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Immune response against <i>Mycobacterium avium</i> subsp. <i>paratuberculosis</i>, Epstein-Barr virus, HERV-K and IRF5 in rheumatoid arthritis
Full text linkRheumatoid arthritis (RA) is an inflammatory disease characterized by synovitis, systemic inflammation, autoantibodies that causes joint damage, disability, decreased quality of life, and cardiovascular and other comorbidities. Its aetiology as well the exact etiopathogenetic mechanisms are not well clear so far. RA is triggered by an interplay between genes and environmental factors.
Several studies showed that microorganisms play an important role in triggering autoimmunity through different mechanisms of action. Viral and bacterial infections, such as those caused by Epstein-Barr virus (EBV), Human Endogenous Retrovirus (HERVs) and mycobacteria, may play a pathogenetic role in RA through immunological cross-reactivity or molecular mimicry. Sardinians have a peculiar genetic background resulting from a long lasting geographical isolation with a strong incidence and prevalence of different autoimmune disease such as RA, multiple sclerosis (MS) and diabetes.
During this PhD course, I have studied the role of EBV, HERV-K and Mycobacterium avium subsp. paratuberculosis (MAP) in RA pathogenesis and other rheumatic diseases for a better understanding of how these infectious agents can lead to a deregulation of transcription factors such as Interferon Regulatory Factor 5 (IRF5) that is important in the regulation of different cells type like macrophages and neutrophils.
Finally, in order to better understand the etiopathogenesis of RA, an animal model has been used to study the molecular mechanisms involved in the above-mentioned diseases and to better understand the link between the environment and genes in RA with an objective to develop new therapeutic strategies
Per un'edizione dell'epistolario di Luigi Pirandello
No full textThe epistolary corpus of Luigi Pirandello, initially thought to be slim, following the research, studies and discoveries of the last thirty years has instead turned out to be very considerable.
This research work consists in the collection, census, reorganisation and systemisation of all the letters published by Pirandello over fifty years (1886-1836) through the comparison of the various printed editions. A further aim is to contribute to the recomposition of Pirandello's epistolary corpus by integrating all the extant material available to date. This material has numerous diverse sources, from monographs to articles in specialist magazines and journals and so has been organized according to thematic criteria or relative to limited periods of time.
The result is a voluminous preparatory work for the realization of a timely updated philological edition of the epistolary production
Grado de influencia ejercido por las designaciones UNESCO sobre la demanda de turismo: caso del Parque Geo-Minero Histórico y Ambiental de Cerdeña
No full textThis PhD thesis in co-tutorship between the University of Seville and the University of Sassari examines the Parco Geominerario Storico e Ambientale della Sardegna (Historical and Environmental Geomining Park of Sardinia) with the aim of understanding the role and degree of influence exercised by the UNESCO recognition on the territories that are part of it, referring mainly to the effects that this designation has on tourism. In addition to the more immediate effects, linked to the fundamental principles of UNESCO, that is protection and conservation of the natural and cultural heritage, it investigates the economic aspects that are important for the people in the territories affected by the interruption of mining activities.
A case study research with a qualitative approach is used; an empirical investigation was chosen to analyse the Park within its real context. A desk and a field analysis were carried out as part of a comparative analysis.
The investigation is about ex mining sites transformed into tourist-cultural resources open to the public and which can be considered products/goods, tourism is, in fact, an economic activity that generates profit (OMT 1998: 16). The research also involves registering methods and annual entrances to these sites, management and funding methods, human resources employed, promotion and communication.
The thesis is structured in five chapters and is written in Spanish, incorporated by two parts in Italian: a summary of the first four chapters and the conclusions.
In the final chapter, it is reported the Park’s exit from UNESCO’s Global Geoparks network, starting from the 1st of January 2020 and the reasons of this pronouncement
La Gestione del servizio culturale tra pubblico, privato e terzo settore: profili organizzativi e funzionali
No full textThe study aims to reconstruct the notion of cultural public service as a mean to ensure the effectiveness of the legal positions acknowledged by the Legislation to every citizen related to cultural heritage. That notion outlines a precise mission that has to be fulfilled by public powers in order to ensure that the cultural heritage is enjoyed by all the population. The study tries to define the means by which this service can be provided. The attention is then focused on the so called third sector with its recently renewed regulations. So the organizational aspects of the third sector entities, and of the foundations particularly, have been studied in deep, since they convey a functional bond on the goods in them conferred that is similar to the functional bond that imposes the common use of cultural heritage. A regulatory structure emerges that takes interest on these legal entities because they can take part in the management of cultural public interests especially if their shareholder is a public administration. The main goal that has to be fulfilled in the provision of cultural public service, in fact, is to coordinate the players involved in a service that appears to be reticular. The instrument detected to do so is the network contract, conveyed by a program agreement among entities that are public administrations in their essence. The solution proposed in these terms is considered to be an innovative way to pursue the complex management of the cultural public service
Qualificazione giuridica e analisi strutturale delle continuità intenzionali: il caso di Damanhur tra sociologia, antropologia giuridica e diritto comparato.
No full textThe purpose of this Doctoral thesis is to analyze from a legal standpoint the new, globalized phenomenon of intentional human communities, in order to understand whether these new types of human col¬lectives can be considered as alternative forms of traditional organizational models and capable of creating new legal systems, starting from the assertion ubi societas, ibi ius. Basing on the definitions elaborated in the field of legal sociology and intentional communities, we analyzed a intentional community’s capacity to produce legal rules that apply to that members. The legal organization of the Community of Damanhur, located in Piedmont (Italy), where there are internal rules of private and public law regulating the life of its members, is a genuine legal system, which poses many problems in relation to Italian law. The new bill submitted to the Italian Parliament in 2017 on the legal recognition of intentional communities could definitively regulate the relationship between an Intentional Community and the State, with the consequent recognition of the existence of ‘autonomous legal systems’ for all Intentional Communities
Valutazione di due differenti tipologie di stress in ambito oncologico veterinario
No full textVeterinary oncology is a specialized branch in continuous growth thanks to the prolongation of the life of
affection animals, which frequently incur tumor pathologies. In addition, pets are increasingly regarded as
family members and for this reason owners have higher expectations of the veterinary services provided.
This document concerns the issue of stress in the field of veterinary oncology, analyzed on two different
fronts. The types of stress analyzed are: “oxidative stress” and the respective role in oncogenesis, but also
the “psychosocial stress” suffered by a group of dog owners for whom a tumor diagnosis was made.
Oxidative stress is a complex and debated topic in the medical field and the techniques for its measurement
are different. In the present study the aim was to measure the redox state in canine cancer patients
through the use of the d-ROMs test and the BAP test. The values of d-ROMs and BAP were measured in 31
dogs with cancer and 28 healthy dogs. The age of all the subjects analyzed had an inverse relationship with
respect to the BAP value, but the group of sick dogs had higher levels, while d-ROMs did not differ between
sick and healthy. No differences were observed between local disease and metastatic or systemic disease,
and no differences were identified between dogs with carcinomas and dogs with lymphoma, but the mean
of the BAP values of these two groups differed significantly from the mean of the BAP values of the healthy
dogs. For both groups the BAP values were found to be within the normal limits. This result could indicate a
compensatory mechanism for oxidative stress. The average of the d-ROMs values, on the other hand, was
increased compared to the normal limits, probably due to a cumulative effect of oxidative stress with
advancing age and any other pathologies not easily diagnosed with the tests performed to select the dogs
healthy. In any case, the number of cases obtained is reduced and there was discrepancy between the
subjects regarding the tumor histotype, the clinical stage and the histological grade. Further studies, with
more patients, could help confirm a possible role of reactive oxygen substances in the development and
progression of tumors and the mechanisms through which the antioxidant barrier acts. Such studies could
also serve to investigate the prognostic value of d-ROMs and BAP and their role in monitoring antitumor
treatment strategies, whether or not associated with a possible therapeutic role of diet-supplemented
antioxidants.
The second part of this document is aimed at investigating the stressful impact that the diagnosis of cancer
on a dog can have on its owner, through the use of the IES-R (Impact of Event Scale - Revised). The IES-R is
not a diagnostic tool, but is used as an indicator of a probable PTSD and is used on different occasions due
to its versatility. In the present study, the diagnosis of cancer on the dog, communicated to the owner, is
considered a stressful event. The people who completed the questionnaire were 21, 12 women and 9 men,
with an average age of 47 years. An IES-R score above 33 indicates a probable post traumatic stress
disorder (PTSD) and the mean score of the people who filled out the questionnaire was 42.7. Sixty-seven
percent of people had a score above 33, with an average of 67. People under the age of 50 had a higher
score than people over the age of 50. Women experienced more avoidance symptoms than men. Based on
these results, it is possible to suspect probable PTSD in most people who have received the news of the
disease in their pet and this reinforces the hypothesis that a pet is considered in all respects a member of
the family. Such findings can be of interest to mental health professionals, but also to veterinarians who
have to deliver bad news to the client. To the author's knowledge, there are currently no similar studies in
veterinary medicine, therefore it might be useful to expand the number of people who fill out the
questionnaire in order to study the many variables that can affect the assessment of people's mental state
and their adaptivity after receiving bad news from their veterinarian
How exome sequencing is shedding light on the complexity of Mendelian disorders: some examples from Sardinia
Full text linkThe total number of Mendelian disorders is estimated to be around 7,000 and while each is individually rare, together, these genetic conditions contribute significantly to morbidity, mortality, and healthcare costs.
In the last decade there has been a paradigm shift in their investigation due to the development of powerful new DNA sequencing technologies, such as whole exome sequencing. Although our knowledge of the diversity of Mendelian phenotypes is progressively increasing, substantial gaps remain. Up to 50% of patients affected by a rare genetic disorder never receive a diagnosis.
We focused our attention on such Mendelian disorders and in a collaborative effort we studied by WES a cohort of heterogeneous samples affected by Crisponi/Cold-induced sweating syndrome-like, syndromic Intellectual Disabilities and Epileptic Encephalopathies.
The results of our work along with others reported in the literature, are contributing to reveal the extensive clinical variability and genetic complexity underlying Mendelian phenotypes and inheritance, to provide insight into study design and approach and analytical strategies and to identify novel mechanisms.
Our increasing knowledge on the genetic basis of rare disorders is shedding light on the “complex” nature of the “simple” Mendelian disorders and that “true monogenic” disorders are very rare, underscoring the current challenges of clinical diagnostics and discovery
Infectious agents of Pacific oysters (Crassostrea gigas) farmed in Sardinia: isolation, molecular characterization, tissue localization and inflammatory reaction
No full textMortality outbreaks in oysters have been globally reported with heavy economic and social impact on Pacific oyster production.
The aim of this study was to evaluate the occurrence and related lesions in target organs of OsHV-1, V. aestuarianus and V. splendidus in oysters (Crassostrea gigas) farmed in Sardinia by a microbiological, biomolecular and histopathological approach.
Four hundred and forty oyster samples were collected from Sardinian lagoons (358 from San Teodoro, 59 from Tortolì, 10 from Marceddì, and 13 from Calich), during 2016, 2017 and 2018 years. In particular, V. aestuarianus positive oysters were sampled in the San Teodoro (85%) and in the Tortoli (12%) lagoons. Mantle was the most affected organ and the highest bacterial load was associated with a moderate to severe hemocytes infiltration (46%) in connective tissue and hemolympahic vessels.
OsHV-1 was detected only in oysters from Tortolì lagoon (47%) and V. splendidus was detected mostly in oysters from Marceddì lagoon (90%), both without tissue lesions.
Overall, a relationship between V. aestuarianus bacterial load, degree of hemocytes infiltration in the mantle tissue and mortality episodes was demonstrated.
To the best of our knowledge, differently from what have been reported in literature, that do not support a primary effect of V. aestuarianus in mortality events, we suggest a potential role of V. aestuarianus in oysters mortality in one of the most devoted lagoon to extensive aquaculture in Sardinia
VAPB aggregates in PBMCs and peripheral mediators of inflammation: new diagnostic perspectives for ALS
No full textPoor knowledge about ALS pathophysiology is the major reason of specific diagnostic tests absence. Many different molecular mechanisms that concur to MNs degeneration have been described and among these, inflammatory process seems to play a role in disease progression. This work was aimed to reach two objectives: to find biomarkers that can help and guide the clinical diagnostic process at an early stage of ALS and to study immune system activity in ALS patients. First we evaluated the role of VAPB, a protein involved in both sporadic (sALS) and familial (fALS) forms of ALS, as a biomarker analysing peripheral blood mononuclear cells (PBMCs) isolated from sALS patients. In the second phase of the study, neuro-inflammatory mediator’s role in disease progression was evaluated by chemokines and cytokines quantification in sera of sALS patients. The data obtained revealed interesting results useful for ALS diagnosis. In fact, a characteristic pattern of VAPB was found in all sALS patients analysed. Of note, this VAPB pattern was absent in our series of controls. The quantification of serum chemokines evidenced a peculiar behaviour of two chemokines: CXCL8 and CCL2 that we found increased in sALS compared to PD and in PD compared to sALS respectively. The analysis of inflammatory mediators in sera together with the identification of VAPB aggregates in PBMCs represent a diagnostic non-invasive, simple, fast, cheap tool useful in clinical practice and for studying ALS patho-mechanisms
Per un approccio bioarcheologico al caso di Sant'Antioco di Bisarcio (Ozieri, SS): tra archeologia, antropologia fisica e paleopatologia
No full textThe PhD project is focused on the bioarchaeological analysis of a cemeterial area in use from the second half of the 1300s and the end of the 1700s in the medieval site of Bisarcio, in the North of Sardinia (Italy), seat of a Diocese for almost 500 years.
On the basis of the historical and archaeological sources, it wants to fill the gaps related to the demographic data applying taphonomic methods trying to reconstruct funerary rituals and the approach to the concept of death of this human group and bioarcheological methods (macroscopic and biomolecular analyses applied on osteological human remains and sepultures soil samples) providing a biological profile of every skeleton examined, type of activity carried out and the pathologies, reconstructing a cross-section of this society, its demographic and social composition, its living conditions, the characterizing pathocenosis, the sanitation practices at the base of its system and the characteristic type of diet.
The data obtained by the analysis of this cemeterial area are compared with the data related to another human sample, from Alghero Lo Quarter, another medieval site, a completely different context, in order to highlight possible similarities or differences between those two human groups, with possible reconstructive hypotheses