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Exploring RHOGTPases: a computational study of protein-protein interactions and drug design
Get PDFThe CDC42 RHOGTPases subfamily (RHOJ, RHOQ, CDC42) is often overexpressed but rarely mutated in cancer. These GTPases play a critical role in governing both the invasiveness of tumor cells into nearby tissues and the ability of endothelial cells to establish blood vessels within tumors. A key pathway involves the interaction between CDC42 proteins and the serine/threonine kinase PAK, which activates downstream signaling. This interaction is a crucial juncture, initiating and transmitting signaling downstream, ultimately influencing cellular behavior and disease progression. Recognizing the importance of this interaction, computer-aided drug design has been utilized to identify a new class of inhibitor compounds specifically targeting the CDC42 subfamily. This strategic approach aimed to interfere in this critical pathway and potentially impede cancer progression. Moreover, the study utilized alchemical free energy calculations to quantitatively and accurately evaluate the effect of mutations at the protein–protein interface, using the CDC42/PAK interaction as a test case. The study demonstrated an excellent agreement between computed and experimental data on binding affinity. A meticulous analysis of the sidechain conformations of the mutated residues was crucial in enhancing the accuracy of the computed estimates, effectively addressing limitations associated with sampling. This study underscored the advantage of integrating alchemical free energy calculations into the design of experimental mutagenesis studies, highlighting the potential for this approach to significantly contribute to understand the complex protein interactions and guide drug development strategies. In accordance with these findings, the study extended the analysis to the RHOA/ROCK1 interface, which is also heavily implicated in cancer. Preliminary results from alchemical free energy calculations on RHOA mutants lay the foundation for utilizing this methodology to identify hotspot residues crucial for the interaction between these two proteins. Ultimately, this method has the potential to facilitate the exploration of new targetable interactions, contributing to the development of novel tailored therapeutics
Work and art. Trade guilds in the Bolognese Renaissance
Get PDFDalla seconda metà del XII secolo allo scorcio del XVIII le corporazioni di mestiere, pur avendo subito profonde modificazioni, mantennero sempre la loro funzione di garante degli interessi delle categorie di cui erano espressione e instaurarono, mediante la redazione di statuti, un meccanismo di solidarietà fra i rispettivi membri. Esse costituirono dunque il principale punto di forza dell’economia cittadina, senza tralasciare l’attività in campo sociale e assistenziale.
La presente ricerca analizza la produzione artistica del Rinascimento bolognese da un punto di vista inedito, quello appunto delle compagnie di mestiere. Se infatti sono già stati condotti significativi studi relativi alla committenza aristocratica, a quella delle confraternite e degli ordini religiosi e a quella connessa allo Studium, mai fino ad ora si è focalizzata l’attenzione sul ruolo rivestito dalle corporazioni nella fioritura delle arti figurative nel XV secolo.
Ad essere indagati sono, insieme ai meccanismi e alle particolari vie che consentirono alle corporazioni di accaparrarsi le prestazioni degli artisti più affermati ma anche quelle di maestri più insoliti, i luoghi destinati ad accogliere le opere da essi realizzate: le cappelle e le sale d’adunanza nelle rispettive residenze, spazi nevralgici della vita corporativa che determinarono la messa a punto di manufatti specifici. Oltre a questi ambienti, destinati alla fruizione degli iscritti, le Arti possedevano una cappella nelle chiese cittadine. Anche tali sacelli furono allestiti con dispendiosi apparati ornamentali, che li portarono a gareggiare, in sontuosità e ricchezza, con quelli posseduti dalle autorità civili e religiose.
Al fine di mettere in luce le peculiarità della committenza artistica delle corporazioni bolognesi, si propone un’analisi comparativa con quella, più diffusamente studiata, delle Scuole di devozione veneziane. La tesi affronta anche argomenti di interesse trasversale, in particolare di natura socioeconomica, come le modalità di accesso e le possibilità di impiego nel mercato artistico bolognese del XV secolo.From the second half of the 12th century to the end of the 18th century, the trade guilds, although profoundly modified, always maintained their function as guarantors of the interests of those categories of which they were expression and established, through drafting statutes, a mechanism of solidarity between their members. They thus constituted the main strength of city’s economy, without neglecting activity in social and welfare fields.
This research examines the artistic production of the Bolognese Renaissance from a new point of view, that of the trade guilds. While significant studies have already been conducted on aristocratic patronage, on that of confraternities and religious orders and on that connected to the Studium, we have never until now focused on the role played by guilds in the flourishing of figurative arts in the 15th century.
My thesis also investigates the spaces destined to house the works made for the guilds, as well as the mechanisms and particular ways in which the guilds were able to employ the artists, sometimes very famous and in other cases more unusual. Among the places possessed by guilds were the chapels and meeting rooms in their residences, key areas that determined a development of specific artefacts. In addition to these locations, intended for the use of members only, the guilds owned a chapel in city churches. These chapels were equipped with elaborate decorations that brought them to compete, in sumptuousness and wealth, with those owned by the civil and religious authorities.
To highlight the peculiarities of the artistic patronage of Bolognese guilds, a comparative analysis with that of the more extensively studied Venetian Schools of Devotion is proposed. My thesis also addresses topics of transversal interest, of a socio-economic nature, such as access and employment opportunities in 15th century Bolognese art market
Struggling for the narrative: communication strategies of the government and the opposition in the non-democratic context (the case of Russia)
Get PDFThis study examines how key actors within authoritarian regimes (government and opposition) use different political communication strategies to achieve their strategic goals: maintaining and changing the political status quo, respectively. I study the Russian case as a prime example of an informational or electoral autocracy. My dissertation explores how the government communicates with its loyal citizens and the vertical power structure, including regional and local subordinates. The research also investigates the opposition's strategies to polarize society and examines public responses to these endeavors. The study highlights how Russian central authorities utilize online citizens’ feedback mechanisms to signal to regional elites that their internal political processes and performance are being monitored. I show that the effectiveness of regional elites in building political machines is associated with the Kremlin's semi-official interactions with the regional elites. Focusing on the opposition, the research specifically analyzes the YouTube community formed around Alexei Navalny. I provide empirical evidence on the relatively short-term affective attunement induced by a leader promising social changes within an authoritarian context. I show how the incivility of messages plays a role in further involving commenters in discussions. Users avoid extreme incivility when interacting with other commenters, but uncivil comments are more likely to start discussion threads. Pro-government sentiments are associated with a subsequent response from Navalny’s supporters to the out-group criticism and contribute to the further formation of hubs with a pro-government narrative. From a broader perspective, the dissertation sheds light on the nature of authoritarian control, which involves not just coercion but also persuasion and gaining the loyalty of citizens. It also reveals that opposition communities on social media in Russia's non-democratic context do not entirely isolate their members from opposing viewpoints. Instead, exposure to contrary ideas unifies the group and strengthens their collective identity
The X-ray appearance of galaxy clusters - properties, discontinuities and anomalies of the intracluster medium distribution
Get PDFThe Intracluster medium (ICM) is the best archive to consult when we want to retrieve information about the past and recent history of galaxy clusters. All those processes that can affect the dynamical state of these systems, such as merger events, are indeed expected to leave traces in the ICM distribution, both in the form of variations of integrated quantities and local edges and discontinuities. The detailed analysis of the X-ray morphology of galaxy clusters and its link to the non-thermal components have been the main goal of this PhD Thesis. Most of the studies carried out to investigate this topic have been realised using the complete XMM-Newton observations of the 118 galaxy clusters that are part of the Cluster HEritage project with XMM-Newton Mass Assembly and Thermodynamics at the Endpoint of structure formation (CHEX-MATE). These X-ray maps allowed us to inspect the ICM distribution of the CHEX-MATE systems looking for an answer to the question: How do galaxy clusters appear
In the shadow of the Counter-Reformation: italian women poets between networks of relations and patronage in the second half of the 16th century
Get PDFQuesto lavoro di ricerca si concentra sulla scrittura femminile del XVI secolo in Italia da una prospettiva storica, culturale e religiosa. Lo studio si focalizza su cinque autrici attive dopo il 1550: Laura Battiferri, Laura Terracina, Chiara Matraini, Moderata Fonte e Lucrezia Marinelli. Sulla base delle loro opere e dei documenti d'archivio, è stato possibile ricostruire la rete di relazioni intrattenuta da ciascuna di loro con i protagonisti della cultura italiana contemporanea. Al centro delle loro attività non ci fu solo la promozione della scrittura femminile, ma anche le nuove idee religiose che circolavano nella penisola al tempo della Riforma. Costoro instaurarono un dialogo costante con altre autrici considerate dei modelli ma anche con umanisti e mecenati che contribuirono al loro successo. Dopo un aumento del numero di scrittrici dopo la morte di Vittoria Colonna, la produzione letteraria femminile sembrò rallentare tra il 1560 e il 1580. Tuttavia, negli anni precedenti la chiusura del Concilio di Trento, la questione confessionale e la scrittura letteraria si erano alimentate a vicenda, in un dialogo costante favorito da poligrafi, editori, letterati e letterate. Quando queste reti scomparvero attorno al 1580, la produzione femminile successiva dovette essere riorientata: le scrittrici procedettero così a costruire uno 'spazio ideale' all'interno del quale fu possibile scambiare idee, libri e approcci religiosi. Questa ricerca riguarda quindi un nodo fondamentale della scrittura femminile durante la Controriforma e fornisce una migliore comprensione di come la produzione femminile fu influenzata dalla pressione religiosa e sociale. Ciò ha portato a ripensare i confini cronologici che i critici solitamente attribuiscono al XVI secolo: i dati raccolti illustrano come il periodo tridentino non sia stato un momento spartiacque oltre il quale la produzione femminile si sarebbe fermata, ma una fase decisiva nell'evoluzione della loro attività letteraria, con un incremento significativo della produzione delle scrittrici.This research work focuses on 16th century women's writing in Italy. The study focuses on five authors active from 1550 onwards: Laura Battiferri, Laura Terracina, Chiara Matraini, Moderata Fonte and Lucrezia Marinelli. On the basis of their works and archive documents, it was possible to reconstruct the network of relationships each of them had with the protagonists of contemporary Italian culture. At the centre of their activities was not only the promotion of women's writing, but also the new religious ideas circulating in the peninsula at the time of the Reformation. They established a constant dialogue with other female authors who were regarded as role models, but also with humanists and patrons who contributed to their success. After an increase in the number of female writers, female literary production seemed to slow down between 1560 and 1580. However, in the years before the closing of the Council of Trent, the confessional question and literary writing had fed off each other, in a constant dialogue fostered by men of letters and women of letters. When these networks disappeared around 1580, subsequent female production had to be reoriented: women writers thus proceeded to construct an 'ideal space' within which it was possible to exchange ideas, books and religious approaches. This research thus concerns a fundamental node of women's writing during the Counter-Reformation and provides a better understanding of how women's production was influenced by religious and social pressure. This has led to a rethinking of the chronological boundaries that critics usually attribute to the 16th century: the data collected illustrate that the Tridentine period was not a watershed moment beyond which women's production would come to a halt, but a decisive phase in the evolution of their literary activity, with a significant increase in the production of women writers
Evaluation of genetic factors involved in the onset of breast muscle abnormalities affecting fast-growing chickens
No full textTo meet the increasing consumer demand for chicken meat, poultry companies implemented intensive breeding programs to improve the productive performances of modern broilers, which indirectly led to the occurrence of muscular abnormalities, namely white striping (WS) and wooden breast (WB) defects. Despite the enormous progress in understanding their primary causes, the precise etiology remains to be clarified. This dissertation aimed at providing new insight on the underlying mechanisms of these abnormalities by implementing different approaches of gene and protein expression analysis. Since the central hypothesis was the differing gene and protein expression profiles of breast muscles affected and unaffected by these defects, the studies dealt with i) investigation of patterns of co-expressed genes associated with the phenotypic traits significantly related to the onset of WS and WB; ii) gene and protein expression analyses of key factors likely involved in the manifestation of these defects by looking at multiple steps of muscle development of broilers selected for different growth rates; and iii) characterization of WB muscles by performing a differential gene expression analysis. The results strengthened the evidence of a complex etiology of these myopathies and put forward molecular and cellular key players potentially involved in the WS and WB onset, such as one of the major extracellular matrix components: the Collagen type IV. Also, genes potentially involved in the molecular alterations characterizing these abnormalities were found, e.g. the peroxisome proliferator-activated receptor co-activator 1 (PCG1) alpha and beta, and the fibro-adipogenic progenitors (FAPs). The outcomes of this thesis also corroborated that vimentin and desmin can be considered potential markers of the regenerative processes occurring in abnormal breast muscles. Overall, these achievements may be useful to reduce the incidence of breast myopathies in broilers by identifying biomarkers likely suitable to exclude broilers prone to develop WS and WB from breeding practices
Innovative technologies for climate-resilient food production systems: strategies to increase resource use efficiency in a vertical farm with artificial light
Get PDFVertical farms (VFs) with artificial light are a typology of indoor urban agriculture systems where all the environmental parameters can be fully controlled. Thanks to the high level of technology adopted in these systems and to the possibility to integrate them within the urban metabolism, VFs have the potential to enhance climate change resilience of crop production. However, in order to maximize resource use efficiency, it is necessary to improve growing conditions according to crops’ need. In this context, the goal of this thesis is the optimization of growing system management and artificial lighting conditions aimed at increasing production and resource use efficiency for lettuce (Lactuca sativa) cultivation in VF. In this work, several cultivation trials were conducted in indoor cultivation systems with LED lights, investigating the variation in morphological, physiological, and biochemical parameters of crops when different growth systems were used or different light conditions were applied (use of pulsed light, variation of spectral conditions, light intensity and photoperiod). The results showed how the use of a high-pressure aeroponic system could increase water use efficiency compared to an ebb and flow system (+114%), and how the water recovery from the growth chamber dehumidifier could reduce water use by 67%, increasing water use efficiency by 206%. The results concerning light management showed the potential of pulsed light in modulating the content of secondary metabolites in leaves and the role of far-red radiation in increasing lighting energy use efficiency compared to a spectrum with only red and blue radiation (increase ranging 29 to 67% depending on the amount of far-red radiation and light intensity provided). Within this work, the effect on lettuce growth, morphology and physiology are discussed within the various chapters to explain the mechanisms leading to a more efficient use of resources in a VF with artificial light
Organized crime, violence and State response
Get PDFThe first chapter of this PhD thesis develops a model analysing the interplay between the Italian state and mafias. I show that targeting criminal profitability reduces conflicts within criminal organizations but increases retaliation against the state, while law enforcement decreases both. Using assassinations of public officers as the dependent variable, I support these findings by exploiting the introduction of Italy's asset forfeiture law and instrumenting confiscations with exogenous variations in US drug demand. This highlights three major epochs of post-WWII Italian history: the corrupted state, the enforcement-retaliation, and the sinking.
Chapter two examines the effects of targeted repression of organized crime on inter-clan violence and illegal activity. We investigate the trade-off between curbing violence and illegal activity. If clans fight for territorial control, targeting the strongest reduces violence; however, if surviving clans are the most productive, it boosts illegal activity and profits. Targeting the weakest clans has opposite effects. If clans maintain a peaceful territory-splitting agreement, targeting the strongest may raise violence by triggering a succession war. Conversely, targeting the weakest may let the strongest thrive peacefully. Our theoretical analysis interprets the evolution of violence and illegal activity after different repressive policies in Italy, Mexico, and Colombia.
Chapter three presents a model revealing that economically disadvantaged factions gain the most from warfare, even if outnumbered or outgunned. This is because they have more to gain and less to lose from the conflict. Targeting the most aggressive belligerents could paradoxically fuel new conflicts, as shifts in asymmetry may tempt rival factions to attack. I test these predictions using a database on militarized interstates disputes spanning the last two centuries and instrumenting countries' GDP per capita differences with exogenous variations in rainfall
From methodological challenges to empirical insights: reassessing income inequality and instability
Get PDFIn the current epoch of globalisation, technological upheaval, and socio-economic transformations, the study of income inequality and instability is paramount. As the world changes and confronts monumental challenges, from financial crises to pandemics and inflation, understanding the nuances and intricacies of income distribution and inequality dynamics helps to effectively identify and mitigate the difficulties that people face while world and national economies evolve.
The title of this manuscript, ”From Methodological Challenges to Empirical Insights: Reassessing Income Inequality and Instability”, encapsulates a journey from grappling with methodological challenges to deriving profound empirical insights into the dynamics of inequality and instability. This thesis is the result of research work that I carried out during my Ph.D. in Economics at the University of Bologna and during my visiting at the Organisation for Economic Co-operation and Development (OECD). It provides a methodological discussion to guide and improve the assessment of income inequality and income instability
The expression of definiteness in Italian narratives by bilingual children: experimental study, and teaching applications
Get PDFThe aim of this study is to analyze the expression of definiteness in a narrative task in Italian administered to bilingual and monolingual children (aged 4;0-8;3 years). Three groups of bilingual children were examined, all with Italian as the societal language and three different family languages: Spanish, Arabic, and Chinese. Noun phrases (NPs) were extracted from narrative productions and coded based on whether the referent in the story was identifiable to the interlocutor. The form of the determiner (definite, indefinite, demonstrative, or bare noun) was also coded. The analysis investigated if the distribution of forms according to identifiability was the same across all groups. The results revealed that all children are sensitive to the abstract dimension of referent identifiability. The groups speaking Arabic and Spanish as their family language showed a distribution of determiners similar to monolinguals, while the Chinese-speaking group emerged as different, displaying a preference for bare nouns or demonstratives when the referent is identifiable. This was interpreted as an effect of the family language on Italian. Examining the impact of internal (linguistic and cognitive) and external (quantity and quality of input) factors, an interplay between morphosyntactic and pragmatic competence in referential choices was observed. Among external factors, linguistically challenging and engaging activities in Italian (e.g., multimedia games, free play with peers, reading) seem to have a positive impact on children’s referential skills. The study concluded with a pedagogical proposal experimenting the positive effects of multilingual narrative as a teaching tool in linguistically super-diverse classrooms