87 research outputs found
A methodology for Institution-Field ranking based on a bidimensional analysis: The IFQ2A-index
The problem of comparing academic institutions in terms of their research production is nowadays a priority issue. This paper proposes a relative bidimensional index that takes into account both the net production and the quality of it, as an attempt to provide a comprehensive and objective way to compare the research output of di erent institutions in a specfic field, using journal contributions and citations. The proposed index is then applied, as a case study, to rank the top Spanish universities in the felds of Chemistry and Computer Science in the period ranging from 2000 until 2009. A comparison with the top 50 universities in the ARWU rankings is also made, showing the proposed ranking is better suited to distinguish among non-elite universitie
N-glycosylation profile analysis of Trastuzumab biosimilar candidates by Normal Phase Liquid Chromatography and MALDI-TOF MS approaches
The pharmaceutical market has entered an era in which the production of new therapeutics is being often replaced by “biosimilars”, copies of already commercialized products waiting for the patents to expire in order to be distributed in a more competitive and affordable manners. Due to its relevance, the ErbB2-targeted monoclonal antibody Trastuzumab (Herceptin) used as breast cancer therapy is one of the main targets in the production of biosimilars. A major challenge is to produce antibodies with the same or the closest N-glycosylation pattern seen in the commercialized drug. Several factors, such as growing conditions or cell types employed, can determine the final composition and structure of the glycans, significantly affecting the properties of the generated antibodies. Therefore, an appropriate characterization is essential. In the present study, we describe two different but complementary strategies to characterize the N-glycosylation of two biosimilar candidates of Trastuzumab. In the first case, N-glycans are fluorescently labeled and separated by Normal Phase HPLC. Different sugars will elute at different times and can be identified using specific oligosaccharide standards. In the second approach, released glycans are permethylated and analyzed by MALDI-TOF MS, being able to determine the structure because of the differential sugar masses.
Biological significance
The characterization of the N-glycosylation sites of therapeutic recombinant monoclonal
antibodies (mAbs) is usually one of the most critical and time consuming steps in the
developing process of biosimilars or any other glycosylated drug. Herein we describe two
different but complementary approaches to characterize mAbs glycosylation patterns, the
use of glycan fluorescence labeling coupled to HPLC and MALDI-TOF MS profile analysis.
This article is part of a Special Issue entitled: HUPO 2014
In Silico Evaluation of Sesquiterpenes and Benzoxazinoids Phytotoxins against M-pro, RNA Replicase and Spike Protein of SARS-CoV-2 by Molecular Dynamics. Inspired by Nature
In the work described here, a number of sesquiterpenes and benzoxazinoids from natural sources, along with their easily accessible derivatives, were evaluated against the main protease, RNA replicase and spike glycoprotein of SARS-CoV-2 by molecular docking. These natural products and their derivatives have previously shown remarkable antiviral activities. The most relevant compounds were the 4-fluoro derivatives of santamarine, reynosin and 2-amino-3H-phenoxazin-3-one in terms of the docking score. Those compounds fulfill the Lipinski's rule, so they were selected for the analysis by molecular dynamics, and the kinetic stabilities of the complexes were assessed. The addition of the 4-fluorobenzoate fragment to the natural products enhances their potential against all of the proteins tested, and the complex stability after 50 ns validates the inhibition calculated. The derivatives prepared from reynosin and 2-amino-3H-phenoxazin-3-one are able to generate more hydrogen bonds with the M-pro, thus enhancing the stability of the protein-ligand and generating a long-term complex for inhibition. The 4-fluoro derivate of santamarine and reynosin shows to be really active against the spike protein, with the RMSD site fluctuation lower than 1.5 angstrom. Stabilization is mainly achieved by the hydrogen-bond interactions, and the stabilization is improved by the 4-fluorobenzoate fragment being added. Those compounds tested in silico reach as candidates from natural sources to fight this virus, and the results concluded that the addition of the 4-fluorobenzoate fragment to the natural products enhances their inhibition potential against the main protease, RNA replicase and spike protein of SARS-CoV-2
Increased Protein Stability and Interleukin-2 Production of a LAT(G131D)Variant With Possible Implications for T Cell Anergy
The adaptor LAT plays a crucial role in the transduction of signals coming from the TCR/CD3 complex. Phosphorylation of some of its tyrosines generates recruitment sites for other cytosolic signaling molecules. Tyrosine 132 in human LAT is essential for PLC-gamma activation and calcium influx generation. It has been recently reported that a conserved glycine residue preceding tyrosine 132 decreases its phosphorylation kinetics, which constitutes a mechanism for ligand discrimination. Here we confirm that a LAT mutant in which glycine 131 has been substituted by an aspartate (LAT(G131D)) increases phosphorylation of Tyr132, PLC-gamma activation and calcium influx generation. Interestingly, the LAT(G131D)mutant has a slower protein turnover while being equally sensitive to Fas-mediated protein cleavage by caspases. Moreover, J.CaM2 cells expressing LAT(G131D)secrete greater amounts of interleukin-2 (IL-2) in response to CD3/CD28 engagement. However, despite this increased IL-2 secretion, J.CaM2 cells expressing the LAT(G131D)mutant are more sensitive to inhibition of IL-2 production by pre-treatment with anti-CD3, which points to a possible role of this residue in the generation of anergy. Our results suggest that the increased kinetics of LAT Tyr132 phosphorylation could contribute to the establishment of T cell anergy, and thus constitutes an earliest known intracellular event responsible for the induction of peripheral tolerance
Rankings ISI: la universidad española en la Web of Science. 2001-2010
A partir de los datos recopilados para la elaboración de los Rankings ISI de las Universidades Españolas según Campos y Disciplinas Científicas (2ª ed. 2011) se presenta el siguiente informe. Su objetivo principal es ofrecer información que no aparece en el site de Rankings ISI por ello en primer ofrecemos un perfil general de la producción de la universidad española en su conjunto en las bases de datos WoS; asimismo, en segundo lugar, se presenta un resumen de la producción y el impacto de las universidades españolas y un análisis centrado en las posiciones en los diferentes campos y disciplinas científicas que las universidades lograron durante los períodos 2001-2010 y 2006-2010
ISI rankings of spanish universities according to fields and scientific disciplines (2nd ed. 2011)
Se presenta la actualización de los Rankings ISI de las universidades españolas según campos y disciplinas científicas (2ª ed. 2011). Se describen los cambios introducidos en este producto desde la 1ª edición entre los que figura la inclusión de 19 disciplinas científicas y la creación de una web dinámica. Asimismo se realizan diversos análisis bibliométricos de los distintos rankings. En primer lugar se muestran la actualización de los datos para los rankings de 12 campos científicos para el quinquenio 2006-2010 analizándose los cambios en las posiciones en relación con el quinquenio 2005-2009. En segundo lugar se presentan los resultados para las 19 disciplinas científicas en el quinquenio 2006-2010 analizándose por un lado la situación del sistema universitario en su conjunto y por otro mostrándose cuáles son las principales universidades. Se concluye que la 2ª edición mejora el análisis de las fortalezas y debilidades del sistema universitario español en lo que atañe a la generación de nuevo conocimiento mediante la publicación científica en el medio internacional, así como ayuda a identificar de una forma más precisa el papel desempeñado por las universidades españolas que destacan en ámbitos más específicos de la producción científica. Gracias a la introducción de dominios temáticos más reducidos que los campos científicos, se perfila mejor el nivel de excelencia de las universidades españolas en la producción de investigación.The update of the ISI rankings of Spanish universities according to fields and scientific disciplines (2nd ed. 2011) is presented. Specifically, in this second edition we focus on the inclusion of 19 new scientific disciplines and the creation of a dynamic new website. Various bibliometric analyses of the different rankings are also shown. Firstly, the updated data for the rankings on 12 scientific fields for the 2006-2010 period are presented focusing on the changes in the positions compared to the 2005-2009 period. Secondly, we present the results in the scientific disciplines during the 2006-2010 period, on the
one hand for the Spanish university system as a whole, and on the other hand showing the major universities in 19 new disciplines. Finally we conclude that the 2nd edition of the ISI Rankings improves the global analysis of strengths and weaknesses in the Spanish higher education system and more precisely profiles the performance of Spanish universities in more specific areas
Contenidos, métodos y representaciones
La Edad Moderna es un período fundamental para la comprensión del mundo y de la sociedad actual. Sin embargo, en España existe una gran distancia entre los libros de texto y las propuestas curriculares ofrecidas en los centros de educación secundaria y el ritmo que sigue la investigación y la innovación en este campo. Conscientes de esta situación, esta obra colectiva gira en torno a tres ejes vertebradores. En primer lugar, se abordan los contenidos; en segundo lugar, los métodos de enseñanza; y, en tercer lugar, las imágenes y las representaciones, muchas veces estereotipadas, existentes sobre esta época en nuestro presente. Los tres bloques recogen numerosas aportaciones tanto desde planteamientos teóricos y de investigación renovados como de propuestas didácticas claras y útiles con las que se pretende contribuir a avanzar en la enseñanza de la Edad Moderna en la Educación Secundaria.Índice
INTRODUCCIÓN. 15 pp.
Francisco García González, Cosme Jesús Gómez Carrasco, Ramón Cózar Gutiérrez y Pedro Martínez Gómez
1.LOS CONTENIDOS SOBRE LA EDAD MODERNA EN EDUCACIÓN SECUNDARIA. 21 pp.
A época moderna nos manuais escolares portugueses: um balanço entre história regulada, história ensinada e história desejada. 23 pp.
Cristina Maia
http://doi.org/10.18239/jornadas_2020.27.01
Análisis del currículum de Historia Moderna en Enseñanza Secundaria desde la pedagogía crítica. 39 pp.
Sofía Díaz de Greñu Domingo
http://doi.org/10.18239/jornadas_2020.27.0
SAR studies of epoxycurcuphenol derivatives on leukemia CT-CD4 cells
Bioactive natural products are a potential source of new pharmaceuticals since they offer new modes of
action and more specific activities. The use of derivatization also enables the optimal structure for their
biological activity to be determined. In this study several epoxycurcuphenol derivatives were synthesized.
The substitution pattern on the aromatic and oxirane rings was varied along with that at the benzylic
position and the length of the side chain was altered. These changes were made in order to gain a
deeper understanding of the structural requirements for activity. The biological activities of these compounds
were evaluated on the human leukemia cell line Jurkat using an antiproliferative assay. The activity
results and structural requirements are discussed
Immune modulation by the hepatitis C virus core protein
Hepatitis C virus (HCV) infection is currently the most important cause of chronic viral
hepatitis in the world and one of the most frequent indications for liver transplantation.
HCV uses different strategies to evade the innate and adaptive immune response,
and this evasion plays a key role in determining viral persistence. Several HCV viral
proteins have been described as immune modulators. In this review, we will focus on
the effect of HCV nucleocapsid core protein in the function of immune cells and its
correlation with the findings observed in HCV chronically infected patients. Effects on
immune cell function related to both extracellular and intracellular HCV core localization
will be considered. This review provides an updated perspective on the mechanisms
involved in HCV evasion related to one single HCV protein, which could become
a key tool in the development of new antiviral strategies able to control and/or eradicate
HCV infection.Ministerio de Educación y Ciencia (España) (SAF2009-09449); Consejería de Salud de la Junta de Andalucía (SAS 111206
Preparation and characterization of fluorescent CdS quantum dots used for the direct detection of GsT fusion proteins
Advances in the life sciences are now closely linked to the availability of new experimental tools that allow for the manipulation of biomolecules and the study of biological processes at the molecular level. In this context, we have optimized a synthesis process to obtain glutathione-capped fluorescent CdS nanoparticles to specifically detect Glutathione S-Transferase (GST) -tagged proteins. Using our method, based on five different heating steps, brightly fluorescent and biocompatible CdS quantum dots of different sizes can be obtained. QD optical behaviour has been evaluated studying both absorbance and fluorescence. For all the samples, the excitonic absorption onset clearly shows a blue shift at 512nm in comparison with that of bulk CdS, due to the quantum confinement effect. At increased average sizes of the nanocrystal, the emission fluorescent band shows a red shift, from 440nm to 540nm. Among different QD solutions, we demonstrate an expansion of the emission range up to ~100 nm, thus improving their features as biomarkers. Moreover we show that optimized glutathione-capped quantum dots can directly bind GST blotted onto polyvinylidene difluoride (PVDF) membranes, and thus are suitable for the direct detection of GST fusion proteins.Proyectos del Ministerio de Innovación y Ciencia (PN/PETRI/PR/2007‐019) y Junta de Andalucía (P08‐CTS‐04348
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