The Role of TGFβ1 and EP Receptors in the Differentiation of Normal and Diseased Lung Fibroblasts

Fibroblasts, and their differentiation into myofibroblasts, are important in the pathology of several lung diseases including asthma and idiopathic pulmonary fibrosis (IPF). The differentiation process is dependent on several factors, such as soluble factors like transforming growth factor beta 1 (TGFβ1) and mechanical signals such as matrix stiffness. Additionally, the soluble arachidonic acid metabolite Prostaglandin E2 (PGE2) prevents TGFβ1 induced differentiation of fibroblasts to myofibroblasts, but the molecular mechanism is not completely understood15. Transient Receptor Potential Vanilloid 4 (TRPV4), a mechanosensitive ion channel, has previously been implicated in the differentiation of cardiac fibroblasts12,13. However, the role of TRPV4 in the differentiation of lung fibroblasts and its contribution to lung diseases such asthma has not been explored. Myofibroblasts express the contractile protein alpha smooth muscle actin (α-SMA) and are also distinguished by their excessive production of extracellular matrix (ECM) proteins such as fibronectin. The expression of α-SMA and ECM proteins has been shown to be mediated by serum response factor (SRF) and its co-activator myocardin related transcription factor (MRTF-A)5,6. Therefore, in the current project, we investigate differences in differentiation state between normal human lung fibroblasts (NHLF) and diseased human lung fibroblasts (DHLF). We show that DHLF have higher basal and increased α-SMA and fibronectin expression than NHLF, indicative of enhanced differentiation potential in DHLF. Additionally, we showed that lung fibroblast differentiation is regulated by TRPV4. Furthermore, we found that PGE2 inhibited TGFβ1-induced differentiation

The Economic Value of Tree Preservation in a Weak Land Development Market Region

New residential development is most often a death sentence for the trees that stand in its way. This behavior might be altered if developers thought there was an economic value to being more selective. Unfortunately, the relationship between tree preservation and new development is not well studied. The purpose of this study was to characterize the economic value gained from the preservation of mature trees during the land development process. The study focused on six counties constituting the greater Cleveland, Ohio, U.S., real estate and land development market. A mixed quantitative and qualitative approach was used. GIS-based data and a series of hedonic models determined the value of tree canopy associated with new home sale prices from 2009 to 2011. Qualitative interviews of development and real estate professionals revealed a nuanced association of value and challenges to tree preservation during the residential land development process. Previous methods for estimating the economic value of trees were moved forward through aerial location of trees on parcels using Google Earth™ and the National Agricultural Imagery Program (NAIP) data and through the mixed-method approach. The study provided information to a state-level agency managing the state’s incentive-based smart growth program

The Economic Value of Tree Preservation in a Weak Land Development Market Region

New residential development is most often a death sentence for the trees that stand in its way. This behavior might be altered if developers thought there was an economic value to being more selective. Unfortunately, the relationship between tree preservation and new development is not well studied. The purpose of this study was to characterize the economic value gained from the preservation of mature trees during the land development process. The study focused on six counties constituting the greater Cleveland, Ohio, U.S., real estate and land development market. A mixed quantitative and qualitative approach was used. GIS-based data and a series of hedonic models determined the value of tree canopy associated with new home sale prices from 2009 to 2011. Qualitative interviews of development and real estate professionals revealed a nuanced association of value and challenges to tree preservation during the residential land development process. Previous methods for estimating the economic value of trees were moved forward through aerial location of trees on parcels using Google Earth™ and the National Agricultural Imagery Program (NAIP) data and through the mixed-method approach. The study provided information to a state-level agency managing the state’s incentive-based smart growth program

Using Typologies to Frame Poverty and Service Delivery in Suburban America

Poverty in the suburbs is growing, but there is great diversity in the rates of growth of poverty as well as causes and consequences of the growth across different kinds of suburbs. Suburban typologies, systems to group different types of suburbs, are a useful tool for understanding the variation among suburbs and highlighting potential strategies for addressing poverty. This paper discusses why typologies of suburban communities are important, what factors have been considered in the development and use of typologies, what typologies have been developed to date, and lastly, how typologies can be used to inform strategies for addressing suburban poverty. Suburban typologies can assist in understanding the variation between suburbs in the overall level, duration, and causes of poverty as well as variation in resources, services, and opportunities available for addressing it (Allard & Roth, 2010; Kneebone & Berube, 2013). For example, suburbs experiencing a sharp increase in poverty coupled with large increases in population may have different social service needs than suburbs with sharp poverty increases and little or no growth in population. The typology research sheds light on those suburbs that are experiencing the most significant impacts from increases in poverty and can identify appropriate policy tools and strategies to help communities cope with poverty. Yet, typologies vary with respect to how suburbs are defined, which suburbs are included, and what factors are considered in their development. Not one consistent definition of suburb is used across the typologies that have been developed. Instead, different researchers classify different geographic areas as suburbs, in part, based on the availability of data. Typologies also differ in the sample of suburbs that are being classified. Some researchers focus on all suburban areas, whereas others focus more narrowly on subsets of suburbs, such as inner-ring suburbs or economically distressed suburbs. Finally, researchers use a range of factors and methodologies to develop these typologies including a number of different economic, demographic, and historical factors (Hanlon, 2010; Hanlon, Vicino, & Short, 2006; Mikelbank, 2004; Orfield & Luce, 2012). Their differences not withstanding, taken together, the suburban typologies that have been developed reveal a number of common findings related to the economic vitality and vulnerability of suburbs. Increasingly larger populations of suburban residents live in communities that do not resemble traditional perceptions of prosperous suburbs. Instead, they live in a diverse set of communities including those characterized by poor economic health with low average income and home values, less housing stability, large populations, diverse family structures and racial composition, and varying levels and composition of employment). Although poverty is increasing in suburbs throughout the country, it is growing fastest in distressed suburbs, which tend to be highly racially segregated and fiscally constrained. Moreover, suburbs closest to central cities are increasingly poor and increasingly non-white. The combination of population growth and economic decline in these communities serve as barriers for addressing the increase in poverty

The Value of Balanced Growth for Transportation

The Ohio Balanced Growth Program is a voluntary, locally-driven, incentive-driven program which aims to encourage compact, nodal development patterns. The Ohio Department of Transportation provided support for this research to evaluate potential links between Balanced Growth-type policy, land use and development patterns, and transportation benefits. A literature review was completed to understand the existing body of knowledge regarding the connection between policy, land use, and transportation. This included a scan of Balanced Growth-type programs across the US. Twenty-six US Metropolitan Statistical Areas (MSAs) were selected and reviewed for general geographic and policy characteristics. Land use and transportation outcome data were examined via scatterplot and linear regression across all of the MSAs. The results were evaluated broadly in light of policy frameworks in effect in each MSA, by categorizing land use policy into “tiers” based on voluntary vs. mandatory provisions, and applicability to private and public investment. Finally, a policy review was completed to understand the potential benefits of policy change at the state, regional, and local agency levels. Significant relationships were found between land use patterns, measured in terms of a sprawl composite index, and transportation outcomes for freeway lane miles, hours of delay, vehicle miles traveled, emissions, and safety. MSAs with “Tier 3” policies (mandatory, rigorous policy affecting both public and private investment) clustered together on both axes (transportation outcomes and sprawl); and MSAs within states clustered together along the sprawl score axis. Otherwise, there was no apparent pattern in the location of policy tiers along either the transportation or land use axes. Possible alternative explanations that could be evaluated in the future include overall transportation investment levels; inter-state and inter-regional travel demand; size and shape of the MSA; and market, economic and social factors. Conclusions included policy recommendations for ODOT in supporting compact, nodal development at the local, regional and state levels. Future study recommendations include pursuing future data collection, monitoring and evaluation over time

The Value of Balanced Growth for Transportation

The Ohio Balanced Growth Program is a voluntary, locally-driven, incentive-driven program which aims to encourage compact, nodal development patterns. The Ohio Department of Transportation provided support for this research to evaluate potential links between Balanced Growth-type policy, land use and development patterns, and transportation benefits. A literature review was completed to understand the existing body of knowledge regarding the connection between policy, land use, and transportation. This included a scan of Balanced Growth-type programs across the US. Twenty-six US Metropolitan Statistical Areas (MSAs) were selected and reviewed for general geographic and policy characteristics. Land use and transportation outcome data were examined via scatterplot and linear regression across all of the MSAs. The results were evaluated broadly in light of policy frameworks in effect in each MSA, by categorizing land use policy into “tiers” based on voluntary vs. mandatory provisions, and applicability to private and public investment. Finally, a policy review was completed to understand the potential benefits of policy change at the state, regional, and local agency levels. Significant relationships were found between land use patterns, measured in terms of a sprawl composite index, and transportation outcomes for freeway lane miles, hours of delay, vehicle miles traveled, emissions, and safety. MSAs with “Tier 3” policies (mandatory, rigorous policy affecting both public and private investment) clustered together on both axes (transportation outcomes and sprawl); and MSAs within states clustered together along the sprawl score axis. Otherwise, there was no apparent pattern in the location of policy tiers along either the transportation or land use axes. Possible alternative explanations that could be evaluated in the future include overall transportation investment levels; inter-state and inter-regional travel demand; size and shape of the MSA; and market, economic and social factors. Conclusions included policy recommendations for ODOT in supporting compact, nodal development at the local, regional and state levels. Future study recommendations include pursuing future data collection, monitoring and evaluation over time

The Value of Balanced Growth for Transportation: Executive Summary

This project evaluates the benefit that programs like the Ohio Balanced Growth Program could bring to transportation agencies in Ohio

Revitalizing Distressed Older Suburbs

Reviews literature on strategies for revitalizing distressed older suburbs. Based on case studies of the most distressed minority suburbs, examines the effectiveness of and best practices for revitalization programs and investments. Makes recommendations

Mesenchymal Stromal Cells and Platelet-Rich Plasma Promote Tendon Allograft Healing in Ovine Anterior Cruciate Ligament Reconstruction

Purpose The effect of bone marrow mesenchymal stromal cells (BMSCs) and platelet-rich plasma (PRP) on tendon allograft maturation in a large animal anterior cruciate ligament (ACL) reconstruction model was reported for the first time. It was hypothesised that compared with non-augmented ACL reconstruction, BMSCs and PRP would enhance graft maturation after 12 weeks and this would be detected using magnetic resonance imaging (MRI). Methods Fifteen sheep underwent unilateral tendon allograft ACL reconstruction using aperture fixation and were randomised into three groups (n = 5). Group 1 received 10 million allogeneic BMSCs in 2 ml fibrin sealant; Group 2 received 12 ml PRP in a plasma clot injected into the graft and bone tunnels; and Group 3 (control) received no adjunctive treatment. At autopsy at 12 weeks, a graft maturation score was determined by the sum for graft integrity, synovial coverage and vascularisation, graft thickness and apparent tension, and synovial sealing at tunnel apertures. MRI analysis (n = 2 animals per group) of the signal–noise quotient (SNQ) and fibrous interzone (FIZ) was used to evaluate intra-articular graft maturation and tendon–bone healing, respectively. Spearman’s rank correlation coefficient (r) of SNQ, autopsy graft maturation score and bone tunnel diameter were analysed. Results The BMSC group (p = 0.01) and PRP group (p = 0.03) had a significantly higher graft maturation score compared with the control group. The BMSC group scored significantly higher for synovial sealing at tunnel apertures (p = 0.03) compared with the control group. The graft maturation score at autopsy significantly correlated with the SNQ (r = − 0.83, p < 0.01). The tunnel diameter of the femoral tunnel at the aperture (r = 0.883, p = 0.03) and mid-portion (r = 0.941, p = 0.02) positively correlated with the SNQ. Conclusions BMSCs and PRP significantly enhanced graft maturation, which indicates that orthobiologics can accelerate the biologic events in tendon allograft incorporation. Femoral tunnel expansion significantly correlated with inferior maturation of the intra-articular graft. The clinical relevance of this study is that BMSCs and PRP enhance allograft healing in a translational model, and biological modulation of graft healing can be evaluated non-invasively using MRI