63 research outputs found
Advances and gaps in SARS-CoV-2 infection models
The global response to Coronavirus Disease 2019 (COVID-19) is now facing new challenges such as vaccine inequity and the emergence of SARS-CoV-2 variants of concern (VOCs). Preclinical models of disease, in particular animal models, are essential to investigate VOC pathogenesis, vaccine correlates of protection and postexposure therapies. Here, we provide an update from the World Health Organization (WHO) COVID-19 modeling expert group (WHO-COM) assembled by WHO, regarding advances in preclinical models. In particular, we discuss how animal model research is playing a key role to evaluate VOC virulence, transmission and immune escape, and how animal models are being refined to recapitulate COVID-19 demographic variables such as comorbidities and age
Transcriptional role of p53 in interferon-mediated antiviral immunity
Tumor suppressor p53 is activated by several stimuli, including DNA damage and oncogenic stress. Previous studies (Takaoka, A., S. Hayakawa, H. Yanai, D. Stoiber, H. Negishi, H. Kikuchi, S. Sasaki, K. Imai, T. Shibue, K. Honda, and T. Taniguchi. 2003. Nature. 424:516–523) have shown that p53 is also induced in response to viral infections as a downstream transcriptional target of type I interferon (IFN) signaling. Moreover, many viruses, including SV40, human papillomavirus, Kaposi's sarcoma herpesvirus, adenoviruses, and even RNA viruses such as polioviruses, have evolved mechanisms designated to abrogate p53 responses. We describe a novel p53 function in the activation of the IFN pathway. We observed that infected mouse and human cells with functional p53 exhibited markedly decreased viral replication early after infection. This early inhibition of viral replication was mediated both in vitro and in vivo by a p53-dependent enhancement of IFN signaling, specifically the induction of genes containing IFN-stimulated response elements. Of note, p53 also contributed to an increase in IFN release from infected cells. We established that this p53-dependent enhancement of IFN signaling is dependent to a great extent on the ability of p53 to activate the transcription of IFN regulatory factor 9, a central component of the IFN-stimulated gene factor 3 complex. Our results demonstrate that p53 contributes to innate immunity by enhancing IFN-dependent antiviral activity independent of its functions as a proapoptotic and tumor suppressor gene
N′-phenylacetohydrazide derivatives as potent Ebola virus entry inhibitors with an improved pharmacokinetic profile
19 p.-6 fig.-7 tab.-1 graph. abst.Ebola virus (EBOV) is a single-strand RNA virus belonging to the Filoviridae family, which has been associated to most Ebola virus disease outbreaks to date, including the West African and the North Kivu epidemics between 2013 and 2022. This unprecedented health emergency prompted the search for effective medical countermeasures. Following up on the carbazole hit identified in our previous studies, we synthetized a new series of compounds, which demonstrated to prevent EBOV infection in cells by acting as virus entry inhibitors. The in vitro inhibitory activity was evaluated through the screening against surrogate models based on viral pseudotypes and further confirmed using replicative EBOV. Docking and molecular dynamics simulations joined to saturation transfer difference–nuclear magnetic resonance (STD–NMR) and mutagenesis experiments to elucidate the biological target of the most potent compounds. Finally, in vitro metabolic stability and in vivo pharmacokinetic studies were performed to confirm their therapeutic potential.The project leading to these results has received funding from “la Caixa” Foundation under the project code LCF/PR/HR19/52160012. This research was partially supported through ERA-NET-2021-862605. Cofounded by AEI, Spain (PCI2021-121939 (C.A.), PID2019-105237GB-I00 (A.C.), PID2021-122825OB (C.A.), and PID2021-122223OB-I00 (C.G.)), Instituto de Salud Carlos III (CIBERINFEC and FIS PI2100989), and the European Commission Horizon 2020 Framework Programme (Project VIRUSCAN FETPROACT-2016: 731868 and Project EPIC-CROWN-2 ID: 101046084). This research work was also funded by the European Commission–NextGenerationEU (Regulation EU 2020/2094), through CSIC’s Global Health Platform (PTI Salud Global). M.M.-T holds a predoctoral FPU grant (FPU18/03493) from MICINNPeer reviewe
Chikungunya Outbreak in the Republic of the Congo, 2019—Epidemiological, Virological and Entomological Findings of a South-North Multidisciplinary Taskforce Investigation
The Republic of Congo (RoC) declared a chikungunya (CHIK) outbreak on 9 February 2019. We conducted a ONE-Human-Animal HEALTH epidemiological, virological and entomological investigation. Methods: We collected national surveillance and epidemiological data. CHIK diagnosis was based on RT-PCR and CHIKV-specific antibodies. Full CHIKV genome sequences were obtained by Sanger and MinION approaches and Bayesian tree phylogenetic analysis was performed. Mosquito larvae and 215 adult mosquitoes were collected in different villages of Kouilou and Pointe-Noire districts and estimates of Aedes (Ae.) mosquitos’ CHIKV-infectious bites obtained. We found two new CHIKV sequences of the East/Central/South African (ECSA) lineage, clustering with the recent enzootic sub-clade 2, showing the A226V mutation. The RoC 2019 CHIKV strain has two novel mutations, E2-T126M and E2-H351N. Phylogenetic suggests a common origin from 2016 Angola strain, from which it diverged around 1989 (95% HPD 1985–1994). The infectious bite pattern was similar for 2017, 2018 and early 2019. One Ae. albopictus pool was RT-PCR positive. The 2019 RoC CHIKV strain seems to be recently introduced or be endemic in sylvatic cycle. Distinct from the contemporary Indian CHIKV isolates and in contrast to the original Central-African strains (transmitted by Ae. aegypti), it carries the A226V mutation, indicating an independent adaptive mutation in response to vector replacement (Ae. albopictus vs Ae. aegypti)
SARS-CoV-2 Variants and Vaccines.
Viral variants of concern may emerge with dangerous resistance to the immunity generated by the current vaccines to prevent coronavirus disease 2019 (Covid-19). Moreover, if some variants of concern have increased transmissibility or virulence, the importance of efficient public health measures and vaccination programs will increase. The global response must be both timely and science based
Animal models for COVID-19
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the aetiological
agent of coronavirus disease 2019 (COVID-19), an emerging respiratory infection
caused by the introduction of a novel coronavirus into humans late in 2019 (frst
detected in Hubei province, China). As of 18 September 2020, SARS-CoV-2 has spread
to 215 countries, has infected more than 30 million people and has caused more than
950,000 deaths. As humans do not have pre-existing immunity to SARS-CoV-2, there
is an urgent need to develop therapeutic agents and vaccines to mitigate the current
pandemic and to prevent the re-emergence of COVID-19. In February 2020, the World
Health Organization (WHO) assembled an international panel to develop animal
models for COVID-19 to accelerate the testing of vaccines and therapeutic agents.
Here we summarize the fndings to date and provides relevant information for
preclinical testing of vaccine candidates and therapeutic agents for COVID-19.info:eu-repo/semantics/acceptedVersio
I Congresso Ibero-Americano de Bibliotecas Escolares
Actas de la primera edición del I Congreso Iberoamericano de Bibliotecas Escolares, CIBES 2015, organizado por la Universidad Carlos III de Madrid (España), la Universidad Estatal Paulista (Brasil) y el Ayuntamiento de Getafe (España). Celebrado: 21 - 23 de octubre de 2015 en la Universidad Estatal Paulista (Marília) y 26 - 28 de octubre de 2015 en la Universidad Carlos III de Madrid (Getafe)Universidad Carlos III de Madrid (España)Universidad Estatal Paulista (Brasil)Ayuntamiento de Getafe (España)Dimensiones y visiones de la biblioteca escolar en una Educación por competencias: la
necesidad de una política estratégica / Miguel Ángel Marzal. -- Getafe ciudad educadora,
lectora y escritora: Bibliotecas escolares / Lourdes Muñoz Santiuste. -- Presente y
futuro: biblioteca escolar-CREA y proyectos interdisciplinares / Rosa Piquín. -- Cultura
en información: un reto esencial de la biblioteca escolar / Mónica Baró. -- Bibliotecas
escolares de Galicia: un mundo de oportunidades a favor de la Educación / Cristina Novoa.
-- 10 años de la Red de Bibliotecas Escolares de Extremadura (REBEX) / Casildo Macías
Pereira. -- Biblioteca Escolar y uso ético de la información para una Cultura de Paz / Ana
Barrero Tíscar. -- Dinamización de la Biblioteca Escolar Plumita durante el curso escolar
2014/15 / María Antonia Cano Cañada. -- Experiencia de la creación de una biblioteca
escolar / Susana Santos Martín. -- Grupo cooperativo Bibliotecas escolares en Red-Albacete
/ José Manuel Garrido Argandoña y Eva Leal Scasso. -- La BCREA "Juan Leiva". El fomento de
la lectura desde la web social / Andrés Pulido Villar. -- Proceso de implantación de una
herramienta de autoevaluación en la red de bibliotecas escolares de Extremadura (REBEX) /
Casildo Macías Pereira. -- La biblioteca escolar: abriendo fronteras / Lorena Verónica
Cabrera Orellana. -- O programa RBE e a avaliaçao das bibliotecas escolares: melhoria,
desenvolvimiento e innovaçao / Elsa Conde. -- Profesional de Biblioteconomía y
Documentación: esencial en la plantilla de la escuela / Pilar del Campo Puerta. -- Una
mirada activa al proceso educativo desde la biblioteca escolar / María Jesús Fontela
Fernández . -- Con otra mirada "La ilustración como vehículo de comunicación y aprendizaje
en las bibliotecas escolares" / Pablo Jurado Sánchez-Galán. -- Fingertips. Recriar a
biblioteca escolar na sala de aula / Rui Alfonso Mateus. -- Hablemos de libros. Cómo
transformar una clase de literatura en una comunidad de interpretación de textos /
Francisco César Díaz Rey. -- Inclusión social de familias inmigrantes a través de un
programa de aprendizaje de la lengua castellana / Ana Carmen Tolino Fernández-Henarejos.
-- O desenvolvimento de atividades de mediação de leitura em biblioteca escolar: o caso da
biblioteca da Escola Sesc de Ensino Médio / Vagner Amaro. -- La biblioteca escolar.
Proceso de enseñanza-aprendizaje de padres a hijos / Ana Carmen Tolino Fernández-
Henarejos. -- Leo con y para los demás / Ismael Fernández Fernández, Ana María Moreno
Vicente y Ana Beatriz Vicente Pérez. -- Nanas y arrullo. Poesía a la deriva / Bernardo
Fuentes Navarrete y Carlos García-Romeral Pérez. -- Gestión y evaluación de servicios
bibliotecarios para personas con dislexia: una biblioteca escolar inclusiva desde una
perspectiva internacional / Carmen Jorge García-Reyes. -- Sueños lectores compartidos
hechos realidad: la biblioteca escolar del C.E.I.P-S.E.S-A.A “LA PAZ” de Albacete / Ana
Rosa Cabañero Tobarra, Juan Manuel Herráez, Eva Leal Scasso, María Marín Sánchez, Ana
Belén Medrano Martínez y María José Nortes Ruipérez. -- El programa biblioteca escuela en
Civican. La literatura como elemento motivador para la alfabetización informacional /
Villar Arellano Yanguas. -- La competencia digital en el diseño curricular: desde la
biblioteca al aula / Felicidad Campal García. -- O deselvomimento da pesquisa escolar por
meio da competência em informaçao / Luciane de Fátima Cavalcante Beckman y Marta Leandro
da Mata. -- Proyecto escolar de investigación documental "Te pillé leyendo" / José Manuel
Garrido Argandoña. -- Aprender com a Biblioteca Escolar: formar para as literacias / Paula
Correia y Isabel Mendinhos. -- Sucedió en el siglo XX / María Antonia Becerra Montalbán,
Ángel Bernabé Muñoz y Sofía Vaz Romero. -- El Club de lectura en la nube / Belén Benito
Blázquez y Ana Ordás García. -- Promover a leitura e a escrita na era digital:
prácticas nas bibliotecas escolares / María Raquel Ramos. -- A biblioteca escolar e o
desafío da interculturalidade: o projeto Ser + cidadao / María da Conceição Tomé. --
Cuando la competencia digital encontró a la alfabetización informacional o Mucho ruido y
pocas nueces / Felicidad Campal García. -- Hora de ler, un programa para el fomento de la
lectura en contexto educativo / Cristina Novoa. -- Hábitos de lectura para las
competencias en información y alfabetización en información en bibliotecas escolares de
Puerto Rico / Karen Denise Centeno Casillas. -- Repositorios digitales en las bibliotecas
escolares andaluzas: situación, modelos y herramientas para su creación / Dolores Olmos
Olmos y Andrés Pulido Villar. -- Trabajando las competencias clave con las aventuras de
Mozarito en Extremadura / María Teresa Carballosa González y María Esther Nieto Vidal. --
Análisis de modelos de evaluación de la web de la biblioteca escolar / Raúl Cremades
García. -- Emociónate con las historias: El bosque de las emociones e historias con mucho
teatro / Esther Luis Pérez y Ana María Peromingo Fernández. -- Biblioteca escolar de
innovación y continuación / E. María Guerrero Palacios y Silvia Mora Ramírez. -- Uso de
estándares y licencias para la creación y difusión de contenidos en las bibliotecas
escolares / José Luis Barreiro Cebey. -- La biblioteca escolar digital móvil / Javier
Fernández Delgado. -- Uso de aplicaciones móviles para el desarrollo de
la competencia lingüística. Proyecto Hansel App Gretel / Dolores Olmos Olmos. -- A memória
e a mediação segundo Vigotski / Leda Maria Araújo, Patricia Celia Santana, Sueli Bortolin
y Leticia Gorri Molina. -- Bibliotecas escolares como tema de estudo dos alunos de
graduação em blioteconomia do Instituto de Ensino Superior da FUNLEC: estado da arte /
Tiago Pereira Nocera y Rodrigo Pereira. -- Ações de mediação da leitura e da informação
em bibliotecas escolares: um olhar sobre as bibliotecas dos Colégios de Aplicação /
Tatyanne Christina Gonçalves Ferreira Valdez y Alberto Calil Júnior. -- Mediação
pedagógica numa biblioteca de escola pública em Londrina / Rovilson José da Silva, Teba
Silva Yllana y Sueli Bortolin. -- Utilização de categorias por cores em sistema de
biblioteca voltado ao público infanto-juvenil / Liliana Giusti Serra. -- Atividades de
ensino dos atos de leitura com crianças em risco social / Adriana Naomi Fukushima da Silva
y Dagoberto Buim Arena. -- Biblioteca escolar: espaço de significados entre
alunos, professores e bibliotecários / Rodrigo Barbosa Paulo, Marisa Xavier, Helen Castro
Casarin y Creuza Barbaroto. -- A Biblioteca Escolar no Contexto da Legislação e
do Processo Educativo / Eliane Lourdes da Silva Moro, Francisca Rosaline Leite Mota y
Raimundo Martins de Lima. -- O jornal impresso como fonte de informação: a importância da
formação de leitores críticos / Mariana Pícaro Cerigatto. -- Bibliotecas escolares no
estado do Rio Grande do Sul: a trajetória de realização dos fóruns gaúchos pela melhoria
das bibliotecas escolares / Eliane Lourdes da Silva Moro y Lizandra Brasil Estabel. -- O
acesso à informação dos usuários surdos na biblioteca escolar / André Luís Onório
Coneglian y Mayara Melo Santana. -- Aprendizagem coletiva de bibliotecários e a
competência de pesquisa dos docentes: o caso do Instituto Federal do Espírito Santo /
Maristela Almeida Mercandeli Rodrigues y Beatriz Quiroz Villardi. -- Biblioteca escolar:
atores, parâmetros e competências / Mavi Galante Mancera Dall´Acqua Carvalho y Claudio
Marcondes de Castro Filho. -- Estratégias de aprendizagem de escrita no
Ensino Fundamental II / Érika Christina Kohle. -- Bebês e livros: leitura nas bebetecas.
Kenia Adriana de Aquino Modesto Silva, Juliane Francischeti Martins Motoyama y Renata
Junqueira de Souza. -- Práticas alternativas para organização de acervos nos espaços de
leitura em ambientes escolares / Luciana Souza Gracioso, Ariovaldo Alves,
Débora Nascimento, Suelen Redondo, Tainara Torika Kiri de Castro, Elizabete Angelon y
Eduardo Barbosa. -- Reflexões sobre a modelagem e criação de uma Rede Virtual de Leitores
para Bibliotecas Escolares / Carla Floriana Martins y Raoni Guerra Rajão. -- Biblioteca
escolar: espaço de formação leitora? / Silvana Ferreira de Souza Balsan y Renata
Junqueira de Souza. -- “Se a Biblioteca Escolar é minha mãe, o Google é meu pai”:
representações da relação entre Biblioteca Escolar e Google no imaginário de
alunos do ensino técnico / Adriana Bogliolo Sirihal-Duarte, Maria L. Amorim Antunes y
Raquel Miranda Vilela Paiva. -- Desafios e propostas para a universalização das
bibliotecas escolares no Brasil e na Espanha / Rodrigo Pereira, Daniela Spudeit y Fernanda
de Sales. -- Bibliotecário educador: possibilidades de atuação no contexto da biblioteca
escolar / André Carlos da Silva, Valéria Martin Valls y Mariana de Paula Silva. -- Uma ONG
para Bibliotecas Escolares : estratégia para ampliar a igualdade e capacidade de acesso
e uso da informação e educação escolar de qualidade / Suelen Camilo Ferreira y Luciana de
Souza Gracioso. -- O aluno com deficência: o papel do bibliotecário na disponibilidade de
recursos acessíveis na biblioteca escolar / Adriano de Sales Coelho, Rosilene de Melo
Oliveira y Marcos Pastana Santos. -- Biblioteca digital virtual e o uso do tablete: uma
possibilidade de construção de novas práticas de leitura na escola / Barbara Cibelli da
Silva Monteagudo y Dagoberto Buim Arena. -- A importância da biblioteca na educação de
crianças de 0 a 3 anos / Yngrid Karolline Mendonça Costa y Cyntia Graziella Guizelim
Simões Girotto. -- Comportamento Informacional de adolescentes: a relação com bibliotecas
e escolas / Nelson Sebastian Silva-Jerez y Helen de Castro S. Casarin
Temporal and spatial analysis of the 2014-2015 Ebola virus outbreak in West Africa
West Africa is currently witnessing the most extensive Ebola virus (EBOV) outbreak so far recorded. Until now, there have been 27,013 reported cases and 11,134 deaths. The origin of the virus is thought to have been a zoonotic transmission from a bat to a two-year-old boy in December 2013 (ref. 2). From this index case the virus was spread by human-to-human contact throughout Guinea, Sierra Leone and Liberia. However, the origin of the particular virus in each country and time of transmission is not known and currently relies on epidemiological analysis, which may be unreliable owing to the difficulties of obtaining patient information. Here we trace the genetic evolution of EBOV in the current outbreak that has resulted in multiple lineages. Deep sequencing of 179 patient samples processed by the European Mobile Laboratory, the first diagnostics unit to be deployed to the epicentre of the outbreak in Guinea, reveals an epidemiological and evolutionary history of the epidemic from March 2014 to January 2015. Analysis of EBOV genome evolution has also benefited from a similar sequencing effort of patient samples from Sierra Leone. Our results confirm that the EBOV from Guinea moved into Sierra Leone, most likely in April or early May. The viruses of the Guinea/Sierra Leone lineage mixed around June/July 2014. Viral sequences covering August, September and October 2014 indicate that this lineage evolved independently within Guinea. These data can be used in conjunction with epidemiological information to test retrospectively the effectiveness of control measures, and provides an unprecedented window into the evolution of an ongoing viral haemorrhagic fever outbreak.status: publishe
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