Common cellular events occur during wound healing and organ regeneration in the sea cucumber Holothuria glaberrima

<p>Abstract</p> <p>Background</p> <p>All animals possess some type of tissue repair mechanism. In some species, the capacity to repair tissues is limited to the healing of wounds. Other species, such as echinoderms, posses a striking repair capability that can include the replacement of entire organs. It has been reported that some mechanisms, namely extracellular matrix remodeling, appear to occur in most repair processes. However, it remains unclear to what extent the process of organ regeneration, particularly in animals where loss and regeneration of complex structures is a programmed natural event, is similar to wound healing. We have now used the sea cucumber <it>Holothuria glaberrima </it>to address this question.</p> <p>Results</p> <p>Animals were lesioned by making a 3–5 mm transverse incision between one of the longitudinal muscle pairs along the bodywall. Lesioned tissues included muscle, nerve, water canal and dermis. Animals were allowed to heal for up to four weeks (2, 6, 12, 20, and 28 days post-injury) before sacrificed. Tissues were sectioned in a cryostat and changes in cellular and tissue elements during repair were evaluated using classical dyes, immmuohistochemistry and phalloidin labeling. In addition, the temporal and spatial distribution of cell proliferation in the animals was assayed using BrdU incorporation. We found that cellular events associated with wound healing in <it>H. glaberrima </it>correspond to those previously shown to occur during intestinal regeneration. These include: (1) an increase in the number of spherule-containing cells, (2) remodeling of the extracellular matrix, (3) formation of spindle-like structures that signal dedifferentiation of muscle cells in the area flanking the lesion site and (4) intense cellular division occurring mainly in the coelomic epithelium after the first week of regeneration.</p> <p>Conclusion</p> <p>Our data indicate that <it>H. glaberrima </it>employs analogous cellular mechanisms during wound healing and organ regeneration. Thus, it is possible that regenerative limitations in some organisms are due either to the absence of particular mechanisms associated with repair or the inability of activating the repair process in some tissues or stages.</p

Cell dedifferentiation and epithelial to mesenchymal transitions during intestinal regeneration in H. glaberrima

<p>Abstract</p> <p>Background</p> <p>Determining the type and source of cells involved in regenerative processes has been one of the most important goals of researchers in the field of regeneration biology. We have previously used several cellular markers to characterize the cells involved in the regeneration of the intestine in the sea cucumber <it>Holothuria glaberrima</it>.</p> <p>Results</p> <p>We have now obtained a monoclonal antibody that labels the mesothelium; the outer layer of the gut wall composed of peritoneocytes and myocytes. Using this antibody we studied the role of this tissue layer in the early stages of intestinal regeneration. We have now shown that the mesothelial cells of the mesentery, specifically the muscle component, undergo dedifferentiation from very early on in the regeneration process. Cell proliferation, on the other hand, increases much later, and mainly takes place in the mesothelium or coelomic epithelium of the regenerating intestinal rudiment. Moreover, we have found that the formation of the intestinal rudiment involves a novel regenerative mechanism where epithelial cells ingress into the connective tissue and acquire mesenchymal phenotypes.</p> <p>Conclusions</p> <p>Our results strongly suggest that the dedifferentiating mesothelium provides the initial source of cells for the formation of the intestinal rudiment. At later stages, cell proliferation supplies additional cells necessary for the increase in size of the regenerate. Our data also shows that the mechanism of epithelial to mesenchymal transition provides many of the connective tissue cells found in the regenerating intestine. These results present some new and important information as to the cellular basis of organ regeneration and in particular to the process of regeneration of visceral organs.</p

Differentiation stage of myeloma plasma cells: biological and clinical significance

[EN] The notion that plasma cells (PCs) are terminally differentiated has prevented intensive research in multiple myeloma (MM) about their phenotypic plasticity and differentiation. Here, we demonstrated in healthy individuals (n = 20) that the CD19 − CD81 expression axis identifies three bone marrow (BM)PC subsets with distinct age-prevalence, proliferation, replication-history, immunoglobulin-production, and phenotype, consistent with progressively increased differentiation from CD19+CD81+ into CD19 − CD81+ and CD19 − CD81 − BMPCs. Afterwards, we demonstrated in 225 newly diagnosed MM patients that, comparing to normal BMPC counterparts, 59% had fully differentiated (CD19 − CD81 −) clones, 38% intermediate-differentiated (CD19 − CD81+) and 3% less-differentiated (CD19+CD81+) clones. The latter patients had dismal outcome, and PC differentiation emerged as an independent prognostic marker for progression-free (HR: 1.7; P = 0.005) and overall survival (HR: 2.1; P = 0.006). Longitudinal comparison of diagnostic vs minimal-residual-disease samples (n = 40) unraveled that in 20% of patients, less-differentiated PCs subclones become enriched after therapy-induced pressure. We also revealed that CD81 expression is epigenetically regulated, that less-differentiated clonal PCs retain high expression of genes related to preceding B-cell stages (for example: PAX5), and show distinct mutation profile vs fully differentiated PC clones within individual patients. Together, we shed new light into PC plasticity and demonstrated that MM patients harbouring less-differentiated PCs have dismal survival, which might be related to higher chemoresistant potential plus different molecular and genomic profiles

Revisitando el cine documental: de Flaherty al webdoc

En los últimos tiempos, y propiciado por el auge de la imagen digital, el género documental ha liderado una importante renovación en sus formas cinematográficas indagando en nuevos lenguajes para la imagen contemporánea. Desdibujando por completo los límites entre la ficción y la no ficción, el documental contemporáneo ha fraccionado algunas de las convenciones asociadas al género, encontrando fácil acomodo entre lo narrativo, lo observacional, lo etnográfico, lo ensayístico, la videocreación, lo autobiográfico y, obviamente, lo experimental. Tras décadas de constante mutación, el cine documental se nos presenta como un fascinante territorio de exploración fílmica, aportando una reflexión sobre las fronteras actuales del lenguaje cinematográfico y que requiere a su vez un nuevo tipo de mirada desde el ámbito académico. Dispuestas así las cosas, el presente libro se propone revisitar el género documental y recoger experiencias e investigaciones que, desde diferentes planteamientos, buscan reflexionar sobre la evolución del propio género desde un enfoque multidisciplinar. De este modo, se pretende establecer un estado de la cuestión con textos vinculados a los disímiles modos de abordar el documental a lo largo de su dilatada historia: estudios historiográficos, análisis fílmicos sustentados en ejemplos concretos de películas o directores de especial interés, investigaciones que ponen en relieve la influencia y consecuencia de la evolución de la tecnología digital e Internet, así como la evolución e innovación en los modos de producción, exhibición y/o distribución por los que el documental ha transitado.Este Libro se ha realizado dentro del Grupo de Investigación GIU 13/21 (2013-2016), MAC (Mutaciones del Audiovisual Contemporáneo) de la Universidad del País Vasco/Euskal Herriko Unibertsitatea (UPV/EHU).La redacción del capítulo "Un lugar ético para las imágenes documentales (en el contexto de las ciencias sociales) / Josetxo Cerdán Los Arcos" fue posible gracias al proyecto de investigación CSO2010/15798 (TRANSCINE), financiado por el Ministerio de Ciencia e Innovación del Gobierno de España. -- La redacción del capítulo "Documentalidad. Cine sin autoría, pedagogías visuales colectivas y valor afectivo / Virginia Villaplana Ruiz" fue posible gracias al proyecto de investigación eDCINEMA: "Hacia el Espacio Digital Europeo", financiado por el Plan Nacional de I+D+i del Ministerio de Economía y Competitividad. Ref. CSO2012-35784. -- La redacción del capítulo "Cosas que hacen crack. Emociones y cinefilia en Color perro que huye (Andrés Duque, 2011) / Miguel Fernández Labayen y Elena Oroz" se ha realizado en el marco del proyecto de investigación CSO2010-15798 (TRANSCINE), "El audiovisual español contemporáneo en el contexto transnacional: aproximaciones cualitativas a sus relaciones transfronterizas", financiado por el Ministerio de Economía y Competitividad del Gobierno de España. -- El capítulo "Aproximación a la no ficción interactiva: panorámica del webdocumental español en la era digital / Robert Arnau Roselló" ha sido financiado con la ayuda del Proyecto de Investigación de la convocatoria Universitat Jaume I-Bancaja, con el título "Análisis de los flujos de transferencia de conocimiento entre los sistemas educativos superiores y la industria del videojuego", código 11I301.01/1, bajo la dirección del Dr. Javier Marzal Felici.Prólogo / J.M. Català Domènech (pp. 9-14). -- Un lugar ético para las imágenes documentales (en el contexto de las ciencias sociales) / Josetxo Cerdán Los Arcos (pp. 17-32). -- Documentalidad. Cine sin autoría, pedagogías visuales colectivas y valor afectivo / Virginia Villaplana Ruiz (pp. 33-54). -- Diseño de títulos en documental: cuestión de etiqueta / Koldo Atxaga Arnedo (pp. 55-65). -- La creación del documental: archivo, recreaciones y entrevistas / Mónica del Sagrario Medina Cuevas y Alejandro Jiménez Arrazquito (pp. 67-76). -- Desterritorialización, modulación y puntos de inflexión en el documental contemporáneo español / Vanesa Fernández Guerra y Estibaliz Alonso Ruiz de Erentzun (pp. 79-103). -- La propuesta de vertebración del Novo Cine Galego: lo procesual y la marca documental / Fernando Redondo Neira y Xurxo González Rodríguez (pp. 105-126). -- Revisión de la etiqueta "Novo Cinema Galego". Testimonios de autor / Beli Martínez Martínez (pp. 127-152). -- El cine de no ficción en los cortometrajes de Kimuak: evoluación, tendencias y nuevas propuestas creativas / Ainhoa Fernández de Arroyabe Olaorut, Nekane E. Zubiaur Gorozika y Iñaki Lazkano Arrillaga (pp. 153-179). -- Cosas que hacen "crack". Emociones y cinefilia en Color perro que huye (Andrés Duque, 2011) / Miguel Fernández Labayen y Elena Oroz (pp. 181- 204). -- Estudio evolutivo del lenguaje narrativo, desde los primeros documentales a las transmedia / Begoña Gutiérrez San Miguel (pp. 207-244). -- La participación ciudadana en el documental colaborativo: hacia nuevas narrativas audiovisuales / Gloria Rosique Cedillo (pp. 245-263). -- Del documental lineal al webdocumental: enunciación y experiencia espectatorial en Gare du Nord de Claire Simon / Amanda Rueda (pp. 265-274). -- El documental multimedia interactivo. Un estudio de caso: En el reino del plomo (En Portada y Lab de RTVE.es, 2013) / Irene Liberia Vayá y Cristina Pérez de Algaba Chicano (pp. 275-299). -- Aproximación a la no ficción interactiva: panorámica del webdocumental español en la era digital / Robert Arnau Roselló (pp. 301-323)

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

Impact of COVID-19 on cardiovascular testing in the United States versus the rest of the world

Objectives: This study sought to quantify and compare the decline in volumes of cardiovascular procedures between the United States and non-US institutions during the early phase of the coronavirus disease-2019 (COVID-19) pandemic. Background: The COVID-19 pandemic has disrupted the care of many non-COVID-19 illnesses. Reductions in diagnostic cardiovascular testing around the world have led to concerns over the implications of reduced testing for cardiovascular disease (CVD) morbidity and mortality. Methods: Data were submitted to the INCAPS-COVID (International Atomic Energy Agency Non-Invasive Cardiology Protocols Study of COVID-19), a multinational registry comprising 909 institutions in 108 countries (including 155 facilities in 40 U.S. states), assessing the impact of the COVID-19 pandemic on volumes of diagnostic cardiovascular procedures. Data were obtained for April 2020 and compared with volumes of baseline procedures from March 2019. We compared laboratory characteristics, practices, and procedure volumes between U.S. and non-U.S. facilities and between U.S. geographic regions and identified factors associated with volume reduction in the United States. Results: Reductions in the volumes of procedures in the United States were similar to those in non-U.S. facilities (68% vs. 63%, respectively; p = 0.237), although U.S. facilities reported greater reductions in invasive coronary angiography (69% vs. 53%, respectively; p < 0.001). Significantly more U.S. facilities reported increased use of telehealth and patient screening measures than non-U.S. facilities, such as temperature checks, symptom screenings, and COVID-19 testing. Reductions in volumes of procedures differed between U.S. regions, with larger declines observed in the Northeast (76%) and Midwest (74%) than in the South (62%) and West (44%). Prevalence of COVID-19, staff redeployments, outpatient centers, and urban centers were associated with greater reductions in volume in U.S. facilities in a multivariable analysis. Conclusions: We observed marked reductions in U.S. cardiovascular testing in the early phase of the pandemic and significant variability between U.S. regions. The association between reductions of volumes and COVID-19 prevalence in the United States highlighted the need for proactive efforts to maintain access to cardiovascular testing in areas most affected by outbreaks of COVID-19 infection

Dietary α‐Linolenic Acid, Marine ω‐3 Fatty Acids, and Mortality in a Population With High Fish Consumption: Findings From the PREvención con DIeta MEDiterránea (PREDIMED) Study

Background: Epidemiological evidence suggests a cardioprotective role of α‐linolenic acid (ALA), a plant‐derived ω‐3 fatty acid. It is unclear whether ALA is beneficial in a background of high marine ω‐3 fatty acids (long‐chain n‐3 polyunsaturated fatty acids) intake. In persons at high cardiovascular risk from Spain, a country in which fish consumption is customarily high, we investigated whether meeting the International Society for the Study of Fatty Acids and Lipids recommendation for dietary ALA (0.7% of total energy) at baseline was related to all‐cause and cardiovascular disease mortality. We also examined the effect of meeting the society's recommendation for long‐chain n‐3 polyunsaturated fatty acids (≥500 mg/day). Methods and Results: We longitudinally evaluated 7202 participants in the PREvención con DIeta MEDiterránea (PREDIMED) trial. Multivariable‐adjusted Cox regression models were fitted to estimate hazard ratios. ALA intake correlated to walnut consumption (r=0.94). During a 5.9‐y follow‐up, 431 deaths occurred (104 cardiovascular disease, 55 coronary heart disease, 32 sudden cardiac death, 25 stroke). The hazard ratios for meeting ALA recommendation (n=1615, 22.4%) were 0.72 (95% CI 0.56–0.92) for all‐cause mortality and 0.95 (95% CI 0.58–1.57) for fatal cardiovascular disease. The hazard ratios for meeting the recommendation for long‐chain n‐3 polyunsaturated fatty acids (n=5452, 75.7%) were 0.84 (95% CI 0.67–1.05) for all‐cause mortality, 0.61 (95% CI 0.39–0.96) for fatal cardiovascular disease, 0.54 (95% CI 0.29–0.99) for fatal coronary heart disease, and 0.49 (95% CI 0.22–1.01) for sudden cardiac death. The highest reduction in all‐cause mortality occurred in participants meeting both recommendations (hazard ratio 0.63 [95% CI 0.45–0.87]). Conclusions: In participants without prior cardiovascular disease and high fish consumption, dietary ALA, supplied mainly by walnuts and olive oil, relates inversely to all‐cause mortality, whereas protection from cardiac mortality is limited to fish‐derived long‐chain n‐3 polyunsaturated fatty acids. Clinical Trial Registration URL: http://www.Controlled-trials.com/. Unique identifier: ISRCTN35739639

VIII Encuentro de Docentes e Investigadores en Historia del Diseño, la Arquitectura y la Ciudad

Acta de congresoLa conmemoración de los cien años de la Reforma Universitaria de 1918 se presentó como una ocasión propicia para debatir el rol de la historia, la teoría y la crítica en la formación y en la práctica profesional de diseñadores, arquitectos y urbanistas. En ese marco el VIII Encuentro de Docentes e Investigadores en Historia del Diseño, la Arquitectura y la Ciudad constituyó un espacio de intercambio y reflexión cuya realización ha sido posible gracias a la colaboración entre Facultades de Arquitectura, Urbanismo y Diseño de la Universidad Nacional y la Facultad de Arquitectura de la Universidad Católica de Córdoba, contando además con la activa participación de mayoría de las Facultades, Centros e Institutos de Historia de la Arquitectura del país y la región. Orientado en su convocatoria tanto a docentes como a estudiantes de Arquitectura y Diseño Industrial de todos los niveles de la FAUD-UNC promovió el debate de ideas a partir de experiencias concretas en instancias tales como mesas temáticas de carácter interdisciplinario, que adoptaron la modalidad de presentación de ponencias, entre otras actividades. En el ámbito de VIII Encuentro, desarrollado en la sede Ciudad Universitaria de Córdoba, se desplegaron numerosas posiciones sobre la enseñanza, la investigación y la formación en historia, teoría y crítica del diseño, la arquitectura y la ciudad; sumándose el aporte realizado a través de sus respectivas conferencias de Ana Clarisa Agüero, Bibiana Cicutti, Fernando Aliata y Alberto Petrina. El conjunto de ponencias que se publican en este Repositorio de la UNC son el resultado de dos intensas jornadas de exposiciones, cuyos contenidos han posibilitado actualizar viejos dilemas y promover nuevos debates. El evento recibió el apoyo de las autoridades de la FAUD-UNC, en especial de la Secretaría de Investigación y de la Biblioteca de nuestra casa, como así también de la Facultad de Arquitectura de la UCC; va para todos ellos un especial agradecimiento

Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study

Background Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate a novel measure of disease progression and to identify genetic markers associated with this progression measure. Methods We generated a progression score on the basis of principal component analysis of prospectively acquired longitudinal changes in motor, cognitive, and imaging measures in the 218 indivduals in the TRACK-HD cohort of Huntington's disease gene mutation carriers (data collected 2008–11). We generated a parallel progression score using data from 1773 previously genotyped participants from the European Huntington's Disease Network REGISTRY study of Huntington's disease mutation carriers (data collected 2003–13). We did a genome-wide association analyses in terms of progression for 216 TRACK-HD participants and 1773 REGISTRY participants, then a meta-analysis of these results was undertaken. Findings Longitudinal motor, cognitive, and imaging scores were correlated with each other in TRACK-HD participants, justifying use of a single, cross-domain measure of disease progression in both studies. The TRACK-HD and REGISTRY progression measures were correlated with each other (r=0·674), and with age at onset (TRACK-HD, r=0·315; REGISTRY, r=0·234). The meta-analysis of progression in TRACK-HD and REGISTRY gave a genome-wide significant signal (p=1·12 × 10−10) on chromosome 5 spanning three genes: MSH3, DHFR, and MTRNR2L2. The genes in this locus were associated with progression in TRACK-HD (MSH3 p=2·94 × 10−8 DHFR p=8·37 × 10−7 MTRNR2L2 p=2·15 × 10−9) and to a lesser extent in REGISTRY (MSH3 p=9·36 × 10−4 DHFR p=8·45 × 10−4 MTRNR2L2 p=1·20 × 10−3). The lead single nucleotide polymorphism (SNP) in TRACK-HD (rs557874766) was genome-wide significant in the meta-analysis (p=1·58 × 10−8), and encodes an aminoacid change (Pro67Ala) in MSH3. In TRACK-HD, each copy of the minor allele at this SNP was associated with a 0·4 units per year (95% CI 0·16–0·66) reduction in the rate of change of the Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score, and a reduction of 0·12 units per year (95% CI 0·06–0·18) in the rate of change of UHDRS Total Functional Capacity score. These associations remained significant after adjusting for age of onset. Interpretation The multidomain progression measure in TRACK-HD was associated with a functional variant that was genome-wide significant in our meta-analysis. The association in only 216 participants implies that the progression measure is a sensitive reflection of disease burden, that the effect size at this locus is large, or both. Knockout of Msh3 reduces somatic expansion in Huntington's disease mouse models, suggesting this mechanism as an area for future therapeutic investigation