Search

Table S1. CGIs methylation values in CLL. (DOCX 13 kb)

Colorectal cancer (CRC) develops through the accumulation of both genetic and epigenetic alterations. However, while the former are already used as prognostic and predictive biomarkers, the latter are less well characterized. Here, performing global methylation analysis on both CRCs and adenomas by Illumina Infinium HumanMethylation450 Bead Chips, we identified a panel of 74 altered CpG islands, demonstrating that the earliest methylation alterations affect genes coding for proteins involved in the crosstalk between cell and surrounding environment. The panel discriminates CRCs and adenomas from peritumoral and normal mucosa with very high specificity (100%) and sensitivity (99.9%). Interestingly, over 70% of the hypermethylated islands resulted in downregulation of gene expression. To establish the possible usefulness of these non-invasive markers for detection of colon cancer, we selected three biomarkers and identified the presence of altered methylation in stool DNA and plasma cell-free circulating DNA from CRC patients.

This study provides an account of how a naturalistic orientation in epistemology known as evolutionary epistemology can benefit from integration with some more recent advancements in cultural evolutionary theory. In particular, this thesis explores the ways in which a Darwinian selective framework of culture provides new insights to rethink unsolved epistemological disputes and problems such as the growth of scientific ideas, the notion of scientific progress, the ‘context distinction’, the theory ladenness of science and a demarcation criterion between science and other cultural realms. All these issues are approached from an evolutionary and selective standpoint that assumes that biological and cultural selection are representative of a wider and more encompassing selective process. Thus, the thesis also explores theoretical disputes concerning the analogies and disanalogies between cultural and biological selection. Five early evolutionary analogies of knowledge accretion are explored in the first chapter setting the context of the debate for the epistemological issues that are connected in the other chapters to cultural evolution. Here, a populationist account of scientific ideas is presented as a viable model to study the conceptual and ‘ideational’ dynamics of change in science. In the last part of this work, my populationist and selective model is applied to study a specific scientific innovation: a molecular technique for taxonomic identification and classification known as DNA barcoding. Finally, the last chapter explores the use of text analysis to investigate the network of concepts and ideas that relate to the ‘DNA barcoding’ concept’. Here, I evaluate the impact of this technique on the fields of taxonomy/systematics, particularly, for what concerns the so called ‘species problem’.

Una determinata realtà sociale talvolta viene considerata statica, priva di potenzialità, arretrata solo perché cosi è più comodo. E' più comoda da studiare, perché ogni atteggiamento preconcetto può essere assunto come dato scientifico. Ma è, soprattutto più comoda da "gestire", perché ogni scompenso, ogni ritardo, è attribuibile serenamente a fattori costituzionali della società stessa. Da Banfield in poi una "società statica" è sempre colpevole: tanto per i suoi mali, quanto dei mali delle "aree più sviluppate". Ma questa idea di staticità e di arretratezza può e deve essere rivista. In questo libro si propone un aspetto particolare del vivere sociale, il rapportarsi del cittadino al diritto e alle istituzioni, come chiave di lettura di un processo generale di mutamento, come indice di una dinamicità che supera le previsioni e le apparenze. Si tratta di un processo discontinuo e non lineare, in cui le categorie di moderno e tradizionale mostrano la loro ineguatezza. Gli stessi riferimenti concettuali ad un "prima" e ad un "dopo" non sono più tanto sicuri, cosi come nel disegno di Escher non si capisce bene qual è il sopra e quale il sotto. Il quadro che emerge è quello di una regione, la Sardegna, in cui le "permanenze" possono essere lette in realtà come "anticipazioni" e il passato e il presente si intersecano per formare una realtà dinamica, la cui problematicità, per essere fattivamente risolta, non necessita tanto di definizioni di specificità, quanto di essere riportata all'interno della problematica generale del nostro tempo.

La Sardegna è sempre in crisi, tutte le sere il progresso è dietro l'angolo, tutte le mattine non c'è ancora. Sono i misteri della transizione (dai modelli di vita rurali a quelli urbani, dall'agricoltura all'industria, dai monti al mare etc.) intorno a cui si esercitano da sempre, secondo meccanismi ormai tanto ripetitivi da essere rituali, molti intellettuali, dipendenti o autonomisti, molte forze politiche, grandi e piccole, dell'isola. Chi scrive questo libro vuole proporre, sulla base di una serie di ricerche di settore di cui si pubblicano i risultati una idea diversa: la Sardegna oggi sta in equilibrio, il suo sviluppo conteneva già in sé l'esigenza dei propri freni, è il suo stare nell'economia-mondo euro-mediterranea a creare la situazione attuale, che non è di transito, ma stabile, anche se di una stabilità fatta di contrasti, di difficoltà, di miserie, ma anche di arricchimenti, di crescita culturale, di nuove sapienze e di nuove figure sociali, spesso, contemporaneamente, vecchie e nuove. Davanti a una situazione stabile non si può intervenire negli stessi termini imposti da una realtà in movimento, da un treno che passa e magari rallenta. Non si può aspettare, che è quello che fanno tutti, ma bisogna decidere. Per questo una ipotesi del genere non è solo scientificamente ma politicamente importante, e se corrode equilibri prestabiliti è un bene, d'altra parte agli autori di questo libro, è già successo altre volte.

Autism spectrum disorders (ASDs) are a group of neurodevelopmental disorders with high heritability, although their underlying genetic factors are still largely unknown. Here we present a comprehensive genetic characterization of two ASD siblings from Sardinia by genome-wide copy number variation analysis and whole exome sequencing (WES), to identify novel genetic alterations associated with this disorder. Single nucleotide polymorphism (SNP) array data revealed a rare microdeletion involving CAPG, ELMOD3, and SH2D6 genes, in both siblings. CAPG encodes for a postsynaptic density (PSD) protein known to regulate spine morphogenesis and synaptic formation. The reduced CAPG mRNA and protein expression levels in ASD patients, in the presence of hemizygosity or a particular genetic and/or epigenetic background, highlighted the functional relevance of CAPG as a candidate gene for ASD. WES analysis led to the identification in both affected siblings of a rare frameshift mutation in VDAC3, a gene intolerant to loss of function mutation, encoding for a voltage-dependent anion channel localized on PSD. Moreover, four missense damaging variants were identified in genes intolerant to loss of function variation encoding for PSD proteins: PLXNA2, KCTD16, ARHGAP21, and SLC4A1. This study identifies CAPG and VDAC3 as candidate genes and provides additional support for genes encoding PSD proteins in ASD susceptibility.

Pilocytic astrocytoma (PA) is the most common glioma in pediatric patients and occurs in different locations. Chromosomal alterations are mostly located at chromosome 7q34 comprising the BRAF oncogene with consequent activation of the mitogen-activated protein kinase pathway. Although genetic and epigenetic alterations characterizing PA from different localizations have been reported, the role of epigenetic alterations in PA development is still not clear. The aim of this study was to investigate whether distinctive methylation patterns may define biologically relevant groups of PAs. Integrated DNA methylation analysis was performed on 20 PAs and 4 normal brain samples by Illumina Infinium HumanMethylation27 BeadChips. We identified distinct methylation profiles characterizing PAs from different locations (infratentorial vs supratentorial) and tumors with onset before and after 3 years of age. These results suggest that PA may be related to the specific brain site where the tumor arises from region-specific cells of origin. We identified and validated in silico the methylation alterations of some CpG islands. Furthermore, we evaluated the expression levels of selected differentially methylated genes and identified two biomarkers, one, IRX2, related to the tumor localization and the other, TOX2, as tumoral biomarker.

The observation of the phenomenon of the deviance in the community of Orgosolo and the contextual need to seek suitable answers in a complex system that comes from the community for the community, are the premises from which arose the "need" to research. The use of a community approach seems to be functional to the complexity of the phenomenon of deviance in the community of Orgosolo, in which considerable cultural, historical, and social aspects are woven together. The method found is the RICERCAZIONE, that also represents the "natural" methodology of the method of social work of community, that allows to know and to find solutions in a context that activates the different involved actors: social and institutional. The social subjects, the citizens of Orgosolo, are called inside this research personally to define, through their perception, the outlines of the phenomenon itself. The engagement of the institutional actors in a shared educational action on the approach of community represents the conclusion of a process designed to the reflection on the phenomenon of the deviance and directed to the co-construction of integrated interventions.

This thesis reflects how people are involved in development projects in the frame of international cooperation. The aim of the work is two fold: on one hand we report on the conceptual limits that we found searching through a wide part of the vast number of sociological essays dealing with the paradigms of development, understood as a system of thought and action imposed on the countries of the ' South ' of the world; on the other hand, through field research, we describe the power relations that exist between the different actors of development in a specific context of Ghana. In the course of the empirical research, we defined the connotative aspects of the present dimensions of power and identified the institutions involved in the development process in the West Mamprusi District. At the heart of the field research stands the study of Chieftaincy with its statutory and non-statutory functions, and the role of the chief as the leader of development in accordance with the 1992 Ghana’s Constitution, but also holder of the “traditional power” according to the “traditional rule” in pre-colonial era. Through semi-structured interviews, we investigated the meaning that the resident population gave to development, participation, and the role of the chief in the villages involved in the International development project Ghaja. This work informs on the risk of losing the early form of participation; indeed, one of the central challenges for a development project to be sustainable is to act in respect of the local structures of power and local forms of participation.

To evaluate the functional effect of short-term supplementation of saffron, a spice containing the antioxidant carotenoids crocin and crocetin, in early age-related macular degeneration (AMD).Twenty-five patients with AMD were randomly assigned to oral saffron 20 mg/d or placebo supplementation over a 3-month period and then reverted to placebo or saffron for a further 3 months. Focal electroretinograms (fERGs) and clinical findings were recorded at baseline and after 3 months of saffron or placebo supplementation. fERGs were recorded in response to a sinusoidally modulated (41 Hz), uniform field presented to the macular region (18°) at different modulations between 16.5% and 93.5%. Main outcome measures were fERG amplitude (in microvolts), phase (in degrees), and modulation thresholds.After saffron, patients' fERGs were increased in amplitude, compared with either baseline or values found after placebo supplementation (mean change after saffron, 0.25 log μV; mean change after placebo, -0.003 log μV; P0.01). fERG thresholds were decreased after saffron supplementation but not placebo, compared with baseline (mean change after saffron, -0.26 log units; mean change after placebo, 0.0003 log units).The results indicate that short-term saffron supplementation improves retinal flicker sensitivity in early AMD. Although the results must be further replicated and the clinical significance is yet to be evaluated, they provide important clues that nutritional carotenoids may affect AMD in novel and unexpected ways, possibly beyond their antioxidant properties. (ClinicalTrials.gov number, NCT00951288.).