338 research outputs found

    The Differential Impact of SRC Expression on the Prognosis of Patients with Head and Neck Squamous Cell Carcinoma

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    Aberrant SRC expression and activation is frequently detected in multiple cancers, and hence, targeting SRC has emerged as a promising therapeutic strategy. Different SRC inhibitors have demonstrated potent anti-tumor activity in preclinical models, although they largely lack clinical efficacy as monotherapy in late-stage solid tumors, including head and neck squamous cell carcinomas (HNSCC). Adequate selection and stratification of patients who may respond to and benefit from anti-SRC therapies is therefore needed to guide clinical trials and treatment efficacy. This study investigates the prognostic significance of active SRC expression in a homogeneous cohort of 122 human papillomavirus (HPV)-negative, surgically treated HNSCC patients. Immunohistochemical evaluation of the active form of SRC by means of anti-SRC Clone 28 monoclonal antibody was specifically performed and subsequently correlated with clinical data. The expression of p-SRC (Tyr419), total SRC, and downstream SRC effectors was also analyzed. Our results uncovered striking differences in the prognostic relevance of SRC expression in HNSCC patients depending on the tumor site. Active SRC expression was found to significantly associate with advanced disease stages, presence of lymph node metastasis, and tumor recurrences in patients with laryngeal tumors, but not in the pharyngeal subgroup. Multivariate Cox analysis further revealed active SRC expression as an independent predictor of cancer-specific mortality in patients with laryngeal carcinomas. Concordantly, expression of p-SRC (Tyr419) and the SRC substrates focal adhesion kinase (FAK) and the Arf GTPase-activating protein ASAP1 also showed specific associations with poor prognosis in the larynx. These findings could have important implications in ongoing Src family kinase (SFK)-based clinical trials, as these new criteria could help to improve patient selection and develop biomarker-stratified trials

    Enterohemorrhagic E. coli Requires N-WASP for Efficient Type III Translocation but Not for EspFU-Mediated Actin Pedestal Formation

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    Upon infection of mammalian cells, enterohemorrhagic E. coli (EHEC) O157:H7 utilizes a type III secretion system to translocate the effectors Tir and EspFU (aka TccP) that trigger the formation of F-actin-rich ‘pedestals’ beneath bound bacteria. EspFU is localized to the plasma membrane by Tir and binds the nucleation-promoting factor N-WASP, which in turn activates the Arp2/3 actin assembly complex. Although N-WASP has been shown to be required for EHEC pedestal formation, the precise steps in the process that it influences have not been determined. We found that N-WASP and actin assembly promote EHEC-mediated translocation of Tir and EspFU into mammalian host cells. When we utilized the related pathogen enteropathogenic E. coli to enhance type III translocation of EHEC Tir and EspFU, we found surprisingly that actin pedestals were generated on N-WASP-deficient cells. Similar to pedestal formation on wild type cells, Tir and EspFU were the only bacterial effectors required for pedestal formation, and the EspFU sequences required to interact with N-WASP were found to also be essential to stimulate this alternate actin assembly pathway. In the absence of N-WASP, the Arp2/3 complex was both recruited to sites of bacterial attachment and required for actin assembly. Our results indicate that actin assembly facilitates type III translocation, and reveal that EspFU, presumably by recruiting an alternate host factor that can signal to the Arp2/3 complex, exhibits remarkable versatility in its strategies for stimulating actin polymerization

    Repetitive N-WASP–Binding Elements of the Enterohemorrhagic Escherichia coli Effector EspFU Synergistically Activate Actin Assembly

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    Enterohemorrhagic Escherichia coli (EHEC) generate F-actin–rich adhesion pedestals by delivering effector proteins into mammalian cells. These effectors include the translocated receptor Tir, along with EspFU, a protein that associates indirectly with Tir and contains multiple peptide repeats that stimulate actin polymerization. In vitro, the EspFU repeat region is capable of binding and activating recombinant derivatives of N-WASP, a host actin nucleation-promoting factor. In spite of the identification of these important bacterial and host factors, the underlying mechanisms of how EHEC so potently exploits the native actin assembly machinery have not been clearly defined. Here we show that Tir and EspFU are sufficient for actin pedestal formation in cultured cells. Experimental clustering of Tir-EspFU fusion proteins indicates that the central role of the cytoplasmic portion of Tir is to promote clustering of the repeat region of EspFU. Whereas clustering of a single EspFU repeat is sufficient to bind N-WASP and generate pedestals on cultured cells, multi-repeat EspFU derivatives promote actin assembly more efficiently. Moreover, the EspFU repeats activate a protein complex containing N-WASP and the actin-binding protein WIP in a synergistic fashion in vitro, further suggesting that the repeats cooperate to stimulate actin polymerization in vivo. One explanation for repeat synergy is that simultaneous engagement of multiple N-WASP molecules can enhance its ability to interact with the actin nucleating Arp2/3 complex. These findings define the minimal set of bacterial effectors required for pedestal formation and the elements within those effectors that contribute to actin assembly via N-WASP-Arp2/3–mediated signaling pathways

    Identification of Motifs of <em>Burkholderia pseudomallei</em>  BimA Required for Intracellular Motility, Actin Binding, and Actin Polymerization

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    Actin-based motility of the melioidosis pathogen Burkholderia pseudomallei requires BimA (Burkholderia intracellular motility A). The mechanism by which BimA mediates actin assembly at the bacterial pole is ill-defined. Toward an understanding of the regions of B. pseudomallei BimA required for intracellular motility and the binding and polymerization of actin, we constructed plasmid-borne bimA variants and glutathione-S-transferase fusion proteins with in-frame deletions of specific motifs. A 13-amino-acid direct repeat and IP(7) proline-rich motif were dispensable for actin binding and assembly in vitro, and expression of the mutated proteins in a B. pseudomallei bimA mutant restored actin-based motility in J774.2 murine macrophage-like cells. However, two WASP homology 2 (WH2) domains were found to be required for actin binding, actin assembly, and plaque formation. A tract of five PDASX direct repeats influenced the polymerization of pyrene-actin monomers in vitro and was required for actin-based motility and intercellular spread, but not actin binding. None of the mutations impaired surface expression or polar targeting of BimA. The number of PDASX repeats varied in natural isolates from two to seven. Such repeats acted additively to promote pyrene-actin polymerization in vitro, with stepwise increases in the rate of polymerization as the number of repeats was increased. No differences in the efficiency of actin tail formation could be discerned between strains expressing BimA variants with two, five, or seven PDASX repeats. The data provide valuable new insights into the role of conserved and variable motifs of BimA in actin-based motility and intercellular spread of B. pseudomallei

    Risk Factors for Intra-Abdominal Candidiasis in Intensive Care Units: Results from EUCANDICU Study

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    Introduction: Intra-abdominal infections represent the second most frequently acquired infection in the intensive care unit (ICU), with mortality rates ranging from 20% to 50%. Candida spp. may be responsible for up to 10–30% of cases. This study assesses risk factors for development of intra-abdominal candidiasis (IAC) among patients admitted to ICU. Methods: We performed a case–control study in 26 European ICUs during the period January 2015–December 2016. Patients at least 18&nbsp;years old who developed an episode of microbiologically documented IAC during their stay in the ICU (at least 48&nbsp;h after admission) served as the case cohort. The control group consisted of adult patients who did not develop episodes of IAC during ICU admission. Matching was performed at a ratio of 1:1 according to time at risk (i.e. controls had to have at least the same length of ICU stay as their matched cases prior to IAC onset), ICU ward and period of study. Results: During the study period, 101 case patients with a diagnosis of IAC were included in the study. On univariate analysis, severe hepatic failure, prior receipt of antibiotics, prior receipt of parenteral nutrition, abdominal drain, prior bacterial infection, anastomotic leakage, recurrent gastrointestinal perforation, prior receipt of antifungal drugs and higher median number of abdominal surgical interventions were associated with IAC development. On multivariate analysis, recurrent gastrointestinal perforation (OR 13.90; 95%&nbsp;CI 2.65–72.82, p = 0.002), anastomotic leakage (OR 6.61; 95%&nbsp;CI 1.98–21.99, p = 0.002), abdominal drain (OR 6.58; 95%&nbsp;CI 1.73–25.06, p = 0.006), prior receipt of antifungal drugs (OR 4.26; 95%&nbsp;CI 1.04–17.46, p = 0.04) or antibiotics (OR 3.78; 95%&nbsp;CI 1.32–10.52, p = 0.01) were independently associated with IAC. Conclusions: Gastrointestinal perforation, anastomotic leakage, abdominal drain and prior receipt of antifungals or antibiotics may help to identify critically ill patients with higher probability of developing IAC. Prospective studies are needed to identify which patients will benefit from early antifungal treatment

    Morphological and molecular analysis of natural hybrids between the diploid Centaurea aspera L. and the tetraploid C. seridis L. (Compositae)

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    [EN] Polyploidy and hybridisation are the basis of the evolution of Centaurea (Compositae). At the El Saler dune field (eastern Spain), the diploid Centaurea aspera ssp. stenophylla and the tetraploid C. seridis ssp. maritima form a polyploid complex in which C. x subdecurrens individuals occur. This polyploid complex was analysed morphologically and genetically, using random amplified polymorphic DNA (RAPD) and tubulin-based polymorphism (TBP) markers. Flow cytometry showed that the hybrids are triploid, which is a rare finding in Centaurea. Morphologically, in contrast to leaf characters, flowering characters clearly discriminated the three taxa. The genetic analyses confirm that C. x subdecurrens is a result of the hybridisation between Centaurea aspera ssp. stenophylla and C. seridis ssp. maritima, and suggest that backcrossing events and gene flow are very rare or absent. Although the hybrids likely represent true F1 offspring, they displayed some genetic diversity that is probably due to the combination of alleles. Genetic diversity was higher in diploid than in tetraploid individuals. This fact, and the high degree of sterility of the triploid hybrids, may reflect a cytotype minority exclusion effect. This may cause spatial segregation, which effectively takes place in the study area. Dune disturbance may lead to an overlapping of the parents' distribution areas, facilitating hybridisation.This work is posthumously dedicated to Antonio Samo Lumbreras, to whom we are very grateful for all his help. This study was sponsored by the Valencian Government (Research Project GVPRE/2008/130) and the Universitat Politecnica de Valencia (Research Project Ref. 3241).Ferriol Molina, M.; Garmendia, A.; Ruiz, J.; Merle Farinós, HB.; Boira Tortajada, H. (2012). Morphological and molecular analysis of natural hybrids between the diploid Centaurea aspera L. and the tetraploid C. seridis L. (Compositae). Plant Biosystems. 146(1):86-100. https://doi.org/10.1080/11263504.2012.727878S86100146

    Sustainable Development, Ecological Complexity, and Environmental Values

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    Sustainable Development, Ecological Complexity, and Environmental Values contributes to expanding the idea of sustainability by integrating different thematic issues related to sustainable development in its threefold consideration (economic, social, and environmental) with regard to the case of the Basque Country. On the global scale, changes have clearly accelerated; ecological and social sustainability are two facets of the same changing reality. First, social sustainability depends on ecological sustainability. If we continue degrading nature's capacity to produce the ecosystems' services (water filtration, climate stabilization, etc) and resources (food, materials), both individuals and nations will be affected by growing pressures and increasing conflicts, as well as by threats to public health and personal safety. Second, ecological sustainability depends on social sustainability, a socially unjust and unfair system wiht an ever-increasing population that is not able to have its needs met will necessarily lead to environmental collapse. In addition, human behavior and the social dynamic often lie at the heart of social and ecological problems. It must be, therefore, assumed that there will not be sustainable development if sustainable societies do not first exist. A sustainable society has the challenge of developing human capital. In this book, these global questions are treated as they relate to specific place and context, the Basque Country and its modern institutions.This book was published with generous financial support from the Basque Government.Introduction—Ignacio Ayestarán and Miren Onaindia ? 1. An Evaluation of Ecosystem Services as a Base for the Sustainable Management of a Region by Miren Onaindia and Gloria Rodríguez-Loinaz ? 2. An Evaluation of Millennium Ecosystems from the Basque Country by Igone Palacios, Izaskun Casada-Arzuaga, Iosu Madariaga, and Xabier Arana ? 3. Climate Change: Activities of the EOLO Group at the University of the Basque Country by Agustín Ezcurra, Jon Sáenz, and Gabriel Ibarra-Berastegi ? 4. The Environmental Value of the Karstic Landscape of the Urdaibai Biosphere Reserve: The Asnarre Promontory (Bizkaia) by Arantza Aranburu, Laura Damas-Mollá, Patxi García-Garmilla, Iñaki Yusta, M. Arriolabengoa, Peru Iridoy, and Eneko Iriarte ? 5. Recent Environmental Transformation of the Bilbao Estuary: Natural and Anthropogenic Processes by Alejandro Cearreta, Maria Jesús Irabien, and Eduardo Leorri ? 6. The Landscape of the Autonomous Community of the Basque Country: The Evolution of Forest Systems by Lorena Peña and Ibone Amezaga ? 7. Critical Theories of Sustainable Development by Eguzki Urteaga ? 8. Bases for the Transition toward a Sustainable Economy by Roberto Bermejo, David Hoyos, and Eneko Garmendia ? 9. Environmental Values, the Epistemology of Complex Problems, and Postnormal Science in the Face of Global Change by Ignacio Ayestáran ? 10. Science, Gender, and Sustainable Development by Teresa Nuño Angós ? 11. Environmental Education as Training: A Case Study at the University of the Basque Country by Araitz Uskola Ibarluzea ? 12. Social Values and Sustainable Practices among Basque Inshore Fishermen by Pío Pérez Aldasoro ? 13. Sustainable Development and the Values of Well-Being and Globalization by Eduardo Rubio Ardanaz, Juan Antonio Rubio-Ardanaz, and Xiao Fang ? Index ? List of Contributor

    Allogamy-Autogamy Switch Enhance Assortative Mating in the Allotetraploid Centaurea seridis L. Coexisting with the Diploid Centaurea aspera L. and Triggers the Asymmetrical Formation of Triploid Hybrids

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    [EN] Hybridization between tetraploids and its related diploids is generally unsuccessful in Centaurea, hence natural formation of triploid hybrids is rare. In contrast, the diploid Centaurea aspera and the allotetraploid C. seridis coexist in several contact zones where a high frequency of triploid hybrids is found. We analyzed the floral biology of the three taxa to identify reproductive isolation mechanisms that allow their coexistence. Flowering phenology was recorded, and controlled pollinations within and between the three taxa were performed in the field. Ploidy level and germination of progeny were also assessed. There was a 50% flowering overlap which indicated a phenological shift. Diploids were strictly allogamous and did not display mentor effects, while tetraploids were found to be highly autogamous. This breakdown of self-incompatibility by polyploids is first described in Centaurea. The asymmetrical formation of the hybrid was also found: all the triploid intact cypselae came from the diploid mothers pollinated by the pollen of tetraploids. Pollen and eggs from triploids were totally sterile, acting as a strong triploid block. These prezygotic isolation mechanisms ensured higher assortative mating in tetraploids than in diploids, improving its persistence in the contact zones. However these mechanisms can also be the cause of the low genetic diversity and high genetic structure observed in C. seridis.Ferriol Molina, M.; Garmendia, A.; Ana Gonzalez; Merle Farinós, HB. (2015). Allogamy-Autogamy Switch Enhance Assortative Mating in the Allotetraploid Centaurea seridis L. Coexisting with the Diploid Centaurea aspera L. and Triggers the Asymmetrical Formation of Triploid Hybrids. PLoS ONE. 10(10):1-13. doi:10.1371/journal.pone.0140465S1131010Jiao, Y., Wickett, N. J., Ayyampalayam, S., Chanderbali, A. S., Landherr, L., Ralph, P. E., … dePamphilis, C. W. (2011). Ancestral polyploidy in seed plants and angiosperms. Nature, 473(7345), 97-100. doi:10.1038/nature09916Wood, T. E., Takebayashi, N., Barker, M. S., Mayrose, I., Greenspoon, P. B., & Rieseberg, L. H. (2009). The frequency of polyploid speciation in vascular plants. Proceedings of the National Academy of Sciences, 106(33), 13875-13879. doi:10.1073/pnas.0811575106ROMASCHENKO, K., ERTUǦRUL, K., SUSANNA, A., GARCIA-JACAS, N., UYSAL, T., & ARSLAN, E. (2004). New chromosome counts in the Centaurea Jacea group (Asteraceae, Cardueae) and some related taxa. Botanical Journal of the Linnean Society, 145(3), 345-352. doi:10.1111/j.1095-8339.2004.00292.xHardy, O. J., de Loose, M., Vekemans, X., & Meerts, P. (2001). Allozyme segregation and inter-cytotype reproductive barriers in the polyploid complex Centaurea jacea. Heredity, 87(2), 136-145. doi:10.1046/j.1365-2540.2001.00862.xKOUTECKÝ, P., BAĎUROVÁ, T., ŠTECH, M., KOŠNAR, J., & KARÁSEK, J. (2011). Hybridization between diploidCentaurea pseudophrygiaand tetraploidC. jacea(Asteraceae): the role of mixed pollination, unreduced gametes, and mentor effects. Biological Journal of the Linnean Society, 104(1), 93-106. doi:10.1111/j.1095-8312.2011.01707.xKoutecký, P. (2012). A diploid drop in the tetraploid ocean: hybridization and long-term survival of a singular population of Centaurea weldeniana Rchb. (Asteraceae), a taxon new to Austria. Plant Systematics and Evolution, 298(7), 1349-1360. doi:10.1007/s00606-012-0641-5Mráz, P., Španiel, S., Keller, A., Bowmann, G., Farkas, A., Šingliarová, B., … Müller-Schärer, H. (2012). Anthropogenic disturbance as a driver of microspatial and microhabitat segregation of cytotypes of Centaurea stoebe and cytotype interactions in secondary contact zones. Annals of Botany, 110(3), 615-627. doi:10.1093/aob/mcs120Olšavská, K., & Löser, C. J. (2013). Mating System and Hybridization of the Cyanus triumfetti and C. montanus Groups (Asteraceae). 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Plant Biosystems - An International Journal Dealing with all Aspects of Plant Biology, 146(sup1), 86-100. doi:10.1080/11263504.2012.727878Ferriol, M., Merle, H., & Garmendia, A. (2014). Microsatellite evidence for low genetic diversity and reproductive isolation in tetraploidCentaurea seridis(Asteraceae) coexisting with diploidCentaurea asperaand triploid hybrids in contact zones. Botanical Journal of the Linnean Society, 176(1), 82-98. doi:10.1111/boj.12194Garmendia, A., Ferriol, M., Juarez, J., Zając, A., Kałużny, K., & Merle, H. (2015). A rare case of a natural contact zone in Morocco between an autopolyploid and an allopolyploid ofCentaurea asperawith sterile tetraploid hybrids. Plant Biology, 17(3), 746-757. doi:10.1111/plb.12284Petit, C., Bretagnolle, F., & Felber, F. (1999). Evolutionary consequences of diploid–polyploid hybrid zones in wild species. Trends in Ecology & Evolution, 14(8), 306-311. doi:10.1016/s0169-5347(99)01608-0Thorsson, A. 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    Anales de Edafología y Agrobiología Tomo 36 Número 1-2

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    Duración efectiva del índice de sequedad, por M. P. Garmendía y J. Garmendía.-- Adsorción y evolución de manganeso en arcillas, por O. Carpena, I. Tovar, A. Lax y F. Costa.-- Ecología de leguminosas en relación con algunos factores ambientales en Guadalajara. I. Aspectos florísticos y relación con la clase ele suelo, por M. Morey.-- Variaciones del contenido de nitrógeno en una plantación de Lolium perenne,por Esther Simón Martínez.-- Predicción de temperaturas máximas diarias, por E. Hernández, J. A. Hernández, J. F. Sánchez y J. Garmendía.-- Efectos del almacenaje sobre las propiedades físicas y biológicas de muestras tamizadas de suelos orgánicos, por F. Díaz-Fierros Viqueiro.-- Morfometría del cuarzo y circón aplicada al estudio genético de un suelo policíclico, por M. C. Villar Celorio.-- Contribución al estudio de la terra rossa española. II. Mineralogía de la fracción arcilla, por L. J. Alías, M. Nieto y J. Albaladejo.-- Entisoles del Campo de Cartagena (Murcia). Características generales y mineralógicas, por L. J. Alías y R. Ortiz Silla.-- Estudio sobre la composición química de variedades de almendra del sureste español, por F. Romojaro, J. F. García y F. J. López Andreu.-- Componentes del plátano canario y sus variaciones durante la maduración, por A. Carlos Blesa, M. A. Rodríguez Raymond y A. Maestre.-- Contribución al estudio de la platanera canaria. Relación entre la actividad respiratoria y la maduración de los plátanos, por A. Carlos Blesa, M. A Rodríguez Raymoud, C. D. Lorenzo e Isabel López.-- Notas.-- Reestructuración del C. S. I. C.-- Nombramiento del Prof. Casas Peláez como Presidente del C. S. I. C. 1.-- Carta del Presidente del C. S. I. C. al personal del mismo.-- Nombramiento del Prof. Snárez y Suárez como Director general de Educación Bastea.-- 6.° Curso Internacional de Fertilidad de Suelos y Nutrición Vegetal.—8ª Reunión Internacional de Micromorfología de Suelos.—19ª Conferencia General de la UNESCO.-- Sociedad Española de Ciencia del Suelo.-- Nombramiento de Secretario del Centro de Edafología y Biología Aplicada de Salamanca.-- Dimisión del Director del Centre de Edafología y Biología Aplicada del Cuarto (Sevilla).-- Propuesta de Director del Centro de Edafología y Biología Aplicada del Cuarto.-- Viaje del Prof. Troncoso.-- Grupo Español de Trabajo del Cuaternario.-- Autorizaciones para realizar función docente.-- Invitaciones a Profesores extranjeros.-- Programa de cooperación internacional con lberoamérica: bolsas de estudio y viaje .-- Conferencia del Prof. Salerno.-- Viaje realizado a Hispanoamérica por el Dr. D. Francisco Girela Vilchez.-- Creación del Centro de Formaci.ón y Promoción de Personal del C. S. I. C. (C. F. P. P.)Peer reviewed2019-08.- CopyBook.- Libnova.- Biblioteca ICA
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