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    Esporre i resti umani. Una questione museologica tra ricerca etica e comunicazione.

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    missin

    Reconstructing the evolutionary path of galaxies: a study of the main properties of early- and late-type galaxies over the redshift range 0.6<z<2.5.

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    The aim of the analysis carried out in this thesis work is twofold. On the one hand we are interested in addressing whether a sample of morphologically selected early-type galaxies (ETGs) differs from a sample of passive galaxies in terms of galaxy statistics. On the other hand we study how the relative abundance of galaxies, the number density, and, the stellar mass density of different morphological types change over the redshift range 0.6 ≤ z ≤ 2:5. Furthermore, we investigated if these galaxies and their properties can provide evidences on the possible variation of the abundance of low-to-high mass stars in galaxies, i.e. the variation of the IMF, with redshift, stellar mass and colours. From the 1302 galaxies brighter than Ks(AB)=22 selected from the GOODS-MUSIC catalogue, we classified the ETGs, i.e. elliptical (E) and spheroidal galaxies (E/S0), on the basis of their morphology and the passive galaxies on the basis of their specific star formation rate (sSFR≤10-11 yr-1). Since the definition of a passive galaxy depends on the model parameters assumed to fit the spectral energy distribution of the galaxy, in addition to the assumed sSFR threshold, we probed the dependence of this definition and selection on the stellar initial mass function (IMF). We find that spheroidal galaxies cannot be distinguished from the other morphological classes on the basis of their low star formation rate, irrespective of the IMF adopted in the models. In particular, we find that a large fraction of passive galaxies (> 30 %) are disc-shaped objects and that the passive selection misses a significant fraction (~ 26 %) of morphologically classified ETGs. Using the sample of 1302 galaxies morphologically classified into spheroidal galaxies (ETGs) and non-spheroidal galaxies (LTGs), we find that the fraction of these two morphological classes is constant over the redshift range 0:6 ≤ z ≤ 2:5, being 20-30 % the fraction of ETGs and 70-80 % the fraction of LTGs. However, at z 3 - 4 X 1011M) does not increase from z ~ 2:5, contrary to the lower mass galaxies. This suggests that the most massive galaxies formed at z > 2:5 - 3 and that the assembly of such high-mass galaxies is not effective at lower redshift. From the analysis f the galaxy SEDs, reproduced with different IMFs, we found that the bulk (> 80%) of the 1302 galaxies are best-fitted with IMFs that contain a greater relative number of low-mass stars compared to a Salpeter IMF. This trend is constant with redshift and galaxy mass, testifying that from our data we do not observe an IMF variation as function of the cosmic time, galaxy mass and galaxy morphology

    Towards making functional size measurement easily usable in practice

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    Functional Size Measurement methods –like the IFPUG Function Point Analysis and COSMIC methods– are widely used to quantify the size of applications. However, the measurement process is often too long or too expensive, or it requires more knowledge than available when development effort estimates are due. To overcome these problems, simplified measurement methods have been proposed. This research explores easily usable functional size measurement method, aiming to improve efficiency, reduce difficulty and cost, and make functional size measurement widely adopted in practice. The first stage of the research involved the study of functional size measurement methods (in particular Function Point Analysis and COSMIC), simplified methods, and measurement based on measurement-oriented models. Then, we modeled a set of applications in a measurement-oriented way, and obtained UML models suitable for functional size measurement. From these UML models we derived both functional size measures and object-oriented measures. Using these measures it was possible to: 1) Evaluate existing simplified functional size measurement methods and derive our own simplified model. 2) Explore whether simplified method can be used in various stages of modeling and evaluate their accuracy. 3) Analyze the relationship between functional size measures and object oriented measures. In addition, the conversion between FPA and COSMIC was studied as an alternative simplified functional size measurement process. Our research revealed that: 1) In general it is possible to size software via simplified measurement processes with acceptable accuracy. In particular, the simplification of the measurement process allows the measurer to skip the function weighting phases, which are usually expensive, since they require a thorough analysis of the details of both data and operations. The models obtained from out dataset yielded results that are similar to those reported in the literature. All simplified measurement methods that use predefined weights for all the transaction and data types identified in Function Point Analysis provided similar results, characterized by acceptable accuracy. On the contrary, methods that rely on just one of the elements that contribute to functional size tend to be quite inaccurate. In general, different methods showed different accuracy for Real-Time and non Real-Time applications. 2) It is possible to write progressively more detailed and complete UML models of user requirements that provide the data required by the simplified COSMIC methods. These models yield progressively more accurate measures of the modeled software. Initial measures are based on simple models and are obtained quickly and with little effort. As V models grow in completeness and detail, the measures increase their accuracy. Developers that use UML for requirements modeling can obtain early estimates of the applications‘ sizes at the beginning of the development process, when only very simple UML models have been built for the applications, and can obtain increasingly more accurate size estimates while the knowledge of the products increases and UML models are refined accordingly. 3) Both Function Point Analysis and COSMIC functional size measures appear correlated to object-oriented measures. In particular, associations with basic object- oriented measures were found: Function Points appear associated with the number of classes, the number of attributes and the number of methods; CFP appear associated with the number of attributes. This result suggests that even a very basic UML model, like a class diagram, can support size measures that appear equivalent to functional size measures (which are much harder to obtain). Actually, object-oriented measures can be obtained automatically from models, thus dramatically decreasing the measurement effort, in comparison with functional size measurement. In addition, we proposed conversion method between Function Points and COSMIC based on analytical criteria. Our research has expanded the knowledge on how to simplify the methods for measuring the functional size of the software, i.e., the measure of functional user requirements. Basides providing information immediately usable by developers, the researchalso presents examples of analysis that can be replicated by other researchers, to increase the reliability and generality of the results

    Quasar physical pairs.

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    missin

    English credit: teoria e storia di una fede vittoriosa.

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    The following dissertation is divided into two parts. The first part is mainly theoretical and deals with one of the major riddles that have obsessed economic thinking at least from the times of Aristotle: the search for a theoretically sound and historically adequate account of the origins of money. The solutions offered, among other thinkers, by Adam Smith, Carl Menger, Alfred Mitchell Innes, Georg Friedrich Knapp, Philip Grierson have broadly been discussed, but eventually they have been found by the author insufficient to solve the mistery. A better result can be obtained if the problem is posed after an intellectual translation operated with the tools offered by analytic philosophy; more than a simple enlargement of the scope of the research, the - Wittgensteinian in spirit - solution I propose is an entirely new perspective that allows to escape the tantalizing finding of an essentialistic definition of money. In this way, the centre of the attention is more on “money” (the word) and less on money as object (the different kind of things taken into account by economic and anthropologic literature). This new point of view is extensively used in the second part of my dissertation, which is mainly historical, and helps to clarify the still unclear role of the so–called “imaginary money” in the economic facts of the Ancien Régime. The last and most extensive chapter of my dissertation deals with the peculiar form of money that emerged from 17th-century England, particularly after the establishment of the Bank of England (1694). The originality of the reconstruction lies in the attempt to explain the birth of credit-money as the birth of new form of popular faith (Creditt)

    Preservation and diffusion of some native Italian chicken breeds.

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    The safeguard of animal biodiversity is a strong objective in developed countries. The genetic variability gives the chance to select individuals more adapted to climatic changes, diseases and potential market variations. Because of the different environments, up to decades ago, Italy showed a considerable biodiversity in native livestock breeds and populations. Within the last one hundred years, the number of endangered native breeds dramatically increased, leading to an irreversible loss of genetic resources. About 60% of chicken breeds reared in Italy until some decades ago are currently disappeared. The reason of this trend is mainly due to the selection of specialized breeds very efficient in converting feed into egg and meat. Contemporarily, the abandoning of rural breeding in favour of intensive farming system which uses few selected chicken lines exacerbates such negative trend. The extant breeds, excluded from commercial selection process, represent an important source of variability. The main critical point of local breeds is generally the low productivity which implies that a large part of body resources are used for maintenance (kinetic activity, immune response) and only the residual are assigned to production traits. This fact implies a low productivity but in the same time renders the animal adaptable to poor environment. In particular seems that such pure breed had more aptitude to elongate and desaturate essential fatty acids (linoleic acid, n-6 and α-linolenic acid, n-3) in their long chain derivates (arachidonic acid-AA, eicosapentaenoic acid-EPA, docosahexaenoic acidDHA), with a consequently greater accumulation on products. This would represent an important goal for the livestock word, since it provides a compromise: between rusticity and economic sustainability and designs a healthier chicken meat for nutritional-conscious consumers, also in accordance with a big problem of the safeguard of the biodiversity. The aim of the present PhD work was to study the adaptation response of local chicken breed to extensive farming conditions. The experimental activity is divided into different experiments where we analyzed the behavior and welfare of different poultry breeds in extensive farming system and the quality of the products (meat and eggs) with a focus on lipid content and the metabolism of Long Chain Polyunsaturated Fatty Acids (LC-PUFA). It was also studied the metabolic pathways of LC-PUFA and how different genotypes respond to feed changes testing the hypothesis that nutrition can influence the ontogenetic development. In detail the effect of extensive farming systems which implies large availability of pasture on different chicken genotypes (local breeds vs commercial hybrids) was compared. The main traits that have been evaluated are: productive performance, health and welfare, immune response and qualitative characteristics of product. Different physiological (IMMUNITY: lysozyme, complement, serum bactericidal activity; OXIDATIVE STATUS: ROS, antioxidant power), and ethological indicators (behavior, tonic immobility, body lesions) have been used for this purpose. Nutritional characteristics of eggs and meat, with particular attention to oxidative and fatty acid profile were studied through the evaluation of TBARS, tocopherols, carotenoids, polyphenols, PUFA n-3 and n-6 content. Great emphasis has been paid to the study of LC-PUFA since local strain seemed more efficient in the synthesis of these fatty acids. In particular in the experiment 1 the adaptive response of Ancona laying hens to extensive farming system in comparison to commercial hybrids has been analyzed. Ancona birds showed a specific ethological profile associated with very good welfare conditions, better immune system and oxidative status. The Ancona breed seems more adapted to less controlled environment and showed a higher percentage of "natural” behavior. Such behaviors are high in energy cost, allowing the more selected birds to save energy which could be reallocated to production traits. At the same time, the lower productivity of Ancona birds resulted in a better balance with the extensive environment, as evidenced by health status and mortality rate. In the experiment 2 the meat traits of six hundred male chicks from slow-growing (Leghorn, Ancona, Cornish x Leghorn), medium-growing (Naked Neck, Kabir) and fast-growing (Ross) strains have been studied. The physiological state of the birds appears to be inversely correlated with the genetic selection, indeed the slow-growing showed more marked natural behaviors, followed by the medium-growing. They showed a good adaptation to extensive environment. Indeed the slow-growth rate is only a prerequisite for adaptability to the extensive system; other traits as the grazing attitude, kinetic activity, body structure and the immune response greatly affect such adaptation. It has been reported that the most relevant role of grass in organic poultry is represented by the intake of several bioactive compounds (i.e. PUFA, vitamins and pigments) with a direct effect on the quality of meat and eggs. For these reasons, it is important to determine the intake and the nutritional relevance of pasture to develop suitable free-range diets and to investigate the transfer of the above-mentioned compounds into the poultry products. In the experiment 3 eggs quality was been assessed. Ancona hens produced a lower number of eggs than commercial line but markedly different from the qualitative point of view. Indeed, Ancona eggs compared to Hy-line had higher carotenoid, polyphenol and tocopherol contents that in turn have a relevant effect on human health. Even the fatty acid profile improved (lower n-6/n-3 ratio; higher C18:3n-3 and LC-PUFA n-3); this latter fact confirms the ability of the hen to elongate/desaturate linolenic acid and to transfer n-3 LC-PUFA to the egg where exert important role during the chick growth. These differences were mainly due to the availability of green pasture and to the higher pasture attitude of Ancona hens. In experiment 4 we analyzed the fatty acid and antioxidant profile of breast meat from chickens reared according to the organic system. The slow-growing strains are egg-type lines which seem to have a higher efficiency in LC-PUFA deposition respecting to meat-type, being that elongation is partly affected by the estrogen level. Concerning the content of saturated fatty acids (SFA), the highest value was observed in fast-growing genotype. However, the meat of slow-growing chickens had lower lipid stability despite higher antioxidant content probably due to the kinetic behavior and the resulting pro-oxidative metabolism. The results of this study indicate that in extensive farming chicken genotypes play an important role in the fatty acid composition of meat. This finding assumes great importance because health concerns over human fat intake are one of the main factors contributing to the decline of meat intake. The observed differences among poultry genotypes indicate that a suitable compromise between rusticity and economic sustainability could be found and a healthier chicken meat for nutrition-conscious consumers could be designed. With the aim to improve the nutritional value of products a relationship between genotype and desaturating ability was evidenced with a significant impact on the PUFA content in the meat. In the experiment 5 we have estimated the lipid indices of six chicken genotype organically reared. We can said that the differences in meat lipid content are affected by breed, and that the pure breed had a two time higher Δ5/Δ6-desaturase index value than medium and fast-growing strains. To confirm our previously estimated, we have evaluated the direct measure of different enzymatic activity and gene expression of the above-mentioned complex in liver mitochondria in the experiment 6. Three groups of laying hens for each genotype (slow-, fast- and slow x fast-growing crossing) were fed with a standard diet. To hatch, 5 chicks/genotype were sacrificed and the liver was taken for enzyme activity and gene expression of Δ6-desaturase. Slow-growing chicken in comparison to fast-growing strain showed a higher desaturase activity. Data showed that the mRNA expression of FADS2 gene is strongly correlated with genetic selection. It seems to be higher in mediumgrowing strains although their enzyme activity was intermediate. Finally, in the experiment 7 we have tested where possible to modified lipid metabolic pathway with dietary supplementation of precursor (linolenic acid) or directly LC-PUFA (EPA and DHA). Three groups of laying hens for each genotype (slow-growing vs fast-growing) were fed with three different diets: control (standard diet), LCPn-3 (standard diet with 3% fish oil) and LNA (standard diet with 10% of linseed). Enzyme activity and gene expression of Δ6-desaturase were assessed to chicks liver as previously mentioned. The results showed that diets slightly affected lipid metabolism whereas the genetic effect was confirmed. Data reported in these last experiments showed that the expression and activity of Δ6-desaturase is strongly correlated with the genotype, so reaching an important objective for the food industry, since dietary modifications do not seem able to change the lipid metabolism. Concluding, my PhD work has the aim to assess the use of Italian local strains in extensive farming system, not just to safeguard the breeds from extinction, but also to exploit them economically, given the higher adaptability to poorer environment and the particular PUFA metabolism. They could represent an important source of gene bank, indeed selection processes and crosses of such strain with other more productive strains, could be a good alternative. In particularly, these genotypes could be exploited as suitable strains for the production of meat and eggs having higher nutritional value

    Clinical and echocardiographic correlates of acute heart failure, cardiogenetic shock and in-hospital mortality in tako-tsubo cardiomyopathy: insights from the “Tako-tsubo Italian Network”.

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    Objective: to determine clinical and echocardiographic correlates of acute heart failure, cardiogenic shock and in-hospital mortality in a large cohort of tako-tsubo cardiomyopathy (TTC) patients. Background: despite good long-term prognosis, life-threatening complications due to hemodynamic instability can occur early in TTC patients. Methods: the study population consisted of 227 patients (66.2 ± 12.2 years; female 90.3%) enrolled in the Tako-tsubo Italian Network, undergoing transthoracic two-dimensional echocardiography on admission and at short-term follow-up [4.3 (4-6) weeks]. Patients were divided into two groups according to the presence or absence of major adverse events, a composite of acute heart failure, cardiogenic shock, and in-hospital mortality. Results: major adverse events occurred in 59 patients (25.9%). Elderly patients aged ≥75 years (42.4 vs 23.8%; p=0.011), left ventricular (LV) ejection fraction (35.1 ± 5.9 vs 38.4 ± 4.6%; p<0.001), wall motion score index (1.9 ± 0.2 vs 1.7 ± 0.2; p<0.001), E/e’ ratio (13.5 ± 4.3 vs 9.9 ± 3.3; p<0.001), LV outflow tract obstruction (23.7 vs 8.9%, p=0.006), pulmonary artery systolic pressure (47.4 ± 12.3 vs 38.0 ± 9.2 mmHg; p<0.001), right ventricular involvement (28.8 vs 9.5%;p<0.001), and reversible moderate to severe mitral regurgitation (49.1 vs 11.9%; p<0.001) were significantly different between groups and were associated with adverse events. At multivariate analysis, LV ejection fraction (HR 0.92; 95%CI: 0.89-0.95; p<0.001), E/e’ ratio (HR 1.13; 95%CI: 1.02-1.24; p=0.011), reversible moderate to severe mitral regurgitation (HR 3.25; 95%CI: 1.16-9.10; p=0.025), and age ≥75 years (HR 2.81; 95%CI: 1.05-7.52; p=0.039) were independent correlates of major adverse events. Conclusions: echocardiographic parameters provide additional information compared to other variables routinely used in clinical practice in identifying patients at higher risk of hemodynamic deterioration and poor in-hospital outcome, allowing prompt institution of appropriate pharmacological treatment and adequate mechanical support

    Molecular aspects of small bowel adenocarcinoma for new therapeutic approaches.

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    Small Bowel Adenocarcinoma (SBA) is a rare and aggressive neoplastic disease. Several aspects of SBA carcinogenesis still need to be elucidated, but risk factors and histomorphological similarities seem to indicate that SBA can follow a carcinogenetic development similar to that proposed for colorectal cancer. At molecular level, at odds with adenocarcinoma arising in the large intestine, very few, and fragmented, information is available for SBA. In general, it has been suggested that the two models of colorectal carcinogenesis can be valid also for SBA. For that reason, chemotherapies set up for the cancers of the large intestine have been applied also for SBA. Therefore, since recent studies led to the introduction of EGFR-targeted therapies in colorectal cancer, the treatment with anti-EGFR drugs can be proposed also for SBA patients. In particular, in colorectal cancer patients it has been demonstrated that KRAS mutations are correlated with the absence of efficacy of EGFR-targeted therapies, and it has been proposed by few studies to investigate additional markers of the EGFR pathway (EGFR gene copy number, BRAF and PIK3CA mutations, as well as PTEN protein expression), in order to increase the predictive power of the efficacy of anti-EGFR drugs. Information regarding these markers in SBA is quite completely missing. Primary aim of the present work was the evaluation, in the same cohort, of all the alterations involved in colorectal carcinogenesis, in order to shed light more deeply about the molecular similarity between SBA and colorectal cancer. Second aim of the present work was to investigate in the same cohort of SBA the aforementioned markers involved in the EGFR pathway, in order to verify if the pattern of these alterations could justify the possible introduction of these therapies also in patients affected by SBA. To do this, for the first aim we investigated -catenin protein expression by immunohistochemistry (IHC), and KRAS and TP53 mutations by direct sequencing, as well as microsatellite instability (MSI) and allelic imbalance of Chromosome 18q MSI by fragment analysis on genomic DNA extracted from formalin-fixed paraffinembedded tissue sections. For the second aim we investigated EGFR gene status by Fluorescent in situ hybridization (FISH), BRAF and PIK3CA mutational status by direct sequencing, as well as PTEN protein expression by IHC, in the same cohort of SBA. We recruited 40 SBA cases from the Institute of Pathology of Locarno (Canton Tessin, Southern Switzerland) and from three institutions of Northern Italy. First aim. -catenin overexpression was observed in 23.6% at nuclear level and in additional 47.3% of cases only at cytoplasmic level, MSI was found in 23.6% of cases, KRAS mutations in 43.6% of cases, TP53 mutations in 29% of cases and allelic imbalance of Chromosome 18q in 75% of cases. All the percentages of alterations and the types of mutations are in line with those identified in the analysis of colorectal cancer patients. Therefore, by the analysis of all these markers in a same cohort, we can confirm that SBA shares the carcinogenetic development with colorectal cancer also at molecular level. Second aim. We identified a copy number gain of EGFR gene in 57.5% of cases, BRAF and PIK3CA mutations in 2.5% and 10.5% of cases respectively, and PTEN loss of expression in 25.6% of cases. Also for the EGFR pathway analysis, percentages of alterations and types of mutations found in SBA are in line with colorectal cancer, even if we did not detect the classical V600E change in the BRAF gene (where, on the contrary, we found a rare mutation, the G596R change). Taking into account the molecular algorithm proposed for the administration of EGFR-targeted therapies in colorectal cancer patients, if we look only at KRAS mutations, we can propose the administration of EGFR-targeted therapies to about 60% of patients (i.e.: KRAS wildtype cases), and to 23% of cases if we base our evaluation on the whole EGFR pathway (i.e.: cases showing, at the same time, EGFR copy number gain, KRAS, BRAF and PIK3CA wild-type sequences, and PTEN normal expression). The treatment with anti-EGFR therapies of a SBA patient of our cohort who developed a metastatic lesion confirmed the relevance of the molecular characterization of the tumor to predict the response to these therapies. In conclusion, our analyses of SBA confirm the feeling that the mechanisms of carcinogenesis of such disease are superimposable with those proposed for colorectal cancer. Therefore, the hypothesis that therapeutic protocols valid for the large intestine can be applied also to SBA patients is supported. As a consequence, the targeted therapies recently introduced in colorectal cancer can be proposed for SBA patients, pending tumor molecular characterization as demonstrated by our case report

    Human tumor retrovirus-host-interaction: role of CIITA in the functional inhibition of HTLV-1 Tax-1 oncogenic protein.

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    Human T-cell Lymphotropic Virus type-1 (HTLV-1) is the causative agent of an aggressive malignancy of CD4+ T lymphocytes. Many evidences have shown that constitutive activation of NF-κB pathway by Tax-1 is crucial for T-cell transformation. Previous results demonstrated that CIITA, the master regulator of MHC class II gene transcription, inhibits HTLV-1 replication by blocking the transcription function of the viral transactivator Tax-1. Here we show that CIITA suppresses also Tax-1-mediated activation of the NF-κB pathway. CIITA interacts with and retains Tax-1 in the detergent unsoluble cell fraction (cytoplasmic debris) and inhibits Tax-1-dependent nuclear translocation of RelA. Moreover, the overexpression of CIITA does not affect Tax-1 interaction with both RelA and IKKγ. Nevertheless, the enzymatic activity of IKK kinase promoted by Tax-1 is impaired in the presence of CIITA. CIITA acts by suppressing at least the canonical NF-κB pathway, in that it also inhibits the activation of NF-κB by Tax-2, which is known to activate NF-κB through the canonical but not the non-canonical pathway. Overall, our results indicate that CIITA, beside acting as viral restriction factor against HTLV-1 infection, might counteract Tax-1 transforming activity. Thus, assessing the molecular basis of CIITA-mediated Tax-1 inhibition may be important in defining new strategies to control HTLV-1 spreading and oncogenic potential

    Identification and modulation of the allograft inflammatory factor-1 (AIF-1) homologous in the medicinal leech Hirudo Medicinalis.

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    Allograft inflammatory factor-1 (AIF-1) is a 17 kDa cytokine-inducible calcium-binding protein that in vertebrates plays an important role in allografts immune response and its expression is mostly limited to the monocyte/macrophage lineage. Recently it was assumed that AIF-1 was a novel molecule involved in inflammatory responses. To better clarify this aspect in the present study we investigated the expression of AIF-1 after bacterial challenge, wounds and tissue transplants and its potential role in regulating the innate immune response in an invertebrate model, the medicinal leech (Hirudo medicinalis). The analysis of an EST library from H. medicinalis CNS, revealed the presence of a gene, named Hmaif-1/alias Hmiba1, showing a high homology with vertebrate aif-1. Immunohistochemistry using an anti-HmAIF-1 polyclonal antibody showed that this protein is constitutively present in spread, CD68+ macrophage-like cells. A few hours after pathogen bacterial injection in the body wall, the amount of these immunopositive cells increases at the injected site, co-expressing HmAIF-1 and the common leukocyte marker CD45. A similar overview was observed in the early stages of wound healing, especially at 24 hours after injury, with a lot of immunopositive cells around the lesion site. Moreover here we demonstrated that the recombinant protein HmAIF-1 induced a massive angiogenesis and it was also a potent chemoattractant for macrophages. After rHmAIF-1 stimulation, macrophage-like cells co-expressed the macrophage marker CD68 and the surface glycoprotein CD45, which in Vertebrates is implicated in the integrinmediated adhesion of macrophages and plays a key role in regulating the functional responsiveness of cells to chemoattractants. We therefore hypothesized that CD45 could play a role for leech macrophage-like cells activation and migration towards the inflammation site and we examined its potential effect on HmAIF-1-induced signaling

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