Study of Candidate Genes for production and carcass traits in Italian Heavy Pigs: identification of a new DNA Markers, Expression Studies and Association Analysis using Different Experimental Design

Heavy pig breeding in Italy is mainly oriented for the production of high quality processed products. Of particular importance is the dry cured ham production, which is strictly regulated and requires specific carcass characteristics correlated with green leg characteristics. Furthermore, as pigs are slaughtered at about 160 kg live weight, the Italian pig breeding sector faces severe problems of production efficiency that are related to all biological aspects linked to growth, feed conversion, fat deposition and so on. It is well known that production and carcass traits are in part genetically determined. Therefore, as a first step to understand genetic basis of traits that could have a direct or indirect impact on dry cured ham production, a candidate gene approach can be used to identify DNA markers associated with parameters of economic importance. In this thesis, we investigated three candidate genes for carcass and production traits (TRIB3, PCSK1, MUC4) in pig breeds used for dry cured ham production, using different experimental approaches in order to find molecular markers associated with these parameters.

Investigating the role of Copy Number Variants in Specific Language Impairment and identification of new candidate genes

Specific language impairment (SLI) is a complex neurodevelopmental disorder defined as an unexpected failure to develop normal language abilities for no obvious reason. Copy number variants (CNVs) are an important source of variation in the susceptibility to neuropsychiatric disorders. Therefore, a CNV study within SLI families was performed to investigate the role of structural variants in SLI. Among the identified CNVs, we focused on CNVs on chromosome 15q11-q13, recurrently observed in neuropsychiatric conditions, and a homozygous exonic microdeletion in ZNF277. Since this microdeletion falls within the AUTS1 locus, a region linked to autism spectrum disorders (ASD), we investigated a potential role of ZNF277 in SLI and ASD. Frequency data and expression analysis of the ZNF277 microdeletion suggested that this variant may contribute to the risk of language impairments in a complex manner, that is independent of the autism risk previously described in this region. Moreover, we identified an affected individual with a dihydropyrimidine dehydrogenase (DPD) deficiency, caused by compound heterozygosity of two deleterious variants in the gene DPYD. Since DPYD represents a good candidate gene for both SLI and ASD, we investigated its involvement in the susceptibility to these two disorders, focusing on the splicing variant rs3918290, the most common mutation in the DPD deficiency. We observed a higher frequency of rs3918290 in SLI cases (1.2%), compared to controls (~0.6%), while no difference was observed in a large ASD cohort. DPYD mutation screening in 4 SLI and 7 ASD families carrying the splicing variant identified six known missense changes and a novel variant in the promoter region. These data suggest that the combined effect of the mutations identified in affected individuals may lead to an altered DPD activity and that rare variants in DPYD might contribute to a minority of cases, in conjunction with other genetic or non-genetic factors.

Staphylococcus aureus bones and joints infections: in vivo studies and host immune response

Abstract The aim of this work was the development of a murine model of septic arthrosynovitis and osteomyelitis caused by Staphylococcus aureus, which could mimic the natural disease occurring in humans and which could be suitable for testing preventive and therapeutic interventions. This model could be particularly useful since S. aureus-mediated joints and bones infections are relevant in humans, both in terms of frequency and severity. Our attention focused in tracking bacterial infiltration in joints and bones over time using different microbiological and hystopathological tools, which allowed us to have a complete overview of the situation and to evaluate the immunological actions undertaken by the host to contain or eradicate the bacterial infection. Antibodies and cytokines profiles, as well as recruitment of host immune cells at joints of immunized and infected mice were therefore monitored for a time period that allowed us to study both the acute and the chronic phases of the disease in situ. Finally the Novartis vaccine formulation proposed against S. aureus infections was tested for its capacity to protect immunized mice from joints infections, and the preventive immunization was compared to a standard antibiotic prophylaxis. The availability of powerful tools to study specific bacterial-mediated diseases is nowadays an important requirement for the scientific community to shed light on the complex interactions between host and pathogens and to test treatments for preventing or contrasting infections. We believe that our work significantly contributes to the overall knowledge in the field of S. aureus-dependent pathologies, opening the possibility for further investigations in several fields of study.

Genus Bifidobacterium: taxonomy studies and gene expression analysis on folate pathway

Folates (vitamin B9) are essential water soluble vitamins, whose deficiency in humans may contribute to the onset of several diseases, such as anaemia, cancer, cardiovascular diseases, neurological problems as well as defects in embryonic development. Human and other mammals are unable to synthesize ex novo folate obtaining it from exogenous sources, via intestinal absorption. Recently the gut microbiota has been identified as an important source of folates and the selection and use of folate producing microorganisms represents an innovative strategy to increase human folate levels. The aim of this thesis was to gain a fundamental understanding of folate metabolism in Bifidobacterium adolescentis. The work was subdivided in three main phases, also aimed to solve different problems encountered working with Bifidobacterium strains. First, a new identification method (based on PCR-RFLP of hsp60 gene) was specifically developed to identify Bifidobacterium strains. Secondly, Bifidobacterium adolescentis biodiversity was explored in order to recognize representing strains of this species to be screened for their folate production ability. Results showed that this species is characterized by a wide variability and support the idea that a possible new taxonomic re-organization would be required. Finally B. adolescentis folate metabolism was studied using a double approach. A quantitative analysis of folate content was complemented by the examination of expression levels of genes involved in folate related pathways. For the normalization process, required to increase the robustness of the qRT-PCR analysis, an appropriate set of reference genes was tested using two different algorithms. Results demonstrate that B.adolescentis strains may represent an endogenous source of natural folate and they could be used to fortify fermented dairy products. This bio-fortification strategy presents many advantages for the consumer, providing native folate forms more bio-available, and not implicated in the discussed controversy concerning the safety of high intake of synthetic folic acid.

Language, action, and sensoriality: a multimodal analysis of interactions in inclusive sport climbing with visually impaired athletes

In sport climbing, athletes with vision impairments are constantly accompanied by their guides – usually trainers – both during the preparatory inspection of the routes and whilst climbing. Trainers are, so to speak, the climbers’ eyes, in the sense that they systematically put their vision in the service of the climbers’ mobility and sporting performance. The synergy between trainers and athletes is based on peculiar, strictly multimodal interactive practices that are focused on the body and on its constantly evolving sensory engagement with the materiality of routes. In this context, sensory perception and embodied actions required to plan and execute the climb are configured as genuinely interactive accomplishments. Drawing on the theoretical framework of Embodied and Situated Cognition and on the methodology of Conversation Analysis, this thesis engages in the multimodal analysis of trainer-athlete interactions in paraclimbing. The analysis is based on a corpus of video recorded climbing sessions. The major findings of the study can be summarized as follows. 1) Intercorporeality is key to interactions between trainers and athletes with visual impairments. The participants orient to perceiving the climbing space and acting in it as a ‘We’. 2) The grammar, lexicon, prosody, and timing of the trainers’ instructions are finely tuned to the ongoing corporeal experience of the climbers. 3) Climbers with visual impairments build their actions by using sensory resources that are provided by their trainers. This result is of particular importance as it shows that resources and constraints for action are in a fundamental way constituted in interaction with Others and with specific socio-material ecologies, rather than being defined a priori by the organs and functions of individuals’ body and mind. Individual capabilities are thus enhanced and extended in interaction, which encourages a more ecological view of (dis)ability.

Applied genomics in livestock: genome-wide association studies and population genomics analysis in pig and rabbit breeds

The domestication and selection processes in pigs and rabbits have resulted in the constitution of multiple breeds with broad phenotypic diversity. Population genomics analysis and Genome-wide association study analysis can be utilized to gain insights into the ancestral origins, genetic diversity, and the presence of lethal mutations across these diverse breeds. In this thesis, we analysed the dataset obtained from three Italian Pig breeds to detect deleterious alleles. We screened the dataset for genetic markers showing homozygous deficiency using two approaches single marker and haplotype-based approach. Moreover, Genome-wide association study analyses were performed to detect genetic markers associated with pigs' reproductive traits. In rabbits, we investigated the application of SNP bead chip for detection signatures of selection in rabbits using different methods. This analysis was implemented for the first time in different fancy and meet rabbit breeds. Multiple approaches were utilized for the detection of the selection of signatures including Fst analysis, ROH analysis, PCAdapt analysis, and haplotype-based analysis. The analysis in pigs was able to identify five putative deleterious SNPs and nine putative deleterious haplotypes in the analysed Italian Pig breeds. The genomic regions of the detected putative deleterious genomic markers harboring loss of function variants such as the Frameshift variant, start lost, and splice donor variant. Those variants are close to important candidate genes such as IGF2BP1, ADGRL4, and HGF. In rabbits, multiple genomic regions were detected to be under selection of signature. These genomic regions harbor candidate genes associated with coat color phenotype (MC1R, TYR, and ASIP), hair structure (LIPH), and body size (HMGA2 and COL2A1). The described results in rabbits and pigs could be used to improve breeding programs by excluding the deleterious genetic markers carriers and incorporating candidate genes for coat color, body size, and meat production in rabbit breeding programs to enhance desired traits

Language and Embodiment: sensory-motor and linguistic-social experience. Evidence on sentence comprehension

In this work I address the study of language comprehension in an “embodied” framework. Firstly I show behavioral evidence supporting the idea that language modulates the motor system in a specific way, both at a proximal level (sensibility to the effectors) and at the distal level (sensibility to the goal of the action in which the single motor acts are inserted). I will present two studies in which the method is basically the same: we manipulated the linguistic stimuli (the kind of sentence: hand action vs. foot action vs. mouth action) and the effector by which participants had to respond (hand vs. foot vs. mouth; dominant hand vs. non-dominant hand). Response times analyses showed a specific modulation depending on the kind of sentence: participants were facilitated in the task execution (sentence sensibility judgment) when the effector they had to use to respond was the same to which the sentences referred. Namely, during language comprehension a pre-activation of the motor system seems to take place. This activation is analogous (even if less intense) to the one detectable when we practically execute the action described by the sentence. Beyond this effector specific modulation, we also found an effect of the goal suggested by the sentence. That is, the hand effector was pre-activated not only by hand-action-related sentences, but also by sentences describing mouth actions, consistently with the fact that to execute an action on an object with the mouth we firstly have to bring it to the mouth with the hand. After reviewing the evidence on simulation specificity directly referring to the body (for instance, the kind of the effector activated by the language), I focus on the specific properties of the object to which the words refer, particularly on the weight. In this case the hypothesis to test was if both lifting movement perception and lifting movement execution are modulated by language comprehension. We used behavioral and kinematics methods, and we manipulated the linguistic stimuli (the kind of sentence: the lifting of heavy objects vs. the lifting of light objects). To study the movement perception we measured the correlations between the weight of the objects lifted by an actor (heavy objects vs. light objects) and the esteems provided by the participants. To study the movement execution we measured kinematics parameters variance (velocity, acceleration, time to the first peak of velocity) during the actual lifting of objects (heavy objects vs. light objects). Both kinds of measures revealed that language had a specific effect on the motor system, both at a perceptive and at a motoric level. Finally, I address the issue of the abstract words. Different studies in the “embodied” framework tried to explain the meaning of abstract words The limit of these works is that they account only for subsets of phenomena, so results are difficult to generalize. We tried to circumvent this problem by contrasting transitive verbs (abstract and concrete) and nouns (abstract and concrete) in different combinations. The behavioral study was conducted both with German and Italian participants, as the two languages are syntactically different. We found that response times were faster for both the compatible pairs (concrete verb + concrete noun; abstract verb + abstract noun) than for the mixed ones. Interestingly, for the mixed combinations analyses showed a modulation due to the specific language (German vs. Italian): when the concrete word precedes the abstract one responses were faster, regardless of the word grammatical class. Results are discussed in the framework of current views on abstract words. They highlight the important role of developmental and social aspects of language use, and confirm theories assigning a crucial role to both sensorimotor and linguistic experience for abstract words.

The language of action. How language translates the dynamics of our actions.

The general aim of the thesis was to investigate how and to what extent the characteristics of action organization are reflected in language, and how they influence language processing and understanding. Even though a huge amount of research has been devoted to the study of the motor effects of language, this issue is very debated in literature. Namely, the majority of the studies have focused on low-level motor effects such as effector-relatedness of action, whereas only a few studies have started to systematically investigate how specific aspects of action organization are encoded and reflected in language. After a review of previous studies on the relationship between language comprehension and action (chapter 1) and a critical discussion of some of them (chapter 2), the thesis is composed by three experimental chapters, each devoted to a specific aspect of action organization. Chapter 3 presents a study designed with the aim to disentangle the effective time course of the involvement of the motor system during language processing. Three kinematics experiments were designed in order to determine whether and, at which stage of motor planning and execution effector-related action verbs influence actions executed with either the same or a different effector. Results demonstrate that the goal of an action can be linguistically re-activated, producing a modulation of the motor response. In chapter 4, a second study investigates the interplay between the role of motor perspective (agent) and the organization of action in motor chains. More specifically, this kinematics study aims at deepening how goal can be translated in language, using as stimuli simple sentences composed by a pronoun (I, You, He/She) and a verb. Results showed that the perspective activated by the pronoun You reflects the motor pattern of the “agent” combined with the chain structure of the verb. These data confirm an early involvement of the motor system in language processing, suggesting that it is specifically modulated by the activation of the agent’s perspective. In chapter 5, the issue of perspective is specifically investigated, focusing on its role in language comprehension. In particular, this study aimed at determining how a specific perspective (induced for example by a personal pronoun) modulates motor behaviour during and after language processing. A classical compatibility effect (the Action-sentence compatibility effect) has been used to this aim. In three behavioural experiments the authors investigated how the ACE is modulated by taking first or third person perspective. Results from these experiments showed that the ACE effect occurs only when a first-person perspective is activated by the sentences used as stimuli. Overall, the data from this thesis contributed to disentangle several aspects of how action organization is translated in language, and then reactivated during language processing. This constitutes a new contribution to the field, adding lacking information on how specific aspects such as goal and perspective are linguistically described. In addition, these studies offer a new point of view to understand the functional implications of the involvement of the motor system during language comprehension, specifically from the point of view of our social interactions.

Populism as a battlefield Populist actors and their representation on social and legacy media during the european parliament elections 2019 in Finland, Italy and the Netherlands

The objective of the present research is to describe and explain populist actors and populism as a concept and their representation on social and legacy media during the 2019 EU elections in Finland, Italy and The Netherlands. This research tackles the topic of European populism in the context of political communication and its relation to both the legacy and digital media within the hybrid media system. Departing from the consideration that populism and populist rhetoric are challenging concepts to define, I suggest that they should be addressed and analyzed through the usage of a combination of methods and theoretical perspectives, namely Communication Studies, Corpus Linguistics, Political theory, Rhetoric and Corpus-Assisted Discourse Studies. This thesis considers data of different provenance. On the one hand, for the Legacy media part, newspapers articles were collected in the three countries under study from the 1st until the 31st of May 2019. Each country’s legacy system is represented by three different quality papers and the articles were collected according to a selection of keywords (European Union Elections and Populism in each of the three languages). On the other hand, the Digital media data takes into consideration Twitter tweets collected during the same timeframe based on particular country-specific hashtags and tweets by identified populist actors. In order to meet the objective of this study, three research questions are posed and the analysis leading to the results are exhaustively presented and further discussed. The results of this research provide valuable and novel insights on how populism as a theme and a concept is being portrayed in the context of the European elections both in legacy and digital media and political communication in general.

Comprendere la lingua dell'economia: un'analisi multidisciplinare di terminologia, comprensione e pianificazione

La tesi si concentra sull'analisi del linguaggio economico, prestando particolare attenzione alla sua terminologia. L'importanza della terminologia economica risiede nella sua capacità di facilitare una comunicazione efficace nel campo dell'economia e di permettere una comprensione più ampia dei fenomeni economici da parte del pubblico. Tuttavia, a causa della sua complessità e specificità, essa può risultare difficile da comprendere per il pubblico laico. La ricerca affronta tre questioni chiave: definire la natura della terminologia economica e l'approccio più adatto per descriverla, determinare il livello di comprensione della terminologia economica e le variabili sociali ad essa correlate, e individuare le strategie migliori per diffondere la terminologia economica nella società. Per rispondere a queste domande, l'indagine si avvale di un approccio multidisciplinare che fonde linguistica, sociolinguistica e terminologia. Il risultato è un'analisi profonda del lessico economico e delle sue collocazioni, della comprensione della terminologia da parte del pubblico e delle strategie per migliorare tale comprensione e la sua diffusione.