Different functional sensitivity to mutation at intersubunit interfaces involved in consecutive stages of foot-and-mouth disease virus assembly

© 2015 The Authors. Small spherical viruses are paradigms of supramolecular self-assembly. Identifying the specific structural determinants for virus assembly provides guidelines to develop new antiviral drugs or engineer modified viral particles for medical or technological applications. However, very few systematic studies have been carried out so far to identify those chemical groups at interfaces between virus capsid subunits that are important for viral assembly and function. Foot-and-mouth disease virus (FMDV) and other picornaviruses are assembled in a stepwise process in which different protein–protein interfaces are formed: 5 protomeric subunits oligomerize to form a pentameric intermediate, and 12 of these stable pentameric building blocks associate to form a labile capsid. In this study, a systematic mutational analysis revealed that very few amino acid side chains involved in substantial interactions between protomers within each pentamer are individually required for virus infectivity. This result contrasts sharply with the previous finding that most amino acid side chains involved in interactions between pentamers during the next assembly step are individually required for infectivity. The dramatic difference in sensitivity to single mutations between the two types of protein–protein interfaces in FMDV is discussed in terms of possible structural strategies for achieving self-assembly and genome uncoating in the face of diverse selective constraints.This work was funded by grants from the Spanish Government (BIO2009-10092 and BIO2012-37649) and Comunidad de Madrid (S-505/MAT-0303) to M. G. M., and by an institutional grant from Fundación Ramón Areces to the Centro de Biología Molecular ‘Severo Ochoa>Peer Reviewe

Relaciones estructura-función en la cápsida del virus de la fiebre aftosa: algunas implicaciones para el desarrrollo de vacunas y antivirales

Tesis doctoral inédita, leída en la Universidad Autónoma de Madrid, Facultad de Ciencias, Departamento de Biología Molecular. Fecha de lectura: 13-07-201

La gestión como un factor clave en la perdurabilidad empresarial : un estudio de la multinacional de moda líder en Latinoamérica: Totto, Nalsani S.A.

Con este estudio se busca explorar, en particular, la importancia de la gestión en el logro de la perdurabilidad de la empresa de origen colombiano Nalsani S.A., la compañía que dio origen a la marca Totto®.This study pretend to explore, in particular, the importance of management in the achievement of perdurability in the Colombian company Nalsani S.A., the company that gave rise to the Totto® brand.Universidad del Rosari

La Retroalimentación como factor indispensable en la educación on-line

El propósito principal de este estudio es sentar las bases para futuras investigaciones alusivas al tema sobre la retroalimentación como una herramienta de interacción en la educación a distancia

A single amino acid substitution in the capsid of foot-and-mouth disease virus can increase acid resistance

Foot-and-mouth disease virus (FMDV) particles lose infectivity due to their disassembly at pH values slightly below neutrality. This acid-dependent disassembly process is required for viral RNA release inside endosomes. To study the molecular determinants of viral resistance to acid-induced disassembly, six FMDV variants with increased resistance to acid inactivation were isolated. Infection by these mutants was more sensitive to drugs that raise the endosomal pH (NH4Cl and concanamycin A) than was infection by the parental C-S8c1 virus, confirming that the increase in acid resistance is related to a lower pH requirement for productive uncoating. Amino acid replacement N17D at the N terminus of VP1 capsid protein was found in all six mutants. This single substitution was shown to be responsible for increased acid resistance when introduced into an infectious FMDV clone. The increased resistance of this mutant against acid-induced inactivation was shown to be due to its increased resistance against capsid dissociation into pentameric subunits. Interestingly, the N17D mutation was located close to but not at the interpentamer interfaces. The mutants described here extend the panel of FMDV variants exhibiting different pH sensitivities and illustrate the adaptive flexibility of viral quasispecies to pH variations.Work at the F.S. laboratory was supported by grants from Ministerio de Ciencia e Innovación (MICINN) BIO2008-0447-C03-01 and CSD2006-0007; work at the M.G.M. laboratory was supported by grants from MICINN (BIO2009-10092) and Comunidad de Madrid (S-2009/MAT/1467). An institutional grant from Fundación Ramón Areces is also acknowledged.Peer Reviewe

Creación de empresa dedicada a la fabricación y comercialización de comida natural para perros

Proyecto de creación de empresa de comida natural para perros, Nevada BARF es una empresa que operará en Bogotá, Colombia, su propósito es la fabricación y venta de alimento natural para perros totalmente personalizado, con el servicio de ventas a domicilio, para distribuir en toda la ciudad de Bogotá. Permitirá a los dueños de las mascotas prolongar sus vidas y alimentarlos de la manera más sana y natural. Además, el producto cuenta con los porcentajes exactos para dar un alimento balanceado a las mascotas en los hogares contando con nutricionistas que apoyan el proceso de fabricación, con un excelente servicio al cliente que le permita a éste realizar la compra desde la comodidad de su casa ya que el producto llegara a su lugar de residencia cuando él lo pida, el producto cuenta con una presentación personalizada en la cual cada pedido para cierta mascota tendrá una imagen de la raza a la cual se le está dando, haciendo sentir comodidad a los clientes y compatibilidad con el producto ya que al ver la cara de sus mascotas plasmadas en el empaque sentirán seguridad.Project business creation natural dog food. Nevada BARF is a company that operate in Bogotá, Colombia, its purpose is the manufacture and sale of natural food for fully customized dog, with sales Service delivery, to distribute throughout Bogotá. It will allow pet owners to prolong their lives and feeding of the healthiest and most natural way. In addition, the product has the exact percentages to give a balanced feed pets in households having nutritionists who support the manufacturing process,’ with excellent customer Service that will allow it to make the purchase from the comfort of your home since the product carne to his place of residence when he asks, the product features a custom presentation in which each order for certain pet will have a picture of the race which is giving. Making feel convenience to customers and compatibility with the product since seeing his pet face reflected in the packaging.Ingeniero (a) IndustrialPregrad

EL TURISMO IDIOMÁTICO COMO UNA PROPUESTA DE MULTIDESTINO EN EL ECUADOR

El presente estudio propone desarrollar al turismo idiomático como una propuesta de multidestino, innovando la oferta turística en el Ecuador. En la actualidad el estudio del idioma, contribuye una fuente de conocimiento, trabajo y de desarrollo, tanto a nivel local, nacional e internacional; investigaciones han demostrado que el idioma español es la segunda lengua más hablada a nivel mundial y cuenta con 329 millones de personas. Esto ha generado un nuevo nicho de mercado dentro del sector turístico, específicamente el estudiantil, es por ello que este análisis desarrolla el perfil de turista idiomático en las poblaciones de Quito, Guayaquil, Cuenca y Montañita, en los distintos centros de enseñanza que son afiliados al AECEE (Ecuadorian Association of Spanish Language Centers)

Modified Metallic Oxides for Efficient Photocatalysis

The aim of the chapter is to present modified materials like alternatives for conventional photocatalyst such as titanium dioxide. Discussion about silver/graphene nanoparticles-modified zinc oxide for the degradation of pollutants like triclosan or bisphenol A, both considered as endocrine disruptors, which affect the hormonal development of humans, is presented. The best conditions to obtain the highest photodegradation degree are established. In addition, the bismuth oxychloride has gained attention during the last 5 years for photocatalysis. In accordance, the obtained results for phenol photodegradation, using such oxychloride, are also presented. In the chapter, the characterization of photocatalyst is reported along with the proposal for mechanisms of action for the modified ZnO photocatalyst and the bismuth oxychloride

Recaudación tributaria en el periodo 2019-2020 de la “Municipalidad distrital de San Mateo”- Lima

El presente trabajo tuvo como objetivo general; conocer los niveles de recaudación tributaria del periodo 2019-2020 en la Municipalidad distrital San Mateo de Huanchor – Lima. El tipo de investigación es descriptiva y el diseño de investigación descriptivapropositiva. Por otra parte, la población estuvo conformada los documentos relacionados con el registro de recaudación de impuestos, desde inicios de funcionamiento hasta la actualidad de la Municipalidad y los contribuyentes, para la muestra son los registros de recaudación de impuestos (predial, arbitrios municipales y agua) del periodo 2019-2020 de la Municipalidad y 100 contribuyentes. Las técnicas e instrumentos utilizados fueron la guía de análisis documental y guía de entrevista y cuestionario. Se pudo concluir que la Municipalidad distrital de San Mateo, se encontró que en el primer periodo estudiado se recaudó más en arbitrios municipales y agua siendo el monto de S/. 1, 339,988.57 y en impuesto predial se recaudó menos que el año siguiente S/. 609,454.36. Por otro lado el año 2020, en arbitrios municipales y agua se recaudó S/.1,194,533.74 y en impuesto predial se recaudó más que el año anterior S/. 748,466.50. Con toda esta información obtenida podemos indicar que la pandemia afecto también en la recaudación periódica de la Municipalidad distrital de San Mateo

Thermostability of the foot-and-mouth disease virus capsid is modulated by lethal and viability-restoring compensatory amino acid substitutions

Infection by viruses depends on a balance between capsid stability and dynamics. This study investigated biologically and biotechnologically relevant aspects of the relationship in foot-and-mouth disease virus (FMDV) between capsid structure and thermostability and between thermostability and infectivity. In the FMDV capsid, a substantial number of amino acid side chains at the interfaces between pentameric subunits are charged at neutral pH. Here a mutational analysis revealed that the essential role for virus infection of most of the 8 tested charged groups is not related to substantial changes in capsid protein expression or processing or in capsid assembly or stability against a thermally induced dissociation into pentamers. However, the positively charged side chains of R2018 and H3141, located at the interpentamer interfaces close to the capsid 2-fold symmetry axes, were found to be critical both for virus infectivity and for keeping the capsid in a state of weak thermostability. A charge-restoring substitution (N2019H) that was repeatedly fixed during amplification of viral genomes carrying deleterious mutations reverted both the lethal and capsid-stabilizing effects of the substitution H3141A, leading to a double mutant virus with close to normal infectivity and thermolability. H3141A and other thermostabilizing substitutions had no detectable effect on capsid resistance to acid-induced dissociation into pentamers. The results suggest that FMDV infectivity requires limited local stability around the 2-fold axes at the interpentamer interfaces of the capsid. The implications for the mechanism of genome uncoating in FMDV and the development of thermostabilized vaccines against foot-and-mouth disease are discussed. IMPORTANCE This study provides novel insights into the little-known structural determinants of the balance between thermal stability and instability in the capsid of foot-and-mouth disease virus and into the relationship between capsid stability and virus infectivity. The results provide new guidelines for the development of thermostabilized empty capsid-based recombinant vaccines against foot-and-mouth disease, one of the economically most important animal diseases worldwid