Cross-species analysis of gene expression in non-model mammals: reproducibility of hybridization on high density oligonucleotide microarrays

BACKGROUND: Gene expression profiles of non-model mammals may provide valuable data for biomedical and evolutionary studies. However, due to lack of sequence information of other species, DNA microarrays are currently restricted to humans and a few model species. This limitation may be overcome by using arrays developed for a given species to analyse gene expression in a related one, an approach known as "cross-species analysis". In spite of its potential usefulness, the accuracy and reproducibility of the gene expression measures obtained in this way are still open to doubt. The present study examines whether or not hybridization values from cross-species analyses are as reproducible as those from same-species analyses when using Affymetrix oligonucleotide microarrays. RESULTS: The reproducibility of the probe data obtained hybridizing deer, Old-World primates, and human RNA samples to Affymetrix human GeneChip(® )U133 Plus 2.0 was compared. The results show that cross-species hybridization affected neither the distribution of the hybridization reproducibility among different categories, nor the reproducibility values of the individual probes. Our analyses also show that a 0.5% of the probes analysed in the U133 plus 2.0 GeneChip are significantly associated to un-reproducible hybridizations. Such probes-called in the text un-reproducible probe sequences- do not increase in number in cross-species analyses. CONCLUSION: Our study demonstrates that cross-species analyses do not significantly affect hybridization reproducibility of GeneChips, at least within the range of the mammal species analysed here. The differences in reproducibility between same-species and cross-species analyses observed in previous studies were probably caused by the analytical methods used to calculate the gene expression measures. Together with previous observations on the accuracy of GeneChips for cross-species analysis, our analyses demonstrate that cross-species hybridizations may provide useful gene expression data. However, the reproducibility and accuracy of these measures largely depends on the use of appropriated algorithms to derive the gene expression data from the probe data. Also, the identification of probes associated to un-reproducible hybridizations-useless for gene expression analyses- in the studied GeneChip, stress the need of a re-evaluation of the probes' performance

Ética y Eficiencia en Empresas de Inserción Laboral

He seguido un método hipotético-deductivo en el sentido más convencional de los términos, obligado a pasar de lo general a lo particular, es decir de las formulaciones teóricas más consistentes a la aplicación en las Empresas de Inserción Laboral. Para ello he seguido un itinerario que describo en los siguientes puntos: i. La investigación analítica de los trabajos académicos más recientes y más relevantes tratando de seleccionar aquellos que se ocupen de la estructura de la Ética Empresarial, más que de asuntos concretos, como situaciones morales o “casos”. ii. Investigar, si hubiere, un nexo de contenidos éticos empresariales que permita elaborar un corpus doctrinae de aplicación empresarial, con rigor académico y aplicabilidad. iii. Integrar de modo congruente las distintas disciplinas académicas que convergen en la elaboración de una Ética Empresarial, que no se alimenta solo de Ética, ya que esta disciplina aplicada a la empresa debe contemplar otras como Filosofía – en particular la Escuela Posmoderna – Antropología y la Psicología Existencial. iv. Aplicación empírica, mediante encuesta debidamente contrastada y testada, a un grupo de E.I.L. de Andalucía, que han solicitado permanecer en el anonimato, dado el origen de sus empleados, calificados como “personas en estado de exclusión social”.El presente documento se ha confeccionado desde los supuestos más consistentes de una Investigación Exploratoria; en efecto los distintos aspectos encontrados por este doctorando ante la investigación de los vínculos entre la Ética y la Eficiencia Empresarial y la posible correlación entre ambas, me llevaron a desistir de utilizar una Investigación Causal. Si bien la implantación de Códigos Éticos es un hecho contrastado en las empresas, no resulta, tras haber examinado algunos de ellos, que su propósito esté más allá del cumplimiento legal afecto a la actividad empresarial y la adopción de medidas que satisfagan la buena imagen, interna y externa, de Responsabilidad Social Empresarial en adelante R.S.E.), incluso la incorporación del sintagma Desarrollo Sostenible. Si los propósitos de las empresas son cualitativos, de estima, aprecio, consideración a partir de la R.S.E., ¿cómo era posible establecer alguna correlación entre Ética Empresarial y Eficiencia cuando la variable Ética era en realidad R.S.E. y la Eficiencia los buenos resultados Fin de Ejercicio y las menciones y galardones obtenidos en reconocimiento de su labor? En la convicción de que la primera tarea consistía en una contribución epistemológica, rediseñé los planos iniciales de la investigación y me adentré en la nueva ruta, cambiando el procedimiento, que expreso en siguiente apartado, esperando suscitar el interés preciso en las organizaciones afectas a la Ética Empresarial, como son Organizaciones Empresariales, Universidades, Empresas de Economía Social y quienes colaboran voluntariamente en cualesquiera de las organizaciones sociales involucradas en actividades de promoción e inclusión laboral

Integrated stress response as a therapeutic target for CNS injuries.

Central nervous system (CNS) injuries, caused by cerebrovascular pathologies or mechanical contusions (e.g., traumatic brain injury, TBI) comprise a diverse group of disorders that share the activation of the integrated stress response (ISR). This pathway is an innate protective mechanism, with encouraging potential as therapeutic target for CNS injury repair. In this review, we will focus on the progress in understanding the role of the ISR and we will discuss the effects of various small molecules that target the ISR on different animal models of CNS injury.post-print825 K

Oligosacáridos utilizados para inhibir la mitosis de los astrocitos y de las células tumorales del sistema nervioso; y procedimiento de obtención de estos oligosacáridos

Traducción de Patente Europea E92923821 (fecha de solicitud, 13/11/1992).-- Prioridad: ES199111139102522.-- Titular: Consejo Superior de Investigaciones Científicas (CSIC).La invención se refiere a oligosacáridos y a preparaciones medicinales que contienen ingredientes orgánicos activos.Peer reviewe

Detection of metabolite changes in C6 glioma cells cultured with antimitotic oleyl glycoside by1H MAS NMR

The synthetic glycoside, oleyl N-acetyl-α-D-glucosaminide (1), was previously shown to exhibit antimitotic activity on rat (C6) and human (U-373) glioma lines. To obtain information about its mechanism of action, metabolite changes in C6 glioma cells were analyzed after treatment with 1 using high-resolution magic angle spinning 1H NMR. Compound 1 caused either a decrease or an increase in the intensity of the signal assigned to coenzyme A (CoA) metabolites depending on the concentration used. The data obtained from the 1H NMR spectra of cells cultured with 1, combined with those obtained after treatment with oleic acid (an inhibitor of acetyl-CoA carboxylase) and phenyl butyrate (a known antineoplastic agent), suggest that 1 may be altering the metabolism of fatty acids and induce apoptosis of C6 glioma cells. These results point to NMR spectroscopy as an efficient technique for monitoring the response of the cells to therapeutic agents.Peer Reviewe

Poly-l/dl-lactic acid films functionalized with collagen IV as carrier substrata for corneal epithelial stem cells

Limbal epithelial stem cells (LESCs) are responsible for the renewal of corneal epithelium. Cultivated limbal epithelial transplantation is the current treatment of choice for restoring the loss or dysfunction of LESCs. To perform this procedure, a substratum is necessary for in vitro culturing of limbal epithelial cells and their subsequent transplantation onto the ocular surface. In this work, we evaluated poly-L/DL-lactic acid 70:30 (PLA) films functionalized with type IV collagen (col IV) as potential in vitro carrier substrata for LESCs. We first demonstrated that PLA-col IV films were biocompatible and suitable for the proliferation of human corneal epithelial cells. Subsequently, limbal epithelial cell suspensions, isolated from human limbal rings, were cultivated using culture medium that did not contain animal components. The cells adhered significantly faster to PLA-col IV films than to tissue culture plastic (TCP). The mRNA expression levels for the LESC specific markers, K15, P63α and ABCG2 were similar or greater (significantly in the case of K15) in limbal epithelial cells cultured on PLA-col IV films than limbal epithelial cells cultured on TCP. The percentage of cells expressing the corneal (K3, K12) and the LESC (P63α, ABCG2) specific markers was similar for both substrata. These results suggest that the PLA-col IV films promoted LESC attachment and helped to maintain their undifferentiated stem cell phenotype. Consequently, these substrata offer an alternative for the transplantation of limbal cells onto the ocular surface.This work was supported by the Carlos III National Institute of Health, Spain (CIBER-BBN and Spanish Network on Cell Therapy, (TerCel RD12/0019/0036), MINECO/FEDER, EU), and the Castilla y León Regional Government, Spain (Regional Center for Regenerative Medicine and Cell Therapy, SAN673/VA/28/08 and SAN126/VA11/09)

Therapeutic Effect of Human Adipose Tissue-Derived Mesenchymal Stem Cells in Experimental Corneal Failure Due to Limbal Stem Cell Niche Damage

Producción CientíficaLimbal stem cells are responsible for the continuous renewal of the corneal epithelium. The destruction or dysfunction of these stem cells or their niche induces limbal stem cell deficiency (LSCD) leading to visual loss, chronic pain, and inflammation of the ocular surface. To restore the ocular surface in cases of bilateral LSCD, an extraocular source of stem cells is needed to avoid dependence on allogeneic limbal stem cells that are difficult to obtain, isolate, and culture. The aim of this work was to test the tolerance and the efficacy of human adipose tissue-derived mesenchymal stem cells (hAT-MSCs) to regenerate the ocular surface in two experimental models of LSCD that closely resemble the different severity grades of the human pathology. hAT-MSCs transplanted to the ocular surface of the partial and total LSCD models developed in rabbits were well tolerated, migrated to inflamed tissues, reduced inflammation, and restrained the evolution of corneal neovascularization and corneal opacity. The expression profile of the corneal epithelial cell markers CK3 and E-cadherin, and the limbal epithelial cell markers CK15 and p63 was lost in the LSCD models, but was partially recovered after hAT-MSC transplantation. For the first time, we demonstrated that hAT-MSCs improves corneal and limbal epithelial phenotypes in animal LSCD models. These results support the potential use of hAT-MSCs as a novel treatment of ocular surface failure due to LSCD. hAT-MSCs represent an available, non-immunogenic source of stem cells that may provide therapeutic benefits in addition to reduce health care expenses.This work was supported by Instituto de Salud Carlos III, CIBER‐BBN, Spain (CB06/01/003 MINECO/FEDER, EU); Regional Center for Regenerative Medicine and Cell Therapy, Castilla y León, Spain; Ministry of Science and Innovation, Spain (SAF2010–14900); Ministry of Economy and Competitiveness and European Regional Development Fund, Spain (SAF2015–63594‐R MINECO/FEDER, EU