Evidence for detrimental cross interactions between reactive oxygen and nitrogen species in Leber's hereditary optic neuropathy cells

Here we have collected evidence suggesting that chronic changes in the NO homeostasis and the rise of reactive oxygen species bioavailability can contribute to cell dysfunction in Leber’s hereditary optic neuropathy (LHON) patients.We report that peripheral blood mononuclear cells (PBMCs), derived froma female LHON patient with bilateral reduced vision and carrying the pathogenic mutation 11778/ND4, display increased levels of reactive oxygen species (ROS) and reactive nitrogen species (RNS), as revealed by flow cytometry, fluorometric measurements of nitrite/nitrate, and 3-nitrotyrosine immunodetection. Moreover, viability assays with the tetrazolium dye MTT showed that lymphoblasts from the same patient are more sensitive to prolonged NO exposure, leading to cell death. Taken together these findings suggest that oxidative and nitrosative stress cooperatively play an important role in driving LHON pathology when excess NO remains available over time in the cell environment

Ripensare la condivisione delle risorse: riflessioni sulla realtà italiana - Rethinking Resource Sharing: Reflections on the Italian situation.

La comunicazione descrive l'attività del Comitato Biblioteche Nilde per la gestione della crescita del Network e l'integrazione con altri sistemi e servizi nazionali ed internazionali. Il CBN si è sforzato di far propri i suggerimenti e le indicazioni del Manifesto Rethinking Resource Sharing, elaborato da un gruppo di bibliotecari statunitensi, partner commerciali e specialisti in automazione per le biblioteche. L'attività si è sostanziata con la partecipazione all'11° Convegno Interlending and Document Supply Conference di Hannover nell'autunno 2009, al quale è stata presentata l'esperienza di NILDE che applica i punti del Manifesto. Nel confronto con queste diverse realtà emerge la necessità di esprimere ancora un rilevante lavoro di indirizzo per colmare le lacune del sistema bibliotecario italiano. Viene espressa infine l’intenzione di giungere alla creazione di un Manifesto Italiano per la condivisione delle risorse che recepisca i valori e le proposte provenienti dal mondo delle biblioteche italiane

Arm trajectories and writing strategy in healthy children

BACKGROUND: Evaluation of elementary writing skills in children is usually obtained with high resolution (and high cost) techniques or with low resolution pen-and-paper tests. In this observational study we tested a quantitative method to obtain normative data to describe arm movement during a writing precursor gesture. METHODS: We recruited 226 healthy children (mean age 9,1 years [range: 6.3 – 11.4 years]), attending primary schools belonging to the “Istituto Comprensivo” of Rivanazzano Terme (Pavia). We asked to drive a cursor through a polygonal path (labyrinth) projected in front of them using a wireless mouse. Dartfish™ video analysis software was used to elaborate images and Excel™, MedCalc™ and Statistica 7™ to analyze values of shoulder, elbow and wrist ranges of motion, arm trajectories, execution times and gesture accuracy. RESULTS: Differences seen in motor strategies, when divided according to attended class, suggest a proximal-distal maturation of motor control. Obtained values were not significantly correlated with variables such as gender, ethnicity or cognitive functioning. CONCLUSIONS: This type of approach to a study of arm movement during childhood represents a valid alternative to other tests, considering that it can differentiate children who perform similarly in the VMI test and is non-invasive, low-cost and easily reproducible

Cataloghi: la sfida della concretezza

The Communication presents the activities of the Catalogs Group "Nilde Libraries Committee, the activities are focused on the national catalogs of libraries participating at the NILDE network. The survey launched in 2006 led to the identification of a significant number of libraries that were not included in any national catalog. Subsequently, a procedure was initiated in which these situations have been regularized and a specific policy has been issued. The members of the "Catalogs Group" contacted the individual responsible for the document delivery service providing assistance to overcome encountered problems. The direct involvement of libraries led to good results so that only 32 libraries (in June 2009) were not yet visible on national catalogs. Of crucial importance was the cooperation with ACNP, which become an active partner of NILDE, encouraging the spread of the Network. The monitoring allowed us to understand the variety of Nilde libraries, covering a wide range of disciplines, located throughout the country. The group is also activated as a result of reports received by the CBN or by the List Nilde-forni, also for what concern the visibility of the catalogs. The adoption of advanced tools for linking, such as SFX, provides a solution to connect their electronic resources and to allow better access to users. For the better management of document delivery would be useful to have a single connection point of an entire virtual library of institution or university. Finally, the importance of cataloging of Open Access journals to promote their visibility through inclusion in the ACNP catalogue and the still open issue of cataloging the electronic resources as with paper publications, are mentioned.La comunicazione presenta l\u27attivit? del "Gruppo cataloghi" del Comitato Biblioteche Nilde (CBN), incentrata sul monitoraggio dell\u27adesione ai cataloghi nazionali da parte delle biblioteche partecipanti al network NILDE. Il rilevamento ? stato avviato nel 2006 ed ha portato all\u27individuazione di un significativo numero di biblioteche che non risultavano in alcun catalogo nazionale. Successivamente sono state avviate le procedure per la regolarizzazione della loro situazione, pubblicando anche un apposito regolamento. I componenti del "Gruppo cataloghi" hanno contattato i singoli responsabili dei servizi di document delivery offrendo assistenza per superare i problemi riscontrati. Il coinvolgimento diretto delle biblioteche ha portato a buoni risultati tanto che al giugno 2009 solo 32 biblioteche non erano ancora visibili sui cataloghi nazionali. Fondamentale la collaborazione con ACNP, che ? diventato un partner attivo di NILDE, favorendone la diffusione. L\u27attivit? di monitoraggio ha permesso di comprendere la variet? di biblioteche Nilde che riunisce biblioteche distribuite su tutto il territorio nazionale, che coprono una ampia gamma di discipline. Il gruppo si ? anche attivato a seguito di segnalazioni di malfunzionamento che pervengono al CBN o alla lista Nilde-forni, anche per quanto riguarda la visibilit? dei cataloghi. L\u27adozione di strumenti avanzati di linking come SFX offre alle istituzioni una soluzione per collegare le loro risorse elettroniche e per consentire un migliore accesso agli utenti. Per la migliore gestione del document delivery sarebbe utile poter disporre di un unico indirizzo e-mail come punto di raccordo di una intera biblioteca virtuale elettronica di ente o di ateneo. Infine vengono citate: l\u27importanza di catalogazione dei periodici Open Access per favorirne la visibilit? grazie all\u27inserimento in ACNP e la problematica ancora aperta della catalogazione completa delle risorse elettroniche al pari di quanto ? avvenuto per i documenti su carta

Correlation between NK function and response to trastuzumab in metastatic breast cancer patients

<p>Abstract</p> <p>Background</p> <p>Trastuzumab is a monoclonal antibody selectively directed against Her2 and approved for the treatment of Her2 overexpressing breast cancer patients. Its proposed mechanisms of action include mediation of antibody-dependent cellular cytotoxicity (ADCC) by triggering FcγRIII on natural killer (NK) cells. This study addresses the correlation between overall NK function and trastuzumab's clinical activity.</p> <p>Subjects and methods</p> <p>Clinical and immunological responses were assessed in 26 patients receiving trastuzumab monotherapy as maintenance management after chemotherapy (8 mg/kg load and then standard doses of 6 mg/kg every 3 weeks). Cytotoxic activity against the MHC class I-negative standard NK target K562 cell line and HER2-specific ADCC against a trastuzumab-coated Her2-positive SKBR3 cell line were assessed in peripheral blood mononuclear cells (PBMC) harvested after the first standard dose. After six months, seventeen patients were scored as responders and nine as non-responders according to the RECIST criteria, while Progression-Free Survival (PFS) was calculated during a 12 months follow-up.</p> <p>Results</p> <p>The responders had significantly higher levels of both NK and ADCC activities (p < 0.05) that were not different from those of eleven normal controls. The NK activity of the non-responders was significantly (p < 0.05) lower than that of the normal controls. At twelve months, there was a marked correlation between PFS and NK activity only. PFS was significantly longer in patients with high levels of NK activity, whereas its pattern was unrelated to high or low ADCC activity.</p> <p>Conclusion</p> <p>One of the mechanisms of action of trastuzumab is NK cell-mediated ADCC lysis of the Her2-positve target cell. We show here that its potency is correlated with the short-term response to treatment, whereas longer protection against tumor expansion seems to be mediated by pure NK activity.</p

NILDE World: un nuovo spazio per la comunità

This paper describes the birth, the development, the structure, and the governance of NILDE World. Designed and managed by the Libraries Committee NILDE, CBN, it is thought as an open space and a virtual place available to the NILDE communit

Clinical efficacy of Enzyme Replacement Therapy in paediatric Hunter patients, an independent study of 3.5 years

BACKGROUND: Hunter Syndrome is an X-linked lysosomal storage disorder due to the deficit of iduronate 2-sulfatase, an enzyme catalysing the degradation of the glycosaminoglycans (GAG) dermatan- and heparan-sulfate. Treatment of the disease is mainly performed by Enzyme Replacement Therapy (ERT) with idursulfase, in use since 2006. Clinical efficacy of ERT has been monitored mainly by the Hunter Outcome Survey (HOS) while very few independent studies have been so far conducted. The present study is a 3.5-years independent follow-up of 27 Hunter patients, starting ERT between 1.6 and 27 years of age, with the primary aim to evaluate efficacy of the therapy started at an early age (<12 years). METHODS: In this study, we evaluated: urinary GAG content, hepato/splenomegaly, heart valvulopathies, otorinolaryngological symptoms, joint range of motion, growth, distance covered in the 6-minute walk test, neurological involvement. For data analysis, the 27 patients were divided into three groups according to the age at start of ERT: ≤5 years, >5 and ≤ 12 years and > 12 years. Patients were analysed both as 3 separate groups and also as one group; in addition, the 20 patients who started ERT up to 12 years of age were analysed as one group. Finally, patients presenting a “severe” phenotype were compared with “attenuated” ones. RESULTS: Data analysis revealed a statistically significant reduction of the urinary GAG in patients ≤5 years and ≤ 12 years and of the hepatomegaly in the group aged >5 and ≤ 12 years. Although other clinical signs improved in some of the patients monitored, statistical analysis of their variation did not reveal any significant changes following enzyme administration. The evaluation of ERT efficacy in relation to the severity of the disease evidenced slightly higher improvements as for hepatomegaly, splenomegaly, otological disorders and adenotonsillar hypertrophy in severe vs attenuated patients. CONCLUSIONS: Although the present protocol of idursulfase administration may result efficacious in delaying the MPS II somatic disease progression at some extent, in this study we observed that several signs and symptoms did not improve during the therapy. Therefore, a strict monitoring of the efficacy obtained in the patients under ERT is becoming mandatory for clinical, ethical and economic reasons. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13023-014-0129-1) contains supplementary material, which is available to authorized users

Author Correction:Transcriptional dysregulation of Interferome in experimental and human Multiple Sclerosis

The original version of this Article contained a typographical error in the spelling of the author Eliana M Coccia, which was incorrectly given as Eliana Coccia. This has now been corrected in the PDF and HTML versions of the Article, and in the accompanying Supplementary Material files

Strategies and Alliances into Action to Improve National Collaboration

The Italian NILDE network of libraries continues to grow through the use of the NILDE system and currently comprises more than 600 Italian librarians and about 10.000 registered end-users.The system allows to daily manage and to record all the Inter-Library-Loan (ILL) operations, with a high national coverage. This paper presents the NILDE network governance and evolution and the strategies that have been put into action to improve collaboration in resource sharing among the participants. These strategies include: &#8722; release of best practices and worst practices; &#8722; activities to promote the knowledge about the network; &#8722; cooperation with the Italian national catalogs and consortia; &#8722; data analysis about ILL and its performance, related to: turn around time, reciprocity factor, requested/supplied documents imbalance analysis, analysis of ILL requested serial titles and their relationship with consortial e-only acquisitions. The availability of such a high volume of ILL data has allowed for the first time to analyze the trends and gaps of ILL and to help future cooperative acquisitions planning

Silver-Catalyzed C-C Bond Formation between Methane and Ethyl Diazoacetate in Supercritical CO2

Even in the context of hydrocarbons’ general resistance to selective functionalization, methane’s volatility and strong bonds pose a particular challenge. We report here that silver complexes bearing perfluorinated indazolylborate ligands catalyze the reaction of methane (CH4) with ethyl diazoacetate (N2CHCO2Et) to yield ethyl propionate (CH3CH2CO2Et). The use of supercritical carbon dioxide (scCO2) as the solvent is key to the reaction’s success. Although the catalyst is only sparingly soluble in CH4/CO2 mixtures, optimized conditions presently result in a 19% yield of ethyl propionate (based on starting quantity of the diazoester) at 40°C over 14 hours.Ministerio de Ciencia e Innovación (grants CTQ2008-00042-BQU, CTQ2007-65251-BQU, and CTQ2007-30762-E), the European Research Area Chemistry Programme (2nd call “Chemical activation of carbon dioxide and methane” contract no. 1736154), the Consolider Ingenio 2010 (grants CSD2006-003 and CSD2007-00006), the Institut de Chimie of the CNRS, the Junta de Andalucía (P07-FQM-2870), and the Generalitat Velenciana (ACOMP/2010/155).We dedicate this work to Professor Ernesto Carmona. Support for this work was provided by the Ministerio de Ciencia e Innovacion (grants CTQ2008-00042-BQU, CTQ2007-65251-BQU, and CTQ2007-30762-E), the European Research Area Chemistry Programme (2nd call "Chemical activation of carbon dioxide and methane" contract no. 1736154), the Consolider Ingenio 2010 (grants CSD2006-003 and CSD2007-00006), the Institut de Chimie of the CNRS, the Junta de Andalucia (P07-FQM-2870), and the Generalitat Velenciana (ACOMP/2010/155). We thank the Servicio Central de Soporte a la Investigacion Experimental (Universidad de Valencia) for access to the instrumental facilities and J. de la Rosa and A. Sanchez de la Campa (Universidad de Huelva) for ICP-MS analyses