Mechanisms of action of hESC-secreted proteins that enhance human and mouse myogenesis.

Adult stem cells grow poorly in vitro compared to embryonic stem cells, and in vivo stem cell maintenance and proliferation by tissue niches progressively deteriorates with age. We previously reported that factors produced by human embryonic stem cells (hESCs) support a robust regenerative capacity for adult and old mouse muscle stem/progenitor cells. Here we extend these findings to human muscle progenitors and investigate underlying molecular mechanisms. Our results demonstrate that hESC-conditioned medium enhanced the proliferation of mouse and human muscle progenitors. Furthermore, hESC-produced factors activated MAPK and Notch signaling in human myogenic progenitors, and Delta/Notch-1 activation was dependent on MAPK/pERK. The Wnt, TGF-β and BMP/pSmad1,5,8 pathways were unresponsive to hESC-produced factors, but BMP signaling was dependent on intact MAPK/pERK. c-Myc, p57, and p18 were key effectors of the enhanced myogenesis promoted by the hECS factors. To define some of the active ingredients of the hESC-secretome which may have therapeutic potential, a comparative proteomic antibody array analysis was performed and identified several putative proteins, including FGF2, 6 and 19 which as ligands for MAPK signaling, were investigated in more detail. These studies emphasize that a youthful signaling of multiple signaling pathways is responsible for the pro-regenerative activity of the hESC factors

hESC-secreted proteins can be enriched for multiple regenerative therapies by heparin-binding.

This work builds upon our findings that proteins secreted by hESCs exhibit pro-regenerative activity, and determines that hESC-conditioned medium robustly enhances the proliferation of both muscle and neural progenitor cells. Importantly, this work establishes that it is the proteins that bind heparin which are responsible for the pro-myogenic effects of hESC-conditioned medium, and indicates that this strategy is suitable for enriching the potentially therapeutic factors. Additionally, this work shows that hESC-secreted proteins act independently of the mitogen FGF-2, and suggests that FGF-2 is unlikely to be a pro-aging molecule in the physiological decline of old muscle repair. Moreover, hESC-secreted factors improve the viability of human cortical neurons in an Alzheimers disease (AD) model, suggesting that these factors can enhance the maintenance and regeneration of multiple tissues in the aging body

Urban greenspace for social integration: Which types of greenspace do new-Swedes prefer and why?

Urban greenspace (UGS) is a key public resource offering a broad range of nature -based solutions and is increasingly looked to as a potential arena to promote social integration in Europe 's increasingly multicultural urban and peri-urban areas. However, relatively little research has explored the preferences and perceptions of immigrants in relation to UGS, especially in European contexts. Without such knowledge, planners risk entrenching planning structures that inadvertently result in segregation and environmental injustice. Using survey and participatory mapping methods with 261 immigrants in eight sampled settlements across Sweden, this study explores which types of UGS foreign -born immigrants in Sweden (i.e., new -Swedes) prefer and why. We found that new -Swedes are frequent users of a wide spectrum of UGS types, with the most preferred types including forests, large parks and lakes. The majority of respondents were satisfied with the quality (73%), availability (68%) and accessibility (76%) of UGS in their hometowns. Our regression analysis identified 51 key factors that had a meaningful effect on preferences for different types of UGS. Key factors were distributed relatively evenly across blocks of predictor variables concerning characteristics of UGS, socio-demographic factors, activity preferences, and perceptions. Our results indicate that new -Swedes ' UGS preferences are broadly comparable with those of the general population in Sweden. We found little evidence to suggest that ethnocultural factors played a major role in the preferences of our respondents. Furthermore, our results suggest that nature -connectedness might be an important determinant of new -Swedes ' UGS preferences. Based on these findings, we highlight several opportunities to further develop UGS strategies to support different dimensions of social integration, e.g., using popular UGS as interactive spaces for cultural learning, as a platform for intercultural contacts and for maintaining cultural traditions, and to contribute towards a greater sense of social membership in their new country. A crucial implication of our study is that the use of UGS to support social integration may further contribute to the increasing complexity of the UGS planning and management challenge. This implies the need for a systems perspective in UGS research, policy -making, planning and management to consider UGS as part of an integrated urban social -ecological system and to coordinate measures across sectors

Salutogenic Affordances and Sustainability: Multiple Benefits With Edible Forest Gardens in Urban Green Spaces

With increased urbanization, ecological challenges such as climate change and loss of biodiversity, and stress-related disorders globally posing a major threat to public health and wellbeing, the development of efficient multiple-use strategies for urban green spaces and infrastructures is of great importance. In addition to benefits such as climate and water regulation, food production, and biodiversity conservation, green spaces and features have been associated with various health and wellbeing outcomes from a psychological perspective. Research suggests links between exposure to green environmental qualities and restoration from psycho-physiological stress and attention fatigue, promotion of physical activity, increased neighborhood satisfaction and even reduced mortality. Especially strong associations have been observed in urban and socio-economically challenged areas. Usually such salutogenic, i.e., health-promoting, effects are explained through theories related to the notion of biophilia, i.e., the idea that humans share innate tendencies to attend to natural environments and features that have been beneficial during evolution. This paper assumes an ecological approach to perception and behavior to be fruitful in order to analyze the salutogenic potential of environments such as urban green spaces and to step beyond the “green vs. gray” dichotomy that has been prevalent through much of the research on health-promoting environments. Through an analysis of environmental affordances for certain perceived qualities such an approach is explored through a proposed concept for urban green space use and management, the edible forest garden. Such gardens, based on agroecological principles, have emerged as one of the most promising models regarding ecologically sustainable food production. In addition to potential contributions of importance for urban sustainability and biodiversity, we argue that the inclusion of edible forest gardens in urban green spaces – today globally dominated by lawns – also potentially could reinforce several affordances of salutogenic importance, both in terms of, e.g., social cohesion but also in regard to restoration from psycho-physiological stress and attention fatigue. Increased opportunities for contact with nature and processes of food production may also reinforce pro-environmental behaviors in the population and thus also affect long-term sustainability

Cost effectiveness of school-located influenza vaccination programs for elementary and secondary school children.

BackgroundStudies have noted variations in the cost-effectiveness of school-located influenza vaccination (SLIV), but little is known about how SLIV's cost-effectiveness may vary by targeted age group (e.g., elementary or secondary school students), or vaccine consent process (paper-based or web-based). Further, SLIV's cost-effectiveness may be impacted by its spillover effect on practice-based vaccination; prior studies have not addressed this issue.MethodsWe performed a cost-effectiveness analysis on two SLIV programs in upstate New York in 2015-2016: (a) elementary school SLIV using a stepped wedge design with schools as clusters (24 suburban and 18 urban schools) and (b) secondary school SLIV using a cluster randomized trial (16 suburban and 4 urban schools). The cost-per-additionally-vaccinated child (i.e., incremental cost-effectiveness ratio (ICER)) was estimated by dividing the incremental SLIV intervention cost by the incremental effectiveness (i.e., the additional number of vaccinated students in intervention schools compared to control schools). We performed deterministic analyses, one-way sensitivity analyses, and probabilistic analyses.ResultsThe overall effectiveness measure (proportion of children vaccinated) was 5.7 and 5.5 percentage points higher, respectively, in intervention elementary (52.8%) and secondary schools (48.2%) than grade-matched control schools. SLIV programs vaccinated a small proportion of children in intervention elementary (5.2%) and secondary schools (2.5%). In elementary and secondary schools, the ICER excluding vaccine purchase was $85.71 and$86.51 per-additionally-vaccinated-child, respectively. When additionally accounting for observed spillover impact on practice-based vaccination, the ICER decreased to $80.53 in elementary schools -- decreasing substantially in secondary schools. (to$53.40). These estimates were higher than the published practice-based vaccination cost (median = $25.50, mean =$45.48). Also, these estimates were higher than our 2009-2011 urban SLIV program mean costs ($65) due to additional costs for use of a new web-based consent system ($12.97 per-additionally-vaccinated-child) and higher project coordination costs in 2015-2016. One-way sensitivity analyses showed that ICER estimates were most sensitive to the SLIV effectiveness.ConclusionsSLIV raises vaccination rates and may increase practice-based vaccination in primary care practices. While these SLIV programs are effective, to be as cost-effective as practice-based vaccination our SLIV programs would need to vaccinate more students and/or lower the costs for consent systems and project coordination.Trial registrationClinicalTrials.gov NCT02227186 (August 25, 2014), updated NCT03137667 (May 2, 2017)

Voluntary climate mitigation by individuals, firms, communities and cities

This poster integrates the results of four different modules of the ClimPol project (Climate Policy Making for Enhanced Technological and Institutional Innovations). These modules deal with climate change mitigation behavior of individuals (ClimPol module B1), firms (D2), small rural/peri-urban communities (B2), and cities and counties (A2). The common topic of voluntary action for climate change mitigation links these modules. We define voluntary action as the action, when an individual, a firm, a community or a city have a negative impact on the natural environment and reduce it without being legally obliged to do so (Thalmann and Baranzini, 2004). Some selected findings of the four modules are presented and integrated with respect to the two guiding questions: Why do individuals, firms, small communities and cities take voluntary action to mitigate climate change? What is the advice for efficient voluntary action

Multiple factors shape the interaction of people with urban greenspace: Sweden as a case study

This study identifies and analyses multiple factors that impact people's interactions with urban greenspace in Sweden. An unrestricted, self-selected online survey was used to collect the data. The survey questions were related to individual characteristics of respondents, including socio-demographic characteristics, self-reported nature connectedness, and self-reported constraints to greenspace usage; perceived characteristics of urban greenspace, including its availability, quality, and accessibility, and benefits and problems; and preferences of respondents regarding types of urban greenspace and activities. Additionally, several spatially explicit variables were included in the analysis. A total of 2806 respondents from 208 (of 290) municipalities completed the survey. Our findings indicate that greenspace users are highly heterogeneous and utilise diverse green spaces along the urban-peri-urban gradient for various benefits. The statistical analyses identified 61 explanatory variables that affect the frequency of interactions with urban greenspace. In addition, we identify key factors that shape critical differences between frequent and infrequent urban users, such as nature connectedness, perceptions of urban greenspace functions, and their perceived accessibility. Our results highlight the complex challenge facing urban planners and managers of green spaces, who have to consider and integrate a vast array of factors influencing the willingness of increasingly diverse urban populations to interact with greenspace

Multivalent glycoconjugates as anti-pathogenic agents

Multivalency plays a major role in biological processes and particularly in the relationship between pathogenic microorganisms and their host that involves protein–glycan recognition. These interactions occur during the first steps of infection, for specific recognition between host and bacteria, but also at different stages of the immune response. The search for high-affinity ligands for studying such interactions involves the combination of carbohydrate head groups with different scaffolds and linkers generating multivalent glycocompounds with controlled spatial and topology parameters. By interfering with pathogen adhesion, such glycocompounds including glycopolymers, glycoclusters, glycodendrimers and glyconanoparticles have the potential to improve or replace antibiotic treatments that are now subverted by resistance. Multivalent glycoconjugates have also been used for stimulating the innate and adaptive immune systems, for example with carbohydrate-based vaccines. Bacteria present on their surfaces natural multivalent glycoconjugates such as lipopolysaccharides and S-layers that can also be exploited or targeted in anti-infectious strategie