ERCC1/XPF protects short telomeres from homologous recombination in Arabidopsis thaliana.

International audienceMany repair and recombination proteins play essential roles in telomere function and chromosome stability, notwithstanding the role of telomeres in "hiding" chromosome ends from DNA repair and recombination. Among these are XPF and ERCC1, which form a structure-specific endonuclease known for its essential role in nucleotide excision repair and is the subject of considerable interest in studies of recombination. In contrast to observations in mammalian cells, we observe no enhancement of chromosomal instability in Arabidopsis plants mutated for either XPF (AtRAD1) or ERCC1 (AtERCC1) orthologs, which develop normally and show wild-type telomere length. However, in the absence of telomerase, mutation of either of these two genes induces a significantly earlier onset of chromosomal instability. This early appearance of telomere instability is not due to a general acceleration of telomeric repeat loss, but is associated with the presence of dicentric chromosome bridges and cytologically visible extrachromosomal DNA fragments in mitotic anaphase. Such extrachromosomal fragments are not observed in later-generation single-telomerase mutant plants presenting similar frequencies of anaphase bridges. Extensive FISH analyses show that these DNAs are broken chromosomes and correspond to two specific chromosome arms. Analysis of the Arabidopsis genome sequence identified two extensive blocks of degenerate telomeric repeats, which lie at the bases of these two arms. Our data thus indicate a protective role of ERCC1/XPF against 3' G-strand overhang invasion of interstitial telomeric repeats. The fact that the Atercc1 (and Atrad1) mutants dramatically potentiate levels of chromosome instability in Attert mutants, and the absence of such events in the presence of telomerase, have important implications for models of the roles of recombination at telomeres and is a striking illustration of the impact of genome structure on the outcomes of equivalent recombination processes in different organisms

Oblivion: autopsy findings of a 31-year-old man with sudden cardiac arrest, a case report of a sequalae of Kawasaki disease

A 31-year-old man presented to the hospital after suffering a sudden cardiac arrest. Despite optimal therapy, the patient passed away. His medical history included febrile rash at age 2. At autopsy, there was aneurysmal dilation and severe coronary artery stenosis by atherosclerotic plaques and myocardial fibrosis. These findings were presumed to be due to complications of Kawasaki disease, given the remote history of severe febrile rash as a toddler and the presence of chronic coronary artery injury, recanalization, and thrombosis with ischemic heart disease leading to sudden cardiac collapse and death

La prensa diaria por dentro : mecanismos de transmisión de estereotipos de género en la prensa de información general

El ámbito de los estudios sobre género y medios de comunicación ha producido últimamente numerosos estudios en la mayor parte de los países de nuestro entorno cultural. Si tradicionalmente se ha recurrido a una metodología cuantitativa y al análisis de contenido como técnica de análisis más utilizada, el presente texto --que no es más que un resumen de un trabajo de investigación mucho más amplio- aborda el estudio de la producción de la información, y en especial de la reproducción de los estereotipos de género, en las salas de redacción de cuatro diarios de información general y una agencia de noticias. Tomando como modelo los estudios etnometodológicos, el trabajo se centra en la observación de los participantes, tratanto de poner en relación los procesos de la producción informativa con los mecanismos que operan, y que hacen o no posible, la inclusión o exclusión de la dimensión de género en la información.The field of gender studies and means of communication has recently produced numerous studies in most of the countries belonging to our cultural environment. If they have traditionally used quantitative methodology and the analysis of content for most of the analysis, the present text --which is no more than the summary of a far broader research studyapproaches the study of the production of information, and particularly the reproduction of gender stereotypes, in the editorial offices of four general information newspapers and one news agency. Taking ethnomethodological studies as a model, the study focuses on observations of the participants, attempting to relate the processes of information production to the mechanisms that operate, and which facilitate (or not) the inclusion or exclusion of the dimension of gender within information

New environmental and spatial approach to Tiwanaku World Heritage site (Bolivia) using remote sensing (UAV and satellite images)

This paper analyses the research carried out in the Tiwanaku World Heritage site in Bolivia, using Unmanned Aerial Vehicles (UAV) and satellite images. The combined use of images with different scales has made it possible to locate many archaeological structures unknown to date (drainage systems, walls, circular crop marks and a possible dock). The Sentinel-2 images, which were processed using principal components analysis and histogram equalization, show the river beds, flood-prone areas and several buried drainage channels surrounding the most important structures. The archaeological evidence obtained with the DTM and natural colour / multispectral images enables us to contrast a new dimension of land and water uses that goes beyond what was known to date. In the same way, these images enable us to understand in detail the environmental characteristics, land use, building distribution and flood defence structures of the Tiwanaku culture throughout its history, within the context of the environmental conditions of the Bolivian altiplano. This investigation allowed collection of new information and posed questions on the relationship of this site with water, as well as a better understanding of the extent and habitat features of this historical population

Calidad en los servicios de salud desde los marcos de sentido de diferentes actores sociales en colombia y brasil

Objetivo Analizar los marcos de sentido en la definición de la calidad de un servicio de salud de los diversos actores sociales en Colombia y Brasil. Método Estudio cualitativo, descriptivo-interpretativo, mediante grupos focales y entrevistas individuales en dos municipios de Colombia y Brasil. Muestra teórica de agentes sociales, buscando variedad del discurso: a. Usuarios y líderes; b. Personal de salud y; c. Formuladores de políticas. Análisis de contenido, con generación mixta de categorías y segmentación de los datos por país, informantes y temas. Resultados Los marcos de sentido desde los cuales construyen la calidad de la atención, usuarios y personal de salud en ambos países, mostraron convergencias en torno a tres grandes ejes: adecuación de la estructura, nivel técnico y humaniza­ción de la atención. Presentaron, no obstante, matices diferenciadores: los usuarios de ambos países profundizan en aspectos estructurales y organizativos como dispo­nibilidad y accesibilidad de recursos, y en aspectos técnicos, como resolutividad y calidad técnica. El personal de salud de Colombia y Brasil mostró similitudes, pero mientras los primeros destacaban más una administración ágil y tiempo de consulta mayor; los segundos, más disposición de personal especializado, materiales e insu­mos suficientes. Por su parte, el marco de sentido de los formuladores emergió del conjunto de normas legales. Conclusiones Los matices aportados por los distintos marcos de sentido de calidad de los actores sociales, indican la necesidad de tenerlos en cuenta en su totalidad, ya que apuntan a diferentes debilidades del sistema. Además, muestran que los usuarios profundizan más en aspectos técnicos del servicio de lo considerado habi­tualmente

Calidad en los servicios de salud desde los marcos de sentido de diferentes actores sociales en colombia y brasil

Objetivo Analizar los marcos de sentido en la definición de la calidad de un servicio de salud de los diversos actores sociales en Colombia y Brasil. Método Estudio cualitativo, descriptivo-interpretativo, mediante grupos focales y entrevistas individuales en dos municipios de Colombia y Brasil. Muestra teórica de agentes sociales, buscando variedad del discurso: a. Usuarios y líderes; b. Personal de salud y; c. Formuladores de políticas. Análisis de contenido, con generación mixta de categorías y segmentación de los datos por país, informantes y temas. Resultados Los marcos de sentido desde los cuales construyen la calidad de la atención, usuarios y personal de salud en ambos países, mostraron convergencias en torno a tres grandes ejes: adecuación de la estructura, nivel técnico y humaniza­ción de la atención. Presentaron, no obstante, matices diferenciadores: los usuarios de ambos países profundizan en aspectos estructurales y organizativos como dispo­nibilidad y accesibilidad de recursos, y en aspectos técnicos, como resolutividad y calidad técnica. El personal de salud de Colombia y Brasil mostró similitudes, pero mientras los primeros destacaban más una administración ágil y tiempo de consulta mayor; los segundos, más disposición de personal especializado, materiales e insu­mos suficientes. Por su parte, el marco de sentido de los formuladores emergió del conjunto de normas legales. Conclusiones Los matices aportados por los distintos marcos de sentido de calidad de los actores sociales, indican la necesidad de tenerlos en cuenta en su totalidad, ya que apuntan a diferentes debilidades del sistema. Además, muestran que los usuarios profundizan más en aspectos técnicos del servicio de lo considerado habi­tualmente

Population Disequilibrium as Promoter of Adaptive Explorations in Hepatitis C Virus

Coronavirus SARS-CoV-2; COVID-19; 2019-nCoV; Virus de l'hepatitis C; Vacunes universalsCoronavirus SARS-CoV-2; COVID-19; 2019-nCoV; Virus de la hepatitis C; Vacunas universalesCoronavirus SARS-CoV-2; COVID-19; 2019-nCoV; Hepatitis C virus; Universal vaccinesReplication of RNA viruses is characterized by exploration of sequence space which facilitates their adaptation to changing environments. It is generally accepted that such exploration takes place mainly in response to positive selection, and that further diversification is boosted by modifications of virus population size, particularly bottleneck events. Our recent results with hepatitis C virus (HCV) have shown that the expansion in sequence space of a viral clone continues despite prolonged replication in a stable cell culture environment. Diagnosis of the expansion was based on the quantification of diversity indices, the occurrence of intra-population mutational waves (variations in mutant frequencies), and greater individual residue variations in mutant spectra than those anticipated from sequence alignments in data banks. In the present report, we review our previous results, and show additionally that mutational waves in amplicons from the NS5A-NS5B-coding region are equally prominent during HCV passage in the absence or presence of the mutagenic nucleotide analogues favipiravir or ribavirin. In addition, by extending our previous analysis to amplicons of the NS3- and NS5A-coding region, we provide further evidence of the incongruence between amino acid conservation scores in mutant spectra from infected patients and in the Los Alamos National Laboratory HCV data banks. We hypothesize that these observations have as a common origin a permanent state of HCV population disequilibrium even upon extensive viral replication in the absence of external selective constraints or changes in population size. Such a persistent disequilibrium—revealed by the changing composition of the mutant spectrum—may facilitate finding alternative mutational pathways for HCV antiviral resistance. The possible significance of our model for other genetically variable viruses is discussed.The work at CBMSO was supported by grants SAF2014-52400-R from Ministerio de Economía y Competitividad (MINECO), SAF2017-87846-R and BFU2017-91384-EXP from Ministerio de Ciencia, Innovación y Universidades (MCIU), PI18/00210 from Instituto de Salud Carlos III, S2013/ABI-2906 (PLATESA from Comunidad de Madrid/FEDER), and S2018/BAA-4370 (PLATESA2 from Comunidad de Madrid/FEDER). C.P. is supported by the Miguel Servet program of the Instituto de Salud Carlos III (CPII19/00001), cofinanced by the European Regional Development Fund (ERDF). CIBERehd (Centro de Investigación en Red de Enfermedades Hepáticas y Digestivas) is funded by Instituto de Salud Carlos III. Institutional grants from the Fundación Ramón Areces and Banco Santander to the CBMSO are also acknowledged. The team at CBMSO belongs to the Global Virus Network (GVN). The work in Barcelona was supported by Instituto de Salud Carlos III, cofinanced by the European Regional Development Fund (ERDF) Grant No. PI19/00301 and by the Centro para el Desarrollo Tecnológico Industrial (CDTI) from the MICIU, Grant No. IDI-20200297. Work at CAB was supported by MINECO grant BIO2016-79618R and PID2019-104903RB-I00 (funded by the EU under the FEDER program) and by the Spanish State research agency (AEI) through project number MDM-2017-0737 Unidad de Excelencia “María de Maeztu”-Centro de Astrobiología (CSIC-INTA). C.G.-C. is supported by predoctoral contract PRE2018-083422 from MCIU. B.M.-G. is supported by predoctoral contract PFIS FI19/00119 from Instituto de Salud Carlos III (Ministerio de Sanidad y Consumo), cofinanced by Fondo Social Europeo (FSE)

Single-cell multi-omic analysis profiles defective genome activation and epigenetic reprogramming associated with human pre-implantation embryo arrest

During pre-implantation stages of mammalian development, maternally stored material promotes both the erasure of the sperm and oocyte epigenetic profiles and is responsible for concomitant genome activation. Here, we have utilized single-cell methylome and transcriptome sequencing (scM&T-seq) to quantify both mRNA expression and DNA methylation in oocytes and a developmental series of human embryos at single-cell resolution. We fully characterize embryonic genome activation and maternal transcript degradation and map key epigenetic reprogramming events in developmentally high-quality embryos. By comparing these signatures with early embryos that have undergone spontaneous cleavage-stage arrest, as determined by time-lapse imaging, we identify embryos that fail to appropriately activate their genomes or undergo epigenetic reprogramming. Our results indicate that a failure to successfully accomplish these essential milestones impedes the developmental potential of pre-implantation embryos and is likely to have important implications, similar to aneuploidy, for the success of assisted reproductive cycles

Differing Requirements for RAD51 and DMC1 in Meiotic Pairing of Centromeres and Chromosome Arms in Arabidopsis thaliana

During meiosis homologous chromosomes pair, recombine, and synapse, thus ensuring accurate chromosome segregation and the halving of ploidy necessary for gametogenesis. The processes permitting a chromosome to pair only with its homologue are not fully understood, but successful pairing of homologous chromosomes is tightly linked to recombination. In Arabidopsis thaliana, meiotic prophase of rad51, xrcc3, and rad51C mutants appears normal up to the zygotene/pachytene stage, after which the genome fragments, leading to sterility. To better understand the relationship between recombination and chromosome pairing, we have analysed meiotic chromosome pairing in these and in dmc1 mutant lines. Our data show a differing requirement for these proteins in pairing of centromeric regions and chromosome arms. No homologous pairing of mid-arm or distal regions was observed in rad51, xrcc3, and rad51C mutants. However, homologous centromeres do pair in these mutants and we show that this does depend upon recombination, principally on DMC1. This centromere pairing extends well beyond the heterochromatic centromere region and, surprisingly, does not require XRCC3 and RAD51C. In addition to clarifying and bringing the roles of centromeres in meiotic synapsis to the fore, this analysis thus separates the roles in meiotic synapsis of DMC1 and RAD51 and the meiotic RAD51 paralogs, XRCC3 and RAD51C, with respect to different chromosome domains