Nueva metodología docente en el Derecho Procesal

La entrada al Espacio Europeo de Educación Superior supone una modificación en las metodologías docentes que, tradicionalmente, se han utilizado en el sistema educativo español hasta la actualidad, donde mayoritariamente las lecciones se efectuaban mediante clases magistrales, con las que, la interacción profesor- alumno era, en muchas ocasiones, insuficiente. Este sistema metodológico es modificado por nuevas opciones de aprendizaje que favorecen una mayor interacción entre profesor y estudiante. Los nuevos métodos docentes deben permitir aumentar la eficacia en los procesos de formación de los titulados, pretendiendo lograr, de este modo, la armonización europea en cuanto a la formación superior. Uno de los principales objetivos que se pretenden conseguir con la utilización de estas metodologías se concreta en una mayor participación del alumno en el proceso de aprendizaje, que facilite la adquisición e interiorización de los conocimientos exigidos en cada materia. De esta forma, el estudiante debe adoptar un papel más activo durante sus estudios y, en especial, en su asistencia a las aulas de nuestras Universidades. El aprendizaje por módulos se configura como una alternativa metodológica que pretende estimular la creatividad del alumno, dejando que se enfrente al estudio directamente, y sea él quien analice los textos normativos, doctrinales y jurisprudenciales, y sea capaz de buscar la información necesaria para resolver problemas y redactar documentos jurídicos, asegurando que los alumnos se incorporen al mercado laboral con unas aptitudes y habilidades propias en las materias que han estudiado durante su educación superior. Fruto de esta nueva forma de enseñar- aprender, el estudiante a través de la adquisición de competencias y habilidades, puede ser evaluado de forma continua durante todo el curso académico por el docente, que de forma periódica y progresiva, examina el nivel de comprensión por parte de alumno en relación a las materias analizadas en clase

Nueva metodología docente en el Derecho Procesal

La entrada al Espacio Europeo de Educación Superior supone una modificación en las metodologías docentes que, tradicionalmente, se han utilizado en el sistema educativo español hasta la actualidad, donde mayoritariamente las lecciones se efectuaban mediante clases magistrales, con las que, la interacción profesor- alumno era, en muchas ocasiones, insuficiente. Este sistema metodológico es modificado por nuevas opciones de aprendizaje que favorecen una mayor interacción entre profesor y estudiante. Los nuevos métodos docentes deben permitir aumentar la eficacia en los procesos de formación de los titulados, pretendiendo lograr, de este modo, la armonización europea en cuanto a la formación superior. Uno de los principales objetivos que se pretenden conseguir con la utilización de estas metodologías se concreta en una mayor participación del alumno en el proceso de aprendizaje, que facilite la adquisición e interiorización de los conocimientos exigidos en cada materia. De esta forma, el estudiante debe adoptar un papel más activo durante sus estudios y, en especial, en su asistencia a las aulas de nuestras Universidades. El aprendizaje por módulos se configura como una alternativa metodológica que pretende estimular la creatividad del alumno, dejando que se enfrente al estudio directamente, y sea él quien analice los textos normativos, doctrinales y jurisprudenciales, y sea capaz de buscar la información necesaria para resolver problemas y redactar documentos jurídicos, asegurando que los alumnos se incorporen al mercado laboral con unas aptitudes y habilidades propias en las materias que han estudiado durante su educación superior.

mRNA-based approach to monitor recombinant gamma-interferon restoration of LPS-induced endotoxin tolerance

Introduction: It is now well accepted that sepsis is associated with the development of a pronounced immunosuppressive state, characterized by severe immune alterations (e.g. reduced proliferative capacity, endotoxin tolerance, apoptosis) participating in increased mortality and susceptibility to nosocomial infections. Efforts are currently aimed at restoring a functional immune response in septic patients. Successful therapydepends on the identification of appropriate immunostimulatory drugs and on the development of suitable biomarkers that could be used to stratify patients and to follow response to treatment.Methods: In this study, we evaluated the ex vivo effect of recombinant interferon gamma (rIFN-g) in restoring monocyte functionality (endotoxin-induced Tumor Necrosis Factor-a production) in a two-hit model of endotoxin tolerance (ET) with peripheral blood mononuclear cells from healthy volunteers and in whole blood of septic shockpatients. Importantly, we used quantitative-reverse transcription polymerase-chain reaction to monitor the effect of rIFN-g on the expression of seven genes known to participate in ET (TNF-a, IL-10, HLA-DRA, CIITA, IRAK-M, ABIN-3 and LY64).Results: Expression analysis of those genes confirmed the presence of an immunosuppression state and the ex vivo restoration of immune functions by rIFN-g. We show for the first time that rIFN-g is able to bypass, at the mRNA level, the effect of negative regulators of the LPS signalling pathway such as IRAK-M, ABIN-3 and LY64.Conclusions: Overall, mRNA expressions of a panel of genes could represent promising candidates for the ex vivo evaluation of rIFN-g effect on monocyte functionality. This ex vivo translational research study demonstrates the potential of a mRNA-based approach to successfully monitor drug efficacy

Tbx1 expression in pharyngeal epithelia is necessary for pharyngeal arch artery development.

During embryonic life, the initially paired pharyngeal arch arteries (PAAs) follow a precisely orchestrated program of persistence and regression that leads to the formation of the mature aortic arch and great vessels. When this program fails, specific cardiovascular defects arise that may be life threatening or mild, according to the identity of the affected artery. Fourth PAA-derived cardiovascular defects occur commonly in DiGeorge syndrome and velocardiofacial syndrome (22q11DS), and in Tbx1(+/-) mice that model the 22q11DS cardiovascular phenotype. Tbx1 is expressed in pharyngeal mesoderm, endoderm and ectoderm, and, in addition, we show that it is expressed in precursors of the endothelial cells that line the PAAs, thus expanding the number of tissues in which Tbx1 is potentially required for fourth PAA development. In this study, we have used cell fate mapping and tissue-specific gene deletion, driven by six different Cre lines, to explore Tbx1 gene-dosage requirements in the embryonic pharynx for fourth PAA development. Through this approach, we have resolved the spatial requirements for Tbx1 in this process, and we show pharyngeal epithelia to be a critical tissue. We also thereby demonstrate conclusively that the role of Tbx1 in fourth PAA development is cell non-autonomous

AT514, a cyclic depsipeptide from Serratia marcescens, induces apoptosis of B-chronic lymphocytic leukemia cells. Interference with the Akt/NF-kB survival pathway

8 páginas, 5 figuras -- PAGS nros. 572-579Clinical treatment of B-cell chronic lymphocytic leukemia (B-CLL) is limited by the progressive drug resistance and nonselectivity of most drugs towards malignant cells. Depsipeptides are present in certain bacteria and display potent antitumor activity. We have studied the effect of the novel cyclodepsipeptide AT514 (serratamolide) from Serratia marcescens on B-CLL cell viability. AT514 induced apoptosis of B-CLL cells from the 21 patients studied, as confirmed by Annexin-V binding and nuclei condensation, with an average IC50 of 13 M. AT514 was effective in those B-CLL cases resistant to fludarabine, but had no effect on normal PBL. AT514 preferentially activated the intrinsic apoptotic pathway, as evidenced by loss of mitochondrial membrane potential, release of cytochrome c and activation of caspase-9 and -3, but not of caspase-8. Importantly, AT514 interfered with phosphatidylinositol-3 kinase and protein kinase C survival signals since it increased the apoptotic effect of LY294002 and BisI inhibitors, and induced Akt dephosphorylation at Ser 473. AT514 also decreased NF-B activity by dramatically reducing the levels of p65 in B-CLL. This was confirmed on functional assays using NF-B-luc-transfected Raji cells and transgenic mice. Our results establish that AT514 induces apoptosis of primary B-CLL cells and could be useful for clinical treatment of this malignancyThis work was supported by grants 08.3/0030.1/2003 from the Comunidad Autónoma de Madrid, SAF2003-00824 from the Ministerio de Ciencia y Tecnología (MCyT), and 01/1183 from Fondo de Investigación Sanitaria (to AGP); and CIDEM Grant 301888 (Generalitat de Catalunya)/Fundació Bosch i Gimpera, to RPT). E Escobar and E López-Martín were supported by fellowships from MCyTPeer reviewe

Endogenous Retroviruses Transcriptional Modulation After Severe Infection, Trauma and Burn

Although human endogenous retroviruses (HERVs) expression is a growing subject of interest, no study focused before on specific endogenous retroviruses loci activation in severely injured patients. Yet, HERV reactivation is observed in immunity compromised settings like some cancers and auto-immune diseases. Our objective was to assess the transcriptional modulation of HERVs in burn, trauma and septic shock patients. We analyzed HERV transcriptome with microarray data from whole blood samples of a burn cohort (n = 30), a trauma cohort (n = 105) and 2 septic shock cohorts (n = 28, n = 51), and healthy volunteers (HV, n = 60). We described expression of the 337 probesets targeting HERV from U133 plus 2.0 microarray in each dataset and then we compared HERVs transcriptional modulation of patients compared to healthy volunteers. Although all 4 cohorts contained critically ill patients, the majority of the 337 HERVs was not expressed (around 74% in mean). Each cohort had differentially expressed probesets in patients compared to HV (from 19 to 46). Strikingly, 5 HERVs were in common in all types of severely injured patients, with 4 being up-modulated in patients. We highlighted co-expressed profiles between HERV and nearby CD55 and CD300LF genes as well as autonomous HERV expression. We suggest an inflammatory-specific HERV transcriptional response, and importantly, we introduce that the HERVs close to immunity-related genes might have a role on its expression

Genomic Relationships, Novel Loci, and Pleiotropic Mechanisms across Eight Psychiatric Disorders

Genetic influences on psychiatric disorders transcend diagnostic boundaries, suggesting substantial pleiotropy of contributing loci. However, the nature and mechanisms of these pleiotropic effects remain unclear. We performed analyses of 232,964 cases and 494,162 controls from genome-wide studies of anorexia nervosa, attention-deficit/hyper-activity disorder, autism spectrum disorder, bipolar disorder, major depression, obsessive-compulsive disorder, schizophrenia, and Tourette syndrome. Genetic correlation analyses revealed a meaningful structure within the eight disorders, identifying three groups of inter-related disorders. Meta-analysis across these eight disorders detected 109 loci associated with at least two psychiatric disorders, including 23 loci with pleiotropic effects on four or more disorders and 11 loci with antagonistic effects on multiple disorders. The pleiotropic loci are located within genes that show heightened expression in the brain throughout the lifespan, beginning prenatally in the second trimester, and play prominent roles in neurodevelopmental processes. These findings have important implications for psychiatric nosology, drug development, and risk prediction.Peer reviewe

The genetics of the mood disorder spectrum:genome-wide association analyses of over 185,000 cases and 439,000 controls

Background Mood disorders (including major depressive disorder and bipolar disorder) affect 10-20% of the population. They range from brief, mild episodes to severe, incapacitating conditions that markedly impact lives. Despite their diagnostic distinction, multiple approaches have shown considerable sharing of risk factors across the mood disorders. Methods To clarify their shared molecular genetic basis, and to highlight disorder-specific associations, we meta-analysed data from the latest Psychiatric Genomics Consortium (PGC) genome-wide association studies of major depression (including data from 23andMe) and bipolar disorder, and an additional major depressive disorder cohort from UK Biobank (total: 185,285 cases, 439,741 controls; non-overlapping N = 609,424). Results Seventy-three loci reached genome-wide significance in the meta-analysis, including 15 that are novel for mood disorders. More genome-wide significant loci from the PGC analysis of major depression than bipolar disorder reached genome-wide significance. Genetic correlations revealed that type 2 bipolar disorder correlates strongly with recurrent and single episode major depressive disorder. Systems biology analyses highlight both similarities and differences between the mood disorders, particularly in the mouse brain cell-types implicated by the expression patterns of associated genes. The mood disorders also differ in their genetic correlation with educational attainment – positive in bipolar disorder but negative in major depressive disorder. Conclusions The mood disorders share several genetic associations, and can be combined effectively to increase variant discovery. However, we demonstrate several differences between these disorders. Analysing subtypes of major depressive disorder and bipolar disorder provides evidence for a genetic mood disorders spectrum