Key components of learning ecologies: a Delphi assessment

This is the accepted version of the following article: González‐Sanmamed, M. , Muñoz‐Carril, P. and Santos‐Caamaño, F. (2019), Key components of learning ecologies: A Delphi assessment. Br J Educ Technol, 50: 1639-1655, which has been published in final form at https://doi.org/10.1111/bjet.12805. This article may be used for non-commercial purposes in accordance with the Wiley Self-Archiving Policy (http://www.wileyauthors.com/self-archiving)The educational landscape has changed in recent years, requiring reflection about new pedagogical methods and theories. There are three important perspectives as drivers of pedagogical reflection: lifelong and life‐wide learning, the idea of learning as a social construct in which internal elements and changing external factors converge, and the recognition of technology as a resource that can promote ubiquitous and expanded learning. Learning ecology has been proposed as a conceptual and empirical framework, but its still emergent nature along with its multidimensionality and complexity require further exploration. The Delphi study we present as part of a broader research project aims to identify the components of learning ecologies. Three panel rounds with international experts were carried out, after which two important dimensions emerged in the structure of learning ecologies. The first is related to intrinsic “learning dispositions,” which is made up of three categories: the subject's ideas about learning, their motivations and expectations. The second dimension, called “learning processes,” comprises four components: relationships, resources, actions and context. The identification of the components of learning ecologies and their influence on formal, non‐formal and informal training processes will provide guidance for educational policies and help to better organize training programmesWe thank the Spanish Ministry of Economy and Competitiveness for their support of our study under a research project entitled “How the best University Teachers Learn: Impact on Learning Ecologies on Quality of Teaching” (ECO4LEARN‐HE) (Reference: EDU2015‐67907‐R)S

Induction of protein citrullination and auto-antibodies production in murine exposed to nickel

Abstract Citrullination, or the post-translational deimination of polypeptide-bound arginine, is involved in several pathological processes in the body, including autoimmunity and tumorigenesis. Recent studies have shown that nanomaterials can trigger protein citrullination, which might constitute a common pathogenic link to disease development. Here we demonstrated auto-antibody production in serum of nanomaterials-treated mice. Citrullination-associated phenomena and PAD levels were found to be elevated in nanomaterials -treated cell lines as well as in the spleen, kidneys and lymph nodes of mice, suggesting a systemic response to nanomaterials injection, and validated in human pleural and pericardial malignant mesothelioma (MM) samples. The observed systemic responses in mice exposed to nanomaterials support the evidence linking exposure to environmental factors with the development of autoimmunity responses and reinforces the need for comprehensive safety screening of nanomaterials. Furthermore, these nanomaterials induce pathological processes that mimic those observed in Pleural MM, and therefore require further investigations into their carcinogenicity

Danger- and pathogen-associated molecular patterns recognition by pattern-recognition receptors and ion channels of the transient receptor potential family triggers the inflammasome activation in immune cells and sensory neurons.

An increasing number of studies show that the activation of the innate immune system and inflammatory mechanisms play an important role in the pathogenesis of numerous diseases. The innate immune system is present in almost all multicellular organisms and its activation occurs in response to pathogens or tissue injury via pattern-recognition receptors (PRRs) that recognize pathogen-associated molecular patterns (PAMPs) or danger-associated molecular patterns (DAMPs). Intracellular pathways, linking immune and inflammatory response to ion channel expression and function, have been recently identified. Among ion channels, the transient receptor potential (TRP) channels are a major family of non-selective cation-permeable channels that function as polymodal cellular sensors involved in many physiological and pathological processes.In this review, we summarize current knowledge of interactions between immune cells and PRRs and ion channels of TRP families with PAMPs and DAMPs to provide new insights into the pathogenesis of inflammatory diseases. TRP channels have been found to interfere with innate immunity via both nuclear factor-kB and procaspase-1 activation to generate the mature caspase-1 that cleaves pro-interleukin-1ß cytokine into the mature interleukin-1ß.Sensory neurons are also adapted to recognize dangers by virtue of their sensitivity to intense mechanical, thermal and irritant chemical stimuli. As immune cells, they possess many of the same molecular recognition pathways for danger. Thus, they express PRRs including Toll-like receptors 3, 4, 7, and 9, and stimulation by Toll-like receptor ligands leads to induction of inward currents and sensitization in TRPs. In addition, the expression of inflammasomes in neurons and the involvement of TRPs in central nervous system diseases strongly support a role of TRPs in inflammasome-mediated neurodegenerative pathologies. This field is still at its beginning and further studies may be required.Overall, these studies highlight the therapeutic potential of targeting the inflammasomes in proinflammatory, autoinflammatory and metabolic disorders associated with undesirable activation of the inflammasome by using specific TRP antagonists, anti-human TRP monoclonal antibody or different molecules able to abrogate the TRP channel-mediated inflammatory signals

Glucagon stimulates hepatic FGF21 secretion through a PKA- and EPAC-dependent posttranscriptional mechanism.

Previous studies have shown that whole body deletion of the glucagon receptor suppresses the ability of starvation to increase hepatic fibroblast growth factor 21 (FGF21) expression and plasma FGF21 concentration. Here, we investigate the mechanism by which glucagon receptor activation increases hepatic FGF21 production. Incubating primary rat hepatocyte cultures with glucagon, dibutyryl cAMP or forskolin stimulated a 3-4-fold increase in FGF21 secretion. The effect of these agents on FGF21 secretion was not associated with an increase in FGF21 mRNA abundance. Glucagon induction of FGF21 secretion was additive with the stimulatory effect of a PPARα activator (GW7647) on FGF21 secretion. Inhibition of protein kinase A (PKA) and downstream components of the PKA pathway [i.e. AMP-activated protein kinase and p38 MAPK] suppressed glucagon activation of FGF21 secretion. Incubating hepatocytes with an exchange protein directly activated by cAMP (EPAC)-selective cAMP analog [i.e. 8-(4-chlorophenylthio)-2'-O-methyladenosine-3', 5'-cyclic monophosphate (cpTOME)], stimulated a 3.9-fold increase FGF21 secretion, whereas inhibition of the EPAC effector, Rap1, suppressed glucagon activation of FGF21 secretion. Treatment of hepatocytes with insulin also increased FGF21 secretion. In contrast to glucagon, insulin activation of FGF21 secretion was associated with an increase in FGF21 mRNA abundance. Glucagon synergistically interacted with insulin to stimulate a further increase in FGF21 secretion and FGF21 mRNA abundance. These results demonstrate that glucagon increases hepatic FGF21 secretion via a posttranscriptional mechanism and provide evidence that both the PKA branch and EPAC branch of the cAMP pathway play a role in mediating this effect. These results also identify a novel synergistic interaction between glucagon and insulin in the regulation of FGF21 secretion and FGF21 mRNA abundance. We propose that this insulin/glucagon synergism plays a role in mediating the elevation in FGF21 production during starvation and conditions related to metabolic syndrome

Glucagon synergistically interacts with insulin to induce FGF21 secretion and FGF21 mRNA abundance.

<p>A: effect of insulin on FGF21 secretion, FGF21 mRNA abundance, and albumin secretion in primary rat hepatocytes incubated in the absence and presence of glucagon. Cells were incubated with or without insulin (50 nM), glucagon (25 nM), or insulin plus glucagon for 6 h. The level of FGF21 and albumin in the culture medium and the abundance of FGF21 mRNA in total RNA of cells incubated no additions were set to 1, and the other values were adjusted proportionately. Values are means ± SE (n = 4). B: effect of different concentrations of insulin on FGF21 mRNA abundance. Hepatocytes were incubated with the indicated concentrations of insulin and glucagon for 6 h. The abundance of FGF21 mRNA in cells incubated with no hormones was set at 1, and the other values were adjusted proportionately. Values are means ± SE (n = 3). * Significantly different (<i>P</i><0.05) from that of cells incubated with no additions. ^# Significantly different (<i>P</i><0.05) from that of cells incubated with glucagon or insulin alone.</p

Glucagon increases FGF21 secretion via a mechanism not involving changes in FGF21 mRNA abundance.

<p>A: effect of different concentrations of glucagon on FGF21 secretion, FGF21 mRNA abundance, and albumin secretion in primary rat hepatocyte cultures. Cells were incubated with the indicated concentrations of glucagon in serum-free Medium 199 for 6 h. The level of FGF21 and albumin in the culture medium and the abundance of FGF21 mRNA in total RNA of cells incubated with 0 nM glucagon (Gln) were set at 1, and the other values were adjusted proportionately. Values are means ± SE (n = 3). B: time course of the effect glucagon on FGF21 secretion, FGF21 mRNA abundance, and albumin secretion. Rat hepatocytes were incubated with or without glucagon (25 nM) for the indicated time periods. The level of FGF21 and albumin in the culture medium and the abundance of FGF21 mRNA in total RNA of cells incubated with no additions (NA) for 2 h were set at 1, and the other values were adjusted proportionately. Values are means ± SE (n = 4). C: the effect of glucagon on FGF21 secretion is reversible. Rat hepatocytes were initially incubated with or without glucagon for 18 h. The culture medium was then replaced with one containing glucagon or NA, and the incubation was continued for 6 h. The level of FGF21 and albumin in the culture medium and the abundance of FGF21 mRNA in total RNA of cells incubated with NA for both treatment periods were set at 1, and the other values were adjusted proportionately. Values are means ± SE (n = 4). D: interaction between glucagon and PPARα in the regulation of FGF21 secretion and FGF21 mRNA abundance. Rat hepatocytes were incubated with or without glucagon (25 nM), GW7647 (1 µM), or glucagon plus GW7647 for 6 h. The level of FGF21 and albumin in the culture medium and the abundance of FGF21 mRNA in total RNA of cells incubated no additions were set to 1, and the other values were adjusted proportionately. Values are means ± SE (n = 3). * Significantly different (<i>P</i><0.05) from that of cells incubated with no additions. ^# Significantly different (<i>P</i><0.05) from that of cells incubated with glucagon or GW7647 alone.</p