Symmetric dithiodigalactoside: strategic combination of binding studies and detection of selectivity between a plant toxin and human lectins

Thioglycosides offer the advantage over O-glycosides to be resistant to hydrolysis. Based on initial evidence of this recognition ability for glycosyldisulfides by screening dynamic combinatorial libraries, we have now systematically studied dithiodigalactoside on a plant toxin (Viscum album agglutinin) and five human lectins (adhesion/growth-regulatory galectins with medical relevance e.g. in tumor progression and spread). Inhibition assays with surface-presented neoglycoprotein and in solution monitored by saturation transfer difference NMR spectroscopy, flanked by epitope mapping, as well as isothermal titration calorimetry revealed binding properties to VAA (Ka: 1560 ± 20 M-1). They were reflected by the structural model and the affinity on the level of toxin-exposed cells. In comparison, galectins were considerably less reactive, with intrafamily grading down to very minor reactivity for tandem-repeat-type galectins, as quantitated by radioassays for both domains of galectin-4. Model building indicated contact formation to be restricted to only one galactose moiety, in contrast to thiodigalactoside. The tested lycosyldisulfide exhibits selectivity between the plant toxin and the tested human lectins, and also between these proteins. Therefore, glycosyldisulfides have potential as chemical platform for inhibitor design

"Click & collect" para una rápida adaptación de la docencia práctica presencial a online en grados universitarios de Ciencias de la Salud

La obligada adaptación del proceso enseñanza/aprendizaje a entornos no presenciales, debido a la expansión del virus SARS-COV-2, ha motivado el diseño y ejecución de herramientas de aprendizaje basadas en TICs, que integren, además de los contenidos indispensables para la adquisición de competencias profesionales, un entorno atractivo para el aprendizaje autónomo de los alumnos. Mediante un paquete informático de implementación rápida ("click & collect") en plataformas virtuales de diferentes universidades, adaptado al nivel medio de conocimientos informáticos del profesorado en Ciencias de la Salud, se han diseñado unas clases prácticas de la asignatura Farmacognosia y Fitoterapia correspondiente a los Grados de Farmacia y Farmacia y Nutricion Humana y Dietética de la UCM y las Universidades CEU San Pablo y CEU Cardenal Herrera. Se han incluido presentaciones ppsx interactivas y micro-vídeos de prácticas reales, incluyendo aciertos y fallos más comunes. En una primera evaluación de su eficacia se han observado resultados muy positivos tanto en el grado de aceptación por los alumnos como por el profesorado. La herramienta diseñada no sólo permitirá una adaptación rápida de la docencia presencial a online, sino que podrá ser empleada para favorecer el aprendizaje presencial y para la formación de postgrado

Neutral pathways and heat flux widths in vertical- and horizontal-target EDGE2D-EIRENE simulations of JET

This paper further analyses the EDGE2D-EIRENE simulations presented by Chankin et al (2017 Nucl. Mater. Energy 12 273), of L-mode JET plasmas in vertical-vertical (VV) and Vertical-horizontal (VH) divertor configurations. As expected, the simulated outer divertor ionisation source peaks near the separatrix in VV and radially further out in VH. We identify the reflections of recycled neutrals from lower divertor tiles as the primary mechanism by which ionisation is concentrated on the outer divertor separatrix in the VV configuration. These lower tile reflection pathways (of neutrals from the outer divertor, and to an even greater extent from the inner divertor) dominate the outer divertor separatrix ionisation. In contrast, the lower-tile-reflection pathways are much weaker in the VH simulation and its outer divertor ionisation is dominated by neutrals which do not reflect from any surfaces. Interestingly, these differences in neutral pathways give rise to strong differences in the heat flux density width λq at the outer divertor entrance: λq = 3.2 mm in VH compared to λq = 11.8 mm in VV. In VH, a narrow channel exists in the near scrape-off-layer (SOL) where the convected heat flux, driven by strong Er × B flow and thermoelectric current, dominates over the conducted heat flux. The width of this channel sets λq and is determined by the radial distance between the separatrix and the ionisation peak in the outer divertor

Observations and modelling of ion cyclotron emission observed in JET plasmas using a sub-harmonic arc detection system during ion cyclotron resonance heating

Peer reviewe

The pathogenesis of primary biliary cirrhosis Patogénesis en cirrosis biliar primaria

Primary biliary cirrhosis (PBC) would develop when the immune system comes across a microorganism with proteins similar to those in the piruvate dehydrogenase complex E2 (PDC-E2), or a neoantigen resulting from a xenobiotic-modified autoantigen. This would lead to an innate immune response where TLRs would play a pivotal mediating role, which would give rise to a local microenvironment favoring an adaptive immune response. Such response would be particularly strong in individuals with selected genetic characteristics. The genetic characteristics underlying this predisposition remain unknown, but they likely entail small numbers of scarcely-active regulatory T cells. The AE2 anion exchanger, which is deficient in patients with PBC, may reduce the number and activity of regulatory T cells. NK cells are also pivotal in the preparation of an adaptive response, as they release a number of cytokines and chemokines that favor and recruit antigen-presenting cells to activate B and T cells - CD4+ Th1 and CD8+. An activation of the former would increase the production of IgM and anti-mitochondrial IgG and IgA antibodies against PDC-E2. An activation of CD8+ cells, also sensitive to PDC-2 as aberrantly expressed on the surface of BECs and SECs, would result in apoptosis for these epithelial cells, and in small bile-duct destruction. Immune response is likely inadequately suppressed because of the small numbers of scarcely-active regulatory T cells, the latter resulting from low genetic expression and activity of the AE2 transporter