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Digital.CSIC (162.855 recursos)

Repositorio institucional del Consejo Superior de Investigaciones Científicas. Digital.CSIC es un depósito de documentos digitales, cuyo objetivo es organizar, archivar, preservar y difundir en modo de acceso abierto la producción intelectual resultante de la actividad investigadora del CSIC.

(CBM) Artículos post-print

Mostrando recursos 1 - 20 de 58

  1. Cell competition may function either as tumour-suppressing or as tumour-stimulating factor in Drosophila

    Ballesteros-Arias, Luna; Morata, Ginés; Saavedra, Verónica
    Drosophila endocytosis-defective cells develop tumour overgrowths in the imaginal discs. We have analysed the tumorigenic potential of cells mutant for Rab5, a gene involved in endocytosis. We found that while a compartment entirely made by Rab5 mutant cells can grow indefinitely, clones of Rab5 cells surrounded by normal cells are eliminated by cell competition. However, when a group of about 400 cells are simultaneously made mutant for Rab5, they form an overgrowing tumour: mutant cells in the periphery are eliminated, but those inside survive and continue proliferating because they are beyond the range of cell competition. These results identify group...

  2. Morphology and DNA barcodes reveal the presence of the non-native land planarian Obama marmorata (Platyhelminthes : Geoplanidae) in Europe

    Lago-Barcia, Domingo; Fernández-Álvarez, Fernando Ángel; Negrete, Lisandro; Brusa, Francisco; Damborenea, Cristina; Grande, Cristina; Noreña, Carolina
    11 pages, 4 figures, 2 tables

  3. Chromosome segregation and organization are targets of 5′-Fluorouracil in eukaryotic cells

    Mojardín, Laura; Botet, Javier; Moreno, Sergio; Salas, Margarita
    The antimetabolite 5′-Fluorouracil (5FU) is an analog of uracil commonly employed as a chemotherapeutic agent in the treatment of a range of cancers including colorectal tumors. To assess the cellular effects of 5FU, we performed a genome-wide screening of the haploid deletion library of the eukaryotic model Schizosaccharomyces pombe. Our analysis validated previously characterized drug targets including RNA metabolism, but it also revealed unexpected mechanisms of action associated with chromosome segregation and organization (post-translational histone modification, histone exchange, heterochromatin). Further analysis showed that 5FU affects the heterochromatin structure (decreased levels of histone H3 lysine 9 methylation) and silencing (down-regulation of...

  4. Psoriasis in humans is associated with down-regulation of galectins in dendritic cells

    Fuente, Hortensia de la; Pérez-Gala, Silvia; Bonay, Pedro; Cruz-Adalia, Aránzazu; Cibrián, Danay; Sánchez-Cuellar, Silvia; Dauden, Esteban; Fresno, Manuel; García-Díez, Amaro; Sánchez-Madrid, Francisco
    We have investigated the expression and role of galectin-1 and other galectins in psoriasis and in the Th1/Th17 effector and dendritic cell responses associated with this chronic inflammatory skin condition. To determine differences between psoriasis patients and healthy donors, expression of galectins was analysed by RT-PCR in skin samples and on epidermal and peripheral blood dendritic cells by immunofluorescence and flow cytometry. In the skin of healthy donors, galectin-1, -3 and -9 were expressed in a high proportion of Langerhans cells. Also, galectins were differentially expressed in peripheral blood dendritic cell subsets; galectin-1 and galectin-9 were highly expressed in peripheral...

  5. Characterization of an immunodominant antigenic epitope from Trypanosoma cruzi as a biomarker of chronic Chagas' disease pathology

    Thomas, María del Carmen; Fernández-Villegas, A.; Carrilero, Bartolomé; Marañón, Concepción; Saura, Daniel; Noya, Óscar; Segovia, Manuel; Alarcón de Noya, Belkisyolé; Alonso, Carlos; López López, Manuel Carlos
    Nowadays, the techniques available for chronic Chagas' disease diagnosis are very sensitive; however, they do not allow discrimination of the patient's clinical stages of the disease. The present paper describes that three out of the five different repeats contained in the Trypanosoma cruzi TcCA-2 membrane protein (3972-FGQAAAGDKPPP, 6303-FGQAAAGDKPAP, and 3973-FGQ AAAGDKPSL) are recognized with high sensitivity (>90%) by sera from chronic Chagas' disease patients and that they are not recognized by sera from patients in the acute phase of the disease. A total of 133 serum samples from chagasic patients and 50 serum samples from healthy donors were tested. In...

  6. Viroporins: Structure and biological functions

    Nieva, José Luis; Madan, Vanesa; Carrasco Llamas, Luis
    Viroporins are small, hydrophobic proteins that are encoded by a wide range of clinically relevant animal viruses. When these proteins oligomerize in host cell membranes, they form hydrophilic pores that disrupt a number of physiological properties of the cell. Viroporins are crucial for viral pathogenicity owing to their involvement in several diverse steps of the viral life cycle. Thus, these viral proteins, which include influenza A virus matrix protein 2 (M2), HIV-1 viral protein U (Vpu) and hepatitis C virus p7, represent ideal targets for therapeutic intervention, and several compounds that block their pore-forming activity have been identified. Here, we...

  7. The P1/P2 proteins of the human ribosomal stalk are required for ribosome binding and depurination by ricin in human cells

    May, Kerrie L.; Li, Xiao-Ping; Martínez-Azorín, Francisco; Ballesta, Juan P. G.; Grela, Przemyslaw; Tchorzewski, Marek; Tumer, Nilgun E.
    Ricin A-chain (RTA) depurinates the sarcin-ricin loop of 28S ribosomal RNA and inhibits protein synthesis in mammalian cells. In yeast, the ribosomal stalk facilitates the interaction of RTA with the ribosome and subsequent depurination. Despite homology between the stalk structures from yeast and humans, there are notable differences. The human ribosomal stalk contains two identical heterodimers of P1 and P2 bound to P0, whereas the yeast stalk consists of two different heterodimers, P1α-P2β and P2α-P1β, bound to P0. RTA exhibits higher activity towards mammalian ribosomes than towards ribosomes from other organisms, suggesting that the mode of interaction with ribosomes may...

  8. The Essential Role of the 3¿ Terminal Template Base in the First Steps of Protein-Primed DNA Replication

    Rodríguez García, Irene; Longás, Elisa; Vega, Miguel de; Salas, Margarita
    Bacteriophages w29 and Nf from Bacillus subtilis start replication of their linear genomes at both ends using a proteinprimed mechanism by means of which the DNA polymerase initiates replication by adding dAMP to the terminal protein, this insertion being directed by the second and third 39 terminal thymine of the template strand, respectively. In this work, we have obtained evidences about the role of the 39 terminal base during the initiation steps of w29 and Nf genome replication. The results indicate that the absence of the 39 terminal base modifies the initiation position carried out by w29 DNA polymerase in...

  9. Segmental uniparental disomy leading to homozygosity for a pathogenic mutation in three recessive metabolic diseases

    Pérez, Belén; Nevado, Julián; Gallego-Villar, Lorena
    Ministerio de Ciencia e Innovación (SAF2010-17272)

  10. Protection against West Nile Virus Infection in Mice after Inoculation with Type I Interferon-Inducing RNA Transcripts

    Rodríguez Pulido, Miguel Ramón; Martín-Acebes, Miguel Ángel; Escribano-Romero, Estela; Blázquez, Ana Belén; Sobrino Castelló, Francisco; Borrego, Belén; Sáiz, Margarita; Saiz, Juan Carlos
    West Nile virus (WNV) is a neurovirulent single stranded RNA mosquito-borne flavivirus, whose main natural hosts are birds, but it also infects humans and horses. Nowadays, no human vaccine is commercially available and clinical treatment is only supportive. Recently, it has been shown that RNA transcripts, mimicking structural domains in the non-coding regions (NCRs) of the foot-and mouth disease virus (FMDV) induce a potent IFN response and antiviral activity in transfected cultured cells, and also reduced mice susceptibility to FMDV. By using different transcripts combinations, administration schedules, and infecting routes and doses, we have demonstrated that these FMDV RNA transcripts...

  11. Pαx6 expression in postmitotic neurons mediates the growth of axons in response to SFRP1

    Sebastián-Serrano, Álvaro; Sandonis Consuegra, África; Cardozo, Marcos; Rodríguez-Tornos, María Fernanda; Bovolenta, Paola; Nieto, Marta
    During development, the mechanisms that specify neuronal subclasses are coupled to those that determine their axonal response to guidance cues. Pax6 is a homedomain transcription factor required for the specification of a variety of neural precursors. After cell cycle exit, Pax6 expression is often shut down in the precursor progeny and most postmitotic neurons no longer express detectable levels of the protein. There are however exceptions and high Pax6 protein levels are found, for example, in postmitotic retinal ganglion cells (RGCs), dopaminergic neurons of the olfactory bulb and the limbic system in the telencephalon. The function of Pax6 in these...

  12. Pharmacological modulation of peritoneal injury induced by dialysis fluids: Is it an option?

    González-Mateo, Guadalupe; Stark Aroeira, Luiz; López Cabrera, Manuel; Ruiz-Ortega, Marta; Ortiz, Alberto; Selgas, Rafael
    FIS (PS09/00447, PI09/00641, PI08/1564); ISCIII-RETIC REDinREN/RD06/0016; Fondecyt 1080083; Comunidad de Madrid/FRACM/S-BIO0283/2006; Ministerio de Ciencia e Innovación (SAF 2007/63648, SAF 2010-21249); CAM S-GEN-0247/2006

  13. Peripheral cholesterol, metabolic disorders and Alzheimer's disease

    Ledesma, M. Dolores; Dotti, Carlos G.
    Strong correlations have been made between high levels of blood cholesterol and the risk to suffer Alzheimer's disease (AD). The question arises on how a peripheral event contributes to a disease that so severely affects the integrity and function of the Central Nervous System. Hypercholesterolemia has been also associated to peripheral metabolic disorders like diabetes, obesity or atherosclerosis that, in turn, predispose to AD. Here we review data, which point to alterations in blood cholesterol levels as a link between these metabolic disorders and AD. We describe and discuss common, cholesterol-related, molecular mechanisms and strategies to fight these conditions that,...

  14. Mutagenesis-mediated virus extinction: Virus-dependent effect of viral load on sensitivity to lethal defection

    Moreno, Héctor; Tejero, Héctor; Torre, Juan Carlos de la; Domingo, Esteban; Martín, Verónica
    Background: Lethal mutagenesis is a transition towards virus extinction mediated by enhanced mutation rates during viral genome replication, and it is currently under investigation as a potential new antiviral strategy. Viral load and virus fitness are known to influence virus extinction. Here we examine the effect or the multiplicity of infection (MOI) on progeny production of several RNA viruses under enhanced mutagenesis. Results: The effect of the mutagenic base analogue 5-fluorouracil (FU) on the replication of the arenavirus lymphocytic choriomeningitis virus (LCMV) can result either in inhibition of progeny production and virus extinction in infections carried out at low multiplicity...

  15. Modulation of foot-and-mouth disease virus pH threshold for uncoating correlates with differential sensitivity to inhibition of cellular Rab GTPases and decreases infectivity in vivo

    Vázquez-Calvo, Ángela; Caridi, Flavia; Rodríguez-Pulido, Miguel; Borrego, Belén; Sáiz, Margarita; Sobrino Castelló, Francisco; Martín-Acebes, Miguel Ángel
    The role of cellular Rab GTPases that govern traffic between different endosome populations was analysed on foot-and-mouth disease virus (FMDV) infection. Changes of viral receptor specificity did not alter Rab5 requirement for infection. However, a correlation between uncoating pH and requirement of Rab5 for infection was observed. A mutant FMDV with less acidic uncoating pH threshold was less sensitive to inhibition of Rab5, whereas another mutant with more acidic requirements was more sensitive to inhibition of Rab5. On the contrary, opposed correlations between uncoating pH and dependence of Rab function were observed upon expression of dominant-negative forms of Rab7 or...

  16. Membrane-active peptides derived from picornavirus 2B viroporin

    Sánchez-Martínez, Silvia; Madan, Vanesa; Carrasco Llamas, Luis; Nieva, José Luis
    Viruses have evolved membrane-restructuring mechanisms for sustaining entry into cells, genome replication and release from host cells. Picornavirus 2B, a non-structural protein required for effective viral replication, functions as a potent intracellular pore-forming toxin by altering the permeability of cellular endomembranes. Two consecutive hydrophobic regions have been identified in 2B protein that could function as an >α-helix-turn-α-helix> hairpin membraneanchor. A peptide derived from the first transmembrane domain comprised a one-helix 2B version that possesses the intrinsic pore-forming activity required to directly and effectively permeabilize the cell plasma membrane. Moreover, this miniaturized form is capable of translocating through the plasma membrane...

  17. Megakaryocytes promote hepatoepithelial liver cell development in E11.5 mouse embryos by cell-to-cell contact and by vascular endothelial growth factor A signaling.

    Serrano, Natalia; Cortegano, Isabel; Ruiz, Carolina; Alía, Mario; Andrés, Belén de; Rejas, M. Teresa; Marcos, Miguel A. R.; Gaspar, María Luisa
    In the mouse embryo, hematopoietic progenitor cells migrate to the fetal liver (FL) between gestational days (E) 9.5 and 10.5, where they rapidly expand to form the main fetal reservoir of hematopoietic cells. The embryonic megakaryocyte progenitors (MKPs) in the E11.5 FL were identified as CD49f(H) CD41(H) (and c-Kit(D)KDR(+)CD42(+)CD9(++)CD31(+)) cells, expressing several hepato-specific proteins. Unlike adult bone marrow megakaryocytes (MKs), embryonic MKPs were CD45(-) and represent an abundant population in the FL. The CD49f(H)CD41(H) MKPs purified by cytometry differentiated in vitro to produce proplatelets, independent of thrombopoietin stimulation, and they responded to stimulation with adenosine diphosphate, thrombin, and the PAR4...

  18. Supercritical fluid extraction of heather (Calluna vulgaris) and evaluation of anti-hepatitis C virus activity of the extracts

    Rodríguez García-Risco, Mónica; Vázquez, Erika; Sheldon, Julie; Steinmann, Eike; Riebesehl, Nina; Fornari, Tiziana; Reglero, Guillermo
    Previous studies using lipid extracts of heather (Calluna vulgaris) leaves showed the presence of high concentrations of ursolic and oleanolic acid. These two compounds have been reported to present antiviral activity against hepatitis C virus (HCV). In this work, the supercritical fluid extraction of heather was studied with the aim of assessing a potential anti-HCV activity of the extracts owing to their triterpenic acid content. Supercritical extraction assays were carried out exploring the pressure range of 20-50. MPa, temperatures of 40-70. °C and 0-15% of ethanol cosolvent. The content of oleanolic and ursolic acid in the extracts were determined, and...

  19. Lipid changes in the aged brain: Effect on synaptic function and neuronal survival

    Ledesma, M. Dolores; Martín, Mauricio G.; Dotti, Carlos G.
    As the brain ages, cognitive and motor performance decline. This decline is thought to be largely due to the accumulation of damaging products from normal oxidative metabolism and to the perturbation of general body homeostasis and brain-circulation separation. Despite this abundance of insults, the aged brain contains few dead neurons, suggesting that aging must be paralleled by triggering or enhancing neuronal survival mechanisms. Recent evidence points to the contribution of changes in the lipid composition of membranes to both age-dependent cognitive decline and robust neuronal survival. In this review, we describe and discuss the current understanding of the roles of...

  20. GTL1 keeps cell growth and nuclear ploidy under control

    Caro, Elena; Desvoyes, Bénédicte; Gutiérrez Armenta, Crisanto
    The endoreplication programme consists of multiple rounds of full genome replication in the absence of any intervening mitosis. This leads to an increase in nuclear ploidy that has been linked to the initiation of cell differentiation and growth. Recent work (Breuer et al, 2012) has identified the GTL1 transcription factor as a master regulator of cell growth through two different mechanisms: one, endoreplication dependent where GTL1 acts as a repressor of the anaphase-promoting complex (APC), and another as a regulator of endoreplication-independent cell growth. © 2012 European Molecular Biology Organization.

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