata” della presente tesi, in quanto tracciare esattamente i confini delle società pubbliche è compito assai complesso, ci si trova spesso innanzi ad una disciplina di difficile collocazione, derivante dalla commistione tra norme privatistiche e deroghe pubblicistiche. L’aspetto maggiormente approfondito in questa seconda parte della presente tesi è stata, come sopra detto, l’estensione della disciplina anticorruttiva alle società partecipate e/o controllate dallo Stato e dagli enti locali. A tal riguardo l’attenzione è stata focalizzata anzitutto sulla Convenzione MEF – ANAC, intesa raggiunta a seguito di un Tavolo congiunto in cui l’ANAC ha adottato delle linee di indirizzo destinate all’intero comparto delle società partecipate dalle Pubbliche Amministrazioni, mentre il MEF con una direttiva si è fatto promotore di una serie di modifiche statutarie in contrasto alla corruzione. L’ultima parte dell’elaborato, affronta il rapporto tra la normativa anticorruzione e il d.lgs. n. 231/2001, partendo dalla disamina di quella che è la responsabilità amministrativa delle persone giuridiche alla luce del decreto 231, ed evidenziando quelli che sono i criteri oggettivi e soggettivi di attribuzione

Group-based Early Start Denver Model: un modello educativo per alunni con Disturbo dello Spettro Autistico nelle scuole dell’infanzia italiane

Research on the implementation of evidence-based-practices in education has increasingly focusedon identifying models for children with autism spectrum disorder (ASD) that can be adaptable inpreschools. This article outlines the main features of the Group-based Early Start Denver Model(G-ESDM), an intervention for children with ASD that has gained prominence in recent years (Vivanti,Duncan, Dawson, Rogers, 2017). Based on the philosophy, principles and strategies of theEarly Start Denver Model (ESDM), the G-ESDM is a manualized evidence-based early interventionthat includes a set of strategies to adapt to the physical and social learning environment in orderto support pupil participation in classroom activities and the school community at large.While the presence of students with Autism Spectrum Disorder (ASD) in Italian school settings representsa challenge for both special education scholars and teachers which has endorsed the paradigmof full inclusion, some reflections on the possibility of promoting the adoption of theG-ESDM in Italian preschools are required. This article outlines the main features of the G-ESDMmodels and concludes by illustrating a possible research itinerary for its implementation in theItalian educational system

Different duplex/quadruplex junctions determine the properties of anti-thrombin aptamers with mixed folding.

Mixed duplex/quadruplex oligonucleotides have attracted great interest as therapeutic targets as well as effective biomedical aptamers. In the case of thrombin-binding aptamer (TBA), the addition of a duplex motif to the G-quadruplex module improves the aptamer resistance to biodegradation and the affinity for thrombin. In particular, the mixed oligonucleotide RE31 is significantly more effective than TBA in anticoagulation experiments and shows a slower disappearance rate in human plasma and blood. In the crystal structure of the complex with thrombin, RE31 adopts an elongated structure in which the duplex and quadruplex regions are perfectly stacked on top of each other, firmly connected by a well-structured junction. The lock-and-key shape complementarity between the TT loops of the G-quadruplex and the protein exosite I gives rise to the basic interaction that stabilizes the complex. However, our data suggest that the duplex motif may have an active role in determining the greater anti-thrombin activity in biological fluids with respect to TBA. This work gives new information on mixed oligonucleotides and highlights the importance of structural data on duplex/quadruplex junctions, which appear to be varied, unpredictable, and fundamental in determining the aptamer functional properties

Heat-shock pretreatment inhibits sorbitol-induced apoptosis in K562, U937 and HeLa cells.

The aim of this study was to determine whether heat-shock pretreatment exerted a protective effect against sorbitol-induced apoptotic cell death in K562, U937 and HeLa cell lines and whether such protection was associated with a decreased cytochrome c release from mithocondria and a decreased activation of caspase-9 and -3. Following heat-shock pretreatment (42 6 0.3C for 1 hr), these cell lines were exposed to sorbitol for 1 hr. Apoptosis was evaluated by DNA fragmentation, whereas caspase-9,-3 activation, cytochrome c release and heat-shock protein70 (HSP70) were assayed by Western Blot. Sorbitol exposure-induced apoptosis in these different cell lines with a marked activation of caspase-9 and caspase- 3, whereas heat-shock pretreatment before sorbitol exposure, induced expression of HSP70 and inhibited sorbitol-mediated cytochrome c release and subsequent activation of caspase-9 and caspase- 3. Similarly, overexpression of HSP70 in the three cell lines studied prevented caspase-9 cleavage and activation as well as cell death. Furthermore, we showed that the mRNA expression of iNOS decreased during both the heat-shock treatment and heat-shock pretreatment before sorbitol exposure. By contrast, the expression of Cu-Zn superoxide dismutase (SOD) and Mn-SOD proteins increased during heat-shock pretreatment before sorbitol exposure. We conclude that, heat-shock pretreatment protects different cell lines against sorbitol-induced apoptosis through a mechanism that is likely to involve SOD family members

Several structural motifs cooperate in determining the highly effective anti-thrombin activity of NU172 aptamer

Despite aptamers are very promising alternative to antibodies, very few of them are under clinical trials or are used as drugs. Among them, NU172 is currently in Phase II as anticoagulant in heart disease treatments. It inhibits thrombin activity much more effectively than TBA, the best-known thrombin binding aptamer. The crystal structure of thrombin-NU172 complex reveals a bimodular duplex/quadruplex architecture for the aptamer, which binds thrombin exosite I through a highly complementary surface involving all three loops of the G-quadruplex module. Although the duplex domain does not interact directly with thrombin, the features of the duplex/quadruplex junction and the solution data on two newly designed NU172 mutants indicate that the duplex moiety is important for the optimization of the protein-ligand interaction and for the inhibition of the enzyme activity. Our work discloses the structural features determining the inhibition of thrombin by NU172 and put the basis for the design of mutants with improved properties

Potential use in the treatment of inflammatory disorders and obesity of selected wild edible plants from Calabria region (Southern Italy)

Abstract The potential role of plants and their metabolites has been recently considered in the search for new well-tolerated anti-arthritic and anti-obesity drugs. This study was designed to assess the potential effectiveness of the methanolic extracts from four wild edible species from Southern Italy, Asparagus officinalis L., Bellis perennis L., Daucus carota L. and Sambucus nigra L. All these plants have a history as anti-rheumatic or anti-arthritic remedies. The chemical constituents were identified through GC–MS and HPTLC analyses and the in vitro antioxidant activity was determined by means of DPPH, ABTS, FRAP-Ferrozine and β-carotene bleaching tests. To assess the anti-inflammatory and anti-arthritic potentials, the capacity to inhibit nitric oxide production in murine macrophage RAW 264.7 cells and protein denaturation was measured. The anti-obesity potential was determined by evaluating the ability of the sample to inhibit pancreatic lipase, a key enzyme for dietary fats absorption. The raw extract of D. carota showed the best inhibitory activity on NO production (IC50 = 45.1 ± 1.0 μg/mL), followed by B. perennis and A. officinalis (IC50 equal to 193.1 ± 3.2 μg/mL and 506.3 ± 5.1 μg/mL, respectively). D. carota induced also inhibitory effects against the heat-induced denaturation of bovine serum albumin (IC50 = 878.7 ± 19.09 μg/mL) and the best lipase inhibitory potential (IC50 = 1.63 ± 0.07 mg/mL). Our findings suggest that this species could be a potential effective therapeutic agent to treat inflammation and arthritis, supporting the traditional popular use of this plant

Thrombin–aptamer recognition: a revealed ambiguity

Aptamers are structured oligonucleotides that recognize molecular targets and can function as direct protein inhibitors. The best-known example is the thrombin-binding aptamer, TBA, a single-stranded 15-mer DNA that inhibits the activity of thrombin, the key enzyme of coagulation cascade. TBA folds as a G-quadruplex structure, as proved by its NMR structure. The X-ray structure of the complex between TBA and human α-thrombin was solved at 2.9-Å resolution, but did not provide details of the aptamer conformation and the interactions with the protein molecule. TBA is rapidly processed by nucleases. To improve the properties of TBA, a number of modified analogs have been produced. In particular, a modified TBA containing a 5′-5′ polarity inversion site, mTBA, has higher stability and higher affinity toward thrombin with respect to TBA, although it has a lower inhibitory activity. We present the crystal structure of the thrombin–mTBA complex at 2.15-Å resolution; the resulting model eventually provides a clear picture of thrombin–aptamers interaction, and also highlights the structural bases of the different properties of TBA and mTBA. Our findings open the way for a rational design of modified aptamers with improved potency as anticoagulant drugs

A Stage-Based Approach to Therapy in Parkinson's Disease.

Parkinson's disease (PD) is a neurodegenerative disorder that features progressive, disabling motor symptoms, such as bradykinesia, rigidity, and resting tremor. Nevertheless, some non-motor symptoms, including depression, REM sleep behavior disorder, and olfactive impairment, are even earlier features of PD. At later stages, apathy, impulse control disorder, neuropsychiatric disturbances, and cognitive impairment can present, and they often become a heavy burden for both patients and caregivers. Indeed, PD increasingly compromises activities of daily life, even though a high variability in clinical presentation can be observed among people affected. Nowadays, symptomatic drugs and non-pharmaceutical treatments represent the best therapeutic options to improve quality of life in PD patients. The aim of the present review is to provide a practical, stage-based guide to pharmacological management of both motor and non-motor symptoms of PD. Furthermore, warning about drug side effects, contraindications, as well as dosage and methods of administration, are highlighted here, to help the physician in yielding the best therapeutic strategies for each symptom and condition in patients with PD