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Insight into the molecular and functional determinants of HP1043, the essential master regulator of Helicobacter pylori.
Helicobacter pylori is one of the most widespread and successful human pathogens, colonizing half of the population stomach mucosa and causing gastric malignancies in 1% of carriers. Due to the increasing number of antimicrobial-resistant strains, in 2017 the WHO included H. pylori among pathogens that pose a major threat for humankind.
In this study, we propose as a molecular target for novel antimicrobial strategies HP1043, an orphan response regulator essential for the viability of H. pylori as it orchestrates all the most important cellular processes. Amino acids most relevant for HP1043 dimerization and target DNA recognition were identified and used to guide an in-silico protein-DNA docking and generate a high-resolution structural model of the interacting HP1043 dimer and its target DNA. The model was experimentally validated and exploited to carry out a virtual screening of small molecule libraries, identifying 8 compounds potentially able to interfere with HP1043 function and likely block H. pylori infection.
A second line of research aimed at the characterization of the regulatory function of HP1043 and the tight mechanisms of regulation of hp1043 gene expression. In particular, we proved a direct interaction between HP1043 and the housekeeping sigma80 factor of the RNA polymerase. A conditional mutant H. pylori strain overexpressing a synthetic copy of the hp1043 gene altered in nucleotide sequence yet encoding the wild-type protein was generated, achieving increased intracellular levels of HP1043. However, overexpression of HP1043 did not result in an upregulation of target genes transcription nor modulation of hp1043 transcript levels, pinpointing the existence of multiple overlayed mechanisms of regulation that affect both protein levels and functionality as well as maintain steady the amount of hp1043 transcript. Finally, we proposed that a mechanism of post-transcriptional regulation could depend on an antisense transcript to the hp1043 gene which was validated in two different strains
New Metal Tetrazolate Complexes: Design, Synthesis, Characterization and Applications
This final thesis is aimed at summarizing the research program I have carried out during my PhD studies, that has been dealing with the design, the preparation, characterization and applications of new Re(I), Ru(II), and Ir(III) metal complexes containing anionic ligands such as 5-aryl tetrazolates [R-CN4]- or their neutral analogues, N-alkyltetrazoles [R-CN4-R1].
Chapter 1 consists of a brief introduction on tetrazoles and metal-tetrazolato complexes, and on the photophysical properties of d6 transition metal complexes.
In chapter 2, the synthesis, characterization and study of the photophysical properties of new luminescent Ir(III)-tetrazolate complexes are discussed. Moreover, the application of one of the new Ir(III)-CN complexes as emissive core in the fabrication of an OLED device is reported.
In chapter 3, the study of the antimicrobial activity of new Ru(II)-alkyltetrazole complexes is reported. When the pentatomic ring was substituted with a long alkyl residue, antimicrobial activity toward Deinococcus radiodurans was observed.
In chapter 4, a new family of luminescent Re(I)-tetrazolate complexes is reported. In this study, different N-alkyl tetrazoles play the role of diimine (diim) ligands in the preparation of new Re(I) tricarbonyl complexes. In addition, absorption and emission titration experiments were performed to study their interaction with Bovine Serum Albumin (BSA).
In chapter 5, the synthesis and characterization of new luminescent Re(I)-tetrazolate complexes are discussed. The use of sulfonated diimine ligands in the preparation of new Re(I) tricarbonyl complexes led to the first example Re(I) complexes for the luminescent staining of proteins.
In chapter 6, the synthesis, a new family of Ir(III)-NO2 tetrazole complexes displaying unexpected photophysical properties are discussed. Moreover, the possibility to tune the luminescent output of such systems upon chemical modification of the pending nitro group was verified by performing reduction tests with sodium dithionite; this represents encouraging evidence for their possible application as hypoxia-responsive luminescent probes in bioimaging
The Use of Habitat Management, Elicitors and Augmentation to Improve Biological Control in Vineyard
Nowadays, pesticides represent the most common tool used to control pests in agriculture. Because of the detrimental effects both on environment and human health related to chemical defence strategies, more ecological approaches need to be tested.
My dissertation aims to evaluate some sustainable biological control strategies in vineyard. Natural enemy (Anagyrus vladimiri Triapitsyn (Hymenoptera: Encyrtidae) and Cryptolaemus montrouzieri (Mulsant) (Coleoptera: Coccinellidae)) were released against mealybugs (Hemiptera: Pseudococcidae) and the role of tending ants was investigated in beneficial-mealybug-ant tritrophic relation. Habitat management approaches were adopted to mitigate Lobesia botrana (Denis & Schiffermüller) (Lepidoptera: Tortricidae) infestation and enhance beneficial activity. Finally, silica gel, a silicon-derived compound, was tested to study its potential role in eliciting plant defence response, including parasitoid attraction. Field trials were carried out in Northern Italy, in important viticultural areas of Lambrusco and Pignoletto wines.
Results showed the great potentiality of A. vladimiri and C. montrouzieri in controlling both Planococcus ficus (Signoret) and Pseudococcus comstocki Kuwana infestation. The use of sugar dispensers to disrupt ant activity increased ecosystem services and reduced mealybug infestation. Ground cover management did not reduce L. botrana infestation, but it boosted parasitoid biodiversity. Finally, the treatments with silica gel enhanced the attraction towards three important Hymenoptera parasitoid families: Mymaridae, Encyrtidae and Braconidae.
In conclusion, these strategies showed a potential both in suppressing pest infestation and enhancing natural enemy activity and attraction. Further studies should focus on combining environmentally-friendly practices, creating a synergistic effect which has the potentiality to reduce or even avoid insecticide treatments in some vineyard context
The merger-driven evolution of early-type galaxies and the connection with their dark matter halos
Massive early-type galaxies (ETGs) are "red and dead" systems mainly composed by old and metal-rich stellar populations. In a cosmological context, present-day ETGs are believed to be the remnants of a complex stellar mass assembly history marked by several mergers, which are the consequence of the underlying hierarchical assembly of their host dark matter halos.
This Ph.D. thesis deals mainly with the merger-driven evolution of ETGs, studying how scaling relations evolve across cosmic time, how the stellar populations of the progenitors settled into the remnant galaxies, and how the mass of the host dark matter halos can be inferred from other galaxy properties.
In the first part, I will present the results of the first systematic study in the literature of the evolution of the scaling relation that links the stellar mass of ETGs to their stellar velocity dispersion. By exploiting a Bayesian hierarchical formalism, I tested different functional forms to investigate how the stellar mass–velocity dispersion relation may vary as a function of redshift.
In the second part, I will illustrate a comparison between observed ETGs from the MaNGA survey and simulated galaxies from the cosmological simulation suite IllustrisTNG. The aim of this project is to provide an interpretative scenario of the stellar mass assembly history of present-day ETGs, comparing the radial distributions of their stellar properties with those of simulated galaxies, in which we can disentangle the role of stars formed in situ and stars formed ex situ.
Finally, I will exhibit the preliminary results of a project aimed at inferring the dark matter mass of halos hosting galaxies of the IllustrisTNG simulation, using Explainable Boosting Machine. I will show the strength of this new machine learning method that allows us to provide a prediction for the dark matter halo mass using several galaxy properties
Submarine Landslides in the Central Mediterranean: Causes and Recurrences
This thesis (SLATE-project, https://www.itn-slate.eu/) is concentrated on submarine landslides in the central Mediterranean Sea. Commonly found in marine and lacustrine environments, submarine landslides represent one of the main mechanisms of sediment transport along continental margins, their volumes can be far larger than any terrestrial landslides and have potential to produce far-reaching tsunamis that can rival those produced by earthquakes. However, many uncertainties remain concerning their preconditioning factors, triggering mechanisms, return frequencies and relationship with climate change as well as their geohazard potential, which vary depending on their location.
Newly identified submarine landslides emplaced in the Gela Basin (GB; south of Sicily, central Mediterranean Sea) were investigated where the particular geodynamic and oceanographic context and the limited extent basin is ideal for submarine landslides research. The investigation through multiple data types including deep boreholes, multi-channel and subbottom seismic profiles, sediment cores and swath bathymetry revealed the emplacement of multiple submarine landslides during the margin outbuilding in the Pliocene-Quaternary with a drastic transition in their volumes and emplacement location at the Middle-Pleistocene Transition (MPT). This change, accompanied by an accelerated margin outbuilding from 150 to 900 m/kyr and growth of the contourite deposits, has been related to the decreasing tectonic activity at the southern front of the Maghrebian fold-and-thrust belt and the climatic changes linked to the switch to the 100-kyr Milankovitch cyclicity. Numerical in-house codes used for the reconstruction of two small-size MTDs located at the ends of the GB show similar potential of generating high-wave tsunamis that can impact the coasts of Malta and Sicily but different triggering mechanisms based on the stability analysis. A multiproxy approach made on the sediment cores revealed that strong bottom currents and very-high sedimentation rate fluctuations, associated with sea-level changes, affected the stability of contourite deposits and contributed to the recurrent emplacement of MTDs
Automatic Speech Recognition (ASR) and NMT for Interlingual and Intralingual Communication: Speech to Text Technology for Live Subtitling and Accessibility.
Considered the increasing demand for institutional translation and the multilingualism of international organizations, the application of Artificial Intelligence (AI) technologies in multilingual communications and for the purposes of accessibility has become an important element in the production of translation and interpreting services (Zetzsche, 2019). In particular, the widespread use of Automatic Speech Recognition (ASR) and Neural Machine Translation (NMT) technology represents a recent development in the attempt of satisfying the increasing demand for interinstitutional, multilingual communications at inter-governmental level (Maslias, 2017). Recently, researchers have been calling for a universalistic view of media and conference accessibility (Greco, 2016). The application of ASR, combined with NMT, may allow for the breaking down of communication barriers at European institutional conferences where multilingualism represents a fundamental pillar (Jopek Bosiacka, 2013). In addition to representing a so-called disruptive technology (Accipio Consulting, 2006), ASR technology may facilitate the communication with non-hearing users (Lewis, 2015). Thanks to ASR, it is possible to guarantee content accessibility for non-hearing audience via subtitles at institutionally-held conferences or speeches. Hence the need for analysing and evaluating ASR output: a quantitative approach is adopted to try to make an evaluation of subtitles, with the objective of assessing its accuracy (Romero-Fresco, 2011). A database of F.A.O.’s and other international institutions’ English-language speeches and conferences on climate change is taken into consideration. The statistical approach is based on WER and NER models (Romero-Fresco, 2016) and on an adapted version. The ASR software solution implemented into the study will be VoxSigma by Vocapia Research and Google Speech Recognition engine. After having defined a taxonomic scheme, Native and Non-Native subtitles are compared to gold standard transcriptions. The intralingual and interlingual output generated by NMT is specifically analysed and evaluated via the NTR model to evaluate accuracy and accessibility
Il discorso istituzionale di commemorazione dell'abolizione della schiavitù e della tratta transatlantica degli schiavi. Analisi del discorso delle giornate commemorative francesi, dell'ONU e dell'Unesco
L’esclavage et la traite des esclaves sont officiellement illégales partout dans le monde, et pourtant l’esclavage demeure un sujet très présent dans le discours public institutionnel ce qui est démontré, entre autres, par la prolifération de journées de commémoration consacrées à ce thème dans les 30 dernières années. Cette recherche analyse, à l’aide des concepts et des catégories de l’analyse du discours française, les textes de ces journées de commémoration françaises, de l’ONU et de l’Unesco. L’objectif est de montrer quels ethos institutionnels (français, de l’ONU et de l’Unesco) sont véhiculés par ces discours (notamment à travers l’interdiscours et les représentations de l’histoire de l’esclavage et de la traite). Plus spécifiquement, on tentera de voir si ces discours constituent une forme de remodelage du discours sur l’identité (nationale ou internationale) et donc forcément sur l’Autre aussi dans le discours institutionnel, ou s’il ne s’agit au contraire que d’une sorte d’auto-absolution pour le passé qui ne fait que renforcer le discours identitaire établi, de façon acritique. À ces fins, la recherche adopte une méthodologie qualitative qui se focalise sur les éléments linguistiques liés à l’interdiscours, l’ethos institutionnel français, onusien et de l’Unesco et la représentation de l’esclavage et de la traite (particulièrement en tant que partie du passé esclavagiste et colonialiste français et européen).Slavery and the slave trade have officially been abolished everywhere in the world, yet there is no doubt slavery as a subject has remained relevant in public institutional discourse. It is deeply connected to a country’s representation of its own past and, therefore, of itself (its ethos). To examine these two elements (primarily in French institutional discourse and secondarily in ONU’s and Unesco’s institutional discourse), this dissertation will analyse the official speeches delivered by French political representatives on days of public commemoration of the abolition of slavery. To better detect its characteristics, the speeches will be compared with their equivalents produced by UN and UNESCO on their commemorative days of the abolition of slavery. Since such days of commemoration have only been instituted in the recent past, the span of time covered by this research is of approximately 30 years. The study uses a purely qualitative methodology and the tools of French discourse analysis and mainly focuses on linguistic choices around institutional ethos (both French and international: ONU’s and Unesco’s), interdiscourse, and slavery and the slave trade as part of the nation’s and Europe’s past. The final aim of the study is to understand whether these days of commemoration act as moments of public self-criticism about a country’s (and Europe’s) colonialist and slaving past, or only as acritical celebration of national and international identities (of former slavery-exploiting countries).La schiavitù e la tratta degli schiavi sono state ufficialmente abolite ovunque nel mondo, e tuttavia la prima resta un argomento importante nel discorso pubblico istituzionale, come testimonia la moltiplicazione di giornate commemorative dagli anni 90 ad oggi. La presente ricerca considera i testi di tali giornate commemorative (sia nazionali, promosse dal governo francese, che internazionali, di ONU e Unesco) e utilizza gli strumenti dell’analisi del discorso di scuola francese al fine di verificare quale tipo di ethos istituzionale sia veicolato da questi discorsi (soprattutto attraverso l’interdiscorso e la rappresentazione della storia di schiavitù e tratta). In particolare, mira a comprendere se le giornate siano un momento di rielaborazione del passato e dell’identità degli ex paesi schiavisti, o se servano al contrario a ribadire un’esaltazione acritica della storia nazionale e internazionale. A tale scopo, la ricerca adotta una metodologia qualitativa focalizzata sugli elementi linguistici legati all’interdiscorso, all’ethos istituzionale francese, dell’ONU e dell’Unesco e alla rappresentazione di schiavitù e tratta (in particolare come parte del passato schiavista e colonialista di Francia ed Europa)
Integrated Information Theory: an Empirically Testable Solution to the Mind-Body Problem
The purpose of this dissertation is to show that consciousness can be studied scientifically and to illustrate a possible way to do it. In particular, I aim to show how Integrated Information Theory (IIT) can provide an empirically testable solution to the mind-body problem. In the first chapter, I introduce the mind-body problem, as the general problem of how mind and matter are related, and the hard problem, as the more specific problem of explaining how consciousness arises from matter. I then proceed to illustrate the terminology and work definitions that I will employ throughout the entire work. In the second chapter, I look at the mind-body problem from a historical perspective. In particular, I go through Galileo’s influential distinction between primary properties and secondary qualities that can be found in his The Assayer. In particular, I argue that what alienates consciousness from objective science is the ill conceptualization of the primary-properties and secondary-qualities distinction. In the next chapter, I illustrate IIT and its axiomatic approach. After an overview of IIT, I discuss what can be called the ‘core’ of the theory: its axioms, its postulates, and its fundamental identity, and I discuss its explanatory structure. Finally, in the last chapter, I engage with the unfolding argument, which has been presented recently as a confutation of IIT. In my analysis, I show how the unfolding argument presents several criticalities. In particular, I argue that the unfolding argument commits to a radical version of functionalism that is unfit to deal with the challenges posed by assessing consciousness in a clinical context. Finally, I show how the notion of science implied by the proponents of the unfolding argument is too strict to be useful to any analysis and it does not consider the debate on the demarcation problem in philosophy of science
Can gut microbiota analysis be beneficial for ex-situ and in-situ conservation of threatened animal species?
Ex-situ conservation and the in-situ conservation of natural habitats are the tools to conserve biodiversity. Habitats and ecosystems have been becoming altered by human activities and a growing number of species requires form of management to ensure their survival. Conservation queries become more complex and urgent. Developing scientifically based and innovative approaches to ex-situ conservation is necessary. Recent studies underline importance of gut microbiome in animal health with implications for animal conservation and management. Animal and human studies have demonstrated that environmental factors can impact gut microbiome composition. Within this scenario, the present work focused on species belonging to different taxa, reptiles and mammals: Aldabrachelys gigantea, the giant tortoise of the Seychelles islands and Indri indri, the greatest leaving lemur of Madagascar. The Seychelles giant tortoise is vulnerable species with declining population, whereas the indri is a critically endangered species that could reach the extinction within 25 years. Both need research to help them to survive. Tortoises live for very long time and to observe how they can afford the environmental changes is very difficult. Indris, instead, are able to survive only in a small area of the Madagascar forest, with a very strong link between the species’ survival and the environment. The obtained results underline importance of environmental factors, both in-situ and ex-situ, for species conservation. Microbiome could help the organisms to respond on a short timescale and cope with, environmental changes. However, species with long generation time might not be able to adapt to fast changes but bacteria with a short generation time can adapt on a shorter timescale allowing the host to cope with fluctuating environment. Gut microbiome plays an important role in an animal’s health and has the potential to improve the management of individuals under human care for conservation purposes
Translation Policies and Practices in European Art Museums
One aspect of globalisation has been a significant increase in international visitors to many museums around the world, challenging museums to cater for an increasingly diverse audience in more than one language. As observed by a number of scholars (Liao 2018, Cranmer 2016, Neather 2012), more research is needed on the role of translation practices in the museum context.
Adopting an action research approach and drawing on qualitative interviews with translation-related staff from a range of European art museums as well as with translation service providers, this study sets out to investigate translation practices and policies in art museums. By adopting the perspective of museums, and their methods in commissioning, managing, and checking translations, the focus of this study is put on organisational and managerial aspects of translation, and the ways in which these contribute to the overall quality of their translations. How are translation projects handled? How are quality requirements communicated? How are multilingual communication strategies agreed upon? How is translator feedback handled? And which tools are employed to efficiently undertake these tasks?
The objective of the research is twofold. On the one hand, it seeks to provide a descriptive analysis of existing translation practices in art museums. On the other hand, the study aims to propose potential enhancements in three key areas: project management, quality assurance and translation technology, within a quality model. The purpose of the model is to improve existing practices which lack systematicity and efficient collaboration.
Translation practices in museums are addressed within a customer-based perspective of translation quality, referring to quality standards for translation ISO 17000 and ISO/TS 11669, thus implying a functionalist approach. In response to the needs and experiences of the interviewed museum staff, a set of guidelines is proposed as a useful instrument for museum professionals involved in translation-related tasks