Los alfares arandinos

En número dedicado a: La provincia de Burgo

Celebrando la cristalografía macromolecular: una perspectiva personal

The twentieth century has seen an enormous advance in the knowledge of the atomic structures that surround us. The discovery of the first crystal structures of simple inorganic salts by the Braggs in 1914, using the diffraction of X-rays by crystals, provided the critical elements to unveil the atomic structure of matter. Subsequent developments in the field leading to macromolecular crystallography are presented with a personal perspective, related to the cultural milieu of Spain in the late 1950’s. The journey of discovery of the author, as he developed professionally, is interwoven with the expansion of macromolecular crystallography from the first proteins (myoglobin, hemoglobin) to the ‘coming of age’ of the field in 1971 and the discoveries that followed, culminating in the determination of the structure of the ribosomes at the turn of the century. A perspective is presented exploring the future of the field and also a reflection about the future generations of Spanish scientists.El siglo XX ha sido testigo del increíble avance que ha experimentado el conocimiento de la estructura atómica de la materia que nos rodea. El descubrimiento de las primeras estructuras atómicas de sales inorgánicas por los Bragg en 1914, empleando difracción de rayos X con cristales, proporcionó los elementos clave para alcanzar tal conocimiento. Posteriores desarrollos en este campo, que condujeron a la cristalografía macromolecular, se presentan aquí desde una perspectiva personal, relacionada con el contexto cultural de la España de la década de los 50. La experiencia del descubrimiento científico, durante mi desarrollo profesional, se integra en el desarrollo de la cristalografía macromolecular, desde las primeras proteínas (míoglobina y hemoglobina), hasta su madurez en 1971 que, con los posteriores descubrimientos, culmina con la determinación del la estructura del ribosoma. Asimismo, se explora el futuro de esta disciplina y se reflexiona sobre el futuro de las próximas generaciones de científicos españoles

Isoxazole-Derived Amino Acids are Bromodomain-Binding Acetyl-Lysine Mimics: Incorporation into Histone H4 Peptides and Histone H3.

A range of isoxazole-containing amino acids was synthesized that displaced acetyl-lysine-containing peptides from the BAZ2A, BRD4(1), and BRD9 bromodomains. Three of these amino acids were incorporated into a histone H4-mimicking peptide and their affinity for BRD4(1) was assessed. Affinities of the isoxazole-containing peptides are comparable to those of a hyperacetylated histone H4-mimicking cognate peptide, and demonstrated a dependence on the position at which the unnatural residue was incorporated. An isoxazole-based alkylating agent was developed to selectively alkylate cysteine residues in situ. Selective monoalkylation of a histone H4-mimicking peptide, containing a lysine to cysteine residue substitution (K12C), resulted in acetyl-lysine mimic incorporation, with high affinity for the BRD4 bromodomain. The same technology was used to alkylate a K18C mutant of histone H3.Pfizer Neusentis for studentship suppor

Ludificación de actividades docentes a través del uso de Twitter en Asignatura de la Facultad de Economía y Empresa y sociología

Memoria ID-0286. Ayudas de la Universidad de Salamanca para la innovación docente, curso 2014-2015

Transient exposure to miR-203 expands the differentiation capacity of pluripotent stem cells

Full differentiation potential along with self‐renewal capacity is a major property of pluripotent stem cells (PSCs). However, the differentiation capacity frequently decreases during expansion of PSCs in vitro . We show here that transient exposure to a single microRNA, expressed at early stages during normal development, improves the differentiation capacity of already‐established murine and human PSCs. Short exposure to miR‐203 in PSCs (mi PSCs) induces a transient expression of 2C markers that later results in expanded differentiation potency to multiple lineages, as well as improved efficiency in tetraploid complementation and human–mouse interspecies chimerism assays. Mechanistically, these effects are at least partially mediated by direct repression of de novo DNA methyltransferases Dnmt3a and Dnmt3b, leading to transient and reversible erasure of DNA methylation. These data support the use of transient exposure to miR‐203 as a versatile method to reset the epigenetic memory in PSCs, and improve their effectiveness in regenerative medicine

Integrated water vapor obtained by satellite-borne instruments: evaluation with GPS measurements in the Iberian Peninsula

Ponencia presentada en: XVIII Congreso de la Asociación Española de Teledetección celebrado en Valladolid del 24 al 27 septiembre 2019.[ES]Este trabajo se centra en comparar los productos de vapor de agua integrado (IWV) de varios satélites respecto a un conjunto de datos en tierra obtenidos de GPS en nueve estaciones de la Península Ibérica. Los instrumentos satelitales son: Global Ozone Monitoring Instrument (GOME-2), Moderate-Resolution Imaging Spectroradiometer (MODIS), Ozone Monitoring Instrument (OMI), Spining Enhanced Visible and InfraRed Imager (SEVIRI), Atmospheric Infrared Sounder (AIRS), y Scanning Imaging Absorption Spectrometer for Atmospheric Chartography (SCIAMACHY). Los productos de estos satélites muestran una buena correlación con respecto al producto de GPS (R2 ~ 0.7). Todos los satélites muestran cierta tendencia a sobrestimar los valores bajos de vapor de agua y a subestimar los altos. Además, la precisión, medida mediante el rango intercuartílico (IQR) también disminuye rápidamente al aumentar el IWV. Por otro lado, otro factor importante es el ángulo solar zenital (SZA) que influye en el rendimiento de los instrumentos satelitales, especialmente aquellos que dependen de la radiación solar. Al aumentar el SZA acercándose a 90°, los instrumentos pierden rendimiento aumentando la sobrestimación y el IQR. Sin embargo, a valores de SZA mayores de 90° (esto es, la noche) los índices calculados no tienen grandes dependencias con el SZA.[EN]This work focuses in the comparison of several integrated water vapor (IWV) from several satellites with respect to a dataset from ground-based GPS IWV, in nine stations at the Iberian Peninsula. The satellite instruments are Global Ozone Monitoring Instrument (GOME-2), Moderate-Resolution Imaging Spectroradiometer (MODIS), Ozone Monitoring Instrument (OMI), Spinning Enhanced Visible and InfraRed Imager (SEVIRI), Atmospheric Infrared Sounder (AIRS), and Scanning Imaging Absorption Spectrometer for Atmospheric Chartography (SCIAMACHY). The products of this instruments show a fair correlation with respect to GPS product (R2 ~ 0.7). All satellites show a certain tendency to overestimation of low IWV values, while underestimating large IWV values. Moreover, the precision is studied using the inter-quartile range (IQR), which also decreases quickly when IWV increases. Another important factor is the solar zenith angle (SZA), which affects the performance of satellite instruments, especially those that are dependent on solar radiation. When SZA increases, going closer to 90°, the instruments had worse performance, increasing overestimation and IQR. Nevertheless, for SZA larger than 90° (that is to say, the night), the indexes do not show large dependencies on SZA

A practical drug discovery project at the undergraduate level

A practical drug discovery project for third-year undergraduates is described. No previous knowledge of medicinal chemistry is assumed. Initial lecture-workshops cover the basic principles; then students are asked to improve the profile of a weakly potent, poorly soluble PI3K inhibitor (1). Compound array design, molecular modelling and screening data analysis are followed by laboratory work in which each student, as part of a team, attempts to synthesise at least two target compounds. The project benefits from significant industrial support, including lectures, student mentoring and consumables. The aim is to make the learning experience as close as possible to real-life industrial situations. Forty-eight target compounds have been prepared, the best of which (5b, 5j, 6b and 6ap) improved the potency and aqueous solubility of the lead compound (1) by 100-1000 fold and 10-fold, respectively

Mycobacterial dihydrofolate reductase inhibitors identified using chemogenomic methods and in vitro validation.

The lack of success in target-based screening approaches to the discovery of antibacterial agents has led to reemergence of phenotypic screening as a successful approach of identifying bioactive, antibacterial compounds. A challenge though with this route is then to identify the molecular target(s) and mechanism of action of the hits. This target identification, or deorphanization step, is often essential in further optimization and validation studies. Direct experimental identification of the molecular target of a screening hit is often complex, precisely because the properties and specificity of the hit are not yet optimized against that target, and so many false positives are often obtained. An alternative is to use computational, predictive, approaches to hypothesize a mechanism of action, which can then be validated in a more directed and efficient manner. Specifically here we present experimental validation of an in silico prediction from a large-scale screen performed against Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis. The two potent anti-tubercular compounds studied in this case, belonging to the tetrahydro-1,3,5-triazin-2-amine (THT) family, were predicted and confirmed to be an inhibitor of dihydrofolate reductase (DHFR), a known essential Mtb gene, and already clinically validated as a drug target. Given the large number of similar screening data sets shared amongst the community, this in vitro validation of these target predictions gives weight to computational approaches to establish the mechanism of action (MoA) of novel screening hit