Search results for "MUTATION"

Investigating the inhibition of FTSJ1 a tryptophan tRNA-specific 2’-O-methyltransferase by NV TRIDs, as a mechanism of readthrough in nonsense mutate…

2023

Abstract: Cystic Fibrosis (CF) is an autosomal recessive genetic disease caused by mutations in the CFTR gene, coding for the CFTR chloride channel. About 10% of the CFTR gene mutations are "stop" mutations, which generate a Premature Termination Codon (PTC), thus synthesizing a truncated CFTR protein. A way to bypass PTC relies on ribosome readthrough, which is the ri-bosome’s capacity to skip a PTC, thus generating a full-length protein. “TRIDs” are molecules exerting ribosome readthrough; for some, the mechanism of action is still under debate. We in-vestigate a possible mechanism of action (MOA) by which our recently synthesized TRIDs, namely NV848, NV914, and NV930, could exert their r…

Readthrough Inducing Drugs (TRIDs) in human fibroblasts harboring the c.5047 C>T (R1683*) nonsense mutation

2022

COMBINING TRANSLATION READTHROUGH INDUCING DRUGS AND NONSENSE MEDIATED DECAY PATWHAY INHIBITION TO THE CFTR RESCUE IN CYSTIC FIBROSIS CELL MODEL SYST…

2021

Nonsense mutations affect 10% of patients with cystic fibrosis and produce a premature termination codon in CFTR (Cystic Fibrosis Transmembrane Conductance Regulator) mRNA causing early termination of translation and leading to lack of CFTR function. A potential therapy for nonsense mutations provides the use of small molecules able to overcome the premature stop codon (PTC) by a readthrough mechanism that lead to synthesis a complete CFTR protein. Despite the good results obtained from this approach, TRIDs efficiency is considerably reduced by the poor amount of target transcript, that is the mRNA containing the PTC. The readthrough, indeed, does not occur on the totality of target transcr…

The retinoblastoma paradigm revisited

2008

Background: Retinoblastoma (Rb) is the most common primary malignant intraocular tumour in childhood. The "two hit" theory, formulated by Knudson in 1971 to explain the variegated clinical expression of the disease, led to the discovery of the so called tumour suppressor genes and the identification of the Rb1 as the prototype of such genes. Mutations of the Rb1 gene are now commonly believed to be the "cause" retinoblastoma, although epidemiological, clinical, and biological evidences argue against it. Material/Methods: The Authors have performed a systematic review of available data concerning clinical and diagnostic aspects of retinoblastoma, including molecular genetics. Meta analysis o…

Translational readthrough inducing drugs: a study of toxicity in mice models and in vitro safety validation of the specific readthrough process.

2022

Objective Nonsense mutations are responsible for 15% of Cystic Fibrosis (CF) patients due to the introduction of a premature stop codon (PTC) in the mRNA and the production of a truncated CFTR (Cystic Fibrosis Transmembrane Conductance Regulator) protein1. A promising therapeutic approach for stop mutations is the suppression therapy by Translational Readthrough Inducing Drugs (TRIDs) to restore the expression of the protein2,3. Recently three new TRIDS (NV848, NV914, NV930) have been proposed and validated by several assays. Our work was focused on TRIDs NV848, NV914, NV930. Important aspects of TRIDs to be evaluated are their specificity towards PTC, to demonstrate that TRIDs do not inter…

X CONVENTION OF INVESTIGATORS IN CYSTIC FIBROSIS.

2012

Background Cystic fibrosis (CF) is caused by mutations in the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR). Approximately 10% (worldwide) of patients have in-frame nonsense mutations (UAA, UAG or UGA class I mutations) in the CF trans-membrane regulator (CFTR) gene that result in premature stop codons (PTCs) in the messenger RNA (mRNA) generating truncated CFTR protein responsible for a severe CF phenotype. Pharmacological approaches have been proposed to directly overcome PTCs. Ataluren (PTC124) a small molecule that mimics the activity of aminoglycosides has been suggested to allow PTCs readthrough and to partially restore the protein function. However, des…

The innovative role of the readthrough inducing drugs in the translation rescue of mRNAs characterized by premature stop codon (PTCs).

Naro. Architetture nei luoghi del dissesto

2013

The reserch has been carried out in the degree laboratory in architectural design by professor G.F. Tuzzolino at the Faculty of Architecture of Palermo. It intends to study the relationship between place and artifice in the historical, landscape, and architectural point of view Naro is a very important city that today appears seriously compromised by incoherent mutations and where you can see the serious problems of hidrogeological disorder.

CubeHarmonic: A new musical instrument based on Rubik{'}s cube with embedded motion sensor

2019

A contemporary challenge involves scientific education and the connection between new technologies and the heritage of the past. CubeHarmonic (CH) joins novelty and tradition, creativity and edu- cation, science and art. It takes shape as a novel musical instrument where magnetic 3D motion tracking technology meets musical per- formance and composition. CH is a Rubik’s cube with a note on each facet, and a chord or chord sequence on each face. The posi- tion of each facet is detected through magnetic 3D motion tracking. While scrambling the cube, the performer gets new chords and new chord sequences. CH can be used to compose, improvise,1 and teach music and mathematics (group theory, permu…

Hypercube + Rubik’s Cube + Music = HyperCubeHarmonic

2022

Musical chords and chord relations can be described through mathematics. Abstract permutations can be visualized through the Rubik’s cube, born as a pedagogical device [7,21]. Permutations of notes can also be heard through the CubeHarmonic, a novel musical instru- ment. Here, we summarize the basic ideas and the state of the art of the physical implementation of CubeHarmonic, discussing its conceptual lift- ing up to the fourth dimension, with the HyperCubeHarmonic (HCH). We present the basics of the hypercube theory and of the 4-dimensional Rubik’s cube, investigating its potential for musical applications. To gain intuition about HCH complexity, we present two practical implementa- tions…