Salt Restriction Leads to Activation of Adult Renal Mesenchymal Stromal Cell-Like Cells via Prostaglandin E2 and E-Prostanoid Receptor 4

Despite the importance of juxtaglomerular (JG) cell recruitment in the pathophysiology of cardiovascular diseases, the mechanisms that underlie renin production under conditions of chronic stimulation remain elusive. We have previously shown that CD44+ mesenchymal-like cells (CD44+ cells) exist in the adult kidney. Under chronic sodium deprivation these cells are recruited to the JG area and differentiate to new renin-expressing cells. Given the proximity of macula densa (MD) to the JG area and the importance of MD released prostanoids in renin synthesis and release, we hypothesized that chronic sodium deprivation induces MD release of prostanoids; stimulating renal CD44+ cell activation and differentiation. CD44+ cells were isolated from adult kidneys and co-cultured with the MD cell line, MMDD1, in normal or low sodium medium. Low sodium stimulated PGE2 production by MMDD1 and induced migration of CD44+ cells. These effects were inhibited by addition of a Cox-2 inhibitor (NS398) or an EP4 receptor antagonist (AH23848) to MMDD1 or CD44+ cells respectively. Addition of PGE2 to CD44+ cells increased cell migration and induced renin expression. In vivo activation of renal CD44+ cells during JG recruitment was attenuated in wild type mice subjected to salt restriction in the presence of Cox-2 inhibitor Rofecoxib. Similar results were observed in EP4 receptor knockout mice subjected to salt restriction. These results show that the PGE2/ EP4 pathway plays a key role in the activation of renal CD44+ MSC-like cells during conditions of JG recruitment; highlighting the importance of this pathway as a key regulatory mechanism of JG recruitment

Using Simulations as a Starting Point for Constructing Meaningful Learning Games

For many school administrators and decision makers, the term “video games” holds numerous cultural associations which make their adoption in the education space challenging. Additionally, the term is so broad that it can sometimes be difficult to communicate explicitly a desire to build learning experiences that go beyond the Drill and Kill edutainment titles that currently dominate most people’s perceptions of educational games. By contrast, the term “simulations” is often well respected among educators, particularly in the natural sciences. With “simulation” already being a full genre of video games, it would seem natural that researchers are beginning to explore the overlaps between simulation games and pedagogical goals that go beyond those found in Drill and Kill games. In this chapter, we survey some of the relevant research concerning both simulations and video games and outline practical pathways through which we can leverage the interest and frameworks designed for simulation construction to facilitate the introduction of video game concepts and experiences into the classroom environment. In particular, we report on the use of Starlogo TNG, a graphical programming environment in which kids themselves can create simulation-based video games, for deepening children’s understanding of scientific concepts

Depauperate Avifauna in Plantations Compared to Forests and Exurban Areas

Native forests are shrinking worldwide, causing a loss of biological diversity. Our ability to prioritize forest conservation actions is hampered by a lack of information about the relative impacts of different types of forest loss on biodiversity. In particular, we lack rigorous comparisons of the effects of clearing forests for tree plantations and for human settlements, two leading causes of deforestation worldwide. We compared avian diversity in forests, plantations and exurban areas on the Cumberland Plateau, USA, an area of global importance for biodiversity. By combining field surveys with digital habitat databases, and then analyzing diversity at multiple scales, we found that plantations had lower diversity and fewer conservation priority species than did other habitats. Exurban areas had higher diversity than did native forests, but native forests outscored exurban areas for some measures of conservation priority. Overall therefore, pine plantations had impoverished avian communities relative to both native forests and to exurban areas. Thus, reports on the status of forests give misleading signals about biological diversity when they include plantations in their estimates of forest cover but exclude forested areas in which humans live. Likewise, forest conservation programs should downgrade incentives for plantations and should include settled areas within their purview

Outcomes for Implementation Research: Conceptual Distinctions, Measurement Challenges, and Research Agenda

An unresolved issue in the field of implementation research is how to conceptualize and evaluate successful implementation. This paper advances the concept of “implementation outcomes” distinct from service system and clinical treatment outcomes. This paper proposes a heuristic, working “taxonomy” of eight conceptually distinct implementation outcomes—acceptability, adoption, appropriateness, feasibility, fidelity, implementation cost, penetration, and sustainability—along with their nominal definitions. We propose a two-pronged agenda for research on implementation outcomes. Conceptualizing and measuring implementation outcomes will advance understanding of implementation processes, enhance efficiency in implementation research, and pave the way for studies of the comparative effectiveness of implementation strategies

Multigene phylogeny of the Mustelidae: Resolving relationships, tempo and biogeographic history of a mammalian adaptive radiation

<p>Abstract</p> <p>Background</p> <p>Adaptive radiation, the evolution of ecological and phenotypic diversity from a common ancestor, is a central concept in evolutionary biology and characterizes the evolutionary histories of many groups of organisms. One such group is the Mustelidae, the most species-rich family within the mammalian order Carnivora, encompassing 59 species classified into 22 genera. Extant mustelids display extensive ecomorphological diversity, with different lineages having evolved into an array of adaptive zones, from fossorial badgers to semi-aquatic otters. Mustelids are also widely distributed, with multiple genera found on different continents. As with other groups that have undergone adaptive radiation, resolving the phylogenetic history of mustelids presents a number of challenges because ecomorphological convergence may potentially confound morphologically based phylogenetic inferences, and because adaptive radiations often include one or more periods of rapid cladogenesis that require a large amount of data to resolve.</p> <p>Results</p> <p>We constructed a nearly complete generic-level phylogeny of the Mustelidae using a data matrix comprising 22 gene segments (~12,000 base pairs) analyzed with maximum parsimony, maximum likelihood and Bayesian inference methods. We show that mustelids are consistently resolved with high nodal support into four major clades and three monotypic lineages. Using Bayesian dating techniques, we provide evidence that mustelids underwent two bursts of diversification that coincide with major paleoenvironmental and biotic changes that occurred during the Neogene and correspond with similar bursts of cladogenesis in other vertebrate groups. Biogeographical analyses indicate that most of the extant diversity of mustelids originated in Eurasia and mustelids have colonized Africa, North America and South America on multiple occasions.</p> <p>Conclusion</p> <p>Combined with information from the fossil record, our phylogenetic and dating analyses suggest that mustelid diversification may have been spurred by a combination of faunal turnover events and diversification at lower trophic levels, ultimately caused by climatically driven environmental changes. Our biogeographic analyses show Eurasia as the center of origin of mustelid diversity and that mustelids in Africa, North America and South America have been assembled over time largely via dispersal, which has important implications for understanding the ecology of mustelid communities.</p

Means versus ends in opaque institutional fields: Trading off compliance and achievement in sustainability standard adoption

__Abstract__ The long-standing discussion on decoupling has recently moved from adopters not implementing the agreed-upon policies to compliant adopters not achieving the goals intended by institutional entrepreneurs. This “means-ends decoupling” prevails especially in highly opaque fields, where practices, causality, and performance are hard to understand and chart. I conceptualize the conditions under which the adoption of institutions in relatively opaque fields leads to the achievement of the envisaged goals. Voluntary sustainability standards governing socioenvironmental issues illustrate these arguments. I argue that the lack of field transparency drives institutional entrepreneurs to create and maintain concrete and uniform rules, apply strong incentives, and disseminate “best practices” to ensure substantive adopter compliance. However, such rigid institutions are ill-equipped to deal with the causal complexity and practice multiplicity underlying opacity while they smother adopter agency. The ensuing tension between substantive compliance and goal achievement leads to an inherent trade-off: institutional entrepreneurs who remedy the policy-practice decoupling may enhance the disparity between means and ends, and vice versa. While sustainability standards and other institutions in highly opaque fields can, therefore, not fully achieve the envisaged goals, the trade-off can be reduced through systemically designed institutions that promote goal internalization and contain niche institutions

A university-based model for supporting computer science curriculum reform

Computer science curriculum reform in the United Kingdom has been subject to substantial scrutiny—as it has in many other countries around the world—with England introducing a radical new computing curriculum from September 2014. However, in Wales—a devolved nation within the UK—political, geographical and socio-cultural issues have to date hindered any substantive educational policy or curriculum reform for computer science. In this paper, we present the activities of Technocamps, a national university-based schools outreach programme founded in 2003, and consider its wider impact on computer science education, schools, pupils and teachers in Wales. In contrast to successful interventions elsewhere in the UK in building and sustaining communities of practice, certain political and cultural challenges in Wales have largely prevented these successful models from being adopted. Through the consideration of the national case study presented in this paper, we demonstrate the necessity of the nation-wide school- and student-focused Technocamps model in building resilient and scalable practitioner-led support networks. Furthermore, with emerging curriculum reform in Wales, we frame the wider opportunity for computer science education and sustainably embedding cross-curricular digital competencies—along with changing the wider public perception and perceived value of computer science as an academic discipline—as a prospective replicable case study of a national engagement model for nations with similar aspirations of developing digitally confident and capable citizens. To this end, we conclude by drawing out the important lessons learnt for consideration when embarking on a programme of national curriculum reform and associated professional development