Luis González - Academia.edu (original) (raw)

Papers by Luis González

SummaryBackgroundA SARS-CoV-2 protein-based heterodimer vaccine, PHH-1V, has been shown to be saf... more SummaryBackgroundA SARS-CoV-2 protein-based heterodimer vaccine, PHH-1V, has been shown to be safe and welltolerated in healthy young adults in a first-in-human, Phase I/IIa study dose-escalation trial. Here, we report the interim results of the Phase IIb HH-2, where the immunogenicity and safety of a heterologous booster with PHH-1V is assessed versus a homologous booster with BNT162b2 at 14, 28 and 98 days after vaccine administration.MethodsThe HH-2 study is an ongoing multicentre, randomised, active-controlled, double-blind, non-inferiority Phase IIb trial, where participants 18 years or older who had received two doses of BNT162b2 were randomly assigned in a 2:1 ratio to receive a booster dose of vaccine —either heterologous (PHH-1V group) or homologous (BNT162b2 group)— in 10 centres in Spain. Eligible subjects were allocated to treatment stratified by age group (18-64 versus ≥65 years) with approximately 10% of the sample enrolled in the older age group. The primary endpoints...

La empresa Grupo Transformador de Llantas nace en el ano 2018 con la idea de ser una empresa prod... more La empresa Grupo Transformador de Llantas nace en el ano 2018 con la idea de ser una empresa productiva y rentable. Haciendo frente a la problematica ambiental, la empresa enfoca su produccion en el manejo de llantas usadas desechadas por diferentes ayuntamientos. Para ello, ha adoptado metodos novedosos de reciclaje de neumaticos. Sin embargo, al ser una empresa joven se ha encontrado con varios retos que limitan su productividad. Debido a esto, los accionistas decidieron adoptar algunas tecnicas exitosas para el analisis y mejora de procesos que son utilizadas por las diferentes industrias a nivel mundial: metodologia lean manufacturing, metodologia 5S, metodo de gestion kaizen, la implementacion de unidades de medicion, entre otras. El presente trabajo describe el proceso y resultado de la aplicacion de estas herramientas, pues a partir de esta estrategia se logro una mejora de 237% en la produccion. Tomando en cuenta que en las primeras mediciones del mes de diciembre de 2018 se...

Mycoplamsa genitalium es un patogeno humano causante de uretritis no gonococica y no causada por ... more Mycoplamsa genitalium es un patogeno humano causante de uretritis no gonococica y no causada por clamidias en hombres y de enfermedad pelvica inflamatoria y cervicitis. Los micoplasmas, ademas de ser muy interesantes para el estudio como celulas minimas (dado el pequeno tamano de su genoma), tambien presentan caracteristicas unicas solo presentes en este genero. En particular, se ha detectado la presencia de mecanismos de adhesion y de motilidad, que ademas de estar implicados en el mecanismo de infeccion, solo se encuentran en este genero. En especial, el mecanismo de motilidad de M. genitalium consta de una estructura polar que contiene un caracteristico citoesqueleto. Se conoce que este citoesqueleto esta formado por varias proteinas implicadas en el proceso de adhesion y motilidad. En los tres primeros capitulos de esta tesis se ha determinado el papel de tres de estas proteinas: MG219, MG318 (tambien llamada P32) y MG386. El estudio se ha realizado gracias a la obtencion de mut...

SummaryCurrent C0VID-19 vaccines have been associated with a decline in infection rates, preventi... more SummaryCurrent C0VID-19 vaccines have been associated with a decline in infection rates, prevention of severe disease and a decrease in mortality rates. However, SARS-CoV-2 variants are continuously evolving, and development of new accessible COVID-19 vaccines is essential to mitigate the pandemic. Here, we present data on preclinical studies in mice of a receptor-binding domain (RBD)-based recombinant protein vaccine (PHH-1V) consisting of an RBD fusion heterodimer comprising the B.1.351 and B.1.1.7 SARS-CoV-2 variants formulated in SQBA adjuvant, an oil-in-water emulsion. A prime-boost immunisation with PHH-1V in BALB/c and K18-hACE2 mice induced a CD4+and CD8+T cell response and RBD-binding antibodies with neutralising activity against several variants, and also showed a good tolerability profile. Significantly, RBD fusion heterodimer vaccination conferred 100% efficacy, preventing mortality in SARS-CoV-2 infected K18-hACE2 mice, but also reducing Beta, Delta and Omicron infectio...

Acta Crystallographica Section D Structural Biology, 2020

Mycoplasma hyopneumoniaeis a prokaryotic pathogen that colonizes the respiratory ciliated epithel... more Mycoplasma hyopneumoniaeis a prokaryotic pathogen that colonizes the respiratory ciliated epithelial cells in swine. Infected animals suffer respiratory lesions, causing major economic losses in the porcine industry. Characterization of the immunodominant membrane-associated proteins fromM. hyopneumoniaemay be instrumental in the development of new therapeutic approaches. Here, the crystal structure of P46, one of the main surface-antigen proteins, fromM. hyopneumoniaeis presented and shows N- and C-terminal α/β domains connected by a hinge. The structures solved in this work include a ligand-free open form of P46 (3.1 Å resolution) and two ligand-bound structures of P46 with maltose (2.5 Å resolution) and xylose (3.5 Å resolution) in open and closed conformations, respectively. The ligand-binding site is buried in the cleft between the domains at the hinge region. The two domains of P46 can rotate with respect to each other, giving open or closed alternative conformations. In agree...

ACS synthetic biology, Jan 22, 2018

Functional genomics studies in minimal mycoplasma cells enable unobstructed access to some of the... more Functional genomics studies in minimal mycoplasma cells enable unobstructed access to some of the most fundamental processes in biology. Conventional transposon bombardment and gene knockout approaches often fail to reveal functions of genes that are essential for viability, where lethality precludes phenotypic characterization. Conditional inactivation of genes is effective for characterizing functions central to cell growth and division, but tools are limited for this purpose in mycoplasmas. Here we demonstrate systems for inducible repression of gene expression based on clustered regularly interspaced short palindromic repeats-mediated interference (CRISPRi) in Mycoplasma pneumoniae and synthetic Mycoplasma mycoides, two organisms with reduced genomes actively used in systems biology studies. In the synthetic cell, we also demonstrate inducible gene expression for the first time. Time-course data suggest rapid kinetics and reversible engagement of CRISPRi. Targeting of six select...

DNA research : an international journal for rapid publication of reports on genes and genomes, 2016

Mycoplasma genitalium is an appealing model of a minimal cell and synthetic biology study, and it... more Mycoplasma genitalium is an appealing model of a minimal cell and synthetic biology study, and it was one of the first organisms whose genome was fully sequenced and chemically synthesized. Despite its usefulness as a model organism, many genetic tools well established for other microorganisms are not currently available in mycoplasmas. We have developed several vectors to adapt the Cre-lox technology for genome engineering in M. genitalium, providing an all-in-one construct that could be also useful to obtain unmarked genetic modifications in many other slow growing microorganisms. This construct contains a modified promoter sequence based in TetR system that exhibits an enhanced control on Cre recombinase expression, virtually abolishing the presence of this recombinase in the absence of inducer. This allows to introduce the Cre recombinase gene and the desired genetic modification in a single transformation step. In addition, this inducible promoter may be a very promising tool f...

Vaccine, Jan 6, 2016

Streptococcus uberis is a worldwide pathogen that causes intramammary infections in dairy cattle.... more Streptococcus uberis is a worldwide pathogen that causes intramammary infections in dairy cattle. Because virulence factors determining the pathogenicity of S. uberis have not been clearly identified so far, a commercial vaccine is not yet available. Different S. uberis strains have the ability to form biofilm in vitro, although the association of this kind of growth with the development of mastitis is unknown. The objective of this study was to evaluate the potential use as vaccine antigens of proteins from S. uberis biofilms, previously identified by proteomic and immunological analyses. The capability of eliciting a protective immune response by targeted candidates was assayed on a murine model. Sera from rabbits immunized with S. uberis biofilm preparations and a convalescent cow intra-mammary infected with S. uberis were probed against cell wall proteins from biofilm and planktonic cells previously separated by two-dimensional gel electrophoresis. Using rabbit immunized serum, ...

Molecular Microbiology, 2016

The cell wall-less bacterium Mycoplasma genitalium uses specialized adhesins located at the termi... more The cell wall-less bacterium Mycoplasma genitalium uses specialized adhesins located at the terminal organelle to adhere to host cells and surfaces. The terminal organelle is a polar structure protruding from the cell body that is internally supported by a cytoskeleton and also has an important role in cell motility. We have engineered a M. genitalium null mutant for MG491 protein showing a massive downstream destabilization of proteins involved in the terminal organelle organization. This mutant strain exhibited striking similarities with the previously isolated MG_218 null mutant strain. Upon introduction of an extra copy of MG_318 gene in both strains, the amount of main adhesins P140 and P110 dramatically increased. These strains were characterized by microcinematography, epifluorescence microscopy and cryo-electron microcopy, revealing the presence of motile cells and filaments in the absence of many proteins considered essential for cell adhesion and motility. These results indicate that adhesin complexes play a major role in the motile machinery of M. genitalium and demonstrate that the rod element of the cytoskeleton core is not the molecular motor propelling mycoplasma cells. These strains containing a minimized motile machinery also provide a valuable cell model to investigate the adhesion and gliding properties of this human pathogen. This article is protected by copyright. All rights reserved.

Lecture Notes in Computer Science

In this article, with the aim to avoid the loss of information that occurs in the usual one-versu... more In this article, with the aim to avoid the loss of information that occurs in the usual one-versus-one SVM decomposition procedure of the two-phases (decomposition, reconstruction) multi-classification scheme tri-class SVM approach is addressed. As the most relevant result, it will be demonstrated the robustness improvement of the proposed scheme based on tri-class machine versus that based on the bi-class machine.

BMC medical genetics, Jan 21, 2004

The present study is an analysis of the frequencies of HLA-A and -B antigens and HLA haplotypes i... more The present study is an analysis of the frequencies of HLA-A and -B antigens and HLA haplotypes in two groups of individuals homozygous for the two main HFE mutations (C282Y and H63D) and a group heterozygous for the S65C mutation. The study population includes: 1123 healthy individuals, 100 homozygous for the C282Y mutation, 138 homozygous for the H63D mutation and 17 heterozygous for the S65C mutation. HFE and HLA alleles were detected using DNA-based and microlymphocytotoxicity techniques respectively. An expected significant association between C282Y and the HLA-A3/B7 haplotype was found, but other HLA haplotypes carrying the -A3 antigen were found: HLA-A3/B62 and HLA-A3/B44. Also, a significant association between H63D mutation and HLA-A29/B44 haplotype was found, and again other HLA haplotypes carrying the HLA-A29 antigen were also found: HLA-A29/B14 and HLA-A29/B62. In addition, the S65C mutation seems to be associated with a HLA haplotype carrying the HLA-A26 antigen. These ...

Persona y Bioética, 2010

requerimientos económicos, políticos y sociales de la comunidad. Sin embargo, en el ámbito de las... more requerimientos económicos, políticos y sociales de la comunidad. Sin embargo, en el ámbito de las profesiones relacionadas con la salud, dicho concepto trasciende este entorno al entrar en juego la perspectiva ética en la que, idealmente, el profesional de la salud antepone los intereses de los demás a los propios. De esta manera, la profesión médica se convierte en una forma de vida regida por principios éticos y guiada por los más altos estándares de profesionalismo, constituyéndose en una vocación y no en una simple ocupación. Para devolver a la profesión médica su vocación distintiva, es esencial analizar las motivaciones intrínsecas y la ética de vida de las nuevas generaciones de médicos y, a partir de ahí, desarrollar —a manera de competencias— conocimientos, habilidades, actitudes y valores que propicien el desarrollo del profesionalismo, logrando fi nalmente una mejor relación médico-paciente, situando el bienestar de este último como principal interés.

The Breast Journal, 2009

Due to scheduled maintenance access to the Wiley Online Library may be disrupted as follows: Satu... more Due to scheduled maintenance access to the Wiley Online Library may be disrupted as follows: Saturday, 16 October - New York 0700 EDT to 0900 EDT; London 1200 BST to 1400 BST; Singapore 1900 SGT to 2100 SGT. ... *Correspondence: Address correspondence ...

PLoS ONE, 2014

A number of adherent mycoplasmas have developed highly complex polar structures that are involved... more A number of adherent mycoplasmas have developed highly complex polar structures that are involved in diverse aspects of the biology of these microorganisms and play a key role as virulence factors by promoting adhesion to host cells in the first stages of infection. Attachment activity of mycoplasma cells has been traditionally investigated by determining their hemadsorption ability to red blood cells and it is a distinctive trait widely examined when characterizing the different mycoplasma species. Despite the fact that protocols to qualitatively determine the hemadsorption or hemagglutination of mycoplasmas are straightforward, current methods when investigating hemadsorption at the quantitative level are expensive and poorly reproducible. By using flow cytometry, we have developed a procedure to quantify rapidly and accurately the hemadsorption activity of mycoplasmas in the presence of SYBR Green I, a vital fluorochrome that stains nucleic acids, allowing to resolve erythrocyte and mycoplasma cells by their different size and fluorescence. This method is very reproducible and permits the kinetic analysis of the obtained data and a precise hemadsorption quantification based on standard binding parameters such as the dissociation constant K d. The procedure we developed could be easily implemented in a standardized assay to test the hemadsorption activity of the growing number of clinical isolates and mutant strains of different mycoplasma species, providing valuable data about the virulence of these microorganisms.

Personality and Individual Differences, 2009

The authors examined the validity of the Spanish-language version of the dispositional resistance... more The authors examined the validity of the Spanish-language version of the dispositional resistance to change (RTC) scale. First, the structural validity of the new questionnaire was evaluated using a nested sequence of confirmatory factor analyses. Second, the external validity of the questionnaire was assessed, using the four higher-order values of the Schwartz's theory and the four dimensions of the RTC scale: routine seeking, emotional reaction, short-term focus and cognitive rigidity. A sample of 553 undergraduate students from Mexico and Spain was used in the analyses. The results confirmed both the construct structure and the external validity of the questionnaire.

Journal of the Optical Society of America A, 2006

Generally, the analysis of corneal topography involves fitting the raw data to a parametric geome... more Generally, the analysis of corneal topography involves fitting the raw data to a parametric geometric model that includes a regular basis surface, plus some sort of polynomial expansion to adjust the more irregular residual component. So far, these parametric models have been used in their canonical form, ignoring that the observation (keratometric) coordinate system is different from corneal axes of symmetry. Here we propose, instead, to use the canonical form when the topography is referenced to the intrinsic corneal system of coordinates, defined by its principal axes of symmetry. This idea is implemented using the general expression of an ellipsoid to fit the raw data given by the instrument. Then, the position and orientation of the three orthogonal semiaxes of the ellipsoid, which define the intrinsic Cartesian system of coordinates for normal corneas, can be identified by passing to the canonical form, by standard linear algebra. This model has been first validated experimentally obtaining significantly lower values for rms fitting error as compared with previous standard models: spherical, conical, and biconical. The fitting residual was then adjusted by a Zernike polynomial expansion. The topographies of 123 corneas were analyzed obtaining their radii of curvature, conic constants, Zernike coefficients, and the direction and position of the optical axis of the ellipsoid. The results were compared with those obtained using the standard models. The general ellipsoid model provides more negative values for the conic constants and lower apex radii (more prolate shapes) than the standard models applied to the same data. If the data are analyzed using standard models, the resulting mean shape of the cornea is consistent with previous studies, but when using the ellipsoid model we find new interesting features: The mean cornea is a more prolate ellipsoid (apical power 50 D), the direction of the optical axis is about 2.3°nasal, and the residual term shows three Zernike coefficients significantly higher than zero (third-order trefoil and fourthand sixth-order spherical). These three nonzero Zernike coefficients are responsible for most of the higherorder aberrations of the average cornea. Finally, we propose and implement a simple method for threedimensional registration of corneal topographies, passing from the general to the canonical form of the ellipsoid.