Cimp-Positive Status is More Representative in Multiple Colorectal Cancers than in Unique Primary Colorectal Cancers

We thank the Tumor Registry of the Pathology Department of the 12 de Octubre University Hospital for providing the paraffin-embedded tissues, and Ron Hartong for his help with the English revision of this manuscript. This work was funded by Projects PI10/00683 and PI16/01650 to J.P, and PI16/01920 to R.G.S, from the Spanish Ministry of Health and Consumer Affairs and FEDER, and by Project 2012-0036 from the Mutua Madrileña Foundation. This work was supported by R01 (CA72851, CA181572, CA184792, CA202797) and U01 (CA187956, CA214254) grants from the National Cancer Institute, NIH; RP140784 from the CancerPrevention Research Institute of Texas; grants from the Baylor Foundation and Baylor Scott & White Research Institute, Dallas, TX, USA to AG.Colorectal cancer (CRC) with CpG island methylator phenotype (CIMP) is recognized as a subgroup of CRC that shows association with particular genetic defects and patient outcomes. We analyzed CIMP status of 229 individuals with CRC using an eight-marker panel (CACNA1G, CDKN2A, CRABP1, IGF2, MLH1, NEUROG1, RUNX3 and SOCS1); CIMP-(+) tumors were defined as having ≥ 5 methylated markers. Patients were divided into individuals who developed a "unique" CRC, which were subclassified into early-onset CRC (EOCRC) and late-onset CRC (LOCRC), and patients with multiple primary CRCs subclassified into synchronous CRC (SCRC) and metachronous CRC (MCRC). We found 9 (15.2%) CIMP-(+) EOCRC patients related with the proximal colon (p = 0.008), and 19 (26.8%) CIMP-(+) LOCRC patients associated with tumor differentiation (p = 0.045), MSI status (p = 0.021) and BRAF mutation (p = 0.001). Thirty-five (64.8%) SCRC patients had at least one CIMP-(+) tumor and 20 (44.4%) MCRC patients presented their first tumor as CIMP-(+). Thirty-nine (72.2%) SCRC patients showed concordant CIMP status in their simultaneous tumors. The differences in CIMP-(+) frequency between groups may reflect the importance of taking into account several criteria for the development of multiple primary neoplasms. Additionally, the concordance between synchronous tumors suggests CIMP status is generally maintained in SCRC patients.S

Scaffold coupling: ERK activation by trans-phosphorylation across different scaffold protein species.

RAS-ERK (extracellular signal-regulated kinase) pathway signals are modulated by scaffold proteins that assemble the components of different kinase tiers into a sequential phosphorylation cascade. In the prevailing model scaffold proteins function as isolated entities, where the flux of phosphorylation events progresses downstream linearly, to achieve ERK phosphorylation. We show that different types of scaffold proteins, specifically KSR1 (kinase suppressor of Ras 1) and IQGAP1 (IQ motif-containing guanosine triphosphatase activating protein 1), can bind to each other, forming a complex whereby phosphorylation reactions occur across both species. MEK (mitogen-activated protein kinase kinase) bound to IQGAP1 can phosphorylate ERK docked at KSR1, a process that we have named trans-phosphorylation. We also reveal that ERK trans-phosphorylation participates in KSR1-regulated adipogenesis, and it also underlies the modest cytotoxicity exhibited by KSR-directed inhibitors. Overall, we identify interactions between scaffold proteins and trans-phosphorylation as an additional level of regulation in the ERK cascade, with broad implications in signaling and the design of scaffold protein-aimed therapeutics

Combined Use of the Ab105-2φΔCI Lytic Mutant Phage and Different Antibiotics in Clinical Isolates of Multi-Resistant Acinetobacter baumannii

Phage therapy is an abandoned antimicrobial therapy that has been resumed in recent years. In this study, we mutated a lysogenic phage from Acinetobacter baumannii into a lytic phage (Ab105-2phi∆CI) that displayed antimicrobial activity against A. baumannii clinical strain Ab177_GEIH-2000 (isolated in the GEIH-REIPI Spanish Multicenter A. baumannii Study II 2000/2010, Umbrella Genbank Bioproject PRJNA422585, and for which meropenem and imipenem MICs of respectively, 32 μg/mL, and 16 μg/mL were obtained). We observed an in vitro synergistic antimicrobial effect (reduction of 4 log–7 log CFU/mL) between meropenem and the lytic phage in all combinations analyzed (Ab105-2phi∆CI mutant at 0.1, 1 and 10 MOI and meropenem at 1/4 and 1/8 MIC). Moreover, bacterial growth was reduced by 8 log CFU/mL for the combination of imipenem at 1/4 MIC plus lytic phage (Ab105-2phi∆CI mutant) and by 4 log CFU/mL for the combination of imipenem at 1/8 MIC plus lytic phage (Ab105-2phi∆CI mutant) at both MOI 1 and 10. These results were confirmed in an in vivo model (G. mellonella), and the combination of imipenem and mutant Ab105-2phi∆CI was most effective (p < 0.05). This approach could help to reduce the emergence of phage resistant bacteria and restore sensitivity to antibiotics used to combat multi-resistant strains of Acinetobacter baumannii

Escribir en la universidad: aplicación de nuevas tecnologías

Depto. de Lengua Española y Teoría de la LiteraturaFac. de FilologíaFALSEsubmitte

Experiencias en el aula: segundo encuentro de prácticas pedagógicas innovadoras

Experiencias de profesores en su quehacer en los distintos ambientes de aprendizaje presenciales y a distancia.La segunda entrega de Experiencias en el aula es una publicación anual que recoge las ponencias ganadoras presentadas en el Segundo Encuentro de Prácticas Pedagógicas Innovadoras, organizado por el Centro de Excelencia Docente aeiou, de la Vicerrectoría General Académica de la Corporación Universitaria Minuto de Dios – UNIMINUTO Todas las ponencias publicadas en la segunda entrega de Experiencias en el aula fueron seleccionadas por evaluadores externos durante la convocatoria al Segundo Encuentro de Prácticas Pedagógicas Innovadoras en el que fueron presentadas; este evento, organizado por el Centro de Excelencia Docente aeiou, y la Vicerrectoría General Académica de la Corporación Universitaria Minuto de Dios- UNIMINUTO, tuvo lugar los días 9 y 10 de octubre de 2017

La renovación de la palabra en el bicentenario de la Argentina : los colores de la mirada lingüística

El libro reúne trabajos en los que se exponen resultados de investigaciones presentadas por investigadores de Argentina, Chile, Brasil, España, Italia y Alemania en el XII Congreso de la Sociedad Argentina de Lingüística (SAL), Bicentenario: la renovación de la palabra, realizado en Mendoza, Argentina, entre el 6 y el 9 de abril de 2010. Las temáticas abordadas en los 167 capítulos muestran las grandes líneas de investigación que se desarrollan fundamentalmente en nuestro país, pero también en los otros países mencionados arriba, y señalan además las áreas que recién se inician, con poca tradición en nuestro país y que deberían fomentarse. Los trabajos aquí publicados se enmarcan dentro de las siguientes disciplinas y/o campos de investigación: Fonología, Sintaxis, Semántica y Pragmática, Lingüística Cognitiva, Análisis del Discurso, Psicolingüística, Adquisición de la Lengua, Sociolingüística y Dialectología, Didáctica de la lengua, Lingüística Aplicada, Lingüística Computacional, Historia de la Lengua y la Lingüística, Lenguas Aborígenes, Filosofía del Lenguaje, Lexicología y Terminología

Combination of resminostat with ruxolitinib exerts antitumor effects in the chick embryo chorioallantoic membrane model for cutaneous T cell lymphoma

The combination of Resminostat (HDACi) and Ruxolitinib (JAKi) exerted cytotoxic effects and inhibited proliferation of CTCL cell lines (MyLa, SeAx) in previously published work. A xenograft tumor formation was produced by implanting the MyLa or SeAx cells on top of the chick embryo chorioallantoic membrane (CAM). The CAM assay protocol was developed to monitor the metastatic properties of CTCL cells and the effects of Resminostat and/or Ruxolitinib in vivo. In the spontaneous CAM assays, Resminostat and Ruxolitinib treatment inhibited the cell proliferation (p < 0.001) of MyLa and SeAx, and induced cell apoptosis (p < 0.005, p < 0.001, respectively). Although monotherapies reduced the size of primary tumors in the metastasis CAM assay, the drug combination exhibited a significant inhibition of primary tumor size (p < 0.0001). Furthermore, the combined treatment inhibited the intravasation of MyLa (p < 0.005) and SeAx cells (p < 0.0001) in the organs, as well as their extravasation to the liver (p < 0.0001) and lung (p < 0.0001). The drug combination also exerted a stronger inhibitory effect in migration (p < 0.0001) rather in invasion (p < 0.005) of both MyLa and SeAx cells. It further reduced p-p38, p-ERK, p-AKT, and p-STAT in MyLa cells, while it decreased p-ERK and p-STAT in SeAx cells in CAM tumors. Our data demonstrated that the CAM assay could be employed as a preclinical in vivo model in CTCL for pharmacological testing. In agreement with previous in vitro data, the combination of Resminostat and Ruxolitinib was shown to exert antitumor effects in CTCL in vivo.This research was funded by a PIE grant (PIE-202020E007) at B.C lab from Consejo Superior de Investigaciones Científicas (CSIC)-MCIU, the Ramon y Cajal Research Program (MCIU, RYC2018-024004-I) and a LA FUNDACIÓ D’ESTUDIS I RECERCA ONCOLÒGICA (FERO) grant (BFERO2021.03)

Genealogía de la familia: Concepciones filosóficas, psicológicas, políticas y sociales Volumen 1

La familia desde una relectura de la política de Aristóteles, elaborado por Pablo Andrés Heredia y Catya Ximena Torres Cordero, en el que se presenta un análisis de la obra de Aristóteles con la finalidad de establecer las diferencias existentes entre las percepciones clásica y moderna sobre la familia; a su vez, los autores se proponen reconocer la relevancia de la familia en la construcción de la sociedad y del Estado a partir del análisis dedos obras de la filosofía política contemporánea: La condición humana deHannah Arendt (1993) y Homo Sacer de Giorgio Agamben (1998); obras que a decir de los autores retoman, extienden el pensamiento aristotélico y establecen una serie de directrices para comprender el lugar de la familia en el ámbito público.

Libro de Actas de las III Jornadas ScienCity 2020: Fomento de la Cultura Científica, Tecnológica y de Innovación en Ciudades Inteligentes

Editorial: Kindle Direct Publishing, Seattle, WS (USA)Actualmente, nuestras ciudades están experimentando una verdadera transformación digital que requiere una atención inmediata en energía, transporte, movilidad, comunicación, seguridad, educación, turismo y aspectos sociales, así como fomentar todas aquellas actuaciones que persigan mejorar la calidad de vida y el desarrollo económico-ambiental sostenible. ScienCity es un foro científico-tecnológico que pretende dar a conocer a la sociedad los conocimientos y tecnologías emergentes siendo investigados en las universidades, informar de experiencias, servicios e iniciativas puestas ya en marcha por instituciones y empresas, llegar hasta decisores políticos que podrían crear sinergias, incentivar la creación de ideas y posibilidades de desarrollo conjuntas, implicar y provocar la participación ciudadana.Junta de Andalucía, Universidad de Huelva y Consejo Social de la Universidad de Huelv