Dictyostelium discoideum, a singular amoeba

[CAT]: Dictyostelium discoideum és una ameba unicel·lular, encara que també presenta una etapa de desenvolupament multicel·lular en el seu cicle biològic. Aquest organisme ha estat utilitzat com un sistema model des de fa més de quaranta anys a causa de la seva similitud funcional amb les cèl·lules de mamífer. A més, mostra molts avantatges experimentals per a estudis de biologia i bioquímica de la cèl·lula. És genèticament manejable i molt accessible per a la manipulació experimental. Les cèl·lules de D. discoideum són molt mòbils i s’han utilitzat àmpliament en estudis del citosquelet cel·lular, la motilitat cel·lular i la migració quimiotàctica. El desenvolupament multicel·lular és relativament simple i ha estat un terreny fèrtil per a l’estudi de l’agregació, la diferenciació cel·lular, la morfogènesi i les vies genètiques i de senyalització que regulen aquests processos. A més, les cèl·lules de D. discoideum són cada vegada més utilitzades per a l’estudi de les malalties humanes. Per exemple, la interacció de cèl·lules amb bacteris patògens, el mecanisme d’acció de diferents drogues, la resistència als medicaments o les bases moleculars de les malalties humanes han estat recentment analitzats en aquest organisme model.[EN]: Dictyostelium discoideum is a unicellular amoeba although it also presents a stage of multi-cellular development in its biological cycle. This organism has been used as a model system for over 40 years given its functional similarity to mammalian cells. In addition, it shows many experimental advantages for biochemical and cell biology studies. It is genetically tractable and highly accessible for experimental manipulation. D. discoideum cells are highly motile and have been extensively used in studies of the cellular cytoskeleton, cell motility and chemotactic migration. Multi-cellular development is relatively simple and has been a fertile ground for the study of aggregation, cell differentiation, morphogenesis, and the genetic and signalling pathways that regulate these processes. In addition D. discoideum cells are being increasingly used for the study of human disease. For example, cell interaction with bacterial pathogens, the mechanism of action of different drugs, drug resistance or the molecular basis of human diseases have been recently studied using this model organism.Peer reviewe

Dictyostelium discoideum, una ameba peculiar

Dictyostelium discoideum és una ameba unicel·lular, encara que també presenta una etapa de desenvolupament multicel·lular en el seu cicle biològic. Aquest organisme ha estat utilitzat com un sistema model des de fa més de quaranta anys a causa de la seva similitud funcional amb les cèl·lules de mamífer. A més, mostra molts avantatges experimentals per a estudis de biologia i bioquímica de la cèl·lula. És genèticament manejable i molt accessible per a la manipulació experimental. Les cèl·lules de D. discoideum són molt mòbils i s'han utilitzat àmpliament en estudis del citosquelet cel·lular, la motilitat cel·lular i la migració quimiotàctica. El desenvolupament multicel·lular és relativament simple i ha estat un terreny fèrtil per a l'estudi de l'agregació, la diferenciació cel·lular, la morfogènesi i les vies genètiques i de senyalització que regulen aquests processos. A més, les cèl·lules de D. discoideum són cada vegada més utilitzades per a l'estudi de les malalties humanes. Per exemple, la interacció de cèl·lules amb bacteris patògens, el mecanisme d'acció de diferents drogues, la resistència als medicaments o les bases moleculars de les malalties humanes han estat recentment analitzats en aquest organisme model.Dictyostelium discoideum, a singular amoeba. Dictyostelium discoideum is a unicellular amoeba although it also presents a stage of multi-cellular development in its biological cycle. This organism has been used as a model system for over 40 years given its functional similarity to mammalian cells. In addition, it shows many experimental advantages for biochemical and cell biology studies. It is genetically tractable and highly accessible for experimental manipulation. D. discoideum cells are highly motile and have been extensively used in studies of the cellular cytoskeleton, cell motility and chemotactic migration. Multi-cellular development is relatively simple and has been a fertile ground for the study of aggregation, cell differentiation, morphogenesis, and the genetic and signalling pathways that regulate these processes. In addition D. discoideum cells are being increasingly used for the study of human disease. For example, cell interaction with bacterial pathogens, the mechanism of action of different drugs, drug resistance or the molecular basis of human diseases have been recently studied using this model organism

Poliadenilación de los RNAs mensajeros durante el desarrollo de Artemia

Tesis inédita de la Universidad Complutense de Madrid, Facultad de Ciencias Biológicas, leída en 1981.Fac. de Ciencias BiológicasTRUEProQuestpu

Poliadenilación de los RNAs mensajeros durante el desarrollo de Artemia

Imagem retirada daqui Acabam de ser publicadas as actas do colóquio "Políticas Públicas para o Património Imaterial na Europa do Sul: percursos, concretizações, perspectivas" realizado a 27-28 de Novembro de 2012, em Lisboa. Trata-se de uma edição em formato digital e que resulta da colaboração entre o CIDEHUS (Universidade de Évora) e a Direcção-Geral do Património Cultural. O livro está disponível aqui. Veja-se o post neste blogue - "O lugar do PCI nas políticas do património", que faz um b..

Poliadenilación de los RNAs mensajeros durante el desarrollo de Artemia

Tesis inédita de la Universidad Complutense de Madrid, Facultad de Ciencias Biológicas, leída en 1981.Fac. de Ciencias BiológicasTRUEProQuestpu

Structural and functional studies of a family of Dictyostelium discoideum developmentally regulated, prestalk genes coding for small proteins

Includes additional file: Structure and chromosomal location of Dictyostelium genes similar to sigN1. In this table the DictyBase database accession number, chromosomal location and exon/intron structure of the genes similar to sigN1 is indicated together with the size of the encoded proteins and their percentage of similarity to SigN1.[Background] The social amoeba Dictyostelium discoideum executes a multicellular development program upon starvation. This morphogenetic process requires the differential regulation of a large number of genes and is coordinated by extracellular signals. The MADS-box transcription factor SrfA is required for several stages of development, including slug migration and spore terminal differentiation.[Results] Subtractive hybridization allowed the isolation of a gene, sigN (SrfA-induced gene N), that was dependent on the transcription factor SrfA for expression at the slug stage of development. Homology searches detected the existence of a large family of sigN-related genes in the Dictyostelium discoideum genome. The 13 most similar genes are grouped in two regions of chromosome 2 and have been named Group1 and Group2 sigN genes. The putative encoded proteins are 87–89 amino acids long. All these genes have a similar structure, composed of a first exon containing a 13 nucleotides long open reading frame and a second exon comprising the remaining of the putative coding region. The expression of these genes is induced at10 hours of development. Analyses of their promoter regions indicate that these genes are expressed in the prestalk region of developing structures. The addition of antibodies raised against SigN Group 2 proteins induced disintegration of multi-cellular structures at the mound stage of development.[Conclusion] A large family of genes coding for small proteins has been identified in D. discoideum. Two groups of very similar genes from this family have been shown to be specifically expressed in prestalk cells during development. Functional studies using antibodies raised against Group 2 SigN proteins indicate that these genes could play a role during multicellular development.This work was supported by grants from the Spanish Ministerio de Educación y Ciencia, Dirección General de Investigación (BMC2002-01501 and BFU2005-00138).Peer reviewe

GSE4, a small dyskerin- and GSE24.2-related peptide, induces telomerase activity, cell proliferation and reduces DNA damage, oxidative stress and cell senescence in dyskerin mutant cells

Dyskeratosis congenita is an inherited disease caused by mutations in genes coding for telomeric components. It was previously reported that expression of a dyskerin-derived peptide, GSE24.2, increases telomerase activity, regulates gene expression and decreases DNA damage and oxidative stress in dyskeratosis congenita patient cells. The biological activity of short peptides derived from GSE24.2 was tested and one of them, GSE4, that probed to be active, was further characterized in this article. Expression of this eleven amino acids long peptide increased telomerase activity and reduced DNA damage, oxidative stress and cell senescence in dyskerin-mutated cells. GSE4 expression also activated c-myc and TERT promoters and increase of c-myc, TERT and TERC expression. The level of biological activity of GSE4 was similar to that obtained by GSE24.2 expression. Incorporation of a dyskerin nuclear localization signal to GSE24.2 did not change its activity on promoter regulation and DNA damage protection. However, incorporation of a signal that increases the rate of nucleolar localization impaired GSE24.2 activity. Incorporation of the dyskerin nuclear localization signal to GSE4 did not alter its biological activity. Mutation of the Aspartic Acid residue that is conserved in the pseudouridine synthase domain present in GSE4 did not impair its activity, except for the repression of c-myc promoter activity and the decrease of c-myc, TERT and TERC gene expression in dyskerin-mutated cells. These results indicated that GSE4 could be of great therapeutic interest for treatment of dyskeratosis congenita patients.This work was supported by grants PI1401495 (supported by FEDER funds) and ER15PR07ACC114/757 (Fondo de Investigaciones Sanitarias, Instituto de Salud Carlos III. Spain), 201320E075 (Consejo Superior de Investigaciones Científicas) and IPT-2012-0674- 090000 (Ministerio de Economía y Competitividad. Spain). CM-G is supported by the CIBER de Enfermedades Raras.Peer Reviewe

Molecular Diagnosis and Precision Therapeutic Approaches for Telomere Biology Disorders

Telomeres are nucleo-protein structures located at the end of chromosomes that protect them from degradation. Telomeres length is maintained by the activity of the telomerase complex. These structures are protected by a specialized protein complex named shelterin. In the absence of telomerase activity and/or protection telomeres are shortened after each round of DNA replication. When a critical size is reached, telomeres are recognized as damaged DNA by the cell p53-dependent DNA-repair system. Persistent activation of this pathway finally results in cell apoptosis or senescence

Original Article Biomarkers of erlotinib response in non-small cell lung cancer tumors that do not harbor the more common epidermal growth factor receptor mutations

Abstract: Non-small cell lung cancer (NSCLC) represents approximately 85% of all lung cancers, which are the leading cause of cancer-related deaths in the world. Tyrosine kinase inhibitors such as erlotinib represent one therapeutic options presently recommended for tumors produced by activating mutations in the gene coding of epidermal growth factor receptor (EGFR). The aim of this study is the identification of possible biomarkers for tumor sensitivity to erlotinib in the absence of the main EGFR mutations. The erlotinib sensitivity of cells isolated from 41 untreated NSCLC patients was determined and compared with the presence of the more frequent EGFR mutations. Several patients had tumor cells highly sensitive to erlitinib in the absence of the EGFR mutations analyzed. The gene expression profile of 3 erlotinib-sensitive tumors was compared with that of 4 resistant tumors by DNA microarray hybridization. Sixteen genes were expressed at significantly higher levels in the resistant tumors than in the sensitive tumors. The possible correlation between erlotinib sensitivity and the expression of these genes was further analyzed using the data for the NSCLC, breast cancer and colon cancer cell lines of the NCI60 collection. The expression of these genes was correlated with the overall survival of 5 patients treated with erlotinib, according to The Cancer Genome Atlas (TCGA) database. Overlapping groups of 7, 5 and 3 genes, including UGT1A6, TRIB3, MET, MMP7, COL17A1, LCN2 and PTPRZ1, whose expression correlated with erlotinib activity was identified. In particular, low MET expression levels showed the strongest correlation

GSE4‐loaded nanoparticles a potential therapy for lung fibrosis that enhances pneumocyte growth, reduces apoptosis and DNA damage

Idiopathic pulmonary fibrosis is a lethal lung fibrotic disease, associated with aging with a mean survival of 2-5 years and no curative treatment. The GSE4 peptide is able to rescue cells from senescence, DNA and oxidative damage, inflammation, and induces telomerase activity. Here, we investigated the protective effect of GSE4 expression in vitro in rat alveolar epithelial cells (AECs), and in vivo in a bleomycin model of lung fibrosis. Bleomycin-injured rat AECs, expressing GSE4 or treated with GSE4-PLGA/PEI nanoparticles showed an increase of telomerase activity, decreased DNA damage, and decreased expression of IL6 and cleaved-caspase 3. In addition, these cells showed an inhibition in expression of fibrotic markers induced by TGF-β such as collagen-I and III among others. Furthermore, treatment with GSE4-PLGA/PEI nanoparticles in a rat model of bleomycin-induced fibrosis, increased telomerase activity and decreased DNA damage in proSP-C cells. Both in preventive and therapeutic protocols GSE4-PLGA/PEI nanoparticles prevented and attenuated lung damage monitored by SPECT-CT and inhibited collagen deposition. Lungs of rats treated with bleomycin and GSE4-PLGA/PEI nanoparticles showed reduced expression of α-SMA and pro-inflammatory cytokines, increased number of pro-SPC-multicellular structures and increased DNA synthesis in proSP-C cells, indicating therapeutic efficacy of GSE4-nanoparticles in experimental lung fibrosis and a possible curative treatment for lung fibrotic patients