Unique populations of lung mast cells are required for antigen-mediated bronchoconstriction: Lung reconstitution ofKitWsh/Wshmice

Studies in both human and mouse indicate that mediators released by mast cells can lead to bronchoconstriction, and thus these are important effector cells in life threatening anaphylaxis. Much of our understanding of the various functions of mast cells emanates from the study of mice lacking theses cells, particularly mice carrying mutations in the tyrosine kinase gene Kit. Definitive evidence for the role of mast cells in the altered immune response requires the demonstration that this response can be normalized by reconstitution of the mice with cultured bone marrow-derived mast cells (BMMCs). While many mast cell niches can be restored with BMMCs, this has not been demonstrated for mast cells present in the airways of the lung, cells poised to mediate bronchoconstriction during allergic responses

Mice Lacking Three Loci Encoding 14 Glutathione Transferase Genes: A Novel Tool for Assigning Function to the GSTP, GSTM, and GSTT Families

Glutathione S-transferases (GSTs) form a superfamily defined by their ability to catalyze the conjugation of glutathione with electrophilic substrates. These enzymes are proposed to play a critical role in protection of cellular components from damage mediated by reactive metabolites. Twenty-two cytosolic GSTs, grouped into seven families, are recognized in mice. This complexity hinders the assignment of function to a subset or family of these genes. We report generation of a mouse line in which the locus encoding three GST gene families is deleted. This includes the four Gstt genes spanning 65 kb on chromosome 10 and the seven Gstm genes found on a 150 kb segment of DNA chromosome 3. In addition, we delete two Gstp genes on chromosome 19 as well as a third related gene located 15 kb telomeric to Gstp1 and Gstp2, which we identify as a potential new member of this gene family. We show that, despite the loss of up to 75% of total GST activity in some tissues from these animals, the mice are healthy and fertile, with normal life expectancy. The normal development and health of these animals make them an appropriate model for defining the role of these families in redox homeostasis and metabolism of drugs and environmental pollutants

Critical Language and Discourse Awareness in Management Education

Communication and, through it, language have become key elements of business and organizational life. How organizations interact within their walls and with the outside world fundamentally affects business processes, creating organizational culture, shaping public perceptions, and influencing consumer choices. This essay calls for a greater acknowledgment of language and communication and suggests that management educators may want to review how they are incorporated in management education curricula. Expanding on the skill-based approach typically adopted in business school classes, the essay points to the utility of exposing business students to the dual function of language as a means of doing work and as a social action that constitutes social reality. Drawing on examples from scholarship in linguistics and discourse analysis, the essay demonstrates that the ability to notice, identify, and reflect on linguistic and discourse practices is a crucial managerial skill. Nurturing such analytical and thinking skills enables people to become not only better communicators but also critical thinkers able to understand and challenge when social control, power, or injustice is enacted in organizations

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

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

Exploring consensus on how to measure smoking cessation. A Delphi study

Background Different criteria regarding outcome measures in smoking research are used, which can lead to confusion about study results. Consensus in outcome criteria may enhance the comparability of future studies. This study aims (1) to provide an overview of tobacco researchers’ considered preferences regarding outcome criteria in randomized controlled smoking cessation trials, and (2) to identify the extent to which researchers can reach consensus on the importance of these outcome criteria. Methods A three-round online Delphi study was conducted among smoking cessation experts. In the first round, the most important smoking cessation outcome measures were collected by means of open-ended questions, which were categorized around self-reported and biochemical validation measures. Experts (n = 17) were asked to name the outcome measures (as well as their assessment method and ideal follow-up period) that they thought were important when assessing smoking-related outcomes. In the second (n = 48) and third rounds (n = 37), a list of outcome measures—identified in the first round—was presented to experts. Asking them to rate the importance of each measure on a seven-point scale. Results Experts reached consensus on several items. For self-reports, experts agreed that prolonged abstinence (6 or/and 12 months), point prevalence abstinence (7 days), continuous abstinence (6 months), and the number of cigarettes smoked (7 days) are important outcome measures. Experts reached consensus that biochemical validation methods should not always be used. The preferred biochemical validation methods were carbon monoxide (expired air) and cotinine (saliva). Preferred follow-ups included 6 and/or 12 months, with or without intermediate measurements. Conclusions Findings suggest only partial compliance with the Russell standard and that more outcome measures may be important (including seven-day point-prevalence abstinence, number of cigarettes smoked, and cotinine when using biochemical validation). This study showed where there is and is not consensus, reflecting the need to develop a more comprehensive standard. For these purposes we provided suggestions for the Russell 2.0 standard