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

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

Mecanismos involucrados en la promoción de crecimiento axonal por la glia envolvente del bulbo olfatorio

Neuroplasticity promoted by olfactory ensheathing cells depends on the expression of several molecules during development, adult life and lesion repair. Diverse molecules including neurotrophins and associated receptors, cellular adhesion molecules, extracellular matrix molecules and molecules associated with myelinization are present in the olfactory system during development. Furthermore, their expression continues into adult life and appears to be associated with cellular replacement and the high degree of plasticity of the olfactory system. Olfactory ensheating cell migration, accompanying growing axons, is observed during development, and trasplanted glia cells enable the navigation of regenerating sensory sprouts through inhibitory gliotic tissue formed after lesion of the central nervous system. The purpose of this review is to provide an insight into the neuroregenerative mechanisms and growth promoting properties of these cells.La actividad que promueve el crecimiento de axones por la glia envolvente (GE) del bulbo olfatorio depende de la expresión de diversas moléculas durante el desarrollo, la vida adulta y la reparación de lesiones nerviosas. Diversas moléculas tales como las neurotrofinas y sus receptores, los factores de crecimiento, las moléculas de adhesión celular, las moléculas de matriz extracelular y las moléculas asociadas con la mielinización son producidas por la glia del sistema olfatorio durante el desarrollo. Su expresión sostenida durante la vida adulta parece estar asociada con el reemplazo celular y la alta plasticidad de este sistema. A su vez, su expresión se involucra en procesos de reparación de lesiones mediados por trasplantes de glia. La migración de la GE, que acompaña axones en crecimiento, se observa durante el desarrollo y en procesos de regeneración luego de una lesión. Los trasplantes de,GE permiten la navegación de brotes regenerantes a través del tejido gliótico inhibidor formado luego de una lesión del sistema nervioso central. El propósito de esta revisión es profundizar en los mecanismos de actividad promotora de crecimiento axonal

Micellar Iron Oxide Nanoparticles Coated with Anti-Tumor Glycosides

The synthesis procedure of nanoparticles based on thermal degradation produces organic solvent dispersible iron oxide nanoparticles (OA-IONP) with oleic acid coating and unique physicochemical properties of the core. Some glycosides with hydrophilic sugar moieties bound to oleyl hydrophobic chains have antimitotic activity on cancer cells but reduced in vivo applications because of the intrinsic low solubility in physiological media, and are prone to enzymatic hydrolysis. In this manuscript, we have synthetized and characterized OA-IONP-based micelles encapsulated within amphiphilic bioactive glycosides. The glycoside-coated IONP micelles were tested as Magnetic Resonance Imaging (MRI) contrast agents as well as antimitotics on rat glioma (C6) and human lung carcinoma (A549) cell lines. Micelle antimitotic activity was compared with the activity of the corresponding free glycosides. In general, all OA-IONP-based micellar formulations of these glycosides maintained their anti-tumor effects, and, in one case, showed an unusual therapeutic improvement. Finally, the micelles presented optimal relaxometric properties for their use as T2-weighed MRI contrast agents. Our results suggest that these bioactive hydrophilic nano-formulations are theranostic agents with synergistic properties obtained from two entities, which separately are not ready for in vivo applications, and strengthen the possibility of using biomolecules as both a coating for OA-IONP micellar stabilization and as drugs for therapy.This research was funded by FP7 Marie Curie Pulmonary imaging network (PINET) and Ministerio de Economia y Competitividad MAT2015-65184-C2-2-R; SAF2016-79593-P; SAF2017-84494-C2-1-R). This work was partially funded by Instituto de Salud Carlos III (DTS16/00059), CNIC (Centro Nacional de Investigaciones Cardiovasculares), and Comunidad de Madrid (B2017-BMD3731 and B2017-BMD3875). We thank Ligue contre le cancer, comite Charentes Maritimes which allows to free up some time to complete the redaction of this manuscript during a grant-not dedicated on this work-agreed to LIENSs, UMR CNRS 7266, La Rochelle.S

The Effect of Antitumor Glycosides on Glioma Cells and Tissues as Studied by Proton HR-MAS NMR Spectroscopy

Abstract The effect of the treatment with glycolipid derivatives on the metabolic profile of intact glioma cells and tumor tissues, investigated using proton high resolution magic angle spinning ( 1 H HR-MAS) nuclear magnetic resonance (NMR) spectroscopy, is reported here. Two compounds were used, a glycoside and its thioglycoside analogue, both showing anti-proliferative activity on glioma C6 cell cultures; however, only the thioglycoside exhibited antitumor activity in vivo. At the drug concentrations showing anti-proliferative activity in cell culture (20 and 40 µM), significant increases in choline containing metabolites were observed in the 1 H NMR spectra of the same intact cells. In vivo experiments in nude mice bearing tumors derived from implanted C6 glioma cells, showed that reduction of tumor volume was associated with significant changes in the metabolic profile of the same intact tumor tissues; and were similar to those observed in cell culture. Specifically, the activity of the compounds is mainly associated with an increase in choline and phosphocholine, in both the cell cultures and tumoral tissues. Taurine, a metabolite that has been considered a biomarker of apoptosis, correlated with the reduction of tumor volume. Thus, the results indicate that the mode of action of the glycoside involves, at least in part, alteration of phospholipid metabolism, resulting in cell death

Association of Rhinitis With Asthma Prevalence and Severity

Multicenter study[Abstract] Asthma and rhinitis often co-exist in the same patient. Although some authors observed a higher prevalence and/or greater severity of asthma in patients with rhinitis, this view is not homogeneous and the debate continues. The aim of our study is to describe the prevalence of rhinitis in children and adolescents and to analyse their relationship with the prevalence of asthma. A multicentre study was conducted using the methodology of the International Study of Asthma and Allergies in Childhood (ISAAC). The target population of the study was all those school children aged 6-7 and 13-14 years from 6 of the main health catchment areas of Galicia (1.9 million inhabitants). The schools required were randomly selected, and all children in the targeted age ranges were included. Multiple logistic regression was used to obtain adjusted prevalence odds ratios (OR) between asthma symptoms of the schoolchildren and rhinitis prevalence. The results were adjusted for parental smoking habits, maternal education level, cat and dog exposure, and obesity. A total of 21,420 valid questionnaires were finally obtained. Rhinitis was associated with a significant increase in the prevalence of asthma in both age groups. The highest OR were 11.375 for exercise induced asthma (EIA) for children with recent rhinoconjunctivitis and 9.807 for children with recent rhinitis in 6-7 years old group. The prevalence OR's are higher in EIA and severe asthmatics. Rhinitis in children and adolescents is associated with a higher prevalence and severity of asthma.This work was funded by the Maria Jose Jove Foundatio

IL-6 serum levels predict severity and response to tocilizumab in COVID-19: An observational study

Background: Patients with coronavirus disaese 2019 (COVID-19) can develop a cytokine release syndrome that eventually leads to acute respiratory distress syndrome requiring invasive mechanical ventilation (IMV). Because IL-6 is a relevant cytokine in acute respiratory distress syndrome, the blockade of its receptor with tocilizumab (TCZ) could reduce mortality and/or morbidity in severe COVID-19. Objective: We sought to determine whether baseline IL-6 serum levels can predict the need for IMV and the response to TCZ. Methods: A retrospective observational study was performed in hospitalized patients diagnosed with COVID-19. Clinical information and laboratory findings, including IL-6 levels, were collected approximately 3 and 9 days after admission to be matched with preadministration and postadministration of TCZ. Multivariable logistic and linear regressions and survival analysis were performed depending on outcomes: need for IMV, evolution of arterial oxygen tension/fraction of inspired oxygen ratio, or mortality. Results: One hundred forty-six patients were studied, predominantly males (66%); median age was 63 years. Forty-four patients (30%) required IMV, and 58 patients (40%) received treatment with TCZ. IL-6 levels greater than 30 pg/mL was the best predictor for IMV (odds ratio, 7.1; P < .001). Early administration of TCZ was associated with improvement in oxygenation (arterial oxygen tension/fraction of inspired oxygen ratio) in patients with high IL-6 (P = .048). Patients with high IL-6 not treated with TCZ showed high mortality (hazard ratio, 4.6; P = .003), as well as those with low IL-6 treated with TCZ (hazard ratio, 3.6; P = .016). No relevant serious adverse events were observed in TCZ-treated patients. Conclusions: Baseline IL-6 greater than 30 pg/mL predicts IMV requirement in patients with COVID-19 and contributes to establish an adequate indication for TCZ administrationThis study was funded by Spanish Ministry of Economy, Industry and Competitiveness (MINECO) and Instituto de Salud Carlos III (grant nos. RD16/0011/0012 and PI18/ 0371 to I.G.A., grant no. PI19/00549 to A.A., and grant no. SAF2017-82886-R to F.S.-M.) and co-funded by the European Regional Development Fund. The study was also funded by ‘‘La Caixa Banking Foundation’’ (grant no. HR17-00016 to F.S.-M.) and ‘‘Fondos Supera COVID19’’ by Banco de Santander and CRUE. None of these sponsors have had any role in study design; in the collection, analysis, and interpretation of data; in the writing of the report; and in the decision to submit the article for publicatio

Derecho ex cathedra. 1847-1936 Diccionario de catedráticos españoles

Edición revisada 2020.Publicación de las entradas biográficas del Diccionario de catedráticos españoles de Derecho, accesible en http://www.uc3m.es/diccionariodecatedraticos. Al dar forma de libro al material hemos prescindido de algunos elementos informativos, que se mantienen en la página electrónica indicada. Se recogen ahora solamente a los ingresados en el cuerpo con anterioridad a la guerra civil.Publication of the biographical entries of the Diccionario de catedráticos españoles de Derecho, accessible at http://www.uc3m.es/diccionariodecatedraticos. By giving those material book form, we have dispensed with some informative elements, however kept on the web page. Only professors apointed prior to the Civil War are now included.Esta publicación forma parte del proyecto “La memoria del jurista español: génesis y desarrollo de las disciplinas jurídicas” (ref. DER2014-55035-C2-1-P/DER2014-55035-C2-2-P), financiado por el Ministerio de Economía, Industria y Competitividad (España)