177,699 research outputs found
Gli scavi nell'abitato ligure del Guardamonte
No full textBreve sintesi dei risultati di un decennio di ricerche nel sito d'altura ligure indagato dall'équipe dell'Università di Milano guidata da Cristina Chiaramonte Treré
Il Pathway di NOTCH nei mielomi multipli : razionale per una possibile terapia inibitoria
No full textNon richiest
Ciclo di conferenze presso l'ASSOCIAZIONE LOMBARDA ARCHEOLOGICA – AMICI DEL MUSEO ARCHEOLOGICO DI MILANO Coordinato dalla professoressa Maria Cristina Chiaramonte dal titolo: Archeologia italica oggi
No full textSi sono tenute 12 conferenze su argomenti inerenti le testimonianze archeologiche dei popoli stanziati nella penisola italica nel corso del I millennio a.C., con particolare attenzione alle genti del versante orientale della dorsale appenninica e della costa adriatica.
Archeologia italica oggi
Giovedì 24 gennaio 2008
Cristina Chiaramonte Treré: I popoli italici tra Etruschi e Greci
Giovedì 7 febbraio 2008
Giorgio Baratti: Pastori e guerrieri sulle vie della transumanza
Giovedì 21 febbraio 2008
Lucia Mordeglia: Le ultime scoperte: gli Italici ai piedi del Gran Sasso
Giovedì 20 marzo 2008
Claudia Lambrugo: Dalla capanna alla casa, abitare in Basilicata tra indigeni e Greci
Giovedì 10 aprile 2008
Rossella Mantia: Abbigliamento femminile dell’aristocrazia italica
Giovedì 24 aprile 2008
Cecilia Scotti: Paestum e Pompei, gli Italici conquistano le città
Giovedì 8 maggio 2008
Matteo Cadario: I santuari italici verso la Romanizzazione
Giovedì 22 maggio 2008
Federica Chiesa: Ornamenti e gioielli etrusco-italici
Inverno-primavera 2009
Patrizia Boccolini: I Veneti “dai bei cavalli”
Lucia Mordeglia: I Liguri dal mito alla realtà archeologica
Giorgio Baratti: Etruschi e Liguri tra Appennino e Tirreno
Rossella Mantia: Il Po, frontiera e ponte tra i popoli della pianur
The echinoderm innate humoral immune response
No full textAbstract: Multicellular organisms have an immune system, which is essential for the survival of living beings. Interest in the immune system has been expanded since common characteristics of innate immunity between Drosophila melanogaster (Meigen, 1830) and mammals were discovered in the 1980. Since then, immunology has mainly focused on the adaptive immune system that seems to be restricted to vertebrates. Unlike the innate immunity, the adaptive one is acquired after exposure to a specific antigen (Ag) and includes: antigen-presenting cells such as macrophages, proliferation of B and T lymphocytes, Ag-specific antibody/cytokine production and immunological memory. Innate immunity is instead a process of cellular defense at low specificity, which is designed to prevent and combat infectious agents that penetrate at the tissue level, and may be the only form of immunity present in invertebrates such as sea urchins. The immune system of invertebrates acts through (i) cellular components (cell-mediated immunity) in which the effectors of defense reactions are represented by immune cells; (ii) soluble factors (humoral immunity), secreted by the immune cells, such as lectins, agglutinins, lysins, antimicrobial peptides and the prophenoloxidase (proPO) activating system, which act in parallel with the immune cells to fight pathogens and other foreign substances. Here we aim to deepen the study on humoral immunity of invertebrates, especially referring to the phylum Echinodermata because of its features shared with protostomes and other deuterostomes, and suggesting a key step during evolution
Myeloid derived-suppressor cells as a potential target of immunotherapy in notch dependent T-cell acute lymphoblastic leukemia
No full textNotch receptors play crucial roles in T-cell development, and their dysregulation leads to the development of T-cell Acute Lymphoblastic Leukemia (T-ALL), a condition that, as of now, lacks a definitive cure. Notch3 transgenic mice (N3-tg) represent a well- established model for T-ALL, where the constitutive activation of the receptor in immature thymocytes initiates an aggressive disease characterized by the expansion of tumoral T cells in the periphery. These tumor cells can trigger a Notch/IL-6-dependent accumulation of Myeloid-Derived Suppressor Cells (MDSCs), which, in turn, support tumor progression. MDSCs are an immature cell subset that inhibits immune responses, creating a conductive environment for tumor growth. Programmed cell death 1 (PD-1) is an inhibitory receptor of immune responses, recognized for its role as a suppressor of T-cell activation and proliferation when interacting with the PD-L1 ligand. MDSCs contribute to tumor progression through various mechanisms, including the expression of PD-L1, resulting in the inhibition of PD-1 expressing cells within the tumor microenvironment, such as T- and NK-cells.
The main aim of my thesis was to identify MDSC targets and mechanisms of action in the tumor microenvironment of our Notch-dependent murine model of T-ALL, with regard to their potential role in inhibiting NK activity, possibly through the PD-1/PD-L1 axis. Thus, this research ultimately aims to develop an innovative combined therapy for T-ALL, targeting tumor T cells, enhancing NK activity, and modulating MDSC function.
My data demonstrated that in N3-tg mice, number and function of NK cells decline significantly, while the percentage of them expressing PD-1 increases, during disease progression. This coincided with an expansion of functional MDSCs and in particular of the PD-L1+ fraction. This inverse correlation suggests us that NK impairment could be driven by MDSCs. Indeed, through in vitro cytotoxicity assay based on co-culture of NK cells with MDSCs, both from spleen of N3-tg mice, we confirmed that MDSCs can significantly hinder NK cell function.
Finally, treating N3-tg mice with anti-PD-L1 blocking antibodies markedly inhibits T- ALL progression, by significantly reductions in splenomegaly and absolute count of tumor cells. Moreover, the treatment led to a substantial decrease in overall MDSC numbers, particularly within the PD-L1-expressing subset. Concurrently, there was a noticeable expansion of PD-1+ NK cells, exhibiting a significantly heightened cytotoxic activity compared to the control group.
In conclusion, my results suggest that in Notch-dependent T-ALL, MDSCs may hinder the anti-tumor activity of NK cells via the PD-1/PD-L1 axis, thus favoring disease progression. Then, molecules and cells of this network could potentially serve as prognostic markers and/or targets for innovative therapies
FRESHWATER CYANOBACTERIA, IDENTIFIED BY MICROSCOPIC AND MOLECULAR INVESTIGATIONS ON A COLONIZED FOUNTAIN SURFACE: A CASE STUDY IN PALERMO (SICILY, ITALY)
No full textCyanobacteria or blue algae are ubiquitously present in both fresh and brackish water
environments. They also grow in conditions of high humidity, colonizing stones or
monuments and fountain surfaces, and creating thick biofilms able to induce biodeterioration
in the constituent materials of artefacts. As well as several photoautotrophic
organisms, cyanobacteria belong to the microorganisms identified as primary colonizers,
playing an important role in stone artwork deterioration.
In this study, an analysis was made of the biofilm collected from the stone fountain of
the Two Dragons in Palermo (Italy), revealing the presence of cyanobacterial colonies by
optical microscopy, due to their peculiar auto-fluorescence. Furthermore, molecular investigations
by qPCR (quantitative Polymerase Chain Reaction) were utilized to gather
quantitative information, and phylogenetics analysis was used to confirm the Thioredoxin
reductase (TrxR) gene as a suitable molecular marker. The results highlight the presence
of cyanobacteria as the main taxa, whose growth is induced by microclimatic and
environmental conditions, and by the physical characteristics of the stone surface.
Identification of microbial populations living on stone artworks is the starting point for
successful control and conservation strategies, which can help to define the correct
protocols to block cellular activity and to find appropriate methods for removing biofilm,
as well as counteracting possible recolonization
Senescence-dependent regulation of type 1 plasminogen activator inhibitor in human vascular endothelial cells
No full textType 1 plasminogen activator inhibitor (PAI-1) is the primary inhibitor plasminogen activator and has been found to be increased in a number of clinical conditions generally defined as prothrombotic. Since in aging and in atherosclerosis the changes observed in the endothelium resemble those of in vitro aged endothelial cells, we have examined the expression of PAI-1 in cells at different population doublings. In senescent endothelial cells, PAI-1 mRNA and protein are constitutively high, but uninducible by exogenous interleukin 1 alpha as well as by the phorbol ester TPA. Interestingly the increase of PAI-1 levels correlates with the upregulation of interleukin 1 alpha, which characterizes endothelial cell senescence. Since PAI-1 expression is not increased in young cells made nondividing by contact inhibition, we anticipate that PAI-1 expression can be used as an appropriate marker of endothelial senescence. Moreover, PAI-1 was not upregulated in senescent or in progeric human fibroblasts, which do not overexpress interleukin 1 alpha, thus suggesting that multiple pathways may exist to regulate aging of human fibroblasts and endothelial cells
Higher order methods for simulating fracturing with applications in multiphysics problems
No full textWe develop higher order finite element methods for fracture mechanics. The framework is cast within the context of conforming finite elements [1]. The method [2] exploits the a priori knowledge of the singular behavior of the fields to construct an alternate regular solution. Solving for the alternate problem yields optimal rates of convergence and high order of accuracy. The salient feature of the method is the lack of additional degrees of freedom in comparison with its standard Galerking finite element formulation. Effectively for the same computational cost we obtain a higher order of accuracy. Along with the above we employ interaction integrals for curvilinear fractures as presented in [3] and generalize their definition for the proposed higher order method. Along with the optimality of the convergence of the solution we showcase the accuracy and the convergent behavior of the computed stress intensity factors. The method is verified with respect several analytical solutions. The applications of the framework are showcased for complex fracturing problems. In particular, simulations of fracture instabilities in thermo elastic materials subjected to large temperature gradients, where oscillatory fracture behavior is expected, will be used to demonstrate the robustness and capabilities of the presented tools. REFERENCES [1] Rangarajan, R., Chiaramonte, M.M., Shen, Y., Hunsweck, M.J., Lew, A.J. Simulating curvilinear crack propagation with universal meshes. Int. J. Numer. Meth. Eng., Submitted. [2] Chiaramonte, M.M., Shen, Y., Lew, A.J. Higher order finite element methods for fracture mechanics. Preprint, 2013. [3] Chiaramonte, M.M., Shen, Y., Keer, L.M., Lew, A.J. Computing stress intensity factors for curvilinear fractures. Preprint, 2013
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