Latest PUBLICATIONS

  • Not unusual, just different! Chemistry, biology and applications of G-quadruplex nucleic acids.
    Publication Date: 01/05/2017, on Biochimica et biophysica acta
    by Giancola C, Montesarchio D
    DOI: 10.1016/j.bbagen.2017.03.022

  • Mutations in the PCYT1A gene are responsible for isolated forms of retinal dystrophy.
    Publication Date: 01/05/2017, on European journal of human genetics : EJHG
    by Testa F, Filippelli M, Brunetti-Pierri R, Di Fruscio G, Di Iorio V, Pizzo M, Torella A, Barillari MR, Nigro V, Brunetti-Pierri N, Simonelli F, Banfi S
    DOI: 10.1038/ejhg.2017.23

    Mutations in the PCYT1A gene have been recently linked to two different phenotypes: one characterized by spondylometaphyseal dysplasia and cone-rod dystrophy (SMD-CRD) and the other by congenital lipodystrophy, severe fatty liver disease, and reduced HDL cholesterol without any retinal or skeletal involvement. Here, we identified, by next generation sequencing, sequence variants affecting function in the PCYT1A gene in three young patients with isolated retinal dystrophy from two different Italian families. A thorough clinical evaluation of the patients, with whole skeleton X-ray, metabolic assessment and liver ultrasound failed to reveal signs of skeletal dysplasia, metabolic and hepatic alterations. This is the first report showing that the PCYT1A gene can be responsible for isolated forms of retinal dystrophy, particularly without any skeletal involvement, thus further expanding the phenotypic spectrum induced by mutations in this gene.

  • Family caregivers' opinions about interaction with the environment in consciousness disorders.
    Publication Date: 01/05/2017, on Rehabilitation psychology
    by Moretta P, Trojano L, Masotta O, Cardinale V, Loreto V, Estraneo A
    DOI: 10.1037/rep0000144

    To assess family caregivers' opinions about level of interaction with the environment in their relatives with disorders of consciousness (DOCs) and to explore psychological features of caregivers whose opinions diverge from clinicians' diagnosis.

  • Studies toward the Synthesis of Smenamide A, an Antiproliferative Metabolite from <i>Smenospongia aurea</i>: Total Synthesis of <i>ent</i>-Smenamide A and 16-<i>epi</i>-Smenamide A.
    Publication Date: 30/04/2017, on ACS omega
    by Caso A, Mangoni A, Piccialli G, Costantino V, Piccialli V
    DOI: 10.1021/acsomega.7b00095

    A chiral pool protocol toward the synthesis of the smenamide family of natural products is described. Two stereoisomers of smenamide A, namely, -smenamide A and 16--smenamide A were synthesized with a 2.6 and 2.5% overall yield, respectively. Their carboxylic acid moieties were assembled starting from -citronellene via two Wittig reactions and a Grignard process. Its coupling with either ()- or ()-dolapyrrolidinone, synthesized from Boc-l-Phe and Boc-d-Phe, respectively, was accomplished by using the Andrus protocol. This work also established the previously unknown relative and absolute configurations of smenamide A.

  • Multiple spinal nerve enlargement and SOS1 mutation: further evidence of overlap between Neurofibromatosis type 1 and Noonan phenotype.
    Publication Date: 29/04/2017, on Clinical genetics
    by Santoro C, Giugliano T, Melone MAB, Cirillo M, Schettino C, Bernardo P, Cirillo G, Perrotta S, Piluso G
    DOI: 10.1111/cge.13047

    Neurofibromatosis type 1 (NF1) has long been considered a well-defined, recognizable monogenic disorder, with neurofibromas constituting a pathognomonic sign. This dogma has been challenged by recent descriptions of patients with enlarged nerves or paraspinal tumors, suggesting that neurogenic tumors and hypertrophic neuropathy may be a complication of Noonan syndrome with multiple lentigines or RASopathy phenotype. We describe a 15-year-old boy, whose mother previously received clinical diagnosis of NF1 due to presence of bilateral cervical and lumbar spinal lesions resembling plexiform neurofibromas and features suggestive of Noonan syndrome. NF1 molecular analysis was negative in the mother. The boy presented with Noonan features, multiple lentigines and pectus excavatum. NGS analysis of all RASopathy genes identified p.Ser548Arg missense mutation in SOS1 in the boy, confirmed in his mother. Brain and spinal MRI scans were negative in the boy. No heart involvement or deafness was observed in proband or mother. This is the first report of a SOS1 mutation associated with hypertrophic neuropathy resembling plexiform neurofibromas, a rare complication in Noonan phenotypes with mutations in RASopathy genes. Our results highlight the overlap between RASopathies, suggesting that NF1 diagnostic criteria need rethinking. Genetic analysis of RASopathy genes should be considered when diagnosis is uncertain.

  • The centrosomal OFD1 protein interacts with the translation machinery and regulates the synthesis of specific targets.
    Publication Date: 27/04/2017, on Scientific reports
    by Iaconis D, Monti M, Renda M, van Koppen A, Tammaro R, Chiaravalli M, Cozzolino F, Pignata P, Crina C, Pucci P, Boletta A, Belcastro V, Giles RH, Maria Surace E, Gallo S, Pende M, Franco B
    DOI: 10.1038/s41598-017-01156-x

    Protein synthesis is traditionally associated with specific cytoplasmic compartments. We now show that OFD1, a centrosomal/basal body protein, interacts with components of the Preinitiation complex of translation (PIC) and of the eukaryotic Initiation Factor (eIF)4F complex and modulates the translation of specific mRNA targets in the kidney. We demonstrate that OFD1 cooperates with the mRNA binding protein Bicc1 to functionally control the protein synthesis machinery at the centrosome where also the PIC and eIF4F components were shown to localize in mammalian cells. Interestingly, Ofd1 and Bicc1 are both involved in renal cystogenesis and selected targets were shown to accumulate in two models of inherited renal cystic disease. Our results suggest a possible role for the centrosome as a specialized station to modulate translation for specific functions of the nearby ciliary structures and may provide functional clues for the understanding of renal cystic disease.

  • Prognostic indicators in pediatric clinically isolated syndrome.
    Publication Date: 25/04/2017, on Annals of neurology
    by Iaffaldano P, Simone M, Lucisano G, Ghezzi A, Coniglio G, Brescia Morra V, Salemi G, Patti F, Lugaresi A, Izquierdo G, Bergamaschi R, Cabrera-Gomez JA, Pozzilli C, Millefiorini E, Alroughani R, Boz C, Pucci E, Zimatore GB, Sola P, Lus G, Maimone D, Avolio C, Cocco E, Sajedi SA, Costantino G, Duquette P, Shaygannejad V, Petersen T, Fernández Bolaños R, Paolicelli D, Tortorella C, Spelman T, Margari L, Amato MP, Comi G, Butzkueven H, Trojano M, ,
    DOI: 10.1002/ana.24938

    To assess prognostic factors for a second clinical attack and a first disability worsening event in pediatric clinically isolated syndrome (pCIS) suggestive of Multiple Sclerosis (MS) patients.

  • First study on the peptidergic innervation of the brain superior sagittal sinus in humans.
    Publication Date: 24/04/2017, on Neuropeptides
    by Sampaolo S, Liguori G, Vittoria A, Napolitano F, Lombardi L, Figols J, Melone MAB, Esposito T, Di Iorio G
    DOI: 10.1016/j.npep.2017.04.008

    The superior sagittal sinus (SSS) of the mammalian brain is a pain-sensitive intracranial vessel thought to play a role in the pathogenesis of migraine headaches. Here, we aimed to investigate the presence and the potential co-localization of some neurotransmitters in the human SSS. Immunohistochemical and double-labeling immunofluorescence analyses were applied to paraformaldehyde-fixed, paraffin-embedded, coronal sections of the SSS. Protein extraction and Western blotting technique were performed on the same material to confirm the morphological data. Our results showed nerve fibers clustered mainly in large bundles tracking parallel to the longitudinal axis of the sinus, close in proximity to the vascular endothelium. Smaller fascicles of fibers encircled the vascular lumen in a spiral fashion, extending through the subendothelial connective tissue. Isolated nerve fibers were observed around the openings of bridging veins in the sinus or around small vessels extending into the perisinusal dura. The neurotransmitters calcitonin gene related peptide (CGRP), substance P (SP), neuronal nitric oxide synthase (nNOS), vasoactive intestinal polypeptide (VIP), tyrosine hydroxylase (TH), and neuropeptide Y (NPY) were found in parietal nerve structures, distributed all along the length of the SSS. Overall, CGRP- and TH-containing nerve fibers were the most abundant. Neurotransmitters co-localized in the same fibers in the following pairs: CGRP/SP, CGRP/NOS, CGRP/VIP, and TH/NPY. Western blotting analysis confirmed the presence of such neurosubstances in the SSS wall. Overall our data provide the first evidence of the presence and co-localization of critical neurotransmitters in the SSS of the human brain, thus contributing to a better understanding of the sinus functional role.

  • The utility of the basophil activation test in the diagnosis of immediate amoxicillin or amoxicillin-clavulanate hypersensitivity in children and adults.
    Publication Date: 21/04/2017, on Italian journal of pediatrics
    by Barni S, Mori F, Valleriani C, Mangone G, Testi S, Saretta F, Sarti L, Pucci N, de Martino M, Azzari C, Novembre E
    DOI: 10.1186/s13052-017-0360-1

    The basophil activation test (BAT), has been proposed as a possible assay for the diagnosis of immediate-type allergy to beta-lactams (BLs). The aim of this study was to assess the utility of BAT in the diagnosis of amoxicillin (AMX) or AMX-clavulanate (AMX-C) IgE-mediated hypersensitivity in children and adults.

  • Apathy in amyotrophic lateral sclerosis: insights from Dimensional Apathy Scale.
    Publication Date: 21/04/2017, on Amyotrophic lateral sclerosis & frontotemporal degeneration
    by Santangelo G, Siciliano M, Trojano L, Femiano C, Monsurrò MR, Tedeschi G, Trojsi F
    DOI: 10.1080/21678421.2017.1313865

    Apathy is associated with cognitive decline and worse survival in amyotrophic lateral sclerosis (ALS); an accurate evaluation of this aspect is relevant in clinical settings. The aims of this study are to evaluate the prevalence of apathy in a large ALS sample, using published diagnostic criteria, and to explore the psychometric properties, the sensitivity and the specificity of the Dimensional Apathy Scale (DAS) as a screening tool for apathy.

  • Psychological distress is associated with altered cognitive functioning in family caregivers of patients with disorders of consciousness.
    Publication Date: 17/04/2017, on Brain injury
    by Moretta P, Masotta O, Crispino E, Castronovo G, Ruvolo S, Montalbano C, Loreto V, Trojano L, Estraneo A
    DOI: 10.1080/02699052.2017.1290278

    To analyse the possible presence of reduced cognitive efficiency in family caregivers of patients with prolonged disorders of consciousness (DOC).

  • Novel human bioactive peptides identified in Apolipoprotein B: Evaluation of their therapeutic potential.
    Publication Date: 15/04/2017, on Biochemical pharmacology
    by Gaglione R, Dell'Olmo E, Bosso A, Chino M, Pane K, Ascione F, Itri F, Caserta S, Amoresano A, Lombardi A, Haagsman HP, Piccoli R, Pizzo E, Veldhuizen EJ, Notomista E, Arciello A
    DOI: 10.1016/j.bcp.2017.01.009

    Host defence peptides (HDPs) are short, cationic amphipathic peptides that play a key role in the response to infection and inflammation in all complex life forms. It is increasingly emerging that HDPs generally have a modest direct activity against a broad range of microorganisms, and that their anti-infective properties are mainly due to their ability to modulate the immune response. Here, we report the recombinant production and characterization of two novel HDPs identified in human Apolipoprotein B (residues 887-922) by using a bioinformatics method recently developed by our group. We focused our attention on two variants of the identified HDP, here named r(P)ApoBL and r(P)ApoBS, 38- and 26-residue long, respectively. Both HDPs were found to be endowed with a broad-spectrum antimicrobial activity while they show neither toxic nor haemolytic effects towards eukaryotic cells. Interestingly, both HDPs were found to display a significant anti-biofilm activity, and to act in synergy with either commonly used antibiotics or EDTA. The latter was selected for its ability to affect bacterial outer membrane permeability, and to sensitize bacteria to several antibiotics. Circular dichroism analyses showed that SDS, TFE, and LPS significantly alter r(P)ApoBL conformation, whereas slighter or no significant effects were detected in the case of r(P)ApoBS peptide. Interestingly, both ApoB derived peptides were found to elicit anti-inflammatory effects, being able to mitigate the production of pro-inflammatory interleukin-6 and nitric oxide in LPS induced murine macrophages. It should also be emphasized that r(P)ApoBL peptide was found to play a role in human keratinocytes wound closure in vitro. Altogether, these findings open interesting perspectives on the therapeutic use of the herein identified HDPs.

  • Repeated transcranial direct current stimulation in prolonged disorders of consciousness: A double-blind cross-over study.
    Publication Date: 15/04/2017, on Journal of the neurological sciences
    by Estraneo A, Pascarella A, Moretta P, Masotta O, Fiorenza S, Chirico G, Crispino E, Loreto V, Trojano L
    DOI: 10.1016/j.jns.2017.02.036

    To evaluate effects of 5 sessions of transcranial direct current stimulation (tDCS) over the left dorsolateral prefrontal cortex in patients with prolonged disorders of consciousness (DOC).

  • Neuropsychological Correlates of Theory of Mind Deficits in Patients With Multiple Sclerosis.
    Publication Date: 13/04/2017, on Neuropsychology
    by Raimo S, Trojano L, Pappacena S, Alaia R, Spitaleri D, Grossi D, Santangelo G
    DOI: 10.1037/neu0000372

    Theory of mind (ToM) is the ability to understand and interpret another person's beliefs, intentions (cognitive ToM) and emotions (affective ToM).

  • Percutaneous Radiofrequency Ablation of Hepatocellular Carcinoma in cirrhosis: analysis of complications in a single center over 20 years.
    Publication Date: 12/04/2017, on The British journal of radiology
    by Giorgio A, Merola MG, Montesarchio L, Merola F, Gatti P, Coppola C, Giorgio V, Calisti G
    DOI: 10.1259/bjr.20160804

    To report on our 20 years' experience on complications after Radiofrequency Ablation (RFA) of Hepatocellular Carcinoma (HCC) in cirrhotic patients.