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Papers by Giorgio Binelli

International journal of molecular sciences, May 10, 2024

Italian Journal of Zoology, 2002

An investigation of the genetic variability of Octopus vulgaris, an intensively harvested species... more An investigation of the genetic variability of Octopus vulgaris, an intensively harvested species, was carried out using a mi crosatellite locus as genetic marker. Samples from one eastern At lantic and nine Mediterranean locations were analysed. In each population, the number of alleles at locus Ov06 varied from four to seven and was 21 overall. Observed and expected heterozy‐gosity values

Scientific Reports, Feb 6, 2019

Cystic fibrosis (CF) is a hereditary disease due to mutations in the CFTR gene and causes mortali... more Cystic fibrosis (CF) is a hereditary disease due to mutations in the CFTR gene and causes mortality in humans mainly due to respiratory infections caused by Pseudomonas aeruginosa. In a previous work we used phage therapy, which is a treatment with a mix of phages, to actively counteract acute P. aeruginosa infections in mice and Galleria mellonella larvae. In this work we apply phage therapy to the treatment of P. aeruginosa PAO1 infections in a CF zebrafish model. The structure of the CFTR channel is evolutionary conserved between fish and mammals and cftr-loss-of-function zebrafish embryos show a phenotype that recapitulates the human disease, in particular with destruction of the pancreas. We show that phage therapy is able to decrease lethality, bacterial burden, and the pro-inflammatory response caused by PAO1 infection. In addition, phage administration relieves the constitutive inflammatory state of CF embryos. To our knowledge, this is the first time that phage therapy is used to cure P. aeruginosa infections in a CF animal model. We also find that the curative effect against PAO1 infections is improved by combining phages and antibiotic treatments, opening a useful therapeutic approach that could reduce antibiotic doses and time of administration. One of the most serious health emergencies in the last decades is the reappearance of bacterial infections 1,2. This serious fallout is a consequence of the rapid spread of resistance towards currently in use antibiotics among pathogenic bacteria together with the difficulty in discovering new effective antibiotics. In addition, the appearance and diffusion of multidrug resistant (MDR) isolates make the situation even worse 3. Thus, alternative therapies are urgently needed and bacteriophages (phages), the natural enemies of bacteria, can be a possible solution. Compared to antibiotics, phages have several advantages: first, they infect only very specific bacterial hosts avoiding damage to healthy commensal microbiota 4 ; second, phages are self-controlling their dose: they multiply when and where the target bacterial host strains are present, increasing their number at the infection site only as long as the target bacteria are eliminated 5 ; lastly, phages are able to kill also MDR bacteria 6. The idea of using phages against bacteria is not new: the first attempts were made almost a century ago 7. However, due to the lack of knowledge of the phage reproductive cycle, the therapy alternated successes and failures and, with the advent of antibiotics, phages were abandoned in the Western world unless for compassionate treatments 8,9 , although they are currently in use in Eastern world. Nowadays, many details of the reproduction of phages have been thoroughly clarified, which facilitate their use in therapy and guidelines have been suggested for preparation and use of phages as therapeutic agents 10. In the last years, an increasing number of reports on the effectiveness of phage therapy in controlling bacterial infections have been provided, ranging from Klebsiella pneumoniae pulmonary infections 11 , Pseudomonas aeruginosa keratitis 12 , or P. aeruginosa infected mice 4,13,14. In a recent report 15 , we isolated and characterized virulent phages capable of infecting P. aeruginosa, and sequenced their genomes to exclude the presence of any gene potentially harmful in therapy. Different phages were mixed in a cocktail and used to treat P. aeruginosa acute infections in mouse and Galleria mellonella larvae. Phage therapy was successful in both model systems. Moreover, we found that the efficacy of the therapy was improved using a phage cocktail compared to the use

PLOS ONE, May 7, 2014

Segregation of mutant mtDNA in human tissues and through the germline is debated, with no consens... more Segregation of mutant mtDNA in human tissues and through the germline is debated, with no consensus about the nature and size of the bottleneck hypothesized to explain rapid generational shifts in mutant loads. We investigated two maternal lineages with an apparently different inheritance pattern of the same pathogenic mtDNA 3243A.G/tRNA Leu(UUR) (MELAS) mutation. We collected blood cells, muscle biopsies, urinary epithelium and hair follicles from 20 individuals, as well as oocytes and an ovarian biopsy from one female mutation carrier, all belonging to the two maternal lineages to assess mutant mtDNA load, and calculated the theoretical germline bottleneck size (number of segregating units). We also evaluated ''mother-to-offspring'' segregations from the literature, for which heteroplasmy assessment was available in at least three siblings besides the proband. Our results showed that mutation load was prevalent in skeletal muscle and urinary epithelium, whereas in blood cells there was an inverse correlation with age, as previously reported. The histoenzymatic staining of the ovarian biopsy failed to show any cytochrome-c-oxidase defective oocyte. Analysis of four oocytes and one offspring from the same unaffected mother of the first family showed intermediate heteroplasmic mutant loads (10% to 75%), whereas very skewed loads of mutant mtDNA (0% or 81%) were detected in five offspring of another unaffected mother from the second family. Bottleneck size was 89 segregating units for the first mother and 84 for the second. This was remarkably close to 88, the number of ''segregating units'' in the ''mother-to-offspring'' segregations retrieved from literature. In conclusion, a wide range of mutant loads may be found in offspring tissues and oocytes, resulting from a similar theoretical bottleneck size.

Conservation Genetics, Jan 27, 2007

Springer eBooks, 1986

Gametophytic selection for important sporophytic traits such as resistence to environmental stres... more Gametophytic selection for important sporophytic traits such as resistence to environmental stresses and to pathogenic toxins has been proposed as a very efficient tool for the improvement of plant breeding methods1,2,3, on the grounds of the existence of an extensive genetic overlap between the gametophytic and sporophytic phases4,5,6.

Embo Molecular Medicine, May 9, 2023

Molecular Genetics And Genomics, Oct 1, 1993

The basic prerequisite for an efficient breeding program to improve levels of resistance to patho... more The basic prerequisite for an efficient breeding program to improve levels of resistance to pathogens in plants is the identification of genes controlling the resistance character. If the response to pathogens is under the control of a multilocus system, the utilization of molecular markers becomes essential. Stalk and ear rot caused by Gibberella zeae is a widespread disease of corn:

Assays that attempt to characterize HIV susceptibility or resistance are among the latest technol... more Assays that attempt to characterize HIV susceptibility or resistance are among the latest technologies that are likely to impact HIV clinical trial design, antiretroviral drug development and patient management. However, at present the Food and Drug Administration (FDA) have yet to approve any phenotypic or genotypic HIV resistance assay and the role of resistance testing in clinical management of patients and in drug development is ill defined. In November 1999, the Division of Antiviral Drug Products at the FDA convened a meeting of its advisory committee to consider the available information about HIV resistance testing, and to generate some recommendations about how these assays could be utilized in antiretroviral drug development. In addition, the committee was presented with several hypothetical regulatory scenarios in order to illustrate how HIV resistance testing might be incorporated in antiretroviral drug development and drug labelling. In this article, we discuss the regulatory history of resistance testing in antimicrobial drug development, the current use of resistance testing for antiretrovirals, as well as a summary of the hypothetical scenarios that were presented to the committee and the discussion of the committee members regarding those scenarios

Multidisciplinary Respiratory Medicine, 2019

Every year, the Italian Cystic Fibrosis Research Foundation (FFC) brings together all its funded ... more Every year, the Italian Cystic Fibrosis Research Foundation (FFC) brings together all its funded researchers from across Italy and beyond, in a Convention where results from FFC projects are shared and debated. These projects are either newly funded, ongoing or recently concluded research. The Proceedings of the 16th Convention of Italian Investigators in Cystic Fibrosis is a supplement of Multidisciplinary Respiratory Medicine reporting results of completed projects which were presented at the FFC 2018 Convention.