664 research outputs found
Un grammatico in officina. Tommaso Ferrando e gli esordi della stampa a Brescia
No full textUn grammatico in officina. Tommaso Ferrando e gli esordi della stampa a Bresci
Il “mito” di Tommaso Ferrando nella storiografia dei sec. XVIII-XX
No full textIl “mito” di Tommaso Ferrando nella storiografia dei sec. XVIII-X
Recruitment of H3.3 histone chaperon activity to R-loops by the Splicing-Factor Proline and Arginine Rich (SFPQ) stabilizes repetitive elements in cancer cells
No full textR-loops are triple-stranded nucleic acid structures containing an RNA moiety paired with its antisense DNA template strand and the loop of the displaced, single-stranded DNA (ssDNA). RNA:DNA hybrids form under normal physiological conditions and exert multiple biological functions. However, persistent R-loops have been shown to mediate replication stress, DNA damage and drive genomic instability, with a particular relevance at vertebrate telomeres.
We recently found that the RNA-binding protein SFPQ has a critical role in limiting R-loops formation at telomeres of human cancer cell. In line with this, loss-of-function SFPQ cells show increased levels of RNA:DNA hybrids, replication stress and DNA damage markers and subsequent genomic instability at telomeres level.
Here we show that SFPQ function is not limited to telomeres, but expands to other non-coding repeat regions in the human genome, as depicted by ChIP-seq analysis, paralleled by increased R-loop levels and genomic instability.
Moreover, SFPQ action is mediated by the its novel interactor DAXX, that allows R-loop suppression by inserting H3.3 histone variant.
Finally, RNA-seq analysis pointed out a SFPQ - R-loop dependent signature of innate immune response activation, unveiling a novel connection between non coding genome regulation and immune response, suggesting SFPQ as putative target for sarcoma treatment.R-loops are triple-stranded nucleic acid structures containing an RNA moiety paired with its antisense DNA template strand and the loop of the displaced, single-stranded DNA (ssDNA). RNA:DNA hybrids form under normal physiological conditions and exert multiple biological functions. However, persistent R-loops have been shown to mediate replication stress, DNA damage and drive genomic instability, with a particular relevance at vertebrate telomeres.
We recently found that the RNA-binding protein SFPQ has a critical role in limiting R-loops formation at telomeres of human cancer cell. In line with this, loss-of-function SFPQ cells show increased levels of RNA:DNA hybrids, replication stress and DNA damage markers and subsequent genomic instability at telomeres level.
Here we show that SFPQ function is not limited to telomeres, but expands to other non-coding repeat regions in the human genome, as depicted by ChIP-seq analysis, paralleled by increased R-loop levels and genomic instability.
Moreover, SFPQ action is mediated by the its novel interactor DAXX, that allows R-loop suppression by inserting H3.3 histone variant.
Finally, RNA-seq analysis pointed out a SFPQ - R-loop dependent signature of innate immune response activation, unveiling a novel connection between non coding genome regulation and immune response, suggesting SFPQ as putative target for sarcoma treatment
On prosperity and posterity: the need for fiscal discipline in a monetary union
No full textWe show how in a Blanchard-Yaari, overlapping generations framework, perfect substitutability of government bonds in Monetary Union tempts governments to exploit the enlarged common pool of savings. In Nash equilibrium all governments increase their bond financed transfers to current generations (prosperity effect) at the expense of future generations (posterity effect). The resulting deficit bias occurs even if one assumes that before Monetary Union countries had eliminated their deficit bias by designing appropriate domestic institutions. The paper provides a rationale for an increased focus on fiscal discipline in Monetary Union, without the need to assume imperfect credibility of existing Treaty provisions or to refer to extreme situations involving sovereign default. We draw on existing empirical evidence to argue that the degree of government bond substitutability within the European Monetary Union is an order of magnitude larger than in the global economy. JEL Classification: D62, E61, E63bond market integration, common pool, European Monetary Union, fiscal discipline, fiscal rules, fiscal spillover effects, overlapping generations
Micro-geometry characterisation of sloped surfaces: an improved methodology for roughness parameters estimation
No full textInfluence of Surface Slope on the Roughness Measurement
No full textInternational standars prescribe procedures for the computation of roughness parameters assuming the surfaces almost plane and perpendicular to the axis of deflection of the instrument stylus. The availability of new measuring instruments, characterised by larger ranges, permits to analyse geometries with important slopes. This paper discusses the errors occuring by the adoption of the conventional measuting techniques when oblique surfaces are examined and proposes a modification of the standard procedure in order to obtain correct results
Regulation and function of R-loops at repetitive elements
No full textR-loops are atypical, three-stranded nucleic acid structures that contain a stretch of RNA:DNA hybrids and an unpaired, single stranded DNA loop. R-loops are physiological relevant and can act as regulators of gene expression, chromatin structure, DNA damage repair and DNA replication. However, unscheduled and persistent R-loops are mutagenic and can mediate replication-transcription conflicts, leading to DNA damage and genome instability if left unchecked. Detailed transcriptome analysis unveiled that 85% of the human genome, including repetitive regions, hold transcriptional activity. This anticipates that R-loops management plays a central role for the regulation and integrity of genomes. This function is expected to have a particular relevance for repetitive sequences that make up to 75% of the human genome. Here, we review the impact of R-loops on the function and stability of repetitive regions such as centromeres, telomeres, rDNA arrays, transposable elements and triplet repeat expansions and discuss their relevance for associated pathological conditions
The DigForSim Agent Based Simulator of People Movements in Crime Scenes
No full textEvidence analysis is one of the Digital Forensics tasks and involves examining fragmented incomplete knowledge and reasoning on it, in order to reconstruct plausible crime scenarios. After more than one year of activity within the DigForASP COST Action, the lack of real data about movements of people in crime scenes emerged as a major limitation to the need of testing the DigForASP prototypes that exploit Artificial Intelligence and Automated Reasoning for evidence analysis.
In this paper we present DigForSim, an Agent Based Modeling and Simulation tool aimed at producing synthetic, controllable data on the movements of agents in the crime scene, in form of files logging the agents’ position at given time points. These log files serve as benchmarks for the DigForASP reasoning prototypes
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