Rapid Prototyping of 3D Biochips for Cell Motility Studies Using Two-Photon Polymerization

The study of cellular migration dynamics and strategies plays a relevant role in the understanding of both physiological and pathological processes. An important example could be the link between cancer cell motility and tumor evolution into metastatic stage. These strategies can be strongly influenced by the extracellular environment and the consequent mechanical constrains. In this framework, the possibility to study the behavior of single cells when subject to specific topological constraints could be an important tool in the hands of biologists. Two-photon polymerization is a sub-micrometric additive manufacturing technique that allows the fabrication of 3D structures in biocompatible resins, enabling the realization of ad hoc biochips for cell motility analyses, providing different types of mechanical stimuli. In our work, we present a new strategy for the realization of multilayer microfluidic lab-on-a-chip constructs for the study of cell motility which guarantees complete optical accessibility and the possibility to freely shape the migration area, to tailor it to the requirements of the specific cell type or experiment. The device includes a series of micro-constrictions that induce different types of mechanical stress on the cells during their migration. We show the realization of different possible geometries, in order to prove the versatility of the technique. As a proof of concept, we present the use of one of these devices for the study of the motility of murine neuronal cancer cells under high physical confinement, highlighting their peculiar migration mechanisms

Intermediate filaments ensure resiliency of single carcinoma cells, while active contractility of the actin cortex determines their invasive potential

During the epithelial-to-mesenchymal transition, the intracellular cytoskeleton undergoes severe reorganization which allows epithelial cells to transition into a motile mesenchymal phenotype. Among the different cytoskeletal elements, the intermediate filaments keratin (in epithelial cells) and vimentin (in mesenchymal cells) have been demonstrated to be useful and reliable histological markers. In this study, we assess the potential invasiveness of six human breast carcinoma cell lines and two mouse fibroblasts cells lines through single cell migration assays in confinement. We find that the keratin and vimentin networks behave mechanically the same when cells crawl through narrow channels and that vimentin protein expression does not strongly correlate to single cells invasiveness. Instead, we find that what determines successful migration through confining spaces is the ability of cells to mechanically switch from a substrate-dependent stress fibers based contractility to a substrate-independent cortical contractility, which is not linked to their tumor phenotype

Holocene atmospheric dust deposition in NW Spain

This is the author accepted manuscript. The final version is available from SAGE Publications via the DOI in this record.Atmospheric dust plays an important role in terrestrial and marine ecosystems, particularly those that are nutrient limited. Despite that most dust originates from arid and semi-arid regions, recent research has shown that past dust events may have been involved in boosting productivity in nutrient-poor peatlands. We investigated dust deposition in a mid-latitude, raised bog, which is surrounded by a complex geology (paragneiss/schist, granite, quartzite and granodiorite). As proxies for dust fluxes, we used accumulation rates of trace (Ti, Zr, Rb, Sr and Y) as well as major (K and Ca) lithogenic elements. The oldest, largest dust deposition event occurred between ~8.6 and ~7.4 ka BP, peaking at ~8.1 ka BP (most probably the 8.2 ka BP event). The event had a large impact on the evolution of the mire, which subsequently transitioned from a fen into a raised bog in ~1500 years. From ~6.7 to ~4.0 ka BP, fluxes were very low, coeval with mid-Holocene forest stability and maximum extent. In the late Holocene, after ~4.0 ka BP, dust events became more prevalent with relatively major deposition at ~3.2–2.5, ~1.4 ka BP and ~0.35–0.05 ka BP, and minor peaks at ~4.0–3.7, ~1.7, ~1.10–0.95 ka BP and ~0.74–0.58 ka BP. Strontium fluxes display a similar pattern between ~11 and ~6.7 ka BP but then became decoupled from the other elements from the mid Holocene onwards. This seems to be a specific signal of the granodiorite batholith, which has an Sr anomaly. The reconstructed variations in dust fluxes bear a strong climatic imprint, probably related to storminess controlled by North Atlantic Oscillation conditions. Complex interactions also arise because of increased pressure from human activities.Natural Environment Research Council (NERC)Consiliencia networkFunding for Consolidation and Structuration of Research Unit

Tunable dual-band filters based on capacitive-loaded stepped-impedance resonators

This paper proposes the design of tunable dual-band filters for multi-band multi-standard systems. The main objective is to provide frequency tunability in the second band while maintaining the first band fixed. To this end, the capacitive-loaded stepped-impedance resonator is used. The work is divided into two main parts. In the first part, a deep analysis of the capacitive-loaded stepped-impedance resonator structure is done, which provides analytical closed-form design equations which eases their design in front of the several approaches available in the literature up to now. The analysis is also particularized for the case of the capacitive-loaded uniform resonator. In the second part, resonators are integrated in two dual-band tunable filters.Postprint (published version

Real-World Safety and Effectiveness Evidence of a Microcrystalline Tyrosine-Associated Mite Allergoid in Children and Adolescents with Allergic Rhinitis

Rinitis al·lèrgica; Infants i adolescents; Tirosina microcristal·linaRinitis alérgica; Niños y adolescentes; Tirosina microcristalinaAllerghic rhinitis; Children and adolescents; Microcrystalline tyrosineEvidence regarding allergen immunotherapy (AIT) in pediatric population is scarce. We have assessed safety and effectiveness of subcutaneous AIT with a microcrystalline tyrosine (MCT)-associated mite allergoid, Acarovac Plus®, in children and adolescents with allergic rhinitis (AR), with and without asthma, in the real-world setting. This was a retrospective, multicenter study including children and adolescents aged 5 years to 17 years with AR, with and without asthma, and sensitized to mites, receiving AIT with Acarovac Plus® during ≥6 months. Primary and secondary objectives were safety and effectiveness, respectively. Effectiveness variables were assessed during 12 months before and after AIT and included unscheduled visits to the healthcare center and emergency room admissions, rhinitis and asthma symptoms according to ARIA and GEMA classifications, respectively, medication use, and patients’ and physicians’ disease perception graded on a visual analog scale (VAS). All 79 patients included had a mean (SD) age of 12.7 (3.3) years. Two patients experienced systemic adverse reactions (none severe). Unscheduled visits to the healthcare center and emergency room admissions decreased (mean (SD) 3.02 [2.48] and 0.63 [1.35] vs. 1.08 [1.38] and 0.09 [0.38], before and after treatment, p < 0.001 and p = 0.001, respectively). After AIT, rhinitis and asthma classification changed (p < 0.0001 for all classifications), showing improvements in symptoms and a significant decrease in rhinitis and use of medication for asthma and VAS scores grading patients’ and physicians’ disease perception (p < 0.001). In conclusion, these results show that AIT with an MCT-associated mite allergoid appears safe and effective in children and adolescents with AR treated in the real-world setting.This study was supported by Allergy Therapeutics Ibérica

Sonic crystal lenses that obey Lensmaker's formula

This paper presents a theoretical study of the phenomenon of acoustic imaging by sonic crystals, which are made of two-dimensional regular arrays of rigid cylinders placed in parallel in air. The scattering of acoustic waves is computed using the standard multiple scattering theory, and the band structures are computed by the plane-wave expansion method. It is shown that properly arranged arrays not only can behave as acoustic lenses, but also the focusing effect can be well described by Lensmaker's formula. Possible applications are also discussed.Comment: 4 pages, 5 figure

Análisis de las predicciones climáticas a partir de distintos servicios climáticos para la programación del riego

Comunicación presentada al XXXVII Congreso Nacional de Riegos, celebrado en Don Benito del 4 al 6 de Junio de 2019 y organizada por la Asociación Española de Riegos y Drenajes y la Universidad de ExtremaduraEl objetivo del estudio es analizar la precisión de los servicios climáticos disponibles mediante su comparación con los datos reales registrados, y mejorar su estimación para el cálculo de la ETo a la hora de efectuar la programación del riego a corto plazo.Generalitat Valenciana, Consellería de Educación, Investigación, Cultura y Deportes: Proyecto AICO 201

Effects of sardine-enriched diet on metabolic control, inflammation and gut microbiota in drug-naïve patients with type 2 diabetes: a pilot randomized trial.

Nutrition therapy is the cornerstone of treating diabetes mellitus. The inclusion of fish (particularly oily fish) at least two times per week is recommended by current international dietary guidelines for type 2 diabetes. In contrast to a large number of human studies examining the effects of oily fish on different cardiovascular risk factors, little research on this topic is available in patients with type 2 diabetes. The aims of this pilot study were to investigate the effects of a sardine-enriched diet on metabolic control, adiponectin, inflammatory markers, erythrocyte membrane fatty acid (EMFA) composition, and gut microbiota in drug-naïve patients with type 2 diabetes. 35 drug-naïve patients with type 2 diabetes were randomized to follow either a type 2 diabetes standard diet (control group: CG), or a standard diet enriched with 100 g of sardines 5 days a week (sardine group: SG) for 6 months. Anthropometric, dietary information, fasting glycated hemoglobin, glucose, insulin, adiponectin, inflammatory markers, EMFA and specific bacterial strains were determined before and after intervention. There were no significant differences in glycemic control between groups at the end of the study. Both groups decreased plasma insulin (SG: -35.3%, P = 0.01, CG: -22.6%, P = 0.02) and homeostasis model of assessment--insulin resistance (HOMA-IR) (SG: -39.2%, P = 0.007, CG: -21.8%, P = 0.04) at 6-months from baseline. However only SG increased adiponectin in plasma compared to baseline level (+40.7%, P = 0.04). The omega-3 index increased 2.6% in the SG compared to 0.6% in the CG (P = 0.001). Both dietary interventions decreased phylum Firmicutes (SG and CG: P = 0.04) and increased E. coli concentrations (SG: P = 0.01, CG: P = 0.03) at the end of the study from baseline, whereas SG decreased Firmicutes/Bacteroidetes ratio (P = 0.04) and increased Bacteroides-Prevotella (P = 0.004) compared to baseline. Although enriching diet with 100 g of sardines 5 days a week during 6 months to a type 2 diabetes standard diet seems to have neutral effects on glycemic control in drug-naïve patients with type 2 diabetes, this nutritional intervention could have beneficial effects on cardiovascular risk. Furthermore, both dietary interventions decreased HOMA-IR and altered gut microbiota composition of drug-naïve patients with type 2 diabetes. Trial number and name of the registry: NCT02294526, ClinicalTrials.gov