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Evaluation of the antiangiogenic and angiopreventive activity of nature-based compounds.
No full textSeveral studies demonstrated that angiogenesis is a limiting process for tumour growth and progression. Consequently it is at the same time a potential target for both preventive and therapeutic interventions. Angiogenesis is a multi-step phenomenon that involves different cell types; in particular endothelial cells, tumour cells and immune cells, which orchestrate an intricate network of stimuli aiming to render tumour microenvironment suitable for malignant progression.
Here we have demonstrated the anti-angiogenic activity of three compounds derived from naturalling occurring sources: hyperforin (from Saint John’s Wort), methyl-2-cyano-3,12-dioxooleana-1,9-dien-28-oate (CDDO-Me) and 1-[2-cyano-3-,12-dioxooleana-1,9(11)-dien-28-oyl]imidazole (CDDO-Im), both synthetic compounds based on oleanolic acids found in citrus fruits. These compounds could be suitable chemoprevention approaches, and the CDDO derivatives are under study for chemotherapeutic application
Caratterizzazione molecolare di gp120 di HIV-1 e loro espressione su particelle simil virali (VLPs) come modello di presentazione antigenica.
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“Lo Stato liberale secolarizzato vive di presupposti che esso non può garantire” (Ernst-Wolfgang Boeckenfoerde): simbolismo della crisi di Stato-società nell’Occidente contemporaneo.
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Role of MeCP2 (Meyhyl CpG-Binding Protein) during replication, epigenetic inheritance and chromocenter organization of pericentric heterochromatin.
No full text“Epigenetic” is a term used to describe mitotically and meiotically heritable states of gene expression that are not due to changes in DNA sequence.
Epigenetic events are important in all aspects of biology such as cell proliferation, development and differentiation. The maintenance of a correct epigenome is fundamental in the proper progression of silencing effect, pivotal during cellular differentiation. Multi-protein complexes required to enable the heterochromatic stable epigenetic inheritance are associated to the structural organization of heterochromatin that is determined at the time of replication, in mid-late S phase.
MeCP2 is a Methyl CpG-binding protein that preferentially binds methylated DNA, localizes with pericentric heterochromatin and it has a key role to mediate large-scale chromatin organization and compaction.
While the impact of loss and mutations of MeCP2 has been extensively studied as cause of RTT and other neurodevelopmental and autismspectrum diseases little is known about its function in pericentric heterochromatin replication, structure and epigenetic inheritance. To test whether MeCP2 has a role in these processes, I used proliferating cells to study the effect of MeCP2 functional ablation during cell-cycle S-phase. I found that MeCP2 is not involved in heterochromatin replication, chromocenter organization and epigenetic modifications (H3K9me3, H4K20me3 and DNA methylation). Interestingly, MeCP2 influences cell cycle progression without triggering a strong apoptotic effect. Intriguingly, low levels of LaminB, LBR and LaminA/C proteins were found, suggesting that MeCP2 could be involved in nuclear lamina organization and/or in the expression of these genes. Besides, MeCP2 silencing determines low levels of EZH2 (component of PRC2, one of the two Polycomb-Repressive Complexes). In the light of this finding is intriguing to investigate the link between MeCP2 and EZH2 due the fact that a large number of neuronal differentiation genes which are required for neuronal development cells are bound by Polycomb complexes, whereas MeCP2 is a transcriptional regulator implicated in development of the brain that is required to interpret the DNA methylation signal in neurons.
In parallel, using different biochemical tools (TAP, gel filtration, mass spectrometry) I investigated the ability of MeCP2 to bind proteins involved in heterochromatin organization. A new interactor Np95, component of pHDBs (pericentric heterochromatin duplication bodies), was found.
My results show that MeCP2 in addition to play a role in maturation of neurons and synaptic plasticity it is implicated in cell proliferation. Besides, MeCP2 might be involved in nuclear envelope stability and/or in the expression of lamins, and in Polycomb proteins pathway. On the basis of this work further experiments should be done to better investigate the new functions of MeCP2
Pharmacological modulation of human polymorphonuclear leukocyte functions: from basic studies to clinical investigations.
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Expression of recombinant proteins in heterologous systems for biotechnological applications.
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Truncated erythropoietin receptor as a selectable marker for gene therapy of haematopoietic stem cells.
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Adpositional grammars: a multilingual grammar formalism for NLP.
No full textIn the field of computational linguistics, the representation of natural languages (NL) in formal grammar terms is a well-known issue and a wicked problem indeed. In fact, some formal grammars lack of lexical and semantic information representation, reducing the linguistic structure to syntax.
On the other side, approaches like dependency grammars lose expressive power, under a computational point of view. Adpositional grammars (adgrams) are a novel grammar formalism that overcomes these limitations.
Adgrams are based on Pennacchietti’s intuition, who put together Brøndal’s logic description of prepositions, Tesnerian notion of valence, Langacker’s cognitive dichotomy trajector/landmark and Silvio Ceccato’s pioneer work in the field on machine translation (MT). The result is a quasiformal description of adpositions, being the junctors of language structure.
This description is called adpositional space. Each adpositional space is made of four adpositional types: Plus (#), Minus ($), Slash (!), Times ()). The resulting structure is cognitively sound and formally inspiring, as adpositional trees (adtrees) can be built as special Porphyrian trees, going beyond the Tesnerian somehow fuzzy concept of dependency.
This dissertation puts Pennacchietti’s work a step forward. In fact, here adgrams consider the ultimate unit of NLs being the morpheme, not the word, and therefore they offer a coherent theory of both morphology and syntax. Hence, the collocation phenomena are considered like zero morphemes.
Moreover, a sharp distinction in the dictionary between the adpositional space, essentially made of closed morphemes, and the lexicon, made of open morphemes. Moving again from Tesnerian structural syntax, open morphemes always have a fundamental grammar character: stative (O), adjunctive (A, as stative modifiers), and verbal (I), circumstantial (E, as verbal modifiers). The Tesnierian approach is validated through Whorf’s research results comparing grammars of typologically distant NLs.
The second part shows that adgrams are computable, as they can be implemented with a strong, robust formalism. A concrete instance of the formal model of adgrams is given through the quasi-natural language Esperanto (QNL, Lyons), showing the linguistic viability of the model. The formal model should be used appropriately in an ad hoc epistemological scenario, called ‘the translation game’, designed as a Gedankenexperiment `a la Turing. A toy example is also given. In the third part the implementation is explained with all its details: the implementation of Esperanto is made in exactly 179 logic formulas, 56 of which are predicates. The formal model is promising to be generalised for any NLs, and how to do this was explained in various points of the third part. Finally, this dissertation shows that adgrams are a powerful NL grammar formalism which is at the same time cross-linguistic, cognitively grounded and formally robust and computationally sound
