Arqus Openness Position Paper

The Openness Position Paper published by the Arqus European University Alliance emphasises that Arqus institutions, in line with the policies, roadmaps and strategies of the EU and a wide range of stakeholders, are striving jointly to make further progress towards realising Open Science. The Position Paper identifies and acknowledges aims and values of Open Science and relates them to values, principles, and standards shared by the Arqus Alliance, followed by a vision for a future with Open Science. In the interest of a nuanced picture, the Position Paper discusses not only desired effects, but also possible areas of tension related to Open Science. It presents a wide range of specific aims and recommendations for each of the eleven elements of Open Science defined by the Arqus Openness Task Force: Governance Publications (including Open Access) Data (including research data management, FAIR and Open Data) Infrastructures (including support staff, Open Science software and tools, repositories, Open Labs) Methods (including source code, preregistration, materials, workflows, protocols, lab notes) Awareness and training (including education of early-stage researchers) Evaluation (including Open Metrics, research assessment, Open Peer Review, rewards and incentives) Communication (including multilingualism) Citizen Science Open Education Open Innovation The Position Paper concludes with an annex that highlights the progress already made in the implementation and support of Open Science practices at Arqus institutions.Cofunded by the Erasmus+Programme of the European Unio

Taking the pulse of Earth's tropical forests using networks of highly distributed plots

Tropical forests are the most diverse and productive ecosystems on Earth. While better understanding of these forests is critical for our collective future, until quite recently efforts to measure and monitor them have been largely disconnected. Networking is essential to discover the answers to questions that transcend borders and the horizons of funding agencies. Here we show how a global community is responding to the challenges of tropical ecosystem research with diverse teams measuring forests tree-by-tree in thousands of long-term plots. We review the major scientific discoveries of this work and show how this process is changing tropical forest science. Our core approach involves linking long-term grassroots initiatives with standardized protocols and data management to generate robust scaled-up results. By connecting tropical researchers and elevating their status, our Social Research Network model recognises the key role of the data originator in scientific discovery. Conceived in 1999 with RAINFOR (South America), our permanent plot networks have been adapted to Africa (AfriTRON) and Southeast Asia (T-FORCES) and widely emulated worldwide. Now these multiple initiatives are integrated via ForestPlots.net cyber-infrastructure, linking colleagues from 54 countries across 24 plot networks. Collectively these are transforming understanding of tropical forests and their biospheric role. Together we have discovered how, where and why forest carbon and biodiversity are responding to climate change, and how they feedback on it. This long-term pan-tropical collaboration has revealed a large long-term carbon sink and its trends, as well as making clear which drivers are most important, which forest processes are affected, where they are changing, what the lags are, and the likely future responses of tropical forests as the climate continues to change. By leveraging a remarkably old technology, plot networks are sparking a very modern revolution in tropical forest science. In the future, humanity can benefit greatly by nurturing the grassroots communities now collectively capable of generating unique, long-term understanding of Earth's most precious forests. Resumen Los bosques tropicales son los ecosistemas más diversos y productivos del mundo y entender su funcionamiento es crítico para nuestro futuro colectivo. Sin embargo, hasta hace muy poco, los esfuerzos para medirlos y monitorearlos han estado muy desconectados. El trabajo en redes es esencial para descubrir las respuestas a preguntas que trascienden las fronteras y los plazos de las agencias de financiamiento. Aquí mostramos cómo una comunidad global está respondiendo a los desafíos de la investigación en ecosistemas tropicales a través de diversos equipos realizando mediciones árbol por árbol en miles de parcelas permanentes de largo plazo. Revisamos los descubrimientos más importantes de este trabajo y discutimos cómo este proceso está cambiando la ciencia relacionada a los bosques tropicales. El enfoque central de nuestro esfuerzo implica la conexión de iniciativas locales de largo plazo con protocolos estandarizados y manejo de datos para producir resultados que se puedan trasladar a múltiples escalas. Conectando investigadores tropicales, elevando su posición y estatus, nuestro modelo de Red Social de Investigación reconoce el rol fundamental que tienen, para el descubrimiento científico, quienes generan o producen los datos. Concebida en 1999 con RAINFOR (Suramérica), nuestras redes de parcelas permanentes han sido adaptadas en África (AfriTRON) y el sureste asiático (T-FORCES) y ampliamente replicadas en el mundo. Actualmente todas estas iniciativas están integradas a través de la ciber-infraestructura de ForestPlots.net, conectando colegas de 54 países en 24 redes diferentes de parcelas. Colectivamente, estas redes están transformando nuestro conocimiento sobre los bosques tropicales y el rol de éstos en la biósfera. Juntos hemos descubierto cómo, dónde y porqué el carbono y la biodiversidad de los bosques tropicales está respondiendo al cambio climático y cómo se retroalimentan. Esta colaboración pan-tropical de largo plazo ha expuesto un gran sumidero de carbono y sus tendencias, mostrando claramente cuáles son los factores más importantes, qué procesos se ven afectados, dónde ocurren los cambios, los tiempos de reacción y las probables respuestas futuras mientras el clima continúa cambiando. Apalancando lo que realmente es una tecnología antigua, las redes de parcelas están generando una verdadera y moderna revolución en la ciencia tropical. En el futuro, la humanidad puede beneficiarse enormemente si se nutren y cultivan comunidades de investigadores de base, actualmente con la capacidad de generar información única y de largo plazo para entender los que probablemente son los bosques más preciados de la tierra. Resumo Florestas tropicais são os ecossistemas mais diversos e produtivos da Terra. Embora uma boa compreensão destas florestas seja crucial para o nosso futuro coletivo, até muito recentemente os esforços de medições e monitoramento foram amplamente desconexos. É essencial formarmos redes para obtermos respostas que transcendem fronteiras e horizontes de agências financiadoras. Neste estudo nós mostramos como uma comunidade global está respondendo aos desafios da pesquisa de ecossistemas tropicais, com equipes diversas medindo florestas, árvore por árvore, em milhares de parcelas monitoradas à longo prazo. Nós revisamos as maiores descobertas científicas deste trabalho, e mostramos também como este processo está mudando a ciência de florestas tropicais. Nossa abordagem principal envolve unir iniciativas de base a protocolos padronizados e gerenciamento de dados a fim de gerar resultados robustos em escalas ampliadas. Ao conectar pesquisadores tropicais e elevar seus status, nosso modelo de Rede de Pesquisa Social reconhece o papel-chave do produtor dos dados na descoberta científica. Concebida em 1999 com o RAINFOR (América do Sul), nossa rede de parcelas permanentes foi adaptada para África (AfriTRON) e Sudeste asiático (T-FORCES), e tem sido extensamente reproduzida em todo o mundo. Agora estas múltiplas iniciativas estão integradas através de uma infraestrutura cibernética do ForestPlots.net, conectando colegas de 54 países de 24 redes de parcelas. Estas iniciativas estão transformando coletivamente o entendimento das florestas tropicais e seus papéis na biosfera. Juntos nós descobrimos como, onde e por que o carbono e a biodiversidade da floresta estão respondendo às mudanças climáticas, e seus efeitos de retroalimentação. Esta duradoura colaboração pantropical revelou um grande sumidouro de carbono persistente e suas tendências, assim como tem evidenciado quais direcionadores são mais importantes, quais processos florestais são mais afetados, onde eles estão mudando, seus atrasos no tempo de resposta, e as prováveis respostas das florestas tropicais conforme o clima continua a mudar. Dessa forma, aproveitando uma notável tecnologia antiga, redes de parcelas acendem faíscas de uma moderna revolução na ciência das florestas tropicais. No futuro a humanidade pode se beneficiar incentivando estas comunidades basais que agora são coletivamente capazes de gerar conhecimentos únicos e duradouros sobre as florestas mais preciosas da Terra. Résume Les forêts tropicales sont les écosystèmes les plus diversifiés et les plus productifs de la planète. Si une meilleure compréhension de ces forêts est essentielle pour notre avenir collectif, jusqu'à tout récemment, les efforts déployés pour les mesurer et les surveiller ont été largement déconnectés. La mise en réseau est essentielle pour découvrir les réponses à des questions qui dépassent les frontières et les horizons des organismes de financement. Nous montrons ici comment une communauté mondiale relève les défis de la recherche sur les écosystèmes tropicaux avec diverses équipes qui mesurent les forêts arbre après arbre dans de milliers de parcelles permanentes. Nous passons en revue les principales découvertes scientifiques de ces travaux et montrons comment ce processus modifie la science des forêts tropicales. Notre approche principale consiste à relier les initiatives de base à long terme à des protocoles standardisés et une gestion de données afin de générer des résultats solides à grande échelle. En reliant les chercheurs tropicaux et en élevant leur statut, notre modèle de réseau de recherche sociale reconnaît le rôle clé de l'auteur des données dans la découverte scientifique. Conçus en 1999 avec RAINFOR (Amérique du Sud), nos réseaux de parcelles permanentes ont été adaptés à l'Afrique (AfriTRON) et à l'Asie du Sud-Est (T-FORCES) et largement imités dans le monde entier. Ces multiples initiatives sont désormais intégrées via l'infrastructure ForestPlots.net, qui relie des collègues de 54 pays à travers 24 réseaux de parcelles. Ensemble, elles transforment la compréhension des forêts tropicales et de leur rôle biosphérique. Ensemble, nous avons découvert comment, où et pourquoi le carbone forestier et la biodiversité réagissent au changement climatique, et comment ils y réagissent. Cette collaboration pan-tropicale à long terme a révélé un important puits de carbone à long terme et ses tendances, tout en mettant en évidence les facteurs les plus importants, les processus forestiers qui sont affectés, les endroits où ils changent, les décalages et les réactions futures probables des forêts tropicales à mesure que le climat continue de changer. En tirant parti d'une technologie remarquablement ancienne, les réseaux de parcelles déclenchent une révolution très moderne dans la science des forêts tropicales. À l'avenir, l'humanité pourra grandement bénéficier du soutien des communautés de base qui sont maintenant collectivement capables de générer une compréhension unique et à long terme des forêts les plus précieuses de la Terre. Abstrak Hutan tropika adalah di antara ekosistem yang paling produktif dan mempunyai kepelbagaian biodiversiti yang tinggi di seluruh dunia. Walaupun pemahaman mengenai hutan tropika amat penting untuk masa depan kita, usaha-usaha untuk mengkaji dan mengawas hutah-hutan tersebut baru sekarang menjadi lebih diperhubungkan. Perangkaian adalah sangat penting untuk mencari jawapan kepada soalan-soalan yang menjangkaui sempadan dan batasan agensi pendanaan. Di sini kami menunjukkan bagaimana sebuah komuniti global bertindak balas terhadap cabaran penyelidikan ekosistem tropika melalui penglibatan pelbagai kumpulan yang mengukur hutan secara pokok demi pokok dalam beribu-ribu plot jangka panjang. Kami meninjau semula penemuan saintifik utama daripada kerja ini dan menunjukkan bagaimana proses ini sedang mengubah bidang sains hutan tropika. Teras pendekatan kami memberi tumpuan terhadap penghubungan inisiatif akar umbi jangka panjang dengan protokol standar serta pengurusan data untuk mendapatkan hasil skala besar yang kukuh. Dengan menghubungkan penyelidik-penyelidik tropika dan meningkatkan status mereka, model Rangkaian Penyelidikan Sosial kami mengiktiraf kepentingan peranan pengasas data dalam penemuan saintifik. Bermula dengan pengasasan RAINFOR (Amerika Selatan) pada tahun 1999, rangkaian-rangkaian plot kekal kami kemudian disesuaikan untuk Afrika (AfriTRON) dan Asia Tenggara (T-FORCES) dan selanjutnya telah banyak dicontohi di seluruh dunia. Kini, inisiatif-inisiatif tersebut disepadukan melalui infrastruktur siber ForestPlots.net yang menghubungkan rakan sekerja dari 54 negara di 24 buah rangkaian plot. Secara kolektif, rangkaian ini sedang mengubah pemahaman tentang hutan tropika dan peranannya dalam biosfera. Kami telah bekerjasama untuk menemukan bagaimana, di mana dan mengapa karbon serta biodiversiti hutan bertindak balas terhadap perubahan iklim dan juga bagaimana mereka saling bermaklum balas. Kolaborasi pan-tropika jangka panjang ini telah mendedahkan sebuah sinki karbon jangka panjang serta arah alirannya dan juga menjelaskan pemandu-pemandu perubahan yang terpenting, di mana dan bagaimana proses hutan terjejas, masa susul yang ada dan kemungkinan tindakbalas hutan tropika pada perubahan iklim secara berterusan di masa depan. Dengan memanfaatkan pendekatan lama, rangkaian plot sedang menyalakan revolusi yang amat moden dalam sains hutan tropika. Pada masa akan datang, manusia sejagat akan banyak mendapat manfaat jika memupuk komuniti-komuniti akar umbi yang kini berkemampuan secara kolektif menghasilkan pemahaman unik dan jangka panjang mengenai hutan-hutan yang paling berharga di dunia

Valutazione delle risposte immunitarie umorali e cellulari di tipo B in soggetti vaccinati con Gardasil o Cervarix

The family of human papillomaviruses comprises over 120 different types that infect cutaneous and mucosal tissues, and among them high-risk genotypes (HPV16, 18, 31, 33, 45, 51, 58 and others) are strongly associated with different cancer in the genital tract in men and women. Low-risk genotypes (HPV6, 11, 40, 43 and others) are found in genital epithelial lesions but rarely detected in malignancies. Cervical cancer is the third most common cancer in women world-wide associated with persistent infection of sexually transmitted high-risk HPV genotypes. In particular, HPV16 and 18 cause more than 70% of invasive cervix cancer in women. Immunocompetent women are able to clear high-risk HPV genotypes infections in 12-18 months. This is accompanied or closely followed by seroconversion against the major coat protein L1. The antibody titres developed during natural infection are low and don’t protect against HPV reinfection, moreover, not all women seroconvert. Approximately 10% of women fail to clear HPV infection resulting in long-term persistent infection that leads to progressive disease. In 2006-2007 two prophylactic vaccines were licenced based on virus-like particles technology: a bivalent HPV16/18 L1 VLP vaccine (Cervarix, GSK) and a tetravalent HPV 6/11/16/18 L1 VLP vaccine (Gardasil, MSD). Both vaccines showed almost 100% efficacy against CIN 2/3 against vaccine-related HPV types in naïve women. The efficacy is considerably lower against HPV types not included in vaccine formulation, and also in women with evidence of previous or current infections of vaccine-related genotypes. Furthermore, both vaccines are safe, and induce high titres of type-specific neutralizing antibodies against both linear and conformational epitopes on capsid protein L1 (4 years follow up of phase III clinical trials) preventing both high risk HPV16 and 18 infection and lesion development in the cervix. In addition, the quadrivalent vaccine is protective against occurrence of external genital warts. Despite this success, several key issues are still open. In fact, reports from phase III studies suggest that the two HPV vaccines may induce different antigen-specific immune responses in terms of intensity and persistence. The generation of memory B-cells and their responses to recall antigens are crucial factors for the long-term efficacy of vaccine induced humoral protection and up to now standardized assays are not commercially available to measure HPV immunity. Moreover, the efficacy in pre- and early adolescents, the primary targets for vaccination, has not been demonstrated. Furthermore, at present, the majority of data available on the two HPV vaccines comes from studies performed by the manufacturers. In this contest, an independent study was designed by enrolling HPV vaccinated women in Veneto and Emilia Romagna Regions to a) set up standardized B-cell elispot assays to measure the frequency of memory B-cells specific to HPV6, 11, 16 and 18 VLPs; b) screen a cohort of HPV vaccinees stratified by age (12 years old vs 20-45 years old) and by time after the 3rd dose of vaccine (1-6 months vs 4 years); c) compare the immune responses of Cervarix and Gardasil HPV vaccines. This study demonstrates that Gardasil induces high and sustained number of memory B-cells against the HPV types included in the vaccine formulation. With regard to the frequency of memory B-cells the vaccine was not influenced by the age of vaccine administration and was similar among the age groups at 1-6 months and 4 years after vaccination. Furthermore, Gardasil induces high antigen-specific IgG titres in both age groups that decrease significantly 4 years after vaccination but remains still detectable. However, the IgG titres were significantly lower in the 20-45 years old group compared to the 12 years old group both both 1-6 months and 4 years after vaccination, and the percentage of vaccinees whom IgG levels were still detectable were significantly lower in the 20-45 years old group compared to the 12 years old group 4 years after the vaccination. Cervarix induces higher B-cell responses (both frequency of memory B-cells and antigen-specific IgG titres) compared to Gardasil in 12 years old vaccinees, tested 1-6 months after vaccination. Evalutation of immune responses in 12-years old Cervarix recipients 4 years after vaccination as well as in 20-45 years old (both 1-6 months and 4 years after vaccination) is in progress.Il carcinoma della cervice uterina rappresenta la seconda causa di morte per tumore tra le giovani donne fra i 15 e i 44 anni, dopo il tumore al seno. Si stimano infatti a livello mondiale 530.000 nuovi casi di tumore cervicale all’anno e circa 275.000 decessi. Lo sviluppo del tumore alla cervice uterina è imputabile all’infezione persistente, sessualmente trasmessa, di alcuni genotipi ad alto rischio di Papillomavirus (HPV); in particolare più del 70% di tutti i tumori cervicali è correlato con la presenza di HPV16 e 18 mentre il rimanente 25% è legato all’infezione causata da altri genotipi di HPV come 31, 33, 45 e 58. Le donne immunocompetenti sono in grado di eliminare spontaneamente le infezioni dei genotipi ad alto rischio in 12-18 mesi. La seroconversione che deriva dall’infezione non avviene in tutte le donne e, laddove succede, i titoli degli anticorpi neutralizzanti sono molto bassi e non proteggono da successive reinfezioni. Inoltre, il 10% delle donne non è in grado di eliminare il virus e l’infezione persistente a livello della mucosa cervicale, è il punto di partenza di una serie di eventi molecolari che portano allo sviluppo di lesioni neoplastiche. Nel 2006-2007 sono stati approvati e commercializzati due vaccini profilattici anti-HPV costituiti dalle proteine L1 del capside virale, assemblate a formare degli pseudovirioni (VLP) tridimensionalmente identici alle particelle virali native ma non infettivi: Cervarix (GSK) contenente le VLP di HPV16 e 18 e Gardasil (Merck) contenente le VLP di HPV6, 11, 16 e 18, quindi protettivo anche nei confronti di infezioni genitali di tipo benigno come i condilomi. Gli studi clinici hanno dimostrato che entrambi i vaccini sono sicuri, capaci di indurre elevati livelli di anticorpi neutralizzanti contro la proteina L1 ed efficaci nel proteggere dall’infezione da parte dei genotipi di HPV presenti nel vaccino. Tuttavia, i vaccini sono in commercio solo da pochi anni e sono necessari ulteriori studi per correlare l’efficacia di protezione con l’entità delle risposte immunitarie indotte. Per studiare l’immunità a lungo termine, la determinazione dei titoli anticorpali (neutralizzanti e non) è uno strumento utile ma non sufficiente, ed è necessario quindi quantificare i linfociti B memoria antigene-specifici. Inoltre, sono ancora pochi i dati disponibili in letteratura sull’induzione delle risposte immunitarie in funzione dell’età di somministrazione del vaccino e soprattutto la maggior parte dei dati di efficacia e di risposte immunitarie indotte da Gardasil e Cervarix provengono dalle aziende che commercializzano i vaccini. In questo contesto, lo studio indipendente da noi eseguito aveva tre obiettivi: 1) sviluppare e standardizzare una metodica di B-cell Elispot per la quantificazione dei linfociti B memoria HPV genotipo-specifici; 2) quantificare i linfociti B memoria e i titoli anticorpali, specifici per ciascun antigene vaccinale, in una popolazione di adolescenti (12 anni) e di donne (20-45 anni) vaccinate con Gardasil o Cervarix, arruolate 1-6 mesi o 4 anni dopo la vaccinazione; 3) comparare l’immunogenicità dei due vaccini anti-HPV. In particolare, ad oggi sono state arruolate 283 volontarie di cui per il vaccino Gardasil n=121 per il gruppo 12 anni, n=112 per il gruppo 20-45 anni e per il vaccino Cervarix n=60 per il gruppo 12 anni. L’arruolamento dei soggetti vaccinati con Cervarix è ancora in corso e lo studio verrà completato nei prossimi 6 mesi. I risultati dello studio hanno dimostrato che le frequenze dei linfociti B memoria HPV genotipo-specifiche indotte dal Gardasil sono elevate 1-6 mesi dopo la vaccinazione in entrambe le coorti di età e, nonostante diminuiscano nel corso del tempo, dopo 4 anni continuano ad essere significativamente elevate indipendentemente dall’età di somministrazione del vaccino. Al contrario, i titoli anticorpali sono influenzati dall’età di somministrazione del vaccino. Infatti, i titoli anticorpali misurati nella coorte di adolescenti sono sempre significativamente superiori rispetto a quelli misurati nella corte delle donne, sia 1-6 mesi sia 4 anni dopo la vaccinazione. In aggiunta, la percentuale di individui i cui titoli anticorpali non sono più misurabili, dopo 4 anni dalla vaccinazione, è significativamente superiore nelle donne rispetto alle adolescenti. Relativamente alla comparazione delle risposte immunitarie indotte dai due vaccini anti-HPV, i risultati preliminari ottenuti in un gruppo di adolescenti vaccinate con Cervarix dimostrano che 1-6 mesi dopo la vaccinazione il Cervarix induce titoli anticorpali e frequenze di linfociti B memoria anti-HPV16 e 18 significativamente superiori rispetto ad adolescenti vaccinate con Gardasil. I risultati ottenuti potranno essere un utile ausilio per il Ministero della Salute per tracciare le linee guida di prevenzione primaria del tumore alla cervice uterina

1,25-Dihydroxyvitamin D3 Upregulates Functional CXCR4 Human Immunodeficiency Virus Type 1 Coreceptors in U937 Minus Clones: NF-κB-Independent Enhancement of Viral Replication

U937 cell clones which sustain efficient or poor replication of human immunodeficiency virus type 1 (HIV-1) (referred to herein as plus clones and minus clones, respectively) have been previously described. 1,25-Dihydroxyvitamin D3 (vitamin D3) potently induced HIV-1 replication and proviral DNA accumulation in minus clones but not in plus clones. Vitamin D3 did not induce NF-κB activation but selectively upregulated CXCR4 expression in minus clones. The CXCR4 ligand stromal-cell derived factor-1 induced Ca(2+) fluxes and inhibited both constitutive and vitamin D3-enhanced HIV replication in minus clones

EIF2A-dependent translational arrest protects leukemia cells from the energetic stress induced by NAMPT inhibition

Cell-cycle analysis andClick-iTdetection of RNA and Protein synthesis. A) Cell-cycle analysis with PI staining of the nuclei after 48 h of treatment. Overnight serum starvation is shown as a positive control of induced cell cycle synchronization in G0/G1 phase. Cell phase analysis was done with ModFit LT 3.2 software by using the Sync Wizard model (30000 cells/sample in biological duplicate). B) Jurkat cells were treated for 48 h with or without (Mock) the indicated concentration of FK866 or for 3 h with 5 μM Actinomycin D, an RNA synthesis blocking agent, then subjected to Click-it biochemistry and flow-cytometry analyses including 7-AAD to identify living cells. C) Jurkat cells were treated for 48 h with or without (Mock) the indicated concentration of FK866 or for 3 h with 350 μM Cycloheximide, as a positive control for protein synthesis inhibition, then stained as in B. In B and C. Experiments were carried out on two biological replicates (50000 events/sample). (PDF 1562 kb

Characterization of a new CDC73 missense mutation that impairs Parafibromin expression and nucleolar localization.

Mutations of the Cell Division Cycle 73 (CDC73) tumor suppressor gene (previously known as HRPT2), encoding for parafibromin, are associated with the Hyperparathyroidism-Jaw Tumor (HPT-JT) syndrome, an autosomal dominant disease whose clinical manifestations are mainly parathyroid tumors and, less frequently, ossifying fibromas of the jaws, uterine and renal tumors. Most mutations of CDC73 are nonsense or frameshift, while missense mutations are rare and generally affect the N-terminal domain of parafibromin, a region that is still poorly characterized. The aim of this study was to characterize a novel somatic CDC73 missense mutation (Ile60Asn) identified in the mandibular tumor of a HPT-JT patient carrying a germline CDC73 inactivating mutation. Immunostaining of the tumor showed reduced nuclear parafibromin immunoreactivity. Western blotting and confocal microscopy of transfected cells demonstrated that the Ile60Asn mutant parafibromin was less expressed than the wild-type protein and exhibited impaired nucleolar localization. Treatment of transfected cells with translation and proteasome inhibitors demonstrated a decreased stability of the Ile60An mutant, partially due to an increase in proteasomal degradation. Overexpression of the Ile60Asn mutant led to increased cell proliferation and to accumulation in the G2/M phase of cell cycle. Moreover, mutant parafibromin lost the ability to down-regulate c-myc expression. In conclusion, our study shows that a missense mutation in the N-terminus of parafibromin, identified in an ossifying fibroma from a HPT-JT patient, stimulated cell proliferation and impaired parafibromin expression and nucleolar localization, suggesting a relevant role of the N-terminal domain for parafibromin function