Instituto Pasteur

Rome, Italy

Instituto Pasteur

Rome, Italy
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Cacci E.,University of Rome La Sapienza | Negri R.,University of Rome La Sapienza | Negri R.,Instituto Pasteur | Biagioni S.,University of Rome La Sapienza | Lupo G.,University of Rome La Sapienza
Current Topics in Medicinal Chemistry | Year: 2017

Neural stem/progenitor cell (NSPC) self-renewal and differentiation in the developing and the adult brain are controlled by extra-cellular signals and by the inherent competence of NSPCs to produce appropriate responses. Stage-dependent responsiveness of NSPCs to extrinsic cues is orchestrated at the epigenetic level. Epigenetic mechanisms such as DNA methylation, histone modifications and non-coding RNA-mediated regulation control crucial aspects of NSPC development and function, and are also implicated in pathological conditions. While their roles in the regulation of stem cell fate have been largely explored in pluripotent stem cell models, the epigenetic signature of NSPCs is also key to determine their multipotency as well as their progressive bias towards specific differentiation outcomes. Here we review recent developments in this field, focusing on the roles of histone methylation marks and the protein complexes controlling their deposition in NSPCs of the developing cerebral cortex and the adult subventricular zone. In this context, we describe how bivalent promoters, carrying antagonistic epigenetic modifications, feature during multiple steps of neural development, from neural lineage specification to neuronal differentiation. Furthermore, we discuss the emerging cross-talk between epigenetic regulators and microRNAs, and how the interplay between these different layers of regulation can finely tune the expression of genes controlling NSPC maintenance and differentiation. In particular, we highlight recent advances in the identification of astrocyte-enriched microRNAs and their function in cell fate choices of NSPCs differentiating towards glial lineages. © 2017 Bentham Science Publishers.


Katz I.S.S.,Instituto Pasteur | Guedes F.,Instituto Pasteur | Fernandes E.R.,Instituto Pasteur | Dos Ramos Silva S.,Instituto Pasteur
Archives of Virology | Year: 2017

Rabies is a lethal disease caused by the neurotropic virus rabies virus (RABV), and it remains an important public health problem globally. It is known that the host immune response is important for control of viral infection and promoting viral clearance. In this context, it is well documented that, in addition to RABV neutralizing antibody, interferons and cell-mediated immunity also have an important role in preventing the establishment of disease. On the other hand, RABV suppresses host immunity through different mechanisms, for example, direct inhibition of host gene expression, sequestration of pathogen-associated molecular patterns, or modification of cytokine signalling pathways, which hinder the protective host immune responses to RABV infection. Here, we review the immunological aspects of rabies, highlighting innate and adaptive immunity, as well as the host evasion immune mechanisms used by the virus. Finally, we briefly discuss how this knowledge can direct new research and be harnessed for future therapeutic strategies. © 2017 Springer-Verlag GmbH Austria


Albas A.,Agencia Paulista de Tecnologia dos Agronegocios | de Souza E.A.N.,Agencia Paulista de Tecnologia dos Agronegocios | Picolo M.R.,Agencia Paulista de Tecnologia dos Agronegocios | Favoretto S.R.,Instituto Pasteur
Revista da Sociedade Brasileira de Medicina Tropical | Year: 2011

Introduction: The Polo da Alta Sorocabana Laboratory in Presidente Prudente, SP, in partnership with other research institutions, conducted studies related to bats from the western region of the State of Sao Paulo, Brazil. Thus, certain situations were investigated, including: a) isolation of the rabies virus from 2006 to 2008; b) identification of respective antigenic variants; and c) characterization of daytime shelters of Desmodus rotundus vampire bats. Methods: Samples for examination originated from nonhematophagous bats forwarded to the laboratory and subjected to direct fluorescent antibody test and mouse inoculation test. Positive samples were characterized by the monoclonal antibody test. Regarding the bats, they were identified and classified and mapping of their shelters was also performed. Results: The laboratory received 1,113 nonhematophagous bats for rabies diagnosis, 11 (1%) of which were positives, and among the positive samples, 5 (45.5%) presented antigenic variant 3 (from the bat Desmodus rotundus) and 4 (36.5%) were compatible with samples derived from Brazilian insectivorous bats. Sixteen vampire bat shelters were investigated and observation confirmed the presence of another 3 species of nonhematophagous bats coexisting with them.Conclusions: The experiments showed that at least 3 antigenic variants of rabies virus are circulating in the region and that the cohabitation of vampire bats with nonhematophag ousbats could be related to the dissemination of the rabies virus.


Federici L.,University of Chieti Pescara | Arcovito A.,Catholic University of the Sacred Heart | Scaglione G.L.,Catholic University of the Sacred Heart | Scaloni F.,Instituto Pasteur | And 6 more authors.
Journal of Biological Chemistry | Year: 2010

Nucleophosmin (NPM1) is a nucleocytoplasmic shuttling phosphoprotein, mainly localized at nucleoli, that plays a key role in ribogenesis, centrosome duplication, and response to stress stimuli. Mutations at the C-terminal domain of NPM1 are the most frequent genetic lesion in acute myeloid leukemia and cause the aberrant and stable translocation of the protein in the cytoplasm. The NPM1 C-terminal domain was previously shown to bind nucleic acids. Here we further investigate the DNA binding properties of the NPM1 C-terminal domain both at the protein and nucleic acid levels; we investigate the domain boundaries and identify key residues for high affinity recognition. Furthermore, we demonstrate that the NPM1 C-terminal domain has a preference for G-quadruplex forming DNA regions and induces the formation of G-quadruplex structures in vitro. Finally we show that a specific sequence found at the SOD2 gene promoter, which was previously shown to be a target of NPM1 in vivo, is indeed folded as a G-quadruplex in vitro under physiological conditions. Our data extend considerably present knowledge on the DNA binding properties of NPM1 and suggest a general role in the transcription of genes characterized by the presence of G-quadruplex forming regions at their promoters. © 2010 by The American Society for Biochemistry and Molecular Biology, Inc.


Marassa A.M.,University of Sao Paulo | Galati E.A.B.,University of Sao Paulo | Bergamaschi D.P.,University of Sao Paulo | Consales C.A.,Instituto Pasteur
Revista da Sociedade Brasileira de Medicina Tropical | Year: 2013

Introduction: The aim of this study was to identify the blood feeding sources of Nyssomyia intermedia (Ny. intermedia) and Nyssomyia neivai (Ny. neivai), which are Leishmania vectors and the predominant sandfl y species in the Ribeira Valley, State of São Paulo, Brazil, an endemic area for cutaneous leishmaniasis. Methods: Specimens were captured monthly between February 2001 and December 2003 on a smallholding and a small farm situated in the Serra district in the Iporanga municipality. The blood meals of 988 engorged females were tested using the avidin-biotin immunoenzymatic enzyme-linked immunosorbent assay (ELISA). Seven blood meal sources were investigated: human, dog, chicken, bovine, pig, horse and rat. Results: The results showed that among the females that fed on one or more blood sources, the respective percentages for Ny. intermedia and Ny. neivai, respectively, were as follows: human (23% and 36.8%), pig (47.4% and 26.4%), chicken (25.7% and 36.8%) and dog (3.9% and 0%), and the differences in the blood sources between the two species were statistically signifi cant (p = 0.043). Conclusions: Both species had predominant reactivity for one or two blood sources, and few showed reactivity indicating three or four sources. Many different combinations were observed among the females that showed reactivity for more than one source, which indicated their opportunistic habits and eclecticism regarding anthropic environmental conditions.


Galati E.A.B.,University of Sao Paulo | Marassa A.M.,Instituto Adolpho Lutz | Goncalves-Andrade R.M.,Instituto Butantan | Consales C.A.,Instituto Pasteur | Bueno E.F.M.,University of Sao Paulo
Revista Brasileira de Entomologia | Year: 2010

The Parque Estadual do Alto Ribeira (PETAR) with about 250 caves, in an Atlantic forest reserve, is an important ecotourist attraction in the Ribeira Valley, an endemic area of American cutaneous leishmaniasis (ACL). With the purpose of investigating Leishmania vector species bothersome to humans the sandfly fauna was identified and some of its ecological aspects in the Santana nucleus, captures were undertaken monthly with automatic light traps in 11 ecotopes, including caves, forests, a camping site and domiciliary environments, and on black and white Shannon traps, from January/2001 to December/2002. A total of 2,449 sandflies representing 21 species were captured. The highest values of abundance obtained in the captures with automatic light traps were for Psathyromyia pascalei and Psychodopygus ayrozai. A total of 107 specimens representing 13 species were captured on black (12 species) and white (6 species) Shannon traps set simultaneously. Psychodopygus geniculatus females predominated on the black (43.75%), and Psathyromyia lanei and Ps. ayrozai equally (32.4%) on the white. Nyssomyia intermedia and Nyssomyia neivai, both implicated in the transmission of ACL in the Brazilian Southeastern region, were also captured. Ny. intermedia predominated in the open camping area. Low frequencies of phlebotomines were observed in the caves, where Evandromyia edwardsi predominated Lutzomyia longipalpis, the main vector of the American visceral leishmaniasis, was aslo present. This is its most southernly reported occurrence in the Atlantic forest.


Haas R.,William Harvey Research Institute | Cucchi D.,William Harvey Research Institute | Cucchi D.,Instituto Pasteur | Smith J.,William Harvey Research Institute | And 4 more authors.
Trends in Biochemical Sciences | Year: 2016

The integration of biochemistry into immune cell biology has contributed immensely to our understanding of immune cell function and the associated pathologies. So far, most studies have focused on the regulation of metabolic pathways during an immune response and their contribution to its success. More recently, novel signalling functions of metabolic intermediates are being discovered that might play important roles in the regulation of immunity. Here we describe the three long-known small metabolites lactate, acetyl-CoA, and succinate in the context of immunometabolic signalling. Functions of these ubiquitous molecules are largely dependent on their intra- and extracellular concentrations as well as their subcompartmental localisation. Importantly, the signalling functions of these metabolic intermediates extend beyond self-regulatory roles and include cell-to-cell communication and sensing of microenvironmental conditions to elicit stress responses and cellular adaptation. © 2016 Elsevier Ltd.


Sauzullo I.,Instituto Pasteur | Vullo V.,Instituto Pasteur | Mastroianni C.M.,Instituto Pasteur
Current Opinion in Infectious Diseases | Year: 2015

Purpose of review The detection of latent tuberculosis infection (LTBI) in different categories of compromised patients is reviewed with focus on the role of strategies incorporating immunodiagnostic tests and analysis of epidemiological and clinical risk factors. Recent findings The development of active tuberculosis (TB) is increased in compromised patients and is closely related to determinants for disease reactivation or newly acquired TB infection. A targeted detection of LTBI in these high-risk groups should be performed especially if preventive treatment is planned. The performance of immunodiagnostic tests is highly variable among different groups of immunocompromised individuals. Findings of cross-sectional studies indicate a better diagnostic accuracy of interferon-γ release assays over the tuberculin skin test. The critical issue is that in low-incidence countries, the positive and negative predictive values of any of immunodiagnostic tests were very poor. A targeted testing process involving analysis of TB risk factors increases the predictive positive values of immunodiagnostic tests and may improve LTBI detection. Summary The LTBI detection in immunocompromised patients is a challenge. The development of new immunological biomarkers and integrated clinical and epidemiological strategies are needed to identify LTBI in compromised individuals and to plan preventive chemotherapies in those at risk of developing active TB. © 2015 Wolters Kluwer Health, Inc. All rights reserved.


Tardani F.,University of Rome La Sapienza | Strobbia P.,University of Rome La Sapienza | Scipioni A.,University of Rome La Sapienza | Scipioni A.,Instituto Pasteur | La Mesa C.,University of Rome La Sapienza
RSC Advances | Year: 2013

Carbon nanotubes reinforce polymer composites providing nanotube-based nanohybrids with potentially outstanding properties. The dispersion quality, however, influences the performances of the resulting materials. Therefore, new preparation procedures and efficient dispersion strategies are needed. A new method encapsulating single-walled carbon nanotubes in a nematic phase of double stranded DNA-water-NaCl is reported here. The procedure relies on osmotic compression and on its role in compacting DNA-nanotube composites. An anionic polymer (sodium dextransulfate) was added to the above dispersions and segregative phase separation was induced. DNA-nanotube composites were concentrated and phase-separated from the coexisting polymer solution. In this way, high concentrations of carbon nanotubes can be incorporated in the DNA-rich phase, inducing a transition from liquid- to solid-like behavior. The resulting nematic fluids are homogeneous and orient when shear stresses are applied. The kinetics of re-alignment was determined by rheological and spectroscopic methods. The effect of the nanotubes on the resulting behavior was accounted for. A slowing down of DNA motion observed in such composite matrices suggests interactions with nanotubes. © 2013 The Royal Society of Chemistry.


Leoni G.,University of Rome La Sapienza | Tramontano A.,University of Rome La Sapienza | Tramontano A.,Instituto Pasteur
Nucleic Acids Research | Year: 2016

It is well established that the correct identification of the messenger RNA targeted by a given microRNA (miRNA) is a difficult problem, and that available methods all suffer from low specificity. We hypothesize that the correct identification of the pairing should take into account the effect of the Argonaute protein (AGO), an essential catalyst of the recognition process. Therefore, we developed a strategy named MiREN for building and scoring three-dimensional models of the ternary complex formed by AGO, a miRNA and 22 nt of a target mRNA that putatively interacts with it. We show here that MiREN can be used to assess the likelihood that an RNA molecule is the target of a given miRNA and that this approach is more accurate than other existing methods, usually based on sequence or sequence-related features. Our results also suggest that AGO plays a relevant role in the selection of the miRNA targets. Our method can represent an additional step for refining predictions made by faster but less accurate classical methods for the identification of miRNA targets. © 2016 The Author(s).

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