Ruolo della Interleuchina-6 nella colite ulcerosa long-standing: regolazione della p53 ed induzione delle cellule mesenchimali epiteliali

L’infiammazione cronica è un fattore di rischio di insorgenza del cancro, e la citochina infiammatoria IL-6 gioca un ruolo importante nella tumorigenesi. In questo studio abbiamo dimostrato che L’IL-6 down-regola l'espressione e l'attività di p53. In linee cellulari umane, IL-6 stimola la trascrizione dell’rRNA mediante espressione della proteina c-myc a livello post-trascrizionale in un meccanismo p38MAPK-dipendente. L'up-regolazione della biogenesi ribosomiale riduce l'espressione di p53 attraverso l'attivazione della via della proteina ribosomale-MDM2. La down-regolazione di p53 produce l’acquisizione di modifiche fenotipiche e funzionali caratteristiche della epitelio mesenchimale di transizione, un processo associato a trasformazione maligna e progressione tumorale. I nostri dati mostrano che questi cambiamenti avvengono anche nelle cellule epiteliali del colon di pazienti affetti da colite ulcerosa, un esempio rappresentativo di una infiammazione cronica soggetta a trasformazione neoplastica, che scompaiono dopo trattamento con farmaci antinfiammatori. Questi risultati svelano un nuovo effetto oncogenico indotto dall’IL-6 che può contribuire notevolmente ad aumentare il rischio di sviluppare il cancro non solo in pazienti con infiammazioni croniche, ma anche in quei pazienti con condizioni patologiche caratterizzate da elevato livello di IL-6 nel plasma, quali l'obesità e e il diabete mellito di tipo 2.

Elettori e partiti nell'Europa contemporanea: Est ed Ovest a confronto

The research is focused on the origin and the structure of the European party systems in long-standing democracies and in post-communist countries. Considering the differences between the western frozen party systems and the eastern unfrozen party systems, we propose a framework of analysis based on the theoretical and conceptual linkage between genetic approach and spatial theories of competition, identified in the normative component of a cleavage. At first, we propose some operational criteria to distinguish the dimensions of competition from the dimensions of identification through the use of the manifesto project surveys. Then, through the data of an expert survey and of some recent electoral mass surveys, we empirically test a set of propositions concerning, on the one hand, the congruence between party policy positions and party-voters policy positions and, on the other hand, the level of correlation between parties positions on different issue dimensions and their placement on the left-right axis.

Higher-Order Concurrency: Expressiveness and Decidability Results

Higher-order process calculi are formalisms for concurrency in which processes can be passed around in communications. Higher-order (or process-passing) concurrency is often presented as an alternative paradigm to the first order (or name-passing) concurrency of the pi-calculus for the description of mobile systems. These calculi are inspired by, and formally close to, the lambda-calculus, whose basic computational step ---beta-reduction--- involves term instantiation. The theory of higher-order process calculi is more complex than that of first-order process calculi. This shows up in, for instance, the definition of behavioral equivalences. A long-standing approach to overcome this burden is to define encodings of higher-order processes into a first-order setting, so as to transfer the theory of the first-order paradigm to the higher-order one. While satisfactory in the case of calculi with basic (higher-order) primitives, this indirect approach falls short in the case of higher-order process calculi featuring constructs for phenomena such as, e.g., localities and dynamic system reconfiguration, which are frequent in modern distributed systems. Indeed, for higher-order process calculi involving little more than traditional process communication, encodings into some first-order language are difficult to handle or do not exist. We then observe that foundational studies for higher-order process calculi must be carried out directly on them and exploit their peculiarities. This dissertation contributes to such foundational studies for higher-order process calculi. We concentrate on two closely interwoven issues in process calculi: expressiveness and decidability. Surprisingly, these issues have been little explored in the higher-order setting. Our research is centered around a core calculus for higher-order concurrency in which only the operators strictly necessary to obtain higher-order communication are retained. We develop the basic theory of this core calculus and rely on it to study the expressive power of issues universally accepted as basic in process calculi, namely synchrony, forwarding, and polyadic communication.

Asymmetric aminocatalysis: a modern strategy for molecules, challenges and life

The studies conducted during my Phd thesis were focused on two different directions: 1. In one case we tried to face some long standing problems of the asymmetric aminocatalysis as the activation of encumbered carbonyl compounds and the control of the diastereoisomeric ratio in the diastero- and enantioselective construction of all carbon substituted quaternary stereocenters adjacent a tertiary one. In this section (Challenges) was described the asymmetric aziridination of ,-unsaturated ketones, the activation of ,-unsaturated -branched aldehydes and the Michael addition of oxindoles to enals and enones. For the activation via iminium ion formation of sterically demanding substrates, as ,-unsaturated ketones and ,-unsaturated -branched aldehydes, we exploited a chiral primary amine in order to overcome the problem of the iminium ion formation between the catalyst and encumbered carbonylic componds. For the control of diastereoisomeric ratio in the diastero- and enantioselective construction of all carbon substituted quaternary stereocenters adjacent a tertiary one we envisaged that a suitable strategy was the Michael addition to 3 substituted oxindoles to enals activated via LUMO-lowering catalysis. In this synthetic protocol we designed a new bifunctional catalyst with an amine moiety for activate the aldehyde and a tioureidic fragment for direct the approach of the oxindole. This part of the thesis (Challenges) could be considered pure basic research, where the solution of the synthetic problem was the goal itself of the research. 2. In the other hand (Molecules) we applied our knowledge about the carbonylic compounds activation and about cascade reaction to the synthesis of three new classes of spirooxindole in enantiopure form. The construction of libraries of these bioactive compounds represented a scientific bridge between medicinal chemistry or biology and the asymmetric catalysis.

An Innovation System Perspective on Adaptation Strategies to Climate Variability and Water Management in India

Government policies play a critical role in influencing market conditions, institutions and overall agricultural productivity. The thesis therefore looks into the history of agriculture development in India. Taking a political economy perspective, the historical account looks at significant institutional and technological innovations carried out in pre- independent and post independent India. It further focuses on the Green Revolution in Asia, as forty years after; the agricultural community still faces the task of addressing recurrent issue of food security amidst emerging challenges, such as climate change. It examines the Green Revolution that took place in India during the late 1960s and 70s in a historical perspective, identifying two factors of institutional change and political leadership. Climate change in agriculture development has become a major concern to farmers, researchers and policy makers alike. However, there is little knowledge on the farmers’ perception to climate change and to the extent they coincide with actual climatic data. Using a qualitative approach,it looks into the perceptions of the farmers in four villages in the states of Maharashtra and Andhra Pradesh. While exploring the adaptation strategies, the chapter looks into the dynamics of who can afford a particular technology and who cannot and what leads to a particular adaptation decision thus determining the adaptive capacity in water management. The final section looks into the devolution of authority for natural resource management to local user groups through the Water Users’ Associations as an important approach to overcome the long-standing challenges of centralized state bureaucracies in India. It addresses the knowledge gap of why some local user groups are able to overcome governance challenges such as elite capture, while others-that work under the design principles developed by Elinor Ostrom. It draws conclusions on how local leadership, can be promoted to facilitate participatory irrigation management.

Attivita' fisica adattata nella riabilitazione post-ictus: Risultati al follow-up di 12 mesi

L’ictus è un importante problema di salute pubblica, è causa di morte e disabilità nella popolazione anziana. La necessità di strategie di prevenzione secondaria e terziaria per migliorare il funzionamento post-ictus e prevenire o ritardare altre condizioni disabilitanti, ha portato l’Italia a sviluppare un intervento di Attività Fisica Adattata (AFA) per l’ictus, che permettesse di migliorare gli esiti della riabilitazione. Obiettivo dello studio è di valutare se l’AFA unita all’Educazione Terapeutica (ET), rispetto al trattamento riabilitativo standard, migliora il funzionamento e la qualità di vita in pazienti con ictus. Studio clinico non randomizzato, in cui sono stati valutati 229 pazienti in riabilitazione post-ictus, 126 nel gruppo sperimentale (AFA+ET) e 103 nel gruppo di controllo. I pazienti sono stati valutati al baseline, a 4 e a 12 mesi di follow-up. Le misure di esito sono il cambiamento a 4 mesi di follow-up (che corrisponde a 2 mesi post-intervento nel gruppo sperimentale) di: distanza percorsa, Berg Balance Scale, Short Physical Performance Battery, e Motricity Index. Le variabili misurate a 4 e a 12 mesi di follow-up sono: Barthel Index, Geriatric Depression Scale, SF-12 e Caregiver Strain Index. La distanza percorsa, la performance fisica, l’equilibrio e il punteggio della componente fisica della qualità di vita sono migliorate a 4 mesi nel gruppo AFA+ET e rimasti stabili nel gruppo di controllo. A 12 mesi di follow-up, il gruppo AFA+ET ottiene un cambiamento maggiore, rispetto al gruppo di controllo, nell’abilità di svolgimento delle attività giornaliere e nella qualità di vita. Infine il gruppo AFA+ET riporta, nell’ultimo anno, un minor numero di fratture e minor ricorso a visite riabilitative rispetto al gruppo di controllo. I risultati confermano che l’AFA+ET è efficace nel migliorare le condizioni cliniche di pazienti con ictus e che gli effetti, soprattutto sulla riabilitazione fisica, sono mantenuti anche a lungo termine.

Alle origini del «romanzo giudiziario» italiano: la figura del delinquente tra letteratura, diritto e scienze mediche

In questo lavoro si conduce un’indagine sulle relazioni tra letteratura, diritto e scienze mediche all’interno del romanzo cosiddetto "giudiziario", sviluppatosi in Italia nel periodo compreso tra l’Unità e i primi anni del XX secolo. La nostra analisi si concentra in particolare sulla costruzione della figura del delinquente, intesa come prodotto specifico della suddetta relazione interdisciplinare. In questa prospettiva, abbiamo rilevato che la caratterizzazione di tale figura costituisce il principale tra i procedimenti narrativi osservabili in vari romanzi del periodo postunitario. Concentrandoci inoltre sulla definizione del genere, abbiamo affrontato l’ormai annoso dibattito sulla nascita (quando non sull’esistenza stessa) del poliziesco italiano, dimostrando come solo all’interno di una stretta relazione tra letteratura, diritto e scienze mediche sia possibile cogliere a pieno il valore di questi romanzi nel processo di costruzione dell’identità nazionale. Il lavoro è diviso in due parti. Nella prima, di carattere storico, si propone una nuova definizione del genere "giudiziario", dopo aver vagliato e discusso le ipotesi sino ad ora avanzate dalla critica. Nella seconda parte si affrontano due casi di studio esemplari: La colonia felice di Carlo Dossi e Il romanzo di Misdea di Edoardo Scarfoglio. Su ognuno di essi abbiamo condotto un’accurata analisi testuale, che ci ha permesso di esaminare la caratterizzazione delle diverse figure delinquenti dimostrando l’efficacia del metodo interdisciplinare adottato con particolare riguardo alle teorie di Cesare Lombroso.

Understanding Recent Developments in the Turkish Labor Market: Empirical Essays with a Gender Focus

This dissertation comprises three essays on the Turkish labor market. The first essay characterizes the distinctive characteristics of the Turkish labor market with the aim of understanding the factors lying behind its long-standing poor performance relative to its European counterparts. The analysis is based on a cross-country comparison among selected European Union countries. Among all the indicators of labor market flexibility, non-wage cost rigidities are regarded as one of the most important factors in slowing down employment creation in Turkey. The second essay focuses on an employment subsidy policy which introduces a reduction in non-wage costs through social security premium incentives granted to women and young men. Exploiting a difference-in-difference-in differences strategy, I evaluate the effectiveness of this policy in creating employment for the target group. The results, net of the recent crisis effect, suggest that the policy accounts for a 1.4% to 1.6% increase in the probability of being hired for women aged 30 to 34 above men of the same age group in the periods shortly after the announcement of the policy. In the third essay of the dissertation, I analyze the labor supply response of married women to their husbands' job losses (AWE). I empirically test the hypothesis of added worker effect for the global economic crisis of 2008 by relying on the Turkey context. Identification is achieved by exploiting the exogenous variation in the output of male-dominated sectors hard-hit by the crisis and the gender-segmentation that characterizes the Turkish labor market. Findings based on the instrumental variable approach suggest that the added worker effect explains up to 64% of the observed increase in female labor force participation in Turkey. The size of the effect depends on how long it takes for wives to adjust their labor supply to their husbands' job losses.

The Integrated European Project "GEHA - GEnetics of Healthy Aging": recruitment, health status assessment and survival of the Italian 90+ sibpairs

The present study is part of the EU Integrated Project “GEHA – Genetics of Healthy Aging” (Franceschi C et al., Ann N Y Acad Sci. 1100: 21-45, 2007), whose aim is to identify genes involved in healthy aging and longevity, which allow individuals to survive to advanced age in good cognitive and physical function and in the absence of major age-related diseases. Aims The major aims of this thesis were the following: 1. to outline the recruitment procedure of 90+ Italian siblings performed by the recruiting units of the University of Bologna (UNIBO) and Rome (ISS). The procedures related to the following items necessary to perform the study were described and commented: identification of the eligible area for recruitment, demographic aspects related to the need of getting census lists of 90+siblings, mail and phone contact with 90+ subjects and their families, bioethics aspects of the whole procedure, standardization of the recruitment methodology and set-up of a detailed flow chart to be followed by the European recruitment centres (obtainment of the informed consent form, anonimization of data by using a special code, how to perform the interview, how to collect the blood, how to enter data in the GEHA Phenotypic Data Base hosted at Odense). 2. to provide an overview of the phenotypic characteristics of 90+ Italian siblings recruited by the recruiting units of the University of Bologna (UNIBO) and Rome (ISS). The following items were addressed: socio-demographic characteristics, health status, cognitive assessment, physical conditions (handgrip strength test, chair-stand test, physical ability including ADL, vision and hearing ability, movement ability and doing light housework), life-style information (smoking and drinking habits) and subjective well-being (attitude towards life). Moreover, haematological parameters collected in the 90+ sibpairs as optional parameters by the Bologna and Rome recruiting units were used for a more comprehensive evaluation of the results obtained using the above mentioned phenotypic characteristics reported in the GEHA questionnaire. 3. to assess 90+ Italian siblings as far as their health/functional status is concerned on the basis of three classification methods proposed in previous studies on centenarians, which are based on: • actual functional capabilities (ADL, SMMSE, visual and hearing abilities) (Gondo et al., J Gerontol. 61A (3): 305-310, 2006); • actual functional capabilities and morbidity (ADL, ability to walk, SMMSE, presence of cancer, ictus, renal failure, anaemia, and liver diseases) (Franceschi et al., Aging Clin Exp Res, 12:77-84, 2000); • retrospectively collected data about past history of morbidity and age of disease onset (hypertension, heart disease, diabetes, stroke, cancer, osteopororis, neurological diseases, chronic obstructive pulmonary disease and ocular diseases) (Evert et al., J Gerontol A Biol Sci Med Sci. 58A (3): 232-237, 2003). Firstly these available models to define the health status of long-living subjects were applied to the sample and, since the classifications by Gondo and Franceschi are both based on the present functional status, they were compared in order to better recognize the healthy aging phenotype and to identify the best group of 90+ subjects out of the entire studied population. 4. to investigate the concordance of health and functional status among 90+ siblings in order to divide sibpairs in three categories: the best (both sibs are in good shape), the worst (both sibs are in bad shape) and an intermediate group (one sib is in good shape and the other is in bad shape). Moreover, the evaluation wanted to discover which variables are concordant among siblings; thus, concordant variables could be considered as familiar variables (determined by the environment or by genetics). 5. to perform a survival analysis by using mortality data at 1st January 2009 from the follow-up as the main outcome and selected functional and clinical parameters as explanatory variables. Methods A total of 765 90+ Italian subjects recruited by UNIBO (549 90+ siblings, belonging to 258 families) and ISS (216 90+ siblings, belonging to 106 families) recruiting units are included in the analysis. Each subject was interviewed according to a standardized questionnaire, comprising extensively utilized questions that have been validated in previous European studies on elderly subjects and covering demographic information, life style, living conditions, cognitive status (SMMSE), mood, health status and anthropometric measurements. Moreover, subjects were asked to perform some physical tests (Hand Grip Strength test and Chair Standing test) and a sample of about 24 mL of blood was collected and then processed according to a common protocol for the preparation and storage of DNA aliquots. Results From the analysis the main findings are the following: - a standardized protocol to assess cognitive status, physical performances and health status of European nonagenarian subjects was set up, in respect to ethical requirements, and it is available as a reference for other studies in this field; - GEHA families are enriched in long-living members and extreme survival, and represent an appropriate model for the identification of genes involved in healthy aging and longevity; - two simplified sets of criteria to classify 90+ sibling according to their health status were proposed, as operational tools for distinguishing healthy from non healthy subjects; - cognitive and functional parameters have a major role in categorizing 90+ siblings for the health status; - parameters such as education and good physical abilities (500 metres walking ability, going up and down the stairs ability, high scores at hand grip and chair stand tests) are associated with a good health status (defined as “cognitive unimpairment and absence of disability”); - male nonagenarians show a more homogeneous phenotype than females, and, though far fewer in number, tend to be healthier than females; - in males the good health status is not protective for survival, confirming the male-female health survival paradox; - survival after age 90 was dependent mainly on intact cognitive status and absence of functional disabilities; - haemoglobin and creatinine levels are both associated with longevity; - the most concordant items among 90+ siblings are related to the functional status, indicating that they contain a familiar component. It is still to be investigated at what level this familiar component is determined by genetics or by environment or by the interaction between genetics, environment and chance (and at what level). Conclusions In conclusion, we could state that this study, in accordance with the main objectives of the whole GEHA project, represents one of the first attempt to identify the biological and non biological determinants of successful/unsuccessful aging and longevity. Here, the analysis was performed on 90+ siblings recruited in Northern and Central Italy and it could be used as a reference for others studies in this field on Italian population. Moreover, it contributed to the definition of “successful” and “unsuccessful” aging and categorising a very large cohort of our most elderly subjects into “successful” and “unsuccessful” groups provided an unrivalled opportunity to detect some of the basic genetic/molecular mechanisms which underpin good health as opposed to chronic disability. Discoveries in the topic of the biological determinants of healthy aging represent a real possibility to identify new markers to be utilized for the identification of subgroups of old European citizens having a higher risk to develop age-related diseases and disabilities and to direct major preventive medicine strategies for the new epidemic of chronic disease in the 21st century.