Material-driven fibronectin assembly for high-efficiency presentation of growth factors

Growth factors (GFs) are powerful signaling molecules with the potential to drive regenerative strategies, including bone repair and vascularization. However, GFs are typically delivered in soluble format at supraphysiological doses because of rapid clearance and limited therapeutic impact. These high doses have serious side effects and are expensive. Although it is well established that GF interactions with extracellular matrix proteins such as fibronectin control GF presentation and activity, a translation-ready approach to unlocking GF potential has not been realized. We demonstrate a simple, robust, and controlled material-based approach to enhance the activity of GFs during tissue healing. The underlying mechanism is based on spontaneous fibrillar organization of fibronectin driven by adsorption onto the polymer poly(ethyl acrylate). Fibrillar fibronectin on this polymer, but not a globular conformation obtained on control polymers, promotes synergistic presentation of integrin-binding sites and bound bone morphogenetic protein 2 (BMP-2), which enhances mesenchymal stem cell osteogenesis in vitro and drives full regeneration of a nonhealing bone defect in vivo at low GF concentrations. This simple and translatable technology could unlock the full regenerative potential of GF therapies while improving safety and cost-effectiveness

Understanding Nanopore Window Distortions in the Reversible Molecular Valve Zeolite RHO

Molecular valves are becoming popular for potential biomedical applications. However, little is known concerning their performance in energy and environmental areas. Zeolite RHO shows unique pore deformations upon changes in hydration, cation siting, cation type, or temperature-pressure conditions. By varying the level of distortion of double eight-rings, it is possible to control the adsorption properties, which confer a molecular valve behavior to this material. We have employed interatomic potentials-based simulations to obtain a detailed atomistic view of the structural distortion mechanisms of zeolite RHO, in contrast with the averaged and space group restricted information provided by diffraction studies. We have modeled four aluminosilicate structures, containing Li$^+$, Na$^+$, K$^+$, Ca$^{2+}$, and Sr$^{2+}$ cations. The distortions of the three different zeolite rings are coupled, and the six- and eight-membered rings are largely flexible. A large dependence on the polarizing power of the extra-framework cations and with the loading of water has been found for the minimum aperture of the eight-membered rings that control the nanovalve effect. The calculated energy barriers for moving the cations across the eight-membered rings are very high, which explains the experimentally observed slow kinetics of the phase transition as well as the appearance of metastable phases

Down-regulation of a pectin acetylesterase gene modifies strawberry fruit cell wall pectin stracture and increases fruit firmness

Antisense-mediated down-regulation of several fruit-specific genes has previously demonstrated how the cell wall disassembly in strawberry fruit is mediated by a series of enzymes that act sequentially (Posé et al. 2011). An interesting example, the silencing of the polygalacturonase gene FaPG1, was also related with a significant increase of the post-harvest strawberry fruit firmness (Posé et al. 2013). Our research group has isolated a pectin acetylesterase gene, FaPAE1, which expression is enhanced during strawberry ripening. The main goal of this work was to elucidate the role of the degree of acetylation in cell wall integrity and fruit firmness through the antisense-mediated down-regulation of FaPAE1 in strawberry plants. Several transgenics lines were generated and 5 of them produced fruits 5-15% firmer than controls. Cell wall from ripe fruits was isolated from two independent transgenic lines and a control line, and sequentially extracted with different solvents (PAW, H2O, CDTA, Na2CO3). Modifications in fraction yield, its sugar composition and the degree of acetylation in each fraction were determined. Higher amounts of CDTA and Na2CO3 fractions were obtained in transgenic fruits, suggesting a decreased pectin solubilization as results of FaPAE1 silencing. Accordingly, the degree of acetylation of the Na2CO3-soluble pectins was greater in the transgenic lines than the control, but the opposite result was found in pectins from the CDTA fraction. These results suggest that PAE is preferentially active in pectis that are tightly bound to the cellulose-hemicellulose network and its activity could reduce the complexity of the cell wall structure, allowing that other hydrolytic enzymes could access the pectin chains. Thus, the increased fruit firmness observed in the transgenic FaPAE1 lines could be attributed to the direct effect of the silencing of the PAE enzyme and also to the indirect effect that the increase of the degree of acetylation of pectins has on the activity of other enzymes involved in the cell wall degradation. * Posé et al. (2011). Genes, Genomes and Genomics, 5 (Special Issue 1):40-48 * Posé et al. (2013). Plant Physiology, 150: 1022-1032 We acknowledge support from the Spanish Ministry of Economy and competitivity and Feder EU Funds (grant reference AGL2011-24814), FPI fellowships support for SP (BES-2006-13626) and CP (BES-2009027985), and grant "Ramón y Cajal" support for AJMA (RYC-2011-08839).Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Comparative study of green sub- and supercritical processes to obtain carnosic acid and carnosol-enriched rosemary extracts with in vitro anti-proliferative sctivity on colon cancer cells

In the present work, four green processes have been compared to evaluate their potential to obtain rosemary extracts with in vitro anti-proliferative activity against two colon cancer cell lines (HT-29 and HCT116). The processes, carried out under optimal conditions, were: (1) pressurized liquid extraction (PLE, using an hydroalcoholic mixture as solvent) at lab-scale; (2) Single-step supercritical fluid extraction (SFE) at pilot scale; (3) Intensified two-step sequential SFE at pilot scale; (4) Integrated PLE plus supercritical antisolvent fractionation (SAF) at pilot scale. Although higher extraction yields were achieved by using PLE (38.46% dry weight), this extract provided the lowest anti-proliferative activity with no observed cytotoxic effects at the assayed concentrations. On the other hand, extracts obtained using the PLE + SAF process provided the most active rosemary extracts against both colon cancer cell lines, with LC50 ranging from 11.2 to 12.4 µg/mL and from 21.8 to 31.9 µg/mL for HCT116 and HT-29, respectively. In general, active rosemary extracts were characterized by containing carnosic acid (CA) and carnosol (CS) at concentrations above 263.7 and 33.9 mg/g extract, respectively. Some distinct compounds have been identified in the SAF extracts (rosmaridiphenol and safficinolide), suggesting their possible role as additional contributors to the observed strong anti-proliferative activity of CA and CS in SAF extracts.This work was supported by the projects AGL2014-53609-P (Ministerio de Economía y Competitividad, Spain) and S2013/ABI-2728 (Comunidad de Madrid).We acknowledge support by the CSIC Open Access Publication Initiative through its Unit of Information Resources for Research (URICI)

Creencias sobre el ‘amor’ en la pareja: Estudio cualitativo en alumnado universitario de diferentes contextos geográficos

El amor y el amor romántico constituyen elementos importantes en la vida de las personas y, por ello, son también temas de interés para las ciencias, especialmente, para las ciencias sociales y de la salud. El objetivo de este trabajo es profundizar en el conocimiento del concepto de amor y las creencias que lo sostienen entre el alumnado universitario, empleando para ello estrategias cualitativas (grupos de discusión) y aportando como novedad la comparación entre alumnado de dos universidades ubicadas en dos contextos geográficos diferentes. Los resultados obtenidos muestran que las creencias en el amor y la aceptación de los mitos del amor romántico son más diferentes entre chicos y chicas que entre entornos geográficos, contribuyendo, por tanto, a consolidar la idea de que el amor es una experiencia fuertemente generizada.Love and romantic love are important elements in people's lives and are therefore also subjects of interest to the science, especially social and health sciences. The aim of this work is to deepen the knowledge of the concept of love, and the beliefs that sustain it among university students, using qualitative strategies (discussion groups) and contributing as a novelty the comparison between students of two universities located in two different geographical contexts. The results obtained show that beliefs in love and acceptance of the myths of romantic love are more different between boys and girls than between geographic contexts, thus contributing to consolidate the idea that love is a strongly generized experience

Genome-wide association studies (GWAS) and their importance in asthma

[EN] Asthma is a complex disease determined by the interaction of different genes and environmental factors. The first genetic investigations in asthma were candidate gene association studies and linkage studies. In recent years research has focused on association studies that scan the entire genome without any prior conditioning hypothesis: the so-called genome-wide association studies (GWAS). The first GWAS was published in 2007, and described a new locus associated to asthma in chromosome 17q12-q21, involving the ORMDL3, GSDMB and ZPBP2 genes (a description of the genes named in the manuscript are listed in Table 1). None of these genes would have been selected in a classical genetic association study since it was not known they could be implicated in asthma. To date, a number of GWAS studies in asthma have been made, with the identification of about 1000 candidate genes. Coordination of the different research groups in international consortiums and the application of new technologies such as new generation sequencing will help discover new implicated genes and improve our understanding of the molecular mechanisms underlying the disease.FEDER funds; Junta de Castilla y León; Fundación Botín-Universidad de Salamanca; Sociedad Española de Alergología e Inmunología Clínica; Fundación Salud 200

Assessing the Mediterranean diet adherence during pregnancy: Practical considerations based on the associations with cardiometabolic risk

Objective: The aim of the present study was to provide practical considerations for assessing MD adherence during pregnancy based on the association with cardiometabolic risk. Study design: Longitudinal study. Main outcome measures: A food frequency questionnaire was fulfilled by 152 pregnant women at the 16th gestational week (g.w.). We calculated the Mediterranean Food Pattern (MFP), the MD Scale (MDScale), the Short MD questionnaire (SMDQ), the MD Score (MedDietScore), and the MD scale for pregnant women (MDS-P). The cardiometabolic risk score consisted of pre-pregnancy body mass index, blood pressure, glucose, triglycerides, and high-density lipoprotein-cholesterol (at 16th and 34th g.w.). Results: Multiple linear regression models showed that the MFP, the MedDietScore, and the SMDQ were associated with lower cardiometabolic risk at the 16th and 34th g.w. (β’s: −0.193 to −0.415, all p < 0.05); and the MDS-P at the 34th g.w. (β = −0.349, p < 0.01). A comparison of these models with the J test showed that the MFP and the MedDietScore outperformed the SMDQ at the 16th g.w. (p's < 0.05); while the MedDietScore outperformed the SMDQ, MFP, and MDS-P (p's < 0.05) at the 34th g.w. Receiver-Operating-Characteristic-derived thresholds for the MFP, MedDietScore and MDS-P indices were 21, 30, and 6 points, respectively, to identify women with high cardiometabolic risk. Conclusion: The MFP and MedDietScore are recommended to assess MD adherence during pregnancy, as these showed the strongest associations with cardiometabolic risk. Our validated thresholds might assist in the detection of poor dietary patterns during pregnancy