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

Associations between eating speed, diet quality, adiposity, and cardiometabolic risk factors

Objective: To assess the associations between eating speed, adiposity, cardiometabolic risk factors, and diet quality in a cohort of Spanish preschool-children. Study design: A cross-sectional study in 1371 preschool age children (49% girls; mean age, 4.8 ± 1.0 years) from the Childhood Obesity Risk Assessment Longitudinal Study (CORALS) cohort was conducted. After exclusions, 956 participants were included in the analyses. The eating speed was estimated by summing the total minutes used in each of the 3 main meals and then categorized into slow, moderate, or fast. Multiple linear and logistic regression models were fitted to assess the β-coefficient, or OR and 95% CI, between eating speed and body mass index, waist circumference, fat mass index (FMI), blood pressure, fasting plasma glucose, and lipid profile. Results: Compared with participants in the slow-eating category, those in the fast-eating category had a higher prevalence risk of overweight/obesity (OR, 2.9; 95% CI, 1.8-4.4; P < .01); larger waist circumference (β, 2.6 cm; 95% CI, 1.5-3.8 cm); and greater FMI (β, 0.3 kg/m2; 95% CI, 0.1-0.5 kg/m2), systolic blood pressure (β, 2.8 mmHg; 95% CI, 0.6-4.9 mmHg), and fasting plasma glucose levels (β, 2.7 mg/dL, 95% CI, 1.2-4.2 mg/dL) but lower adherence to the Mediterranean diet (β, −0.5 points; 95% CI, −0.9 to −0.1 points). Conclusions: Eating fast is associated with higher adiposity, certain cardiometabolic risk factors, and lower adherence to a Mediterranean diet. Further long-term and interventional studies are warranted to confirm these associations

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

Investigation into the formation of the scrape-off layer density shoulder in JET ITER-like wall L-mode and H-mode plasmas

The low temperature boundary layer plasma (Scrape-Off-Layer or SOL) between the hot core and the surrounding vessel determines the level of power-loading, erosion and implantation of material surfaces, and thus the viability of tokamak-based fusion as an energy source. This study explores mechanisms affecting the formation of flattened density profiles, so-called ‘density shoulders’, in the low-field side (LFS) SOL, which modify ion and neutral fluxes to surfaces – and subsequent erosion. There is evidence against local enhancement of ionization inducing shoulder formation. We find that increases in SOL parallel resistivity, Λdiv (=[L||νei Ωi ]/cs Ωe), postulated to lead to shoulder growth through changes in SOL turbulence characteristics, correlates with increases in upstream SOL shoulder amplitude, As only under a subset of conditions (D2-fuelled L-mode density scans with outer strike point on the horizontal target). Λdiv fails to correlate with As for cases of N2 seeding or during sweeping of the strike point across the horizontal target. The limited correlation of Λdiv with As was also found for H-mode discharges. Thus, while Λdiv above a threshold of ~1 may be necessary for shoulder formation and/or growth, another shoulder mechanism is required. More significantly we find that in contrast to parallel resistivity, outer divertor recycling as quantified by the total outer divertor Balmer Dα emission, I-Dα, does scale with shoulder amplitude where Λdiv does and even where Λdiv fails. Divertor recycling could lead to SOL density shoulder formation through: a) reducing the parallel to the field flow (loss) of ions out of the SOL to the divertor; and b) changes in radial electric fields which lead to ExB poloidal flows as well as potentially affecting the SOL turbulence birth characteristics. Thus changes in divertor recycling may be the sole process in bringing about SOL density shoulders or in tandem with parallel resistivity

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