1,022 research outputs found
UHRF1 coordinates DNA methylation and histone post-translational modifications in colon cancer .
No full textIn Colorectal cancer (CRC) genetic and epigenetic alterations are tightly connected, although these interactions on the patient’s outcome are not clearly understood.
A peculiar subclass of sporadic CRC tumors, is characterized by Microsatellite instability (MSI), due to hyper-methylated promoter of MHL1 gene and subsequent inactivation of the mismatch repair (MMR) mechanism, and the hypermethylation of CpG islands phenotype (CIMP), mediated by the hyper-methylation of promoter regions of several tumor suppressor genes (TSGs). This subclass carries a good prognosis and presents an inverse correlation with genomic and chromosome instability (CIN), together with a higher levels of DNA methylation at global level, compared to other CRCs. Among the epigenetic alterations, DNA methylation and histone modifications rearrangements are extremely important steps during tumorigenesis. UHRF1 is a key master epigenetic regulator that couples the maintenance of DNA methylation through the cell cycle with the histone-modification pattern. It monoubiquitinates H3K18/23 enabling the correct localization and activation of DNMT1 on the specific sites. UHRF1 is overexpressed in several cancer types mediating the hypermethylation of promoter regions of the TSGs and coordinating their heterochromatic silencing.
Relying on the idea that UHRF1 could play a crucial role in the modulation of DNA methylation changes, the overall aim of this PhD thesis was to evaluate the role of UHRF1 in the coordination of DNA methylation and histone post-translational modifications both at genome-wide and at locus specific level in CRCs.
Unexpectedly, we found that in CRC tissues UHRF1 was higher in tumors with microsatellite instability (MSI CRC), which have a better prognosis, compared to the stable ones (MSS CRC). MSI tumors were also characterized by higher levels of DNA methylation compared to the MSS. The UHRF1 knock-down in a MSI CRC cell line (RKO cells) induced an overall decrease in DNA methylation (RRB-seq analysis, pyrosequencing and MS-MLPA) both at global level and at gene promoters without affecting DNMTs levels, as observed by WB and RNA-seq analysis. ChIP experiments showed that UHRF1 depletion reduces DNMT1 binding to both repetitive elements (LINE-1) and specific gene promoters (MLH1, CDH1), decreasing H3K9me3 and increasing H3K4me3 on those hypo-methylated loci. RNA-seq data analysis showed that UHRF1 loss interferes with several important pathways, among others cell cycle, growth and proliferation. SILAC LC-MS/MS analysis showed that in RKO cells, UHRF1 loss decreases the overall presence of H3K23ub (» 30%) and H3K18ub (» 8%).
These results, together with the published findings, led us to hypothesize a model in which the loss of UHRF1 directly impairs the DNA methylation maintenance by reducing H3K18/K23ub and consequently DNMT1 activity and, indirectly, impairs the binding of Suv39H1, the histone methyl transferase (HMT) responsible for H3K9me3, to both genome-wide and promoter specific loci. These changes led to a severe chromatin rearrangement of heterochromatic signatures toward a more open and transcriptionally accessible structure, probably due to the disruption of the axis UHRF1-H3ub-DNMT1-HMTs. Our molecular data, together with the analysis performed on CRC samples, led us to speculate that the better prognosis correlated with MSI-CRC model, could reside in the UHRF1-high levels that result in a sort of protective condition for the genome integrity, maintaining the global DNA methylation level closer to the normal mucosae, and probably counteracting the hyper-methylation of TSGs
A Florentine family in crisis: the Strozzi in the fifteenth century.
No full textPhDIn 1434 the Strozzi lineage had held a leading position in
Florentine society and government for at least one hundred and fifty
years, and was one of the largest and wealthiest of the city's
patrician lineages. The records of the catasto of 1427 and of the
scrutiny of 1433 are used to give a profile of the dominant social,
economic and political position of the Strozzi before the advent of
Medicean dominance. Their record of electoral success, and the
political and cultural leadership of influential and respected men
such as Palla di Nofri and Matteo di Simone, with other factors, put
the Strozzi amongst the greatest enemies of the victorious Medicean
regime of late 1434. The effects of political opposition and exile
on the lineage are examined both directly, through records of office-holding,
and indirectly through such indicators as marriage alliances
and household wealth. The two most prominent lines of the Strozzi
were exiled after 1434. Palla di Nofri's life and preoccupations in
his Paduan exile are examined, together with the lives of his sons;
none of these Strozzi ever returned to Florence, pursued as they were
by the enmity of the Medicean regime. The very different careers of
Filippo di Matteo and his brother Lorenzo are also examined: how they
succeeded in founding a lucrative bank in Naples, and in returning to
Florence to 'rebuild' (rifare) the position of the Strozzi lineage
there. The final decades of the century saw the Strozzi in an
economically more secure position, due substantially to the efforts
of Filippo. Except for a very small number of its members admitted
into the regime, most of the lineage is here shown to have remained
excluded from significant political office until after the fall of
the Medici regime in 1494
The self motor evaluation/assessment in professional training of learning support teachers
No full textOne of the most significant experiences of SISS on the motor –training plan, which allowed in some cases the
implementation of activity of research-action, was the motor- sports laboratory. The activity of laboratory in the
motor- sports field and the motor subjects, along with specific training, represents in the SSIS (Specialization
School Teaching Secondary) area an innovative element. This also gave a strong contribute to the definition of a
new professional profile of the teacher that has in it those transversal skills needed to promote a new teaching,
finding the necessary balances between the cognitive moment and the applicative and operative one
Vues présentes sur le celtique cisalpin
No full textPresent views on Cisalpine Celtic.
During the last twenty years, the knowledge of Lepontic and of Italian Gaulish has been notably enriched by very important finds, and also by numerous studies. The author proposes a synthesis of all new linguistical and cultural data provided by epigraphy in this particular resort.Dans les vingt dernières années la connaissance du lépontique et du gaulois d’Italie a été notablement enrichie par certaines trouvailles fort importantes ainsi que par de nombreuses études. Tableau synthétique des nouvelles données linguistiques et culturelles apportées par l’épigraphie de ce domaine.Motta Filippo. Vues présentes sur le celtique cisalpin. In: Etudes Celtiques, vol. 29, 1992. Actes du IXe congrès international d'études celtiques. Paris, 7-12 juillet 1991. Deuxième partie : Linguistique, littératures. pp. 311-318
The Dielectric Behavior of Protected HKUST-1
No full textWe investigated the adsorption properties and the dielectric behavior of a very well-known metal-organic framework (MOF), namely Cu3(BTC)2 (known as HKUST-1; BTC = 1,3,5-benzenetricarboxylate), before and after protection with some amines. This treatment has the purpose of reducing the inherent hygroscopic nature of HKUST-1, which is a serious drawback in its ap-plication of as low-dielectric-constant (low-κ) material. Moreover, we investigated the structure of HKUST-1 under a strong electric field, confirming the robustness of the framework. Even under dielectric perturbation, the water molecules adsorbed by the MOF remained almost invisible to X-ray diffraction, apart from those directly bound to the metal ions. However, the replacement of H2O with a more visible guest molecule such as CH2Br2 made the cavity that traps the guest more visible. Finally, in this work we demonstrate that impedance spectroscopy is a valuable tool for identifying water sorption in porous materials, providing information that is complementary to that of adsorption isotherms
Elementi di base per lo studio e l’analisi del “Marketing dello sport e del turismo sportivo e la gestione degli impianti motorio-sportivi in Italia
No full textEvaluating the integration of the sensory-motor abilities to facilitate teaching-learning processes: a comparison between Italian and Indian models of teaching through the use of VMI test
No full textOcchi pieni e mani vaganti. Movimenti, emozioni, astrazioni.
No full textFilippo FIMIANI, Occhi pieni e mani vaganti. Movimenti, emozioni, astrazioni, «Fata Morgana», 12/2010, pp. 147-164. ISSN 1970-5786.
ITALIANO. Una piccola sequenza da un episodio della serie televisiva Mad Men in cui la relazione sensoriale emozionale tra lo spettatore e un corpo in movimento, precisamente un corpo danzante, è l’oggetto di questo articolo, che intende così verificare la cosiddetta naturalizzazione della fenomenologia e del corpo vissuto operata dalle scienze cognitive applicate agli studi visuali. L’autore mostra anche i rapporti tra la cosiddetta simulazione incarnata e una memoria simbolica e iconografica profonda, e discute in particolare la polarità tra proiezione e introiezione, attività e passività nell’esperienza empatica delle immagini in movimento.A short filmic example from the AMC's award-winning series Mad Men in which the sensorial and emotional relationship between the spectator and a moving body, i.e., a dancing body, is explicitly put into play. The essay wants to deal with the so called naturalization of phenomenology and of the living body, trained by the cognitive sciences reading the visuality. The author shows the relationship between the so called ‘embodied Simulation’ and a symbolic and iconographic deep memory of the pictures, and he gives an in-depth attention to the polarity between projections and introjections, activity and passivity of the spectator’s body during the empathic experience of the moving pictures
Multiple political geographies
No full textThis chapter delves into the multifaceted realm of political geography within the context of the journal Political Geography. The author, who has held various editorial positions within the journal, navigates the intricate terrain of diversity and inclusion, exploring the challenges posed by linguistic and cultural biases inherent in academic publishing. The chapter critically examines efforts to mitigate barriers and broaden the scope of political geography, questioning the adequacy of current approaches. Through a reflective analysis, the author elucidates the complex dynamics of political geography as a subdiscipline, shedding light on both the impediments and possibilities it offers to researchers and students
Testing the performance of an innovative markerless technique for quantitative and qualitative gait analysis
No full textGait abnormalities such as high stride and step frequency/cadence (SF-stride/second, CAD-step/second), stride variability (SV) and low harmony may increase the risk of injuries and be a sentinel of medical conditions. This research aims to present a new markerless video-based technology for quantitative and qualitative gait analysis. 86 healthy individuals (mead age 32 years) performed a 90 s test on treadmill at self-selected walking speed. We measured SF and CAD by a photoelectric sensors system; then, we calculated average ± standard deviation (SD) and within-subject coefficient of variation (CV) of SF as an index of SV. We also recorded a 60 fps video of the patient. With a custom-designed web-based video analysis software, we performed a spectral analysis of the brightness over time for each pixel of the image, that reinstituted the frequency contents of the videos. The two main frequency contents (F1 and F2) from this analysis should reflect the forcing/dominant variables, i.e., SF and CAD. Then, a harmony index (HI) was calculated, that should reflect the proportion of the pixels of the image that move consistently with F1 or its supraharmonics. The higher the HI value, the less variable the gait. The correspondence SF-F1 and CAD-F2 was evaluated with both paired t-Test and correlation and the relationship between SV and HI with correlation. SF and CAD were not significantly different from and highly correlated with F1 (0.893 ± 0.080 Hz vs. 0.895 ± 0.084 Hz, p < 0.001, r2 = 0.99) and F2 (1.787 ± 0.163 Hz vs. 1.791 ± 0.165 Hz, p < 0.001, r2 = 0.97). The SV was 1.84% ± 0.66% and it was significantly and moderately correlated with HI (0.082 ± 0.028, p < 0.001, r2 = 0.13). The innovative video-based technique of global, markerless gait analysis proposed in our study accurately identifies the main frequency contents and the variability of gait in healthy individuals, thus providing a time-efficient, low-cost means to quantitatively and qualitatively study human locomotion
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