Latest PUBLICATIONS

  • A novel CISD2 intragenic deletion, optic neuropathy and platelet aggregation defect in Wolfram syndrome type 2.
    Publication Date: 24/07/2014, on BMC medical genetics
    by Mozzillo E, Delvecchio M, Carella M, Grandone E, Palumbo P, Salina A, Aloi C, Buono P, Izzo A, D'Annunzio G, Vecchione G, Orrico A, Genesio R, Simonelli F, Franzese A
    DOI: 10.1186/1471-2350-15-88

    Wolfram Syndrome type 2 (WFS2) is considered a phenotypic and genotypic variant of WFS, whose minimal criteria for diagnosis are diabetes mellitus and optic atrophy. The disease gene for WFS2 is CISD2. The clinical phenotype of WFS2 differs from WFS1 for the absence of diabetes insipidus and psychiatric disorders, and for the presence of bleeding upper intestinal ulcers and defective platelet aggregation. After the first report of consanguineous Jordanian patients, no further cases of WFS2 have been reported worldwide. We describe the first Caucasian patient affected by WFS2.

  • Bis-indole derivatives with antitumor activity turn out to be specific ligands of human telomeric G-quadruplex.
    Publication Date: 24/07/2014, on Frontiers in chemistry
    by Amato J, Iaccarino N, Pagano B, Morigi R, Locatelli A, Leoni A, Rambaldi M, Zizza P, Biroccio A, Novellino E, Randazzo A
    DOI: 10.3389/fchem.2014.00054

    Bis-indolinone derivatives having either 2,6-disubstituted pyridine core (1a and 1b) or 1,10-disubstituted phenanthroline core (2a and 2b), already known to have antitumor activity, have been tested as potential G-quadruplex binders. Compounds 2a and 2b are able to selectively stabilize G-quadruplex over duplex DNA, and also to discriminate among different G-quadruplex structures, having a particular affinity for the parallel form of the human telomeric G-quadruplex. Both compounds are also able to induce telomeric DNA damage that may explain the activity of these compounds.

  • Synthesis and pharmacological evaluation of modified adenosines joined to mono-functional platinum moieties.
    Publication Date: 03/07/2014, on Molecules (Basel, Switzerland)
    by D'Errico S, Oliviero G, Borbone N, Piccialli V, Pinto B, De Falco F, Maiuri MC, Carnuccio R, Costantino V, Nici F, Piccialli G
    DOI: 10.3390/molecules19079339

    The synthesis of four novel platinum complexes, bearing N6-(6-amino-hexyl)adenosine or a 1,6-di(adenosin-N6-yl)-hexane respectively, as ligands of mono-functional cisplatin or monochloro(ethylendiamine)platinum(II), is reported. The chemistry exploits the high affinity of the charged platinum centres towards the N7 position of the adenosine base system and a primary amine of an alkyl chain installed on the C6 position of the purine. The cytotoxic behaviour of the synthesized complexes has been studied in A549 adenocarcinomic human alveolar basal epithelial and MCF7 human breast adenocarcinomic cancer cell lines, in order to investigate their effects on cell viability and proliferation.

  • Structural connectivity in a single case of progressive prosopagnosia: the role of the right inferior longitudinal fasciculus.
    Publication Date: 01/07/2014, on Cortex; a journal devoted to the study of the nervous system and behavior
    by Grossi D, Soricelli A, Ponari M, Salvatore E, Quarantelli M, Prinster A, Trojano L
    DOI: 10.1016/j.cortex.2012.09.010

    Progressive prosopagnosia (PP) is a clinical syndrome characterized by a progressive and selective inability to recognize and identify faces of familiar people. Here we report a patient (G.S.) with PP, mainly related to a prominent deficit in recognition of familiar faces, without a semantic (cross-modal) impairment. An in-depth evaluation showed that his deficit extended to other classes of objects, both living and non-living. A follow-up neuropsychological assessment did not reveal substantial changes after about 1 year. Structural MRI showed predominant right temporal lobe atrophy. Diffusion tensor imaging was performed to elucidate structural connectivity of the inferior longitudinal fasciculus (ILF) and the inferior fronto-occipital fasciculus (IFOF), the two major tracts that project through the core fusiform region to the anterior temporal and frontal cortices, respectively. Right ILF was markedly reduced in G.S., while left ILF and IFOFs were apparently preserved. These data are in favour of a crucial role of the neural circuit subserved by right ILF in the pathogenesis of PP.

  • Attentional biases toward threat: the concomitant presence of difficulty of disengagement and attentional avoidance in low trait anxious individuals.
    Publication Date: 01/07/2014, on Frontiers in psychology
    by Sagliano L, Trojano L, Amoriello K, Migliozzi M, D'Olimpio F
    DOI: 10.3389/fpsyg.2014.00685

    Attentional biases toward threats (ABTs) have been described in high anxious individuals and in clinical samples whereas they have been rarely reported in non-clinical samples (Bar-Haim et al., 2007; Cisler and Koster, 2010). Three kinds of ABTs have been identified (facilitation, difficulty of disengagement, and avoidance) but their mechanisms and time courses are still unclear. This study aimed to understand ABTs mechanisms and timing in low trait anxiety (LTA) and high trait anxiety (HTA) anxious individuals. In particular, in an exogenous cueing task we used threatening or neutral stimuli as peripheral cues with three presentation times (100, 200, or 500 ms). The main results showed that HTA individuals have an attentional facilitation bias at 100 ms (likely automatic in nature) whereas LTA individuals show attentional avoidance and difficulty to disengage from threatening stimuli at 200 ms (likely related to a strategic processing). Such findings demonstrate that threat biases attention with specific mechanisms and time courses, and that anxiety levels modulate attention allocation.

  • A study of the psychological distress in family caregivers of patients with prolonged disorders of consciousness during in-hospital rehabilitation.
    Publication Date: 01/07/2014, on Clinical rehabilitation
    by Moretta P, Estraneo A, De Lucia L, Cardinale V, Loreto V, Trojano L
    DOI: 10.1177/0269215514521826

    To study psychological distress in a sample of caregivers of patients affected by prolonged disorders of consciousness during hospital stay in the Neurorehabilitation Unit.

  • PTEN deficiency and mutant p53 confer glucose-addiction to thyroid cancer cells: impact of glucose depletion on cell proliferation, cell survival, autophagy and cell migration.
    Publication Date: 01/07/2014, on Genes & cancer
    by Morani F, Phadngam S, Follo C, Titone R, Thongrakard V, Galetto A, Alabiso O, Isidoro C
    DOI: 10.18632/genesandcancer.21

    Proliferating cancer cells oxidize glucose through the glycolytic pathway. Since this metabolism is less profitable in terms of ATP production, cancer cells consume large quantity of glucose, and those that experience insufficient blood supply become glucose-addicted. We have analyzed the response to glucose depletion in WRO and FTC133 follicular thyroid cancer cells, which differ in the expression of two key regulators of the glucose metabolism. WRO cells, which express wild type p53 and PTEN, showed a higher rate of cell proliferation and were much less sensitive to glucose-depletion than FTC133 cells, which are PTEN null and express mutant p53. Glucose depletion slowed-down the autophagy flux in FTC133 cells, not in WRO cells. In a wound-healing assay, WRO cells were shown to migrate faster than FTC133 cells. Glucose depletion slowed down the cell migration rate, and these effects were more evident in FTC133 cells. Genetic silencing of either wild-type PTEN or p53 in WRO cells resulted in increased uptake of glucose, whereas the ectopic expression of PTEN in FTC133 cells resulted in diminished glucose uptake. In conclusion, compared to WRO, FTC133 cells were higher glucose up-taker and consumer. These data do not support the general contention that cancer cells lacking PTEN or expressing the mutant p53R273H are more aggressive and prone to better face glucose depletion. We propose that concurrent PTEN deficiency and mutant p53 leads to a glucose-addiction state that renders the cancer cell more sensitive to glucose restriction. The present observation substantiates the view that glucose-restriction may be an adjuvant strategy to combat these tumours.

  • Macular abnormalities in Italian patients with retinitis pigmentosa.
    Publication Date: 01/07/2014, on The British journal of ophthalmology
    by Testa F, Rossi S, Colucci R, Gallo B, Di Iorio V, della Corte M, Azzolini C, Melillo P, Simonelli F
    DOI: 10.1136/bjophthalmol-2013-304082

    To investigate the prevalence of macular abnormalities in a large Caucasian cohort of patients affected by retinitis pigmentosa (RP).

  • Wilson disease protein ATP7B utilizes lysosomal exocytosis to maintain copper homeostasis.
    Publication Date: 23/06/2014, on Developmental cell
    by Polishchuk EV, Concilli M, Iacobacci S, Chesi G, Pastore N, Piccolo P, Paladino S, Baldantoni D, van IJzendoorn SC, Chan J, Chang CJ, Amoresano A, Pane F, Pucci P, Tarallo A, Parenti G, Brunetti-Pierri N, Settembre C, Ballabio A, Polishchuk RS
    DOI: 10.1016/j.devcel.2014.04.033

    Copper is an essential yet toxic metal and its overload causes Wilson disease, a disorder due to mutations in copper transporter ATP7B. To remove excess copper into the bile, ATP7B traffics toward canalicular area of hepatocytes. However, the trafficking mechanisms of ATP7B remain elusive. Here, we show that, in response to elevated copper, ATP7B moves from the Golgi to lysosomes and imports metal into their lumen. ATP7B enables lysosomes to undergo exocytosis through the interaction with p62 subunit of dynactin that allows lysosome translocation toward the canalicular pole of hepatocytes. Activation of lysosomal exocytosis stimulates copper clearance from the hepatocytes and rescues the most frequent Wilson-disease-causing ATP7B mutant to the appropriate functional site. Our findings indicate that lysosomes serve as an important intermediate in ATP7B trafficking, whereas lysosomal exocytosis operates as an integral process in copper excretion and hence can be targeted for therapeutic approaches to combat Wilson disease.

  • Abnormal thalamic function in patients with vestibular migraine.
    Publication Date: 10/06/2014, on Neurology
    by Russo A, Marcelli V, Esposito F, Corvino V, Marcuccio L, Giannone A, Conforti R, Marciano E, Tedeschi G, Tessitore A
    DOI: 10.1212/WNL.0000000000000496

    To investigate the functional response of neural pathways associated with vestibular stimulation in patients with vestibular migraine (VM).

  • High grade glioblastoma is associated with aberrant expression of ZFP57, a protein involved in gene imprinting, and of CPT1A and CPT1C that regulate fatty acid metabolism.
    Publication Date: 01/06/2014, on Cancer biology & therapy
    by Cirillo A, Di Salle A, Petillo O, Melone MA, Grimaldi G, Bellotti A, Torelli G, De' Santi MS, Cantatore G, Marinelli A, Galderisi U, Peluso G
    DOI: 10.4161/cbt.28408

    The diagnosis of glioblastoma is still based on tumor histology, but emerging molecular diagnosis is becoming an important part of glioblastoma classification. Besides the well-known cell cycle-related circuitries that are associated with glioblastoma onset and development, new insights may be derived by looking at pathways involved in regulation of epigenetic phenomena and cellular metabolism, which may both be highly deregulated in cancer cells. We evaluated if in glioblastoma patients the high grade of malignancy could be associated with aberrant expression of some genes involved in regulation of epigenetic phenomena and lipid metabolism. We measured the mRNA levels of ZFP57, TRIM28, CPT1A, CPT1B, and CPT1C in a cohort of 80 patients divided in two groups: grade II and grade IV. We evidenced that high grade glioblastoma is associated with increased level of ZFP57, a protein involved in gene imprinting, and aberrant expression of CPT1A and CPT1C, regulators of fatty acid oxidation. Our study may pave the way to identify new markers that could be potentially useful for diagnosis and/or prognosis of glioblastoma.

  • Dilated Virchow-Robin spaces and multiple sclerosis: 3 T magnetic resonance study.
    Publication Date: 01/06/2014, on La Radiologia medica
    by Conforti R, Cirillo M, Saturnino PP, Gallo A, Sacco R, Negro A, Paccone A, Caiazzo G, Bisecco A, Bonavita S, Cirillo S
    DOI: 10.1007/s11547-013-0357-9

    The aim of this study was to assess differences in the presence, size, number and site of dilated cerebral Virchow-Robin spaces (VRSd) between patients with multiple sclerosis (MS) in the inactive phase and healthy controls, and between MS patients with disabling (MSd) or nondisabling (MSnd) disease.

  • Sleep disorders in myotonic dystrophy type 2: a controlled polysomnographic study and self-reported questionnaires.
    Publication Date: 01/06/2014, on European journal of neurology
    by Romigi A, Albanese M, Placidi F, Izzi F, Liguori C, Marciani MG, Mercuri NB, Terracciano C, Vitrani G, Petrucci A, Di Gioia B, Massa R
    DOI: 10.1111/ene.12226

    There is a paucity of data available regarding the occurrence of sleep disorders in myotonic dystrophy type 2 (DM2). In this study the sleep-wake cycle and daytime sleepiness were investigated in DM2 patients and compared with results from healthy subjects and myotonic dystrophy type 1 (DM1) patients.

  • G-quadruplex on oligo affinity support (G4-OAS): an easy affinity chromatography-based assay for the screening of G-quadruplex ligands.
    Publication Date: 06/05/2014, on Analytical chemistry
    by Musumeci D, Amato J, Randazzo A, Novellino E, Giancola C, Montesarchio D, Pagano B
    DOI: 10.1021/ac500444m

    A simple, cheap, and highly reproducible affinity chromatography-based method has been developed for the screening of G-quadruplex binders. The tested compounds were flowed through a polystyrene resin functionalized with an oligonucleotide able to form, in proper conditions, a G-quadruplex structure. Upon cation-induced control of the folding/unfolding processes of the immobilized G-quadruplex-forming sequence, small molecules specifically interacting with the oligonucleotide structure were first captured and then released depending on the used working solution. This protocol, first optimized for different kinds of known G-quadruplex ligands and then applied to a set of putative ligands, has allowed one to fully reuse the same functionalized resin batch, recycled for several tens of experiments without loss in efficiency and reproducibility.

  • Golgi sorting regulates organization and activity of GPI proteins at apical membranes.
    Publication Date: 01/05/2014, on Nature chemical biology
    by Paladino S, Lebreton S, Tivodar S, Formiggini F, Ossato G, Gratton E, Tramier M, Coppey-Moisan M, Zurzolo C
    DOI: 10.1038/nchembio.1495

    Here we combined classical biochemistry with new biophysical approaches to study the organization of glycosylphosphatidylinositol (GPI)-anchored proteins (GPI-APs) with high spatial and temporal resolution at the plasma membrane of polarized epithelial cells. We show that in polarized MDCK cells, after sorting in the Golgi, each GPI-AP reaches the apical surface in homoclusters. Golgi-derived homoclusters are required for their subsequent plasma membrane organization into cholesterol-dependent heteroclusters. By contrast, in nonpolarized MDCK cells, GPI-APs are delivered to the surface as monomers in an unpolarized manner and are not able to form heteroclusters. We further demonstrate that this GPI-AP organization is regulated by the content of cholesterol in the Golgi apparatus and is required to maintain the functional state of the protein at the apical membrane. Thus, in contrast to fibroblasts, in polarized epithelial cells, a selective cholesterol-dependent sorting mechanism in the Golgi regulates both the organization and function of GPI-APs at the apical surface.