Documentos sobre Enrique IV de Castilla y su tiempo. Volumen I

El libro ofrece una colección de 4.152 documentos de la época de Enrique IV de Castilla (1454-1474) editados de forma resumida, entresacados de diversos archivos españoles. La mayor parte procede de las colecciones bibliográficas y documentales de la Real Academia de la Historia, como las de Luis de Salazar y Castro, Salvá, Lorich, Catedrales de España y colección Diplomática Española, sin olvidar algunos manuscritos singulares de la misma biblioteca. Igualmente se han vaciado algunos fondos de la Biblioteca Nacional de Madrid y Archivo General de Simancas, así como del Archivo Municipal de Sevilla. El marco cronológico se ha ampliado a los últimos años del reinado de Juan II y primeros de los Reyes Católicos debido a la abundancia de noticias relacionadas con este rey. El criterio temático es flexible, ya que no se ha limitado la búsqueda a la documentación expedida por la cancillería regia. Esta obra pretende ofrecer una herramienta de trabajo a los especialistas en el siglo XV castellano

Atypical soluble guanylyl cyclases control brain size in Drosophila

Hypoxia-induced proliferation of neural stem cells has a crucial role in brain development. In the brain of Drosophila melanogaster, the optic lobe exhibits progressive hypoxia during larval development. Here, we investigate an alternative oxygen-sensing mechanism within this brain compartment, distinct from the canonical hypoxia signaling pathway mediated by HIF. Using genetic tools, immunostaining, and confocal microscopy, we demonstrate that the loss of the atypical soluble guanylyl cyclase (asGC) subunit Gyc88E, or the ectopic expression of Gyc89Db in neural stem cells leads to increased optic lobe volume. We propose the existence of a link between cGMP signaling and neurogenesis in the developing brain.Dirección Nacional de Innovación, Ciencia y TecnologíaAgencia Nacional de Investigación e Innovació

The atypical soluble guanylyl cyclase subunit Gyc89Db does not control neuroepithelial proliferation in Drosophila larval brain

We investigated the role of oxygen-sensing atypical guanylyl cyclase subunit Gyc89Db in the developing brain. Despite its expression in the hypoxic neuroepithelium of the larval optic lobe of Drosophila, loss-of-function mutants and ectopic expression did not alter neuroepithelial cell number or proliferation. Notably, while ectopic expression of Gyc89Db increases optic lobe volume and neuroblast numbers, our negative results suggest that these effects manifest earlier in development without persistent alteration of the neuroepithelium, through mechanisms that might be independent of neuroepithelial proliferation.Dirección Nacional de Innovación Ciencia y Tecnología - Ministerio de Educación y CulturaAgencia Nacional de Investigación e Innovació

Compartment and cell-type specific hypoxia responses in the developing Drosophila brain

Material suplementario: https://bio.biologists.org/lookup/doi/10.1242/bio.053629.supplementalEnvironmental factors such as the availability of oxygen are instructive cues that regulate stem cell maintenance and differentiation. We used a genetically encoded biosensor to monitor the hypoxic state of neural cells in the larval brain of Drosophila. The biosensor reveals brain compartment and cell-type specific levels of hypoxia. The values correlate with differential tracheolation that is observed throughout development between the central brain and the optic lobe. Neural stem cells in both compartments show the strongest hypoxia response while intermediate progenitors, neurons and glial cells reveal weaker responses. We demonstrate that the distance between a cell and the next closest tracheole is a good predictor of the hypoxic state of that cell. Our study indicates that oxygen availability appears to be the major factor controlling the hypoxia response in the developing Drosophila brain and that cell intrinsic and cell-type specific factors contribute to modulate the response in an unexpected manner.ANII: FCE_3_2013_1_10073

An improved catalogue of putative synaptic genes defined exclusively by temporal transcription profiles through an ensemble machine learning approach

Background: Assembly and function of neuronal synapses require the coordinated expression of a yet undetermined set of genes. Previously, we had trained an ensemble machine learning model to assign a probability of having synaptic function to every protein-coding gene in Drosophila melanogaster. This approach resulted in the publication of a catalogue of 893 genes which we postulated to be very enriched in genes with a still undocumented synaptic function. Since then, the scientific community has experimentally identified 79 new synaptic genes. Here we use these new empirical data to evaluate our original prediction. We also implement a series of changes to the training scheme of our model and using the new data we demonstrate that this improves its predictive power. Finally, we added the new synaptic genes to the training set and trained a new model, obtaining a new, enhanced catalogue of putative synaptic genes. Results: The retrospective analysis demonstrate that our original catalogue was significantly enriched in new synaptic genes. When the changes to the training scheme were implemented using the original training set we obtained even higher enrichment. Finally, applying the new training scheme with a training set including the 79 new synaptic genes, resulted in an enhanced catalogue of putative synaptic genes. Here we present this new catalogue and announce that a regularly updated version will be available online at: Http://synapticgenes.bnd.edu.uy Conclusions: We show that training an ensemble of machine learning classifiers solely with the whole-body temporal transcription profiles of known synaptic genes resulted in a catalogue with a significant enrichment in undiscovered synaptic genes. Using new empirical data provided by the scientific community, we validated our original approach, improved our model an obtained an arguably more precise prediction. This approach reduces the number of genes to be tested through hypothesis-driven experimentation and will facilitate our understanding of neuronal function. Availability: Http://synapticgenes.bnd.edu.uyFil: Pazos Obregón, Flavio. Instituto de Investigaciones Biológicas "Clemente Estable"; UruguayFil: Palazzo, Martin. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigación en Biomedicina de Buenos Aires - Instituto Partner de la Sociedad Max Planck; ArgentinaFil: Soto, Pablo. Instituto de Investigaciones Biológicas "Clemente Estable"; UruguayFil: Guerberoff, Gustavo. Universidad de la República; UruguayFil: Yankilevich, Patricio. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigación en Biomedicina de Buenos Aires - Instituto Partner de la Sociedad Max Planck; ArgentinaFil: Cantera, Rafael. Instituto de Investigaciones Biológicas "Clemente Estable"; Urugua

Disruption of hemocyte differentiation and distribution in Drosophila Ptr23c mutants

In Drosophila, hemocytes are essential for development and immunity, with their differentiation and spatial distribution under strict regulation. Here, we examine the effect of the Ptr23c null mutation in embryonic hemocyte development. Contrary to our initial hypothesis, Ptr does not regulate hemocyte number, as the mutation did not affect the total number of hemocytes, apoptosis, mitosis, or the balance between major subpopulations. However, Ptr23c mutants displayed disrupted distribution and premature hemocyte differentiation, marked by accelerated maturation at stage 12. Despite this early differentiation, Ptr23c embryos exhibited a 50% reduction in mature hemocytes by stage 16, as quantified by serpent-driven mCherry expression. Our findings establish Ptr as a regulator of hemocyte distribution and differentiation timing during normal embryogenesis, possibly through modulation of the serpent pathway.Comisión Sectorial de Investigación CientíficaPrograma de Desarrollo de las Ciencias Básica

Effectiveness of the Epley’s maneuver performed in primary care to treat posterior canal benign paroxysmal positional vertigo: study protocol for a randomized controlled trial

BACKGROUND: Vertigo is a common medical condition with a broad spectrum of diagnoses which requires an integrated approach to patients through a structured clinical interview and physical examination. The main cause of vertigo in primary care is benign paroxysmal positional vertigo (BPPV), which should be confirmed by a positive D-H positional test and treated with repositioning maneuvers. The objective of this study is to evaluate the effectiveness of Epley’s maneuver performed by general practitioners (GPs) in the treatment of BPPV. METHODS/DESIGN: This study is a randomized clinical trial conducted in the primary care setting. The study’s scope will include two urban primary care centers which provide care for approximately 49,400 patients. All patients attending these two primary care centers, who are newly diagnosed with benign paroxysmal positional vertigo, will be invited to participate in the study and will be randomly assigned either to the treatment group (Epley’s maneuver) or to the control group (a sham maneuver). Both groups will receive betahistine. Outcome variables will be: response to the D-H test, patients’ report on presence or absence of vertigo during the previous week (dichotomous variable: yes/no), intensity of vertigo symptoms on a Likert-type scale in the previous week, total score on the Dizziness Handicap Inventory (DHI) and quantity of betahistine taken. We will use descriptive statistics of all variables collected. Groups will be compared using the intent-to-treat approach and either parametric or nonparametric tests, depending on the nature and distribution of the variables. Chi-square test or Fisher’s exact test will be conducted to compare categorical measures and Student’s t-test or Mann–Whitney U-test will be used for intergroup comparison variables. DISCUSSION: Positive results from our study will highlight that treatment of benign paroxysmal positional vertigo can be performed by trained general practitioners (GPs) and, therefore, its widespread practice may contribute to improve the quality of life of BPPV patients. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01969513

A FRET-based cGMP biosensor in Drosophila

CUTie2 is a FRET-based cGMP biosensor tested so far only in cells. To expand its use to multicellular organisms we generated two transgenic Drosophila melanogaster strains that express the biosensor in a tissue-dependent manner. CUTie2 expression and subcellular localization was verified by confocal microscopy. The performance of CUTie2 was analyzed on dissected larval brains by hyperspectral microscopy and flow cytometry. Both approaches confirmed its responsivity, and the latter showed a rapid and reversible change in the fluorescence of the FRET acceptor upon cGMP treatment. This validated reporter system may prove valuable for studying cGMP signaling at organismal level.Agencia Nacional de Investigación e InnovaciónDirección Nacional de Innovación, Ciencia y Tecnologí

Putative synaptic genes defined from a Drosophila whole body developmental transcriptome by a machine learning approach

BACKGROUND: Assembly and function of neuronal synapses require the coordinated expression of a yet undetermined set of genes. Although roughly a thousand genes are expected to be important for this function in Drosophila melanogaster, just a few hundreds of them are known so far. RESULTS: In this work we trained three learning algorithms to predict a “synaptic function” for genes of Drosophila using data from a whole-body developmental transcriptome published by others. Using statistical and biological criteria to analyze and combine the predictions, we obtained a gene catalogue that is highly enriched in genes of relevance for Drosophila synapse assembly and function but still not recognized as such. CONCLUSIONS: The utility of our approach is that it reduces the number of genes to be tested through hypothesis-driven experimentation. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12864-015-1888-3) contains supplementary material, which is available to authorized users

Gene function prediction in five model eukaryotes exclusively based on gene relative location through machine learning

The function of most genes is unknown. The best results in automated function prediction are obtained with machine learning-based methods that combine multiple data sources, typically sequence derived features, protein structure and interaction data. Even though there is ample evidence showing that a gene’s function is not independent of its location, the few available examples of gene function prediction based on gene location rely on sequence identity between genes of different organisms and are thus subjected to the limitations of the relationship between sequence and function. Here we predict thousands of gene functions in five model eukaryotes (Saccharomyces cerevisiae, Caenorhabditis elegans, Drosophila melanogaster, Mus musculus and Homo sapiens) using machine learning models exclusively trained with features derived from the location of genes in the genomes to which they belong. Our aim was not to obtain the best performing method to automated function prediction but to explore the extent to which a gene's location can predict its function in eukaryotes. We found that our models outperform BLAST when predicting terms from Biological Process and Cellular Component Ontologies, showing that, at least in some cases, gene location alone can be more useful than sequence to infer gene function.ANII: FSDA_1_2017_1_1424