Molecular mapping of the regenerative niche in a murine model of myocardial infarction

Adult stem cells are distributed through the whole organism, and present a great potential for the therapy of different types of disease. For the design of efficient therapeutic strategies, it is important to have a more detailed understanding of their basic biological characteristics, as well as of the signals produced by damaged tissues and to which they respond. Myocardial infarction (MI), a disease caused by a lack of blood flow supply in the heart, represents the most common cause of morbidity and mortality in the Western world. Stem cell therapy arises as a promising alternative to conventional treatments, which are often ineffective in preventing loss of cardiomyocytes and fibrosis. Cell therapy protocols must take into account the molecular events that occur in the regenerative niche of MI. In the present study, we investigated the expression profile of ten genes coding for chemokines or cytokines in a murine model of MI, aiming at the characterization of the regenerative niche. MI was induced in adult C57BL/6 mice and heart samples were collected after 24 h and 30 days, as well as from control animals, for quantitative RT-PCR. Expression of the chemokine genes CCL2, CCL3, CCL4, CCL7, CXCL2 and CXCL10 was significantly increased 24 h after infarction, returning to baseline levels on day 30. Expression of the CCL8 gene significantly increased only on day 30, whereas gene expression of CXCL12 and CX3CL1 were not significantly increased in either ischemic period. Finally, expression of the IL-6 gene increased 24 h after infarction and was maintained at a significantly higher level than control samples 30 days later. These results contribute to the better knowledge of the regenerative niche in MI, allowing a more efficient selection or genetic manipulation of cells in therapeutic protocols.

ATG based combination therapy - a novel clinically relevant approach to promote regulation and induce long-term allograft survival

Regulatory T cells (Treg) actively regulate alloimmune responses and promote transplantation tolerance. Polyclonal anti-thymocyte globulin (ATG), a widely used induction therapy in clinical organ transplantation, depletes peripheral T cells. However, resistance to tolerance induction is seen with certain T cell depleting strategies and is attributed to alterations in the balance of naïve, memory and regulatory T cells. Here we report a novel reagent, murine ATG (mATG), depletes T cells but preferentially spares CD25+ natural Tregs which limit skewing of T cell repertoire toward T-effector-memory (Tem) phenotype among the recovering T cells. T-cell depletion with mATG combined with CTLA4Ig and Sirolimus synergize to prolong graft survival by tipping the Treg/Tem balance further in favor of Tregs by preserving Tregs, facilitating generation of new Tregs by a conversion mechanism and limiting Tem expansion in response to alloantigen and homeostatic proliferation. These results provide the rationale for translating such novel combination therapies to promote tolerance in primate and human organ transplantation.

Ancient Greek harbours used as geo-archives for palaeotsunami research : case studies from Krane (Cefalonia), Lechaion (Gulf of Corinth) and Kyllini (Peloponnese)

Since historical times, coastal areas throughout the eastern Mediterranean are exposed to tsunami hazard. For many decades the knowledge about palaeotsunamis was solely based on historical accounts. However, results from timeline analyses reveal different characteristics affecting the quality of the dataset (i.e. distribution of data, temporal thinning backward of events, local periodization phenomena) that emphasize the fragmentary character of the historical data. As an increasing number of geo-scientific studies give convincing examples of well dated tsunami signatures not reported in catalogues, the non-existing record is a major problem to palaeotsunami research. While the compilation of historical data allows a first approach in the identification of areas vulnerable to tsunamis, it must not be regarded as reliable for hazard assessment. Considering the increasing economic significance of coastal regions (e.g. for mass tourism) and the constantly growing coastal population, our knowledge on the local, regional and supraregional tsunami hazard along Mediterranean coasts has to be improved. For setting up a reliable tsunami risk assessment and developing risk mitigation strategies, it is of major importance (i) to identify areas under risk and (ii) to estimate the intensity and frequency of potential events. This approach is most promising when based on the analysis of palaeotsunami research seeking to detect areas of high palaeotsunami hazard, to calculate recurrence intervals and to document palaeotsunami destructiveness in terms of wave run-up, inundation and long-term coastal change. Within the past few years, geo-scientific studies on palaeotsunami events provided convincing evidence that throughout the Mediterranean ancient harbours were subject to strong tsunami-related disturbance or destruction. Constructed to protect ships from storm and wave activity, harbours provide especially sheltered and quiescent environments and thus turned out to be valuable geo-archives for tsunamigenic high-energy impacts on coastal areas. Directly exposed to the Hellenic Trench and extensive local fault systems, coastal areas in the Ionian Sea and the Gulf of Corinth hold a considerably high risk for tsunami events, respectively.Geo-scientific and geoarcheaological studies carried out in the environs of the ancient harbours of Krane (Cefalonia Island), Lechaion (Corinth, Gulf of Corinth) and Kyllini (western Peloponnese) comprised on-shore and near-shore vibracoring and subsequent sedimentological, geochemical and microfossil analyses of the recovered sediments. Geophysical methods like electrical resistivity tomography and ground penetrating radar were applied in order to detect subsurface structures and to verify stratigraphical patterns derived from vibracores over long distances. The overall geochronological framework of each study area is based on radiocarbon dating of biogenic material and age determination of diagnostic ceramic fragments. Results presented within this study provide distinct evidence of multiple palaeotsunami landfalls for the investigated areas. Tsunami signatures encountered in the environs of Krane, Lechaion and Kyllini include (i) coarse-grained allochthonous marine sediments intersecting silt-dominated quiescent harbour deposits and/or shallow marine environments, (ii) disturbed microfaunal assemblages and/or (iii) distinct geochemical fingerprints as well as (iv) geo-archaeological destruction layers and (v) extensive units of beachrock-type calcarenitic tsunamites. For Krane, geochronological data yielded termini ad or post quem (maximum ages) for tsunami event generations dated to 4150 ± 60 cal BC, ~ 3200 ± 110 cal BC, ~ 650 ± 110 cal BC, and ~ 930 ± 40 cal AD, respectively. Results for Lechaion suggest that the harbour was hit by strong tsunami impacts in the 8th-6th century BC, the 1st-2nd century AD and in the 6th century AD. At Kyllini, the harbour site was affected by tsunami impact in between the late 7th and early 4th cent. BC and between the 4th and 6th cent. AD. In case of Lechaion and Kyllini, the final destruction of the harbour facilities also seems to be related to the tsunami impact. Comparing the tsunami signals obtained for each study areas with geo-scientific data from palaeotsunami events from other sites indicates that the investigated harbour sites represent excellent geo-archives for supra-regional mega-tsunamis.

Tradurre il genere documentario : Due proposte di sottotitolaggio del documentario Little Land a confronto

The aim of this thesis is to discuss the main translation issues encountered while performing a double version of the subtitles of the documentary “Little Land” from English into Italian. The main motivation behind my choice is a personal interest in the subtitling field applied to the documentary filmic genre. This project is divided into two parts. The first part constitutes the theoretical basis of the thesis and is divided in three chapters. The first chapter introduces the documentary “Little Land” and analyses its main features and characteristics. The second chapter is devoted to documentary studies and theory of documentary, including the historical overview of the changes of this filmic genre and an overview of its market potential in order to meet both the audience and the director’s requirements. The third chapter deals with audiovisual translation as a discipline, and analyses the main translation techniques adopted for the documentary genre: dubbing, voice-over and subtitling. The subtitling section is particularly rich, and a discussion of the use of double and pivot subtitles and the possibilities of subtitling for accessibility issues is included. The second part constitutes the practical development of the theories introduced and dealt with in the first part. Chapter four provides an overview of the history of the Cineteca di Bologna, for whom I worked as a subtitler, and explains the guide lines and equipment required in order to perform the manual launch of the subtitles during their festival Human Rights Nights. The fifth and final chapter provides an analysis of the second version of the subtitles, meant for TV broadcasting, and highlights the main issues encountered during the translation process, both from a structural and a lexical point of view. A discussion of the different translation strategies adopted is provided, in a constant comparison with the first version of the subtitles. The function of self-reflection and self-observation in translation is also examined. Appendix A and B contain the interviews with “Little Land”’s director and protagonist respectively, Appendix C contains the subtitles table.

Mood and nonmood components of perceived stress and exacerbation of Crohnʼs disease

BACKGROUND: Diverse psychological factors are involved in the pathophysiology of stress. In order to devise effective intervention strategies, it is important to elucidate which factors play the most important role in the association between psychological stress and exacerbation of Crohn's disease (CD). We hypothesized that the association between perceived stress and exacerbation of CD would remain after removal of mood and anxiety components, which are largely involved in stress perception. METHODS: In all, 468 adults with CD were recruited and followed in different hospitals and private practices of Switzerland for 18 months. At inclusion, patients completed the Perceived Stress Questionnaire and anxiety and depression were assessed using the Hospital Anxiety and Depression Scale. During the follow-up, gastroenterologists assessed whether patients presented with a CD exacerbation. By means of binary logistic regression analysis, we estimated the factor by which one standard deviation of perceived stress would increase the odds of exacerbation of CD with and without controlling for anxiety and depression. RESULTS: The odds of exacerbation of CD increased by 1.85 times (95% confidence interval 1.43-2.40, P < 0.001) for 1 standard deviation of perceived stress. After removing the anxiety and depression components, the residuals of perceived stress were no longer associated with exacerbation of CD. CONCLUSIONS: The association between perceived stress and exacerbation of CD was fully attributable to the mood components, specifically anxiety and depression. Future interventional studies should evaluate the treatment of anxiety and depression as a strategy for potential prevention of CD exacerbations. (Inflamm Bowel Dis 2011;).

Chapter IV: Treatment of critical limb ischaemia

Recommendations stated in the TASC II guidelines for the treatment of peripheral arterial disease (PAD) regard a heterogeneous group of patients ranging from claudicants to critical limb ischaemia (CLI) patients. However, specific considerations apply to CLI patients. An important problem regarding the majority of currently available literature that reports on revascularisation strategies for PAD is that it does not focus on CLI patients specifically and studies them as a minor part of the complete cohort. Besides the lack of data on CLI patients, studies use a variety of endpoints, and even similar endpoints are often differentially defined. These considerations result in the fact that most recommendations in this guideline are not of the highest recommendation grade. In the present chapter the treatment of CLI is not based on the TASC II classification of atherosclerotic lesions, since definitions of atherosclerotic lesions are changing along the fast development of endovascular techniques, and inter-individual differences in interpretation of the TASC classification are problematic. Therefore we propose a classification merely based on vascular area of the atherosclerotic disease and the lesion length, which is less complex and eases the interpretation. Lesions and their treatment are discussed from the aorta downwards to the infrapopliteal region. For a subset of lesions, surgical revascularisation is still the gold standard, such as in extensive aorto-iliac lesions, lesions of the common femoral artery and long lesions of the superficial femoral artery (>15 cm), especially when an applicable venous conduit is present, because of higher patency and limb salvage rates, even though the risk of complications is sometimes higher than for endovascular strategies. It is however more and more accepted that an endovascular first strategy is adapted in most iliac, superficial femoral, and in some infrapopliteal lesions. The newer endovascular techniques, i.e. drug-eluting stents and balloons, show promising results especially in infrapopliteal lesions. However, most of these results should still be confirmed in large RCTs focusing on CLI patients. At some point when there is no possibility of an endovascular nor a surgical procedure, some alternative non-reconstructive options have been proposed such as lumbar sympathectomy and spinal cord stimulation. But their effectiveness is limited especially when assessing the results on objective criteria. The additional value of cell-based therapies has still to be proven from large RCTs and should therefore still be confined to a research setting. Altogether this chapter summarises the best available evidence for the treatment of CLI, which is, from multiple perspectives, completely different from claudication. The latter also stresses the importance of well-designed RCTs focusing on CLI patients reporting standardised endpoints, both clinical as well as procedural.

Improved effectiveness of partner notification for patients with sexually transmitted infections: systematic review

OBJECTIVE: To examine the effectiveness of methods to improve partner notification by patient referral (index patient has responsibility for informing sex partners of their exposure to a sexually transmitted infection). DESIGN: Systematic review of randomised trials of any intervention to supplement simple patient referral. DATA SOURCES: Seven electronic databases searched (January 1990 to December 2005) without language restriction, and reference lists of retrieved articles. REVIEW METHODS: Selection of trials, data extraction, and quality assessment were done by two independent reviewers. The primary outcome was a reduction of incidence or prevalence of sexually transmitted infections in index patients. If this was not reported data were extracted according to a hierarchy of secondary outcomes: number of partners treated; number of partners tested or testing positive; and number of partners notified, located, or elicited. Random effects meta-analysis was carried out when appropriate. RESULTS: 14 trials were included with 12 389 women and men diagnosed as having gonorrhoea, chlamydia, non-gonococcal urethritis, trichomoniasis, or a sexually transmitted infection syndrome. All studies had methodological weaknesses that could have biased their results. Three strategies were used. Six trials examined patient delivered partner therapy. Meta-analysis of five of these showed a reduced risk of persistent or recurrent infection in patients with chlamydia or gonorrhoea (summary risk ratio 0.73, 95% confidence interval 0.57 to 0.93). Supplementing patient referral with information for partners was as effective as patient delivered partner therapy. Neither strategy was effective in women with trichomoniasis. Two trials found that providing index patients with chlamydia with sampling kits for their partners increased the number of partners who got treated. CONCLUSIONS: Involving index patients in shared responsibility for the management of sexual partners improves outcomes. Health professionals should consider the following strategies for the management of individual patients: patient delivered partner therapy, home sampling for partners, and providing additional information for partners.

Guidelines for the use and interpretation of assays for monitoring cell death in higher eukaryotes

Cell death is essential for a plethora of physiological processes, and its deregulation characterizes numerous human diseases. Thus, the in-depth investigation of cell death and its mechanisms constitutes a formidable challenge for fundamental and applied biomedical research, and has tremendous implications for the development of novel therapeutic strategies. It is, therefore, of utmost importance to standardize the experimental procedures that identify dying and dead cells in cell cultures and/or in tissues, from model organisms and/or humans, in healthy and/or pathological scenarios. Thus far, dozens of methods have been proposed to quantify cell death-related parameters. However, no guidelines exist regarding their use and interpretation, and nobody has thoroughly annotated the experimental settings for which each of these techniques is most appropriate. Here, we provide a nonexhaustive comparison of methods to detect cell death with apoptotic or nonapoptotic morphologies, their advantages and pitfalls. These guidelines are intended for investigators who study cell death, as well as for reviewers who need to constructively critique scientific reports that deal with cellular demise. Given the difficulties in determining the exact number of cells that have passed the point-of-no-return of the signaling cascades leading to cell death, we emphasize the importance of performing multiple, methodologically unrelated assays to quantify dying and dead cells.

Promoting Local Innovations: A tool for adaptation to climate change and sustainable development in Mountains

Throughout their history mountain communities have had to adapt to changing environmental and socio-economic conditions. They have developed strategies and specialized knowledge to sustain their livelihoods in a context of adverse climatic events and constant change. As negotiations and discussions on climate change emphasize the critical need for locally relevant and community owned adaptation strategies, there is a need for new tools to capitalize on this local knowledge and endogenous potential for innovation. The toolkit Promoting Local Innovation (PLI) was designed by the Centre for Development and Environment (CDE) of the University of Bern, Switzerland, to facilitate a participatory social learning process which identifies locally available innovations that can be implemented for community development. It is based on interactive pedagogy and joint learning among different stakeholders in the local context. The tried-and-tested tool was developed in the Andean region in 2004, and then used in International Union for Conservation of Nature (IUCN) climate change adaptation projects in Thailand, Burkina Faso, Senegal, and Chile. These experiences showed that PLI can be used to involve all relevant stakeholders in establishing strategies and actions needed for rural communities to adapt to climate change impacts, while building on local innovation potential and promoting local ownership

Body composition and all-cause mortality in subjects older than 65 y.

BACKGROUND A low or high body mass index (BMI) has been associated with increased mortality risk in older subjects without taking fat mass index (FMI) and fat-free mass index (FFMI) into account. This information is essential because FMI is modulated through different healthcare strategies than is FFMI. OBJECTIVE We aimed to determine the relation between body composition and mortality in older subjects. DESIGN We included all adults ≥65 y old who were living in Switzerland and had a body-composition measurement by bioelectrical impedance analysis at the Geneva University Hospitals between 1990 and 2011. FMI and FFMI were divided into sex-specific quartiles. Quartile 1 (i.e., the reference category) corresponded to the lowest FMI or FFMI quartile. Mortality data were retrieved from the hospital database, the Geneva death register, and the Swiss National Cohort until December 2012. Comorbidities were assessed by using the Cumulative Illness Rating Scale. RESULTS Of 3181 subjects included, 766 women and 1007 men died at a mean age of 82.8 and 78.5 y, respectively. Sex-specific Cox regression models, which were used to adjust for age, BMI, smoking, ambulatory or hospitalized state, and calendar time, showed that body composition did not predict mortality in women irrespective of whether comorbidities were taken into account. In men, risk of mortality was lower with FFMI in quartiles 3 and 4 [HR: 0.78 (95% CI: 0.62, 0.98) and 0.64 (95% CI: 0.49, 0.85), respectively] but was not affected by FMI. When comorbidities were adjusted for, FFMI in quartile 4 (>19.5 kg/m(2)) still predicted a lower risk of mortality (HR: 0.72; 95% CI: 0.54, 0.96). CONCLUSIONS Low FFMI is a stronger predictor of mortality than is BMI in older men but not older women. FMI had no impact on mortality. These results suggest potential benefits of preventive interventions with the aim of maintaining muscle mass in older men. This trial was registered at clinicaltrials.gov as NCT01472679.

Analysis of left ventricular function of the mouse heart during experimentally induced hyperthyroidism and recovery

Many of the clinical manifestations of hyperthyroidism are due to the ability of thyroid hormones to alter myocardial contractility and cardiovascular hemodynamics, leading to cardiovascular impairment. In contrast, recent studies highlight also the potential beneficial effects of thyroid hormone administration for clinical or preclinical treatment of different diseases such as atherosclerosis, obesity and diabetes or as a new therapeutic approach in demyelinating disorders. In these contexts and in the view of developing thyroid hormone-based therapeutic strategies, it is, however, important to analyze undesirable secondary effects on the heart. Animal models of experimentally induced hyperthyroidism therefore represent important tools for investigating and monitoring changes of cardiac function. In our present study we use high-field cardiac MRI to monitor and follow-up longitudinally the effects of prolonged thyroid hormone (triiodothyronine) administration focusing on murine left ventricular function. Using a 9.4 T small horizontal bore animal scanner, cinematographic MRI was used to analyze changes in ejection fraction, wall thickening, systolic index and fractional shortening. Cardiac MRI investigations were performed after sustained cycles of triiodothyronine administration and treatment arrest in adolescent (8 week old) and adult (24 week old) female C57Bl/6 N mice. Triiodothyronine supplementation of 3 weeks led to an impairment of cardiac performance with a decline in ejection fraction, wall thickening, systolic index and fractional shortening in both age groups but with a higher extent in the group of adolescent mice. However, after a hormonal treatment cessation of 3 weeks, only young mice are able to partly restore cardiac performance in contrast to adult mice lacking this recovery potential and therefore indicating a presence of chronically developed heart pathology.

SABR for early-stage lung cancer: Early-adoption and future directions

Early-stage lung cancer incidence among older adults is expected to increase due to demographic trends and CT-based screening, yet optimal treatment of lung cancer in the elderly remains controversial. There are several accepted strategies for treating lung cancer including surgery, conventional radiation, and stereotactic ablative body radiotherapy (SABR). However, there are currently no randomized controlled trials to help distinguish the comparative effectiveness of these various strategies. This is an unfortunate omission as lung cancer causes the most deaths among all cancers in the United States (as well as the entire world). SABR holds particular promise as it is a completely non-invasive, ambulatory technique for achieving cure without an operation, thus avoiding the risks of surgery and the associated pre-operative and post-operative costs. To provide fair view of the potential effect on SABR on controlling lung cancer in the United States, a systematic review of SABR with a focus on its achieved outcomes, toxicities, and comparison to conventional radiation and surgical options is presented. ^

Agriculture Plus Plus : growth strategy for Myanmar agriculture

The development of agriculture is a main pillar of Myanmar’s growth strategies. It is natural for the Myanmar government to prioritize agriculture as a source of economic growth, since it accounted for 36% of GDP, employs a majority of labor force, and generates nearly 30% of exports as of 2010. Although the agricultural share in GDP and employment usually declines as an economy grows, it is not a sunset industry in Myanmar. Methods exist for increasing agriculture’s value added other than the growth of labor and land inputs. The key is to enhance three productivity measures: labor, land, and total productivity. We call this strategy "Agriculture Plus Plus."

Sensitization profiles and cross-reactivity among plant allergens. Molecular mechanisms of food allergy development and the role of enhancers

La prevalencia de las alergias está aumentando desde mediados del siglo XX, y se estima que actualmente afectan a alrededor del 2-8 % de la población, pero las causas de este aumento aún no están claras. Encontrar el origen del mecanismo por el cual una proteína inofensiva se convierte en capaz de inducir una respuesta alérgica es de vital importancia para prevenir y tratar estas enfermedades. Aunque la caracterización de alérgenos relevantes ha ayudado a mejorar el manejo clínico y a aclarar los mecanismos básicos de las reacciones alérgicas, todavía queda un largo camino para establecer el origen de la alergenicidad y reactividad cruzada. El objetivo de esta tesis ha sido caracterizar las bases moleculares de la alergenicidad tomando como modelo dos familias de panalergenos (proteínas de transferencia de lípidos –LTPs- y taumatinas –TLPs-) y estudiando los mecanismos que median la sensibilización y la reactividad cruzada para mejorar tanto el diagnóstico como el tratamiento de la alergia. Para ello, se llevaron a cabo dos estrategias: estudiar la reactividad cruzada de miembros de familias de panalérgenos; y estudiar moléculas-co-adyuvantes que pudieran favorecer la capacidad alergénica de dichas proteínas. Para estudiar la reactividad cruzada entre miembros de la misma familia de proteínas, se seleccionaron LTPs y TLPs, descritas como alergenos, tomando como modelo la alergia a frutas. Por otra parte, se estudiaron los perfiles de sensibilización a alérgenos de trigo relacionados con el asma del panadero, la enfermedad ocupacional más relevante de origen alérgico. Estos estudios se llevaron a cabo estandarizando ensayos tipo microarrays con alérgenos y analizando los resultados por la teoría de grafos. En relación al estudiar moléculas-co-adyuvantes que pudieran favorecer la capacidad alergénica de dichas proteínas, se llevaron a cabo estudios sobre la interacción de los alérgenos alimentarios con células del sistema inmune humano y murino y el epitelio de las mucosas, analizando la importancia de moléculas co-transportadas con los alérgenos en el desarrollo de una respuesta Th2. Para ello, Pru p 3(LTP y alérgeno principal del melocotón) se selección como modelo para llevarlo a cabo. Por otra parte, se analizó el papel de moléculas activadoras del sistema inmune producidas por patógenos en la inducción de alergias alimentarias seleccionando el modelo kiwi-alternaria, y el papel de Alt a 1, alérgeno mayor de dicho hongo, en la sensibilización a Act d 2, alérgeno mayor de kiwi. En resumen, el presente trabajo presenta una investigación innovadora aportando resultados de gran utilidad tanto para la mejora del diagnóstico como para nuevas investigaciones sobre la alergia y el esclarecimiento final de los mecanismos que caracterizan esta enfermedad. ABSTRACT Allergies are increasing their prevalence from mid twentieth century, and they are currently estimated to affect around 2-8% of the population but the underlying causes of this increase remain still elusive. The understanding of the mechanism by which a harmless protein becomes capable of inducing an allergic response provides us the basis to prevent and treat these diseases. Although the characterization of relevant allergens has led to improved clinical management and has helped to clarify the basic mechanisms of allergic reactions, it seems justified in aspiring to molecularly dissecting these allergens to establish the structural basis of their allergenicity and cross-reactivity. The aim of this thesis was to characterize the molecular basis of the allergenicity of model proteins belonging to different families (Lipid Transfer Proteins –LTPs-, and Thaumatin-like Proteins –TLPs-) in order to identify mechanisms that mediate sensitization and cross reactivity for developing new strategies in the management of allergy, both diagnosis and treatment, in the near future. With this purpose, two strategies have been conducted: studies of cross-reactivity among panallergen families and molecular studies of the contribution of cofactors in the induction of the allergic response by these panallergens. Following the first strategy, we studied the cross-reactivity among members of two plant panallergens (LTPs , Lipid Transfer Proteins , and TLPs , Thaumatin-like Proteins) using the peach allergy as a model. Similarly, we characterized the sensitization profiles to wheat allergens in baker's asthma development, the most relevant occupational disease. These studies were performed using allergen microarrays and the graph theory for analyzing the results. Regarding the second approach, we analyzed the interaction of plant allergens with immune and epithelial cells. To perform these studies , we examined the importance of ligands and co-transported molecules of plant allergens in the development of Th2 responses. To this end, Pru p 3, nsLTP (non-specific Lipid Transfer Protein) and peach major allergen, was selected as a model to investigate its interaction with cells of the human and murine immune systems as well as with the intestinal epithelium and the contribution of its ligand in inducing an allergic response was studied. Moreover, we analyzed the role of pathogen associated molecules in the induction of food allergy. For that, we selected the kiwi- alternaria system as a model and the role of Alt a 1 , major allergen of the fungus, in the development of Act d 2-sensitization was studied. In summary, this work presents an innovative research providing useful results for improving diagnosis and leading to further research on allergy and the final clarification of the mechanisms that characterize this disease.