Private concession contracts for toll roads in Spain: analysis and recommendations.

Spain has a long history of using the private sector to help build and operate public infrastructure, particularly roads. This article presents new data about toll motorways. The authors found that contracts in Spain are characterized by significant traffic overestimations and frequent renegotiations, which can lead to toll modifications or longer contracts. They suggest reasons for this and some solutions—both of which have significance for other countries

The generation of student engagement as a cognition-affect-behaviour process in a Twitter learning experience

Twitter is a microblog that allows users to interact about a topic in online discussion. This makes it an interesting interactive tool with possibilities to increase student engagement and learning performance through active collaboration in an informal learning environment. However, few articles take a quantitative approach to investigate the creation of student engagement using this social networking site. To address this gap, we propose a series of activities conducted through Twitter to analyse the engagement generation process in a sample of 110 students in the first year of a business and administration degree at a large Spanish university. The results show that the engagement process is created through active collaborative learning and enjoyment, and that engaged students are more satisfied with the activity and perceive greater learning performance. This leads us to recommend teachers to encourage active and collaborative activities to make students more engaged and satisfied, and improve their performance.es consisting of applying the concepts studied in class to practical environments, and activities where students browse for online information and take part in a debate, are more enjoyable

Allosteric modulation of the CXCR4:CXCL12 axis by targeting receptor nanoclustering via the TMV-TMVI domain

CXCR4 is a ubiquitously expressed chemokine receptor that regulates leukocyte trafficking and arrest in both homeostatic and pathological states. It also participates in organogenesis, HIV-1 infection, and tumor development. Despite the potential therapeutic benefit of CXCR4 antagonists, only one, plerixafor (AMD3100), which blocks the ligand-binding site, has reached the clinic. Recent advances in imaging and biophysical techniques have provided a richer understanding of the membrane organization and dynamics of this receptor. Activation of CXCR4 by CXCL12 reduces the number of CXCR4 monomers/dimers at the cell membrane and increases the formation of large nanoclusters, which are largely immobile and are required for correct cell orientation to chemoattractant gradients. Mechanistically, CXCR4 activation involves a structural motif defined by residues in TMV and TMVI. Using this structural motif as a template, we performed in silico molecular modeling followed by in vitro screening of a small compound library to identify negative allosteric modulators of CXCR4 that do not affect CXCL12 binding. We identified AGR1.137, a small molecule that abolishes CXCL12-mediated receptor nanoclustering and dynamics and blocks the ability of cells to sense CXCL12 gradients both in vitro and in vivo while preserving ligand binding and receptor internalization.</jats:p

Effects of Cortisol Administered through Slow-Release Implants on Innate Immune Responses in Rainbow Trout (Oncorhynchus mykiss)

Cortisol is a key hormone in the fish stress response with a well-known ability to regulate several physiological functions, including energy metabolism and the immune system. However, data concerning cortisol effects on fish innate immune system using a more controlled increase in cortisol levels isolated from any other stress related signaling is scarce. The present study describes the effect of doses of cortisol corresponding to acute and chronic levels on the complement and lysozyme activity in plasma of the rainbow trout (Oncorhynchus mykiss). We also evaluated the effects of these cortisol levels (from intraperitoneally implanted hydrocortisone) on the mRNA levels quantified by RT-qPCR of selected key immune-related genes in the liver, head kidney, and spleen. For that purpose, 60 specimens of rainbow trout were divided in to two groups: a control group injected with a coconut oil implant and another group injected with the same implant and cortisol (50 μg cortisol/g body weight). Our results demonstrate the role of cortisol as a modulator of the innate immune response without the direct contribution of other stress axes. Our results also show a relationship between the complement and lysozyme activity in plasma and mRNA levels in liver, supporting the important role of this organ in producing these immune system proteins after a rise of cortisol in the fish plasma