Reduced Susceptibility to Two-Stage Skin Carcinogenesis in Mice with Epidermis-Specific Deletion of Cd151

Altered expression of the tetraspanin CD151 is associated with skin tumorigenesis; however, whether CD151 is causally involved in the tumorigenic process is not known. To evaluate its role in tumor formation, we subjected epidermis-specific Cd151 knockout mice to chemical skin carcinogenesis. Mice lacking epidermal Cd151 developed fewer and smaller tumors than wild-type mice after treatment with 7,12-dimethylbenzanthracene (DMBA)/12-O-tetradecanoylphorbol-13-acetate (TPA). Furthermore, Cd151-null epidermis showed a reduced hyperproliferative response to short-term treatment with TPA as compared with wild-type skin, whereas epidermal turnover was increased. Tumors were formed in equal numbers after DMBA-only treatment. We suggest that DMBA-initiated keratinocytes lacking Cd151 leave their niches in the epidermis and hair follicles in response to TPA treatment and subsequently are lost by differentiation. Because genetic ablation of Itga3 also reduced skin tumor formation, we tested whether reduced expression of α3 could further suppress tumor formation in epidermis-specific Cd151 knockout mice. Although DMBA/TPA-induced formation of skin tumors was similar in compound heterozygotes for Cd151 and Itga3 to that in wild-type mice, heterozygosity for Itga3 on a Cd151-null background diminished tumorigenesis, suggesting genetic interaction between the two genes. We thus identify CD151 as a critical factor in TPA-dependent skin carcinogenesis

Climate Change and Sea Ice: Local Observations from the Canadian Western Arctic

Can local observations and indigenous knowledge be used to provide information that complements research on climate change? Using participatory research methodology and semi-directed interviews, we explored local and traditional knowledge about changes in sea ice in the area of Sachs Harbour, Northwest Territories. In this small Inuvialuit community, we interviewed all of the 16 community members and elders considered to be local experts on sea ice to ask about their observations. We organized their comments under the headings multiyear ice, first-year ice, fractures and pressure ridges, breakup and freeze-up seasons, and other climate-related variables that influence sea ice (such as changes in winter, spring and summer temperatures, wind, rain, and thunderstorms). Observations were remarkably consistent in providing evidence of local change in such variables as multiyear ice distribution, first-year ice thickness, and ice breakup dates. The changes observed in the 1990s were said to be without precedent and outside the normal range of variation. In assessing the relevance of Inuvialuit knowledge to scientific research on climate change, we note some of the areas in which sharing of information between the two systems of knowledge may be mutually beneficial. These include the analysis of options for adapting to climate change and the generation of research questions and hypotheses for future studies.Est-ce que les observations locales et le savoir des Autochtones peuvent aider à fournir de l'information complétant la recherche sur le changement climatique? En faisant appel à une méthodologie de recherche participative et des entrevues semi-dirigées, on a examiné le savoir local et traditionnel concernant les changements de la banquise dans la région de Sachs Harbour (Territoires du Nord-Ouest). Dans cette petite communauté inuvialuite, on a interviewé les 16 membres et aînés de la communauté considérés comme des experts locaux de la banquise pour les interroger sur leurs observations. On a organisé leurs commentaires sous les rubriques suivantes: glace pluriannuelle, glace de l'année, crêtes de fractures et de pression, saisons de débâcle et d'engel, ainsi que d'autres variables reliées au climat qui influencent la banquise (comme les changements dans les températures hivernale, printanière et estivale, le vent, la pluie et les orages). Il y avait une concordance frappante dans les observations quant aux preuves de changements à l'échelle locale dans des variables comme la distribution de la glace pluriannuelle, l'épaisseur de la glace de l'année et les dates de la débâcle. Les changements observés au cours des années 1990 étaient, selon les Autochtones, sans précédent et ils dépassaient la gamme normale des variations. En évaluant la pertinence du savoir des Inuvialuits pour la recherche scientifique sur le changement climatique, on souligne certains des domaines dans lesquels le partage de l'information entre les deux systèmes de savoir pourrait être mutuellement profitable. Ces domaines comprennent l'analyse des options visant l'adaptation au changement climatique et la formulation de questions et hypothèses de recherche pour des études ultérieures

Kidney failure in mice lacking the tetraspanin CD151

The tetraspanin CD151 is a cell-surface molecule known for its strong lateral interaction with the laminin-binding integrin α3β1. Patients with a nonsense mutation in CD151 display end-stage kidney failure associated with regional skin blistering and sensorineural deafness, and mice lacking the integrin α3 subunit die neonatally because of severe abnormalities in the lung and kidney epithelia. We report the generation of Cd151-null mice that recapitulate the renal pathology of human patients, i.e., with age they develop massive proteinuria caused by focal glomerulosclerosis, disorganization of the glomerular basement membrane, and tubular cystic dilation. However, neither skin integrity nor hearing ability are impaired in the Cd151-null mice. Furthermore, we generated podocyte-specific conditional knockout mice for the integrin α3 subunit that show renal defects similar to those in the Cd151 knockout mice. Our results support the hypothesis that CD151 plays a key role in strengthening α3β1-mediated adhesion in podocytes

What traits are carried on mobile genetic elements, and why?

Although similar to any other organism, prokaryotes can transfer genes vertically from mother cell to daughter cell, they can also exchange certain genes horizontally. Genes can move within and between genomes at fast rates because of mobile genetic elements (MGEs). Although mobile elements are fundamentally self-interested entities, and thus replicate for their own gain, they frequently carry genes beneficial for their hosts and/or the neighbours of their hosts. Many genes that are carried by mobile elements code for traits that are expressed outside of the cell. Such traits are involved in bacterial sociality, such as the production of public goods, which benefit a cell's neighbours, or the production of bacteriocins, which harm a cell's neighbours. In this study we review the patterns that are emerging in the types of genes carried by mobile elements, and discuss the evolutionary and ecological conditions under which mobile elements evolve to carry their peculiar mix of parasitic, beneficial and cooperative genes

Stakeholder engagement in the design of scenarios of technology-enhanced tourism services

The rapid uptake of mobile and digital technologies has the potential to radically transform city-visiting experiences. This will result in a transition from technology that is owned and delivered by tourism organisations towards software developed by third party organisations that is owned and managed directly by tourists. Tourism providers in destinations must collaborate in service provision in order to develop integrated services to meet the needs of tourists and remain competitive. This paper argues that scenario-based design (SBD) offers a useful tool to generate innovative ideas for destination service development and to break down barriers to collaboration amongst tourism stakeholders. We report a study, which engaged city stakeholders in envisioning innovative, technology-based tourism services. We outline this process, discuss the value of SBD in multi-stakeholder service design, and make recommendations for future work in this area

Emotional induction through music: Measuring cardiac and electrodermal responses of emotional states and their persistence

The Supplementary Material for this article can be foundonlineat:https://www.frontiersin.org/articles/10.3389/fpsyg.2019.00451/full#supplementary-materialEmotional inductions through music (EIM) procedures have proved to evoke genuine emotions according to neuroimaging studies. However, the persistence of the emotional states after being exposed to musical excerpts remains mostly unexplored. This study aimed to investigate the curve of emotional state generated by an EIM paradigm over a 6-min recovery phase, monitored with valence and arousal self-report measures, and physiological parameters. Stimuli consisted of a neutral and two valenced musical excerpts previously reported to generate such states. The neutral excerpt was composed in a minimalist form characterized by simple sonorities, rhythms, and patterns; the positive excerpt had fast tempo and major tones, and the negative one was slower in tempo and had minor tone. Results of 24 participants revealed that positive and negative EIM effectively induced self-reported happy and sad emotions and elicited higher skin conductance levels (SCL). Although self-reported adjectives describing evoked-emotions states changed to neutral after 2 min in the recovery phase, the SCL data suggest longer lasting arousal for both positive and negative emotional states. The implications of these outcomes for musical research are discussed.We would like to thank all the participants who collaborated in this study and the reviewers whose suggestions helped to improve the quality of the manuscript. We acknowledge the financial support of the Brazilian National Council for Scientific and Technological Development (CNPq-grant 229520/2013-8) and also the Portuguese National Funding Agency for Science, Research and Technology (FCT-SFRH/BPD/91347/2012). Moreover, we want to thank the Psychology Research Centre (UID/PSI/01662/2013), the University of Minho, which is supported by the FCT and the Portuguese Ministry of Science, Technology and Higher Education through national funds and co-financed by FEDER through COMPETE2020 under the PT2020 Partnership Agreement (POCI-01-0145-FEDER-007653). And finally, we want to thank the Research Centre for Human Development (CEDH) also supported by the FCT (UID/CED/4872/2016)

The extractive industries and development: The resource curse at the micro, meso and macro levels

The resource curse literature has necessarily evolved in a rather fragmented way. While economists, political economists and political scientists have largely focused on the role of mineral abundance in long-term growth with the analysis largely confined to the country (macro) or regional (meso) level, anthropologists, sociologists and other social scientists have explored the development impacts of extractive industries at the community (micro) level. While this has provided a rigorous and comprehensive exploration of extractive industries and their impacts, causal factors that bridge and/or leap-frog these levels tend not to be accounted for. In this paper we examine the evolution of the literature across disciplinary lines and different levels of scale to assess the current status of resource curse debates. In so doing, we aim to explore how an integration of the various multi-scale approaches can help address the persistent problem of the resource curse

Training of patient and consumer representatives in the basic competencies of evidence-based medicine: a feasibility study

<p>Abstract</p> <p>Background</p> <p>Evidence-based medicine (EBM) has become standard approach in medicine. Patients and health authorities increasingly claim active patient roles in decision making. Education to cope with these roles might be useful. We investigated the feasibility, acceptability and possible impact of EBM training courses for patient and consumer representatives.</p> <p>Methods</p> <p>We designed a generic one-week EBM course based on previous experience with EBM courses for non-medical health professionals. A course specific competence test has been developed and validated to measure EBM skills. Formative and summative evaluation of the course comprised: 1) EBM skills; 2) individual learning goals; 3) self-reported implementation after six months using semi-structured interviews; 4) group-based feedback by content analysis. EBM skills' achievement was compared to results gathered by a group of undergraduate University students of Health Sciences and Education who had attended a comparable EBM seminar.</p> <p>Results</p> <p>Fourteen EBM courses were conducted including 161 participants without previous EBM training (n = 54 self-help group representatives, n = 64 professional counsellors, n = 36 patient advocates, n = 7 others); 71% had a higher education degree; all but five finished the course. Most participants stated personal learning goals explicitly related to practicing EBM such as acquisition of critical appraisal skills (n = 130) or research competencies (n = 67). They rated the respective relevance of the course on average with 80% (SD 4) on a visual analogue scale ranging from 0 to 100%.</p> <p>Participants passed the competence test with a mean score of 14.7 (SD 3.0, n = 123) out of 19.5 points. The comparison group of students achieved a mean score of 14.4 (SD 3.3, n = 43). Group-based feedback revealed increases of self confidence, empowerment through EBM methodology and statistical literacy, and acquisition of new concepts of patient information and counselling. Implementation of EBM skills was reported by 84 of the 129 (65%) participants available for follow-up interviews. Barriers included lack of further support, limited possibilities to exchange experiences, and feeling discouraged by negative reactions of health professionals.</p> <p>Conclusions</p> <p>Training in basic EBM competencies for selected patient and consumer representatives is feasible and accepted and may affect counselling and advocacy activities. Implementation of EBM skills needs support beyond the training course.</p