Chlorinated Guaiane-Type Sesquiterpene Lactones as Cytotoxic Agents against Human Tumor Cells

This article belongs to the Section Bioactives and Nutraceuticals.Guaiane-type sesquiterpene lactones are naturally occurring compounds which have attracted attention due to their array of biological activities. In this study, chlorinated guaianolides 1–8, isolated from plants of the genus Centaurea, were evaluated against the human leukemia cell lines HL-60, U-937, a specific U-937 cell line that overexpresses the anti-apoptotic Bcl-2 protein and the human melanoma cell line SK-MEL-1. This established the relevant structure-growth inhibition relationships. Chlorohyssopifolins A (1), C (3) and D (4) and linichlorin A (6) were the most potent compounds in terms of inducing growth inhibition in the four cell lines. IC50 values were below 10 μM in all cases. Chlorohyssopifolins A (1) and D (4) and linichlorin A (6) were potent apoptotic inducers in human U-937 leukemia cells, as determined by fluorescent microscopy and flow cytometry, and their mechanism of action was associated with cytochrome c release, caspase activation and poly(ADP-ribose)polymerase cleavage. Overall this study shows that guaianolides induce cytotoxicity against human tumor cells and provides important insights into the cell death pathways that are involved.This research was funded by FEDER and AGENCIA CANARIA DE INVESTIGACIÓN, INNOVACIÓN Y SOCIEDAD DE LA INFORMACIÓN (PROID2017010095 FEDER/ACIISI) and in part by the Spanish Ministry of Science, Innovation and Universities and the European Regional Development Fund (PGC2018-094503-B-C21)

De Novo Sporophyte Transcriptome Assembly and Functional Annotation in the Endangered Fern Species Vandenboschia speciosa (Willd.) G. Kunkel

We sequenced the sporophyte transcriptome of Killarney fern (Vandenboschia speciosa (Willd.) G. Kunkel). In addition to being a rare endangered Macaronesian-European endemism, this species has a huge genome (10.52 Gb) as well as particular biological features and extreme ecological requirements. These characteristics, together with the systematic position of ferns among vascular plants, make it of high interest for evolutionary, conservation and functional genomics studies. The transcriptome was constructed de novo and contained 36,430 transcripts, of which 17,706 had valid BLAST hits. A total of 19,539 transcripts showed at least one of the 7362 GO terms assigned to the transcriptome, whereas 6547 transcripts showed at least one of the 1359 KEGG assigned terms. A prospective analysis of functional annotation results provided relevant insights on genes involved in important functions such as growth and development as well as physiological adaptations. In this context, a catalogue of genes involved in the genetic control of plant development, during the vegetative to reproductive transition, in stress response as well as genes coding for transcription factors is given. Altogether, this study provides a first step towards understanding the gene expression of a significant fern species and the in silico functional and comparative analyses reported here provide important data and insights for further comparative evolutionary studies in ferns and land plants in general.Spanish Ministerio de Economía y Competitividad and FEDER founds, grant: CGL2010-14856 (subprograma BOS)

Identification and Characterization of TALE Homeobox Genes in the Endangered Fern Vandenboschia speciosa

We report and discuss the results of a quantitative reverse transcription polymerase chain reaction (qRT-PCR) analysis of the expression patterns of seven three amino acid loop extension (TALE) homeobox genes (four KNOTTED-like homeobox (KNOX) and three BEL1-like homeobox (BELL) genes) identified after next generation sequencing (NGS) and assembly of the sporophyte and gametophyte transcriptomes of the endangered fern species Vandenboschia speciosa. Among the four KNOX genes, two belonged to the KNOX1 class and the other two belonged to the KNOX2 class. Analysis of the deduced amino acid sequences supported the typical domain structure of both types of TALE proteins, and the homology to TALE proteins of mosses, lycophytes, and seed plant species. The expression analyses demonstrate that these homeodomain proteins appear to have a key role in the establishment and development of the gametophyte and sporophyte phases of V. speciosa lifecycle, as well as in the control of the transition between both phases. Vandenboschia speciosa VsKNAT3 (a KNOX2 class protein) as well as VsBELL4 and VsBELL10 proteins have higher expression levels during the sporophyte program. On the contrary, one V. speciosa KNOX1 protein (VsKNAT6) and one KNOX2 protein (VsKNAT4) seem important during the development of the gametophyte phase. TALE homeobox genes might be among the key regulators in the gametophyte-to-sporophyte developmental transition in regular populations that show alternation of generations, since some of the genes analyzed here (VsKNAT3, VsKNAT6, VsBELL4, and VsBELL6) are upregulated in a non-alternating population in which only independent gametophytes are found (they grow by vegetative reproduction outside of the range of sporophyte distribution). Thus, these four genes might trigger the vegetative propagation of the gametophyte and the repression of the sexual development in populations composed of independent gametophytes. This study represents a comprehensive identification and characterization of TALE homeobox genes in V. speciosa, and gives novel insights about the role of these genes in fern development.This research has been financed by the Spanish Ministerio de Economía y Competitividad and FEDER founds, grant: CGL2010-14856 (subprograma BOS).M. Bakkali wishes to thank the Spanish Ministerio de Economía y Competitividad for granting him with a Ramón y Cajal Fellowship, the BFU2010-16438 grant, and an FPI studentship to R. Martín-Blázquez

SQLab: Laboratorio virtual lenguaje SQL

En este proyecto se ha desarrollado un corrector automático de consultas SQL. Aunque estas herramientas suelen ser de propósito general, en este caso tiene un carácter docente, permitiendo a los estudiantes perfeccionar y afianzar los conocimientos adquiridos de forma autónoma, sin la necesaria supervisión de un profesor que valide las soluciones que proponen a los diferentes problemas que se les plantean. Los docentes podrán agilizar el proceso de corrección de los ejercicios así como realizar un seguimiento del avance de los alumnos, lo que le permitirá detectar aquellos aspectos en los que debe incidir más, así como seleccionar ejercicios orientados a reforzar determinados conocimientos

Preferential Occupancy of R2 Retroelements on the B Chromosomes of the Grasshopper Eyprepocnemis plorans

R2 non-LTR retrotransposons exclusively insert into the 28S rRNA genes of their host, and are expressed by co-transcription with the rDNA unit. The grasshopper Eyprepocnemis plorans contains transcribed rDNA clusters on most of its A chromosomes, as well as non-transcribed rDNA clusters on the parasitic B chromosomes found in many populations. Here the structure of the E. plorans R2 element, its abundance relative to the number of rDNA units and its retrotransposition activity were determined. Animals screened from five populations contained on average over 12,000 rDNA units on their A chromosomes, but surprisingly only about 100 R2 elements. Monitoring the patterns of R2 insertions in individuals from these populations revealed only low levels of retrotransposition. The low rates of R2 insertion observed in E. plorans differ from the high levels of R2 insertion previously observed in insect species that have many fewer rDNA units. It is proposed that high levels of R2 are strongly selected against in E. plorans, because the rDNA transcription machinery in this species is unable to differentiate between R2-inserted and uninserted units. The B chromosomes of E. plorans contain an additional 7,000 to 15,000 rDNA units, but in contrast to the A chromosomes, from 150 to over 1,500 R2 elements. The higher concentration of R2 in the inactive B chromosomes rDNA clusters suggests these chromosomes can act as a sink for R2 insertions thus further reducing the level of insertions on the A chromosomes. These studies suggest an interesting evolutionary relationship between the parasitic B chromosomes and R2 elements.This study was supported by grants from the Spanish Ministerio de Ciencia y Tecnología (CGL2009-11917) and Plan Andaluz de Investigacion (CVI-6649), and was partially performed by FEDER funds and a grant from the National Institutes of Health (GM42790)

B-Chromosome Ribosomal DNA Is Functional in the Grasshopper Eyprepocnemis plorans

B-chromosomes are frequently argued to be genetically inert elements, but activity for some particular genes has been reported, especially for ribosomal RNA (rRNA) genes whose expression can easily be detected at the cytological level by the visualization of their phenotypic expression, i.e., the nucleolus. The B24 chromosome in the grasshopper Eyprepocnemis plorans frequently shows a nucleolus attached to it during meiotic prophase I. Here we show the presence of rRNA transcripts that unequivocally came from the B24 chromosome. To detect these transcripts, we designed primers specifically anchoring at the ITS-2 region, so that the reverse primer was complementary to the B chromosome DNA sequence including a differential adenine insertion being absent in the ITS2 of A chromosomes. PCR analysis carried out on genomic DNA showed amplification in B-carrying males but not in B-lacking ones. PCR analyses performed on complementary DNA showed amplification in about half of B-carrying males. Joint cytological and molecular analysis performed on 34 B-carrying males showed a close correspondence between the presence of B-specific transcripts and of nucleoli attached to the B chromosome. In addition, the molecular analysis revealed activity of the B chromosome rDNA in 10 out of the 13 B-carrying females analysed. Our results suggest that the nucleoli attached to B chromosomes are actively formed by expression of the rDNA carried by them, and not by recruitment of nucleolar materials formed in A chromosome nucleolar organizing regions. Therefore, B-chromosome rDNA in E. plorans is functional since it is actively transcribed to form the nucleolus attached to the B chromosome. This demonstrates that some heterochromatic B chromosomes can harbour functional genes.This study was supported by a grant from the Spanish Ministerio de Ciencia e Innovación (CGL2009-11917), and was partially performed by FEDER funds. M. Ruiz-Estévez was supported by a fellowship (FPU) from the Spanish Ministerio de Ciencia e Innovación

Docencia en Derecho y Proceso: hacia un aprendizaje de calidad en la Universidad

Presentación / Esther Pillado González (pp. 11-13). -- La adaptación de la asignatura derecho procesal penal al grado en la Universidad Carlos III de Madrid: un proceso aún inconcluso / Juan Manuel Alcoceba Gil (pp. 17-26). -- Role playing, cooperación competitiva y method case en la docencia-aprendizaje del Derecho Procesal / Cristina Alonso Salgado (pp. 27-35). -- Esquemas y materiales básicos para explicar en el grado en derecho el sistema de impugnación de actos jurídicos de las administraciones públicas en España / Roberto O. Bustillo Bolado (pp. 37-40). -- Nuevas herramientas y técnicas para la docencia del derecho / Juan Cámara Ruiz (pp. 41-51). -- Novas técnicas na docência em direito / Marco Carvalho Gonçalves (pp. 53-60). -- Experiência de lecionação em Direito em cursos não jurídicos – a lecionação da UC de Direito das Crianças e Jovens ao Mestrado em Intervenção Psicossocial com Crianças, Jovens e Famílias do Instituto de Educação / Cristina M. A. Dias (pp. 61-67). -- Los programas universitarios para mayores: la docencia en Derecho en la Universidad de Vigo / Teresa Estévez Abeleira (pp. 69-79). -- El aprendizaje activo del Derecho Procesal / María Dolores Fernández Fustes (81-92). -- El aprendizaje como método de adquirir los conocimientos / Raquel López Jiménez (pp. 93-101). -- Alumnado con necesidades especiales en el grado en derecho: el reto de la normalización e inclusión / Ángel M. Mariño de Andrés y M. Teresa Martínez Táboas (pp. 103-110). -- Docencia y proceso penal: intentando experimentar el proceso / Sabela Oubiña Barbolla (pp. 111-127). -- La integración de las redes sociales en la enseñanza del Derecho Penal / Natalia Pérez Rivas (pp. 129-135). -- Análisis y prospectiva de una plataforma e-learning en ciencias jurídicas / Amparo Rodríguez Damián, Margarita Pino Juste, Arturo Casar Sarasola y Manuel Pérez Cota (pp. 137-149). -- La evaluación de competencias en las materias “prácticas externas” del Máster Universitario en Abogacía: problemas y retos / Mónica Siota Álvarez (pp. 151-164). -- La enseñanza del derecho procesal a través del método del caso / Helena Soleto Muñoz (pp. 165-178). -- A aprendizagem activa do Direito Processual – reflexão sobre velhos hábitos e novas práticas / Lurdes Varregoso Mesquita (pp. 179-189). -- Acão executiva e metodologia aplicada – demonstração de caso / Lurdes Varregoso Mesquita, Diana Leiras (pp. 191-201). -- Derecho Constitucional y género / Almudena Bergareche Gros (pp. 205-216). -- Aproximación al fenómeno de la violencia de género a través de las novelas como recurso didáctico / María Castro Corredoira (pp. 217-227). -- La formación en género en derecho penal: el cine como recurso didáctico / Natalia Pérez Rivas, Fernando Vázquez-Portomeñe Seijas (pp. 229-240). -- Cuestiones controvertidas de la docencia en el ámbito del derecho constitucional: la perspectiva de género y el principio de transversalidad / Pablo Riquelme Vázquez (pp. 241-253). -- Storytelling y cine extranjero en la explicación del sistema de justicia penal español / Cristina Alonso Salgado (pp. 257-263). -- Direito e Cinema. Breve reflexão a partir da experiência da docência ao 1.º ano do curso de Direito / Maria Clara Calheiros (pp. 265-273). -- El cine como opción pedagógica en la enseñanza del derecho penal / Fernando Vázquez-Portomeñe Seijas y María Castro Corredoira (pp. 275-286). -- El jurista del siglo XXI y la Universidad del siglo pasado: ¿realidades irreconciliables? / Amaya Arnáiz Serrano (pp. 289-307). -- La formación del abogado del siglo XXI / Emiliano Carretero Morales (pp. 309-321). -- El cambio del perfil del alumno y su influencia a la enseñanza superior / Anna Fiodorova (pp. 323-335). -- La enseñanza del derecho en el marco Bolonia: reflexiones en base a las distintas tradiciones jurídicas / Mercedes Llorente Sánchez-Arjona (pp. 337-355)

CIBERER : Spanish national network for research on rare diseases: A highly productive collaborative initiative

Altres ajuts: Instituto de Salud Carlos III (ISCIII); Ministerio de Ciencia e Innovación.CIBER (Center for Biomedical Network Research; Centro de Investigación Biomédica En Red) is a public national consortium created in 2006 under the umbrella of the Spanish National Institute of Health Carlos III (ISCIII). This innovative research structure comprises 11 different specific areas dedicated to the main public health priorities in the National Health System. CIBERER, the thematic area of CIBER focused on rare diseases (RDs) currently consists of 75 research groups belonging to universities, research centers, and hospitals of the entire country. CIBERER's mission is to be a center prioritizing and favoring collaboration and cooperation between biomedical and clinical research groups, with special emphasis on the aspects of genetic, molecular, biochemical, and cellular research of RDs. This research is the basis for providing new tools for the diagnosis and therapy of low-prevalence diseases, in line with the International Rare Diseases Research Consortium (IRDiRC) objectives, thus favoring translational research between the scientific environment of the laboratory and the clinical setting of health centers. In this article, we intend to review CIBERER's 15-year journey and summarize the main results obtained in terms of internationalization, scientific production, contributions toward the discovery of new therapies and novel genes associated to diseases, cooperation with patients' associations and many other topics related to RD research