Engineered microenvironments for synergistic VEGF - integrin signalling during vascularization

We have engineered polymer-based microenvironments that promote vasculogenesis both in vitro and in vivo through synergistic integrin-growth factor receptor signalling. Poly(ethyl acrylate) (PEA) triggers spontaneous organization of fibronectin (FN) into nanonetworks which provide availability of critical binding domains. Importantly, the growth factor binding (FNIII12-14) and integrin binding (FNIII9-10) regions are simultaneously available on FN fibrils assembled on PEA. This material platform promotes synergistic integrin/VEGF signalling which is highly effective for vascularization events in vitro with low concentrations of VEGF. VEGF specifically binds to FN fibrils on PEA compared to control polymers (poly(methyl acrylate), PMA) where FN remains in a globular conformation and integrin/GF binding domains are not simultaneously available. The vasculogenic response of human endothelial cells seeded on these synergistic interfaces (VEGF bound to FN assembled on PEA) was significantly improved compared to soluble administration of VEGF at higher doses. Early onset of VEGF signalling (PLCγ1 phosphorylation) and both integrin and VEGF signalling (ERK1/2 phosphorylation) were increased only when VEGF was bound to FN nanonetworks on PEA, while soluble VEGF did not influence early signalling. Experiments with mutant FN molecules with impaired integrin binding site (FN-RGE) confirmed the role of the integrin binding site of FN on the vasculogenic response via combined integrin/VEGF signalling. In vivo experiments using 3D scaffolds coated with FN and VEGF implanted in the murine fat pad demonstrated pro-vascularization signalling by enhanced formation of new tissue inside scaffold pores. PEA-driven organization of FN promotes efficient presentation of VEGF to promote vascularization in regenerative medicine applications

Statistics anxiety in university students in assessment situations

[EN] Many students have feelings of state anxiety when exams, and these feelings probably affect their performance. Statistics courses have been identified as producing the most anxiety. The purpose of our study is to measure statistics anxiety throughout an academic course (pre-test and three assessments) in order to observe its change and analyze the relationship between statistics anxiety and academic achievement. The sample is composed of 30 Psychology students taking a course in research designs and statistics (26.7% men and 73.3% women) with a mean age of 20.31 years (SD = 3.76). The results show that the students begin with a high level of statistics anxiety that gradually declines as the course progresses and they study the course materials. Moreover, the final achievement in the subject maintains an inverse relationship with the level of statostics anxiety. The recommendation is to present the detailed contents of the teaching guide on the first day of the course in order to reduce students' anxiety and uncertainty when beginning a statistics course.http://ocs.editorial.upv.es/index.php/HEAD/HEAD18Frias-Navarro, D.; Monterde-I-Bort, H.; Navarro-Gonzalez, N.; Molina-Palomero, O.; Pascual-Soler, M.; Perezgonzalez, J.; Longobardi, C. (2018). Statistics anxiety in university students in assessment situations. Editorial Universitat Politècnica de València. 337-345. https://doi.org/10.4995/HEAD18.2018.7990OCS33734

Implications of Halo Inside-out Growth on the X-Ray Properties of Nearby Galaxy Systems within the Preheating Scenario

We present an entirely analytic model for a preheated, polytropic intergalactic medium in hydrostatic equilibrium within a NFW dark halo potential in which the evolution of the halo structure between major merger events proceeds inside-out by accretion. This model is used to explain, within a standard $\Lambda$CDM cosmogony, the observed X-ray properties of nearby relaxed, non-cooling flow groups and clusters of galaxies. We find that our preferred solution to the equilibrium equations produces scaling relations in excellent agreement with observations, while simultaneously accounting for the typical structural characteristics of the distribution of the diffuse baryons. In the class of preheating models, ours stands out because it offers a unified description of the intrahalo medium for galaxy systems with total masses above \sm 2\times 10^{13}\msun, does not produce baryonic configurations with large isentropic cores, and reproduces faithfully the observed behavior of the gas entropy at large radii. All this is achieved with a moderate level of energy injection of about half a keV, which can be easily accommodated within the limits of the total energy released by the most commonly invoked feedback mechanisms, as well as with a polytropic index of 1.2, consistent with both many observational determinations and predictions from high-resolution gas-dynamical simulations of non-cooling flow clusters. More interestingly, our scheme offers a physical motivation for the adoption of this specific value of the polytropic index, as it is the one that best ensures the conservation after halo virialization of the balance between the total specific energies of the gas and dark matter components for the full range of masses investigated.Comment: 18 pages, 11 figures, accepted for publication in the Astrophysical Journa

Self-gravitating branes of codimension 4 in Lovelock gravity

We construct a familly of exact solutions of Lovelock equations describing codimension four branes with discrete symmetry in the transverse space. Unlike what is known from pure Einstein gravity, where such brane solutions of higher codimension are singular, the solutions we find, for the complete Lovelock theory, only present removable singularities. The latter account for a localised tension-like energy-momentum tensor on the brane, in analogy with the case of a codimension two self-gravitating cosmic string in pure Einstein gravity. However, the solutions we discuss present two main distinctive features : the tension of the brane receives corrections from the induced curvature of the brane's worldsheet and, in a given Lovelock theory, the spectrum of possible values of the tension is discrete. These solutions provide a new framework for the study of higher codimension braneworlds.Comment: 22 page

Comparative transcriptome analysis reveals key epigenetic targets in SARS-CoV-2 infection

COVID-19 is an infection caused by SARS-CoV-2 (Severe Acute Respiratory Syndrome coronavirus 2), which has caused a global outbreak. Current research efforts are focused on the understanding of the molecular mechanisms involved in SARS-CoV-2 infection in order to propose drug-based therapeutic options. Transcriptional changes due to epigenetic regulation are key host cell responses to viral infection and have been studied in SARS-CoV and MERS-CoV; however, such changes are not fully described for SARS-CoV-2. In this study, we analyzed multiple transcriptomes obtained from cell lines infected with MERS-CoV, SARS-CoV and SARS-CoV-2, and from COVID-19 patient-derived samples. Using integrative analyses of gene co-expression networks and de-novo pathway enrichment, we characterize different gene modules and protein pathways enriched with Transcription Factors or Epifactors relevant for SARS-CoV-2 infection. We identified EP300, MOV10, RELA and TRIM25 as top candidates, and more than 60 additional proteins involved in the epigenetic response during viral infection that have therapeutic potential. Our results show that targeting the epigenetic machinery could be a feasible alternative to treat COVID-19.Comment: 33 pages, 2 tables, 5 figures, 4 supplementary figure

Combination of polymeric superplasticizers, water repellents and pozzolanic agents to improve air lime-based grouts for historic masonry repair

This paper presents the experimental procedure to develop air lime-based injection grouts including polymeric superplasticizers, a water repellent agent and pozzolanic agents as additives. Research focuses on the development of grouts to improve various characteristics simultaneously combining different additions and admixtures. Aiming to improve the injectability of the grouts, in this study different polymeric superplasticizers were added, namely polycarboxylated-ether derivative (PCE), polynaphthalene sulfonate (PNS) and condensate of melamine-formaldehyde sulfonate (SMFC). Sodium oleate was also used as a water repellent agent to reduce the water absorption. The enhancement of the strength and setting time was intended by using microsilica and metakaolin as pozzolanic mineral additions. Compatibility between the different admixtures and action mechanism of the different polymers were studied by means of zeta potential and adsorption isotherms measurements. Diverse grout mixtures were produced and investigated assessing their injectability, fluidity, stability, compressive strength, hydrophobicity and durability. This research leads to several suitable mixtures produced by using more than one component to enhance efficiency and to provide better performance of grouts. According to the results, the grout composed of air lime, metakaolin, sodium oleate and PCE was found the most effective composition improving the mechanical strength, injectability and hydrophobicity

Magnetic and structural-properties of electrodeposited Co1-xPx amorphous ribbons

The specific magnetic moment, coercive force, anisotropy field, and saturation magnetostriction constant have been measured in Co(1-x)P(x) amorphous ribbons with 0.04 less-than-or-equal-to x less-than-or-equal-to 0.27. Differential scanning calorimetry, x-ray diffraction, and transmission electron microscopy analysis have been made in order to study the transition from the amorphous state to the crystalline one. Results suggest that transition takes place when x decreases from 0.19

Amyloid- β reduces the expression of neuronal FAIM-L, thereby shifting the inflammatory response mediated by TNF α from neuronal protection to death

The brains of patients with Alzheimer's disease (AD) present elevated levels of tumor necrosis factor- α (TNF α), a cytokine that has a dual function in neuronal cells. On one hand, TNF α can activate neuronal apoptosis, and on the other hand, it can protect these cells against amyloid- β (A β) toxicity. Given the dual behavior of this molecule, there is some controversy regarding its contribution to the pathogenesis of AD. Here we examined the relevance of the long form of Fas apoptotic inhibitory molecule (FAIM) protein, FAIM-L, in regulating the dual function of TNF α. We detected that FAIM-L was reduced in the hippocampi of patients with AD. We also observed that the entorhinal and hippocampal cortex of a mouse model of AD (PS1xAPP) showed a reduction in this protein before the onset of neurodegeneration. Notably, cultured neurons treated with the cortical soluble fractions of these animals showed a decrease in endogenous FAIM-L, an effect that is mimicked by the treatment with A β -derived diffusible ligands (ADDLs). The reduction in the expression of FAIM-L is associated with the progression of the neurodegeneration by changing the inflammatory response mediated by TNF α in neurons. In this sense, we also demonstrate that the protection afforded by TNF α against A β toxicity ceases when endogenous FAIM-L is reduced by short hairpin RNA (shRNA) or by treatment with ADDLs. All together, these results support the notion that levels of FAIM-L contribute to determine the protective or deleterious effect of TNF α in neuronal cells

Dietary patterns and difficulty conceiving: a nested case–control study

Objective: To investigate potential associations between dietary patterns (defined using factor analysis) and difficulty conceiving. Design: Case–control study nested in a Spanish cohort of university graduates (Seguimiento Universidad de Navarra [SUN] Project). Setting: Female university graduates all over Spain participating in the SUN Project. Patient(s): A total of 485 women, aged 20–45 years, reporting having presented with difficulty getting pregnant, and 1,669 age-matched controls who had at least one child. Intervention(s): None. Main Outcome Measure(s): Reported difficulty getting pregnant. Data were collected from baseline and follow-up questionnaires of the SUN Project. Results: Two dietary patterns were identified. They were labeled as “Mediterranean-type” and “Western-type” patterns. A lower risk of difficulty getting pregnant was apparent in the highest quartile of adherence to the Mediterranean-type pattern compared with the lowest quartile (odds ratio 0.56, 95% confidence interval 0.35–0.95). Greater adherence to the Western-type dietary pattern showed no association with this outcome. Conclusion: A greater adherence to the Mediterranean-type dietary pattern may enhance fertility. Further evidence about the relationship between this dietary pattern and fertility is needed to develop nutritional interventions for women desiring to get pregnant