Quantitative Analysis of differential phosphorylation in a PKC1 overexpression

Comunicaciones a congreso

Incorporation of ZnO Nanoparticles into Soy Protein-Based Bioplastics to Improve Their Functional Properties

The union of nanoscience (nanofertilization) with controlled release bioplastic systems could be a key factor for the improvement of fertilization in horticulture, avoiding excessive contamination and reducing the price of the products found in the current market. In this context, the objective of this work was to incorporate ZnO nanoparticles in soy protein-based bioplastic processed using injection moulding. Thus, the concentration of ZnO nanoparticles (0 wt%, 1.0 wt%, 2.0 wt%, 4.5 wt%) and mould temperature (70 °C, 90 °C and 110 °C) were evaluated through a mechanical (flexural and tensile properties), morphological (microstructure and nanoparticle distribution) and functional (water uptake capacity, micronutrient release and biodegradability) characterization. The results indicate that these parameters play an important role in the final characteristics of the bioplastics, being able to modify them. Ultimately, this study increases the versatility and functionality of the use of bioplastics and nanofertilization in horticulture, helping to prevent the greatest environmental impact caused.Ministerio de Ciencia e Innovación of the Spanish Government and FEDER (UE), grant number RTI2018-097100-B-C2

Body mass index best predicts recovery of recombinant factor VIII in underweight to obese patients with severe haemophilia A

Background Factor VIII (FVIII) products are usually dosed according to body weight (BW). This may lead to under- or over-dosing in underweight or obese patients, respectively. Objective This article evaluates the pharmacokinetics (PK) of recombinant FVIII concentrate, particularly recovery, in relation to body mass index (BMI) and other body composition descriptors. Materials and Methods Thirty-five previously treated adults with severe haemophilia A from five BMI categories (underweight, normal, overweight, obese class I and II/III) were included. PK was evaluated after 50 IU per kilogram of BW single-dose recombinant FVIII (turoctocog alfa). The body composition variable was based on measurements of weight, height, bioimpedance analysis, and dual-energy X-ray absorptiometry. A dosing model was derived to achieve similar peak FVIII activity levels across BMI categories. Results A statistically significant positive association between BMI and C30min, IR30min, and AUC0–inf was observed; CL and Vss showed a significant negative association with BMI; t½ was independent of BMI and other parameters. The dosing model introduced a correction factor ‘M’ for each BMI category, based on linear regression analysis of C30min against BMI, which ranged from 0.55 for underweight to 0.39 for obese class II/III. This model achieved similar peak FVIII activity levels across BMI categories, estimating an average dose adjustment of þ243.3 IU (underweight) to –1,489.6 IU (obese class II/III) to achieve similar C30min. Conclusion BMI appears to be the best predictor of recombinant FVIII recovery; however, PK endpoints were also dependent on other body composition variables. The model demonstrated that dosing can be adjusted for individual BMI to achieve better FVIII predictability across BMI categoriesThis work was funded by Novo Nordisk A/S (Bagsværd, Denmark)

Development of biopolymer-based hydrogels from pork collagen for Tissue Engineering

El desarrollo de biomateriales abarca tres etapas diferentes: selección de materia prima, técnica de procesado y caracterización del producto final. Entre ellos, los hidrogeles se han presentado como candidatos potenciales en aplicaciones farmacéuticas y biomédicas por sus propiedades fisicoquímicas. La mayor parte de los estudios sobre hidrogeles se basan en polímeros naturales por sus excelentes propiedades biológicas. Sin embargo, su procesado es complejo, puesto que se han de controlar parámetros como el tiempo de gelificación, el pH de la disolución y la temperatura de gelificación. No obstante, también es importante seleccionar y caracterizar adecuadamente la materia prima, ya que afecta a las propiedades de los hidrogeles obtenidos. Por tanto, el objetivo de este trabajo es optimizar el proceso de fabricación de hidrogeles de colágeno, evaluando tanto la materia prima a utilizar como los parámetros de procesado que pueden influir en el proceso. Dicha evaluación se ha llevado a cabo mediante el estudio de sus propiedades mecánicas, morfológicas y biológicas. Los resultados muestran como los parámetros definidos durante el procesado del hidrogel son claves en las propiedades finales obtenidas. Además, algunos de ellos presentan adecuadas propiedades para su potencial uso en Ingeniería de Tejidos.The development of biomaterials encompasses three different stages: selection of the raw material, processing technique and characterization of the final product. Among them, hydrogels have been presented as potential candidates in pharmaceutical and biomedical applications due to their physicochemical properties. Most of the studies about hydrogels are based on natural polymers for their excellent biological properties. However, their processing is complex, since several parameters need to be controlled such as gelation time, pH of the solution and gelation temperature. Nevertheless, it is also important to select and characterize the raw material before the fabrication of the hydrogels. Therefore, the objective of the work is to optimize the hydrogel fabrication, evaluating both the raw material to be used and the processing parameters that can influence the process. This evaluation has been carried out by studying its mechanical, morphological and biological properties. Results show how the parameters defined during the hydrogel processing are essential in the final properties obtained. In addition, some of the systems have suitable properties for their potential use in Tissue Engineering.Ministerio de Ciencia e Innovación-Agencia Estatal de Investigación (España) RTI2018-097100-B-C21Ministerio de Educación y Formación Profesional (España) FPU2017/0171

Biocompatible and Thermoresistant Hydrogels Based on Collagen and Chitosan

Hydrogels are considered good biomaterials for soft tissue regeneration. In this sense, collagen is the most used raw material to develop hydrogels, due to its high biocompatibility. However, its low mechanical resistance, thermal stability and pH instability have generated the need to look for alternatives to its use. In this sense, the combination of collagen with another raw material (i.e., polysaccharides) can improve the final properties of hydrogels. For this reason, the main objective of this work was the development of hydrogels based on collagen and chitosan. The mechanical, thermal and microstructural properties of the hydrogels formed with different ratios of collagen/chitosan (100/0, 75/25, 50/50, 25/75 and 0/100) were evaluated after being processed by two variants of a protocol consisting in two stages: a pH change towards pH 7 and a temperature drop towards 4 °C. The main results showed that depending on the protocol, the physicochemical and microstructural properties of the hybrid hydrogels were similar to the unitary system depending on the stage carried out in first place, obtaining FTIR peaks with similar intensity or a more porous structure when chitosan was first gelled, instead of collagen. As a conclusion, the synergy between collagen and chitosan improved the properties of the hydrogels, showing good thermomechanical properties and cell viability to be used as potential biomaterials for Tissue Engineering.Ministerio de Ciencia e Innovación RTI2018-097100-B-C2

Fructose crosslinked scaffolds obtained with collagen via freeze-drying for Tissue Engineering

La Ingeniería de Tejidos ha propiciado el desarrollo de andamios con mejores propiedades que pueden cumplir su propósito de una mejor regeneración de tejidos, mejorando consecuentemente la calidad de vida de las personas. Los andamios son matrices cuya función principal es dar soporte a la adhesión celular y su posterior crecimiento, lo que lleva a la regeneración del tejido dañado. El colágeno es una de las proteínas más abundantes en animales y biopolímero ampliamente utilizado en Ingeniería de Tejidos, por su estructura, biocompatibilidad y la facilidad de su modificación y procesabilidad. En este estudio se prepararán y caracterizarán andamios de colágeno con diferentes concentraciones y técnicas de procesamiento, mediante la obtención de hidrogeles y aerogeles, atendiendo especialmente a su morfología y propiedades mecánicas. Además, se utilizó fructosa como agente químico de entrecruzamiento para estudiar su influencia en las propiedades de los andamios. Los resultados obtenidos revelaron que los andamios con mayores concentraciones de colágeno eran más rígidos y deformables. Comparando ambos sistemas, los aerogeles eran más rígidos pero los hidrogeles, aunque más deformables y con mayor homogeneidad de tamaño de poro. La adición de fructosa produjo un ligero aumento de la deformación crítica, junto con un aumento del módulo elástico.Tissue Engineering has led to the development of this field by designing scaffolds with better properties that can fulfill its purpose of better tissue regeneration, consequently improving people’s quality of life. Scaffolds are matrix, predominantly composed by polymeric materials, which main function is giving support to cell adhesion and the subsequently growth, leading to the regeneration of the damaged tissue. Collagen is one of the most abundant proteins in animals and widely used biopolymer in Tissue Engineering, due to its structure, biocompatibility and the ease of its modification and processability. In this study, collagen scaffolds with different concentrations and processing techniques, by obtaining hydrogels and aerogels, will be prepared and then characterized, specially looking at its morphology and mechanical properties. Moreover, fructose was added as a chemical crosslinking agent to study the influence on scaffolds’ properties. The results obtained revealed that scaffolds with higher collagen concentrations were stiffer and more deformable. Comparing both systems, aerogels were stiffer but hydrogels were more deformable and with higher pore size homogeneity. Fructose addition produced a slight increase in the critical strain, together with an increase in the elastic modulus.MINECO/AEI/FEDER, EU RTI2018-097100-B-C21Ministerio de Educación y Formación Profesional FPU2017/0171

Educating in antimicrobial resistance awareness: adaptation of the Small World Initiative program to service-learning.

The Small World Initiative (SWI) and Tiny Earth are a consolidated and successful education programs rooted in the USA that tackle the antibiotic crisis by a crowdsourcing strategy. Based on active learning, it challenges young students to discover novel bioactive-producing microorganisms from environmental soil samples. Besides its pedagogical efficiency to impart microbiology content in academic curricula, SWI promotes vocations in research and development in Experimental Sciences and, at the same time, disseminates the antibiotic awareness guidelines of the World Health Organization. We have adapted the SWI program to the Spanish academic environment by a pioneering hierarchic strategy based on service-learning that involves two education levels (higher education and high school) with different degrees of responsibility. Throughout the academic year, 23 SWI teams, each consisting of 3-7 undergraduate students led by one faculty member, coordinated off-campus programs in 22 local high schools, involving 597 high school students as researchers. Post-survey-based evaluation of the program reveals a satisfactory achievement of goals: acquiring scientific abilities and general or personal competences by university students, as well as promoting academic decisions to inspire vocations for science- and technology-oriented degrees in younger students, and successfully communicating scientific culture in antimicrobial resistance to a young stratum of society

Unraveling the effect of silent, intronic and missense mutations on VWF splicing : contribution of next generation sequencing in the study of mRNA

Large studies in von Willebrand disease patients, including Spanish and Portuguese registries, led to the identification of >250 different mutations. It is a challenge to determine the pathogenic effect of potential splice site mutations on VWF mRNA. This study aimed to elucidate the true effects of 18 mutations on VWF mRNA processing, investigate the contribution of next-generation sequencing to in vivo mRNA study in von Willebrand disease, and compare the findings with in silico prediction. RNA extracted from patient platelets and leukocytes was amplified by RT-PCR and sequenced using Sanger and next generation sequencing techniques. Eight mutations affected VWF splicing: c.1533+1G>A, c.5664+2T>C and c.546G>A (p.=) prompted exon skipping; c.3223-7_3236dup and c.7082-2A>G resulted in activation of cryptic sites; c.3379+1G>A and c.7437G>A) demonstrated both molecular pathogenic mechanisms simultaneously; and the p.Cys370Tyr missense mutation generated two aberrant transcripts. Of note, the complete effect of three mutations was provided by next generation sequencing alone because of low expression of the aberrant transcripts. In the remaining 10 mutations, no effect was elucidated in the experiments. However, the differential findings obtained in platelets and leukocytes provided substantial evidence that four of these would have an effect on VWF levels. In this first report using next generation sequencing technology to unravel the effects of VWF mutations on splicing, the technique yielded valuable information. Our data bring to light the importance of studying the effect of synonymous and missense mutations on VWF splicing to improve the current knowledge of the molecular mechanisms behind von Willebrand disease. identifier:02869074