Latest PUBLICATIONS

  • An innovative strategy for the molecular diagnosis of Usher syndrome identifies causal biallelic mutations in 93% of European patients.
    Publication Date: 01/12/2016, on European journal of human genetics : EJHG
    by Bonnet C, Riahi Z, Chantot-Bastaraud S, Smagghe L, Letexier M, Marcaillou C, Lefèvre GM, Hardelin JP, El-Amraoui A, Singh-Estivalet A, Mohand-Saïd S, Kohl S, Kurtenbach A, Sliesoraityte I, Zobor D, Gherbi S, Testa F, Simonelli F, Banfi S, Fakin A, Glavač D, Jarc-Vidmar M, Zupan A, Battelino S, Martorell Sampol L, Claveria MA, Catala Mora J, Dad S, Møller LB, Rodriguez Jorge J, Hawlina M, Auricchio A, Sahel JA, Marlin S, Zrenner E, Audo I, Petit C
    DOI: 10.1038/ejhg.2016.99

    Usher syndrome (USH), the most prevalent cause of hereditary deafness-blindness, is an autosomal recessive and genetically heterogeneous disorder. Three clinical subtypes (USH1-3) are distinguishable based on the severity of the sensorineural hearing impairment, the presence or absence of vestibular dysfunction, and the age of onset of the retinitis pigmentosa. A total of 10 causal genes, 6 for USH1, 3 for USH2, and 1 for USH3, and an USH2 modifier gene, have been identified. A robust molecular diagnosis is required not only to improve genetic counseling, but also to advance gene therapy in USH patients. Here, we present an improved diagnostic strategy that is both cost- and time-effective. It relies on the sequential use of three different techniques to analyze selected genomic regions: targeted exome sequencing, comparative genome hybridization, and quantitative exon amplification. We screened a large cohort of 427 patients (139 USH1, 282 USH2, and six of undefined clinical subtype) from various European medical centers for mutations in all USH genes and the modifier gene. We identified a total of 421 different sequence variants predicted to be pathogenic, about half of which had not been previously reported. Remarkably, we detected large genomic rearrangements, most of which were novel and unique, in 9% of the patients. Thus, our strategy led to the identification of biallelic and monoallelic mutations in 92.7% and 5.8% of the USH patients, respectively. With an overall 98.5% mutation characterization rate, the diagnosis efficiency was substantially improved compared with previously reported methods.

  • Chloromethylhalicyclamine B, a Marine-Derived Protein Kinase CK1δ/ε Inhibitor.
    Publication Date: 23/11/2016, on Journal of natural products
    by Esposito G, Bourguet-Kondracki ML, Mai LH, Longeon A, Teta R, Meijer L, Van Soest R, Mangoni A, Costantino V
    DOI: 10.1021/acs.jnatprod.6b00939

    The halogenated alkaloid chloromethylhalicyclamine B (1), together with the known natural compound halicyclamine B (2), was isolated from the extract of the sponge Acanthostrongylophora ingens. The structure of compound 1 was determined by spectroscopic means, and it was shown that 1 is produced by reaction of 2 with CH2Cl2 used for extraction. Compound 1 was a selective CK1δ/ε inhibitor with an IC50 of 6 μM, while the natural compound 2 was inactive. The absolute configuration of 1 was determined by quantum mechanical calculation of its ECD spectrum, and this also determined the previously unknown absolute configuration of the parent halicyclamine B (2). Computational studies, validated by NOESY data, showed that compound 1 can efficiently interact with the ATP-binding site of CK1δ in spite of its globular structure, very different from the planar structure of known inhibitors of CK1δ. This opens the way to the design of a new structural type of CK1δ/ε inhibitors.

  • Correction: Systemic Delivery of Recombinant Brain Derived Neurotrophic Factor (BDNF) in the R6/2 Mouse Model of Huntington's Disease.
    Publication Date: 23/11/2016, on PloS one
    by Giampà C, Montagna E, Dato C, Melone MA, Bernardi G, Fusco FR
    DOI: 10.1371/journal.pone.0166102

    [This corrects the article DOI: 10.1371/journal.pone.0064037.].

  • Systematic screening of Retinopathy in Diabetes (REaD project): an Italian implementation campaign.
    Publication Date: 21/11/2016, on European journal of ophthalmology
    by Porta M, Boscia F, Lanzetta P, Mannucci E, Menchini U, Simonelli F
    DOI: 10.5301/ejo.5000912

    To evaluate the use of telemedicine retinal screening in Italy and to identify potential elements of implementation of this system.

  • G-quadruplex-based aptamers against protein targets in therapy and diagnostics.
    Publication Date: 16/11/2016, on Biochimica et biophysica acta
    by Platella C, Riccardi C, Montesarchio D, Roviello GN, Musumeci D
    DOI: 10.1016/j.bbagen.2016.11.027

    Nucleic acid aptamers are single-stranded DNA or RNA molecules identified to recognize with high affinity specific targets including proteins, small molecules, ions, whole cells and even entire organisms, such as viruses or bacteria. They can be identified from combinatorial libraries of DNA or RNA oligonucleotides by SELEX technology, an in vitro iterative selection procedure consisting of binding (capture), partitioning and amplification steps. Remarkably, many of the aptamers selected against biologically relevant protein targets are G-rich sequences that can fold into stable G-quadruplex (G4) structures. Aiming at disseminating novel inspiring ideas within the scientific community in the field of G4-structures, the emphasis of this review is placed on: 1) recent advancements in SELEX technology for the efficient and rapid identification of new candidate aptamers (introduction of microfluidic systems and next generation sequencing); 2) recurrence of G4 structures in aptamers selected by SELEX against biologically relevant protein targets; 3) discovery of several G4-forming motifs in important regulatory regions of the human or viral genome bound by endogenous proteins, which per se can result into potential aptamers; 4) an updated overview of G4-based aptamers with therapeutic potential and 5) a discussion on the most attractive G4-based aptamers for diagnostic applications. This article is part of a Special Issue entitled "G-quadruplex" Guest Editor: Dr. Concetta Giancola and Dr. Daniela Montesarchio.

  • Discovery of the first dual G-triplex/G-quadruplex stabilizing compound: a new opportunity in the targeting of G-rich DNA structures?
    Publication Date: 09/11/2016, on Biochimica et biophysica acta
    by Amato J, Pagano A, Cosconati S, Amendola G, Fotticchia I, Iaccarino N, Marinello J, De Magis A, Capranico G, Novellino E, Pagano B, Randazzo A
    DOI: 10.1016/j.bbagen.2016.11.008

    Guanine-rich DNA motifs can form non-canonical structures known as G-quadruplexes, whose role in tumorigenic processes makes them attractive drug-target candidates for cancer therapy. Recent studies revealed that the folding and unfolding pathways of G-quadruplexes proceed through a quite stable intermediate named G-triplex.

  • CLINICAL PRESENTATION AND DISEASE COURSE OF USHER SYNDROME BECAUSE OF MUTATIONS IN MYO7A OR USH2A.
    Publication Date: 08/11/2016, on Retina (Philadelphia, Pa.)
    by Testa F, Melillo P, Bonnet C, Marcelli V, de Benedictis A, Colucci R, Gallo B, Kurtenbach A, Rossi S, Marciano E, Auricchio A, Petit C, Zrenner E, Simonelli F
    DOI: 10.1097/IAE.0000000000001389

    To evaluate differences in the visual phenotype and natural history of Usher syndrome caused by mutations in MYO7A or USH2A, the most commonly affected genes of Usher syndrome Type I (USH1) and Type II (USH2), respectively.

  • Closing-in is Related to Daily Living Functioning in Patients With Mild-to-Moderate Alzheimer Disease.
    Publication Date: 04/11/2016, on Alzheimer disease and associated disorders
    by De Lucia N, Grossi D, Trojano L
    DOI: 10.1097/WAD.0000000000000165

  • Antineoplastic-related cardiotoxicity, morphofunctional aspects in a murine model: contribution of the new tool 2D-speckle tracking.
    Publication Date: 02/11/2016, on OncoTargets and therapy
    by Coppola C, Riccio G, Barbieri A, Monti MG, Piscopo G, Rea D, Arra C, Maurea C, De Lorenzo C, Maurea N
    DOI: 10.2147/OTT.S106528

    Considering that global left ventricular systolic radial strain is a sensitive technique for the early detection of left ventricular dysfunction due to antineoplastics and the analysis of segmental myocardial contractility, we evaluated this technique for early detection of trastuzumab-related cardiotoxicity by comparing it with cardiac structural damage.

  • Sorafenib Combined with Radio-frequency Ablation Compared with Sorafenib Alone in Treatment of Hepatocellular Carcinoma Invading Portal Vein: A Western Randomized Controlled Trial.
    Publication Date: 01/11/2016, on Anticancer research
    by Giorgio A, Merola MG, Montesarchio L, Merola F, Santoro B, Coppola C, Gatti P, Amendola F, DI Sarno A, Calvanese A, Matteucci P, Giorgio V
    DOI: 10.21873/anticanres.11211

    To compare in a randomized controlled trial (RCT) 3-year survival of cirrhotic patients with hepatocellular carcinoma (HCC) accompanied by portal vein tumor thrombus (PVTT) treated with sorafenib plus percutaneous radiofrequency ablation (RFA) of both intraparenchymal HCC and PVTT (combination Group) or sorafenib alone (sorafenib-alone Group).

  • Eye movements reveal mechanisms underlying attentional biases towards threat.
    Publication Date: 01/11/2016, on Cognition & emotion
    by Sagliano L, D'Olimpio F, Taglialatela Scafati I, Trojano L
    DOI: 10.1080/02699931.2015.1055712

    Mechanisms underlying attentional biases towards threat (ABTs), such as attentional avoidance and difficulty of disengagement, are still unclear. To address this issue, we recorded participants' eye movements during a dot detection task in which threatening or neutral stimuli served as peripheral cues. We evaluated response times (RTs) in trials where participants looked at the central fixation cross (not at the cues), as they were required, and number and duration of (unwanted) fixations towards threatening or neutral cues; in all analyses trait anxiety was treated as a covariate. Difficulty in attentional disengagement (longer RTs) was found when peripheral threatening stimuli were presented for 100 ms. Moreover, we observed significantly shorter (unwanted) fixations on threatening than on neutral peripheral stimuli, compatible with an avoidance bias, for longer presentation times. These findings demonstrate that, independent of trait anxiety levels, disengagement bias occurs without eye movements, whereas eye movements are implied in threat avoidance.

  • Sporadic cerebral amyloid angiopathy as a cause of relapsing lobar hemorrhage, convexal subarachnoid hemorrhage and cortical superficial siderosis.
    Publication Date: 01/11/2016, on Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology
    by Conforti R, Sardaro A, Cirillo S, Parlato C
    DOI: 10.1007/s10072-016-2624-8

  • The EDSS integration with the Brief International Cognitive Assessment for Multiple Sclerosis and orientation tests.
    Publication Date: 01/11/2016, on Multiple sclerosis (Houndmills, Basingstoke, England)
    by Saccà F, Costabile T, Carotenuto A, Lanzillo R, Moccia M, Pane C, Russo CV, Barbarulo AM, Casertano S, Rossi F, Signoriello E, Lus G, Brescia Morra V
    DOI: 10.1177/1352458516677592

    Despite cognitive tests have been validated in multiple sclerosis (MS), a neuropsychological evaluation is not implemented in the Expanded Disability Status Scale (EDSS) scoring.

  • Neuromuscular transmission abnormalities in myotonic dystrophy type 1: A neurophysiological study.
    Publication Date: 01/11/2016, on Clinical neurology and neurosurgery
    by Bombelli F, Lispi L, Porrini SC, Giacanelli M, Terracciano C, Massa R, Petrucci A
    DOI: 10.1016/j.clineuro.2016.08.020

    Weakness and fatigue are frequent symptoms in myotonic dystrophy type 1 (DM1), mainly as a result of muscle impairment. However, neuromuscular junction (NMJ) abnormalities could play an additional role in determining these manifestations. We aimed to document the possible NMJ involvement in DM1.

  • Profiling Carbonylated Proteins in Heart and Skeletal Muscle Mitochondria from Trained and Untrained Mice.
    Publication Date: 07/10/2016, on Journal of proteome research
    by Carpentieri A, Gamberi T, Modesti A, Amoresano A, Colombini B, Nocella M, Bagni MA, Fiaschi T, Barolo L, Gulisano M, Magherini F
    DOI: 10.1021/acs.jproteome.6b00475

    Understanding the relationship between physical exercise, reactive oxygen species, and skeletal muscle modification is important in order to better identify the benefits or the damages that appropriate or inappropriate exercise can induce. Heart and skeletal muscles have a high density of mitochondria with robust energetic demands, and mitochondria plasticity has an important role in both the cardiovascular system and skeletal muscle responses. The aim of this study was to investigate the influence of regular physical activity on the oxidation profiles of mitochondrial proteins from heart and tibialis anterior muscles. To this end, we used the mouse as animal model. Mice were divided into two groups: untrained and regularly trained. The carbonylated protein pattern was studied by two-dimensional gel electrophoresis followed by Western blot with anti-dinitrophenyl hydrazone antibodies. Mass spectrometry analysis allowed the identification of several different protein oxidation sites, including methionine, cysteine, proline, and leucine residues. A large number of oxidized proteins were found in both untrained and trained animals. Moreover, mitochondria from skeletal muscles and heart showed almost the same carbonylation pattern. Interestingly, exercise training seems to increase the carbonylation level mainly of mitochondrial proteins from skeletal muscle.