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La donazione di organi. Una rilettura critica a partire da un punto di vista filosofico.
No full textLa filosofia ha dimostrato che la paura della morte costringe l’uomo a ripensare al proprio rapporto anima-corpo. In questo lavoro di ricerca si è pertanto scelto di partire dalla domanda edipica, ossia da quella domanda che sta alla base di ogni domanda. Il richiamo alla morte, limite ed origine di ogni nostra narrazione, è in essa evidente ed, infatti, è proprio qui che culmina la questione del soggetto umano. Noto è poi il fatto che la piena consapevolezza di sé la si raggiunge proprio grazie all’angoscia della morte. Per dimostrare praticamente quest’assunto filosofico si è messo in evidenza il nesso tra questa paura e il mondo dei trapianti d’organo. Per farlo si è provato a far dialogare saperi eterogenei, dall’arte alla filosofia ed alla clinica. L’impostazione dialettica propria del pensiero hegeliano si è rivelata essere un interessante filo rosso da seguire. Quello che ne è emerso è un percorso dialettico che tenta di offrire una nuova prospettiva per indagare non già temi propri della filosofia politica o del diritto, ma bensì tre concetti fondamentali del mondo trapiantologico: la morte (tesi), il corpo (antitesi) ed il dono (sintesi). Ognuno di questi capitoli, poi, in accordo con Hegel, è a sua volta composto da una prima parte filosofico antropologica (tesi), una seconda tecnica e scientifica (antitesi) ed una rilettura critica conclusiva (sintesi). Infine si è teorizzata la necessità di esorcizzare la paura della morte (tesi) per superare il dualismo anima e corpo (antitesi) ed arrivare così a comprendere che accettare di diventare donatori di organi può diventare un eccellente strumento per riguadagnare l’immortalità da tempo perduta (sintesi)
Immunohistochemical expression and molecular analysis of epidermal growth factor receptor mutations in lung adenocarcinoma.
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Molecular and cellular processes of the innate immune response in insects: investigation on the immune modulation induced by entomopathogenic nematodes
No full textAim of this project was to investigate relationships between Rhynchophorus ferrugineus or Galleria mellonella and the entomopathogenic nematode Steinernema carpocapsae. In particular, the work was focused on the immune response of the insect host either in naïve larvae or in larvae infected with entomoparasites. We analyzed different immunological processes: the activity and modulation of prophenoloxidase-phenoloxidase (proPO) system, the cell-mediated encapsulation, the antimicrobial peptides (AMPs) inducible response and finally the phagocytosis activity of the host hemocytes. Furthermore, we investigated the immune depressive and immune evasive strategies of the parasite. Our results indicated that R. ferrugineus has an efficient immune system; however, in the early phase of infection, the presence of S. carpocapsae induces a strong inhibition of the host proPO system. In addition, the parasite does not seem to be susceptible to the encapsulation by host hemocytes; the parasite mimetic properties seem to be related to the structure of its body surface. S. carpocapsae, before the release of its symbiotic bacteria (X. nematophila), depresses and elude the host immune defenses, with the aim to create a favorable environment for its symbionts responsible of the septicemic death of the insect host. Besides, our results have demonstrated that X. nematophila is able to inhibit the synthesis and the activity of antimicrobial peptides. X .nematophila elude the recognition by hemocytes since it is not engulfed by the host cells. It is evident that the nematode and its symbiotic bacteria cooperate to elude and inhibit immune responses of the insect host. This study provides data that can help to a better understand of the relationships between parasites and their hosts
Aeromonas spp: model for monitoring the impact and diffusion of antibiotic compounds in water environments.
No full textAntibiotic resistant bacteria and antibiotic resistance genes cause increasing problems in clinical setting and are worldwide considered emerging environmental contaminants, but little is known about their fate in the receiving environment and how natural microbial populations may be affected. In the environment, antibiotic resistant bacteria (e.g. pathogen) may die but their resistance determinants may become part of the environmental gene pool via horizontal gene transfer to environmental bacteria. From this localization, resistance genes may move back to human and animal bacteria via food and drinking water. Natural environment, especially water, is considered a “hot spot” for spread of antibiotics resistance in this scenario Aeromonas spp. were considered the model of hydric microorganisms exposed to the actions of residual antibiotic compounds and to the aquatic resistome, whereas Faecal Coliforms represented the allochthonous population contaminating the aquatic environment. In order to investigate how these two bacterial populations could be influenced by potential antibiotic pollution, we want to examine the presence, the distribution and the transferability of transposons, integrons, and plasmids in Aeromonas spp. and Faecal Coliforms isolated from different aquatic environments submitted to a diverse degree of antibiotic contamination. In this work, we want to highlight if there are common genetic determinants in the two populations and check the potential transferability of these genetic determinants. Conjugation, natural transformation and transduction are the three mechanisms of horizontal antibiotic resistance genes transfer among bacteria. Additionally, we want to investigate if Aeromonas could also be a good donor in mating experiments with other bacteria and if it is able to naturally acquired free DNA from the environment and if Aeromonas DNA could be incorporated by natural competent bacteria. Finally we want to study lytic and lysogenic bacteriophages of Aeromonas spp., investigate the presence of resistance genes on phage DNA and evaluate if phage can transfer these resistance genes by transduction experiments
Evaluation of microarray technology and cell line models in modern toxicology
No full textModern toxicology puts together existing knowledge of classical biology with new technologies to study effects of perturbations and to predict adverse outcomes resulting from those perturbations.
Modern toxicology employs high throughput technology as microarray and cell lines as in vitro models to investigate the effect of potential toxic compounds.
In my thesis I evaluate the usefulness and reproducibility of microarray technology and cell line models. I have been mainly interested in the study of the effects on the regulation of gene transcription in cell lines. I used HepG2 cell line as a model for liver to study cadmium-induced cytotoxicity, Caco-2 as model for intestinal epithelial to study nanoparticles and HeLa cells from cervical cancer to evaluate genomic instability.
Cadmium is currently classified as carcinogen for human. In my first study, gene expression is used to explain the possible toxic mechanism of cadmium carcinogenity, using HepG2 cell line. A suggested mechanism of cadmium-induced carcinogenicity involves defects in the cell response to DNA damage and in the resistance to apoptosis. In this regard, I focused on the tumour suppressor protein P53, since its inactivation is a common feature found in human cancers and it is a crucial component of the cellular response to DNA damage. The results presented in this thesis demonstrate that in HepG2 cells exposed to cadmium, P53 was correctly moved and accumulated into the nucleus to accomplish its function as a transcription factor. However, in spite of this correct nuclear localization, the signals for the cell cycle arrest were not activated. In this context, the important mediator of cell cycle arrest P21, a P53 downstream protein, was upregulated at the gene level but not at the protein level. These results could be explained by the involvement of a post-transcriptional activity mediated by miRNA, as demonstrated by the upregulation of mir-372 in cadmium-treated HepG2 cells, which was able to affect p21 expression and to promote cell proliferation.
Recent advances in materials science have resulted in the creation of particles in the nano-scale range and their use is spreading. This creates the need to evaluate their possible toxic effect on human health. In the second study, gene expression is applied to evaluate nanoparticle effect on Caco-2 cells as in vitro model of intestinal epithelial cells. The main focus was to compare the effect of gold nanoparticles (AuNP) of two sizes (30 nm and 5 nm), using microarray technology. Smaller AuNPs (5 nm) inhibit Caco-2 cell growth. Gene expression analysis shows a broad range of responses induced by small size AuNPs. A bioinformatics reconstruction of the possible pathways regulated by smaller AuNPs indicates that Caco-2 cells activate defence responses even if it was not enough to prevent the observed toxic effect. The response at the transcriptome level upon exposure to larger AuNPs (30 nm) is very weak. This effect can be due to the low uptake of these larger AuNPs. The third study focuses on the issue concerning cell line variability using different batches of HeLa cells obtained from different laboratories. The microarray expression analysis was performed on different batches of HeLa cells exposed to hypoxic conditions. In response to a hypoxic stimulus, each cell line batch activated different pathways, although the regulation of genes related to hypoxia is conserved. A genetic analysis show the high level of extensive chromosome instability in HeLa clones obtained from different laboratories. Each clone accumulates genomic variability in a time-dependent manner. The large differences in gene expression profiles suggest that the use of uncharacterized clones may lead to faulty conclusions and to irreproducible results in studies of gene function and pathway analysis.
In the three papers presented in this thesis I have not only shown the reproducibility of microarray by comparison to real time PCR, the gold standard technique for mRNA quantification, but also the potential to create possible model for the mechanistic effects on biological pathways.
In my thesis I have used different cell lines as in vitro models. They have shown that they have many advantages and that can give strong support for modern toxicology and be used to study biological mechanism. However, a possible drawback, which should be taken into account, is highlighted in the third study showing a high variability in the responses of different batches of the same cell line
In vitro studies of te novel protein Q7: role on hyaluronian regulation in breast tumor microenvironment
No full textCancer is a group of multifactorial diseases, which involves variations in multiple genes, often coupled with environmental causes. It is characterized by uncontrolled growth of cells that are able to divide continually and invade into surrounding tissues. In Italy, breast cancer is the most common cancer form among women, accounting for over 20% of the cancer cases and about 15% of the mortality (Jemal et al., 2011). Dysregulation of the composition of the extracellular matrix (ECM) is associated with cancer, by facilitating cell growth, survival and invasion. Among various ECM glycosaminoglycans, hyaluronan (HA) has a remarkable structural importance but also a role in regulating cellular processes through a binding with membrane receptors and activation of signalling pathways. The role of HA in tumour cells’ functions depends on its molar mass which is regulated by the enzymes that synthesize HA, i.e. hyaluronan synthases (HAS), and hyaluronidases (HYALs). Alterations of these metabolic enzymes are correlated with breast cancer progression.
In this thesis, we aimed to explore the role of crosstalk between tumour cells and stroma, focusing our attention to the HA regulation. Specifically, we studied the mechanism by which proteins secreted by breast tumour cells alter HA metabolizing enzymes and its synthesis in the stromal cells.
Recently, in our laboratory we discovered a new protein in the conditioned medium (CM) of a breast tumour cell line, called “Uncharacterized protein of c10orf118” or “Q7z3e2”. For simplicity, this protein is called “Q7”. Further studies on the two well-known breast cancer cell lines MCF-7 (low invasive cells) and MDA-MB231 (high invasive cells) demonstrated a higher expression and secretion of Q7 in tumour cells than in normal cells. Information obtained from bioinformatics databanks (the Ensemble website) showed that the gene for Q7 is located on human chromosome 10 in the region q25.3. The gene is composed of 18 exons and there are six splicing variants, but only four of them code for proteins. The secreted isoform found in the CM of breast cancer cell lines is the full-length isoform that consists of 898 aminoacids and has a molecular weight of 104 kDa.
In the literature and in our data, it was shown that co-culture of breast cancer cells with fibroblasts results to an induction of HAS2 in fibroblasts and an increase of the secreted HA. Among the three HASes, HAS2 isoform was the most expressed and induced by breast tumour cells CM in fibroblasts, whereas HAS1 was not detected. When fibroblasts were treated with CM from MCF-7 cells, in the absence of Q7, the relative expression of HAS2 was significantly decreased. This last data was further confirmed when fibroblasts were treated with a recombinant protein of Q7 and a HAS2 induction and HA increase were observed.
To sum up, the data of this thesis demonstrate that the novel protein Q7 may play a key role in the increment of pericellular HA and in the breast tumour progression
The benefits of biodiversity conservation through the Italian Marine Protected Areas: application of a Choice experiment in Portofino for the monetary valuation of three ecosystem services.
No full textThe biodiversity of the seas and oceans is gradually declining due to the exploitation of resources, habitat destruction, pollution, the introduction of alien species, and climate change and related perturbations of ocean biogeochemistry. In this context, it has been necessary over time to establish areas of protected sea in order to conserve marine biodiversity and ecosystem services that it provides.
In Italy have been established, to date, 27 Marine Protected Areas (MPAs) and 2 Underwater Parks, with the aim to preserve and conserve endangered species, critical habitats, fish stocks, the landscape features, cultural biodiversity, and historical and archeological heritage.
However, the funds allocated by the government to the Italian MPAs were progressively reduced from 2008 to 2015.
In this study, we aim to estimate the economic value of changes in ecosystem services from the political scenario in which the annual funding from the State for the conservation of marine biodiversity through the Italian MPAs remains current, to the political scenario in which the funds are increased to allow for more conservation. To meet this aim, we implemented a Choice experiment at the Portofino Marine Protected Area. In our research we accompanied the choice set by an additional questionnaire designed to obtain information to make supplementary considerations on ecosystem services. Questionnaires were put to a sample of 150 people, interviewed face-to-face at the commune of Portofino (a municipality included in the Marine Protected Area of Portofino, Liguria, Italy) during the summer of 2014.
We carried out the research at the Portofino MPA, which is one of the 27 Italian Marine Protected Areas, because the director gave us the availability to perform the study in the territory and provided us with information about the management of the MPA.
We have estimated the implicit prices of the three ecosystem services (Climate regulation, Aesthetic benefits, Food) on the basis of the coefficients obtained using a multinomial logit model where the dependent variable is represented by the choice of respondents (Option A, Option B or Status quo in the choice set), and the independent variables are the ecosystem services and the attribute Cost of Choice experiment; the willingness to pay was estimated by dividing the coefficients of the attributes of the services with the coefficient of the attribute Cost.
Implicit prices are interpreted as the incremental willingness to pay (WTP), through an increase in a national tax for Italian Marine Protected Areas per annum per household, for a change in any of the ecosystem services. Our results show that people is willing to pay € 9.77 per household per year for an increase of the ecosystem service Climate regulation, through greater protection of Posidonia oceanica meadows by the Italian Marine Protected Areas, in comparison to have a level of the ecosystem service that is maintained at the current level. For the ecosystem service Aesthetic benefits provided by the coralligenous, the WTP is € 10.06 per household per year. For the ecosystem service Food, the WTP is € 9.87 per household per year. The total WTP of each family for an increase in the flow of the three ecosystem services through the Italian MPAs is 29.7 euro per household per year. These values are related to changes in the flow of ecosystem services from the political scenario in which the annual funding from the State for the conservation of marine biodiversity through the Italian MPAs remains current, to the political scenario in which the funds are increased to allow for more conservation.
If we consider that from 2008 to present the budget of the Ministry of the Environment with regard to the MPAs has been reduced by 50% (source: Italian Ministry of the Environment, Land and Sea), our research indicates that it is beneficial and desirable a reversal of the trend towards an increase in public funding for Italian MPAs.
Additional applications of Choice experiment for the valuation of ecosystem services provided by Italian MPAs, which take the conclusions and considerations of our study into account, might extent the scope of the research. In particular, it is useful to apply the method to the other Italian MPAs and to a selected sample of the Italian population representative with regard to the socio-demographic
Astrophysical sources for the observed electron and positron axcess at high energy with AMS-02 experiment.
No full textCosmic ray electrons and positrons represent only _ 1% of the total particles which reach the Earth. The standard scenario predicts that the main component of the electron spectrum is the one produced by supernova remnants, while positrons are supposed to be mainly originated from the decay of muons produced by cosmic ray interactions with the interstellar medium. In the last years, space born experiments, like AMS-02, have detected an anomalous electron and positron abundance with respect to the theoretical model predictions, for energy above _ 10 GeV, where the solar modulation e_ects are negligible. This di_erence, between data and model prediction, shows an extra contribution suggesting an equal amount for both electrons and positrons. These kinds of particles, with an initial energy of 100 GeV, can travel at most for _ 2 kpc; thus, a source of electron-positron pairs is expected inside this region. We studied the contribution from Vela-X Pulsar Wind Nebula starting from its photon spectrum; a di_usion model is applied from the source up to the Solar System and the propagated spectra are compared with the AMS-02 data. Above 100 GeV, Vela-X is the main candidate to contribute to the observed excess and it could give an anisotropic signal in the arrival cosmic ray directions
L’analisi del modello di sviluppo albanese nel periodo post-comunismo: il cambiamento economico e la specializzazione.
No full textThis dissertation examines the model of economic development in Albania during the political-economic transition of 90-ies, mainly with regard to the economic change, trading specialization and restructuring of economy.
The main hypothesis of this study is the possibility to enable the development of the country through the export orientation as well as the potential restructuring of the actual manufacturing structure, focusing especially on new sectors such as industry, and also not overlooking those in which Albania has already paved its way of development, like agriculture. Also, by a thorough analysis of conditions, on a national and international scale, it is expounded on the reality that characterized Albania after the fall of socialist system, and highlighting strong points and lost possibilities in the realm of economic development process. With the analysis of the characteristics of this process, we have intended to highlight the problems and difficulties that have been evident during the transition period in Albania.
We have mainly carried out a thorough analysis of primary problems which have hindered the economic development of the country for a long time, from the beginning of ’90-ies and onwards. In addition, we have evaluated the policies and instruments of economic development, which on one hand, may be important for the economic policy in the following years, but on the other side, they serve to comprehend the conditions that favor investments. These investments indicate the role that a good investment plays in the civil society, with reference to the aspect of employment and increase of people welfare.
Concerning the employment in question, it is noted that the undertaken reforms during the beginning of `90-ies, have not produced the expected effects. Economic transformation in Albania was more difficult than being considered. Or rather, first monetary reforms that their primary aim was to stabilize the inflation, licensing inhibition (staff dismissing) by the public enterprises and public enterprises privatization, did not build a solid base in order to enhance the economic development of the country.
The economy and price liberalization initiating since 1992 along with massive privatization of public enterprises induced in a paradoxical way a paralyzation of the country’s production and a substantial deterioration of the trade balance. Albania was transformed from an isolated country that had “embraced” the motto: to produce everything by ourselves, had to abandon this philosophy, by becoming day by day dependent on import, with a high unemployment rate and with a social context of extreme economic poverty, a thing which stimulated the domestic population to emigrate towards industrial and developed countries. Consequently, these reforms have generated effects, which are nowadays being reflected in trade exchanges. Trade liberalization and the interference lack of the state in the economy, after 40 years of protectionism, brought about the restructuring of domestic production, in which the industrial sector was the most damaged. This phenomenon was at that period called the deindustrialization of the country. In fact, it is detected that all production activities were redimensioning or completely disappearing in the field of heavy, chemical, textile and food industry. With a primitive technology, the enterprises were not able to produce qualitative products that competed in the market, and under such circumstances, there occurred the shrinkage in the production activities towards their final closure. A part of light industry continued in the years to come to produce less than the production capacities at their disposal. Whereas, in the sector of agriculture, agrarian reform fragmented the enterprises and this led to direct management of rural areas families and consequently losing the quality and production technology. The lack of technology caused the decline of productivity and market competition, which later would rise to auto-consumption production.
In the following years, after the fall of communist regime, home policy-makers demanded a rapid polarization economy in those sectors reflecting comparative advantages for Albania that derived from the raw material availability such as: chrome, iron-nickel, petroleum and copper, geographical position and the level of a very low pay.
The main objective of this study is precisely the analysis of the typical economic aspects and the decisions made by the governance in the aforementioned period with the aim and hope to present a detailed and clear panorama of the economic transition and with its progress in Albania. In the first phases, Albania experienced what was later defined by the World Bank as a growth without development.
The study of the economic development model in Albania for a long-term period, allows on one hand the clear designation of different approaches followed by the governments in order to manage the economic policy, while on the other side, it highlights the choices and “errors” made by the economic policy. Based on these data, we have attempted to define the instruments and strategies that a certain state applies to generate a substantial change of the development model, from the labor intensive production, remittances, financings or aids by the international institutions and the raw material export, to a new development model which focuses on raw material transformation, production growth in various sectors of economy, the import decline and export increase.
In this study, it is demonstrated that through raw material transformation such as petroleum processing, is guaranteed the home market demand, the export and consequently the improvement of trade balance.
Furthermore, this study shows the geography of trade exchanges where Italy was the primary trade partner of Albania: exports towards Italy and Greece made up to 83% of the total export and 44% of total imports in 2006. 72% of exports and 26% of imports went and came from Italy. After 2006, with the membership of Albania in CEFTA (Central European Free Trade Agreement), it is observed a redimensioning of import-exports in favor of the countries of CEFTA. Generally speaking or either in particular, it is observed an increase of imports from China and exports towards Spain and Turkey. As far as the construction of trade is concerned, due to the membership of Albania in CEFTA, this is relevant for the “meat” product and no other.
From the qualitative and quantitative analysis of the Albanian economy, it is noticed that during transition, with the pass of time, Albania has made a good performance of the economic growth (with the exception of last years that growth has been retarded). Anyhow, it is clear that this growth is probably not stable with time and it does not possess the accurate capacities to generate incomes and enough employment for the domestic population. For this reason, we can say that the Albanian economy is facing a crossroad: it should go ahead with a “low” development direction which enables (as it occurs nowadays) sufficient rise in employment with a low pay and being concentrated in the sector which does not control autonomously in the future. Otherwise, it should choose a direction with a high development, by promoting the hidden capacities which are expected to give a hop in sectoral as the only ones, by ensuring simultaneous stability of the future incomes and the possibility to itself govern the progress of the country development.
In this dissertation, we have noted that the policies and strategies implemented by the Albanian governments in the years of transition have not fully worked out. This has occurred due to an increase in the gross production, real incomes in economy and employment, but on the other side these have not been sufficient in order to narrow the existing gap in developed countries. The employment and incomes are very low and as a result, they do not develop important complementarities and sectoral interdependencies. Most of all, they do not stimulate consumption and investments in order to consolidate production and promote domestic product export.
This study concludes in an analysis of the economic policy implemented in Albania during the recent years, in which the state shows a low protagonism in the economic development. Also, several strategies for development have been compiled and their application has encountered several problems. The economic and industrial policy in the country does not intend to create other new sectors, but rather the consolidation of the existing ones, considered as significant for the economic development of the country.
Whereas, with the investigation of the structural problems of the economy, the government has acknowledged that free market has not fully guaranteed investments and capital in new and existing activities, so as to engender a rise in productivity, i.e. development.
Governments have avoided their intervention in the economy and have regarded the market as the best mechanism for the income distribution, an issue that is questioned by our analysis.
As a conclusion, we can say that structural reforms should be coupled with horizontal policies that reinforce the institutions, technical competencies and above all policies of structural transformation. Accordingly, good governance on one hand should fight corruption and on the other hand, revitalize the economy of the country
A novel role of CDKL5 in the regulation of mitotic spindle assembly and microtubule organization.
No full textMutations in the CDKL5# gene, located on Xp22, are the main cause of CDKL56 disorder characterized by the onset of epilepsy before 3 months of age, severe developmental delay and RTT6like features. Besides its functions in post6mitotic neurons, a recent work shows that the loss of CDKL5 influences the proliferation rate of neuronal precursors suggesting its role also in proliferating cells. However, the molecular mechanism through which CDKL5 acts on this cellular process is still unknown.
In this study we demonstrate the presence of CDKL5 at the mitotic centrosome and midbody. Importantly, the ablation of CDKL5 induces prolonged prometaphases, aberrant/multipolar spindle assembly and misaligned chromosomes. Furthermore, we show that, similar to many centrosomal proteins, CDKL5 influences microtubule organization. At the molecular level, we find that CDKL5 interacts with the scaffold protein IQGAP1, a regulator of Rac1, which regulates many cytoskeleton functions thanks to its ability to interact both with actin and plus end microtubule binding proteins (+TIPs). CDKL5 is required for the correct localization of IQGAP1 at the leading edge of polarized cells and down6regulation of CDKL5 reduces the capacity of IQGAP1 to interact with its effector proteins Rac1 and CLIP170, a +TIP that promotes microtubule stabilization at the cell cortex. Altogether, our data suggest that CDKL5 influences cell cycle progression through its centrosomal accumulation and cellular morphology through its interaction with microtubule associated proteins. We believe that these data will pave the way for a further understanding of the impact of CDKL5 in neuronal and non6neuronal cell