La ruta de MAPK de integridad celular es antagonista de la GTPasa Rho1 en la levadura de fisión Schizosaccharomyces pombe

Trabajo presentado al "XXIII Congreso Nacional de Microbiología" celebrado en Salamanca del 11 al 14 de julio de 2011.-- et al.Peer Reviewe

Spatial Regulation of Cdc42 During Cytokinesis

5 pages, 2 figures.-- PMID: 17637568 [PubMed].-- Printed version published on Jul 15, 2007.Cdc42 GTPase plays a critical role in the establishment of cell polarity in most eukaryotic organisms. Cdc42 active state, as that of other GTPases, depends on the bound nucleotide. The protein with GTP is active, and only in this state can it interact with different target effector proteins. The spatio-temporal control of Cdc42 activity is therefore necessary to generate growth polarity. In fission yeast cells, Cdc42 mainly localizes to the division area, and also to the growing tips and to some internal membranes. While the role of Cdc42 in apical growth is well defined, no role has been described for Cdc42 in the process of cell division. Fission yeast Cdc42 activity is regulated by two specific guanidine nucleotide exchange factors (GEFs), Scd1, and Gef1. We discuss here how Hob3, a BAR domain containing protein similar to human BIN3 and S. cerevisiae Rsv161, may be required to recruit Cdc42 to the cell division site as well as for the activation of this GTPase mediated by Gef1. We also discuss the possible role of Cdc42 in the contraction of the actomyosin ring necessary for cytokinesis.This work was supported by Grant BIO2004-0834 from the Comision Interministerial de Ciencia y Tecnología, Spain.Peer reviewe

Influence of a Concurrent Exercise Training Intervention during Pregnancy on Maternal and Arterial and Venous Cord Serum Cytokines: The GESTAFIT Project

The aim of the present study was to analyze the influence of a supervised concurrent exercise-training program, from the 17th gestational week until delivery, on cytokines in maternal (at 17th and 35th gestational week, and at delivery) and arterial and venous cord serum. Fifty-eight Caucasian pregnant women (age: 33.5 +/- 4.7 years old, body mass index: 23.6 +/- 4.1kg/m(2)) from the GESTAFIT Project (exercise (n = 37) and control (n = 21) groups) participated in this quasi-experimental study (per-protocol basis). The exercise group followed a 60-min 3 days/week concurrent (aerobic-resistance) exercise-training from the 17th gestational week to delivery. Maternal and arterial and venous cord serum cytokines (fractalkine, interleukin (IL)-1 beta, IL-6, IL-8, IL-10, interferon (IFN)-gamma, and tumor necrosis factor (TNF)-alpha) were assessed using Luminex xMAP technology. In maternal serum (after adjusting for the baseline values of cytokines), the exercise group decreased TNF-alpha (from baseline to 35th week, p = 0.02), and increased less IL-1 beta (from baseline to delivery, p = 0.03) concentrations than controls. When adjusting for other potential confounders, these differences became non-significant. In cord blood, the exercise group showed reduced arterial IL-6 and venous TNF-alpha (p = 0.03 and p = 0.001, respectively) and higher concentrations of arterial IL-1 beta (p = 0.03) compared to controls. The application of concurrent exercise-training programs could be a strategy to modulate immune responses in pregnant women and their fetuses. However, future research is needed to better understand the origin and clearance of these cytokines, their role in the maternal-placental-fetus crosstalk, and the influence of exercise interventions on them

Refinement of computational identification of somatic copy number alterations using DNA methylation microarrays illustrated in cancers of unknown primary

High-throughput genomic technologies are increasingly used in personalized cancer medicine. However, computational tools to maximize the use of scarce tissues combining distinct molecular layers are needed. Here we present a refined strategy, based on the R-package 'conumee', to better predict somatic copy number alterations (SCNA) from deoxyribonucleic acid (DNA) methylation arrays. Our approach, termed hereafter as 'conumee-KCN', improves SCNA prediction by incorporating tumor purity and dynamic thresholding. We trained our algorithm using paired DNA methylation and SNP Array 6.0 data from The Cancer Genome Atlas samples and confirmed its performance in cancer cell lines. Most importantly, the application of our approach in cancers of unknown primary identified amplified potentially actionable targets that were experimentally validated by Fluorescence in situ hybridization and immunostaining, reaching 100% specificity and 93.3% sensitivity

Modulation of folic acid bioaccessibility by encapsulation in pH-responsive gated mesoporous silica particles

[EN] A study on the controlled release of folic acid (FA) from pH-responsive gated mesoporous silica particles (MSP) is reported. The MCM-41 support was synthesized using tetraethyl orthosilicate (TEOS) as hydrolytic inorganic precursor and the surfactant hexadecyltrimethylammonium bromide (CTAB) as porogen species. Calcination of the mesostructured phase resulted in the starting solid. This solid was loaded with FA to obtain the initial support S0. Moreover, this FA-loaded material was further functionalized with 3-[2-(2-aminoethylamino)ethylamino]propyltrimethoxysilane (N3) in order to obtain the gated polyamine-functionalised material S1. Solids S0 and S1 were characterized using standard solid state procedures. It was found that the functionalization process and the inclusion of FA on the pores did not modify the mesoporous structure of the starting material. FA delivery studies in water with solids S0 and S1 were carried out in water at pH 2 and 7.5. S0 was not able to completely inhibit FA delivery at acidic pH yet a rapid FA release at neutral pH was observed in few minutes. In contrast, S1 was tightly capped at pH 2 and displayed a sustained delivery of FA when the pH was switched to 7.5. In the second part of the study, FA loading and functionalization of S1-like supports was optimized. In particular, solids loaded with FA in phosphate buffered saline (PBS) and capped with N3 in acetate buffer at pH 2 exhibited a delivery capacity up to 95 μg FA/mg solid. Finally, FA release from the selected optimized supports was studied following an in vitro digestion procedure. The results showed that amine-capped MSP were not only able to hinder the release of the vitamin in gastric fluids (pH 2), but were also capable of deliver progressively the FA in presence of a simulated intestinal juice (pH 7.5) offering a suitable mechanism to control the bioaccessibility of the vitaminAuthors gratefully acknowledge the financial support from the Ministerio de Economia y Competitividad (Projects AGL201239597-C02 and MAT2012-38429-004-01) and the Generalitat Valenciana (project PROMETEO/2009/016). E.P. is grateful to the Ministerio de Ciencia e Innovacion for his Grant (AP2008-00620). C.C. thanks the Generalitat Valenciana for her post-doctoral contract VALi+D.Pérez-Esteve, É.; Fuentes López, A.; Coll Merino, MC.; Acosta, C.; Bernardos Bau, A.; Amoros Del Toro, PJ.; Marcos Martínez, MD.... (2015). Modulation of folic acid bioaccessibility by encapsulation in pH-responsive gated mesoporous silica particles. Microporous and Mesoporous Materials. 202:124-132. https://doi.org/10.1016/j.micromeso.2014.09.049S12413220

Ceramic foam supported active materials for boron remediation in water

Due to the narrowrange between boron necessities and toxicity in the environment, there is a high interest in the design of effective boron remediation procedures. We have previously reported a promising boron adsorptionmaterial based on the affinity of boron aqueous species for cis-diol groups that were anchored on differentmesoporous silica matrices.However, the small particle size of these systemsmakes themdifficult to be applied on real remediation situations. In this context we report herein a novel systemfor boron adsorption fromaqueous solutions inwhich the high boron affinity for functionalized mesoporousmaterials is combined with themechanical properties of ceramic foams as macroscopic supports. The efficiency of these new composites for boron removal is very high and comparable with the parent microparticulated adsorbent.Financial support from the Spanish Government (Project MAT2009-14564-C04-01 and MAT2009-14564-C04-04, and MAT2012-38429-C04-01 and MAT2012-38429-C04-02) and the Generalitat Valenciana (Project PROMETEO/2009/016) is gratefully acknowledged. C.S. thanks the MICINN for a predoctoral fellowship.Sanfeliu Cano, C.; Martínez-Máñez, R.; Sancenón Galarza, F.; Soto Camino, J.; Amoros Del Toro, PJ.; Marcos Martínez, MD. (2015). Ceramic foam supported active materials for boron remediation in water. Desalination. 374:10-19. https://doi.org/10.1016/j.desal.2015.06.020S101937

Amidase-responsive controlled release of antitumoral drug into intracellular media using gluconamide-capped mesoporous silica nanoparticles

MCM-41 silica nanoparticles were used as inorganic scaffolding to prepare a nanoscopic-capped hybrid material S1, which was able to release an entrapped cargo in the presence of certain enzymes, whereas in the absence of enzymes, a zero release system was obtained. S1 was prepared by loading nanoparticles with Safranine O dye and was then capped with a gluconamide derivative. In the absence of enzymes, the release of the dye from the aqueous suspensions of S1 was inhibited as a result of the steric hindrance imposed by the bulky gluconamide derivative, the polymerized gluconamide layer and the formation of a dense hydrogen-bonded network around the pore outlets. Upon the addition of amidase and pronase enzymes, delivery of Safranine O dye was observed due to the enzymatic hydrolysis of the amide bond in the anchored gluconamide derivative. S1 nanoparticles were not toxic for cells, as demonstrated by cell viability assays using HeLa and MCF-7 cell lines, and were associated with lysosomes, as shown by confocal microscopy. Finally, the S1¿CPT material loaded with the cytotoxic drug camptothecin and capped with the gluconamide derivative was prepared. The HeLa cells treated with S1¿CPT underwent cell death as a result of material internalization, and of the subsequent cellular enzyme-mediated hydrolysis and aperture of the molecular gate, which induced the release of the camptothecin cargo.We thank the Spanish Government (Project MAT2009-14564-C04 and SAF2010-15512) and the Generalitat Valenciana (Project PROMETEO/2009/016and/2010/005) for support. I. C. thanks the Universitat Politecnica de Valencia for her fellowship. L. M. thanks the Generalitat Valenciana for her post-doctoral VALi+d contract. E. A. and C. T. also thank the CIBER-BBN for contracts. We thank Eva Maria Lafuente Villarreal and Alberto Hernandez Cano from the Confocal Microscopy service of CIPF and the Electronic Microscopy service of UPV for their technical support.Candel Busquets, I.; Aznar Gimeno, E.; Mondragón Martínez, L.; De La Torre Paredes, C.; Martínez Mañez, R.; Sancenón Galarza, F.; Marcos Martínez, MD.... (2012). Amidase-responsive controlled release of antitumoral drug into intracellular media using gluconamide-capped mesoporous silica nanoparticles. Nanoscale. 4(22):7237-7245. https://doi.org/10.1039/c2nr32062bS7237724542

Delivery modulation in silica mesoporous supports via alkyl chain pore outlet decoration

This article focuses on the study of the release rate in a family of modified silica mesoporous supports. A collection of solids containing ethyl, butyl, hexyl, octyl, decyl, octadecyl, docosyl, and triacontyl groups anchored on the pore outlets of mesoporous MCM-41 has been prepared and characterized. Controlled release from pore voids has been studied through the delivery of the dye complex tris(2,2¿-bipyridyl)ruthenium(II). Delivery rates were found to be dependent on the alkyl chain length anchored on the pore outlets of the mesoporous scaffolding. Moreover, release rates follow a Higuchi diffusion model, and Higuchi constants for the different hybrid solids have been calculated. A decrease of the Higuchi constants was observed as the alkyl chain used to tune the release profile is longer, confirming the effect that the different alkyl chains anchored into the pore mouths exerted on the delivery of the cargo. Furthermore, to better understand the relation between pore outlets decoration and release rate, studies using molecular dynamics simulations employing force-field methods have been carried out. A good agreement between the calculations and the experimental observations was observed.Financial support from the Spanish Government (projects MAT2009-14564-C04-01 and MAT2009-14564-C04-04) and the Generalitat Valencia (project PROMETEO/2009/016) is gratefully acknowledged.Aznar Gimeno, E.; Sancenón Galarza, F.; Marcos Martínez, MD.; Martínez Mañez, R.; Stroeve, P.; Cano, J.; Amoros Del Toro, P. (2012). Delivery modulation in silica mesoporous supports via alkyl chain pore outlet decoration. Langmuir. 28:2986-2996. https://doi.org/10.1021/la204438jS298629962