0000000001081729
AUTHOR
A. Di Leonardo
Assignment of enolase processed pseudogene (ENO1P) to human chromosome 1 bands 1q41→q42
Retinoblastoma epidemiology: Does the evidence matter?
It has been proposed that retinoblastoma is 'caused' by two sequential mutations affecting the RB1 gene, but this is a rather outdated view of cancer aetiology that does not take into account a large amount of new acquisitions such as chromosomal and epigenetic alterations. Retinoblastoma remains probably the only cancer in which the rather simplistic 'two hit' mutational model is still considered of value, although cancer is known to be associated with genomic and microsatellite instability, defects of the DNA mismatch repair system, alterations of DNA methylation and hystone acethylation/deacethylation, and aneuploidy. Moreover, as it is shown herein, the predictions made by the 'two hit'…
The retinoblastoma paradigm revisited
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…
Integrated computational and experimental approaches for the identification of new molecules with readthrough activity on premature termination codons (PTCs) in cystic fibrosis cells
Modulation of induced reversion frequency by nucleotide pool imbalance as a tool for mutant characterization.
Addition of thymidine (TdR) or deoxycytidine (CdR) to the culture medium during posttreatment incubation affected the frequency of mutagen-induced reversion in three hypoxanthine-guanine phosphoribosyl transferase-deficient mutants of V79 Chinese hamster cells. With two of the mutants (E20 and I3), reversions induced by N-ethylnitrosourea, ethyl methanesulfonate, and methyl methanesulfonate were enhanced by TdR and were either decreased (E20) or not affected (I3) by CdR. With the third mutant (E21), alkylating agent-induced reversions were enhanced by CdR and decreased by TdR. Finally, 6-amino-2-hydroxypurine induced reversions were enhanced by TdR in mutant I3 and were decreased by TdR or …
PROPAGATION OF HYPERCONCENTRATED FLOWS IN PROTECTION CHANNELS AROUND URBAN AREAS: EXPERIMENTAL INVESTIGATION
Gene amplification in fibroblasts from ataxia telangiectasia (AT) patients and in X-ray hypersensitive AT-like Chinese hamster mutants
In search of functions involved in the regulation of gene amplification, and given the relevance of chromosome breakage in initiating the process, we analyzed the gene amplification ability of cells hypersensitive to inducers of DNA double-strand breaks and defective in cell cycle control: two human fibroblast strains derived from patients affected by ataxia telangiectasia (AT) and two hamster mutant cell lines belonging to complementation group XRCC8 of the rodent X-ray-sensitive mutants. These mutants are considered hamster models of AT cells. To measure gene amplification, the frequency and the rate of occurrence of N-(phosphonacetyl)-l-aspartate resistant cells were determined. In both …
Novel molecules for the readthrough of PTCs in biological model systems and in cystic fibrosis cells
Hyper-concentrated flows: experimental investigation of effect of inflow parameters and sediment concentration on propagation process
Debris-flows runout estimations are of crucial importance to delineate the potentially hazardous areas and to make reliable assessment of the level of risk of urban areas. Especially in recent years, several researches have been conducted in order to define predicitive models. But, existing runout estimation methods need input parameters that can be difficult to estimate. Recent experimental researches have also allowed the assessment of the physics of the debris flows. But, the major part of the experimental studies analyze the basic kinematic conditions which determine the phenomenon evolution. Experimental program has been recently conducted at the Hydraulic laboratory of the Department …
Monitoring of surface velocity of hyper-concentrated flow in a laboratory flume by means of fully-digital PIV
This paper investigates the utility and the efficiency of the digital image-technique for remote monitoring of surface velocity in hyper-concentrated flow by the aid of data collected during experiments conducted in the laboratory flume. In particular the present paper attention is focused on the estimation procedure of the velocity vectors and on their sensitivity with parameters (number of images, spatial resolution of interrogation area, ) of the images processing procedure.
Optimization of a new lead promoting the readthrough of the nonsense mutations for CFTR rescue in human CF cells
Optimization of a new lead promoting the readthrough of the nonsense mutations for CFTR rescue in human CF cells Laura Lentini, Raffaella Melfi, Sara Baldassano, Marco Tutone, Aldo Di Leonardo, Andrea Pace, Ivana Pibiri Department of Biological, Chemical and Pharmaceutical Sciences and Technologies (STEBICEF), University of Palermo Background and rationale Cystic Fibrosis patients with nonsense mutations in the CFTR gene have a more severe form of the disease. Nonsense mutations represent about 10% of the mutations that affect the CFTR gene and they are frequently associated to the classical F508 mutation (1). A potential treatment for this genetic alteration is to promote the translationa…
Cytogenetic manifestations associated with the reversion, by gene amplification, at the HGPRT locus in V79 Chinese hamster cells.
SummarySome HGPRT spontaneous revertants were isolated from a mutant line (E2) of V79 Chinese hamster cells and phenotypically characterized. Dot–Blot hybridization with a32P-Iabelled HGPRT probe revealed an increase in the number of HGPRT sequences in some of these revertants, suggesting the occurrence of gene amplification. Cytogenetic analysis performed in three of these revertants showed a characteristic abnormally banding region (ABR) on the elongated p arm of theXchromosome.In Situhybridization in one revertant (RHE2) showed that the amplified sequences reside on the p+arm of theXchromsome in two different localizations. Because of the very probable clonal origin of the revertant, the…