Latest PUBLICATIONS

  • WITHDRAWN:A Practical Approach for Management of QT Prolongation Induced by Anticancer Drugs.
    Publication Date: 14/03/2016, on The oncologist
    by Maurea N, Coppola C, Piscopo G, Galletta F, Riccio G, De Lorenzo C
    DOI: 10.1634/theoncologist.2015-0313

    Ahead of Print article withdrawn by publisher.

  • Rhodopsin targeted transcriptional silencing by DNA-binding.
    Publication Date: 14/03/2016, on eLife
    by Botta S, Marrocco E, de Prisco N, Curion F, Renda M, Sofia M, Lupo M, Carissimo A, Bacci ML, Gesualdo C, Rossi S, Simonelli F, Surace EM
    DOI: 10.7554/eLife.12242

    Transcription factors (TFs) operate by the combined activity of their DNA-binding domains (DBDs) and effector domains (EDs) enabling the coordination of gene expression on a genomic scale. Here we show that in vivo delivery of an engineered DNA-binding protein uncoupled from the repressor domain can produce efficient and gene-specific transcriptional silencing. To interfere with RHODOPSIN (RHO) gain-of-function mutations we engineered the ZF6-DNA-binding protein (ZF6-DB) that targets 20 base pairs (bp) of a RHOcis-regulatory element (CRE) and demonstrate Rho specific transcriptional silencing upon adeno-associated viral (AAV) vector-mediated expression in photoreceptors. The data show that the 20 bp-long genomic DNA sequence is necessary for RHO expression and that photoreceptor delivery of the corresponding cognate synthetic trans-acting factor ZF6-DB without the intrinsic transcriptional repression properties of the canonical ED blocks Rho expression with negligible genome-wide transcript perturbations. The data support DNA-binding-mediated silencing as a novel mode to treat gain-of-function mutations.

  • Comparing Alzheimer's and Parkinson's diseases networks using graph communities structure.
    Publication Date: 02/03/2016, on BMC systems biology
    by Calderone A, Formenti M, Aprea F, Papa M, Alberghina L, Colangelo AM, Bertolazzi P
    DOI: 10.1186/s12918-016-0270-7

    Recent advances in large datasets analysis offer new insights to modern biology allowing system-level investigation of pathologies. Here we describe a novel computational method that exploits the ever-growing amount of "omics" data to shed light on Alzheimer's and Parkinson's diseases. Neurological disorders exhibit a huge number of molecular alterations due to a complex interplay between genetic and environmental factors. Classical reductionist approaches are focused on a few elements, providing a narrow overview of the etiopathogenic complexity of multifactorial diseases. On the other hand, high-throughput technologies allow the evaluation of many components of biological systems and their behaviors. Analysis of Parkinson's Disease (PD) and Alzheimer's Disease (AD) from a network perspective can highlight proteins or pathways common but differently represented that can be discriminating between the two pathological conditions, thus highlight similarities and differences.

  • Recognition disorders for famous faces and voices: a review of the literature and normative data of a new test battery.
    Publication Date: 01/03/2016, on Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology
    by Quaranta D, Piccininni C, Carlesimo GA, Luzzi S, Marra C, Papagno C, Trojano L, Gainotti G
    DOI: 10.1007/s10072-015-2437-1

    Several anatomo-clinical investigations have shown that familiar face recognition disorders not due to high level perceptual defects are often observed in patients with lesions of the right anterior temporal lobe (ATL). The meaning of these findings is, however, controversial, because some authors claim that these patients show pure instances of modality-specific 'associative prosopagnosia', whereas other authors maintain that in these patients voice recognition is also impaired and that these patients have a 'multimodal person recognition disorder'. To solve the problem of the nature of famous faces recognition disorders in patients affected by right ATL lesions, it is therefore very important to verify with formal tests if these patients are or are not able to recognize others by voice, but a direct comparison between the two modalities is hindered by the fact that voice recognition is more difficult than face recognition. To circumvent this difficulty, we constructed a test battery in which subjects were requested to recognize the same persons (well-known at the national level) through their faces and voices, evaluating familiarity and identification processes. The present paper describes the 'Famous People Recognition Battery' and reports the normative data necessary to clarify the nature of person recognition disorders observed in patients affected by right ATL lesions.

  • Body Constraints on Motor Simulation in Autism Spectrum Disorders.
    Publication Date: 01/03/2016, on Journal of autism and developmental disorders
    by Conson M, Hamilton A, De Bellis F, Errico D, Improta I, Mazzarella E, Trojano L, Frolli A
    DOI: 10.1007/s10803-015-2652-x

    Developmental data suggested that mental simulation skills become progressively dissociated from overt motor activity across development. Thus, efficient simulation is rather independent from current sensorimotor information. Here, we tested the impact of bodily (sensorimotor) information on simulation skills of adolescents with Autism Spectrum Disorders (ASD). Typically-developing (TD) and ASD participants judged laterality of hand images while keeping one arm flexed on chest or while holding both arms extended. Both groups were able to mentally simulate actions, but this ability was constrained by body posture more in ASD than in TD adolescents. The strong impact of actual body information on motor simulation implies that simulative skills are not fully effective in ASD individuals.

  • Treatment withdrawal in relapsing-remitting multiple sclerosis: a retrospective cohort study.
    Publication Date: 01/03/2016, on European journal of neurology
    by Lus G, Signoriello E, Maniscalco GT, Bonavita S, Signoriello S, Gallo C
    DOI: 10.1111/ene.12790

    To investigate the effect of drug withdrawal on the course of relapsing-remitting multiple sclerosis (RR-MS).

  • Erratum to: Increased risk of tumor in DM1 is not related to exposure to common lifestyle risk factors.
    Publication Date: 01/03/2016, on Journal of neurology
    by Bianchi ML, Leoncini E, Masciullo M, Modoni A, Gadalla SM, Massa R, Botta A, Rastelli E, Terracciano C, Antonini G, Bucci E, Petrucci A, Costanzi S, Santoro M, Boccia S, Silvestri G
    DOI: 10.1007/s00415-016-8068-5

  • Increased risk of tumor in DM1 is not related to exposure to common lifestyle risk factors.
    Publication Date: 01/03/2016, on Journal of neurology
    by Bianchi ML, Leoncini E, Masciullo M, Modoni A, Gadalla SM, Massa R, Rastelli E, Terracciano C, Antonini G, Bucci E, Petrucci A, Costanzi S, Santoro M, Boccia S, Silvestri G
    DOI: 10.1007/s00415-015-8006-y

    Recent studies documented an increased risk of neoplasm in patients with myotonic dystrophies (DM). Yet, none of these studies evaluated the contribution of common cancer risk factors in such observation. In this study, we included a cohort of patients (n = 255) with an established molecular diagnosis of DM type 1 (DM1), and who receives their treatment in one of the four centers with recognized expertise in neuromuscular disorders in Rome. We estimated the prevalence of benign and malignant tumors, and assessed if lifestyle factors and/or specific disease features would be associated to their occurrence. Overall, 59 benign tumors in 54 patients and 19 malignant tumors in 17 patients were diagnosed. The most common malignant neoplasms were cancers of the skin (31.6%), thyroid (21.0%), ovary (10.5%), and breast (10.5%). Uterine fibroid was the most common benign tumor (37.6%) in women, while pilomatricoma was the most common in men (28.6%). Age at enrollment (OR = 1.02, 95% CI 1.00-1.05), and female gender (OR = 5.71, 95% CI 2.90-11.22) were associated with tumor development in DM1 patients, while thyroid disorders was associated with malignant tumors only in women (OR = 5.12, 95% CI 1.35-19.37). There was no association between tumor development and evaluated lifestyle factors. In conclusion, the lack of association between common cancer risk factors and tumor development in DM1 support a pathogenic link between tumors and DM1 itself, emphasizing the need for a systematic surveillance. Our observation of an association between thyroid diseases in women and cancer development needs confirmation.

  • The Addenbrooke's Cognitive Examination Revised (ACE-R) and its sub-scores: normative values in an Italian population sample.
    Publication Date: 01/03/2016, on Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology
    by Siciliano M, Raimo S, Tufano D, Basile G, Grossi D, Santangelo F, Trojano L, Santangelo G
    DOI: 10.1007/s10072-015-2410-z

    The Addenbrooke's Cognitive Examination Revised (ACE-R) is a rapid screening battery, including five sub-scales to explore different cognitive domains: attention/orientation, memory, fluency, language and visuospatial. ACE-R is considered useful in discriminating cognitively normal subjects from patients with mild dementia. The aim of present study was to provide normative values for ACE-R total score and sub-scale scores in a large sample of Italian healthy subjects. Five hundred twenty-six Italian healthy subjects (282 women and 246 men) of different ages (age range 20-93 years) and educational level (from primary school to university) underwent ACE-R and Montreal Cognitive Assessment (MoCA). Multiple linear regression analysis revealed that age and education significantly influenced performance on ACE-R total score and sub-scale scores. A significant effect of gender was found only in sub-scale attention/orientation. From the derived linear equation, a correction grid for raw scores was built. Inferential cut-offs score were estimated using a non-parametric technique and equivalent scores (ES) were computed. Correlation analysis showed a good significant correlation between ACE-R adjusted scores with MoCA adjusted scores (r = 0.612, p < 0.001). The present study provided normative data for the ACE-R in an Italian population useful for both clinical and research purposes.

  • Intragenic G-quadruplex structure formed in the human CD133 and its biological and translational relevance.
    Publication Date: 29/02/2016, on Nucleic acids research
    by Zizza P, Cingolani C, Artuso S, Salvati E, Rizzo A, D'Angelo C, Porru M, Pagano B, Amato J, Randazzo A, Novellino E, Stoppacciaro A, Gilson E, Stassi G, Leonetti C, Biroccio A
    DOI: 10.1093/nar/gkv1122

    Cancer stem cells (CSCs) have been identified in several solid malignancies and are now emerging as a plausible target for drug discovery. Beside the questionable existence of CSCs specific markers, the expression of CD133 was reported to be responsible for conferring CSC aggressiveness. Here, we identified two G-rich sequences localized within the introns 3 and 7 of the CD133 gene able to form G-quadruplex (G4) structures, bound and stabilized by small molecules. We further showed that treatment of patient-derived colon CSCs with G4-interacting agents triggers alternative splicing that dramatically impairs the expression of CD133. Interestingly, this is strongly associated with a loss of CSC properties, including self-renewing, motility, tumor initiation and metastases dissemination. Notably, the effects of G4 stabilization on some of these CSC properties are uncoupled from DNA damage response and are fully recapitulated by the selective interference of the CD133 expression.In conclusion, we provided the first proof of the existence of G4 structures within the CD133 gene that can be pharmacologically targeted to impair CSC aggressiveness. This discloses a class of potential antitumoral agents capable of targeting the CSC subpopulation within the tumoral bulk.

  • Intracranial extension of orbital inflammatory pseudotumor: a case report and literature review.
    Publication Date: 29/02/2016, on BMC neurology
    by Tedeschi E, Ugga L, Caranci F, Califano F, Cocozza S, Lus G, Brunetti A
    DOI: 10.1186/s12883-016-0550-2

    Orbital inflammatory pseudotumor is a rare inflammatory condition of unknown cause that may extend intracranially, usually as a dural-based infiltrate. Here we report the first case of orbital pseudotumor presenting with intra-axial Magnetic Resonance Imaging (MRI) changes.

  • Epithelioid angiosarcoma arising in schwannoma of the kidney: report of the first case and review of the literature.
    Publication Date: 03/02/2016, on World journal of surgical oncology
    by Iannaci G, Crispino M, Cifarelli P, Montella M, Panarese I, Ronchi A, Russo R, Tremiterra G, Luise R, Sapere P
    DOI: 10.1186/s12957-016-0789-5

    Schwannoma and angiosarcoma are infrequent pathologies that have been rarely reported in the kidney. Angiosarcoma is an uncommon malignant tumor presenting a recognizable vascular differentiation. It can develop in any site but the most common locations include the skin, soft tissues, breast, bone, liver, and spleen while renal localization has been very rarely reported in the literature. Schwannoma is a benign peripheral nerve sheath tumor composed of cells with the immunophenotype and ultrastructural features of differentiated Schwann cells. It has a wide anatomical distribution but the most frequent locations include subcutaneous tissues of the extremities and the head and neck region and the retroperitoneal and mediastinal soft tissues. The occurrence of an angiosarcoma in a pre-existing schwannoma is an extremely rare event with <20 cases reported in worldwide literature. In the present study, a renal case of angiosarcoma arising in schwannoma is presented with a detailed review of the pertinent literature.

  • Mutations in CTNNA1 cause butterfly-shaped pigment dystrophy and perturbed retinal pigment epithelium integrity.
    Publication Date: 01/02/2016, on Nature genetics
    by Saksens NT, Krebs MP, Schoenmaker-Koller FE, Hicks W, Yu M, Shi L, Rowe L, Collin GB, Charette JR, Letteboer SJ, Neveling K, van Moorsel TW, Abu-Ltaif S, De Baere E, Walraedt S, Banfi S, Simonelli F, Cremers FP, Boon CJ, Roepman R, Leroy BP, Peachey NS, Hoyng CB, Nishina PM, den Hollander AI
    DOI: 10.1038/ng.3474

    Butterfly-shaped pigment dystrophy is an eye disease characterized by lesions in the macula that can resemble the wings of a butterfly. Here we report the identification of heterozygous missense mutations in the CTNNA1 gene (encoding α-catenin 1) in three families with butterfly-shaped pigment dystrophy. In addition, we identified a Ctnna1 missense mutation in a chemically induced mouse mutant, tvrm5. Parallel clinical phenotypes were observed in the retinal pigment epithelium (RPE) of individuals with butterfly-shaped pigment dystrophy and in tvrm5 mice, including pigmentary abnormalities, focal thickening and elevated lesions, and decreased light-activated responses. Morphological studies in tvrm5 mice demonstrated increased cell shedding and the presence of large multinucleated RPE cells, suggesting defects in intercellular adhesion and cytokinesis. This study identifies CTNNA1 gene variants as a cause of macular dystrophy, indicates that CTNNA1 is involved in maintaining RPE integrity and suggests that other components that participate in intercellular adhesion may be implicated in macular disease.

  • The 5-HT7 receptor triggers cerebellar long-term synaptic depression via PKC-MAPK.
    Publication Date: 01/02/2016, on Neuropharmacology
    by Lippiello P, Hoxha E, Speranza L, Volpicelli F, Ferraro A, Leopoldo M, Lacivita E, Perrone-Capano C, Tempia F, Miniaci MC
    DOI: 10.1016/j.neuropharm.2015.10.019

    The 5-HT7 receptor (5-HT7R) mediates important physiological effects of serotonin, such as memory and emotion, and is emerging as a therapeutic target for the treatment of cognitive disorders and depression. Although previous studies have revealed an expression of 5-HT7R in cerebellum, particularly at Purkinje cells, its functional role and signaling mechanisms have never been described. Using patch-clamp recordings in cerebellar slices of adult mice, we investigated the effects of a selective 5-HT7R agonist, LP-211, on the main plastic site of the cerebellar cortex, the parallel fiber-Purkinje cell synapse. Here we show that 5-HT7R activation induces long-term depression of parallel fiber-Purkinje cell synapse via a postsynaptic mechanism that involves the PKC-MAPK signaling pathway. Moreover, a 5-HT7R antagonist abolished the expression of PF-LTD, produced by pairing parallel fiber stimulation with Purkinje cell depolarization; whereas, application of a 5-HT7R agonist impaired LTP induced by 1 Hz parallel fiber stimulation. Our results indicate for the first time that 5-HT7R exerts a fine regulation of cerebellar bidirectional synaptic plasticity that might be involved in cognitive processes and neuropsychiatric disorders involving the cerebellum.

  • Preferential interaction of the Alzheimer peptide Aβ-(1-42) with Omega-3-containing lipid bilayers: structure and interaction studies.
    Publication Date: 01/02/2016, on FEBS letters
    by Emendato A, Spadaccini R, De Santis A, Guerrini R, D'Errico G, Picone D
    DOI: 10.1002/1873-3468.12082

    Many age-related neurodegenerative diseases, including Alzheimer Disease (AD), are elicited by an interplay of genetic, environmental, and dietary factors. Food rich in Omega-3 phospholipids seems to reduce the AD incidence. To investigate the molecular basis of this beneficial effect, we have investigated by CD and ESR studies the interaction between the Alzheimer peptide Aβ-(1-42) and biomimetic lipid bilayers. The inclusion of 1,2-didocosahexaenoyl-sn-glycero-3-phosphocholine does not change significantly the bilayers organization, but favors its Aβ-(1-42) interaction. The Omega-3 lipid amount modulates the effect intensity, suggesting a peptide selectivity for membranes containing polyunsatured fatty acids (PUFA) and providing hints for the mechanism and therapy of AD.