18 research outputs found
Trypanosoma rangeli: growth in mammalian cells in vitro and action of a repositioned drug (17-AAG) and a natural extract (Artemisia sp. essential oil)
Trypanosoma rangeli and T. cruzi are both parasitic unicellular species that infect humans. Unlike T. cruzi, the causative agent of Chagas disease, T. rangeli is an infective and non-pathogenic parasite for humans, but pathogenic for vectors from the Rhodnius genus. Because both species can coexist in different hosts and overlap their infective cycles but very little is known about the infection of T. rangeli in mammalian cells, we decided to characterize both the development of this parasite in cell culture and the effect of therapeutic agents with potential trypanocidal action on it. We found that T. rangeli exhibits a cycle of infection in Vero cells similar to that for T. cruzi and that the repurposed drug, 17-AAG, and the natural extract Artemisia sp. essential oil produce a toxic effect on epimastigotes showing a trypanocidal action from the fifth day of culture. Both treatments also affected the infection of trypomastigotes and reduced the capacity of replication of amastigotes of T. rangeli. Since T. cruzi / T. rangeli coinfection cases have been reported, the finding of drugs with potential activity against both species could be significant in the future. Furthermore, studies of susceptibility of both species to drugs could also help to know the different mechanisms of pathogenicity in humans displayed by T. cruzi that are absent in T. rangeli.Fil: Cimador, Ana Laura. Universidad "Juan Agustín Maza". Facultad de Farmacia y Bioquímica; ArgentinaFil: Galante, Emeli Luciana. Universidad "Juan Agustín Maza". Facultad de Farmacia y Bioquímica; ArgentinaFil: Muñoz, Lucila Ibel. Universidad "Juan Agustín Maza". Facultad de Farmacia y Bioquímica; ArgentinaFil: Romano, Patricia Silvia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; Argentina. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas; ArgentinaFil: Losinno, Antonella Denise. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas; Argentina. Universidad "Juan Agustín Maza". Facultad de Farmacia y Bioquímica; ArgentinaFil: Vanrell, Maria Cristina. Universidad "Juan Agustín Maza". Facultad de Farmacia y Bioquímica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; Argentina. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas; Argentin
Multicomponent Synthesis of Polyphenols and Their In Vitro Evaluation as Potential \u3b2-Amyloid Aggregation Inhibitors
While plant polyphenols possess a variety of biological properties, exploration of chemical
diversity around them is still problematic. Here, an example of application of the Ugi multicomponent
reaction to the combinatorial assembly of artificial, yet \u201cnatural-like\u201d, polyphenols is presented. The
synthesized compounds represent a second-generation library directed to the inhibition of \u3b2-amyloid
protein aggregation. Chiral enantiopure compounds, and polyphenol-\u3b2-lactam hybrids have been
prepared too. The biochemical assays have highlighted the importance of the key pharmacophores in
these compounds. A lead for inhibition of aggregation of truncated protein A\u3b2pE3-42 was selected
Specific ADAM10 inhibitors localize in exosome-like vesicles released by Hodgkin lymphoma and stromal cells and prevent sheddase activity carried to bystander cells
Shedding of ADAM10 substrates, like TNFa, MICA or CD30, is reported to affect both anti-tumor immune response and antibody-drug-conjugate (ADC)-based immunotherapy. Soluble forms of these molecules and ADAM10 can be carried and spread in the microenvironment by exosomes released by tumor cells. We reported new ADAM10 inhibitors able to prevent MICA shedding in Hodgkin lymphoma (HL), leading to recognition of HL cells by cytotoxic lymphocytes. In this paper, we show that the mature bioactive form of ADAM10 is released in exosome-like vesicles (ExoV) by HL cells and lymph node mesenchymal stromal cells (MSC). We demonstrate that ADAM10 inhibitors are released in ExoV by MSC or HL cells, endocytosed by bystander cells and localized in the endolysosomal compartment in HL MSC. ExoV released by HL cells can enhance MICA shedding by MSC, while ExoV from MSC induce TNFa or CD30 shedding by HL cells. Of note, ADAM10 sheddase activity carried by ExoV is prevented with the ADAM10 inhibitors LT4 and CAM29, pretreating either the ExoVproducing or the ExoV-receiving cells. In particular, both inhibitors reduce CD30 shedding maintaining the anti-tumor effects of the ADC Brentuximab-Vedotin or the anti-CD30 Iratumumab on HL cells. Thus, spreading of ADAM10 activity due to ExoV can result in the release of cytokines, like TNFa,a lymphoma growth factor, or soluble molecules, like sMICA or sCD30, that potentially interfere with host immune surveillance or immunotherapy. ADAM10 blockers can interfere with this process, allowing the development of anti-lymphoma immune response and/or efficient ADC-based or human antibody-based immunotherapy
Identification of a high affinity binding site for abscisic acid on human lanthionine synthetase component C-like protein 2
Lanthionine synthetase component C-like protein 2 (LANCL2) has been identified as the mammalian receptor mediating the functional effects of the universal stress hormone abscisic acid (ABA) in mammals. ABA stimulates insulin independent glucose uptake in myocytes and adipocytes via LANCL2 binding in vitro, improves glucose tolerance in vivo and induces brown fat activity in vitro and in vivo. The emerging role of the ABA/LANCL2 system in glucose and lipid metabolism makes it an attractive target for pharmacological interventions in diabetes mellitus and the metabolic syndrome. The aim of this study was to investigate the presence of ABA binding site(s) on LANCL2 and identify the amino acid residues involved in ABA binding. Equilibrium binding assays ([3H]-ABA saturation binding and surface plasmon resonance analysis) suggested multiple ABA-binding sites, prompting us to perform a computational study that indicated one putative high-affinity and two low-affinity binding sites. Site-directed mutagenesis (single mutant R118I, triple mutants R118I/R22I/K362I and R118I/S41A/E46I) and equilibrium binding experiments on the mutated LANCL2 proteins identified a high-affinity ABA-binding site involving R118, with a KD of 2.6 nM ± 1.2 nM, as determined by surface plasmon resonance. Scatchard plot analysis of binding curves from both types of equilibrium binding assays revealed a Hill coefficient >1, suggesting cooperativity of ABA binding to LANCL2. Identification of the high-affinity ABA-binding site is expected to allow the design of ABA agonists/antagonists, which will help to understand the role of the ABA/LANCL2 system in human physiology and disease
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
Effects of Prion Protein on A\u3b242 and Pyroglutamate-Modified A\u3b2p\u3953-42 Oligomerization and Toxicity
Soluble A\u3b2 oligomers are widely recognized as the toxic forms responsible for triggering AD, and A\u3b2 receptors are hypothesized to represent the first step in a neuronal cascade leading to dementia. Cellular prion protein (PrP) has been reported as a high-affinity binder of A\u3b2 oligomers. The interactions of PrP with both A\u3b242 and the highly toxic N-truncated pyroglutamylated species (A\u3b2pE3-42) are here investigated, at a molecular level, by means of ThT fluorescence, NMR and TEM. We demonstrate that soluble PrP binds both A\u3b242 and A\u3b2pE3-42, preferentially interacting with oligomeric species and delaying fibril formation. Residue level analysis of A\u3b242 oligomerization process reveals, for the first time, that PrP is able to differently interact with the forming oligomers, depending on the aggregation state of the starting A\u3b242 sample. A distinct behavior is observed for A\u3b242 1-30 region and C-terminal residues, suggesting that PrP protects A\u3b242 N-tail from entangling on the mature NMR-invisible fibril, consistent with the hypothesis that A\u3b242 N-tail is the locus of interaction with PrP. PrP/A\u3b2pE3-42 interactions are here reported for the first time. All interaction data are validated and complemented by cellular tests performed on Wt and PrP-silenced neuronal cell lines, clearly showing PrP dependent A\u3b2 oligomer cell internalization and toxicity. The ability of soluble PrP to compete with membrane-anchored PrP for binding to A\u3b2 oligomers bears relevance for studies of druggable pathways
Differential toxicity, conformation and morphology of typical initial aggregation states of Aβ1-42 and Aβpy3-42 beta-amyloids
Among the different species of water-soluble β-peptides (Aβ1-42, Aβ1-40 and N-terminal truncated Aβ-peptides), Aβpy3-42 is thought to play a relevant role in Alzheimer's pathogenesis due to its abundance, resistance to proteolysis, fast aggregation kinetics, dynamic structure and high neurotoxicity. To evaluate the specific structural characteristics and neurotoxicity of Aβpy3-42, we separated different aggregation states of Aβ1-42 and Aβpy3-42 using fast protein liquid chromatography, isolating in both cases three peaks that corresponded to sa (small), ma (medium) and la (large) aggregates.
Conformational analysis, by circular dichroism showed a prevailing random coil conformation for sa and ma, and typical β-sheet conformation for la. AFM and TEM show differential structural features between the three aggregates of a given β-peptide and among the aggregate of the two β-peptides. The potential toxic effects of the different aggregates were evaluated using human neuroblastoma SH-SY5Y cells in the MTT reduction, in the xCELLigence System, and in the Annexin V binding experiments. In the case of Aβ1-42 the most toxic aggregate is la, while in the case of Aβpy3-42 both sa and la are equally toxic. Aβ aggregates were found to be internalized in the cells, as estimated by confocal immunofluorescence microscopy, with a higher effect observed for Aβpy3-42, showing a good correlation with the toxic effects. Together these experiments allowed the discrimination of the intermediate states more responsible of oligomer toxicity, providing new insights on the correlation between the aggregation process and the toxicity and confirming the peculiar role in the pathogenesis of Alzheimer disease of Aβpy3-42 peptide
Multicomponent, Fragment-Based, Synthesis of Polyphenol-containing Peptidomimetics and their Inhibiting Activity on Beta Amyloid Oligomerization
A new and concise fragment-based approach towards artificial (but "natural-based") complex polyphenols has been developed, exploiting the Ugi multicomponent reaction of phenol-containing simple substrates. The resulting library of compounds has been tested for the capacity to inhibit \u3b2-amyloid protein aggregation, as a possible strategy to develop new chemical entities to be used as a prevention or a therapy for Alzheimer's disease. Some of the members of the library have demonstrated, in Thioflavin assays, a highly promising activity in inhibiting aggregation for two \u3b2-amyloid peptides: A\u3b21-42 and the truncated A\u3b2pE3-42