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Search Results: 1 - 10 of 465675 matches for " Felix A Rey "
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Rubella Virus: First Calcium-Requiring Viral Fusion Protein
Mathieu Dubé,Felix A. Rey,Margaret Kielian
PLOS Pathogens , 2014, DOI: doi/10.1371/journal.ppat.1004530
Abstract: Rubella virus (RuV) infection of pregnant women can cause fetal death, miscarriage, or severe fetal malformations, and remains a significant health problem in much of the underdeveloped world. RuV is a small enveloped RNA virus that infects target cells by receptor-mediated endocytosis and low pH-dependent membrane fusion. The structure of the RuV E1 fusion protein was recently solved in its postfusion conformation. RuV E1 is a member of the class II fusion proteins and is structurally related to the alphavirus and flavivirus fusion proteins. Unlike the other known class II fusion proteins, however, RuV E1 contains two fusion loops, with a metal ion complexed between them by the polar residues N88 and D136. Here we demonstrated that RuV infection specifically requires Ca2+ during virus entry. Other tested cations did not substitute. Ca2+ was not required for virus binding to cell surface receptors, endocytic uptake, or formation of the low pH-dependent E1 homotrimer. However, Ca2+ was required for low pH-triggered E1 liposome insertion, virus fusion and infection. Alanine substitution of N88 or D136 was lethal. While the mutant viruses were efficiently assembled and endocytosed by host cells, E1-membrane insertion and fusion were specifically blocked. Together our data indicate that RuV E1 is the first example of a Ca2+-dependent viral fusion protein and has a unique membrane interaction mechanism.
Structural Basis of HCV Neutralization by Human Monoclonal Antibodies Resistant to Viral Neutralization Escape
Thomas Krey ,Annalisa Meola,Zhen-yong Keck,Laurence Damier-Piolle,Steven K. H. Foung,Felix A. Rey
PLOS Pathogens , 2013, DOI: 10.1371/journal.ppat.1003364
Abstract: The high mutation rate of hepatitis C virus allows it to rapidly evade the humoral immune response. However, certain epitopes in the envelope glycoproteins cannot vary without compromising virus viability. Antibodies targeting these epitopes are resistant to viral escape from neutralization and understanding their binding-mode is important for vaccine design. Human monoclonal antibodies HC84-1 and HC84-27 target conformational epitopes overlapping the CD81 receptor-binding site, formed by segments aa434–446 and aa610–619 within the major HCV glycoprotein E2. No neutralization escape was yet observed for these antibodies. We report here the crystal structures of their Fab fragments in complex with a synthetic peptide comprising aa434–446. The structures show that the peptide adopts an α-helical conformation with the main contact residues F442 and Y443 forming a hydrophobic protrusion. The peptide retained its conformation in both complexes, independently of crystal packing, indicating that it reflects a surface feature of the folded glycoprotein that is exposed similarly on the virion. The same residues of E2 are also involved in interaction with CD81, suggesting that the cellular receptor binds the same surface feature and potential escape mutants critically compromise receptor binding. In summary, our results identify a critical structural motif at the E2 surface, which is essential for virus propagation and therefore represents an ideal candidate for structure-based immunogen design for vaccine development.
Modeling an Evolutionary Conserved Circadian Cis-Element
Eric R Paquet,Guillaume Rey,Felix Naef
PLOS Computational Biology , 2008, DOI: 10.1371/journal.pcbi.0040038
Abstract: Circadian oscillator networks rely on a transcriptional activator called CLOCK/CYCLE (CLK/CYC) in insects and CLOCK/BMAL1 or NPAS2/BMAL1 in mammals. Identifying the targets of this heterodimeric basic-helix-loop-helix (bHLH) transcription factor poses challenges and it has been difficult to decipher its specific sequence affinity beyond a canonical E-box motif, except perhaps for some flanking bases contributing weakly to the binding energy. Thus, no good computational model presently exists for predicting CLK/CYC, CLOCK/BMAL1, or NPAS2/BMAL1 targets. Here, we use a comparative genomics approach and first study the conservation properties of the best-known circadian enhancer: a 69-bp element upstream of the Drosophila melanogaster period gene. This fragment shows a signal involving the presence of two closely spaced E-box–like motifs, a configuration that we can also detect in the other four prominent CLK/CYC target genes in flies: timeless, vrille, Pdp1, and cwo. This allows for the training of a probabilistic sequence model that we test using functional genomics datasets. We find that the predicted sequences are overrepresented in promoters of genes induced in a recent study by a glucocorticoid receptor-CLK fusion protein. We then scanned the mouse genome with the fly model and found that many known CLOCK/BMAL1 targets harbor sequences matching our consensus. Moreover, the phase of predicted cyclers in liver agreed with known CLOCK/BMAL1 regulation. Taken together, we built a predictive model for CLK/CYC or CLOCK/BMAL1-bound cis-enhancers through the integration of comparative and functional genomics data. Finally, a deeper phylogenetic analysis reveals that the link between the CLOCK/BMAL1 complex and the circadian cis-element dates back to before insects and vertebrates diverged.
Human Monoclonal Antibodies to a Novel Cluster of Conformational Epitopes on HCV E2 with Resistance to Neutralization Escape in a Genotype 2a Isolate
Zhen-yong Keck,Jinming Xia,Yong Wang,Wenyan Wang,Thomas Krey,Jannick Prentoe,Thomas Carlsen,Angela Ying-Jian Li,Arvind H. Patel,Stanley M. Lemon,Jens Bukh,Felix A. Rey,Steven K. H. Foung
PLOS Pathogens , 2012, DOI: 10.1371/journal.ppat.1002653
Abstract: The majority of broadly neutralizing antibodies to hepatitis C virus (HCV) are against conformational epitopes on the E2 glycoprotein. Many of them recognize overlapping epitopes in a cluster, designated as antigenic domain B, that contains residues G530 and D535. To gain information on other regions that will be relevant for vaccine design, we employed yeast surface display of antibodies that bound to genotype 1a H77C E2 mutant proteins containing a substitution either at Y632A (to avoid selecting non-neutralizing antibodies) or D535A. A panel of nine human monoclonal antibodies (HMAbs) was isolated and designated as HC-84-related antibodies. Each HMAb neutralized cell culture infectious HCV (HCVcc) with genotypes 1–6 envelope proteins with varying profiles, and each inhibited E2 binding to the viral receptor CD81. Five of these antibodies neutralized representative genotypes 1–6 HCVcc. Epitope mapping identified a cluster of overlapping epitopes that included nine contact residues in two E2 regions encompassing aa418–446 and aa611–616. Effect on virus entry was measured using H77C HCV retroviral pseudoparticles, HCVpp, bearing an alanine substitution at each of the contact residues. Seven of ten mutant HCVpp showed over 90% reduction compared to wild-type HCVpp and two others showed approximately 80% reduction. Interestingly, four of these antibodies bound to a linear E2 synthetic peptide encompassing aa434–446. This region on E2 has been proposed to elicit non-neutralizing antibodies in humans that interfere with neutralizing antibodies directed at an adjacent E2 region from aa410–425. The isolation of four HC-84 HMAbs binding to the peptide, aa434–446, proves that some antibodies to this region are to highly conserved epitopes mediating broad virus neutralization. Indeed, when HCVcc were passaged in the presence of each of these antibodies, virus escape was not observed. Thus, the cluster of HC-84 epitopes, designated as antigenic domain D, is relevant for vaccine design for this highly diverse virus.
Palabras y proyectos de mujeres socialistas a través de sus revistas (1900-1956)
Rey,Ana Lía;
Mora (Buenos Aires) , 2011,
Abstract: this article intends to summarize the state of the art reached so far on the studies on publications for female readership. our main interest is to take into consideration some characteristics of the first steps of a publishing project, either individual or collective, trying to expose the ideological agreements needed to define a public position and the search of issues and personnel to work in the magazine. we seek to reflect the utopia represented by a group of women who dared to organize magazines and show their point of view, from the early years of the xxth century to the citizenship extension period. these magazines were published in la plata and buenos aires and they share in common that they were directed by women. the magazines are: nosotras (1902) and la nueva mujer (1910), published in la plata, and unión y labor (1909), nuestra causa (1919), vida femenina (1934) and ciudadanas (1956), published in buenos aires. every one of them was conceived in the socialist party or related to freethinkers organizations. these female groups public interventions were usually inspired by the seek of political and social equality with men. general aspects of each publication are described here, but simultaneously, these allow to open a wider horizon of investigation that deals with the search of gender identity.
El cuerpo en la construcción de la identidad de los sordos
Rey,María Inés;
Papeles de trabajo - Centro de Estudios Interdisciplinarios en Etnoling???-stica y Antropolog?-a Socio-Cultural , 2008,
Abstract: from the normalize institutions (medicine, education, family), the deaf ones are thought as patients to rehabilitating by means of the education of the speech. bodies are controlled, there transform the experiences of the deafness and of the deaf being. the deaf ones are defined by themselves as a linguistic community by own cultural characteristics. argentinian signs language embody historical phenomena, politician - cultural and the break with the biological concept of the deaf identity.
Palabras y proyectos de mujeres socialistas a través de sus revistas (1900-1956)
Ana Lía Rey
Mora (Buenos Aires) , 2011,
Abstract: El artículo se propone realizar un estado del arte sobre los estudios existentes hasta el momento sobre las publicaciones dedicadas al público femenino. Nuestro principal interés es pensar el momento en que se inicia un proyecto editorial colectivo o individual, descubrir la puesta en marcha de acuerdos ideológicos que permiten una definición pública y la búsqueda de personas y temas para preparar una revista. Pensar en la utopía del comienzo de un pu ado de mujeres que se lanzaron a producir revistas, entre principios del siglo XX y la ampliación de la ciudadanía política, y dar a conocer sus puntos de vista. Estas revistas fueron publicadas en la ciudad de La Plata y en la de Buenos Aires, y su característica común es que sus directoras fueron mujeres. Nos referimos a Nosotras (1902)y a La Nueva Mujer (1910), publicadas en la ciudad platense, y a Unión y Labor (1909), Nuestra Causa (1919), Vida femenina (1934) y Ciudadanas (1956), editadas en Buenos Aires. Todas ellas fueron gestadas en el seno del partido socialista o dentro de organizaciones de librepensadores. La intervención pública de estos grupos femeninos fue, generalmente, a través de la búsqueda de igualdad con los varones en términos políticos y sociales. Cada una de las publicaciones es presentada en sus aspectos más generales pero ellos nos permiten abrir un horizonte de investigación donde cada una de estas empresas editoriales denota la relevancia que tuvieron para la búsqueda de identidad de género. This article intends to summarize the state of the art reached so far on the studies on publications for female readership. Our main interest is to take into consideration some characteristics of the first steps of a publishing project, either individual or collective, trying to expose the ideological agreements needed to define a public position and the search of issues and personnel to work in the magazine. We seek to reflect the utopia represented by a group of women who dared to organize magazines and show their point of view, from the early years of the XXth century to the citizenship extension period. These magazines were published in La Plata and Buenos Aires and they share in common that they were directed by women. The magazines are: Nosotras (1902) and La Nueva Mujer (1910), published in La Plata, and Unión y Labor (1909), Nuestra Causa (1919), Vida Femenina (1934) and Ciudadanas (1956), published in Buenos Aires. Every one of them was conceived in the Socialist Party or related to freethinkers organizations. These female groups public interventions were usually inspired by the see
Tempranos reclamos de una ley que tardó en llegar: A propósito del texto de Carolina Muzilli "El divorcio"
Ana Lía Rey
Mora (Buenos Aires) , 2012,
Estudio sismotectonico de Las Serranias Levantinas
Annals of Geophysics , 1961, DOI: 10.4401/ag-5279
Abstract: .
Antas no cami o. Prehistoria e Arqueoloxía nos Cami os Xacobeos do Norte
Carneiro Rey, Juan A.
Cuadernos de Estudios Gallegos , 2005,
Abstract: We deal in this paper with the recent prehistoric record to be found along the northern route of the pilgrimage to Santiago de Compostela. To start with, we analyze the physical environment and the archaeological remains that have a wide cultural scope, ranging from the Paleolithic to the Medieval ages. We carry on with a review of the earlier research on this topic, from the XIX century onwards. Lastly, we trace the spatial distribution of the megalithic phenomenon in two of the most outstanding areas from this route, Terra Cha and Terra de Melide where, like in other peninsular zones, funerary mounds are commonly linked to old paths that communicate the highlands with the valleys below. [gl] Neste traballo estúdase a Prehistoria recente nas terras polas que transcorre un dos caminos de peregrinación a Santiago de Compostela: o Cami o do Norte. En primeiro lugar analizamos o entorno xeográfíco e os restos arqueolóxicos, que conforman unha riqueza cultural que vai dende o Paleolítico ata o mundo romano e a época medieval. A continuación faise unha escolma dos estudos pioneiros levados a cabo nesa zona desde o século XIX. Por último se rexistra a distribución espacial do fenómeno tumular nas dúas áreas mais salientables do itinerario: a Terra Cha e a Terra de Melide. Ao igual que noutros lugares de Galicia e da Península, os túmulos megalíticos están vinculados a antigos cami os e sitúanse en zonas de paso que comunican as terras altas coas baixas.
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