Gilliom, R.; Hogue, T. S.; McCray, J. E.
There is a need for improved parameterization of stormwater best management practices (BMP) performance estimates to improve modeling of urban hydrology, planning and design of green infrastructure projects, and water quality crediting for stormwater management. Percent removal is commonly used to estimate BMP pollutant removal efficiency, but there is general agreement that this approach has significant uncertainties and is easily affected by site-specific factors. Additionally, some fraction of monitored BMPs have negative percent removal, so it is important to understand the probability that a BMP will provide the desired water quality function versus exacerbating water quality problems. The widely used k-C* equation has shown to provide a more adaptable and accurate method to model BMP contaminant attenuation, and previous work has begun to evaluate the strengths and weaknesses of the k-C* method. However, no systematic method exists for obtaining first-order removal rate constants needed to use the k-C* equation for stormwater BMPs; thus there is minimal application of the method. The current research analyzes existing water quality data in the International Stormwater BMP Database to provide screening-level parameterization of the k-C* equation for selected BMP types and analysis of factors that skew the distribution of efficiency estimates from the database. Results illustrate that while certain BMPs are more likely to provide desired contaminant removal than others, site- and design-specific factors strongly influence performance. For example, bioretention systems show both the highest and lowest removal rates of dissolved copper, total phosphorous, and total nitrogen. Exploration and discussion of this and other findings will inform the application of the probabilistic pollutant removal rate constants. Though data limitations exist, this research will facilitate improved accuracy of BMP modeling and ultimately aid decision-making for stormwater quality
Van Wyk, Llewellyn V
Full Text Available the generation of electricity from renewable sources such as wind, water and solar. Grey infrastructure – In the context of storm water management, grey infrastructure can be thought of as the hard, engineered systems to capture and convey runoff..., pumps, and treatment plants. Green infrastructure reduces energy demand by reducing the need to collect and transport storm water to a suitable discharge location. In addition, green infrastructure such as green roofs, street trees and increased...
Minnesota Department of Natural Resources — This Green Infrastructure data is comprised of 3 similar ecological corridor data layers ? Metro Conservation Corridors, green infrastructure analysis in counties...
Christopher M. Chini
Full Text Available Green infrastructure is a unique combination of economic, social, and environmental goals and benefits that requires an adaptable framework for planning, implementing, and evaluating. In this study, we propose an experimental framework for policy, implementation, and subsequent evaluation of green stormwater infrastructure within the context of sociotechnical systems and urban experimentation. Sociotechnical systems describe the interaction of complex systems with quantitative and qualitative impacts. Urban experimentation—traditionally referencing climate change programs and their impacts—is a process of evaluating city programs as if in a laboratory setting with hypotheses and evaluated results. We combine these two concepts into a singular framework creating a policy feedback cycle (PFC for green infrastructure to evaluate municipal green infrastructure plans as an experimental process within the context of a sociotechnical system. After proposing and discussing the PFC, we utilize the tool to research and evaluate the green infrastructure programs of 27 municipalities across the United States. Results indicate that green infrastructure plans should incorporate community involvement and communication, evaluation based on project motivation, and an iterative process for knowledge production. We suggest knowledge brokers as a key resource in connecting the evaluation stage of the feedback cycle to the policy phase. We identify three important needs for green infrastructure experimentation: (i a fluid definition of green infrastructure in policy; (ii maintenance and evaluation components of a green infrastructure plan; and (iii communication of the plan to the community.
Lõhmus, Mare; Balbus, John
Increasing urban green and blue structure is often pointed out to be critical for sustainable development and climate change adaptation, which has led to the rapid expansion of greening activities in cities throughout the world. This process is likely to have a direct impact on the citizens' quality of life and public health. However, alongside numerous benefits, green and blue infrastructure also has the potential to create unexpected, undesirable, side-effects for health. This paper considers several potential harmful public health effects that might result from increased urban biodiversity, urban bodies of water, and urban tree cover projects. It does so with the intent of improving awareness and motivating preventive measures when designing and initiating such projects. Although biodiversity has been found to be associated with physiological benefits for humans in several studies, efforts to increase the biodiversity of urban environments may also promote the introduction and survival of vector or host organisms for infectious pathogens with resulting spread of a variety of diseases. In addition, more green connectivity in urban areas may potentiate the role of rats and ticks in the spread of infectious diseases. Bodies of water and wetlands play a crucial role in the urban climate adaptation and mitigation process. However, they also provide habitats for mosquitoes and toxic algal blooms. Finally, increasing urban green space may also adversely affect citizens allergic to pollen. Increased awareness of the potential hazards of urban green and blue infrastructure should not be a reason to stop or scale back projects. Instead, incorporating public health awareness and interventions into urban planning at the earliest stages can help insure that green and blue infrastructure achieves full potential for health promotion.
Full Text Available Increasing urban green and blue structure is often pointed out to be critical for sustainable development and climate change adaptation, which has led to the rapid expansion of greening activities in cities throughout the world. This process is likely to have a direct impact on the citizens’ quality of life and public health. However, alongside numerous benefits, green and blue infrastructure also has the potential to create unexpected, undesirable, side-effects for health. This paper considers several potential harmful public health effects that might result from increased urban biodiversity, urban bodies of water, and urban tree cover projects. It does so with the intent of improving awareness and motivating preventive measures when designing and initiating such projects. Although biodiversity has been found to be associated with physiological benefits for humans in several studies, efforts to increase the biodiversity of urban environments may also promote the introduction and survival of vector or host organisms for infectious pathogens with resulting spread of a variety of diseases. In addition, more green connectivity in urban areas may potentiate the role of rats and ticks in the spread of infectious diseases. Bodies of water and wetlands play a crucial role in the urban climate adaptation and mitigation process. However, they also provide habitats for mosquitoes and toxic algal blooms. Finally, increasing urban green space may also adversely affect citizens allergic to pollen. Increased awareness of the potential hazards of urban green and blue infrastructure should not be a reason to stop or scale back projects. Instead, incorporating public health awareness and interventions into urban planning at the earliest stages can help insure that green and blue infrastructure achieves full potential for health promotion.
Diana Olegovna Dushkova
Full Text Available The paper presents a concept of urban green infrastructure and analyzes the features of its implementation in the urban development programmes of German cities. We analyzed the most shared articles devoted to the urban green infrastructure to see different approaches to definition of this term. It is based on materials of field research in the cities of Berlin and Leipzig in 2014-2015, international and national scientific publications. During the process of preparing the paper, consultations have been held with experts from scientific institutions and Administrations of Berlin and Leipzig as well as local experts from environmental organizations of both cities. Using the German cities of Berlin and Leipzig as examples, this paper identifies how the concept can be implemented in the program of urban development. It presents the main elements of green city model, which include mitigation of negative anthropogenic impact on the environment under the framework of urban sustainable development. Essential part of it is a complex ecological policy as a major necessary tool for the implementation of the green urban infrastructure concept. This ecological policy should embody not only some ecological measurements, but also a greening of all urban infrastructure elements as well as implementation of sustainable living with a greater awareness of the resources, which are used in everyday life, and development of environmental thinking among urban citizens. Urban green infrastructure is a unity of four main components: green building, green transportation, eco-friendly waste management, green transport routes and ecological corridors. Experience in the development of urban green infrastructure in Germany can be useful to improve the environmental situation in Russian cities.
The report outlines the 2012 technical assistance for Clarkesville, GA to develop a Green Infrastructure Implementation Strategy, which provides the basic building blocks for a green infrastructure plan:
Green infrastructure, such as rain gardens, green roofs, porous pavement, cisterns, and constructed wetlands, is becoming an increasingly attractive way to recharge aquifers and reduce the amount of stormwater runoff that flows into wastewater treatment plants or into waterbodies...
Hansen, Rieke; Olafsson, Anton Stahl; van der Jagt, Alexander P.N.
green space functions or the purposive design and management of multifunctional parks. Based on the findings, we arrive at five recommendations for promoting multifunctional urban green infrastructure in densifying urban areas: 1) undertake systematic spatial assessments of all urban green (and blue....... Further, spatial assessment, strategic planning and site design need to 4) consider synergies, trade-offs and the capacity of urban green spaces to provide functions as part of the wider green infrastructure network; and 5) largely benefit from cooperation between different sectors and public departments......Urban green infrastructure planning aims to develop green space networks on limited space in compact cities. Multifunctionality is considered key to achieving this goal as it supports planning practice that considers the ability of green spaces to provide multiple benefits concurrently. However...
Green infrastructure is an approach to managing wet weather flows using systems and practices that mimic natural processes. It is designed to manage stormwater as close to its source as possible and protect the quality of receiving waters. Although most green infrastructure practices were first developed in temperate climates, green infrastructure also can be a cost-effective approach to stormwater management and water conservation in arid and semi-arid regions, such as those found in the western and southwestern United States. Green infrastructure practices can be applied at the site, neighborhood and watershed scales. In addition to water management and conservation, implementing green infrastructure confers many social and economic benefits and can address issues of environmental justice. The U.S. Environmental Protection Agency (EPA) commissioned a literature review to identify the state-of-the science practices dealing with water control and conservation in arid and semi-arid regions, with emphasis on these regions in the United States. The search focused on stormwater control measures or practices that slow, capture, treat, infiltrate and/or store runoff at its source (i.e., green infrastructure). The material in Chapters 1 through 3 provides background to EPA’s current activities related to the application of green infrastructure practices in arid and semi-arid regions. An introduction to the topic of green infrastructure in arid and semi-arid regions i
Christopher M. Chini; James F. Canning; Kelsey L. Schreiber; Joshua M. Peschel; Ashlynn S. Stillwell
Green infrastructure is a unique combination of economic, social, and environmental goals and benefits that requires an adaptable framework for planning, implementing, and evaluating. In this study, we propose an experimental framework for policy, implementation, and subsequent evaluation of green stormwater infrastructure within the context of sociotechnical systems and urban experimentation. Sociotechnical systems describe the interaction of complex systems with quantitative and qualitative...
Diana Olegovna Dushkova; Sergey Nikolaevich Kirillov
The paper presents a concept of urban green infrastructure and analyzes the features of its implementation in the urban development programmes of German cities. We analyzed the most shared articles devoted to the urban green infrastructure to see different approaches to definition of this term. It is based on materials of field research in the cities of Berlin and Leipzig in 2014-2015, international and national scientific publications. During the process of preparing the paper, consultations...
Hopkins, Kristina G.; Grimm, Nancy B.; York, Abigail M.
Communities are faced with the challenge of meeting regulatory requirements mandating reductions in water pollution from stormwater and combined sewer overflows (CSO). Green stormwater infrastructure and gray stormwater infrastructure are two types of water management strategies communities can use to address water pollution. In this study, we used long-term control plans from 25 U.S. cities to synthesize: the types of gray and green infrastructure being used by communities to address combined sewer overflows; the types of goals set; biophysical characteristics of each city; and factors associated with the governance of stormwater management. These city characteristics were then used to identify common characteristics of “green leader” cities—those that dedicated >20% of the control plan budget in green infrastructure. Five “green leader” cities were identified: Milwaukee, WI, Philadelphia, PA, Syracuse, NY, New York City, NY, and Buffalo, NY. These five cities had explicit green infrastructure goals targeting the volume of stormwater or percentage of impervious cover managed by green infrastructure. Results suggested that the management scale and complexity of the management system are less important factors than the ability to harness a “policy window” to integrate green infrastructure into control plans. Two case studies—Philadelphia, PA, and Milwaukee, WI—indicated that green leader cities have a long history of building momentum for green infrastructure through a series of phases from experimentation, demonstration, and finally—in the case of Philadelphia—a full transition in the approach used to manage CSOs.
Van der Velde, J.R.T.; De Wit, S.I.
The appreciation of green infrastructures as ‘nature’ by urban communities presents a critical challenge for the green infrastructure concept. While many green infrastructures focus on functional considerations, their refinement as places where concepts of nature are represented and where nature can
Ballestero, T. P.; Watts, A. W.; Houle, J. J.; Puls, T. A.
Urbanization radically alters hydrology, with impacts from very local to regional scales. Green Infrastructure techniques use natural processes to restore hydrologic function, and provide multiple companion benefits such as energy savings, increased green space, improved ecosystems, etc. Although science can clearly demonstrate the benefits and cost saving associated with Green Infrastructure (see for example Forging The Link http://www.unh.edu/unhsc/forgingthelink ), many community decision makers continue to be reluctant to incorporate these more effective methods into standard planning practices. In spite of the wealth of evidence, communities are very slow to codify and adopt the practices, commonly waiting for regulatory or legal directives to force them down the path. Barriers to implementation include misconceptions of performance, reliability and cost, often fed by a local ';expert' who is trusted member of the community. For Green Infrastructure to be effective, implementation must become a standard practice, rather than an innovation; the methods and concepts must be integrated into planning DNA. Fundamentally, successful green infrastructure implementation comes down to changing behavior, perceptions, and priorities, and fostering trust in the science. We will present: data on the cost and effectiveness of using Green Infrastructure to restore damaged urban hydrology, incorporating methods into urban planning tools, and an ongoing science collaborative project engaging stakeholders directly in the development and optimization of Green Infrastructure tools.
Maryati, Sri; Humaira, An Nisaa'Siti
Green infrastructure has several benefits compared to grey infrastructure in term of environmental services and sustainability, such as reducing energy consumption, improving air quality, providing carbon sequestration, and increasing property values. Nevertheless in practice, the implementation of the concept in Indonesia is still limited. Implementation of the certain concept has to be guided in planning document. In this paper, green infrastructure concept in the current spatial plan and other planning documents is assessed. The purpose of this research is to figure out how far the green infrastructure concept is integrated into planning system, based on the analysis of planning documents in Citarum Watershed and expert interviews with local stakeholders. Content analysis method is used to analyze the documents and result of interview. The result shows that green infrastructure concept has not been accommodated in spatial plan or other planning documents widely. There are some challenges in implementing the concept including reward and punishment system (incentive and disincentive), coordination, and lack of human resources.
The transversal and interdisciplinary quality of landscape makes it an essential and useful element in regional and local planning. On the other hand, Green Infrastructures provide an exceptional tool to put in relation different planning scales and offer new possibilities and functions for the design and management of open spaces. The Strategic Plan for the Calderona Mountain Range (Valencia province, Spain) shows how these two concepts: Landscape and Green Infrastructure can work hand in...
Coutts, Christopher; Hahn, Micah
Contemporary ecological models of health prominently feature the natural environment as fundamental to the ecosystem services that support human life, health, and well-being. The natural environment encompasses and permeates all other spheres of influence on health. Reviews of the natural environment and health literature have tended, at times intentionally, to focus on a limited subset of ecosystem services as well as health benefits stemming from the presence, and access and exposure to, green infrastructure. The sweeping influence of green infrastructure on the myriad ecosystem services essential to health has therefore often been underrepresented. This survey of the literature aims to provide a more comprehensive picture-in the form of a primer-of the many simultaneously acting health co-benefits of green infrastructure. It is hoped that a more accurately exhaustive list of benefits will not only instigate further research into the health co-benefits of green infrastructure but also promote consilience in the many fields, including public health, that must be involved in the landscape conservation necessary to protect and improve health and well-being.
Coutts, Christopher; Hahn, Micah
Contemporary ecological models of health prominently feature the natural environment as fundamental to the ecosystem services that support human life, health, and well-being. The natural environment encompasses and permeates all other spheres of influence on health. Reviews of the natural environment and health literature have tended, at times intentionally, to focus on a limited subset of ecosystem services as well as health benefits stemming from the presence, and access and exposure to, green infrastructure. The sweeping influence of green infrastructure on the myriad ecosystem services essential to health has therefore often been underrepresented. This survey of the literature aims to provide a more comprehensive picture—in the form of a primer—of the many simultaneously acting health co-benefits of green infrastructure. It is hoped that a more accurately exhaustive list of benefits will not only instigate further research into the health co-benefits of green infrastructure but also promote consilience in the many fields, including public health, that must be involved in the landscape conservation necessary to protect and improve health and well-being. PMID:26295249
By capturing and redistributing rain water or runoff in plant-soil systems such as green roofs, rain gardens or swales, green infrastructure restores natural hydrologic cycles and reduces runoff from overburdened gray infrastructure. Targeted ecosystem restoration, contaminant fi...
Soz, Salman Anees; Kryspin-Watson, Jolanta; Stanton-Geddes, Zuzana
This Knowledge Note explores the role of green infrastructure solutions in urban flood risk management. Green infrastructure solutions represent an approach that focuses on using natural processes for managing wet weather impacts while delivering environmental, social, and economic benefits. Green infrastructure solutions, such as wetlands, bioshields, buffer zones, green roofing, street s...
Beery, Thomas H; Raymond, Christopher M; Kyttä, Marketta; Olafsson, Anton Stahl; Plieninger, Tobias; Sandberg, Mattias; Stenseke, Marie; Tengö, Maria; Jönsson, K Ingemar
Concern for a diminished human experience of nature and subsequent decreased human well-being is addressed via a consideration of green infrastructure's potential to facilitate unplanned or incidental nature experience. Incidental nature experience is conceptualized and illustrated in order to consider this seldom addressed aspect of human interaction with nature in green infrastructure planning. Special attention has been paid to the ability of incidental nature experience to redirect attention from a primary activity toward an unplanned focus (in this case, nature phenomena). The value of such experience for human well-being is considered. The role of green infrastructure to provide the opportunity for incidental nature experience may serve as a nudge or guide toward meaningful interaction. These ideas are explored using examples of green infrastructure design in two Nordic municipalities: Kristianstad, Sweden, and Copenhagen, Denmark. The outcome of the case study analysis coupled with the review of literature is a set of sample recommendations for how green infrastructure can be designed to support a range of incidental nature experiences with the potential to support human well-being.
Catalina VIEIRA MEJÍA
Full Text Available A variety of similarities between green infrastructure and the German landscape planning can be found in comparing the approaches of the two planning instruments. Principles of green infrastructure such as multifunctionality, the multi-scale approach and connectivity show correspondences with landscape planning elements. However, some differences are apparent. The objective of this paper is to determine whether the main aims of these two frameworks overlap. It also seeks to deduce what benefits from ecosystem services could be provided by integrating the green infrastructure approach into the German landscape planning system. The results show that the green infrastructure concept is not well-known in German planning practice, although its principles are generally implemented through traditional landscape planning. Nevertheless, green infrastructure could act as a supplementary approach to current landscape planning practices by improving public acceptance and strengthening the social focus of the current landscape planning system.
Beery, Thomas H; Raymond, Christopher M; Kyttä, Marketta
of such experience for human well-being is considered. The role of green infrastructure to provide the opportunity for incidental nature experience may serve as a nudge or guide toward meaningful interaction. These ideas are explored using examples of green infrastructure design in two Nordic municipalities...... to consider this seldom addressed aspect of human interaction with nature in green infrastructure planning. Special attention has been paid to the ability of incidental nature experience to redirect attention from a primary activity toward an unplanned focus (in this case, nature phenomena). The value...
Sercaianu, Mihai; Petrescu, Florian; Aldea, Mihaela; Oana, Luca; Rotaru, George
In the last decade, reducing urban pollution and improving quality of public spaces became a more and more important issue for public administration authorities in Romania. The paper describes the development of a web-GIS solution dedicated to monitoring of the green infrastructure in Bucharest, Romania. Thus, the system allows the urban residents (citizens) to collect themselves and directly report relevant information regarding the current status of the green infrastructure of the city. Consequently, the citizens become an active component of the decision-support process within the public administration. Besides the usual technical characteristics of such geo-information processing systems, due to the complex legal and organizational problems that arise in collecting information directly from the citizens, additional analysis was required concerning, for example, local government involvement, environmental protection agencies regulations or public entities requirements. Designing and implementing the whole information exchange process, based on the active interaction between the citizens and public administration bodies, required the use of the "citizen-sensor" concept deployed with GIS tools. The information collected and reported from the field is related to a lot of factors, which are not always limited to the city level, providing the possibility to consider the green infrastructure as a whole. The "citizen-request" web-GIS for green infrastructure monitoring solution is characterized by a very diverse urban information, due to the fact that the green infrastructure itself is conditioned by a lot of urban elements, such as urban infrastructures, urban infrastructure works and construction density.
Thewodros K. Geberemariam
Full Text Available Drainage system infrastructures in most urbanized cities have reached or exceeded their design life cycle and are characterized by running with inadequate capacity. These highly degraded infrastructures are already overwhelmed and continued to impose a significant challenge to the quality of water and ecological systems. With predicted urban growth and climate change the situation is only going to get worse. As a result, municipalities are increasingly considering the concept of retrofitting existing stormwater drainage systems with green infrastructure practices as the first and an important step to reduce stormwater runoff volume and pollutant load inputs into combined sewer systems (CSO and wastewater facilities. Green infrastructure practices include an open green space that can absorb stormwater runoff, ranging from small-scale naturally existing pocket of lands, right-of-way bioswales, and trees planted along the sidewalk as well as large-scale public parks. Despite the growing municipalities’ interest to retrofit existing stormwater drainage systems with green infrastructure, few studies and relevant information are available on their performance and cost-effectiveness. Therefore, this paper aims to help professionals learn about and become familiar with green infrastructure, decrease implementation barriers, and provide guidance for monitoring green infrastructure using the combination of survey questionnaires, meta-narrative and systematic literature review techniques.
Sarah J. Tayouga
Full Text Available Green infrastructure is defined as any type of infrastructure that has the purpose of lessening the burden of development on the environment and/or has the aim of providing ecosystem services, such as runoff management, air temperature reduction, carbon sequestration, and habitat provisioning. Despite these potential benefits and a recent increase in popularity, the widespread use of green infrastructure has been limited. To ascertain why this may be the case, we asked: What are the socio-ecological factors that influence the adoption of green infrastructure? To answer this question, we carried out a review of the literature. We found 32 papers addressing our research topic, three quarters of which were published since 2009. Based on the results and conclusions of the articles we reviewed, we identify six factors that influence the adoption of green infrastructure: Education, the Provision of Ecosystem Services, Financial Incentives, Coordination Among Actors, Laws and Policies, and Planning Recommendations. We present a model of the direct and indirect effects of each factor on the adoption of green infrastructure and investigate the geographic variability of factors. Our results indicate that Education, the Provision of Ecosystem Services, and Financial Incentives are the most influential factors affecting the adoption of green infrastructure because they are supported by the greatest number of articles regardless of location of study and have the greatest number of linkages with other factors and adoption in our model. We conclude with evidence-based strategies to promote the use of green infrastructure in order to create more sustainable environments.
Evaluates Omaha’s current process for assessing green infrastructure projects and recommends improvements for comparing green and gray infrastructure. Compares Omaha’s design criteria to other cities. Reviews other US programs with rights-of-way criteria.
The objective of this project is to modify and refine existing models and develop new tools to support decision making for the complete green infrastructure (GI) project lifecycle, including the planning and implementation of stormwater control in urban and agricultural settings,...
This publication aims to help local governments, water utilities, nonprofit organizations, neighborhood groups, and other stakeholders integrate green infrastructure strategies into plans that can transform their communities.
Gehrels, H.; Meulen, van der Suzanne; Schasfoort, F.; Bosch, Peter; Brolsma, R.; Dinther, van D.; Geerling, G.J.; Goossens, M.; Jacobs, C.M.J.; jong, de Merijn; Kok, Sien; Massop, H.T.L.
This report focuses on developing concepts and design principles for blue and green infrastructure that not only support climate resilience but also contribute to a healthy and liveable urban environment. We will first assess the effectiveness of blue and green infrastructure on the basis of
Dec 20, 2017 ... utilisation of urban green infrastructure was influenced by different ... one the main a visiting site for watching football and conducting physical exercises ..... Green Spaces and Emergency Shelters-Thinking after. Wenchuan ...
Full Text Available Green Infrastructure is ‘an interconnected network of green space that conserves natural ecosystem values and functions and provides associated benefits to human populations’ [1, p. 12]. It contributes to long term strategic development goals for data and information management. The research paper was introduced with the aim to protect green areas in urban environment by improving biodiversity, leisure and recreation, tidal and fluvial flood risk management, grey water treatment and quality of life. Planning and design of green system should provide appropriate responses to the distinctive local circumstances. Green spaces encourage social interactions, form new places to practise sport and contribute to public health and fitness, as well as have indirect benefits for a range of environmental services. The research hypothesis is that Green Infrastructure is a framework for conservation and development and we need to design Green Infrastructure systems strategically to connect across urban, suburban, rural and wilderness landscapes and incorporate green space elements and functions at the state, regional, community, neighbourhood and site scales . Analysis and design of emerging Green Infrastructure system take a holistic view which links related physical, environmental, economic, social and cultural aspects of local communities.
ZULIAN GRAZIA; THIJSSEN MARTIJN; GUENTHER SUSANN; MAES JOACHIM
EnRoute stands for Enhancing Resilience of urban ecosystems through green infrastructure. EnRoute is a project of the European Commission in the framework of the EU Biodiversity Strategy and the Green Infrastructure Strategy. EnRoute provides scientific knowledge of how urban ecosystems can support urban planning at different stages of policy and for various spatial scales and how to help policy-making for sustainable cities. It aims to promote the application of urban green infrastructur...
Angelstam, Per; Khaulyak, Olha; Yamelynets, Taras; Mozgeris, Gintautas; Naumov, Vladimir; Chmielewski, Tadeusz J; Elbakidze, Marine; Manton, Michael; Prots, Bohdan; Valasiuk, Sviataslau
The functionality of forest patches and networks as green infrastructure may be affected negatively both by expanding road networks and forestry intensification. We assessed the effects of (1) the current and planned road infrastructure, and (2) forest loss and gain, on the remaining large forest landscape massifs as green infrastructure at the EU's eastern border region in post-socialistic transition. First, habitat patch and network functionality in 1996-98 was assessed using habitat suitability index modelling. Second, we made expert interviews about road development with planners in 10 administrative regions in Poland, Belarus and Ukraine. Third, forest loss and gain inside the forest massifs, and gain outside them during the period 2001-14 were measured. This EU cross-border region hosts four remaining forest massifs as regional green infrastructure hotspots. While Poland's road network is developing fast in terms of new freeways, city bypasses and upgrades of road quality, in Belarus and Ukraine the focus is on maintenance of existing roads, and no new corridors. We conclude that economic support from the EU, and thus rapid development of roads in Poland, is likely to reduce the permeability for wildlife of the urban and agricultural matrix around existing forest massifs. However, the four identified forest massifs themselves, forming the forest landscape green infrastructure at the EU's east border, were little affected by road development plans. In contrast, forest loss inside massifs was high, especially in Ukraine. Only in Poland forest loss was balanced by gain. Forest gain outside forest massifs was low. To conclude, pro-active and collaborative spatial planning across different sectors and countries is needed to secure functional forest green infrastructure as base for biodiversity conservation and human well-being. Copyright © 2017. Published by Elsevier Ltd.
Allegheny County / City of Pittsburgh / Western PA Regional Data Center — Parcel scale green infrastructure siting and cost effectiveness analysis. You can find more details at the project's website.
Green infrastructure can be a cost-effective approach for reducing stormwater runoff and improving water quality as a result, but it could also bring co-benefits for air quality: less impervious surfaces and more vegetation can decrease the urban heat island effect, and also result in more removal of air pollutants via dry deposition with increased vegetative surfaces. Cooler surface temperatures can also decrease ozone formation through the increases of NOx titration; however, cooler surface temperatures also lower the height of the boundary layer resulting in more concentrated pollutants within the same volume of air, especially for primary emitted pollutants (e.g. NOx, CO, primary particulate matter). To better understand how green infrastructure impacts air quality, the interactions between all of these processes must be considered collectively. In this study, we use a comprehensive coupled meteorology-air quality model (WRF-CMAQ) to simulate the influence of planned land use changes that include green infrastructure in Kansas City (KC) on regional meteorology and air quality. Current and future land use data was provided by the Mid-America Regional Council for 2012 and 2040 (projected land use due to population growth, city planning and green infrastructure implementation). These land use datasets were incorporated into the WRF-CMAQ modeling system allowing the modeling system to propagate the changes in vegetation and impervious surface coverage on meteoro
Jensen, Jesper Ole
Building green has to balance between fitting into the specific local conditions and being different from them. But being too different leads to conflicts – too much adaptation destroys the greenness of the building. In relation to infrastructure, it is argued that green buildings can have the role...... as supporter, symbol or stranger. Through three case studies of green buildings in Denmark the relation between buildings and infrastructure is explored, and discussed in relation to the future role of green buildings....
The benefits of green infrastructure (GI) in controlling urban hydrologic processes have largely focused on practical matters like stormwater management, which drives the planning stage. Green Infrastructure design and implementation usually takes into account physical site chara...
Young, Robert; Zanders, Julie; Lieberknecht, Katherine; Fassman-Beck, Elizabeth
During a National Science Foundation (US) funded "International Greening of Cities Workshop" in Auckland, New Zealand, participants agreed an effective urban green infrastructure (GI) typology should identify cities' present stage of GI development and map next steps to mainstream GI as a component of urban infrastructure. Our review reveals current GI typologies do not systematically identify such opportunities. We address this knowledge gap by developing a new typology incorporating political, economic, and ecological forces shaping GI implementation. Applying this information allows symmetrical, place-based exploration of the social and ecological elements driving a city's GI systems. We use this information to distinguish current levels of GI development and clarify intervention opportunities to advance GI into the mainstream of metropolitan infrastructure. We employ three case studies (San Antonio, Texas; Auckland, New Zealand; and New York, New York) to test and refine our typology.
Keeley, Melissa; Koburger, Althea; Dolowitz, David P; Medearis, Dale; Nickel, Darla; Shuster, William
Green infrastructure is a general term referring to the management of landscapes in ways that generate human and ecosystem benefits. Many municipalities have begun to utilize green infrastructure in efforts to meet stormwater management goals. This study examines challenges to integrating gray and green infrastructure for stormwater management, informed by interviews with practitioners in Cleveland, OH and Milwaukee WI. Green infrastructure in these cities is utilized under conditions of extreme fiscal austerity and its use presents opportunities to connect stormwater management with urban revitalization and economic recovery while planning for the effects of negative- or zero-population growth. In this context, specific challenges in capturing the multiple benefits of green infrastructure exist because the projects required to meet federally mandated stormwater management targets and the needs of urban redevelopment frequently differ in scale and location.
Prapaspongsa, Trakarn; Davidson, Cliff I.; Jindal, Ranjina
infrastructure frameworks with indicators from green building rating systems (LEED 2009, BCA Green Mark 4.0, CASBEE, and TREES-NC 1.0). The climate change mitigation and adaptation framework addresses benefits from applying different GI technologies as well as limitations in existing rating systems and the green......Climate change has threatened global security of ecosystems, human health and natural resources. These threats have increased demand for various mitigation technology solutions as well as effective strategies for adapting to anticipated impacts. Green infrastructure (GI) technologies such as green...... roofs and urban forestry are viewed as ones of the best climate adaptation strategies in cities. This study aims to develop a framework for climate change mitigation and adaptation (CCMA) in cities by using green infrastructure technologies. The framework is established by integrating existing green...
Kate Zidar; Timothy A. Bartrand; Charles H. Loomis; Chariss A. McAfee; Juliet M. Geldi; Gavin J. Rigall; Franco Montalto
While the Philadelphia Water Department (PWD) is counting on Green Stormwater Infrastructure (GI) as a key component of its long-term plan for reducing combined sewer overflows, many community stakeholders are also hoping that investment in greening can help meet other ancillary goals, collectively referred to as sustainable redevelopment. This study investigates the challenges associated with implementation of GI in Point Breeze, a residential neighborhood of South Philadelphia. The project ...
Full Text Available Green infrastructure consists of ecosystems that provide valuable services to urban areas. Constructed ecosystems, including green roofs, bioretention systems, constructed wetlands and bioreactors are artificial, custom-built components of green infrastructure that are becoming more common in cities. Small size, strong spatial boundaries, ecological novelty and the role of human design characterize all constructed ecosystems, influencing their functions and interactions with other urban ecosystems. Here I outline the relevance of ecology and evolution in understanding the functioning of constructed ecosystems. In turn, a research focus on the distinctive aspects of constructed ecosystems can contribute to fundamental science.
The City of Kansas City, Mo., Water Services Department is implementing a pilot project to measure and evaluate the performance of green infrastructure. Information obtained through this pilot project will be used to guide the design of green solutions throughout Kansas City und...
Nathaniel S. Cormier
Full Text Available This paper presents diverse typologies of urban open space designed as green infrastructure in the american cities of Seattle and Portland. In these cities of the Pacific Northwest, landscape design is viewed as much more than mere beautification of the urban environment, but as pieces of a high-performance infrastructure that protects and even improves urban hydrology, climate, and ecology. Green infrastructure is a landscape approach that creates a distinctive local landscape identity and a more sustainable urban environment.
Calfapietra, Carlo; Samson, Roeland; O'Brien, Liz; Ostoić, Silvija; Sanesi, Giovanni; Amo, Rocío
This book focuses on urban "green infrastructure" – the interconnected web of vegetated spaces like street trees, parks and peri-urban forests that provide essential ecosystem services in cities. The green infrastructure approach embodies the idea that these services, such as storm-water runoff control, pollutant filtration and amenities for outdoor recreation, are just as vital for a modern city as those provided by any other type of infrastructure. Ensuring that these ecosystem services are indeed delivered in an equitable and sustainable way requires knowledge of the physical attributes of trees and urban green spaces, tools for coping with the complex social and cultural dynamics, and an understanding of how these factors can be integrated in better governance practices. By conveying the findings and recommendations of COST Action FP1204 GreenInUrbs, this volume summarizes the collaborative efforts of researchers and practitioners from across Europe to address these challenges. .
Klemm, Wiebke; Lenzholzer, Sanda; Brink, van den Adri
In the context of global warming and increasing urban climate problems, urban green spaces and elements have been recognized as a strategy for urban climate adaptation. Yet, despite increasing scientific evidence of the positive impacts that urban green infrastructure (UGI) is having on the urban
Low-income and minority neighborhoods frequently lack healthful resources to which wealthier communities have access. Though important, the addition of facilities such as recreation centers can be costly and take time to implement. Urban green infrastructure, such as street trees...
William, Reshmina; Garg, Jugal; Stillwell, Ashlynn S.
Green stormwater infrastructure has been demonstrated as an innovative water resources management approach that addresses multiple challenges facing urban environments. However, there is little consensus on what policy strategies can be used to best incentivize green infrastructure adoption by private landowners. Game theory, an analysis framework that has historically been under-utilized within the context of stormwater management, is uniquely suited to address this policy question. We used a cooperative game theory framework to investigate the potential impacts of different policy strategies used to incentivize green infrastructure installation. The results indicate that municipal regulation leads to the greatest reduction in pollutant loading. However, the choice of the "best" regulatory approach will depend on a variety of different factors including politics and financial considerations. Large, downstream agents have a disproportionate share of bargaining power. Results also reveal that policy impacts are highly dependent on agents' spatial position within the stormwater network, leading to important questions of social equity and environmental justice.
So Yoon Kim
Full Text Available Increasing precipitation by climate change and the growing number of impervious areas present greater risk of disaster damage in urban areas. Urban green infrastructure can be an effective mitigation alternative in highly developed and concentrated area. This study investigates the effect of various types of urban green infrastructure on mitigating disaster damage in Korea. Tobit model is used to analyze the factors that determine disaster damage. Damage variation is predicted with scenarios of RCP 8.5 and urban green spaces. Seventy-four districts and counties in seven metropolitan areas are defined as the unit and the period from 2005 to 2013 is considered in the analysis. The results indicate that higher urban green ratio, sewer length, financial independence rate, and local government’s budget are relating to lower disaster damage. Based on a precipitation level of RCP 8.5 scenario in 2050, an increase in economic damage is expected to range from 262 to 1086%. However, with an increase in urban green ratio by 10%, increased economic damage is only expected to range from 217 to 1013%. The results suggest that green spaces play important role to mitigate precipitation related disasters. Highly concentrated urban areas need to consider various types of urban green infrastructure to prepare for an increase in precipitation due to climate change.
The development of impervious surfaces in urban and suburban catchments affects their hydrological behavior by decreasing infiltration, increasing peak hydrograph response following rainfall events, and ultimately increasing the total volume of water and mass of pollutants reaching streams. These changes have deleterious effects on downstream surface waters. Consequently, strategies to mitigate these impacts are now components of contemporary urban development and stormwater management. This study evaluates the effectiveness of landscape green infrastructure (GI) in reducing stormwater runoff volumes and controlling peak flows in four subdivision-scale suburban catchments (1.88 – 12.97 acres) in Montgomery County, MD, USA. Stormwater flow rates during runoff events were measured in five minute intervals at each catchment outlet. One catchment was built with GI vegetated swales on all parcels with the goal of intercepting, conveying, and infiltrating stormwater before it enters the sewer network. The remaining catchments were constructed with traditional gray infrastructure and “end-of-pipe” best management practices (BMPs) that treat stormwater before entering streams. This study compared characteristics of rainfall-runoff events at the green and gray infrastructure sites to understand their effects on suburban hydrology. The landscape GI strategy generally reduced rainfall-runoff ratios compared to gray infrastructure because of increased infiltration, ul
Paulina SCHIAPPACASSE; Bernhard MÜLLER
Green infrastructure programmes and strategies are regarded as planning opportunities to promote sustainable and resilient urban development. However, the discourse about green infrastructure policy and its effectiveness has pointed to the limited success in practical implementation. Since the green infrastructure has no planning status in its own right, it depends on being embedded in comprehensive urban and regional planning approaches if it is to have an impact on sustainable and resilient...
Buijs, Arjen E.; Mattijssen, Thomas JM; Van der Jagt, Alexander PN
Active citizens may contribute to the environmental, social, and institutional resilience of cities. This review discusses how citizen initiatives protect biodiversity hotspots, contribute to social cohesion, institutional innovation, and diversity in urban green space management. Challenges...... related to social inclusiveness, ecological connectivity and continuity suggest government involvement is pertinent, but needs to be refocused. To maximise environmental outcomes of active citizenship, governments may adopt an enabling and stimulating governance style that harnesses the transformative...... potential of active citizenship. This paper argues for mosaic governance to work with the heterogeneous array of people, institutions, and spatial practices associated with active citizenship. Mosaic governance aims for a context-sensitive way of urban green infrastructure planning, enhancing relationships...
Saaroni, H.; Amorim, J.H.; Hiemstra, J.A.; Pearlmutter, D.
The combined trends of urban heat island intensification and global warming are focusing attention on greening of cities as a tool for urban heat mitigation. Our study examines the range of research approaches and findings regarding the role of urban green infrastructure (UGI) in mitigating urban
Jefferson, A.; Avellaneda, P. M.; Jarden, K. M.; Turner, V. K.; Grieser, J.
Distributed green infrastructure approaches to stormwater management that can be retrofit into existing development are of growing interest, but questions remain about their effectiveness at the watershed-scale. In suburban northeastern Ohio, homeowners on a residential street with 55% impervious surface were given the opportunity for free rain barrels, rain gardens, and bioretention cells. Of 163 parcels, only 22 owners (13.5%) chose to participate, despite intense outreach efforts. After pre-treatment monitoring, 37 rain barrels, 7 rain gardens, and 16 street-side bioretention cells were installed in 2013-2014. Using a paired watershed approach, a reduction in up to 33% of peak flow and 40% of total runoff volume per storm was measured in the storm sewer. Using the monitoring data, a calibrated and validated SWMM model was built to explore the long-term effectiveness of the green infrastructure against a wider range of hydrological conditions. Model results confirm the effectiveness of green infrastructure in reducing surface runoff and increasing infiltration and evaporation. Based on 20 years of historical precipitation data, the model shows that the green infrastructure is capable of reducing flows by >40% at the 1, 2, and 5 year return period, suggesting some resilience to projected increases in precipitation intensity in a changing climate. Further, in this project, more benefit is derived from the street-side bioretention cells than from the rain barrels and gardens that treat rooftop runoff. Substantial hydrological gains were achieved despite low homeowner participation. Surveys indicate that many residents viewed stormwater as the city's problem and had negative perceptions of green infrastructure, despite slightly pro-environment values generally. Overall, this study demonstrates green infrastructure's hydrological effectiveness but raises challenging questions about overcoming social barriers retrofits at the neighborhood scale.
Liu, Wen; Chen, Weiping; Feng, Qi; Peng, Chi; Kang, Peng
Cost-benefit analysis is demanded for guiding the plan, design and construction of green infrastructure practices in rapidly urbanized regions. We developed a framework to calculate the costs and benefits of different green infrastructures on stormwater reduction and utilization. A typical community of 54,783 m 2 in Beijing was selected for case study. For the four designed green infrastructure scenarios (green space depression, porous brick pavement, storage pond, and their combination), the average annual costs of green infrastructure facilities are ranged from 40.54 to 110.31 thousand yuan, and the average of the cost per m 3 stormwater reduction and utilization is 4.61 yuan. The total average annual benefits of stormwater reduction and utilization by green infrastructures of the community are ranged from 63.24 to 250.15 thousand yuan, and the benefit per m 3 stormwater reduction and utilization is ranged from 5.78 to 11.14 yuan. The average ratio of average annual benefit to cost of four green infrastructure facilities is 1.91. The integrated facilities had the highest economic feasibility with a benefit to cost ratio of 2.27, and followed by the storage pond construction with a benefit to cost ratio of 2.14. The results suggested that while the stormwater reduction and utilization by green infrastructures had higher construction and maintenance costs, their comprehensive benefits including source water replacements benefits, environmental benefits and avoided cost benefits are potentially interesting. The green infrastructure practices should be promoted for sustainable management of urban stormwater.
J.D Wickham; Kurt H. Riitters; T.G. Wade; P. Vogt
Green infrastructure is a popular framework for conservation planning. The main elements of green infrastructure are hubs and links. Hubs tend to be large areas of ânaturalâ vegetation and links tend to be linear features (e.g., streams) that connect hubs. Within the United States, green infrastructure projects can be characterized as: (...
Wendel, Heather E Wright; Downs, Joni A; Mihelcic, James R
Urban green space and water features provide numerous social, environmental, and economic benefits, yet disparities often exist in their distribution and accessibility. This study examines the link between issues of environmental justice and urban water management to evaluate potential improvements in green space and surface water access through the revitalization of existing engineered water infrastructures, namely stormwater ponds. First, relative access to green space and water features were compared for residents of Tampa, Florida, and an inner-city community of Tampa (East Tampa). Although disparities were not found in overall accessibility between Tampa and East Tampa, inequalities were apparent when quality, diversity, and size of green spaces were considered. East Tampa residents had significantly less access to larger, more desirable spaces and water features. Second, this research explored approaches for improving accessibility to green space and natural water using three integrated stormwater management development scenarios. These scenarios highlighted the ability of enhanced water infrastructures to increase access equality at a variety of spatial scales. Ultimately, the "greening" of gray urban water infrastructures is advocated as a way to address environmental justice issues while also reconnecting residents with issues of urban water management.
Using interdisciplinary approaches to urban water management strategies can yield benefits for sustainability. While green infrastructure (GI) has primarily been used to increase infiltration/redistribution and reduce runoff in urban areas, the physical siting of GI can provide o...
Kopeva, Alla; Ivanova, Olga; Khrapko, Olga
The purpose of this study is to identify the facilities of green infrastructure that are able to improve living conditions in an urban environment in high-rise residential apartments buildings on steep slopes in the city of Vladivostok. Based on the analysis of theoretical sources and practices that can be observed in the world, green infrastructure facilities have been identified. These facilities meet the criteria of the sustainable development concept, and can be used in the city of Vladivostok. They include green roofs, green walls, and greening of disturbed slopes. All the existing high-rise apartments buildings situated on steep slopes in the city of Vladivostok, have been studied. It is concluded that green infrastructure is necessary to be used in new projects connected with designing and constructing of residential apartments buildings on steep slopes, as well as when upgrading the projects that have already been implemented. That will help to regulate the ecological characteristics of the sites. The results of the research can become a basis for increasing the sustainability of the habitat, and will facilitate the adoption of decisions in the field of urban design and planning.
Full Text Available The purpose of this study is to identify the facilities of green infrastructure that are able to improve living conditions in an urban environment in high-rise residential apartments buildings on steep slopes in the city of Vladivostok. Based on the analysis of theoretical sources and practices that can be observed in the world, green infrastructure facilities have been identified. These facilities meet the criteria of the sustainable development concept, and can be used in the city of Vladivostok. They include green roofs, green walls, and greening of disturbed slopes. All the existing high-rise apartments buildings situated on steep slopes in the city of Vladivostok, have been studied. It is concluded that green infrastructure is necessary to be used in new projects connected with designing and constructing of residential apartments buildings on steep slopes, as well as when upgrading the projects that have already been implemented. That will help to regulate the ecological characteristics of the sites. The results of the research can become a basis for increasing the sustainability of the habitat, and will facilitate the adoption of decisions in the field of urban design and planning.
Green infrastructure represents a broad set of site- to landscape-scale practices that can be flexibly implemented to increase sewershed retention capacity, and can thereby improve on the management of water quantity and quality. Although much green infrastructure presents as for...
Bado, R. A.; Fekete, B. M.; Khanbilvardi, R.
Impervious surfaces in urban areas generate excess runoff, which in turn causes flooding, combined sewer overflows, and degradation of adjacent surface waters. Municipal environmental protection agencies have shown a growing interest in mitigating these effects with 'green' infrastructure practices that partially restore the perviousness and water holding capacity of urban centers. Assessment of the performance of current and future green infrastructure projects is hindered by the lack of adequate hydrological modeling tools; conventional techniques fail to account for the complex flow pathways of urban environments, and detailed analyses are difficult to prepare for the very large domains in which green infrastructure projects are implemented. Currently, no standard toolset exists that can rapidly and conveniently predict runoff, consequent inundations, and sewer overflows at a city-wide scale. We demonstrate how streamlined modeling techniques can be used with open-source GIS software to efficiently model runoff in large urban catchments. Hydraulic parameters and flow paths through city blocks, roadways, and sewer drains are automatically generated from GIS layers, and ultimately urban flow simulations can be executed for a variety of rainfall conditions. With this methodology, users can understand the implications of large-scale land use changes and green/gray storm water retention systems on hydraulic loading, peak flow rates, and runoff volumes.
Kate Zidar; Maryse Belliveau-Nance; Anthony Cucchi; Danielle Denk; Andrew Kricun; Shaun O’Rourke; Shudipto Rahman; Sri Rangarajan; Eric Rothstein; Justin Shih; Franco Montalto
This study demonstrates a decision-support framework for planning Green Infrastructure (GI) systems that maximize urban ecosystem services in Camden, NJ. Seven key ecosystem services are evaluated (urban agriculture expansion, combined sewer overflow reduction, heat island reduction, flooding reduction, capacity building/green jobs expansion, fitness expansion, and stress reduction), to produce a normalized value for each service for each drainage sub-basin within the city. Gaps in ecosystem ...
Full Text Available This study demonstrates a decision-support framework for planning Green Infrastructure (GI systems that maximize urban ecosystem services in Camden, NJ. Seven key ecosystem services are evaluated (urban agriculture expansion, combined sewer overflow reduction, heat island reduction, flooding reduction, capacity building/green jobs expansion, fitness expansion, and stress reduction, to produce a normalized value for each service for each drainage sub-basin within the city. Gaps in ecosystem services are then mapped and utilized to geographically prioritize different kinds of multifunctional GI. Conceptual designs are developed for four site typologies: parks, schools, vacant lots, and brownfield sites. For one demonstration site, additional analysis is presented on urban engagement, life cycle cost reduction, and new sources of funding. What results is an integrated, long-term vision where multifunctional GI systems can be readily customized to meet multiple needs within urban communities. This study provides a portable and replicable framework for leveraging the regulatory requirement to manage stormwater to meet broader urban revitalization goals, all through a decentralized network of green infrastructure assets.
Carli D. Flynn
Full Text Available Stormwater management has long been a critical societal and environmental challenge for communities. An increasing number of municipalities are turning to novel approaches such as green infrastructure to develop more sustainable stormwater management systems. However, there is a need to better understand the technological decision-making processes that lead to specific outcomes within urban stormwater governance systems. We used the social-ecological system (SES framework to build a classification system for identifying significant variables that influence urban stormwater governance decisions related to green infrastructure adoption. To adapt the framework, we relied on findings from observations at national stormwater meetings in combination with a systematic literature review on influential factors related to green infrastructure adoption. We discuss our revisions to the framework that helped us understand the decision by municipal governments to adopt green infrastructure. Remaining research needs and challenges are discussed regarding the development of an urban stormwater SES framework as a classification tool for knowledge accumulation and synthesis.
Wang, Z.; Yang, J.
Urban green infrastructure offers arid cities an attractive means of mitigation/adaptation to environmental challenges of elevated thermal stress, but imposes the requirement of outdoor irrigation that aggravates the stress of water resource management. Future development of cities is inevitably constrained by the limited availability of water resources, under challenges of emergent climate change and continuous population growth. This study used the Weather Research and Forecasting model with urban dynamics to assess the potential water buffering capacity of urban green infrastructure in arid environments and its implications for sustainable urban planning. The Phoenix metropolitan area, Arizona, United States, is adopted as a testbed with two hypothetical cases, viz. the water-saving and the fully-greening scenarios investigated. Modifications of the existing green infrastructure and irrigation practices are found to significantly influence the thermal environment of Phoenix. In addition, water saving by xeriscaping (0.77 ± 0.05 × 10^8 m^3) allows the region to support 19.8% of the annual water consumption by the projected 2.62 million population growth by 2050, at a cost of an increase in urban ambient temperature of about 1 o^C.
Carter, Timothy; Fowler, Laurie
Traditional construction practices provide little opportunity for environmental remediation to occur in urban areas. As concerns for environmental improvement in urban areas become more prevalent, innovative practices which create ecosystem services and ecologically functional land cover in cities will be in higher demand. Green roofs are a prime example of one of these practices. The past decade has seen the North American green roof industry rapidly expand through international green roof conferences, demonstration sites, case studies, and scientific research. This study evaluates existing international and North American green roof policies at the federal, municipal, and community levels. Green roof policies fall into a number of general categories, including direct and indirect regulation, direct and indirect financial incentives, and funding of demonstration or research projects. Advantages and disadvantages of each category are discussed. Salient features and a list of prompting standards common to successfully implemented green roof strategies are then distilled from these existing policies. By combining these features with data collected from an experimental green roof site in Athens, Georgia, the planning and regulatory framework for widespread green roof infrastructure can be developed. The authors propose policy instruments be multi-faceted and spatially focused, and also propose the following recommendations: (1) Identification of green roof overlay zones with specifications for green roofs built in these zones. This spatial analysis is important for prioritizing areas of the jurisdiction where green roofs will most efficiently function; (2) Offer financial incentives in the form of density credits and stormwater utility fee credits to help overcome the barriers to entry of the new technology; (3) Construct demonstration projects and institutionalize a commitment greening roofs on publicly-owned buildings as an effective way of establishing an educated
Carter, Timothy; Fowler, Laurie
Traditional construction practices provide little opportunity for environmental remediation to occur in urban areas. As concerns for environmental improvement in urban areas become more prevalent, innovative practices which create ecosystem services and ecologically functional land cover in cities will be in higher demand. Green roofs are a prime example of one of these practices. The past decade has seen the North American green roof industry rapidly expand through international green roof conferences, demonstration sites, case studies, and scientific research. This study evaluates existing international and North American green roof policies at the federal, municipal, and community levels. Green roof policies fall into a number of general categories, including direct and indirect regulation, direct and indirect financial incentives, and funding of demonstration or research projects. Advantages and disadvantages of each category are discussed. Salient features and a list of prompting standards common to successfully implemented green roof strategies are then distilled from these existing policies. By combining these features with data collected from an experimental green roof site in Athens, Georgia, the planning and regulatory framework for widespread green roof infrastructure can be developed. The authors propose policy instruments be multi-faceted and spatially focused, and also propose the following recommendations: (1) Identification of green roof overlay zones with specifications for green roofs built in these zones. This spatial analysis is important for prioritizing areas of the jurisdiction where green roofs will most efficiently function; (2) Offer financial incentives in the form of density credits and stormwater utility fee credits to help overcome the barriers to entry of the new technology; (3) Construct demonstration projects and institutionalize a commitment greening roofs on publicly-owned buildings as an effective way of establishing an educated
Miles, B.; Band, L. E.
To meet water quality goals stormwater utilities and not-for-profit watershed organizations in the U.S. are working with citizens to design and implement green infrastructure on residential land. Green infrastructure, as an alternative and complement to traditional (grey) stormwater infrastructure, has the potential to contribute to multiple ecosystem benefits including stormwater volume reduction, carbon sequestration, urban heat island mitigation, and to provide amenities to residents. However, in small (1-10-km2) medium-density urban watersheds with heterogeneous land cover it is unclear whether stormwater retrofits on residential parcels significantly contributes to reduce stormwater volume at the watershed scale. In this paper, we seek to improve understanding of how small-scale redistribution of water at the parcel scale as part of green infrastructure implementation affects urban water budgets and stormwater volume across spatial scales. As study sites we use two medium-density headwater watersheds in Baltimore, MD and Durham, NC. We develop ecohydrology modeling experiments to evaluate the effectiveness of redirecting residential rooftop runoff to un-altered pervious surfaces and to engineered rain gardens to reduce stormwater runoff. As baselines for these experiments, we performed field surveys of residential rooftop hydrologic connectivity to adjacent impervious surfaces, and found low rates of connectivity. Through simulations of pervasive adoption of downspout disconnection to un-altered pervious areas or to rain garden stormwater control measures (SCM) in these catchments, we find that most parcel-scale changes in stormwater fate are attenuated at larger spatial scales and that neither SCM alone is likely to provide significant changes in streamflow at the watershed scale.
Demuzere, M; Orru, K; Heidrich, O; Olazabal, E; Geneletti, D; Orru, H; Bhave, A G; Mittal, N; Feliu, E; Faehnle, M
In order to develop climate resilient urban areas and reduce emissions, several opportunities exist starting from conscious planning and design of green (and blue) spaces in these landscapes. Green urban infrastructure has been regarded as beneficial, e.g. by balancing water flows, providing thermal comfort. This article explores the existing evidence on the contribution of green spaces to climate change mitigation and adaptation services. We suggest a framework of ecosystem services for systematizing the evidence on the provision of bio-physical benefits (e.g. CO2 sequestration) as well as social and psychological benefits (e.g. improved health) that enable coping with (adaptation) or reducing the adverse effects (mitigation) of climate change. The multi-functional and multi-scale nature of green urban infrastructure complicates the categorization of services and benefits, since in reality the interactions between various benefits are manifold and appear on different scales. We will show the relevance of the benefits from green urban infrastructures on three spatial scales (i.e. city, neighborhood and site specific scales). We will further report on co-benefits and trade-offs between the various services indicating that a benefit could in turn be detrimental in relation to other functions. The manuscript identifies avenues for further research on the role of green urban infrastructure, in different types of cities, climates and social contexts. Our systematic understanding of the bio-physical and social processes defining various services allows targeting stressors that may hamper the provision of green urban infrastructure services in individual behavior as well as in wider planning and environmental management in urban areas. Copyright © 2014 Elsevier Ltd. All rights reserved.
Green infrastructure is a widely used framework for conservation planning in the United States and elsewhere. The main components of green infrastructure are hubs and corridors. Hubs are large areas of natural vegetation, and corridors are linear features that connect hubs. W...
Charles M. Rogers
Full Text Available Green infrastructure refers to a type of land use design that mimics the natural water cycle by using the infiltration capacities of vegetation, soils, and other natural processes to mitigate stormwater runoff. As a multifunctional landscape, urban agriculture should be seen as a highly beneficial tool for urban planning not only because of its ability to function as a green stormwater management strategy, but also due to the multiple social and environmental benefits it provides. In 2012, the city of Austin adopted a major planning approach titled the “Imagine Austin Comprehensive Plan” (IACP outlining the city’s vision for future growth and land use up to 2039. The plan explicitly addresses the adoption of green infrastructure as a target for future land use with urban agriculture as a central component. Addressing this area of land use planning will require tools that can locate suitable areas within the city ideal for the development of green infrastructure. In this study, a process was developed to create a spatially explicit method of siting urban agriculture as a green infrastructure tool in hydrologically sensitive areas, or areas prone to runoff, in east Austin. The method uses geospatial software to spatially analyze open access datasets that include land use, a digital elevation model, and prime farmland soils. Through this method a spatial relationship can be made between areas of high surface runoff and where the priority placement of urban farms should be sited as a useful component of green infrastructure. Planners or geospatial analysts could use such information, along with other significant factors and community input, to aid decision makers in the placement of urban agriculture. This spatially explicit approach for siting potential urban farms, will support the integration of urban agriculture as part of the land use planning of Austin.
Jia, Z; Tang, S; Luo, W; Li, S; Zhou, M
As small scale green infrastructures, rain gardens have been widely advocated for urban stormwater management in the contemporary low impact development (LID) era. This paper presents a simple method that consists of hydrological models and the matching plots of nomographs to provide an informative and practical tool for rain garden sizing and hydrological evaluation. The proposed method considers design storms, infiltration rates and the runoff contribution area ratio of the rain garden, allowing users to size a rain garden for a specific site with hydrological reference and predict overflow of the rain garden under different storms. The nomographs provide a visual presentation on the sensitivity of different design parameters. Subsequent application of the proposed method to a case study conducted in a sub-humid region in China showed that, the method accurately predicted the design storms for the existing rain garden, the predicted overflows under large storm events were within 13-50% of the measured volumes. The results suggest that the nomographs approach is a practical tool for quick selection or assessment of design options that incorporate key hydrological parameters of rain gardens or other infiltration type green infrastructure. The graphic approach as displayed by the nomographs allow urban planners to demonstrate the hydrological effect of small scale green infrastructure and gain more support for promoting low impact development. Copyright © 2016 Elsevier Ltd. All rights reserved.
William, R. K.; Garg, J.; Stillwell, A. S.
While green stormwater infrastructure is a useful approach in addressing multiple challenges facing the urban environment, little consensus exists on how to best incentivize its adoption by private landowners. Game theory, a field of study designed to model conflict and cooperation between two or more agents, is well-suited to address this policy question. We used a cooperative game theory framework to analyze the impacts of three different policy approaches frequently used to incentivize the uptake of green infrastructure by private landowners: municipal regulation, direct grants, and stormwater fees. The results indicate that municipal regulation leads to the greatest environmental benefits; however, the choice of "best" regulatory approach is dependent on a variety of different factors including political and financial considerations. Policy impacts are also highly dependent on agents' spatial positions within the stormwater network. This finding leads to important questions of social equity and environmental justice.
Van Wyk, Llewellyn V
Full Text Available The development and maintenance of infrastructure is crucial to improving economic growth and quality of life (WEF 2013). Urban infrastructure typically includes bulk services such as water, sanitation and energy (typically electricity and gas...
Full Text Available Climate change will further induce a generalized rise in temperature, heat waves, exacerbation of heat island effect, alteration of the precipitation regime variability with higher occurrence of high precipitation and flood events, reduction of quantity and quality of freshwater resources, disruption of agricultural production, leading to food security risk, degradation of recreational and aesthetic amenities, and loss of biodiversity. On other hand, Green Infrastructure, that is, the network of natural and semi-natural spaces within and around urban spaces, brings a constructive and protecting element that may mitigate and adapt to the local level impacts of climate change, strengthening local resilience. This paper presents a comparative study of various green infrastructures’ implementation based on analytics in the United States of America, United Kingdom and Portugal, and focuses on the degree of its alignment with the public policies of mitigation and adaptation to the impacts of climate change. Pursuant to the identification of successes and failures, this paper infers common strategies, goals and benchmarking on outcomes for more adequate decision implementation and sustainable spatial planning, considering the importance of green infrastructure.
Sheffield, United Kingdom (UK) was the world centre for the steel and cutlery industries. However, those industries have been in decline and the city has been in the process of re-inventing itself over the past 20 years. Sheffield is now known as the UK's greenest city in terms of the amount of woodland, parkland and open spaces within its city limits. The city of Sheffield has also developed a unique partnership approach to promote green roof infrastructure as the most visible and high-profile signal of intent and symbol of low environmental impact building design and construction. This partnership involves Sheffield's Green Roof Forum, comprising the University of Sheffield's multi-disciplinary centre of excellence in green roof research; Sheffield City Council; Groundwork Sheffield, an urban economic and environmental regeneration agency; and city Architects and developers. This partnership meets six times a year to raise the profile of green roofs within the city and region, and to develop strategies to increase the uptake and implementation of green roof infrastructure in the region. This paper discussed the partnership, the Green Room Forum, accomplishments to date in promoting green roofs in the city, and the strategy for the Sheffield region to become a leader in green roof implementation and associated green technologies. The strategy is presented in two parts: consultation and research to identify the nature of market failure and devising methods to overcome that failure. The green roof strategy is being implemented through a program entitled Building Greener, Building Smarter and consists of four inter-linked strands. These strands were discussed in detail and included getting buy-in, demonstrating benefit, establishing the business case, and changing plans and practices. 3 tabs., 1 ref
Seo, Y.; Hwang, J.; Kwon, Y.
The existence of impervious areas is one of the most distinguishing characteristics of urban catchments. It decreases infiltration and increases direct runoff in urban catchments. The recent introduction of green infrastructure in urban catchments for the purpose of sustainable development contributes to the decrease of the directly connected impervious areas (DCIA) by isolating existing impervious areas and consequently, to the flood risk mitigation. This study coupled the width function-based instantaneous hydrograph (WFIUH), which is able to handle the spatial distribution of the impervious areas, with the concept of the DCIA to assess the impact of decreasing DCIA on the shape of direct runoff hydrographs. Using several scenarios for typical green infrastructure and corresponding changes of DCIA in a test catchment, this study evaluated the effect of green infrastructure on the shape of the resulting direct runoff hydrographs and peak flows. The results showed that the changes in the DCIA immediately affects the shape of the direct runoff hydrograph and decreases peak flows depending on spatial implementation scenarios. The quantitative assessment of the spatial distribution of impervious areas and also the changes to the DCIA suggests effective and well-planned green infrastructure can be introduced in urban environments for flood risk management.
Rai, A.; Minsker, B. S.
Urbanization over the last century has degraded our natural water resources by increasing storm-water runoff, reducing nutrient retention, and creating poor ecosystem health downstream. The loss of tree canopy and expansion of impervious area and storm sewer systems have significantly decreased infiltration and evapotranspiration, increased stream-flow velocities, and increased flood risk. These problems have brought increasing attention to catchment-wide implementation of green infrastructure (e.g., decentralized green storm water management practices such as bioswales, rain gardens, permeable pavements, tree box filters, cisterns, urban wetlands, urban forests, stream buffers, and green roofs) to replace or supplement conventional storm water management practices and create more sustainable urban water systems. Current green infrastructure (GI) practice aims at mitigating the negative effects of urbanization by restoring pre-development hydrology and ultimately addressing water quality issues at an urban catchment scale. The benefits of green infrastructure extend well beyond local storm water management, as urban green spaces are also major contributors to human health. Considerable research in the psychological sciences have shown significant human health benefits from appropriately designed green spaces, yet impacts on human wellbeing have not yet been formally considered in GI design frameworks. This research is developing a novel computational green infrastructure (GI) design framework that integrates hydrologic requirements with criteria for human wellbeing. A supervised machine learning model is created to identify specific patterns in urban green spaces that promote human wellbeing; the model is linked to RHESSYS model to evaluate GI designs in terms of both hydrologic and human health benefits. An application of the models to Dead Run Watershed in Baltimore showed that image mining methods were able to capture key elements of human preferences that could
Gehrels, H.; Meulen, S. vsn der; Schasfoort, F.; Bosch, P.R.; Brolsma, R.; Dinter, D. van; Geerling, G.J.; Goossen, M.; Jacobs, C.; Jong, M. de; Kok, S.; Massop, H.; Oste, L.; Perez-Soba, M.; Rovers, V.; Smit, A.; Verweij, P.; Vries, B. de; Weijers, E.
There is a growing awareness in cities throughout the world that green and blue infrastructure can offer a wide range of ecosystem services to support a healthy urban environment. For example, landscape architects explore possibilities in their design of the urban landscape to use the potential of
Erika S. Svendsen; Jacqueline W.T. Lu
On March 5-6, 2010, over two hundred researchers and practitioners came together at The New School to showcase scientific innovation in the field of urban forestry and greening. The MillionTreesNYC, Green Infrastructure and Urban Ecology Research Symposium engaged professionals from a broad range of disciplines including sociology, planning,...
Endreny, T. A.; Ulgiati, S.; Santagata, R.
Cities can invest in green infrastructure to purposefully couple water with urban tree growth, thereby generating ecosystem services and supporting human wellbeing as advocated by United Nations sustainable development initiatives. This research estimates the value of tree-based ecosystem services in order to help megacities assess the benefits relative to the costs of such investments. We inventoried tree cover across the metropolitan area of 10 megacities, in 5 continents and biomes, and developed biophysical scaling equations using i-Tree tools to estimate the tree cover value to reductions in air pollution, stormwater, building energy, and carbon emissions. Metropolitan areas ranged from 1173 to 18,720 sq km (median value 2530 sq km), with median tree cover 21%, and potential additional tree cover 19%, of this area. Median tree cover density was 39 m2/capita (compared with global value of 7800 m2/capita), with lower density in desert and tropical biomes, and higher density in temperate biomes. Using water to support trees led to median benefits of 1.2 billion/yr from reductions in CO, NO2, SO2, PM10, and PM2.5, 27 million/yr in avoided stormwater processing by wastewater facilities, 1.2 million/yr in building energy heating and cooling savings, and 20 million/yr in CO2 sequestration. These ecosystem service benefits contributed between 0.1% and 1% of megacity GDP, with a median contribution of 0.3%. Adjustment of benefit value between different city economies considered factors such as purchasing power parity and emergy to money ratio conversions. Green infrastructure costs billions of dollars less than grey infrastructure, and stormwater based grey infrastructure provides fewer benefits. This analysis suggests megacities should invest in tree-based green infrastructure to maintain and increase ecosystem service benefits, manage their water resources, and improve human wellbeing.
Finka, Maroš; Ondrejička, Vladimír; Jamečný, Ľubomír; Husár, Milan
The dialogue among the decision makers and stakeholders is a crucial part of any decision-making processes, particularly in case of integrated transportation planning and planning of green infrastructure where a multitude of actors is present. Although the theory of public participation is well-developed after several decades of research, there is still a lack of practical guidelines due to the specificity of public participation challenges. The paper presents a model of public participation for integrated transport and green infrastructure planning for international project TRANSGREEN covering the area of five European countries - Slovakia, Czech Republic, Austria, Hungary and Romania. The challenge of the project is to coordinate the efforts of public actors and NGOs in international environment in oftentimes precarious projects of transport infrastructure building and developing of green infrastructure. The project aims at developing and environmentally-friendly and safe international transport network. The proposed public participation procedure consists of five main steps - spread of information (passive), collection of information (consultation), intermediate discussion, engagement and partnership (empowerment). The initial spread of information is a process of communicating with the stakeholders, informing and educating them and it is based on their willingness to be informed. The methods used in this stage are public displays, newsletters or press releases. The second step of consultation is based on transacting the opinions of stakeholders to the decision makers. Pools, surveys, public hearings or written responses are examples of the multitude of ways to achieve this objective and the main principle of openness of stakeholders. The third step is intermediate discussion where all sides of are invited to a dialogue using the tools such as public meetings, workshops or urban walks. The fourth step is an engagement based on humble negotiation, arbitration and
Full Text Available Urban ecology provides the theoretical foundation for assessing the interaction between man and nature in cities. Nature seems to be reduced and malfunctioning, resulting into a decrease in the ecosystem services provided to humans. The new method, based on assessing the green infrastructure, is designed to replace monetary and carbon footprint assessments and be particularly relevant for the urban areas, which grow and change fast and are the main drivers of environmental changes. This study uses 2005-2007 CORINE and Urban Atlas data to look at Bucharest. The results show that, despite of the method, the area occupied by the green infrastructure represents about 1/3 of the total area, corresponding to 50 m2/person, although the green spaces only account for 6.5 m2/person, which is far below the European average (26 m2/person.
Eric Kuehler; Jon Hathaway; Andrew Tirpak
The use of green infrastructure for reducing stormwater runoff is increasingly common. One underâstudied component of the green infrastructure network is the urban forest system. Trees can play an important role as the âfirst line of defenseâ for restoring more natural hydrologic regimes in urban watersheds by intercepting rainfall, delaying runoff, infiltrating, and...
Abhijith, K. V.; Kumar, Prashant; Gallagher, John; McNabola, Aonghus; Baldauf, Richard; Pilla, Francesco; Broderick, Brian; Di Sabatino, Silvana; Pulvirenti, Beatrice
Intensifying the proportion of urban green infrastructure has been considered as one of the remedies for air pollution levels in cities, yet the impact of numerous vegetation types deployed in different built environments has to be fully synthesised and quantified. This review examined published literature on neighbourhood air quality modifications by green interventions. Studies were evaluated that discussed personal exposure to local sources of air pollution under the presence of vegetation in open road and built-up street canyon environments. Further, we critically evaluated the available literature to provide a better understanding of the interactions between vegetation and surrounding built-up environments and ascertain means of reducing local air pollution exposure using green infrastructure. The net effects of vegetation in each built-up environment are also summarised and possible recommendations for the future design of green infrastructure are proposed. In a street canyon environment, high-level vegetation canopies (trees) led to a deterioration in air quality, while low-level green infrastructure (hedges) improved air quality conditions. For open road conditions, wide, low porosity and tall vegetation leads to downwind pollutant reductions while gaps and high porosity vegetation could lead to no improvement or even deteriorated air quality. The review considers that generic recommendations can be provided for vegetation barriers in open road conditions. Green walls and roofs on building envelopes can also be used as effective air pollution abatement measures. The critical evaluation of the fundamental concepts and the amalgamation of key technical features of past studies by this review could assist urban planners to design and implement green infrastructures in the built environment.
Raffaele Pelorosso; Federica Gobattoni; Maria Nicolina Ripa; Antonio Leone
Planning of ecosystem services provided by the Urban Green Infrastructure (UGI) is a key issue for urban sustainability. Planning strategies driven by the second law of thermodynamics (SLT) are innovative approaches to sustainability but they are still in seminal phase. In this article, a coupled review of SLT within spatial planning is accomplished looking at the main applications in urban green infrastructure (UGI) planning. The work has supported the definition of a preliminary low-entropy...
Tiwary, A.; Williams, L. D.; Heidrich, O.; Namdeo, A.; Bandaru, V.; Calfapietra, Carlo
Roč. 208, jan (2016), s. 209-220 ISSN 0269-7491 Institutional support: RVO:67179843 Keywords : Green infrastructure * Multi-functional * Pollution * Performance index * Streetscape Subject RIV: EH - Ecology, Behaviour Impact factor: 5.099, year: 2016
Ka Po John Yau
Full Text Available Objective: To assess whether in-vitro osteogenic differentiation of human dental pulp mesenchymal stem cells can be induced by transient transfection with the gene encoding human bone morphogenic protein 7 (BMP7. Materials and Methods: A mesenchymal stem cell population was isolated from the dental pulp of two extracted permanent premolars, expanded and characterized. The human BMP7 gene, as a recombinant pcDNA3.1/V5-His-TOPO-BMP7 plasmid, was transfected into the cells. Three negative controls were used: No plasmid, empty vector, and an unrelated vector encoding green fluorescent protein. After the interval of 24 and 48 h, mRNA levels of alkaline phosphatase and osteocalcin as markers of in-vitro osteogenic differentiation were measured by real-time polymerase chain reaction and standardized against β-actin mRNA levels. Results: The level of alkaline phosphatase mRNA was significantly higher for the BMP7 group than for all three negative controls 48 h after transfection (706.9 vs. 11.24 for untransfected cells, 78.05 for empty vector, and 73.10 for green fluorescent protein vector. The level of osteocalcin mRNA was significantly higher for the BMP7 group than for all three negative controls 24 h after transfection (1.0, however, decreased after another 24 h. Conclusions: In-vitro osteoblastic differentiation of human dental pulp mesenchymal stem cells, as indicated by expression of alkaline phosphatase and osteocalcin, can be induced by transient transfection with the BMP7 gene.
Gao, H.; Yamazaki, D.; Finley, T.; Bohn, T. J.; Low, G.; Sabo, J. L.
Water infrastructure lies at the heart of the challenges and opportunities of Integrated Water Resource Management (IWRM). Green infrastructure (e.g., wetlands restoration) presents an alternative to its hard-path counterpart - gray infrastructure, which often has external, economic and unmeasured ecological costs. But the science framework to prioritize green infrastructure buildout is nascent. In this study, we addressed this gap in Brazos River basin in Texas, in the context of corporate decisions to secure water supplies for various water stewardship objectives. We developed a physically-based tool to quantify the potential for wetland restoration to restore desired flows (hydrology), and a financial framework for comparing its cost-benefit with heightening an existing dam (conservation finance). Our framework has three components. First, we harnessed a topographic index (HAND) to identify the potential wetlands sites. Second, we coupled a land surface model (VIC) with a hydrodynamic model (CaMa-Flood) to investigate the effects of wetland size, location, and vegetation on hydrology. Finally, we estimated the net present value, indirect rate of return and payback period for green (wetlands) vs. gray (reservoir expansion) infrastructure. We found wetlands have more substantial impact on peak flow than baseflow. Interestingly, wetlands can improve baseflow reliability but not directly except with the largest (>400 km2) projects. Peak flow reduction volumes of wetlands if used as credits towards reservoir flood-control storage provide adequate conservation storage to deliver guaranteed reliability of baseflow. Hence, the synergy of existing dams with newly created wetlands offers a promising natural solution to increase water supply resilience, while green projects also generate revenue compared to their gray counterparts. This study demonstrates the possibility of using innovative engineering design to synergize green and gray infrastructures to convert water
In 2010, Kansas City, MO (KCMO) signed a consent degree with EPA on combined sewer overflows. The City decided to use adaptive management in order to extensively utilize green infrastructure (GI) in lieu of, and in addition to, gray structural controls. KCMO installed 130 GI sto...
EPA Report Abstract: Infiltration-based green infrastructure and related retrofits for sewershed-level rainfall and stormwater volume capture (e.g., rain gardens, cisterns, etc.) are increasingly being recognized as management options to reduce stormwater volume contribution into...
Full Text Available Recent research suggests future alterations in rainfall patterns due to climate variability, affecting public safety and health in urban areas. Urban growth, one of the main drivers of change in the current century, will also affect these conditions. Traditional drainage approaches using grey infrastructure offer low adaptation to an uncertain future. New methodologies of stormwater management focus on decentralized approaches in a long-term planning framework, including the use of Green Infrastructure (GI. This work presents a novel methodology to select, evaluate, and place different green-grey practices (or measures for retrofitting urban drainage systems. The methodology uses a hydrodynamic model and multi-objective optimization to design solutions at a watershed level. The method proposed in this study was applied in a highly urbanized watershed to evaluate the effect of these measures on Combined Sewer Overflows (CSO quantity. This approach produced promising results and may become a useful tool for planning and decision making of drainage systems.
Vegetation can be an important component of urban green infrastructure. Its structure is a complex result of the socio-ecological milieu and management decisions, and it can influence numerous ecohydrological processes such as stormwater interception and evapotranspiration. Despi...
Montgomery, James A; Klimas, Christie A; Arcus, Joseph; DeKnock, Christian; Rico, Kathryn; Rodriguez, Yarency; Vollrath, Katherine; Webb, Ellen; Williams, Allison
This paper describes the results of a preliminary project conducted by a team of DePaul University undergraduate students and staff from the Gary Comer Youth Center located on Chicago's South Side. The team assessed soil quality on 116 samples collected among four abandoned residential lots adjacent to the Comer Center. Soil quality data will be used in a follow-up study to determine the suitability of each lot for green infrastructure implementation. Green infrastructure may be a useful approach for providing ecosystem services and mitigating food deserts in inner-city communities. Soil quality on all lots was poor. All soils had pH >8.0, low biological activity, and low N mineralization potential. The soils were rich in available P and had mean total Pb concentrations above the USEPA threshold (400 mg kg) for children's playlots. Mean bioavailable Pb on the largest of the four lots was 12% of total Pb, indicating that most of the total Pb is not bioavailable. This result is encouraging because high bioavailable Pb concentrations are linked with negative health effects, particularly in children. All lots had NO-N concentrations below those considered to be appropriate for plant growth. On the other hand, no significant differences in mean concentrations of the other analytes were found. The poor soil quality in the four lots presents an opportunity to use green infrastructure to enhance ecosystem services, improve community and environmental health, and provide more equitable access to green space. Copyright © by the American Society of Agronomy, Crop Science Society of America, and Soil Science Society of America, Inc.
Band, L. E.
The management of water is among the most important attributes of urbanization. Provision of sufficient quantities and quality of freshwater, treatment and disposal of wastewater and flood protection are critical for urban sustainability. Over the last century, two major shifts in water management paradigms have occurred, the first to improve public health with the provision of infrastructure for centralized sanitary effluent collection and treatment, and the rapid drainage and routing of stormwater. A current shift in paradigm is now occurring in response to the unintended consequences of sanitary and stormwater management, which have degraded downstream water bodies and shifted flood hazard downstream. Current infrastructure is being designed and implemented to retain, rather than rapidly drain, stormwater, with a focus on infiltration based methods. In urban areas, this amounts to a shift in hydrologic behavior to depression focused recharge. While stormwater is defined as surface flow resulting from developed areas, an integrated hydrologic systems approach to urban water management requires treatment of the full critical zone. In urban areas this extends from the top of the vegetation and building canopy, to a subsurface depth including natural soils, fill, saprolite and bedrock. In addition to matric and network flow in fracture systems, an urban "karst" includes multiple generations of current and past infrastructure, which has developed extensive subsurface pipe networks for supply and drainage, enhancing surface/groundwater flows and exchange. In this presentation, Band will discuss the need to focus on the urban critical zone, and the development and adaptation of new modeling and analytical approaches to understand and plan green infrastructure based on surface/groundwater/ecosystem interactions, and implications for the restoration and new design of cities.
Green infrastructure is an approach to managing wet weather flows using systems and practices that mimic natural processes. It is designed to manage stormwater as close to its source as possible and protect the quality of receiving waters. Although most green infrastructure pract...
Michon, Frédéric; Forest, Loïc; Collomb, Elodie; Demongeot, Jacques; Dhouailly, Danielle
Summary During embryonic development, feathers first appear as primordia consisting of an epidermal placode associated with a dermal condensation. In most previous studies, the BMPs have been proposed to function as inhibitors of the formation of cutaneous appendages. We showed that the function of BMPs is quite nuanced: BMP-2 and BMP-7, which are expressed in both skin components, act antagonistically and yet are both involved in the dermal condensations formation. BMP-7, the first to be expressed, is implicated in chemotaxis which leads to cell recruitment to the condensation, whereas BMP-2, which is expressed later, leads to an arrest of cell migration, likely via its modulation of EIIIA Fibronectin domain and α4-Integrin expression. We also propose a mathematical model, a reaction-diffusion system, based on cell proliferation, chemotaxis and the timing of BMP-2 and BMP-7 expression, which simulates the endogenous situation and reproduces the negative effects of excess BMP-2 or BMP-7 on feather patterning. PMID:18635609
Green infrastructure is quickly gaining ground as a less costly, greener alternative to traditional methods of stormwater management. One popular form of green infrastructure is the use of rain gardens to capture and infiltrate stormwater in to the ground. We used life cycle asse...
Full Text Available Over the last few decades, the globalization phenomenon has determined the exponential development - from an economic, cultural and political standpoint - of traffic flows, the number of means and infrastructures involved in communication and exchange. At the same time, these represent one of the most complicated environmental issues of contemporary times, but perhaps also one of the most outstanding opportunities for setting up processes aimed at upgrading the territory and its constructions, towards environmental regeneration and social reorganization. These, in turn, would produce and spread (as in some already established examples of infrastructure upgrading innovative and more sustainable forms of urban lifestyles. The present contribution aims at illustrating the former, beginning with research and experiments involving the development of eco-friendly meta-design models for the correct employment of “green technologies” in: meta-project research for small mobility facilities; expansion and redevelopment works for the Stazione Termini; experiments in design for some energy-efficient underground metro stops in Rome.
Laura Estefanía Quintero González
Full Text Available The current global demographic explosion has impacted in an excessive growth of cities, with urban areas invading key environmental places and with it, reducing the possibility of keeping good public spaces. Tunja is one of the growing cities of Colombia and its central zone needs an alternative of recovery and generation of public green spaces to avoid densification. The research proposes: firstly, to determine the availability of existing public space in the urban area of Tunja through a characterization and availability diagnosis; and, secondly, to formulate specific types of green infrastructure. By considering the regular state conditions of the existing public space network and the inequality in the spatial connectivity of the places within the system, a proposal of types of vegetated infrastructures is given to improve both existing and potentially places.
The report outlines technical assistance to develop green infrastructure scenarios for the Zidell Yards site consistent with the constraints of a recently remediated brownfield that can be implemented within a 15-20 year time horizon.
Dong, Xin; Guo, Hao; Zeng, Siyu
In recent years, the concept transition from fail-safe to safe-to-fail makes the application of resilience analysis popular in urban drainage systems (UDSs) with various implications and quantifications. However, most existing definitions of UDSs resilience are confined to the severity of flooding, while uncertainties from climate change and urbanization are not considered. In this research, we take into account the functional variety, topological complexity, and disturbance randomness of UDSs and define a new formula of resilience based on three parts of system severity, i.e. social severity affected by urban flooding, environmental severity caused by sewer overflow, and technological severity considering the safe operation of downstream facilities. A case study in Kunming, China is designed to compare the effect of green and grey infrastructure strategies on the enhancement of system resilience together with their costs. Different system configurations with green roofs, permeable pavement and storage tanks are compared by scenario analysis with full consideration of future uncertainties induced by urbanization and climate change. The research contributes to the development of sustainability assessment of urban drainage system with consideration of the resilience of green and grey infrastructure under future change. Finding the response measures with high adaptation across a variety of future scenarios is crucial to establish sustainable urban drainage system in a long term. Copyright © 2017. Published by Elsevier Ltd.
In 2010, Kansas City, MO (KCMO) signed a consent degree with EPA on combined sewer overflows. The City decided to use adaptive management in order to extensively utilize green infrastructure (GI) in lieu of, and in addition to, structural controls. KCMO installed 130 GI storm con...
Shuster, W.; Schifman, L. A.; Herrmann, D.
Green infrastructure represents a broad set of site- to landscape-scale practices that can be flexibly implemented to increase sewershed retention capacity, and can thereby improve on the management of water quantity and quality. Although much green infrastructure presents as formal engineered designs, urbanized landscapes with highly-interspersed pervious surfaces (e.g., right-of-way, parks, lawns, vacant land) may offer ecosystem services as passive, infiltrative green infrastructure. Yet, infiltration and drainage processes are regulated by soil surface conditions, and then the layering of subsoil horizons, respectively. Drawing on a unique urban soil taxonomic and hydrologic dataset collected in 12 cities (each city representing a major soil order), we determined how urbanization processes altered the sequence of soil horizons (compared to pre-urbanized reference soil pedons) and modeled the hydrologic implications of these shifts in layering with an unsaturated zone code (HYDRUS2D). We found that the different layering sequences in urbanized soils render different types and extents of supporting (plant-available soil water), provisioning (productive vegetation), and regulating (runoff mitigation) ecosystem services.
LID and Green Infrastructure is a cost-effective, resilient approach to stormwater management. Projects that reduce flood losses may be eligible for grant funding through FEMA and may allow communities to claim points through FEMA's rating system -CRS
Erika S. Svendsen; Mary E. Northridge; Sara S. Metcalf
One of the enduring lessons of cities is the essential relationship between grey infrastructure (e.g., streets and buildings) and green infrastructure (e.g., parks and open spaces). The design and management of natural resources to enhance human health and well-being may be traced back thousands of years to the earliest urban civilizations. From the irrigation projects...
Full Text Available Rendu-Osler-Weber syndrome, also known as hereditary hemorrhagic telangiectasia (HHT, is an autosomal dominant vascular disorder. Three genes are causally related to HHT: the ENG gene encoding endoglin, a co-receptor of the TGFß family (HHT1, the ACVRL1 gene encoding ALK1 (activin receptor-like kinase 1, a type I receptor of the TGFß family (HHT2, and the SMAD4 gene, encoding a transcription factor critical for this signaling pathway. Bone morphogenetic proteins (BMPs are growth factors of the TGFß family. Among them, BMP9 and BMP10 have been shown to bind directly with high affinity to ALK1 and endoglin, and BMP9 mutations have recently been linked to a vascular-anomaly syndrome that has phenotypic overlap with HHT. BMP9 and BMP10 are both circulating cytokines in blood, and the current working model is that BMP9 and BMP10 maintain a quiescent endothelial state that is dependent on the level of ALK1/endoglin activation on endothelial cells. In accordance with this model, to explain the etiology of HHT we hypothesize that a deficient BMP9/BMP10/ALK1/endoglin pathway may lead to re-activation of angiogenesis or a greater sensitivity to an angiogenic stimulus. Resulting endothelial hyperproliferation and hypermigration may lead to vasodilatation and formation of arteriovenous malformation (AVM. HHT would thus result from a defect in the angiogenic balance. This review will focus on the emerging role played by BMP9 and BMP10 in the development of this disease and the therapeutic approaches that this opens.
Management of urban hydrologic processes using green infrastructure (GI) has largely focused on storm water management. Thus, design and implementation of GI usually rely on physical site characteristics and local rainfall patterns, and do not typically account for human or socia...
Full Text Available Nowadays, the high power consumption of data centers is the biggest challenge to making cloud computing greener. Many researchers are still seeking effective solutions to reduce or harvest the energy produced at data centers. To address this challenge, we propose a green cloud infrastructure which provides security and efficiency based on energy harvesting (EH-GC. The EH-GC is basically focused on harvesting the heat energy produced by data centers in the Infrastructure-as-a-Service (IaaS infrastructure. A pyroelectric material is used to generate the electric current from heat using the Olsen cycle. In order to achieve efficient green cloud computing, the architecture utilizes a genetic algorithm for proper virtual machine allocation, taking into consideration less Service Level Agreement (SLA violations. The architecture utilizes Multivariate Correlation Analysis (MCA correlation analysis based on a triangular map area generation to detect Denial of Service (DoS attacks in the data center layer of the IaaS. Finally, the experimental analysis is explained based on the energy parameter, which proves that our model is efficient and secure, and that it efficiently reuses the energy emitted from the data center.
Dunnett, N. [Univ. of Sheffield, Western Bank, Sheffield (United Kingdom). Dept. of Landscape
Sheffield, United Kingdom (UK) was the world centre for the steel and cutlery industries. However, those industries have been in decline and the city has been in the process of re-inventing itself over the past 20 years. Sheffield is now known as the UK's greenest city in terms of the amount of woodland, parkland and open spaces within its city limits. The city of Sheffield has also developed a unique partnership approach to promote green roof infrastructure as the most visible and high-profile signal of intent and symbol of low environmental impact building design and construction. This partnership involves Sheffield's Green Roof Forum, comprising the University of Sheffield's multi-disciplinary centre of excellence in green roof research; Sheffield City Council; Groundwork Sheffield, an urban economic and environmental regeneration agency; and city Architects and developers. This partnership meets six times a year to raise the profile of green roofs within the city and region, and to develop strategies to increase the uptake and implementation of green roof infrastructure in the region. This paper discussed the partnership, the Green Room Forum, accomplishments to date in promoting green roofs in the city, and the strategy for the Sheffield region to become a leader in green roof implementation and associated green technologies. The strategy is presented in two parts: consultation and research to identify the nature of market failure and devising methods to overcome that failure. The green roof strategy is being implemented through a program entitled Building Greener, Building Smarter and consists of four inter-linked strands. These strands were discussed in detail and included getting buy-in, demonstrating benefit, establishing the business case, and changing plans and practices. 3 tabs., 1 ref.
Full Text Available An important increase in flood risk levels is expected in future decades in many areas around the globe. In addition, the traditional approaches for flood management offer options with low sustainability. As a response, the use of non-traditional drainage measures, also called green infrastructures, has been increasingly suggested in the last years. One important reason for their increasing popularity has been the co-benefits that they offer to the environment. The development of an efficient planning for sustainable urban drainage systems is a complex process that needs the involvement of multiple stakeholders. Moreover, the measures to be adopted should be evaluated considering their potential to achieve multiple benefits related to human well-being, rather than just to flood risk management. In this work, we propose a framework for the selection of green infrastructures on the basis of a co-benefits analysis. The aim is to include the achievement of co-benefits and human well-being into decision-making for flood management, considering the stakeholders’ perceptions to define the most important benefits to be enhanced. The application of the framework presented here to a case study in Ayutthaya, Thailand, shows the importance of including different stakeholder’s opinions. In addition, it shows that decision makers should consider locally defined co-benefits as well as flood risk reduction when defining which green infrastructures to apply.
Di Pasquale, Elisa; Brivanlou, Ali H.
Bone morphogenetic protein 15 (BMP15) belongs to an unusual subgroup of the transforming growth factor β (TGFβ) superfamily of signaling ligands as it lacks a key cysteine residue in the mature region required for proper intermolecular dimerization. Naturally occurring BMP15 mutation leads to early ovarian failure in humans, and BMP15 has been shown to activate the Smad1/5/8 pathway in that context. Despite its important role in germ cell specification, the embryological function of BMP15 remains unknown. Surprisingly, we find that during early Xenopus embryogenesis BMP15 acts solely as an inhibitor of the Smad1/5/8 pathway and the Wnt pathway. BMP15 gain-of-function leads to embryos with secondary ectopic heads and to direct neural induction in intact explants. BMP15 inhibits BMP4-mediated epidermal induction in dissociated explants. BMP15 strongly inhibits BRE response induced by BMP4 and blocks phosphorylation and activation of Smad1/5/8 MH2-domain. Mechanistically, BMP15 protein specifically interacts with BMP4 protein, suggesting inhibition upstream of receptor binding. Loss-of-function experiments using morpholinos or a naturally occurring human BMP15 dominant-negative mutant (BMP15-Y235C) leads to embryos lacking head. BMP15-Y235C also eliminates the inhibitory activity of BMP15 on BRE (BMP-responsive element). Finally, we show that BMP15 inhibits the canonical branch of the Wnt pathway, upstream of β-catenin. We, thus, demonstrate that BMP15 is necessary and sufficient for the specification of dorso-anterior structures and highlight novel mechanisms of BMP15 function that strongly suggest a reinterpretation of its function in ovaries specially for ovarian failure. PMID:19553676
Managers of urban watersheds with excessive nutrient loads are more frequently turning to green infrastructure (GI) to manage their water quality impairments. The effectiveness of GI is dependent on a number of factors, including (1) the type and placement of GI within the waters...
Green infrastructure can be a cost-effective approach for reducing stormwater runoff and improving water quality as a result, but it could also bring co-benefits for air quality: less impervious surfaces and more vegetation can decrease the urban heat island effect, and also resu...
Michelle C. Kondo; Sarah C. Low; Jason Henning; Charles C. Branas
We investigated the health and safety effects of urban green stormwater infrastructure (GSI) installments. We conducted a difference-in-differences analysis of the effects of GSI installments on health (e.g., blood pressure, cholesterol and stress levels) and safety (e.g., felonies, nuisance and property crimes, narcotics crimes) outcomes from 2000 to 2012 in...
Full Text Available The main objective of the study was (1 to assess the level of negative impact of the road transport sector on the green infrastructure; (2 to compare the policy on green infrastructure with the actual direction of changes in transport systems; (3 to assess plans for transport development and some predictions on future impact. The research was carried out in the Poznan Metropolitan Area with the use of kernel density estimation (GIS. The analyses show that the key problem is the fragmentation of valuable natural areas and the routing of high traffic intensity roads through and nearby these areas which cause conflicts. The most negative transportation influence occurs in the agglomeration centre, where the quality of the environment is already low. At the same time existing land-use and transport strategies propose solutions neutralizing these negative impacts. Nevertheless current trends and especially new transport investment seem to negate official strategies and intensify the negative impacts on the green infrastructure.
Full Text Available While the Philadelphia Water Department (PWD is counting on Green Stormwater Infrastructure (GI as a key component of its long-term plan for reducing combined sewer overflows, many community stakeholders are also hoping that investment in greening can help meet other ancillary goals, collectively referred to as sustainable redevelopment. This study investigates the challenges associated with implementation of GI in Point Breeze, a residential neighborhood of South Philadelphia. The project team performed a detailed study of physical, social, legal, and economic conditions in the pilot neighborhood over the course of several years, culminating in the development of an agent-based model simulation of GI implementation. The model evaluates a whether PWD’s GI goals can be met in a timely manner, b what kinds of assumptions regarding participation would be needed under different theoretical GI policies, and c the extent to which GI could promote sustainable redevelopment. The model outcomes underscore the importance of private land in helping PWD achieve its GI goals in Point Breeze. Achieving a meaningful density of GI in the neighborhoods most in need of sustainable redevelopment may require new and creative strategies for GI implementation tailored for the types of land present in those particular communities.
Andersson, Erik; Barthel, Stephan; Borgström, Sara; Colding, Johan; Elmqvist, Thomas; Folke, Carl; Gren, Åsa
Within-city green infrastructure can offer opportunities and new contexts for people to become stewards of ecosystem services. We analyze cities as social-ecological systems, synthesize the literature, and provide examples from more than 15 years of research in the Stockholm urban region, Sweden. The social-ecological approach spans from investigating ecosystem properties to the social frameworks and personal values that drive and shape human interactions with nature. Key findings demonstrate that urban ecosystem services are generated by social-ecological systems and that local stewards are critically important. However, land-use planning and management seldom account for their role in the generation of urban ecosystem services. While the small scale patchwork of land uses in cities stimulates intense interactions across borders much focus is still on individual patches. The results highlight the importance and complexity of stewardship of urban biodiversity and ecosystem services and of the planning and governance of urban green infrastructure.
Jacqueline W.T. Lu; Megan Shane; Erika Svendsen; Lindsay Campbell; Cristiana Fragola; Marianne Krasny; Gina Lovasl; David Maddox; Simon McDonnell; P. Timon McPhearson; Franco Montalto; Andrew Newman; Ellen Pehek; Ruth A. Rae; Richard Stedman; Keith G. Tidball; Lynne Westphal; Tom Whitlow
MillionTreesNYC is a citywide, public-private initiative with an ambitious goal: to plant and care for one million new trees across New York City's five boroughs by 2017. The Spring 2009 workshop MillionTreesNYC, Green Infrastructure, and Urban Ecology: Building a Research Agenda brought together more than 100 researchers, practitioners and New York City...
Hegetschweiler, K. Tessa; de Vries, Sjerp; Arnberger, Arne
and supply factors together. The aim was to provide an overview of this highly interdisciplinary research, to describe how these linkages are being made and to identify which factors significantly influence dependent variables such as levels of use, activities or health and well-being benefits. Commonly used......Urban green infrastructure provides a number of cultural ecosystem services that are greatly appreciated by the public. In order to benefit from these services, actual contact with the respective ecosystem is often required. Furthermore, the type of services offered depend on the physical...... characteristics of the ecosystem. We conducted a review of publications dealing with demand or social factors such as user needs, preferences and values as well as spatially explicit supply or physical factors such as amount of green space, (bio)diversity, recreational infrastructure, etc. and linking demand...
Taşlı, P Neslihan; Aydın, Safa; Yalvaç, Mehmet Emir; Sahin, Fikrettin
Bone morphogenetic proteins (BMPs) initiate, promote, and maintain odontogenesis and osteogenesis. In this study, we studied the effect of bone morphogenic protein 2 (BMP 2) and bone morphogenic protein 7 (BMP 7) as differentiation inducers in tooth and bone regeneration. We compared the effect of BMP 2 and BMP 7 on odontogenic and osteogenic differentiation of human tooth germ stem cells (hTGSCs). Third molar-derived hTGSCs were characterized with mesenchymal stem cell surface markers by flow cytometry. BMP 2 and BMP 7 were transfected into hTGSCs and the cells were seeded onto six-well plates. One day after the transfection, hTGSCs were treated with odontogenic and osteogenic mediums for 14 days. For confirmation of odontogenic and osteogenic differentiation, mRNA levels of BMP2, BMP 7, collagen type 1 (COL1A), osteocalsin (OCN), and dentin sialophosphoprotein (DSPP) genes were measured by quantitative real-time PCR. In addition to this, immunocytochemistry was performed by odontogenic and osteogenic antibodies and mineralization obtained by von Kossa staining. Our results showed that the BMP 2 and BMP 7 both promoted odontogenic and osteogenic differentiation of hTGSCs. Data indicated that BMP 2 treatment and BMP 7 treatment induce odontogenic differentiation without affecting each other, whereas they induce osteogenic differentiation by triggering expression of each other. These findings provide a feasible tool for tooth and bone tissue engineering.
Green infrastructure at the parcel scale provides critical ecosystem goods and services when these services (such as flood mitigation) must be provided locally. Here we report on an approach that encourages suburban landowners to mitigate impervious surfaces on their properties t...
Intensifying the proportion of urban green infrastructure has been considered as one of the remedies for air pollution levels in cities, yet the impact of numerous vegetation types deployed in different built environments has to be fully synthesised and quantified. This review ex...
The Water Services Department (WSD) in Kansas City, Missouri (KCMO) has conducted extensive modeling and economic studies of its combined sewer system (CSS) over the last several years. A number of green infrastructure (GI) solutions were identified and constructed to reduce dis...
Full Text Available This paper investigates contemporary approaches defined by the policies, programs or standards that favor green infrastructure in urban planning for cooling urban environments with special reference to Serbian experiences. The research results reveal an increasing emphasis on the multifunctionality of green infrastructure as well the determination to the development of policies, guidelines and standards with the support of the overall community. Further, special importance is given to policies that promote ‘cool communities’ strategies resulting in the increase of vegetation-covered areas, what has contributed in adapting urban environments to the impacts of climate change. In addition, this research indicates the important role of local authorities and planners in Serbia in promoting planning policies and programs that take into consideration the role of green infrastructure in terms of improving climatic conditions, quality of life and reducing energy needed for cooling and heating. [Projekat Ministarstva nauke Republike Srbije, br. TR 36035: Spatial, ecological, energy, and social aspects of developing settlements and climate change - mutual impacts i br. 43007: The investigation of climate change and its impacts, climate change adaptation and mitigation
Pan, Haichun; Zhang, Honghao; Abraham, Ponnu; Komatsu, Yoshihiro; Lyons, Karen; Kaartinen, Vesa; Mishina, Yuji
Craniosynostosis is caused by premature fusion of one or more sutures in an infant skull, resulting in abnormal facial features. The molecular and cellular mechanisms by which genetic mutations cause craniosynostosis are incompletely characterized, and many of the causative genes for diverse types of syndromic craniosynostosis have not yet been identified. We previously demonstrated that augmentation of BMP signaling mediated by a constitutively active BMP type IA receptor (ca-BmpR1A) in neural crest cells (ca1A hereafter) causes craniosynostosis and superimposition of heterozygous null mutation of Bmpr1a rescues premature suture fusion (ca1A;1aH hereafter). In this study, we superimposed heterozygous null mutations of the other two BMP type I receptors, Bmpr1b and Acvr1 (ca1A;1bH and ca1A;AcH respectively hereafter) to further dissect involvement of BMP-Smad signaling. Unlike caA1;1aH, ca1A;1bH and ca1A;AcH did not restore the craniosynostosis phenotypes. In our in vivo study, Smad-dependent BMP signaling was decreased to normal levels in mut;1aH mice. However, BMP receptor-regulated Smads (R-Smads; pSmad1/5/9 hereafter) levels were comparable between ca1A, ca1A;1bH and ca1A;AcH mice, and elevated compared to control mice. Bmpr1a, Bmpr1b and Acvr1 null cells were used to examine potential mechanisms underlying the differences in ability of heterozygosity for Bmpr1a vs. Bmpr1b or Acvr1 to rescue the mut phenotype. pSmad1/5/9 level was undetectable in Bmpr1a homozygous null cells while pSmad1/5/9 levels did not decrease in Bmpr1b or Acvr1 homozygous null cells. Taken together, our study indicates that different levels of expression and subsequent activation of Smad signaling differentially contribute each BMP type I receptor to BMP-Smad signaling and craniofacial development. These results also suggest differential involvement of each type 1 receptor in pathogenesis of syndromic craniosynostoses. Copyright © 2017 Elsevier Inc. All rights reserved.
Levet, Sandrine; Ouarné, Marie; Ciais, Delphine; Coutton, Charles; Subileau, Mariela; Mallet, Christine; Ricard, Nicolas; Bidart, Marie; Debillon, Thierry; Faravelli, Francesca; Rooryck, Caroline; Feige, Jean-Jacques; Tillet, Emmanuelle; Bailly, Sabine
The transition to pulmonary respiration after birth requires rapid alterations in the structure of the mammalian cardiovascular system. One dramatic change that occurs is the closure of the ductus arteriosus (DA), an arterial connection in the fetus that directs blood flow away from the pulmonary circulation. Two members of the TGFβ family, bone morphogenetic protein 9 (BMP9) and BMP10, have been recently involved in postnatal angiogenesis, both being necessary for remodeling of newly formed microvascular beds. The aim of the present work was to study whether BMP9 and BMP10 could be involved in closure of the DA. We found that Bmp9 knockout in mice led to an imperfect closure of the DA. Further, addition of a neutralizing anti-BMP10 antibody at postnatal day 1 (P1) and P3 in these pups exacerbated the remodeling defect and led to a reopening of the DA at P4. Transmission electron microscopy images and immunofluorescence stainings suggested that this effect could be due to a defect in intimal cell differentiation from endothelial to mesenchymal cells, associated with a lack of extracellular matrix deposition within the center of the DA. This result was supported by the identification of the regulation by BMP9 and BMP10 of several genes known to be involved in this process. The involvement of these BMPs was further supported by human genomic data because we could define a critical region in chromosome 2 encoding eight genes including BMP10 that correlated with the presence of a patent DA. Together, these data establish roles for BMP9 and BMP10 in DA closure. PMID:26056270
Wang, Yafei; Bakker, Frank; Groot, de Rudolf; Wörtche, Heinrich; Leemans, Rik
This study analyzed how the variations of plant area index (PAI) and weather conditions alter the influence of urban green infrastructure (UGI) on microclimate. To observe how diverse UGIs affect the ambient microclimate through the seasons, microclimatic data were measured during the growing
Hegetschweiler, K.T.; Vries, de Sjerp; Arnberger, Arne; Bell, Simon; Brennan, Michael; Siter, Nathan; Olafsson, Anton Stahl; Voigt, Annette; Hunziker, Marcel
Urban green infrastructure provides a number of cultural ecosystem services that are greatly appreciated by the public. In order to benefit from these services, actual contact with the respective ecosystem is often required. Furthermore, the type of services offered depend on the physical
Pinho, Pedro; Correia, Otília; Lecoq, Miguel; Munzi, Silvana; Vasconcelos, Sasha; Gonçalves, Paula; Rebelo, Rui; Antunes, Cristina; Silva, Patrícia; Freitas, Catarina; Lopes, Nuno; Santos-Reis, Margarida; Branquinho, Cristina
Forested areas within cities host a large number of species, responsible for many ecosystem services in urban areas. The biodiversity in these areas is influenced by human disturbances such as atmospheric pollution and urban heat island effect. To ameliorate the effects of these factors, an increase in urban green areas is often considered sufficient. However, this approach assumes that all types of green cover have the same importance for species. Our aim was to show that not all forested green areas are equal in importance for species, but that based on a multi-taxa and functional diversity approach it is possible to value green infrastructure in urban environments. After evaluating the diversity of lichens, butterflies and other-arthropods, birds and mammals in 31 Mediterranean urban forests in south-west Europe (Almada, Portugal), bird and lichen functional groups responsive to urbanization were found. A community shift (tolerant species replacing sensitive ones) along the urbanization gradient was found, and this must be considered when using these groups as indicators of the effect of urbanization. Bird and lichen functional groups were then analyzed together with the characteristics of the forests and their surroundings. Our results showed that, contrary to previous assumptions, vegetation density and more importantly the amount of urban areas around the forest (matrix), are more important for biodiversity than forest quantity alone. This indicated that not all types of forested green areas have the same importance for biodiversity. An index of forest functional diversity was then calculated for all sampled forests of the area. This could help decision-makers to improve the management of urban green infrastructures with the goal of increasing functionality and ultimately ecosystem services in urban areas. Copyright © 2016 Elsevier Inc. All rights reserved.
Cameron, Ross W. F.; Blanuša, Tijana
Background Green infrastructure is a strategic network of green spaces designed to deliver ecosystem services to human communities. Green infrastructure is a convenient concept for urban policy makers, but the term is used too generically and with limited understanding of the relative values or benefits of different types of green space and how these complement one another. At a finer scale/more practical level, little consideration is given to the composition of the plant communities, yet this is what ultimately defines the extent of service provision. This paper calls for greater attention to be paid to urban plantings with respect to ecosystem service delivery and for plant science to engage more fully in identifying those plants that promote various services. Scope Many urban plantings are designed based on aesthetics alone, with limited thought on how plant choice/composition provides other ecosystem services. Research is beginning to demonstrate, however, that landscape plants provide a range of important services, such as helping mitigate floods and alleviating heat islands, but that not all species are equally effective. The paper reviews a number of important services and demonstrates how genotype choice radically affects service delivery. Conclusions Although research is in its infancy, data are being generated that relate plant traits to specific services, thereby helping identify genotypes that optimize service delivery. The urban environment, however, will become exceedingly bland if future planting is simply restricted to monocultures of a few ‘functional’ genotypes. Therefore, further information is required on how to design plant communities where the plants identified (1) provide more than a single benefit (multifunctionality), (B) complement each other in maximizing the range of benefits that can be delivered in one location, and (3) continue to maintain public acceptance through diversity. The identification/development of functional
Cameron, Ross W F; Blanuša, Tijana
Green infrastructure is a strategic network of green spaces designed to deliver ecosystem services to human communities. Green infrastructure is a convenient concept for urban policy makers, but the term is used too generically and with limited understanding of the relative values or benefits of different types of green space and how these complement one another. At a finer scale/more practical level, little consideration is given to the composition of the plant communities, yet this is what ultimately defines the extent of service provision. This paper calls for greater attention to be paid to urban plantings with respect to ecosystem service delivery and for plant science to engage more fully in identifying those plants that promote various services. Many urban plantings are designed based on aesthetics alone, with limited thought on how plant choice/composition provides other ecosystem services. Research is beginning to demonstrate, however, that landscape plants provide a range of important services, such as helping mitigate floods and alleviating heat islands, but that not all species are equally effective. The paper reviews a number of important services and demonstrates how genotype choice radically affects service delivery. Although research is in its infancy, data are being generated that relate plant traits to specific services, thereby helping identify genotypes that optimize service delivery. The urban environment, however, will become exceedingly bland if future planting is simply restricted to monocultures of a few 'functional' genotypes. Therefore, further information is required on how to design plant communities where the plants identified (1) provide more than a single benefit (multifunctionality), (B) complement each other in maximizing the range of benefits that can be delivered in one location, and (3) continue to maintain public acceptance through diversity. The identification/development of functional landscape plants is an exciting and
Wang, Ranran; Eckelman, Matthew J; Zimmerman, Julie B
A consequential life cycle assessment (LCA) is conducted to evaluate the trade-offs between water quality improvements and the incremental climate, resource, and economic costs of implementing green (bioretention basin, green roof, and permeable pavement) versus gray (municipal separate stormwater sewer systems, MS4) alternatives of stormwater infrastructure expansions against a baseline combined sewer system with combined sewer overflows in a typical Northeast US watershed for typical, dry, and wet years. Results show that bioretention basins can achieve water quality improvement goals (e.g., mitigating freshwater eutrophication) for the least climate and economic costs of 61 kg CO2 eq. and $98 per kg P eq. reduction, respectively. MS4 demonstrates the minimum life cycle fossil energy use of 42 kg oil eq. per kg P eq. reduction. When integrated with the expansion in stormwater infrastructure, implementation of advanced wastewater treatment processes can further reduce the impact of stormwater runoff on aquatic environment at a minimal environmental cost (77 kg CO2 eq. per kg P eq. reduction), which provides support and valuable insights for the further development of integrated management of stormwater and wastewater. The consideration of critical model parameters (i.e., precipitation intensity, land imperviousness, and infrastructure life expectancy) highlighted the importance and implications of varying local conditions and infrastructure characteristics on the costs and benefits of stormwater management. Of particular note is that the impact of MS4 on the local aquatic environment is highly dependent on local runoff quality indicating that a combined system of green infrastructure prior to MS4 potentially provides a more cost-effective improvement to local water quality.
The U.S. EPA is evaluating the effectiveness of green infrastructure (GI) stormwater best management practices (BMPs) on stream habitat at the small watershed (< HUC12) scale in New England. Predictive models for thermal regime and substrate characteristics (substrate size, % em...
Full Text Available As heart failure due to myocardial infarction remains a leading cause of morbidity worldwide, cell-based cardiac regenerative therapy using cardiac progenitor cells (CPCs could provide a potential treatment for the repair of injured myocardium. As adult CPCs may have limitations regarding tissue accessibility and proliferative ability, CPCs derived from embryonic stem cells (ESCs could serve as an unlimited source of cells with high proliferative ability. As one of the CPCs that can be derived from embryonic stem cells, Isl1 expressing cardiac progenitor cells (Isl1-CPCs may serve as a valuable source of cells for cardiac repair due to their high cardiac differentiation potential and authentic cardiac origin. In order to generate an unlimited number of Isl1-CPCs, we used a previously established an ESC line that allows for isolation of Isl1-CPCs by green fluorescent protein (GFP expression that is directed by the mef2c gene, specifically expressed in the Isl1 domain of the anterior heart field. To improve the efficiency of cardiac differentiation of Isl1-CPCs, we studied the role of Bmp4 in cardiogenesis of Isl1-CPCs. We show an inductive role of Bmp directly on cardiac progenitors and its enhancement on early cardiac differentiation of CPCs. Upon induction of Bmp4 to Isl1-CPCs during differentiation, the cTnT+ cardiomyocyte population was enhanced 2.8±0.4 fold for Bmp4 treated CPC cultures compared to that detected for vehicle treated cultures. Both Bmp4 treated and untreated cardiomyocytes exhibit proper electrophysiological and calcium signaling properties. In addition, we observed a significant increase in Tbx5 and Tbx20 expression in differentiation cultures treated with Bmp4 compared to the untreated control, suggesting a link between Bmp4 and Tbx genes which may contribute to the enhanced cardiac differentiation in Bmp4 treated cultures. Collectively these findings suggest a cardiomyogenic role for Bmp4 directly on a pure population of
Semeraro, Teodoro; Aretano, Roberta; Pomes, Alessandro
The concept of Green Infrastructure (GI) emphasises the quality as well as quantity of urban, peri-urban greens spaces and natural areas, their multifunctional role, and the importance of interconnections between habitats. If a Green Infrastructure is proactively planned, developed, and maintained it has the potential to guide urban development by providing a framework for economic growth and nature conservation. GI includes parks and reserves, sporting fields, riparian areas like stream and river banks, greenways and trails, community gardens, street trees, and nature conservation areas, as well as less conventional spaces such as green walls, green alleyways, and cemeteries. Today we have to face new challenges about increasing energy use, decreasing water resources, limited spaces and ecological preservation. This problem must be solved in a sustainable way using innovative GI that combine technology with landscape design by enhancing ecosystem services provision. The aim of this research is to evaluate and develop multifunctional role of GI in terms of biodiversity and ecosystem services’ enhancement by taking into account two case study in southern Italy: Constructed Treatment and photovoltaic energy plants. An effective way of tackling water resource problem is to use Constructed Treatment Wetlands (CTW) as low-cost alternative to conventional secondary or tertiary wastewater treatment. For this purpose, an annual monitoring of fauna and vegetation was carried out in order to identify species of national and international interest strongly related to the new habitats availability. Results have shown the ability of CTW in providing ancillary benefits, well beyond the primary aim of water purification, such as sustaining wildlife habitats and biodiversity at local and global scales, as well as its potential role in terms of recreational and educational opportunities. In the second case, we developed a GI project idea that proposes to evolve the photovoltaic
This paper outlines a life-cycle cost analysis comparing a green (rain gardens) and gray (tunnels) infrastructure combination to a gray-only option to control combined sewer overflow in the Turkey Creek Combined Sewer Overflow Basin, in Kansas City, MO. The plan area of this Bas...
Barlow, A J; Francis-West, P H
The facial primordia initially consist of buds of undifferentiated mesenchyme, which give rise to a variety of tissues including cartilage, muscle and nerve. These must be arranged in a precise spatial order for correct function. The signals that control facial outgrowth and patterning are largely unknown. The bone morphogenetic proteins Bmp-2 and Bmp-4 are expressed in discrete regions at the distal tips of the early facial primordia suggesting possible roles for BMP-2 and BMP-4 during chick facial development. We show that expression of Bmp-4 and Bmp-2 is correlated with the expression of Msx-1 and Msx-2 and that ectopic application of BMP-2 and BMP-4 can activate Msx-1 and Msx-2 gene expression in the developing facial primordia. We correlate this activation of gene expression with changes in skeletal development. For example, activation of Msx-1 gene expression across the distal tip of the mandibular primordium is associated with an extension of Fgf-4 expression in the epithelium and bifurcation of Meckel's cartilage. In the maxillary primordium, extension of the normal domain of Msx-1 gene expression is correlated with extended epithelial expression of shh and bifurcation of the palatine bone. We also show that application of BMP-2 can increase cell proliferation of the mandibular primordia. Our data suggest that BMP-2 and BMP-4 are part of a signalling cascade that controls outgrowth and patterning of the facial primordia.
Golden, Heather E; Hoghooghi, Nahal
Urbanizing environments alter the hydrological cycle by redirecting stream networks for stormwater and wastewater transmission and increasing impermeable surfaces. These changes thereby accelerate the runoff of water and its constituents following precipitation events, alter evapotranspiration processes, and indirectly modify surface precipitation patterns. Green infrastructure, or low-impact development (LID), can be used as a standalone practice or in concert with gray infrastructure (traditional stormwater management approaches) for cost-efficient, decentralized stormwater management. The growth in LID over the past several decades has resulted in a concomitant increase in research evaluating LID efficiency and effectiveness, but mostly at localized scales. There is a clear research need to quantify how LID practices affect water quantity (i.e., runoff and discharge) and quality at the scale of catchments. In this overview, we present the state of the science of LID research at the local scale, considerations for scaling this research to catchments, recent advances and findings in scaling the effects of LID practices on water quality and quantity at catchment scales, and the use of models as novel tools for these scaling efforts.
Full Text Available Across the world governments make decisions on climate change and environmental pollution saying that is the most important goal for the future of their states. Accumulation of environmental problems was done in decades of irrational and unplanned exploitation. Industrialization itself is not a bad thing for humanity , but how this is achieved can be detrimental to the future of global society. Environment reverses the conditions created for man in so many thousands of years: thus, economic life is becoming increasingly difficult through its activities. Plants and animals disappear land turns into deserts, people get sick. The present paper attempts to find solutions to a global, national and regional situation, referring to those types of infrastructure viable to produce clean energy in Romania. This paper argues the need of green energy and propose alternative and environmentally friendly cleaner solutions.
This webinar describes the use of VELMA, a spatially-distributed ecohydrological model, to identify green infrastructure (GI) best management practices for protecting water quality in intensively managed watersheds. The seminar will include a brief description of VELMA and an ex...
This document is a summary of the green infrastructure reports, journal articles, and conference proceedings published to date. This summary will be updated as more reports are completed. The Environmental Protection Agency’s Office of Research and Development has an ambitious ...
Stokes-Draut, J. R.; Taptich, M. N.; Horvath, A.
Cities throughout the U.S. are seeking efficient ways to manage stormwater for many reasons, including flood control, pollution management, water supply augmentation and to prepare for a changing climate. Traditionally, cities have relied primarily on gray infrastructure, namely sewers, storage and treatment facilities. In these systems, urban runoff, its volume increasing as impervious surfaces expand, is channeled to a wastewater plant where it is mixed with raw sewage prior to treatment or it is discharged, generally untreated, to local water bodies. These facilities are inflexible and expensive to build and maintain. Many systems are deteriorating and/or approaching, if not exceeding, their design capacity. Increasingly, more innovative approaches that integrate stormwater management into the natural environment and that make sense at both local and regional scales are sought. Identifying the best stormwater solution will require evaluating the life-cycle economic costs associated with these alternatives, including costs associated with construction, operation, and maintenance including regulatory and permitting costs, financing, as well as other indirect costs (e.g., avoided wastewater processing or system capacity expansion, increased property value) and non-economic co-benefits (i.e, aesthetics, habitat provision). Beyond conventional life-cycle costing, applying life-cycle assessment (LCA) will contribute to more holistic and sustainable decision-making. LCA can be used to quantitatively track energy use, greenhouse gas emissions, and other environmental effects associated with constructing, operating, and maintaining green and gray infrastructure, including supply chain contributions. We will present the current state of knowledge for implementing life-cycle costing and LCA into stormwater management decisions for green, gray and hybrid infrastructure.
Catalano De Sousa, M.; Erispaha, A.; Spatari, S.; Montalto, F.
Decentralized approaches to managing urban stormwater through use of green infrastructure (GI) often lead to system-wide efficiency gains within the urban watershed's energy supply system. These efficiencies lead to direct greenhouse gas (GHG) emissions savings, and also restore some ecosystem functions within the urban landscape. We developed a consequential life cycle assessment (LCA) model to estimate the life cycle energy, global warming potential (GWP), and payback times for each if GI were applied within a select neighborhood in New York City. We applied the SIMAPRO LCA software and the economic input-output LCA (EIO-LCA) tool developed by Carnegie Mellon University. The results showed that for a new intersection installation highlighted in this study a conventional infrastructure construction would emit and use approximately 3 times more for both CO2 and energy than a design using GI. Two GI benefits were analyzed with regards to retrofitting the existing intersection. The first was related to the savings in energy and CO2 at the Waste Water Treatment Plant via runoff reduction accrued from GI use. The second benefit was related to the avoided environmental costs associated with an additional new grey infrastructure installation needed to prevent CSO in case of no GI implementation. The first benefit indicated a high payback time for a GI installation in terms of CO2 and energy demand (80 and 90 years respectively) and suggest a slow energy and carbon recovery time. However, concerning to the second benefit, GI proved to be a sustainable alternative considering the high CO2 releases (429 MTE) and energy demand (5.5 TJ) associated with a grey infrastructure construction.
James F. Canning
Full Text Available Agricultural intensification has had the undesirable effect of degrading water quality throughout the United States. Nitrate pollution presents a difficult problem for rural and urban communities, and it contributes to the immense Gulf of Mexico Hypoxia Zone. Current U.S. policy prohibits regulation of agricultural runoff because it is a nonpoint source. The Raccoon River Watershed upstream of Des Moines, Iowa, USA has some of the highest nitrate levels in the nation, and the drinking water utility in Des Moines unsuccessfully pursued litigation against drainage districts in the watershed. We propose a cooperative solution between urban residents and upstream rural residents—namely, the installation of agricultural green infrastructure in the form of riparian buffers throughout the watershed enabled by the principles of water quality trading. We compare this distributed, green approach with a centralized, gray approach (i.e., building a new nitrate removal facility at the drinking water utility. Using terrain analysis, we determined that first-order streams are the most fitting location for riparian buffers. We estimate the buffer installation to cost between $155–$185 million; maintenance of the current nitrate removal facility will cost $72 million, while a new facility could cost up to $184 million. Riparian buffer installation offers more indirect, non-quantified benefits than maintaining or building new centralized, gray treatment (e.g., living-wage jobs and in-stream water quality improvement. Our analysis could act as a model for water quality trading and distributed agricultural green infrastructure in other communities facing similar water quality challenges.
Singh, Bijay; Jiang, Tao; Kim, You-Kyoung; Kang, Sang-Kee; Choi, Yun-Jaie; Cho, Chong-Su
Swine dysentery is a contagious mucohaemorrhagic colitis of pigs that is caused by anaerobic intestinal spirochaete Brachyspira hyodysenteriae. Recently, an outer membrane lipoprotein of B. hyodysenteriae (BmpB) has been identified, and the mice or pigs immunized with a recombinant BmpB generated antibodies recognizing the native BmpB of B. hyodysenteriae. In this study, we cloned, expressed and purified BmpB protein from E. coli and used it as a vaccine candidate for oral delivery. The BmpB was encapsulated into the pH-sensitive and thiolated Eudragit microspheres (TEMS). The sizes of the microspheres ranged from 5-20 μ. About 22-34% of BmpB were released from the BmpB-loaded TEMS within 24 h at stomach pH 2.0 whereas the release of BmpB from the BmpB-loaded TEMS was 35% in the first one hour and reached 81% within 24 h at intestinal pH 7.2. These data revealed that the BmpB could be protected in the harsh gastric condition. Mucoadhesive experiment in vitro showed that TEMS have high binding affinity with the mucin glycoproteins of porcine intestine. Finally, in vitro production of cytokines from immune cells treated with the BmpB-loaded TEMS suggested that the TEMS would be a promising approach for oral delivery of BmpB as vaccine candidate.
Nijhuis, S.; Jauslin, D.; De Vries, C.
Flowscapes explores infrastructure as a type of landscape and landscape as a type of infrastructure, and is focused on landscape architectonic design of transportation-, green- and water infrastructures. These landscape infrastructures are considered armatures for urban and rural development. With
Rai, A.; Minsker, B. S.
In this work we introduce a novel dataset GRID: GReen Infrastructure Detection Dataset and a framework for identifying urban green storm water infrastructure (GI) designs (wetlands/ponds, urban trees, and rain gardens/bioswales) from social media and satellite aerial images using computer vision and machine learning methods. Along with the hydrologic benefits of GI, such as reducing runoff volumes and urban heat islands, GI also provides important socio-economic benefits such as stress recovery and community cohesion. However, GI is installed by many different parties and cities typically do not know where GI is located, making study of its impacts or siting new GI difficult. We use object recognition learning methods (template matching, sliding window approach, and Random Hough Forest method) and supervised machine learning algorithms (e.g., support vector machines) as initial screening approaches to detect potential GI sites, which can then be investigated in more detail using on-site surveys. Training data were collected from GPS locations of Flickr and Instagram image postings and Amazon Mechanical Turk identification of each GI type. Sliding window method outperformed other methods and achieved an average F measure, which is combined metric for precision and recall performance measure of 0.78.
Expression of human bone morphogenetic protein (BMP-2 and BMP-4 genes in transgenic bovine fibroblasts Expressão dos genes bone morphogenetic protein (BMP-2 e BMP-4 em fibroblastos bovinos transgênicos
Full Text Available cDNAs dos genes bone morphogenetic protein-2 (BMP-2 e bone morphogenetic protein-4 (BMP-4 foram sintetizados a partir de RNA total extraído de tecidos ósseos de pacientes que apresentavam trauma facial (fraturas do maxilar entre o 7º e o 10º dia pós-trauma e clonados num vetor para expressão em células mamíferas, sob controle do promotor de citomegalovírus (CMV. Os vetores contendo os genes BMP-2 e o BMP-4 foram utilizados para a transfecção de fibroblastos bovinos. mRNAs foram indiretamente detectados por RT-PCR nas células transfectadas. As proteínas BMP-2 e BMP-4 foram detectadas mediante análises de Western blot. Os resultados demonstram a possibilidade de produção desses fatores de crescimento celular em fibroblastos bovinos. Essas células poderão ser utilizadas como fontes doadoras de material genético para a técnica de transferência nuclear na geração de animais transgênicos.
Tiwary, A.; Williams, I.D.; Heidrich, O.; Namdeo, A.; Bandaru, V.; Calfapietra, C.
This paper presents a performance evaluation framework for streetscape vegetation. A performance index (PI) is conceived using the following seven traits, specific to the street environments – Pollution Flux Potential (PFP), Carbon Sequestration Potential (CSP), Thermal Comfort Potential (TCP), Noise Attenuation Potential (NAP), Biomass Energy Potential (BEP), Environmental Stress Tolerance (EST) and Crown Projection Factor (CPF). Its application is demonstrated through a case study using fifteen street vegetation species from the UK, utilising a combination of direct field measurements and inventoried literature data. Our results indicate greater preference to small-to-medium size trees and evergreen shrubs over larger trees for streetscaping. The proposed PI approach can be potentially applied two-fold: one, for evaluation of the performance of the existing street vegetation, facilitating the prospects for further improving them through management strategies and better species selection; two, for planning new streetscapes and multi-functional biomass as part of extending the green urban infrastructure. - Highlights: • A performance evaluation framework for streetscape vegetation is presented. • Seven traits, relevant to street vegetation, are included in a performance index (PI). • The PI approach is applied to quantify and rank fifteen street vegetation species. • Medium size trees and evergreen shrubs are found more favourable for streetscapes. • The PI offers a metric for developing sustainable streetscape green infrastructure. - A performance index is developed and applied to fifteen vegetation species indicating greater preference to medium size trees and evergreen shrubs for streetscaping.
Johnson, T. E.; Butcher, J.; Sarkar, S.; Clark, C.
Climate change could significantly alter the occurrence and management of urban stormwater runoff quantity and quality. Responding to this challenge requires an improved understanding of potential changes together with the effectiveness of management responses for reducing impacts under range of potential future climatic conditions. Traditional gray stormwater infrastructure generally uses single-purpose, hard structures including detention basins and storm sewers to dispose of rainwater. Green infrastructure (GI) uses vegetation and soil to manage rainwater where it falls. GI has been gaining in popularity, and has been shown to provide a number of benefits for adapting to climate change including effects on stormwater quantity, quality and carbon and nutrient biogeochemical cycling. Uncertainty remains, however, due to limited understanding of GI performance in different hydroclimatic and urban settings, and in response to changes in climate. In this study we use simulation modeling to assess the impacts of climate change on both gray (wet ponds) and green infrastructure practices (green roofs, swales, bioretention) in different hydroclimatic and urban settings. Simulations were conducted using RHESSYs, a mechanistic, hydrologic and biogeochemical model, for 36 characteristic urban "archetypes" (AUSs) representing different development patterns and GI practices found in typical U.S. cities. Climate change scenarios are based on dynamically and temporally downscaled, mid-21st century climate model output from the North American Regional Climate Change Assessment Program (NARCCAP). Results suggest altered mass and energy inputs will cause changes in performance of these practices for water quantity, water quality, and carbon sequestration that vary across the country. Infrastructure design should take these potential changes into consideration.
Liao, Hongxing; Zhong, Zhixiong; Liu, Zhanliang; Li, Liangping; Ling, Zemin; Zou, Xuenong
The aim of the present study was to investigate the potential of bone mesenchymal stem cells (BMSCs) treated with a combination of vascular endothelial growth factor (VEGF) and bone morphogenetic protein-6 (BMP-6) genes for the treatment of avascular necrosis of the femoral head (ANFH). Rat BMSCs were isolated and purified using a density gradient centrifugation method. The purity and characteristics of the BMSCs were detected by cell surface antigens identification using flow cytometry. The experimental groups were administered with one of the following adeno-associated virus (AAV) vector constructs: AAV-green fluorescent protein (AAV-GFP), AAV-BMP-6, AAV-VEGF or AAV-VEGF-BMP-6. The expression of VEGF and BMP-6 was detected by reverse transcription-quantitative polymerase chain reaction, western blotting and ELISA assays. The effects of VEGF and BMP-6 on BMSCs were evaluated by angiogenic and osteogenic assays. The transfected BMSCs were combined with a biomimetic synthetic scaffold poly lactide-co-glycolide (PLAGA) and they were then subcutaneously implanted into nude mice. After four weeks, the implants were analyzed with histology and subsequent immunostaining to evaluate the effects of BMSCs on blood vessel and bone formation in vivo . In the AAV-VEGF-BMP-6 group, the expression levels of VEGF and BMP-6 were significantly increased and human umbilical vein endothelial cells tube formation was significantly enhanced compared with other groups. Capillaries and bone formation in the AAV-VEGF-BMP-6 group was significantly higher compared with the other groups. The results of the present study suggest that BMSCs expressing both VEGF and BMP-6 induce an increase in blood vessels and bone formation, which provides theoretical support for ANFH gene therapy.
Denjean, Benjamin; Altamirano, Mónica A; Graveline, Nina; Giordano, Raffaele; van der Keur, Peter; Moncoulon, David; Weinberg, Josh; Máñez Costa, María; Kozinc, Zdravko; Mulligan, Mark; Pengal, Polona; Matthews, John; van Cauwenbergh, Nora; López Gunn, Elena; Bresch, David N
This paper proposes a conceptual framework to systematize the use of Nature-based solutions (NBS) by integrating their resilience potential into Natural Assurance Scheme (NAS), focusing on insurance value as corner stone for both awareness-raising and valuation. As such one of its core goal is to align research and pilot projects with infrastructure development constraints and priorities. Under NAS, the integrated contribution of natural infrastructure to Disaster Risk Reduction is valued in the context of an identified growing need for climate robust infrastructure. The potential of NAS benefits and trade-off are explored by through the alternative lens of Disaster Resilience Enhancement (DRE). Such a system requires a joint effort of specific knowledge transfer from research groups and stakeholders to potential future NAS developers and investors. We therefore match the knowledge gaps with operational stages of the development of NAS from a project designer perspective. We start by highlighting the key role of the insurance industry in incentivizing and assessing disaster and slow onset resilience enhancement strategies. In parallel we place the public sector as potential kick-starters in DRE initiatives through the existing initiatives and constraints of infrastructure procurement. Under this perspective the paper explores the required alignment of Integrated Water resources planning and Public investment systems. Ultimately this will provide the possibility for both planners and investors to design no regret NBS and mixed Grey-Green infrastructures systems. As resources and constraints are widely different between infrastructure development contexts, the framework does not provide explicit methodological choices but presents current limits of knowledge and know-how. In conclusion the paper underlines the potential of NAS to ease the infrastructure gap in water globally by stressing the advantages of investment in the protection, enhancement and restoration of
Yao, Shaomian; Prpic, Veronica; Pan, Fenghui; Wise, Gary E.
The dental follicle appears to regulate both the alveolar bone resorption and bone formation needed for tooth eruption. Tumor necrosis factor-alpha ( TNF-α) gene expression is maximally upregulated at postnatal day 9 in the rat dental follicle of the 1st mandibular molar, a time that correlates with rapid bone growth at the base of the tooth crypt, as well as a minor burst of osteoclastogenesis. TNF-α expression is correlated with the expression of bone morphogenetic protein-2 (BMP-2), a molecule expressed in the dental follicle that can promote bone formation. Because BMP-2 signaling may be augmented by bone morphogenetic protein-3 (BMP-3), it was the objective of this study to determine 1) if the dental follicle expresses BMP-3 and 2) if TNF-α stimulates the dental follicle cells to express BMP-2 and BMP-3. Dental follicles were collected from different postnatal ages of rat pups. Dental follicle cells were incubated with TNF-α to study its dosage and time-course effects on gene expression of BMP-2 and BMP-3, as determined by real-time RT-PCR. Next, immunostaining was conducted to confirm if the protein was synthesized and ELISA of the conditioned medium was conducted to determine if BMP-2 was secreted. We found that BMP-3 expression is correlated with the expression of TNF-α in the dental follicle and TNF-α significantly increased BMP-2 and BMP-3 expression in vitro. Immunostaining and ELISA showed that BMP-2 and BMP-3 were synthesized and secreted. This study suggests that TNF-α can upregulate the expression of bone formation genes that may be needed for tooth eruption. PMID:20067418
Erika S. Svendsen
Full Text Available The MillionTreesNYC Subcommittee on Research and Evaluation was formed shortly following the 2007 launch of MillionTreesNYC, a citywide, public-private initiative with an ambitious goal: to plant and care for one million new trees across New York City’s five boroughs by 2017. Members of this committee are comprised of academics, government researchers and local practitioners with experience in the fields of natural resource management and community development.On March 5-6, 2010, over two hundred researchers and practitioners came together at The New School to showcase scientific innovation in the field of urban forestry and greening. The MillionTreesNYC, Green Infrastructure and Urban Ecology Research Symposium engaged professionals from a broad range of disciplines including sociology, planning, epidemiology, earth sciences, hydrology, forestry, ecology, and design who were uniquely positioned to discuss new ideas.
Phippard, D J; Weber-Hall, S J; Sharpe, P T; Naylor, M S; Jayatalake, H; Maas, R; Woo, I; Roberts-Clark, D; Francis-West, P H; Liu, Y H; Maxson, R; Hill, R E; Dale, T C
Expression of the Msx-1 and Msx-2 homeobox genes have been shown to be coordinately regulated with the Bmp-2 and Bmp-4 ligands in a variety of developing tissues. Here we report that transcripts from all four genes are developmentally regulated during both foetal and postnatal mammary gland development. The location and time-course of the Bmp and Msx expression point to a role for Msx and Bmp gene products in the control of epithelial-mesenchymal interactions. Expression of Msx-2, but not Msx-1, Bmp-2 or Bmp-4 was decreased following ovariectomy, while expression of the human Msx-2 homologue was regulated by 17beta-oestradiol in the MCF-7 breast cancer cell line. The regulation of Msx-2 expression by oestrogen raises the possibility that hormonal regulation of mammary development is mediated through the control of epithelial-mesenchymal interactions.
Full Text Available Podocyte injury is the first step in the progression of glomerulosclerosis. Previous studies have demonstrated the beneficial effect of bone morphogenetic protein 7 (Bmp7 in podocyte injury and the existence of native Bmp signaling in podocytes. Local activity of Bmp7 is controlled by cell-type specific Bmp antagonists, which inhibit the binding of Bmp7 to its receptors. Here we show that the product of Twisted gastrulation (Twsg1, a Bmp antagonist, is the central negative regulator of Bmp function in podocytes and that Twsg1 null mice are resistant to podocyte injury. Twsg1 was the most abundant Bmp antagonist in murine cultured podocytes. The administration of Bmp induced podocyte differentiation through Smad signaling, whereas the simultaneous administration of Twsg1 antagonized the effect. The administration of Bmp also inhibited podocyte proliferation, whereas simultaneous administration of Twsg1 antagonized the effect. Twsg1 was expressed in the glomerular parietal cells (PECs and distal nephron of the healthy kidney, and additionally in damaged glomerular cells in a murine model of podocyte injury. Twsg1 null mice exhibited milder hypoalbuminemia and hyperlipidemia, and milder histological changes while maintaining the expression of podocyte markers during podocyte injury model. Taken together, our results show that Twsg1 plays a critical role in the modulation of protective action of Bmp7 on podocytes, and that inhibition of Twsg1 is a promising means of development of novel treatment for podocyte injury.
Lee, Joong Gwang; Nietch, Christopher T.; Panguluri, Srinivas
Urban stormwater runoff quantity and quality are strongly dependent upon catchment properties. Models are used to simulate the runoff characteristics, but the output from a stormwater management model is dependent on how the catchment area is subdivided and represented as spatial elements. For green infrastructure modeling, we suggest a discretization method that distinguishes directly connected impervious area (DCIA) from the total impervious area (TIA). Pervious buffers, which receive runoff from upgradient impervious areas should also be identified as a separate subset of the entire pervious area (PA). This separation provides an improved model representation of the runoff process. With these criteria in mind, an approach to spatial discretization for projects using the US Environmental Protection Agency's Storm Water Management Model (SWMM) is demonstrated for the Shayler Crossing watershed (SHC), a well-monitored, residential suburban area occupying 100 ha, east of Cincinnati, Ohio. The model relies on a highly resolved spatial database of urban land cover, stormwater drainage features, and topography. To verify the spatial discretization approach, a hypothetical analysis was conducted. Six different representations of a common urbanscape that discharges runoff to a single storm inlet were evaluated with eight 24 h synthetic storms. This analysis allowed us to select a discretization scheme that balances complexity in model setup with presumed accuracy of the output with respect to the most complex discretization option considered. The balanced approach delineates directly and indirectly connected impervious areas (ICIA), buffering pervious area (BPA) receiving impervious runoff, and the other pervious area within a SWMM subcatchment. It performed well at the watershed scale with minimal calibration effort (Nash-Sutcliffe coefficient = 0.852; R2 = 0.871). The approach accommodates the distribution of runoff contributions from different spatial components and
Burke, Rebecca M; Norman, Timothy A; Haydar, Tarik F; Slack, Barbara E; Leeman, Susan E; Blusztajn, Jan Krzysztof; Mellott, Tiffany J
Bone morphogenetic protein 9 (BMP9) promotes the acquisition of the cholinergic phenotype in basal forebrain cholinergic neurons (BFCN) during development and protects these neurons from cholinergic dedifferentiation following axotomy when administered in vivo. A decline in BFCN function occurs in patients with Alzheimer's disease (AD) and contributes to the AD-associated memory deficits. We infused BMP9 intracerebroventricularly for 7 d in transgenic AD model mice expressing green fluorescent protein specifically in cholinergic neurons (APP.PS1/CHGFP) and in wild-type littermate controls (WT/CHGFP). We used 5-mo-old mice, an age when the AD transgenics display early amyloid deposition and few cholinergic defects, and 10-mo-old mice, by which time these mice exhibit established disease. BMP9 infusion reduced the number of Aβ42-positive amyloid plaques in the hippocampus and cerebral cortex of 5- and 10-mo-old APP.PS1/CHGFP mice and reversed the reductions in choline acetyltransferase protein levels in the hippocampus of 10-mo-old APP.PS1/CHGFP mice. The treatment increased cholinergic fiber density in the hippocampus of both WT/CHGFP and APP.PS1/CHGFP mice at both ages. BMP9 infusion also increased hippocampal levels of neurotrophin 3, insulin-like growth factor 1, and nerve growth factor and of the nerve growth factor receptors, tyrosine kinase receptor A and p75/NGFR, irrespective of the genotype of the mice. These data show that BMP9 administration is effective in reducing the Aβ42 amyloid plaque burden, reversing cholinergic neuron abnormalities, and generating a neurotrophic milieu for BFCN in a mouse model of AD and provide evidence that the BMP9-signaling pathway may constitute a therapeutic target for AD.
Yu, Ya Ping; Yin, Hai Wei; Kong, Fan Hua; Wang, Jing Jing; Xu, Wen Bin
Based on ArcGIS, Erdas, GuidosToolbox, Conefor and other software platforms, using morphological spatial pattern analysis (MSPA) and landscape connectivity analysis methods, this paper quantitatively analysed the scale effect, edge effect and distance effect of the Nanjing urban green infrastructure network pattern in 2013 by setting different pixel sizes (P) and edge widths in MSPA analysis, and setting different dispersal distance thresholds in landscape connectivity analysis. The results showed that the type of landscape acquired based on the MSPA had a clear scale effect and edge effect, and scale effects only slightly affected landscape types, whereas edge effects were more obvious. Different dispersal distances had a great impact on the landscape connectivity, 2 km or 2.5 km dispersal distance was a critical threshold for Nanjing. When selecting the pixel size 30 m of the input data and the edge wide 30 m used in the morphological model, we could get more detailed landscape information of Nanjing UGI network. Based on MSPA and landscape connectivity, analysis of the scale effect, edge effect, and distance effect on the landscape types of the urban green infrastructure (UGI) network was helpful for selecting the appropriate size, edge width, and dispersal distance when developing these networks, and for better understanding the spatial pattern of UGI networks and the effects of scale and distance on the ecology of a UGI network. This would facilitate a more scientifically valid set of design parameters for UGI network spatiotemporal pattern analysis. The results of this study provided an important reference for Nanjing UGI networks and a basis for the analysis of the spatial and temporal patterns of medium-scale UGI landscape networks in other regions.
Ke, Yuanyuan; Yu, Yan; Tong, Yan
Selecting urban ecological patches is of great significance for constructing urban green infrastructure network, protecting urban biodiversity and ecological environment. With the support of GIS technology, a criterion for selecting sources of patches was developed according to existing planning. Then ecological source patches of terrestrial organism, aquatic and amphibious organism were selected in Wuhan city. To increase the connectivity of the ecological patches and achieve greater ecological protection benefits, the green infrastructure networks in Wuhan city were constructed with the minimum path analysis method. Finally, the characteristics of ecological source patches were analyzed with landscape metrics, and ecological protection importance degree of ecological source patches were evaluated comprehensively. The results showed that there were 23 important ecological source patches in Wuhan city, among which Sushan Temple Forest Patch, Lu Lake and Shangshe Lake Wetland Patch were the most important in all kinds of patches for ecological protection. This study can provide a scientific basis for the preservation of urban ecological space, the delineation of natural conservation areas and the protection of biological diversity.
Full Text Available Planning of ecosystem services provided by the Urban Green Infrastructure (UGI is a key issue for urban sustainability. Planning strategies driven by the second law of thermodynamics (SLT are innovative approaches to sustainability but they are still in seminal phase. In this article, a coupled review of SLT within spatial planning is accomplished looking at the main applications in urban green infrastructure (UGI planning. The work has supported the definition of a preliminary low-entropy UGI planning strategy (Pelorosso, Gobattoni, & Leone, 2017 but it also aims to contribute to the improvement and/or development of even more solid planning strategies based on SLT. In particular, a systemic review of UGI planning and thermodynamics has been carried out to identify all the occurrences to date in the scientific literature. Secondly, a scoping review of SLT-related concepts of exergy, entropy and urban metabolism is presented in order to investigate the main applications of, and gaps in, urban spatial planning. Results indicate that UGI and ecosystem service planning based on SLT is a relatively new field of research. Moreover, some general indications are derived for the development of spatial UGI planning strategies based on SLT.
Xu, Haishun; Chen, Liang; Zhao, Bing; Zhang, Qiuzhuo; Cai, Yongli
Urban underlying surface has been greatly changed with rapid urbanization, considered to be one of the major causes for the destruction of urban natural hydrological processes. This has imposed a huge challenge for stormwater management in cities. There has been a shift from gray water management to green stormwater management thinking. The green stormwater infrastructure (GSI) is regarded as an effective and cost-efficient stormwater management eco-landscape approach. China's GSI practice and the development of its theoretical framework are still in the initial stage. This paper presents an innovative framework for stormwater management, integrating green stormwater infrastructure and landscape security patterns on a regional scale based on an urban master plan. The core concept of green stormwater infrastructure eco-planning is to form an interconnected GSI network (i.e., stormwater management landscape security pattern) which consists of the location, portion, size, layout, and structure of GSI so as to efficiently safeguard natural hydrological processes. Shanghai Lingang New City, a satellite new town of Shanghai, China was selected as a case study for GSI studies. Simulation analyses of hydrological processes were carried out to identify the critical significant landscape nodes in the highpriority watersheds for stormwater management. GSI should be planned and implemented in these identified landscape nodes. The comprehensive stormwater management landscape security pattern of Shanghai Lingang New City is designed with consideration of flood control, stormwater control, runoff reduction, water quality protection, and rainwater utilization objectives which could provide guidelines for smart growth and sustainable development of this city.
The Automated Geospatial Watershed Assessment (AGWA) Urban tool provides a step-by-step process to model subdivisions using the KINEROS2 model, with and without Green Infrastructure (GI) practices. AGWA utilizes the Kinematic Runoff and Erosion (KINEROS2) model, an event driven, ...
Work carried out during this master’s thesis is about urban greening and its close integration with district energy systems. Urban greening is the fact to develop green infrastructures (parks, street trees, ...) instead of grey infrastructures (buildings, roads, ...) in cities. Despite that the actual economic value of green infrastructure is less appreciated at first glance and very difficult to valorize, urban greening has many undeniable advantages such as reducing pollution and heat islan...
Gordon, B. L.; Ajami, N.; Quesnel, K.
Aging infrastructure, population growth, and urbanization are demanding new approaches to management of all components of the urban water cycle, including stormwater. Traditionally, urban stormwater infrastructure was designed to capture and convey rainfall-induced runoff out of a city through a network of curbs, gutters, drains, and pipes, also known as grey infrastructure. These systems were planned with a single-purpose and designed under the assumption of hydrologic stationarity, a notion that no longer holds true in the face of a changing climate. One solution gaining momentum around the world is green infrastructure (GI). Beyond stormwater quality improvement and quantity reduction (or technical benefits), GI solutions offer many environmental, economic, and social benefits. Yet many practical barriers have prevented the widespread adoption of these systems worldwide. At the center of these challenges is the inability of stakeholders to know how to monitor, measure, and assess the multi-sector performance of GI systems. Traditional grey infrastructure projects require different monitoring strategies than natural systems; there are no overarching policies on how to best design GI monitoring and evaluation systems and measure performance. Previous studies have attempted to quantify the performance of GI, mostly using one evaluation method on a specific case study. We use a case study approach to address these knowledge gaps and develop a conceptual model of how to evaluate the performance of GI through the lens of financing. First, we examined many different case studies of successfully implemented GI around the world. Then we narrowed in on 10 exemplary case studies. For each case studies, we determined what performance method the project developer used such as LCA, TBL, Low Impact Design Assessment (LIDA) and others. Then, we determined which performance metrics were used to determine success and what data was needed to calculate those metrics. Finally, we
Full Text Available During development, bone morphogenetic proteins (BMPs exert important functions in several tissues by regulating signaling for cell differentiation and migration. In vivo the extracellular matrix (ECM not only provides a support for adherent cells, but also presents a reservoir of growth factors (GFs. Several constituents of the ECM provide adhesive cues, which serve as binding sites for cell transmembrane receptors, such as integrins, which convey adhesion-mediated signaling to the intracellular compartment. Integrins do not function alone but rather crosstalk and cooperate with other receptors, such as GF receptors, in regulating cell responses to extracellular signals. To this, we present here the immobilization of BMP-2 onto cellular fibronectin (cFN, a key protein of the ECM, to investigate their impact on GF-mediated signaling and migration.Following biotinylation, BMP-2 was linked to biotinylated cFN using NeutrAvidin (NA as cross-linker. Characterization with QCM-D and ELISA confirmed the efficient immobilization of BMP-2 on cFN over a period of 24 h.To validate the bioactivity of matrix-immobilized BMP-2 (iBMP-2 we investigated short- and long-term responses of C2C12 myoblasts in comparison to soluble BMP-2 (sBMP-2 or in absence of GFs. Similarly to sBMP-2, iBMP-2 triggered Smad 1/5 phosphorylation and translocation into the nucleus corresponding to the activation of BMP-mediated Smad-dependent pathway. Additionally, successful suppression of myotube formation was observed after six days.We next implemented this approach to fabricate cFN micro patterned stripes by soft lithography. These stripes only allowed cell-surface interaction on the pattern due to passivation of the surface in between, thus serving as platform for studies on directed cell migration. During a 10 h-period, cells showed an increased migratory activity upon BMP-2 exposure.Thus, this versatile tool retains the GF's bioactivity and allows the presentation of ECM
Zhang, Han; Klausen, Christian; Zhu, Hua; Chang, Hsun-Ming; Leung, Peter C K
Adequate production of progesterone by the corpus luteum is critical to the successful establishment of pregnancy. In animal models, bone morphogenetic protein (BMP) 4 and BMP7 have been shown to suppress either basal or gonadotropin-induced progesterone production, depending on the species examined. However, the effects of BMP4 and BMP7 on progesterone production in human granulosa cells are unknown. In the present study, we used immortalized (SVOG) and primary human granulosa-lutein cells to investigate the effects of BMP4 and BMP7 on steroidogenic acute regulatory protein (StAR) expression and progesterone production and to examine the underlying molecular mechanism. Treatment of primary and immortalized human granulosa cells with recombinant BMP4 or BMP7 decreased StAR expression and progesterone accumulation. In SVOG cells, the suppressive effects of BMP4 and BMP7 on StAR expression were blocked by pretreatment with inhibitors of activin receptor-like kinase (ALK)2/3/6 (dorsomorphin) or ALK2/3 (DMH1) but not ALK4/5/7 (SB-431542). Moreover, small interfering RNA-mediated depletion of ALK3, but not ALK2 or ALK6, reversed the effects of BMP4 and BMP7 on StAR expression. Likewise, BMP4- and BMP7-induced phosphorylation of SMAD 1/5/8 was reversed by treatment with DMH1 or small interfering RNA targeting ALK3. Knockdown of SMAD4, the essential common SMAD for BMP/TGF-β signaling, abolished the effects of BMP4 and BMP7 on StAR expression. Our results suggest that BMP4 and BMP7 down-regulate StAR and progesterone production via ALK3 and SMAD1/5/8-SMAD4 signaling in human granulosa-lutein cells.
Full Text Available China’s green investment needs up to 2020 are ¥1.7 trillion–2.9 trillion CNY ($274 billion–468 billion USD per year. Estimates of financing requirements are provided for multiple sectors, including sustainable energy, infrastructure (including for environmental protection, environmental remediation, industrial pollution control, energy and water efficiency, and green products. The context to China’s green financing is discussed, covering urbanization, climate change, interactions between infrastructure sectors, and the transformation of industry. Much of the infrastructure financing will occur in cities, with a focus on equity, environmental protection, and quality of life under the National New-Type Urbanization Plan (2014–2020. China has implemented many successful policies in the building sector, but there is still considerable scope for improvement in the energy efficiency of Chinese buildings. China is currently pursuing low-carbon growth strategies that are consistent with its overall environmental and quality-of-life objectives. Beyond 2020, China’s future as an ecologically balanced civilization will rest on the implementation of a central infrastructure policy: China 2050 High Renewable Energy Penetration Scenario and Roadmap Study. As exemplified by the Circular Economy Development Strategy and Near-Term Action Plan, an essential part of China’s green industrial transformation involves engineering systems that conserve materials, thereby reducing or even eliminating wastes. To better understand changes to China’s economy under its green transformation and to unlock large potential sources of finance, it is necessary to undertake a fuller examination of all of China’s infrastructure sectors, particularly freight rail infrastructure and ports. Large investments are required to clean up a legacy of environmental contamination of soil and groundwater and to reduce industrial pollution. Transformation of the power sector
Zinski, Joseph; Bu, Ye; Wang, Xu; Dou, Wei; Umulis, David; Mullins, Mary C
A morphogen gradient of Bone Morphogenetic Protein (BMP) signaling patterns the dorsoventral embryonic axis of vertebrates and invertebrates. The prevailing view in vertebrates for BMP gradient formation is through a counter-gradient of BMP antagonists, often along with ligand shuttling to generate peak signaling levels. To delineate the mechanism in zebrafish, we precisely quantified the BMP activity gradient in wild-type and mutant embryos and combined these data with a mathematical model-based computational screen to test hypotheses for gradient formation. Our analysis ruled out a BMP shuttling mechanism and a bmp transcriptionally-informed gradient mechanism. Surprisingly, rather than supporting a counter-gradient mechanism, our analyses support a fourth model, a source-sink mechanism, which relies on a restricted BMP antagonist distribution acting as a sink that drives BMP flux dorsally and gradient formation. We measured Bmp2 diffusion and found that it supports the source-sink model, suggesting a new mechanism to shape BMP gradients during development.
Tóthmérész, Béla; Mitchley, Jonathan; Jongepierová, Ivana; Baasch, Annett; Fajmon, Karel; Kirmer, Anita; Prach, Karel; Řehounková, Klára; Tischew, Sabine; Twiston-Davies, Grace; Dutoit, Thierry; Buisson, Elise; Jeunatre, Renaud; Valkó, Orsolya; Deák, Balázs; Török, Péter
Sustaining the human well-being and the quality of life, it is essential to develop and support green infrastructure (strategically planned network of natural and semi-natural areas with other environmental features designed and managed to deliver a wide range of ecosystem services). For developing and sustaining green infrastructure the conservation and restoration of biodiversity in natural and traditionally managed habitats is essential. Species-rich landscapes in Europe have been maintained over centuries by various kinds of low-intensity use. Recently, they suffered by losses in extent and diversity due to land degradation by intensification or abandonment. Conservation of landscape-scale biodiversity requires the maintenance of species-rich habitats and the restoration of lost grasslands. We are focusing on landscape-level restoration studies including multiple sites in wide geographical scale (including Czech Republic, France, Germany, Hungary, and UK). In a European-wide perspective we aimed at to address four specific questions: (i) What were the aims and objectives of landscape-scale restoration? (ii) What results have been achieved? (iii) What are the costs of large-scale restoration? (iv) What policy tools are available for the restoration of landscape-scale biodiversity? We conclude that landscape-level restoration offers exciting new opportunities to reconnect long-disrupted ecological processes and to restore landscape connectivity. Generally, these measures enable to enhance the biodiversity at the landscape scale. The development of policy tools to achieve restoration at the landscape scale are essential for the achievement of the ambitious targets of the Convention on Biological Diversity and the European Biodiversity Strategy for ecosystem restoration.
Nishio, Kensuke; Ozawa, Yasumasa; Ito, Hisanori; Kifune, Takashi; Narita, Tatsuya; Iinuma, Toshimitsu; Gionhaku, Nobuhito; Asano, Masatake
Bone morphogenetic proteins (BMPs) are members of the transforming growth factor-β (TGF-β) superfamily. Recently, BMP7 has been demonstrated to be produced by salivary glands and contribute to embryonic branching in mice. The BMP7 in saliva is thought to be delivered to the oral cavity and is expected to contact with stratified squamous epithelial cells which line the surface of oral mucosa. In this study, we attempted to investigate the effects of BMP7 on oral epithelial cells. The expression of BMP receptors was examined by reverse transcriptase-polymerase chain reaction (RT-PCR). OSCCs were stimulated with human recombinant BMP7 (hrBMP7) and the phosphorylation status of Smad1/5/8 was examined by western blotting. For microarray analysis, Ca9-22 cells were stimulated with 100 ng/mL of hrBMP7 and total RNA was extracted and subjected to real-time PCR. The 5'-untranslated region (5'-UTR) of IL-17 F gene was cloned to pGL4-basic vector and used for luciferase assay. Ca9-22 cells were pre-incubated with DM3189, a specific inhibitor of Smad1/5/8, for inhibition assay. All isoforms of type I and type II BMP receptors were expressed in both Ca9-22 and HSC3 cells and BMP7 stimulation resulted in the phosphorylation of Smad1/5/8 in both cell lines. The microarray analysis revealed the induction of interleukin-17 F (IL-17 F), netrin G2 (NTNG2) and hyaluronan synthase 1 (HAS1). Luciferase assay using the 5'-UTR of the IL-17 F gene revealed transcriptional regulation. Induced IL-17 F production was further confirmed at the protein level by ELISA. Smad1/5/8 inhibitor pretreatment decreased IL-17 F expression levels in the cells.
Full Text Available Bone morphogenetic proteins (BMPs regulate various biological processes, mostly mediated by cells of mesenchymal origin. However, the roles of BMPs in epithelial cells are poorly understood. Here, we demonstrate that, in polarized epithelial cells, BMP signals are transmitted from BMP receptor complexes exclusively localized at the basolateral surface of the cell membrane. In addition, basolateral stimulation with BMP increased expression of components of tight junctions and enhanced the transepithelial resistance (TER, counteracting reduction of TER by treatment with TGF-β or an anti-tumor drug. We conclude that BMPs maintain epithelial polarity via intracellular signaling from basolaterally localized BMP receptors.
Beck, Stayce E; Carethers, John M
Bone morphogenetic protein (BMP), a member of the transforming growth factor beta family, classically utilizes the SMAD signaling pathway for its growth suppressive effects,and loss of this signaling cascade may accelerate cell growth. In the colon cancer predisposition syndrome Juvenile Polyposis, as well as in the late progression stages of nonsyndromic colorectal cancers, SMAD4 function is typically abrogated. Here, we utilized the SMAD4-null SW480 colon cancer cell line to examine BMPs effect on a potential target gene, PTEN, and how its expression might be regulated. Initial treatment of the SMAD4-null cells with BMP resulted in mild growth suppression, but with prolonged exposure to BMP, the cells become growth stimulatory, which coincided with observed decreases in transcription and translation of PTEN, and with corresponding increases in phospho-AKT protein levels. BMP-induced PTEN suppression was mediated via the RAS/ERK pathway, as pharmacologic inhibition of RAS/ERK, or interference with protein function in the cytosol by DN-RAS prevented BMP-induced growth promotion and changes in PTEN levels, as did treatment with noggin, a BMP ligand inhibitor. Thus, BMP downregulates PTEN via RAS/ERK in a SMAD4-null environment that contributes to cell growth, and constitutes a SMAD4-independent but BMP-responsive signaling pathway.
Knockaert, Marie; Sapkota, Gopal; Alarcón, Claudio; Massagué, Joan; Brivanlou, Ali H.
Smad transcription factors are key signal transducers for the TGF-β/bone morphogenetic protein (BMP) family of cytokines and morphogens. C-terminal serine phosphorylation by TGF-β and BMP membrane receptors drives Smads into the nucleus as transcriptional regulators. Dephosphorylation and recycling of activated Smads is an integral part of this process, which is critical for agonist sensing by the cell. However, the nuclear phosphatases involved have remained unknown. Here we provide functional, biochemical, and embryological evidence identifying the SCP (small C-terminal domain phosphatase) family of nuclear phosphatases as mediators of Smad1 dephosphorylation in the BMP signaling pathway in vertebrates. Xenopus SCP2/Os4 inhibits BMP activity in the presumptive ectoderm and leads to neuralization. In Xenopus embryos, SCP2/Os4 and human SCP1, 2, and 3 cause selective dephosphorylation of Smad1 compared with Smad2, inhibiting BMP- and Smad1-dependent transcription and leading to the induction of the secondary dorsal axis. In human cells, RNAi-mediated depletion of SCP1 and SCP2 increases the extent and duration of Smad1 phosphorylation in response to BMP, the transcriptional action of Smad1, and the strength of endogenous BMP gene responses. The present identification of the SCP family as Smad C-terminal phosphatases sheds light on the events that attenuate Smad signaling and reveals unexpected links to the essential phosphatases that control RNA polymerase II in eukaryotes. PMID:16882717
Ian P M Tomlinson
Full Text Available Genome-wide association studies (GWAS have identified 14 tagging single nucleotide polymorphisms (tagSNPs that are associated with the risk of colorectal cancer (CRC, and several of these tagSNPs are near bone morphogenetic protein (BMP pathway loci. The penalty of multiple testing implicit in GWAS increases the attraction of complementary approaches for disease gene discovery, including candidate gene- or pathway-based analyses. The strongest candidate loci for additional predisposition SNPs are arguably those already known both to have functional relevance and to be involved in disease risk. To investigate this proposition, we searched for novel CRC susceptibility variants close to the BMP pathway genes GREM1 (15q13.3, BMP4 (14q22.2, and BMP2 (20p12.3 using sample sets totalling 24,910 CRC cases and 26,275 controls. We identified new, independent CRC predisposition SNPs close to BMP4 (rs1957636, P = 3.93×10(-10 and BMP2 (rs4813802, P = 4.65×10(-11. Near GREM1, we found using fine-mapping that the previously-identified association between tagSNP rs4779584 and CRC actually resulted from two independent signals represented by rs16969681 (P = 5.33×10(-8 and rs11632715 (P = 2.30×10(-10. As low-penetrance predisposition variants become harder to identify-owing to small effect sizes and/or low risk allele frequencies-approaches based on informed candidate gene selection may become increasingly attractive. Our data emphasise that genetic fine-mapping studies can deconvolute associations that have arisen owing to independent correlation of a tagSNP with more than one functional SNP, thus explaining some of the apparently missing heritability of common diseases.
This is a presentation on the basics of green roof technology. The presentation highlights some of the recent ORD research projects on green roofs and provides insight for the end user as to the benefits for green roof technology. It provides links to currently available EPA rep...
Vierikko, Kati; Elands, Birgit; Niemelä, Jari; Andersson, Erik; Buijs, Arjen; Fischer, Leonie Katharina; Haase, Dagmar; Kabisch, Nadja; Kowarik, Ingo; Luz, Ana Catarina; Olafsson Stahl, Anton; Száraz, Luca; van der Jagt, Sander; Konijnendijk van den Bosch, Cecil
Traditionally, biocultural diversity (BCD) has been researched in non-western and indigenous societies. Recently, it has also been applied in urbanized and industrialized societies, in particular for the planning and management of urban green infrastructure (UGI). Diversity in human and biological
The United States Environmental Protection Agency evaluated the performance of a hybrid green-gray infrastructure pilot project installed into the Marlborough Neighborhood by the Kansas City Water Services Department. Kansas City installed 135 vegetated SCMs, 24,290 square feet o...
Spatari, Sabrina; Yu Ziwen; Montalto, Franco A.
Low Impact Development (LID) is part of a new paradigm in urban water management that aims to decentralize water storage and movement functions within urban watersheds. LID strategies can restore ecosystem functions and reduce runoff loadings to municipal water pollution control facilities (WPCF). This research examines the avoided energy and greenhouse gas (GHG) emissions of select LID strategies using life cycle assessment (LCA) and a stochastic urban watershed model. We estimate annual energy savings and avoided GHG emissions of 7.3 GJ and 0.4 metric tons, respectively, for a LID strategy implemented in a neighborhood in New York City. Annual savings are small compared to the energy and GHG intensity of the LID materials, resulting in slow environmental payback times. This preliminary analysis suggests that if implemented throughout an urban watershed, LID strategies may have important energy cost savings to WPCF, and can make progress towards reducing their carbon footprint. - Highlights: → LCA methods can identify environmental tradeoffs for urban low impact development. → Energy and GHG payback time is sensitive to LID construction material choice. → LCA of LID upscaled from street to watershed level is expected to be nonlinear. - The benefits of low impact development and green infrastructure in cities can be modeled using life cycle assessment to understand and guide decisions for meeting sustainability goals.
Lloyd Clare M
Full Text Available Abstract Background Airway remodelling is thought to be under the control of a complex group of molecules belonging to the Transforming Growth Factor (TGF-superfamily. The Bone Morphogenetic Proteins (BMPs belong to this family and have been shown to regulate fibrosis in kidney and liver diseases. However, the role of BMPs in lung remodelling remains unclear. BMPs may regulate tissue remodelling in asthma by controlling TGF-β-induced profibrotic functions in lung fibroblasts. Methods Cell cultures were exposed to TGF-β1 alone or in the presence of BMP-4 or BMP-7; control cultures were exposed to medium only. Cell proliferation was assessed by quantification of the incorporation of [3H]-thymidine. The expression of the mRNA encoding collagen type I and IV, tenascin C and fibronectin in normal human lung fibroblasts (NHLF was determined by real-time quantitative PCR and the main results were confirmed by ELISA. Cell differentiation was determined by the analysis of the expression of α-smooth muscle actin (α-SMA by western blot and immunohistochemistry. The effect on matrix metalloproteinase (MMP activity was assessed by zymography. Results We have demonstrated TGF-β1 induced upregulation of mRNAs encoding the extracellular matrix proteins, tenascin C, fibronectin and collagen type I and IV when compared to unstimulated NHLF, and confirmed these results at the protein level. BMP-4, but not BMP-7, reduced TGF-β1-induced extracellular matrix protein production. TGF-β1 induced an increase in the activity of the pro-form of MMP-2 which was inhibited by BMP-7 but not BMP-4. Both BMP-4 and BMP-7 downregulated TGF-β1-induced MMP-13 release compared to untreated and TGF-β1-treated cells. TGF-β1 also induced a myofibroblast-like transformation which was partially inhibited by BMP-7 but not BMP-4. Conclusions Our study suggests that some regulatory properties of BMP-7 may be tissue or cell type specific and unveil a potential regulatory role for
Yang Yang; Theodore A. Endreny; David J. Nowak
Impervious land cover was the choice for many urban development projects in order to accelerate runoff and reduce the depth and duration of local flooding, however this led to increases in downstream runoff characterized by large, flashy peak flows. Urban ecosystem restoration now involves slowing down urban runoff to restore local hydrology with green infrastructure,...
Gonzalez-Duque, Jose Antonio; Panagopoulos, Thomas
Modern cities have to reconcile the needs of the citizens for green areas considering the evolutionary trends of the city, especially in terms of growth and the required transformation in modern times. The present study attempts to analyze and evaluate the amount and distribution of the existing urban green space and the requirements of those green areas by the public. The green infrastructure of the city of Faro was evaluated with three methods: landscape assessment using modules, spatial as...
Full Text Available Endoglin (ENG/CD105 is an essential endothelial cell co-receptor of the transforming growth factor β (TGF-β superfamily, mutated in hereditary hemorrhagic telangiectasia type 1 (HHT1 and involved in tumor angiogenesis and preeclampsia. Here, we present crystal structures of the ectodomain of human ENG and its complex with the ligand bone morphogenetic protein 9 (BMP9. BMP9 interacts with a hydrophobic surface of the N-terminal orphan domain of ENG, which adopts a new duplicated fold generated by circular permutation. The interface involves residues mutated in HHT1 and overlaps with the epitope of tumor-suppressing anti-ENG monoclonal TRC105. The structure of the C-terminal zona pellucida module suggests how two copies of ENG embrace homodimeric BMP9, whose binding is compatible with ligand recognition by type I but not type II receptors. These findings shed light on the molecular basis of the BMP signaling cascade, with implications for future therapeutic interventions in this fundamental pathway.
Sansalone, John; Raje, Saurabh; Kertesz, Ruben; Maccarone, Kerrilynn; Seltzer, Karl; Siminari, Michele; Simms, Peter; Wood, Brandon
The built environs alter hydrology and water resource chemistry. Florida is subject to nutrient criteria and is promulgating “no-net-load-increase” criteria for runoff and constituents (nutrients and particulate matter, PM). With such criteria, green infrastructure, hydrologic restoration, indirect reuse and source control are potential design solutions. The study simulates runoff and constituent load control through urban source area re-design to provide long-term “no-net-load-increases”. A long-term continuous simulation of pre- and post-development response for an existing surface parking facility is quantified. Retrofits include a biofiltration area reactor (BAR) for hydrologic and denitrification control. A linear infiltration reactor (LIR) of cementitious permeable pavement (CPP) provides infiltration, adsorption and filtration. Pavement cleaning provided source control. Simulation of climate and source area data indicates re-design achieves “no-net-load-increases” at lower costs compared to standard construction. The retrofit system yields lower cost per nutrient load treated compared to Best Management Practices (BMPs). -- Continuous simulation of climate and site data demonstrate that urban re-design using green infrastructure can provide long-term “no-net-load-increases” at a lower costs compared to BMPs
van Heijster, Peter; Hardway, Heather; Kaper, Tasso J; Bradham, Cynthia A
Bone morphogen proteins (BMPs) are distributed along a dorsal-ventral (DV) gradient in many developing embryos. The spatial distribution of this signaling ligand is critical for correct DV axis specification. In various species, BMP expression is spatially localized, and BMP gradient formation relies on BMP transport, which in turn requires interactions with the extracellular proteins Short gastrulation/Chordin (Chd) and Twisted gastrulation (Tsg). These binding interactions promote BMP movement and concomitantly inhibit BMP signaling. The protease Tolloid (Tld) cleaves Chd, which releases BMP from the complex and permits it to bind the BMP receptor and signal. In sea urchin embryos, BMP is produced in the ventral ectoderm, but signals in the dorsal ectoderm. The transport of BMP from the ventral ectoderm to the dorsal ectoderm in sea urchin embryos is not understood. Therefore, using information from a series of experiments, we adapt the mathematical model of Mizutani et al. (2005) and embed it as the reaction part of a one-dimensional reaction-diffusion model. We use it to study aspects of this transport process in sea urchin embryos. We demonstrate that the receptor-bound BMP concentration exhibits dorsally centered peaks of the same type as those observed experimentally when the ternary transport complex (Chd-Tsg-BMP) forms relatively quickly and BMP receptor binding is relatively slow. Similarly, dorsally centered peaks are created when the diffusivities of BMP, Chd, and Chd-Tsg are relatively low and that of Chd-Tsg-BMP is relatively high, and the model dynamics also suggest that Tld is a principal regulator of the system. At the end of this paper, we briefly compare the observed dynamics in the sea urchin model to a version that applies to the fly embryo, and we find that the same conditions can account for BMP transport in the two types of embryos only if Tld levels are reduced in sea urchin compared to fly. Copyright © 2014 Elsevier Ltd. All rights
Anna L Javier
Full Text Available Cellular responses to Bmp ligands are regulated at multiple levels, both extracellularly and intracellularly. Therefore, the presence of these growth factors is not an accurate indicator of Bmp signaling activity. While a common approach to detect Bmp signaling activity is to determine the presence of phosphorylated forms of Smad1, 5 and 8 by immunostaining, this approach is time consuming and not quantitative. In order to provide a simpler readout system to examine the presence of Bmp signaling in developing animals, we developed BRE-gal mouse embryonic stem cells and a transgenic mouse line that specifically respond to Bmp ligand stimulation. Our reporter identifies specific transcriptional responses that are mediated by Smad1 and Smad4 with the Schnurri transcription factor complex binding to a conserved Bmp-Responsive Element (BRE, originally identified among Drosophila, Xenopus and human Bmp targets. Our BRE-gal mES cells specifically respond to Bmp ligands at concentrations as low as 5 ng/ml; and BRE-gal reporter mice, derived from the BRE-gal mES cells, show dynamic activity in many cellular sites, including extraembryonic structures and mammary glands, thereby making this a useful scientific tool.
Full Text Available Osteoblasts are bone-forming cells that differentiate from mesenchymal stem cells. Differentiation processes are coordinately and dynamically controlled in the mesenchymal cells by specific signal transduction pathways. Bone morphogenetic proteins (BMPs, members of the TGF-β superfamily, induce not only bone formation in vivo, but also osteoblast differentiation of mesenchymal cells in vitro. BMP signals are transduced from plasma membrane receptors to the nucleus through both Smad-dependent and -independent pathways, and are regulated by many extracellular and intercellular proteins that interact with BMPs or components of BMP signaling pathways. To understand the molecular mechanisms underlying the role of BMPs in osteoblast differentiation, it is important to elucidate the BMP signaling transduction pathways that are active during osteoblast differentiation. In this review, we summarize the BMP signaling pathways that are known to function in osteoblast development. We also describe our recent findings regarding the molecular mechanisms underlying the cross-talk between BMP/Smad and NF-κB pathways in osteoblast differentiation.
Liu, Yaoze; Theller, Lawrence O; Pijanowski, Bryan C; Engel, Bernard A
The adverse impacts of urbanization and climate change on hydrology and water quality can be mitigated by applying green infrastructure practices. In this study, the impacts of land use change and climate change on hydrology and water quality in the 153.2 km(2) Trail Creek watershed located in northwest Indiana were estimated using the Long-Term Hydrologic Impact Assessment-Low Impact Development 2.1 (L-THIA-LID 2.1) model for the following environmental concerns: runoff volume, Total Suspended Solids (TSS), Total Phosphorous (TP), Total Kjeldahl Nitrogen (TKN), and Nitrate+Nitrite (NOx). Using a recent 2001 land use map and 2050 land use forecasts, we found that land use change resulted in increased runoff volume and pollutant loads (8.0% to 17.9% increase). Climate change reduced runoff and nonpoint source pollutant loads (5.6% to 10.2% reduction). The 2050 forecasted land use with current rainfall resulted in the largest runoff volume and pollutant loads. The optimal selection and placement of green infrastructure practices using L-THIA-LID 2.1 model were conducted. Costs of applying green infrastructure were estimated using the L-THIA-LID 2.1 model considering construction, maintenance, and opportunity costs. To attain the same runoff volume and pollutant loads as in 2001 land uses for 2050 land uses, the runoff volume, TSS, TP, TKN, and NOx for 2050 needed to be reduced by 10.8%, 14.4%, 13.1%, 15.2%, and 9.0%, respectively. The corresponding annual costs of implementing green infrastructure to achieve the goals were $2.1, $0.8, $1.6, $1.9, and $0.8 million, respectively. Annual costs of reducing 2050 runoff volume/pollutant loads were estimated, and results show green infrastructure annual cost greatly increased for larger reductions in runoff volume and pollutant loads. During optimization, the most cost-efficient green infrastructure practices were selected and implementation levels increased for greater reductions of runoff and nonpoint source pollutants
Babovic, Filip; Mijic, Ana; Madani, Kaveh
Urban areas around the world are growing in size and importance; however, cities experience elevated risks of pluvial flooding due to the prevalence of impermeable land surfaces within them. Urban planners and engineers encounter a great deal of uncertainty when planning adaptations to these flood risks, due to the interaction of multiple factors such as climate change and land use change. This leads to conditions of deep uncertainty. Blue-Green (BG) solutions utilise natural vegetation and processes to absorb and retain runoff while providing a host of other social, economic and environmental services. When utilised in conjunction with Decision Making under Deep Uncertainty (DMDU) methodologies, BG infrastructure provides a flexible and adaptable method of "no-regret" adaptation; resulting in a practical, economically efficient, and socially acceptable solution for flood risk mitigation. This work presents the methodology for analysing the impact of BG infrastructure in the context of the Adaptation Tipping Points approach to protect against pluvial flood risk in an iterative manner. An economic analysis of the adaptation pathways is also conducted in order to better inform decision-makers on the benefits and costs of the adaptation options presented. The methodology was applied to a case study in the Cranbrook Catchment in the North East of London. Our results show that BG infrastructure performs better under conditions of uncertainty than traditional grey infrastructure.
Xie, Xiaohua; Liu, Chao; Zhang, Hua; Jani, Priyam H; Lu, Yongbo; Wang, Xiaofang; Zhang, Bin; Qin, Chunlin
Amelogenesis Imperfecta (AI) can be caused by the deficiencies of enamel matrix proteins, molecules responsible for the transportation and secretion of enamel matrix components, and proteases processing enamel matrix proteins. In the present study, we discovered the double deletion of bone morphogenetic protein 2 (Bmp2) and bone morphogenetic protein 4 (Bmp4) in the dental epithelium by K14-cre resulted in hypoplastic enamel and reduced density in X-ray radiography as well as shortened enamel rods under scanning electron microscopy. Such enamel phenotype was consistent with the diagnosis of hypoplastic amelogenesis imperfecta. Histological and molecular analyses revealed that the removal of matrix proteins in the mutant enamel was drastically delayed, which was coincided with the greatly reduced expression of matrix metalloproteinase 20 (MMP20) and kallikrein 4 (KLK4). Although the expression of multiple enamel matrix proteins was down-regulated in the mutant ameloblasts, the cleavage of ameloblastin was drastically impaired. Therefore, we attributed the AI primarily to the reduction of MMP20 and KLK4. Further investigation found that BMP/Smad4 signaling pathway was down-regulated in the K14-cre;Bmp2(f/f);Bmp4(f/f)ameloblasts, suggesting that the reduced MMP20 and KLK4 expression may be due to the attenuated epithelial BMP/Smad4 signaling.
Engström, Rebecka; Destouni, Georgia; Howells, Mark
Green Roofs have the potential to provide multiple services in cities. Besides acting as carbon sinks, providing noise reduction and decreasing air pollution - without requiring any additional "land-use" in a city (only roof-use), green roofs have a quantifiable potential to reduce direct and indirect energy and water use. They enhance the insulating capacity of a conventional residential roof and thereby decrease both cooling demands in summer and heating demands in winter. The former is further mitigated by the cooling effect of evapotranspiration from the roofs In New York City green roofs are additionally a valuable component of reducing "combined sewer overflows", as these roofs can retain storm water. This can improve water quality in the city's rivers as well as decrease the total volume of water treated in the city's wastewater treatment plants, thereby indirectly reduce energy demands. The impacts of green roofs on NYC's water-energy nexus has been initially studied (Engström et. al, forthcoming). The present study expands that work to more comprehensively investigate the potential of this type of nature-based solution in a dense city. By employing Geographical Information Systems analysis, the roof top area of New York City is analysed and roof space suitable for green roofs of varying types (ranging from extensive to intensive) are mapped and quantified. The total green roof area is then connected with estimates of potential water-energy benefits (and costs) of each type of green roof. The results indicate where green roofs can be beneficially installed throughout the city, and quantifies the related impacts on both water and energy use. These outputs can provide policy makers with valuable support when facing investment decisions in green infrastructure, in a city where there is great interest for these types of nature-based solutions.
Baptist, Matilda; Panagabko, Candace; Nickels, Jonathan D; Katsaras, John; Atkinson, Jeffrey
Previous work revealed that α-tocopherol transfer protein (α-TTP) co-localizes with bis(monoacylglycero)phosphate (BMP) in late endosomes. BMP is a lipid unique to late endosomes and is believed to induce membrane curvature and support the multivesicular nature of this organelle. We examined the effect of BMP on α-TTP binding to membranes using dual polarization interferometry and vesicle-binding assay. α-TTP binding to membranes is increased by the curvature-inducing lipid BMP. α-TTP binds to membranes with greater affinity when they contain the 2,2'-BMP versus 3,1'-BMP isomers.
Nijhuis, S.; Jauslin, D.T.; Van der Hoeven, F.D.
Social, cultural and technological developments of our society are demanding a fundamental review of the planning and design of its landscapes and infrastructures, in particular in relation to environmental issues and sustainability. Transportation, green and water infrastructures are important
Wang, Yafei; Bakker, Frank; de Groot, Rudolf; Wörtche, Heinrich; Leemans, Rik
This study analyzed how the variations of plant area index (PAI) and weather conditions alter the influence of urban green infrastructure (UGI) on microclimate. To observe how diverse UGIs affect the ambient microclimate through the seasons, microclimatic data were measured during the growing season at five sites in a local urban area in The Netherlands. Site A was located in an open space; sites B, C, and D were covered by different types and configurations of green infrastructure (grove, a single deciduous tree, and street trees, respectively); and site E was adjacent to buildings to study the effects of their façades on microclimate. Hemispherical photography and globe thermometers were used to quantify PAI and thermal comfort at both shaded and unshaded locations. The results showed that groves with high tree density (site B) have the strongest effect on microclimate conditions. Monthly variations in the differences of mean radiant temperature (∆Tmrt) between shaded and unshaded areas followed the same pattern as the PAI. Linear regression showed a significant positive correlation between PAI and ∆Tmrt. The difference of daily average air temperature (∆T a ) between shaded and unshaded areas was also positively correlated to PAI, but with a slope coefficient below the measurement accuracy (±0.5 °C). This study showed that weather conditions can significantly impact the effectiveness of UGI in regulating microclimate. The results of this study can support the development of appropriate UGI measures to enhance thermal comfort in urban areas.
Despite the increasing use of urban stormwater green infrastructure (SGI), including detention ponds and rain gardens, few studies have quantified the cumulative effects of multiple SGI projects on hydrology and water quality at the watershed scale. To assess the effects of SGI, Baltimore County, MD, Montgomery County, MD, and Washington, DC, were selected based on the availability of data on SGI, water quality, and stream flow. The watershed scale impact of SGI was evaluated by assessing how increased spatial density of SGI correlates with stream hydrology and nitrogen exports over space and time. The most common SGI types were detention ponds (58%), followed by marshes (12%), sand filters (9%), wet ponds (7%), infiltration trenches (4%), and rain gardens (2%). When controlling for watersheds size and percent impervious surface cover, watersheds with greater amounts of SGI (>10% SGI) have 44% lower peak runoff, 26% less frequent runoff events, and 26% less variable runoff than watersheds with lower SGI. Watersheds with more SGI also show 44% less NO3− and 48% less total nitrogen exports compared to watersheds with minimal SGI. There was no significant reduction in combined sewer overflows in watersheds with greater SGI. Based on specific SGI types, infiltration trenches (R2 = 0.35) showed the strongest correlation with hydrologic metrics, likely due to their ability to attenuate flow, while bioretention (R2 = 0.19) and wet ponds (R2 = 0.12) showed stronger
Abdelwahid, E; Rice, D; Pelliniemi, L J; Jokinen, E
The bone morphogenetic proteins BMP-2 and BMP-4 and the homeobox gene MSX-2 are required for normal development of many embryonic tissues. To elucidate their possible roles during the remodeling of the tubular heart into a fully septated four-chambered heart, we have localized the mRNA of Bmp-2, Bmp-4, Msx-2 and apoptotic cells in the developing mouse heart from embryonic day (E)11 to E17. mRNA was localized by in situ hybridization, and apoptotic cells by TUNEL (TDT-mediated dUTP-biotin nick end-labeling) as well as by transmission electron microscopy. By analyzing adjacent serial sections, we demonstrated that the expression of Msx-2 and Bmp-2 strikingly overlapped in the atrioventricular canal myocardium, in the atrioventricular junctional myocardium, and in the maturing myocardium of the atrioventricular valves. Bmp-4 was expressed in the outflow tract myocardium and in the endocardial cushion of the outflow tract ridges from E12 to E14. Msx-2 appeared in the mesenchyme of the atrioventricular endocardial cushion from E11 to E14, while Bmp-2 and Bmp-4 were detected between E11 and E14. Apoptotic cells were also detected in the mesenchyme of the endocardial cushion between E12 and E14. Our results suggest that BMP-2 and MSX-2 are tightly linked to the formation of the atrioventricular junction and valves and that BMP-4 is involved in the development of the outflow tract myocardium and of the endocardial cushion. In addition, BMP-2, BMP-4 and MSX-2 and apoptosis seem to be associated with differentiation of the endocardial cushion.
Tiwary, Abhishek; Kumar, Prashant
This paper evaluates the role of urban green infrastructure (GI) in maintaining integrity of built-space. The latter is considered as a lateral ecosystem function, worth including in future assessments of integrated ecosystem services. The basic tenet is that integrated green-grey infrastructures (GGIs) would have three influences on built-spaces: (i) reduced wind withering from flow deviation; (ii) reduced material corrosion/degeneration from pollution removal; and (iii) act as a biophysical buffer in altering the micro-climate. A case study is presented, combining the features of computational fluid dynamics (CFD) in micro-environmental modelling with the emerging science on interactions of GGIs. The coupled seasonal dynamics of the above three effects are assessed for two building materials (limestone and steel) using the following three scenarios: (i) business as usual (BAU), (ii) summer (REGEN-S), and (iii) winter (REGEN-W). Apparently, integrated ecosystem service from green-grey interaction, as scoped in this paper, has strong seasonal dependence. Compared to BAU our results suggest that REGEN-S leads to slight increment in limestone recession (<10%), mainly from exacerbation in ozone damage, while large reduction in steel recession (up to 37%) is observed. The selection of vegetation species, especially their bVOC emission potential and seasonal foliage profile, appears to play a vital role in determining the impact GI has on the integrity of the neighbouring built-up environment. Copyright © 2014 Elsevier B.V. All rights reserved.
Maes, Joachim; Barbosa, Ana; Baranzelli, Claudia; Zulian, Grazia; Batista E Silva, Filipe; Vandecasteele, Ine; Hiederer, Roland; Liquete, Camino; Paracchini, Maria Luisa; Mubareka, Sarah; Jacobs-Crisioni, Chris; Castillo, Carolina Perpiña; Lavalle, Carlo
Green infrastructure (GI), a network of nature, semi-natural areas and green space, delivers essential ecosystem services which underpin human well-being and quality of life. Maintaining ecosystem services through the development of GI is therefore increasingly recognized by policies as a strategy to cope with potentially changing conditions in the future. This paper assessed how current trends of land-use change have an impact on the aggregated provision of eight ecosystem services at the regional scale of the European Union, measured by the Total Ecosystem Services Index (TESI8). Moreover, the paper reports how further implementation of GI across Europe can help maintain ecosystem services at baseline levels. Current demographic, economic and agricultural trends, which affect land use, were derived from the so called Reference Scenario. This scenario is established by the European Commission to assess the impact of energy and climate policy up to 2050. Under the Reference Scenario, economic growth, coupled with the total population, stimulates increasing urban and industrial expansion. TESI8 is expected to decrease across Europe between 0 and 5 % by 2020 and between 10 and 15 % by 2050 relative to the base year 2010. Based on regression analysis, we estimated that every additional percent increase of the proportion of artificial land needs to be compensated with an increase of 2.2 % of land that qualifies as green infrastructure in order to maintain ecosystem services at 2010 levels.
The US EPA is developing assessment tools to evaluate the effectiveness of green infrastructure (GI) applied in stormwater best management practices (BMPs) at the small watershed (HUC12 or finer) scale. Based on analysis of historical monitoring data using boosted regression tre...
Darner, R.; Shuster, W.
Expansion of the urban environment can alter the landscape and creates challenges for how cities deal with energy and water. Large volumes of stormwater in areas that have combined septic and stormwater systems present on challenge. Managing the water as near to the source as possible by creates an environment that allows more infiltration and evapotranspiration. Stormwater control measures (SCM) associated with this type of development, often called green infrastructure, include rain gardens, pervious or porous pavements, bioswales, green or blue roofs, and others. In this presentation, we examine the hydrology of green infrastructure in urban sewersheds in Cleveland and Columbus, OH. We present the need for data throughout the water cycle and challenges to collecting field data at a small scale (single rain garden instrumented to measure inflows, outflow, weather, soil moisture, and groundwater levels) and at a macro scale (a project including low-cost rain gardens, highly engineered rain gardens, groundwater wells, weather stations, soil moisture, and combined sewer flow monitoring). Results will include quantifying the effectiveness of SCMs in intercepting stormwater for different precipitation event sizes. Small scale deployment analysis will demonstrate the role of active adaptive management in the ongoing optimization over multiple years of data collection.
Zakin, Lise; Reversade, Bruno; Kuroda, Hiroki; Lyons, Karen M; De Robertis, Eddy M
Sirenomelia or mermaid-like phenotype is one of the principal human congenital malformations that can be traced back to the stage of gastrulation. Sirenomelia is characterized by the fusion of the two hindlimbs into a single one. In the mouse, sirens have been observed in crosses between specific strains and as the consequence of mutations that increase retinoic acid levels. We report that the loss of bone morphogenetic protein 7 (Bmp7) in combination with a half dose or complete loss of twisted gastrulation (Tsg) causes sirenomelia in the mouse. Tsg is a Bmp- and chordin-binding protein that has multiple effects on Bmp metabolism in the extracellular space; Bmp7 is one of many Bmps and is shown here to bind to Tsg. In Xenopus, co-injection of Tsg and Bmp7 morpholino oligonucleotides (MO) has a synergistic effect, greatly inhibiting formation of ventral mesoderm and ventral fin tissue. In the mouse, molecular marker studies indicate that the sirenomelia phenotype is associated with a defect in the formation of ventroposterior mesoderm. These experiments demonstrate that dorsoventral patterning of the mouse posterior mesoderm is regulated by Bmp signaling, as is the case in other vertebrates. Sirens result from a fusion of the hindlimb buds caused by a defect in the formation of ventral mesoderm.
Stantzou, Amalia; Schirwis, Elija; Swist, Sandra; Alonso-Martin, Sonia; Polydorou, Ioanna; Zarrouki, Faouzi; Mouisel, Etienne; Beley, Cyriaque; Julien, Anaïs; Le Grand, Fabien; Garcia, Luis; Colnot, Céline; Birchmeier, Carmen; Braun, Thomas; Schuelke, Markus; Relaix, Frédéric; Amthor, Helge
Postnatal growth of skeletal muscle largely depends on the expansion and differentiation of resident stem cells, the so-called satellite cells. Here, we demonstrate that postnatal satellite cells express components of the bone morphogenetic protein (BMP) signaling machinery. Overexpression of noggin in postnatal mice (to antagonize BMP ligands), satellite cell-specific knockout of Alk3 (the gene encoding the BMP transmembrane receptor) or overexpression of inhibitory SMAD6 decreased satellite cell proliferation and accretion during myofiber growth, and ultimately retarded muscle growth. Moreover, reduced BMP signaling diminished the adult satellite cell pool. Abrogation of BMP signaling in satellite cell-derived primary myoblasts strongly diminished cell proliferation and upregulated the expression of cell cycle inhibitors p21 and p57 In conclusion, these results show that BMP signaling defines postnatal muscle development by regulating satellite cell-dependent myofiber growth and the generation of the adult muscle stem cell pool. © 2017. Published by The Company of Biologists Ltd.
Nijhuis, S.; Jauslin, D.T.; Van der Hoeven, F.D.
Social, cultural and technological developments of our society are demanding a fundamental review of the planning and design of its landscapes and infrastructures, in particular in relation to environmental issues and sustainability. Transportation, green and water infrastructures are important agents that facilitate processes that shape the built environment and its contemporary landscapes. With movement and flows at the core, these landscape infrastructures facilitate aesthetic, functional,...
Kee, Hae Jin; Cho, Soo-Na; Kim, Gwi Ran; Choi, Sin Young; Ryu, Yuhee; Kim, In Kyeom; Hong, Young Joon; Park, Hyung Wook; Ahn, Youngkeun; Cho, Jeong Gwan; Park, Jong Chun; Jeong, Myung Ho
Vascular calcification is associated with increased risk of morbidity and mortality in patients with cardiovascular diseases, chronic kidney diseases, and diabetes. Gallic acid, a natural compound found in gallnut and green tea, is known to be antifungal, antioxidant, and anticancer. Here we investigated the effect of gallic acid on vascular smooth muscle cell (VSMC) calcification and the underlying mechanism. Gallic acid inhibited inorganic phosphate-induced osteoblast differentiation markers as well as calcification phenotypes (as determined by calcium deposition, Alizarin Red, and Von Kossa staining). Knockdown of BMP2 or Noggin blocked phosphate-induced calcification. Gallic acid suppressed phosphorylation of Smad1/5/8 protein induced by inorganic phosphate. Taken together, we suggest that gallic acid acts as a novel therapeutic agent of vascular calcification by mediating BMP2-Smad1/5/8 signaling pathway. Copyright © 2014 Elsevier Inc. All rights reserved.
Mitrofan, Claudia-Gabriela; Appleby, Sarah L; Nash, Gerard B; Mallat, Ziad; Chilvers, Edwin R; Upton, Paul D; Morrell, Nicholas W
Bone morphogenetic proteins 9 and 10 (BMP9/BMP10) are circulating cytokines with important roles in endothelial homeostasis. The aim of this study was to investigate the roles of BMP9 and BMP10 in mediating monocyte-endothelial interactions using an in vitro flow adhesion assay. Herein, we report that whereas BMP9/BMP10 alone had no effect on monocyte recruitment, at higher concentrations both cytokines synergized with tumor necrosis factor-α (TNFα) to increase recruitment to the vascular endothelium. The BMP9/BMP10-mediated increase in monocyte recruitment in the presence of TNFα was associated with up-regulated expression levels of E-selectin, vascular cell adhesion molecule (VCAM-1), and intercellular adhesion molecule 1 (ICAM-1) on endothelial cells. Using siRNAs to type I and II BMP receptors and the signaling intermediaries (Smads), we demonstrated a key role for ALK2 in the BMP9/BMP10-induced surface expression of E-selectin, and both ALK1 and ALK2 in the up-regulation of VCAM-1 and ICAM-1. The type II receptors, BMPR-II and ACTR-IIA were both required for this response, as was Smad1/5. The up-regulation of cell surface adhesion molecules by BMP9/10 in the presence of TNFα was inhibited by LDN193189, which inhibits ALK2 but not ALK1. Furthermore, LDN193189 inhibited monocyte recruitment induced by TNFα and BMP9/10. BMP9/10 increased basal IκBα protein expression, but did not alter p65/RelA levels. Our findings suggest that higher concentrations of BMP9/BMP10 synergize with TNFα to induce the up-regulation of endothelial selectins and adhesion molecules, ultimately resulting in increased monocyte recruitment to the vascular endothelium. This process is mediated mainly via the ALK2 type I receptor, BMPR-II/ACTR-IIA type II receptors, and downstream Smad1/5 signaling. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.
Changes in vegetation cover associated with urban planning efforts may affect regional meteorology and air quality. Here we use a comprehensive coupled meteorology-air quality model (WRF-CMAQ) to simulate the influence of planned land use changes from green infrastructure impleme...
Wild, T C; Henneberry, J; Gill, L
The valuation of urban water management practices and associated nature-based solutions (NBS) is highly contested, and is becoming increasingly important to cities seeking to increase their resilience to climate change whilst at the same time facing budgetary pressures. Different conceptions of 'values' exist, each being accompanied by a set of potential measures ranging from calculative practices (closely linked to established market valuation techniques) - through to holistic assessments that seek to address wider concerns of sustainability. Each has the potential to offer important insights that often go well beyond questions of balancing the costs and benefits of the schemes concerned. However, the need to address - and go beyond - economic considerations presents policy-makers, practitioners and researchers with difficult methodological, ethical and practical challenges, especially when considered without the benefit of a broader theoretical framework or in the absence of well-established tools (as might apply within more traditional infrastructural planning contexts, such as the analysis of transport interventions). Drawing on empirical studies undertaken in Sheffield over a period of 10 years, and delivered in partnership with several other European cities and regions, we compare and examine different attempts to evaluate the benefits of urban greening options and future development scenarios. Comparing these different approaches to the valuation of nature-based solutions alongside other, more conventional forms of infrastructure - and indeed integrating both 'green and grey' interventions within a broader framework of infrastructures - throws up some surprising results and conclusions, as well as providing important sign-posts for future research in this rapidly emerging field. Copyright © 2017 Elsevier Inc. All rights reserved.
Norrie, Jacqueline L; Lewandowski, Jordan P; Bouldin, Cortney M; Amarnath, Smita; Li, Qiang; Vokes, Martha S; Ehrlich, Lauren I R; Harfe, Brian D; Vokes, Steven A
Mutations in the Bone Morphogenetic Protein (BMP) pathway are associated with a range of defects in skeletal formation. Genetic analysis of BMP signaling requirements is complicated by the presence of three partially redundant BMPs that are required for multiple stages of limb development. We generated an inducible allele of a BMP inhibitor, Gremlin, which reduces BMP signaling. We show that BMPs act in a dose and time dependent manner in which early reduction of BMPs result in digit loss, while inhibiting overall BMP signaling between E10.5 and E11.5 allows polydactylous digit formation. During this period, inhibiting BMPs extends the duration of FGF signaling. Sox9 is initially expressed in normal digit ray domains but at reduced levels that correlate with the reduction in BMP signaling. The persistence of elevated FGF signaling likely promotes cell proliferation and survival, inhibiting the activation of Sox9 and secondarily, inhibiting the differentiation of Sox9-expressing chondrocytes. Our results provide new insights into the timing and clarify the mechanisms underlying BMP signaling during digit morphogenesis. Copyright © 2014 Elsevier Inc. All rights reserved.
Full Text Available Background/Aims: Transplantation of mesenchymal stem cells (MSCs has therapeutic effects on various diseases, while its effect on developing cirrhosis as well as the underlying mechanism remained largely unknown. Methods: Twenty C57BL/6 mice were randomly separated into 2 groups of ten each. One group received transplantation of MSCs, while the other group received saline as control. The mice then received intraperitoneal injection of carbon tetrachloride (CCl4 twice per week for 8 weeks to develop cirrhosis. After another 4 weeks, the levels of cirrhosis in these mice were evaluated by liver fibrosis area, portal pressure, sodium balance and excretion. Transcripts of transforming growth factor β 1 (TGFβ1 and bone morphogenic protein 7 (BMP7 in the mouse livers were quantified by RT-qPCR. BMP7-depleted MSCs were prepared and applied in this model, and compared to MSCs. Results: Liver fibrosis, portal hypertension and sodium retention that were developed by CCl4, were all significantly alleviated by MSCs transplantation, which decreased TGFβ1 levels and increased BMP7 levels in the injured liver. MSCs were found to express extremely high levels of BMP7. Knockdown of BMP7 in MSCs completely abolished the protective effect of MSCs against CCl4-induced cirrhosis. Conclusions: MSCs mitigate cirrhosis through their production of BMP7 against the fibrogenic effect of TGFβ1 in the injured liver.
Full Text Available Nowadays, topics like natural capital assessment, ecosystem services and green infrastructure have become frequent subjects of a number of national and international projects accomplished on local, regional, national and cross-frontier levels. These projects respond to the deterioration of biotopes due to their fragmentation and degradation as a result of constructions and tourism/recreation. This situation requires an economic assessment of ecosystems from the view point of their capacities to satisfy human necessities with simultaneous conservation of the environmental quality, and the optimal status of landscape diversity both in rural and urban areas. The aim of the Green Infrastructure initiative is to stop the loss of land as an irreplaceable natural resource and to contribute to the inclusion of ecological and sustainability aspects into the spatial planning and regional development in rural and urban areas. Green Infrastructure is the tool that may reduce the loss of ecosystem services connected with future occupation of land and improve functions of land. It may support ecological measures aimed at conservation of agricultural landscape and adoption of measures in the sphere of forest and water economies. Important role in the assessment of ecosystems is played not only by the scientists but also by experts and the public at large. This is the reason why ever more stakeholders possessing knowledge of local territory and personal life experience participate in these projects. Their judgments and views, often bearing information important for the above-mentioned assessment, are applied to proposed measures aimed at the improvement of environmental quality and quality of life in terms of sustainability. This article brings the possible example of how to include a selected sample of stakeholders into the assessment of natural capital and ecosystem services on local level in the frame of Green Infrastructure. The aim of this paper is to
Wu, Li-An; Yuan, Guohua; Yang, Guobin; Ortiz-Gonzalez, Iris; Yang, Wuchen; Cui, Yong; MacDougall, Mary; Donly, Kevin J.; Harris, Stephen; Chen, Shuo
Generation of a floxed Bmp2/4 osteoblast cell line is a valuable tool for studying the modulatory effects of Bmp2 and Bmp4 on osteoblast differentiation as well as relevant molecular events. In this study, primary floxed Bmp2/4 mouse osteoblasts were cultured and transfected with simian virus 40 large T-antigen. Transfection was verified by polymerase chain reaction (PCR) and immunohistochemistry. To examine the characteristics of the transfected cells, morphology, proliferation and mineralization were analyzed, expression of cell-specific genes including Runx2, ATF4, Dlx3, Osx, dentin matrix protein 1, bone sialoprotein, osteopontin, osteocalcin, osteonectin and collagen type I was detected. These results show that transfected floxed Bmp2/4 osteoblasts bypassed senescence with a higher proliferation rate, but retain the genotypic and phenotypic characteristics similar to the primary cells. Thus, we for the first time demonstrate the establishment of an immortalized mouse floxed Bmp2/4 osteoblast cell line.
Wu, Li-An [Department of Pediatric Dentistry, The University of Texas Health Science Center at San Antonio, TX (United States); Department of Pediatric Dentistry, School of Stomatology, The Fourth Military Medical University, Xi-an (China); Yuan, Guohua; Yang, Guobin [Department of Pediatric Dentistry, The University of Texas Health Science Center at San Antonio, TX (United States); Key Laboratory of Oral Biomedical Engineering Ministry of Education, Wuhan (China); Ortiz-Gonzalez, Iris [Department of Pediatric Dentistry, The University of Texas Health Science Center at San Antonio, TX (United States); Yang, Wuchen; Cui, Yong [Department of Periodontics, Dental School, The University of Texas Health Science Center at San Antonio, TX (United States); MacDougall, Mary [Department of Oral/Maxillofacial Surgery, University of Alabama, Birmingham, AL (United States); Donly, Kevin J. [Department of Pediatric Dentistry, The University of Texas Health Science Center at San Antonio, TX (United States); Harris, Stephen [Department of Periodontics, Dental School, The University of Texas Health Science Center at San Antonio, TX (United States); Chen, Shuo, E-mail: firstname.lastname@example.org [Department of Pediatric Dentistry, The University of Texas Health Science Center at San Antonio, TX (United States)
Generation of a floxed Bmp2/4 osteoblast cell line is a valuable tool for studying the modulatory effects of Bmp2 and Bmp4 on osteoblast differentiation as well as relevant molecular events. In this study, primary floxed Bmp2/4 mouse osteoblasts were cultured and transfected with simian virus 40 large T-antigen. Transfection was verified by polymerase chain reaction (PCR) and immunohistochemistry. To examine the characteristics of the transfected cells, morphology, proliferation and mineralization were analyzed, expression of cell-specific genes including Runx2, ATF4, Dlx3, Osx, dentin matrix protein 1, bone sialoprotein, osteopontin, osteocalcin, osteonectin and collagen type I was detected. These results show that transfected floxed Bmp2/4 osteoblasts bypassed senescence with a higher proliferation rate, but retain the genotypic and phenotypic characteristics similar to the primary cells. Thus, we for the first time demonstrate the establishment of an immortalized mouse floxed Bmp2/4 osteoblast cell line.
Xia, Yin; Babitt, Jodie L; Bouley, Richard; Zhang, Ying; Da Silva, Nicolas; Chen, Shanzhuo; Zhuang, Zhenjie; Samad, Tarek A; Brenner, Gary J; Anderson, Jennifer L; Hong, Charles C; Schneyer, Alan L; Brown, Dennis; Lin, Herbert Y
The neuronal adhesion protein Dragon acts as a bone morphogenetic protein (BMP) coreceptor that enhances BMP signaling. Given the importance of BMP signaling in nephrogenesis and its putative role in the response to injury in the adult kidney, we studied the localization and function of Dragon in the kidney. We observed that Dragon localized predominantly to the apical surfaces of tubular epithelial cells in the thick ascending limbs, distal convoluted tubules, and collecting ducts of mice. Dragon expression was weak in the proximal tubules and glomeruli. In mouse inner medullary collecting duct (mIMCD3) cells, Dragon generated BMP signals in a ligand-dependent manner, and BMP4 is the predominant endogenous ligand for the Dragon coreceptor. In mIMCD3 cells, BMP4 normally signaled through BMPRII, but Dragon enhanced its signaling through the BMP type II receptor ActRIIA. Dragon and BMP4 increased transepithelial resistance (TER) through the Smad1/5/8 pathway. In epithelial cells isolated from the proximal tubule and intercalated cells of collecting ducts, we observed coexpression of ActRIIA, Dragon, and BMP4 but not BMPRII. Taken together, these results suggest that Dragon may enhance BMP signaling in renal tubular epithelial cells and maintain normal renal physiology.
Full Text Available Background/Aims: New strategies for the prevention and treatment of cirrhosis are urgently needed for improving therapeutic outcome. A role of microRNAs (miRNAs in the pathogenesis of cirrhosis has been recently acknowledged, whereas the exact involved miRNAs as well as the associated molecular signaling pathways have not been determined. Specifically, the studies on the relationship between miR-22 and bone morphogenic protein 7 (BMP7 in the development of cirrhosis are lacking. Methods: We examined the correlation of the levels of miR-22 and bone morphogenic protein 7 (BMP7 in the liver biopsies from patients with cirrhosis. We examined overexpression or suppression of miR-22 on BMP7 in hepatocytes. We examined the binding of miR-22 to the 3'-UTR of BMP7 mRNA. Finally, in a carbon tetrachloride (CCl4-induced cirrhosis model in mice, we gave mice adeno-associated viruses carrying antisense of miR-22, and examined its effects on BMP7 levels and the hallmarks of cirrhosis. Results: The levels of miR-22 and BMP7 in the liver biopsies from patients were strongly and inversely correlated. MiR-22 inhibited BMP7 expression in hepatocytes, through directly binding the 3'-UTR of BMP7 mRNA. Expression of antisense miR-22 significantly attenuated the levels of liver fibrosis, portal hypertension and sodium retention caused by CCl4, possibly through upregulation of BMP7. Conclusions: MiR-22 promotes the development of cirrhosis through BMP7 suppression.
Shi, Jia; Yoshino, Osamu; Osuga, Yutaka; Akiyama, Ikumi; Harada, Miyuki; Koga, Kaori; Fujimoto, Akihisa; Yano, Tetsu; Taketani, Yuji
To examine the relevance of growth differentiation factor 3 (GDF-3) and bone morphogenetic protein (BMP) cytokines in human ovary. Molecular studies. Research laboratory. Eight women undergoing salpingo-oophorectomy and 30 women undergoing ovarian stimulation for in vitro fertilization. Localizing GDF-3 protein in human ovaries; granulosa cells (GC) cultured with GDF-3, BMP-6, or BMP-7 followed by RNA extraction. The localization of GDF-3 protein in normal human ovaries via immunohistochemical analysis, GDF-3 messenger RNA (mRNA) expression evaluation via quantitative real-time reverse transcription and polymerase chain reaction (RT-PCR), and evaluation of the effect of GDF-3 on leuteinizing hormone (LH) receptor mRNA expression via quantitative real-time RT-PCR. In the ovary, BMP cytokines, of the transforming growth factor beta (TGF-β) superfamily, are known as a luteinization inhibitor by suppressing LH receptor expression in GC. Growth differentiation factor 3, a TGF-β superfamily cytokine, is recognized as an inhibitor of BMP cytokines in other cells. Immunohistochemical analysis showed that GDF-3 was strongly detected in the GC of antral follicles. An in vitro assay revealed that BMP-6 or BMP-7 induced GDF-3 mRNA in GC. Also, GDF-3 increased LH receptor mRNA expression and inhibited the effect of BMP-7, which suppressed the LH receptor mRNA expression in GC. GDF-3, induced with BMP-6 and BMP-7, might play a role in folliculogenesis by inhibiting the effect of BMP cytokines. Copyright © 2012 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.
Despite the increasing use of urban stormwater green infrastructure (SGI), including detention ponds and rain gardens, few studies have quantified the cumulative effects of multiple SGI projects on hydrology and water quality at the watershed scale. To assess the effects of SGI, ...
Full Text Available Pulmonary arterial hypertension (PAH is a disease of progressively increasing pulmonary vascular resistance, associated with mutations of the type 2 receptor for the BMP pathway, BMPR2. The canonical signaling pathway for BMPR2 is through the SMAD family of transcription factors. BMPR2 is expressed in every cell type, but the impact of BMPR2 mutations affecting SMAD signaling, such as Bmpr2delx4+, had only previously been investigated in smooth muscle and endothelium. In the present study, we created a mouse with universal doxycycline-inducible expression of Bmpr2delx4+ in order to determine if broader expression had an impact relevant to the development of PAH. We found that the most obvious phenotype was a dramatic, but patchy, increase in pulmonary inflammation. We crossed these double transgenic mice onto an NF-κB reporter strain, and by luciferase assays on live mice, individual organs and isolated macrophages, we narrowed down the origin of the inflammatory phenotype to constitutive activation of tissue macrophages. Study of bone marrow-derived macrophages from mutant and wild-type mice suggested a baseline difference in differentiation state in Bmpr2 mutants. When activated with LPS, both mutant and wild-type macrophages secrete BMP pathway inhibitors sufficient to suppress BMP pathway activity in smooth muscle cells (SMC treated with conditioned media. Functionally, co-culture with macrophages results in a BMP signaling-dependent increase in scratch closure in cultured SMC. We conclude that SMAD signaling through BMP is responsible, in part, for preventing macrophage activation in both live animals and in cells in culture, and that activated macrophages secrete BMP inhibitors in sufficient quantity to cause paracrine effect on vascular smooth muscle.
Kondo, Michelle C; Sharma, Raghav; Plante, Alain F; Yang, Yunwen; Burstyn, Igor
Green stormwater infrastructure (GSI) is designed to capture stormwater for infiltration, detention, evapotranspiration, or reuse. Soils play a key role in stormwater interception at these facilities. It is important to assess whether contamination is occurring in GSI soils because urban stormwater drainage areas often accumulate elements of concern. Soil contamination could affect hydrologic and ecosystem functions. Maintenance workers and the public may also be exposed to GSI soils. We investigated soil elemental concentrations, categorized as macro- and micronutrients, heavy metals, and other elements, at 59 GSI sites in the city of Philadelphia. Non-GSI soil samples 3 to 5 m upland of GSI sites were used for comparison. We evaluated differences in elemental composition in GSI and non-GSI soils; the comparisons were corrected for the age of GSI facility, underlying soil type, street drainage, and surrounding land use. Concentrations of Ca and I were greater than background levels at GSI sites. Although GSI facilities appear to accumulate Ca and I, these elements do not pose a significant human health risk. Elements of concern to human health, including Cd, Hg, and Pb, were either no different or were lower in GSI soils compared with non-GSI soils. However, mean values found across GSI sites were up to four times greater than soil cleanup objectives for residential use. Copyright © by the American Society of Agronomy, Crop Science Society of America, and Soil Science Society of America, Inc.
Gabriel Liu, MBBCh, MSc, FRCS, FAMS (Orth
Full Text Available RhBMP-2 is a bone fusion enhancer commonly used in scoliosis reconstruction surgery. It is delivered via an absorbable collagen sponge but has been known to migrate away from its delivery site. RhBMP-2 extravasation in surgical drainage has been noted during first two days post-surgery. Cell savers are widely used in scoliosis reconstruction to limit transfusion requirements and are commonly deployed in cases where rhBMP-2 is used for fusion augmentation. It is not known whether rhBMP-2 is present in salvaged blood or filtered away during cell saver recycling. Through this case series of four patients who underwent scoliosis reconstruction, we assess cell saver efficacy in filtering rhBMP-2 molecules by quantifying the amount of rhBMP-2 present in salvaged blood obtained after postoperative drainage recycling by OrthoPAT® cell saver and comparing it to rhBMP-2 leakage in postoperative drainage without cell saver recycling. We report an almost 10-fold reduction of rhBMP-2 concentration in salvaged blood obtained after cell saver recycling of postoperative drainage, suggesting cell saver effectiveness in filtering rhBMP-2 molecules.
Full Text Available Neural stem cells (NSCs are self-renewing multipotent progenitors that generate both neurons and glia. The precise control of NSC behavior is fundamental to the architecture and function of the central nervous system. We previously demonstrated that the orphan nuclear receptor TLX is required for postnatal NSC activation and neurogenesis in the neurogenic niche. Here, we show that TLX modulates BMP-SMAD signaling to control the timing of postnatal astrogenesis. Genes involved in the BMP signaling pathway, such as Bmp4, Hes1, and Id3, are upregulated in postnatal brains lacking Tlx. Chromatin immunoprecipitation and electrophoretic mobility shift assays reveal that TLX can directly bind the enhancer region of Bmp4. In accordance with elevated BMP signaling, the downstream effectors SMAD1/5/8 are activated by phosphorylation in Tlx mutant mice. Consequently, Tlx mutant brains exhibit an early appearance and increased number of astrocytes with marker expression of glial fibrillary acidic protein (GFAP and S100B. Taken together, these results suggest that TLX tightly controls postnatal astrogenesis through the modulation of BMP-SMAD signaling pathway activity.
Qin, Song; Niu, Wenze; Iqbal, Nida; Smith, Derek K; Zhang, Chun-Li
Neural stem cells (NSCs) are self-renewing multipotent progenitors that generate both neurons and glia. The precise control of NSC behavior is fundamental to the architecture and function of the central nervous system. We previously demonstrated that the orphan nuclear receptor TLX is required for postnatal NSC activation and neurogenesis in the neurogenic niche. Here, we show that TLX modulates bone morphogenetic protein (BMP)-SMAD signaling to control the timing of postnatal astrogenesis. Genes involved in the BMP signaling pathway, such as Bmp4, Hes1, and Id3, are upregulated in postnatal brains lacking Tlx. Chromatin immunoprecipitation and electrophoretic mobility shift assays reveal that TLX can directly bind the enhancer region of Bmp4. In accordance with elevated BMP signaling, the downstream effectors SMAD1/5/8 are activated by phosphorylation in Tlx mutant mice. Consequently, Tlx mutant brains exhibit an early appearance and increased number of astrocytes with marker expression of glial fibrillary acidic protein (GFAP) and S100B. Taken together, these results suggest that TLX tightly controls postnatal astrogenesis through the modulation of BMP-SMAD signaling pathway activity.
Full Text Available TGFβ and BMP signaling pathways exhibit antagonistic activities during the development of many tissues. Although the crosstalk between BMP and TGFβ signaling pathways is well established in bone development, the relationship between these two pathways is less well defined during cartilage development and postnatal homeostasis. We generated hypomorphic mouse models of cartilage-specific loss of BMP and TGFβ signaling to assess the interaction of these pathways in postnatal growth plate homeostasis. We further used the chondrogenic ATDC5 cell line to test effects of BMP and TGFβ signaling on each other's downstream targets. We found that conditional deletion of Smad1 in chondrocytes resulted in a shortening of the growth plate. The addition of Smad5 haploinsufficiency led to a more severe phenotype with shorter prehypertrophic and hypertrophic zones and decreased chondrocyte proliferation. The opposite growth plate phenotype was observed in a transgenic mouse model of decreased chondrocytic TGFβ signaling that was generated by expressing a dominant negative form of the TGFβ receptor I (ΔTβRI in cartilage. Histological analysis demonstrated elongated growth plates with enhanced Ihh expression, as well as an increased proliferation rate with altered production of extracellular matrix components. In contrast, in chondrogenic ATDC5 cells, TGFβ was able to enhance BMP signaling, while BMP2 significantly reduces levels of TGF signaling. In summary, our data demonstrate that during endochondral ossification, BMP and TGFβ signaling can have antagonistic effects on chondrocyte proliferation and differentiation in vivo. We also found evidence of direct interaction between the two signaling pathways in a cell model of chondrogenesis in vitro.
Information about the San Francisco Bay Water Quality Project (SFBWQP) Urban Greening Bay Area, a large-scale effort to re-envision urban landscapes to include green infrastructure (GI) making communities more livable and reducing stormwater runoff.
Volk, S W; Luvalle, P; Leask, T; Leboy, P S
Bone morphogenetic proteins (BMPs) were originally identified by their ability to induce ectopic bone formation and have been shown to promote both chondrogenesis and chondrocyte hypertrophy. BMPs have recently been found to activate a membrane serine/threonine kinase signaling mechanism in a variety of cell types, but the downstream effectors of BMP signaling in chondrocyte differentiation remain unidentified. We have previously reported that BMP-2 markedly stimulates type X collagen expression in prehypertrophic chick sternal chondrocytes, and that type X collagen mRNA levels in chondrocytes cultured under serum-free (SF) conditions are elevated 3- to 5-fold within 24 h. To better define the molecular mechanisms of induction of chondrocyte hypertrophy by BMPs, we examined the effect of BMPs on type X collagen production by 15-day chick embryo sternal chondrocytes cultured under SF conditions in the presence or absence of 30 ng/ml BMP-2, BMP-4, or BMP-7. Two populations of chondrocytes were used: one representing resting cartilage isolated from the caudal third of the sterna and the second representing prehypertrophic cartilage from the cephalic third of the sterna. BMP-2, BMP-4, and BMP-7 all effectively promoted chondrocyte maturation of cephalic sternal chondrocytes as measured by high levels of alkaline phosphatase, diminished levels of type II collagen, and induction of the hypertrophic chondrocyte-specific marker, type X collagen. To test whether BMP control of type X collagen expression occurs at the transcriptional level, we utilized plasmid constructs containing the chicken collagen X promoter and 5' flanking regions fused to a reporter gene. Constructs were transiently transfected into sternal chondrocytes cultured under SF conditions in the presence or absence of 30 ng/ml BMP-2, BMP-4, or BMP-7. A 533 bp region located 2.4-2.9 kb upstream from the type X collagen transcriptional start site was both necessary and sufficient for strong BMP responsiveness
Shiela C Samson
Full Text Available The 3-O-sulfotransferase (3-OST family catalyzes rare modifications of glycosaminoglycan chains on heparan sulfate proteoglycans, yet their biological functions are largely unknown. Knockdown of 3-OST-7 in zebrafish uncouples cardiac ventricular contraction from normal calcium cycling and electrophysiology by reducing tropomyosin4 (tpm4 expression. Normal 3-OST-7 activity prevents the expansion of BMP signaling into ventricular myocytes, and ectopic activation of BMP mimics the ventricular noncontraction phenotype seen in 3-OST-7 depleted embryos. In 3-OST-7 morphants, ventricular contraction can be rescued by overexpression of tropomyosin tpm4 but not by troponin tnnt2, indicating that tpm4 serves as a lynchpin for ventricular sarcomere organization downstream of 3-OST-7. Contraction can be rescued by expression of 3-OST-7 in endocardium, or by genetic loss of bmp4. Strikingly, BMP misregulation seen in 3-OST-7 morphants also occurs in multiple cardiac noncontraction models, including potassium voltage-gated channel gene, kcnh2, affected in Romano-Ward syndrome and long-QT syndrome, and cardiac troponin T gene, tnnt2, affected in human cardiomyopathies. Together these results reveal 3-OST-7 as a key component of a novel pathway that constrains BMP signaling from ventricular myocytes, coordinates sarcomere assembly, and promotes cardiac contractile function.
Mekala, Gayathri Devi; Jones, Roger N; MacDonald, Darla Hatton
In an effort to increase the livability of its cities, public agencies in Australia are investing in green infrastructure to improve public health, reduce heat island effects and transition toward water sensitive urban design. In this paper, we present a simple and replicable approach to building a business case for green infrastructure. This approach requires much less time and resources compared to other methods for estimating the social and economic returns to society from such investments. It is a pragmatic, reasonably comprehensive approach that includes socio-demographic profile of potential users and catchment analysis to assess the economic value of community benefits of the investment. The approach has been applied to a case study area in the City of Brimbank, a western suburb of Greater Melbourne. We find that subject to a set of assumptions, a reasonable business case can be made. We estimate potential public benefits of avoided health costs of about AU$75,049 per annum and potential private benefits of AU$3.9 million. The project area is one of the most poorly serviced areas in the municipality in terms of quality open spaces and the potential beneficiaries are from relatively low income households with less than average health status and education levels. The values of cultural (recreational benefits, avoided health costs, and increased property values) and regulating (reduction in heat island effect and carbon sequestration) ecosystem services were quantified that can potentially offset annual maintenance costs.
Mekala, Gayathri Devi; Jones, Roger N.; MacDonald, Darla Hatton
In an effort to increase the livability of its cities, public agencies in Australia are investing in green infrastructure to improve public health, reduce heat island effects and transition toward water sensitive urban design. In this paper, we present a simple and replicable approach to building a business case for green infrastructure. This approach requires much less time and resources compared to other methods for estimating the social and economic returns to society from such investments. It is a pragmatic, reasonably comprehensive approach that includes socio-demographic profile of potential users and catchment analysis to assess the economic value of community benefits of the investment. The approach has been applied to a case study area in the City of Brimbank, a western suburb of Greater Melbourne. We find that subject to a set of assumptions, a reasonable business case can be made. We estimate potential public benefits of avoided health costs of about AU75,049 per annum and potential private benefits of AU3.9 million. The project area is one of the most poorly serviced areas in the municipality in terms of quality open spaces and the potential beneficiaries are from relatively low income households with less than average health status and education levels. The values of cultural (recreational benefits, avoided health costs, and increased property values) and regulating (reduction in heat island effect and carbon sequestration) ecosystem services were quantified that can potentially offset annual maintenance costs.
Morse, N.; Walter, T.
The need for resilient infrastructure and cities in the face of climate change has prompted an expansion of green infrastructure (GI) in suburban and urban areas. However, some researchers have begun to question if these engineered and vegetated systems could be contributing excess greenhouse gas (GHG) emissions. They theorize that the often inundated GI practices may be hot-spots for biogeochemical processes emitting GHGs. However, no studies have compared passive GI to the only available alternative for water treatment: conventional wastewater treatment plants (WWTPs). This study monitored the nitrous oxide (N2O) and methane (CH4) emissions from two GI detention basins in Ithaca, NY and compared these emissions with reported and modeled on-site emissions from WWTPs. One basin was often saturated ("Wet Basin"), while the other drained quickly and was rarely saturated ("Dry Basin"). The Wet Basin emitted more GHGs than nearby reference turfgrass (92 vs. 5 mg CO2 eq m-2 hr-), while the Dry Basin emitted less than reference turfgrass (0.9 vs 4 mg CO2 eq m-2 hr-). However, both basins emitted far less GHGs than conventional WWTPs. According to EPA calculations, aerobic WWTPs emit approximately 1,079 mg CO2 eq L-1, and the Wet and Dry Basin emitted roughly 117-516 and 0.28-2.56 mg CO2 eq L-1, respectively. Thus, on a per volume of water treated basis, conventional WWTPs are emitting approximately 3 and 750 times more GHGs than GI Wet and Dry Basins, respectively. This study highlights how passive GI provides a valuable ecosystem service (i.e., stormwater treatment) while producing less GHGs than WWTPs.
Bell, C.; Li, Y.; Lopez, E.; Hogue, T. S.
Decision support tools that quantitatively estimate the cost and performance of infrastructure alternatives are valuable for urban planners. Such a tool is needed to aid in planning stormwater projects to meet diverse goals such as the regulation of stormwater runoff and its pollutants, minimization of economic costs, and maximization of environmental and social benefits in the communities served by the infrastructure. This work gives a brief overview of an integrated decision support tool, called i-DST, that is currently being developed to serve this need. This presentation focuses on the development of a default database for the i-DST that parameterizes water quality treatment efficiency of stormwater best management practices (BMPs) by region. Parameterizing the i-DST by region will allow the tool to perform accurate simulations in all parts of the United States. A national dataset of BMP performance is analyzed to determine which of a series of candidate regionalizations explains the most variance in the national dataset. The data used in the regionalization analysis comes from the International Stormwater BMP Database and data gleaned from an ongoing systematic review of peer-reviewed and gray literature. In addition to identifying a regionalization scheme for water quality performance parameters in the i-DST, our review process will also provide example methods and protocols for systematic reviews in the field of Earth Science.
Guo, Feng; Feng, Junsheng; Wang, Feng; Li, Wentong; Gao, Qingping; Chen, Zhuo; Shoff, Lisa; Donly, Kevin J; Gluhak-Heinrich, Jelica; Chun, Yong Hee Patricia; Harris, Stephen E; MacDougall, Mary; Chen, Shuo
Although Bmp2 is essential for tooth formation, the role of Bmp2 during enamel formation remains unknown in vivo. In this study, the role of Bmp2 in regulation of enamel formation was investigated by the Bmp2 conditional knock out (Bmp2 cKO) mice. Teeth of Bmp2 cKO mice displayed severe and profound phenotypes with asymmetric and misshaped incisors as well as abrasion of incisors and molars. Scanning electron microscopy analysis showed that the enamel layer was hypoplastic and enamel lacked a typical prismatic pattern. Teeth from null mice were much more brittle as tested by shear and compressive moduli. Expression of enamel matrix protein genes, amelogenin, enamelin, and enamel-processing proteases, Mmp-20 and Klk4 was reduced in the Bmp2 cKO teeth as reflected in a reduced enamel formation. Exogenous Bmp2 up-regulated those gene expressions in mouse enamel organ epithelial cells. This result for the first time indicates Bmp2 signaling is essential for proper enamel development and mineralization in vivo. © 2015 Wiley Periodicals, Inc.
Lennon, Mick; Scott, Mark J.; Collier, Marcus; Foley, Karen
The 'landscape' approach to planning and design has long since advanced a social ecological perspective that conceives ecosystems health and human well-being as mutually constitutive. However, conventional public sector organisational arrangements segregate and discretely administer development issues, thereby militating against the holistic viewpoint necessary to redress the entwined nature of complex planning issues. The emergence and continuing evolution of green infrastructure (GI) thinki...
Swartz, Mary E.; McCarthy, Neil; Norrie, Jacqueline L.; Eberhart, Johann K.
The endodermal pouches are a series of reiterated structures that segment the pharyngeal arches and help pattern the vertebrate face. Multiple pathways regulate the complex process of endodermal development, including the Bone morphogenetic protein (Bmp) pathway. However, the role of Bmp signaling in pouch morphogenesis is poorly understood. Using genetic and chemical inhibitor approaches, we show that pouch morphogenesis requires Bmp signaling from 10-18 h post-fertilization, immediately following gastrulation. Blocking Bmp signaling during this window results in morphological defects to the pouches and craniofacial skeleton. Using genetic chimeras we show that Bmp signals directly to the endoderm for proper morphogenesis. Time-lapse imaging and analysis of reporter transgenics show that Bmp signaling is necessary for pouch outpocketing via the Fibroblast growth factor (Fgf) pathway. Double loss-of-function analyses demonstrate that Bmp and Fgf signaling interact synergistically in craniofacial development. Collectively, our analyses shed light on the tissue and signaling interactions that regulate development of the vertebrate face. PMID:27122171
Tiwary, A; Williams, I D; Heidrich, O; Namdeo, A; Bandaru, V; Calfapietra, C
This paper presents a performance evaluation framework for streetscape vegetation. A performance index (PI) is conceived using the following seven traits, specific to the street environments - Pollution Flux Potential (PFP), Carbon Sequestration Potential (CSP), Thermal Comfort Potential (TCP), Noise Attenuation Potential (NAP), Biomass Energy Potential (BEP), Environmental Stress Tolerance (EST) and Crown Projection Factor (CPF). Its application is demonstrated through a case study using fifteen street vegetation species from the UK, utilising a combination of direct field measurements and inventoried literature data. Our results indicate greater preference to small-to-medium size trees and evergreen shrubs over larger trees for streetscaping. The proposed PI approach can be potentially applied two-fold: one, for evaluation of the performance of the existing street vegetation, facilitating the prospects for further improving them through management strategies and better species selection; two, for planning new streetscapes and multi-functional biomass as part of extending the green urban infrastructure. Copyright © 2015 Elsevier Ltd. All rights reserved.
Kabir, Md Imran; Daly, Edoardo; Maggi, Federico
In urban environments, the breakdown of chemicals and pollutants, especially ions and metal compounds, can be favoured by green water infrastructures (GWIs). The overall aim of this review is to set the basis to model GWIs using deterministic approaches in contrast to empirical ones. If a better picture of chemicals and pollutant input and an improved understanding of hydrological and biogeochemical processes affecting these pollutants were known, GWIs could be designed to efficiently retain these pollutants for site-specific meteorological patterns and pollutant load. To this end, we surveyed the existing literature to retrieve a comprehensive dataset of anions and cations, and alkaline and transition metal pollutants incoming to urban environments. Based on this survey, we assessed the pollution load and ecological risk indexes for metals. The existing literature was then surveyed to review the metal retention efficiency of GWIs, and possible biogeochemical processes related to inorganic metal compounds were proposed that could be integrated in biogeochemical models of GWIs. © 2013.
The presentation on the title subject comprises Motivation for Green Gas; Potential and application; Green Gas and SNG implementation; Biomass availability and import; Economy of SNG production; and the SNG development trajectory. SNG stands for Synthetic Natural Gas
Ge, Gaoxiang; Greenspan, Daniel S
The astacin family (M12A) of the metzincin subclan MA(M) of metalloproteinases has been detected in developing and mature individuals of species that range from hydra to humans. Functions of this family of metalloproteinase vary from digestive degradation of polypeptides, to biosynthetic processing of extracellular proteins, to activation of growth factors. This review will focus on a small subgroup of the astacin family; the bone morphogenetic protein 1 (BMP1)/Tolloid (TLD)-like metalloproteinases. In vertebrates, the BMP1/TLD-like metalloproteinases play key roles in regulating formation of the extracellular matrix (ECM) via biosynthetic processing of various precursor proteins into mature functional enzymes, structural proteins, and proteins involved in initiating mineralization of the ECM of hard tissues. Roles in ECM formation include: processing of the C-propeptides of procollagens types I-III, to yield the major fibrous components of vertebrate ECM; proteolytic activation of the enzyme lysyl oxidase, necessary to formation of covalent cross-links in collagen and elastic fibers; processing of NH2-terminal globular domains and C-propeptides of types V and XI procollagen chains to yield monomers that are incorporated into and control the diameters of collagen type I and II fibrils, respectively; processing of precursors for laminin 5 and collagen type VII, both of which are involved in securing epidermis to underlying dermis; and maturation of small leucine-rich proteoglycans. The BMP1/TLD-related metalloproteinases are also capable of activating the vertebrate transforming growth factor-beta (TGF-beta)-like "chalones" growth differentiation factor 8 (GDF8, also known as myostatin), and GDF11 (also known as BMP11), involved in negative feedback inhibition of muscle and neural tissue growth, respectively; by freeing them from noncovalent latent complexes with their cleaved prodomains. BMP1/TLD-like proteinases also liberate the vertebrate TGF
Dhakal, Krishna P; Chevalier, Lizette R
Green infrastructure (GI) revitalizes vegetation and soil, restores hydro-ecological processes destroyed by traditional urbanization, and naturally manages stormwater on-site, offering numerous sustainability benefits. However, despite being sustainable and despite being the object of unrelenting expert advocacy for more than two decades, GI implementation remains slow. On the other hand, the practice of traditional gray infrastructure, which is known to have significant adverse impacts on the environment, is still ubiquitous in urban areas throughout the world. This relationship between knowledge and practice seems unaccountable, which has not yet received adequate attention from academia, policy makers, or research communities. We deal with this problem in this paper. The specific objective of the paper is to explore the barriers to GI, and suggest policies that can both overcome these barriers and expedite implementation. By surveying the status of implementation in 10 US cities and assessing the relevant city, state and federal policies, we identified 29 barriers and grouped them into 5 categories. The findings show that most of the barriers stem from cognitive limitations and socio-institutional arrangements. Accordingly, we suggest 33 policies, also grouped into 5 categories, which span from conducting public education and awareness programs to changing policies and governance structures. Copyright © 2017 Elsevier Ltd. All rights reserved.
Kuo, Dian-Han; Weisblat, David A
Bone morphogenetic protein (BMP) signaling is broadly implicated in dorsoventral (DV) patterning of bilaterally symmetric animals [1-3], and its role in axial patterning apparently predates the birth of Bilateria [4-7]. In fly and vertebrate embryos, BMPs and their antagonists (primarily Sog/chordin) diffuse and interact to generate signaling gradients that pattern fields of cells [8-10]. Work in other species reveals diversity in essential facets of this ancient patterning process, however. Here, we report that BMP signaling patterns the DV axis of segmental ectoderm in the leech Helobdella, a clitellate annelid (superphylum Lophotrochozoa) featuring stereotyped developmental cell lineages, but the detailed mechanisms of DV patterning in Helobdella differ markedly from fly and vertebrates. In Helobdella, BMP2/4s are expressed broadly, rather than in dorsal territory, whereas a dorsally expressed BMP5-8 specifies dorsal fate by short-range signaling. A BMP antagonist, gremlin, is upregulated by BMP5-8 in dorsolateral, rather than ventral territory, and yet the BMP-antagonizing activity of gremlin is required for normal ventral cell fates. Gremlin promotes ventral fates without disrupting dorsal fates by selectively inhibiting BMP2/4s, not BMP5-8. Thus, DV patterning in the development of the leech revealed unexpected evolutionary plasticity of the conserved BMP patterning system, presumably reflecting its adaptation to different modes of embryogenesis. Copyright © 2011 Elsevier Ltd. All rights reserved.
Ellman, Michael B; Kim, Jaesung; An, Howard S; Chen, Di; Kc, Ranjan; Li, Xin; Xiao, Guozhi; Yan, Dongyao; Suh, Joon; van Wjnen, Andre J; Wang, James H-C; Kim, Su-Gwan; Im, Hee-Jeong
Bone-morphogenetic protein-7 (BMP7) is a well-known anabolic and anti-catabolic growth factor on intervertebral disc (IVD) matrix and cell homeostasis. Similarly, Lactoferricin B (LfcinB) has recently been shown to have pro-anabolic, anti-catabolic, anti-oxidative and/or anti-inflammatory effects in bovine disc cells in vitro. In this study, we investigated the potential benefits of using combined peptide therapy with LfcinB and BMP7 for intervertebral disc matrix repair and to understand cellular and signaling mechanisms controlled by these factors. We studied the effects of BMP7 and LfcinB as individual treatments and combined therapy on bovine nucleus pulposus (NP) cells by assessing proteoglycan (PG) accumulation and synthesis, and the gene expression of matrix protein aggrecan and transcription factor SOX-9. We also analyzed the role of Noggin, a BMP antagonist, in IVD tissue and examined its effect after stimulation with LfcinB. To understand the molecular mechanisms by which LfcinB synergizes with BMP7, we investigated the ERK-SP1 axis as a downstream intracellular signaling regulator involved in BMP7 and LfcinB-mediated activities. Treatment of bovine NP cells cultured in alginate with LfcinB plus BMP7 synergistically stimulates PG synthesis and accumulation in part by upregulation of aggrecan gene expression. The synergism results from LfcinB-mediated activation of Sp1 and SMAD signaling pathways by (i) phosphorylation of SMAD 1/5/8; (ii) downregulation of SMAD inhibitory factors [i.e., noggin and SMAD6 (inhibitory SMAD)]; and (iii) upregulation of SMAD4 (universal co-SMAD). These data indicate that LfcinB-suppression of Noggin may eliminate the negative feedback of BMP7, thereby maximizing biological activity of BMP7 and ultimately shifting homeostasis to a pro-anabolic state in disc cells. We propose that combination growth factor therapy using BMP7 and LfcinB may be beneficial for treatment of disc degeneration. Copyright © 2013 Elsevier B.V. All
Intini, Giuseppe; Nyman, Jeffry S.
Bone fractures remain a serious health burden and prevention and enhanced healing of fractures has been obtained by augmenting either BMP or Wnt signaling. However, whether BMP and Wnt signaling are both required or are self-sufficient for anabolic and fracture healing activities has never been fully elucidated. Mice haploinsufficient for Dkk1 (Dkk1+/−) exhibit a high bone mass phenotype due to an up-regulation of canonical Wnt signaling while mice lacking Bmp2 expression in the limbs (Bmp2c/c;Prx1::cre) succumb to spontaneous fracture and are unable to initiate fracture healing; combined, these mice offer an opportunity to examine the requirement for activated BMP signaling on the anabolic and fracture healing activity of Wnts. When Dkk1+/− mice were crossed with Bmp2c/c;Prx1::cre mice, the offspring bearing both genetic alterations were unable to increase bone mass and heal fractures, indicating that increased canonical Wnt signaling is unable to exploit its activity in absence of Bmp2. Thus, our data suggest that BMP signaling is required for Wnt-mediated anabolic activity and that therapies aimed at preventing fractures and fostering fracture repair may need to target both pathways for maximal efficacy. PMID:25603465
Full Text Available We propose a methodological approach to identify a multifunctional green infrastructure (GI on the basis of four values (conservation value, natural value, recreation value and anthropic heritage that represent many functions (biodiversity conservation, supply of ecosystem services, recreation, identity building performed by the landscape. By taking the Italian region of Sardinia as a case study, we argue that the methodology can support the making of landscape plans as understood in the European Landscape Convention. Moreover, we propose and implement a methodology to identify ecological corridors (ECs connecting Natura 2000 sites (N2Ss, based on the prioritization of functional land patches related to their suitability to ecosystem services delivery, paying particular attention to biodiversity maintenance and enhancement, and taking Sardinia as spatial regional context. The methodology consists of two steps: (i identifying the most suitable patches to be included in ECs on the basis of their connectivity, that is, on their negative attitude towards contributing to landscape fragmentation; (ii assessing, through a discrete-choice-model, the suitability of these ECs to be included in a regional GI, starting from the territorial taxonomy based on biodiversity characteristics related to N2Ss, habitat suitability, and recreational and landscape potentials.
Cohen Clemens D
Full Text Available Abstract Background Bone Morphogenetic Protein (BMP-7 is protective in different animal models of acute and chronic kidney disease. Its role in human kidneys, and in particular hypertensive nephrosclerosis, has thus far not been described. Methods BMP-7 mRNA was quantified using real-time PCR and localised by immunostaining in tissue samples from normal and nephrosclerotic human kidneys. The impact of angiotensin (AT-II and the AT-II receptor antagonist telmisartan on BMP-7 mRNA levels and phosphorylated Smad 1/5/8 (pSmad 1/5/8 expression was quantified in proximal tubular cells (HK-2. Functional characteristics of BMP-7 were evaluated by testing its influence on TGF-β induced epithelial-to-mesenchymal transition (EMT, expression of TGF-β receptor type I (TGF-βRI and phosphorylated Smad 2 (pSmad 2 as well as on TNF-α induced apoptosis of proximal tubular cells. Results BMP-7 was predominantly found in the epithelia of the distal tubule and the collecting duct and was less abundant in proximal tubular cells. In sclerotic kidneys, BMP-7 was significantly decreased as demonstrated by real-time PCR and immunostaining. AT-II stimulation in HK-2 cells led to a significant decrease of BMP-7 and pSmad 1/5/8, which was partially ameliorated upon co-incubation with telmisartan. Only high concentrations of BMP-7 (100 ng/ml were able to reverse TNF-α-induced apoptosis and TGF-β-induced EMT in human proximal tubule cells possibly due to a decreased expression of TGF-βRI. In addition, BMP-7 was able to reverse TGF-β-induced phosphorylation of Smad 2. Conclusions The findings suggest a protective role for BMP-7 by counteracting the TGF-β and TNF-α-induced negative effects. The reduced expression of BMP-7 in patients with hypertensive nephrosclerosis may imply loss of protection and regenerative potential necessary to counter the disease.
Slattery, Martha L.; Lundgreen, Abbie; Herrick, Jennifer S.; Kadlubar, Susan; Caan, Bette J.; Potter, John D.; Wolff, Roger K.
Bone morphogenetic proteins (BMP) are part of the TGF-β-signaling pathway; genetic variation in these genes may be involved in colorectal cancer. In this study we evaluated the association between genetic variation in BMP1 (11 tagSNPs), BMP2 (5 tagSNPs), BMP4 (3 tagSNPs), BMPR1A (9 tagSNPs), BMPR1B (21 tagSNPs), BMPR2 (11 tagSNPs), and GDF10 (7 tagSNPs) with risk of colon and rectal cancer and tumor molecular phenotype. We used data from population-based case-control studies (colon cancer n=1574 cases, 1970 controls; rectal cancer n=791 cases, 999 controls). We observed that genetic variation in BMPR1A, BMPR1B, BMPR2, BMP2, and BMP4 was associated with risk of developing colon cancer, with 20 to 30% increased risk for most high-risk genotypes. A summary of high-risk genotypes showed over a twofold increase in colon cancer risk at the upper risk category (OR 2.49 95% CI 1.95, 3.18). BMPR2, BMPR1B, BMP2, and GDF10 were associated with rectal cancer. BMPR2 rs2228545 was associated with an almost twofold increased risk of rectal cancer. The risk associated with the highest category of the summary score for rectal cancer was 2.97 (95% CI 1.87, 4.72). Genes in the BMP-signaling pathway were consistently associated with CIMP+ status in combination with both KRAS-mutated and MSI tumors. BMP genes interacted statistically significantly with other genes in the TGF-β-signaling pathway, including TGFβ1, TGFβR1, Smad 3, Smad 4, and Smad 7. Our data support a role for genetic variation in BMP-related genes in the etiology of colon and rectal cancer. One possible mechanism is via the TGF-β-signaling pathway. PMID:21387313
Since 2010, the State of California has required construction operators to utilize the electronic Storm Water Application and Report Tracking System (SMARTS) for construction projects covered by the General Construction Permit. The General Construction permit encourages BMP and G...
Faucette, Britt; Cardoso, Fatima; Mulbry, Walter; Millner, Pat
Urban storm water runoff poses a substantial threat of pollution to receiving surface waters. Green infrastructure, low impact development, green building ordinances, National Pollutant Discharge Elimination System (NPDES) storm water permit compliance, and Total Maximum Daily Load (TMDL) implementation strategies have become national priorities; however, designers need more sustainable, low-cost solutions to meet these goals and guidelines. The objective of this study was to determine the multiple-event removal efficiency and capacity of compost filter socks (FS) and filter socks with natural sorbents (NS) to remove soluble phosphorus, ammonium-nitrogen, nitrate-nitrogen, E. coli, Enterococcus, and oil from urban storm water runoff. Treatments were exposed to simulated storm water pollutant concentrations consistent with urban runoff originating from impervious surfaces, such as parking lots and roadways. Treatments were exposed to a maximum of 25 runoff events, or when removal efficiencies were < or = 25%, whichever occurred first. Experiments were conducted in triplicate. The filter socks with natural sorbents removed significantly greater soluble phosphorus than the filter socks alone, removing a total of 237 mg/linear m over eight runoff events, or an average of 34%. The filter socks with natural sorbents removed 54% of ammonium-nitrogen over 25 runoff events, or 533 mg/linear m, and only 11% of nitrate-nitrogen, or 228 mg/linear m. The filter socks and filter socks with natural sorbents both removed 99% of oil over 25 runoff events, or a total load of 38,486 mg/linear m. Over 25 runoff events the filter socks with natural sorbents removed E. coli and Enteroccocus at 85% and 65%, or a total load of 3.14 CFUs x 10(8)/ linear m and 1.5 CFUs x 10(9)/linear m, respectively; both were significantly greater than treatment by filter socks alone. Based on these experiments, this technique can be used to reduce soluble pollutants from storm water over multiple runoff
Li Huiwu; Dai Kerong; Tang Tingting; Zhang Xiaoling; Yan Mengning; Lou Jueren
In this study, we reported that the adipose-derived stromal cells (ADSCs) genetically modified by bone morphogenetic protein 2 (BMP-2) healed critical-sized canine ulnar bone defects. First, the osteogenic and adipogenic differentiation potential of the ADSCs derived from canine adipose tissue were demonstrated. And then the cells were modified by the BMP-2 gene and the expression and bone-induction ability of BMP-2 were identified. Finally, the cells modified by BMP-2 gene were applied to a β-tricalcium phosphate (TCP) carrier and implanted into ulnar bone defects in the canine model. After 16 weeks, radiographic, histological, and histomorphometry analysis showed that ADSCs modified by BMP-2 gene produced a significant increase of newly formed bone area and healed or partly healed all of the bone defects. We conclude that ADSCs modified by the BMP-2 gene can enhance the repair of critical-sized bone defects in large animals
Rojnik, Matija; Jevnikar, Zala; Mirkovic, Bojana; Janes, Damjan; Zidar, Nace; Kikelj, Danijel; Kos, Janko
Background Cathepsin H is a cysteine protease considered to play a major role in tumor progression, however, its precise function in tumorigenesis is unclear. Cathepsin H was recently proposed to be involved in processing of bone morphogenetic protein 4 (BMP-4) in mice. In order to clarify whether cathepsin H also regulates BMP-4 in humans, its impact on BMP-4 expression, processing and degradation was investigated in prostate cancer (PC-3), osteosarcoma (HOS) and pro-monocytic (U937) human cell lines. Materials and methods BMP-4 expression was founded to be regulated by cathepsin H using PCR array technology and confirmed by real time PCR. Immunoassays including Western blot and confocal microscopy were used to evaluate the influence of cathepsin H on BMP-4 processing. Results In contrast to HOS, the expression of BMP-4 mRNA in U937 and PC3 cells was significantly decreased by cathepsin H. The different regulation of BMP-4 synthesis could be associated with the absence of the mature 28 kDa cathepsin H form in HOS cells, where only the intermediate 30 kDa form was observed. No co-localization of BMP-4 and cathepsin H was observed in human cell lines and the multistep processing of BMP-4 was not altered in the presence of specific cathepsin H inhibitor. Isolated cathepsin H does not cleave mature recombinant BMP-4, neither with its amino- nor its endopeptidase activity. Conclusions Our results exclude direct proteolytic processing of BMP-4 by cathepsin H, however, they provide support for its involvement in the regulation of BMP-4 expression. PMID:22933963
Massoudieh, A.; Alikhani, J.
Models that allow for design considerations of green infrastructure (GI) practices to control stormwater runoff and associated contaminants have received considerable attention in recent years. To be used to evaluate the effect design configurations on the long-term performance of GIs, models should be able to consider processes within GIs with good fidelity. In this presentation, a sophisticated, yet flexible tool for hydraulic and water quality assessment of GIs will be introduced. The tool can be used by design engineers and researchers to capture and explore the effect of design factors and properties of the media employed in the performance of GI systems at a relatively small scale. We deemed it essential to have a flexible GI modeling tool that is capable of simulating GI system components and specific biogeochemical processes affecting contaminants such as evapotranspiration, plant uptake, reactions, and particle-associated transport accurately while maintaining a high degree of flexibility to account for the myriad of GI alternatives. The mathematical framework for a stand-alone GI performance assessment tool has been developed and will be demonstrated. The process-based model framework developed here can be used to model a diverse range of GI practices such as stormwater ponds, green roofs, retention ponds, bioretention systems, infiltration trench, permeable pavement and other custom-designed combinatory systems. An example of the application of the system to evaluate the performance of a rain-garden system will be demonstrated.
Kanaparthi, M. B.
In India urban population is growing day by day which is causing air pollution less air quality finally leading to climate change and global warming. To mitigate the effect of the climate change we need to plant more trees in the urban area. The objective of this study is develop a plan to improve the urban Green Infrastructure (GI) to fight against the climate change and global warming. Improving GI is a challenging and difficult task in the urban areas because land unavailability of land, to overcome the problem greenways is a good the solution. Greenway is a linear open space developed along the rivers, canals, roads in the urban areas to form a network of green spaces. Roads are the most common structures in the urban area. The idea is to develop the greenways alongside the road to connecting the different green spaces. Tree crowns will act as culverts to connect the green spaces. This will require the spatial structure of the green space, distribution of trees along the roads and the gap areas along the road where more trees can be planted. This can be achieved with help of high resolution Satellite Imagery and the object extraction techniques. This study was carried in the city Bhimavaram which is located in state Andhra Pradesh. The final outcome of this study is potential gap areas for planting trees in the city.
Full Text Available Endocardial to mesenchymal transformation (EMT is a fundamental cellular process required for heart valve formation. Notch, Wnt and Bmp pathways are known to regulate this process. To further address how these pathways coordinate in the process, we specifically disrupted Notch1 or Jagged1 in the endocardium of mouse embryonic hearts and showed that Jagged1-Notch1 signaling in the endocardium is essential for EMT and early valvular cushion formation. qPCR and RNA in situ hybridization assays reveal that endocardial Jagged1-Notch1 signaling regulates Wnt4 expression in the atrioventricular canal (AVC endocardium and Bmp2 in the AVC myocardium. Whole embryo cultures treated with Wnt4 or Wnt inhibitory factor 1 (Wif1 show that Bmp2 expression in the AVC myocardium is dependent on Wnt activity; Wnt4 also reinstates Bmp2 expression in the AVC myocardium of endocardial Notch1 null embryos. Furthermore, while both Wnt4 and Bmp2 rescue the defective EMT resulting from Notch inhibition, Wnt4 requires Bmp for its action. These results demonstrate that Jagged1-Notch1 signaling in endocardial cells induces the expression of Wnt4, which subsequently acts as a paracrine factor to upregulate Bmp2 expression in the adjacent AVC myocardium to signal EMT.
Full Text Available Abstract Background The robust expression of BMP4 in the incipient sensory organs of the inner ear suggests possible roles for this signaling protein during induction and development of auditory and vestibular sensory epithelia. Homozygous BMP4-/- animals die before the inner ear's sensory organs develop, which precludes determining the role of BMP4 in these organs with simple gene knockout experiments. Results Here we use a chicken otocyst culture system to perform quantitative studies on the development of inner ear cell types and show that hair cell and supporting cell generation is remarkably reduced when BMP signaling is blocked, either with its antagonist noggin or by using soluble BMP receptors. Conversely, we observed an increase in the number of hair cells when cultured otocysts were treated with exogenous BMP4. BMP4 treatment additionally prompted down-regulation of Pax-2 protein in proliferating sensory epithelial progenitors, leading to reduced progenitor cell proliferation. Conclusion Our results implicate BMP4 in two events during chicken inner ear sensory epithelium formation: first, in inducing the switch from proliferative sensory epithelium progenitors to differentiating epithelial cells and secondly, in promoting the differentiation of hair cells within the developing sensory epithelia.
Leclère, Lucas; Rentzsch, Fabian
Patterning of the metazoan dorsoventral axis is mediated by a complex interplay of BMP signaling regulators. Repulsive guidance molecule (RGM) is a conserved BMP coreceptor that has not been implicated in axis specification. We show that NvRGM is a key positive regulator of BMP signaling during secondary axis establishment in the cnidarian Nematostella vectensis. NvRGM regulates first the generation and later the shape of a BMP-dependent Smad1/5/8 gradient with peak activity on the side opposite the NvBMP/NvRGM/NvChordin expression domain. Full knockdown of Smad1/5/8 signaling blocks the formation of endodermal structures, the mesenteries, and the establishment of bilateral symmetry, while altering the gradient through partial NvRGM or NvBMP knockdown shifts the boundaries of asymmetric gene expression and the positioning of the mesenteries along the secondary axis. These findings provide insight into the diversification of axis specification mechanisms and identify a previously unrecognized role for RGM in BMP-mediated axial patterning. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.
Szláma, György; Vásárhelyi, Viktor; Trexler, Mária; Patthy, László
The NTR domain of WFIKKN1 protein has been shown to have significant affinity for the prodomain regions of promyostatin and latent myostatin but the biological significance of these interactions remained unclear. In view of its role as a myostatin antagonist, we tested the assumption that WFIKKN1 inhibits the release of myostatin from promyostatin and/or latent myostatin. WFIKKN1 was found to have no effect on processing of promyostatin by furin, the rate of cleavage of latent myostatin by BMP1, however, was significantly enhanced in the presence of WFIKKN1 and this enhancer activity was superstimulated by heparin. Unexpectedly, WFIKKN1 was also cleaved by BMP1 and our studies have shown that the KKN1 fragment generated by BMP1-cleavage of WFIKKN1 contributes most significantly to the observed enhancer activity. Analysis of a pro-TGF-β -based homology model of homodimeric latent myostatin revealed that the BMP1-cleavage sites are buried and not readily accessible to BMP1. In view of this observation, the most plausible explanation for the BMP1-enhancer activity of the KKN1 fragment is that it shifts a conformational equilibrium of latent myostatin from the closed circular structure of the homodimer to a more open form, making the cleavage sites more accessible to BMP1. On the other hand, the observation that the enhancer activity of KKN1 is superstimulated in the presence of heparin is explained by the fact KKN1, latent myostatin, and BMP1 have affinity for heparin and these interactions with heparin increase the local concentrations of the reactants thereby facilitating the action of BMP1. Furin: EC 18.104.22.168; BMP1, bone morphogentic protein 1 or procollagen C-endopeptidase: EC 22.214.171.124. © 2016 The Authors. The FEBS Journal published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.
Ferri-Lagneau, Karine F.; Moshal, Karni S.; Grimes, Matthew; Zahora, Braden; Lv, Lishuang; Sang, Shengmin; Leung, TinChung
Background Anemia is a hematologic disorder with decreased number of erythrocytes. Erythropoiesis, the process by which red blood cells differentiate, are conserved in humans, mice and zebrafish. The only known agents available to treat pathological anemia are erythropoietin and its biologic derivatives. However, erythropoietin therapy elicits unwanted side-effects, high cost and intravenous or subcutaneous injection, warranting the development of a more cost effective and non-peptide alternative. Ginger (Zingiber officinale) has been widely used in traditional medicine; however, to date there is no scientific research documenting the potential of ginger to stimulate hematopoiesis. Methodology/Principal Findings Here, we utilized gata1:dsRed transgenic zebrafish embryos to investigate the effect of ginger extract on hematopoiesis in vivo and we identified its bioactive component, 10-gingerol. We confirmed that ginger and 10-gingerol promote the expression of gata1 in erythroid cells and increase the expression of hematopoietic progenitor markers cmyb and scl. We also demonstrated that ginger and 10-gingerol can promote the hematopoietic recovery from acute hemolytic anemia in zebrafish, by quantifying the number of circulating erythroid cells in the dorsal aorta using video microscopy. We found that ginger and 10-gingerol treatment during gastrulation results in an increase of bmp2b and bmp7a expression, and their downstream effectors, gata2 and eve1. At later stages ginger and 10-gingerol can induce bmp2b/7a, cmyb, scl and lmo2 expression in the caudal hematopoietic tissue area. We further confirmed that Bmp/Smad pathway mediates this hematopoiesis promoting effect of ginger by using the Bmp-activated Bmp type I receptor kinase inhibitors dorsomorphin, LND193189 and DMH1. Conclusions/Significance Our study provides a strong foundation to further evaluate the molecular mechanism of ginger and its bioactive components during hematopoiesis and to investigate their
Zheng, Guang Bin; Yoon, Byung-Hak; Lee, Jae Hyup
Activin A/BMP-2 chimera (AB204) could promote bone healing more effectively than recombinant bone morphogenetic protein 2 (rhBMP-2) with much lower dose in a rodent model, but there is no report about the effectiveness of AB204 in a large animal model. The purpose of this study was to compare the osteogenesis and fusion rate between AB204 and rhBMP-2 using biphasic calcium phosphate (BCP) as a carrier in a beagle's posterolateral lumbar fusion model. This is a randomized control animal study. Seventeen male beagle dogs were included. Bilateral posterolateral fusion was performed at the L1-L2 and L4-L5 levels. Biphasic calcium phosphate (2 cc), rhBMP-2 (50 µg)+BCP (2 cc), or AB204 (50 µg)+BCP (2 cc) were implanted into the intertransverse space randomly. X-ray was performed at 4 and 8 weeks. After 8 weeks, the animals were sacrificed, and new bone formation and fusion rate were evaluated by manual palpation, computed tomography (CT), and undecalcified histology. The AB204 group showed significantly higher fusion rate (90%) than the rhBMP-2 group (15%) or the Osteon group (6.3%) by manual palpation. On x-ray and CT assessment, fusion rate and the volume of newly formed bone were also significantly higher in AB204 group than other groups. In contrast, more osteolysis was found in rhBMP-2 group (40%) than in AB204 group (10%) on CT study. In histologic results, new bone formation was sufficient between transverse processes in AB204 group, and obvious trabeculation and bone remodeling were observed. But in rhBMP-2 group, new bone formation was less than AB204 group and osteolysis was observed between the intertransverse spaces. A low dose of AB204 with BCP as a carrier significantly promotes the fusion rate in a large animal model when compared with the rhBMP-2. These findings demonstrate that AB204 could be an alternative to rhBMP-2 to improve fusion rate. Copyright © 2017 Elsevier Inc. All rights reserved.
Minina, E; Wenzel, H M; Kreschel, C; Karp, S; Gaffield, W; McMahon, A P; Vortkamp, A
During endochondral ossification, two secreted signals, Indian hedgehog (Ihh) and parathyroid hormone-related protein (PTHrP), have been shown to form a negative feedback loop regulating the onset of hypertrophic differentiation of chondrocytes. Bone morphogenetic proteins (BMPs), another family of secreted factors regulating bone formation, have been implicated as potential interactors of the Ihh/PTHrP feedback loop. To analyze the relationship between the two signaling pathways, we used an organ culture system for limb explants of mouse and chick embryos. We manipulated chondrocyte differentiation by supplementing these cultures either with BMP2, PTHrP and Sonic hedgehog as activators or with Noggin and cyclopamine as inhibitors of the BMP and Ihh/PTHrP signaling systems. Overexpression of Ihh in the cartilage elements of transgenic mice results in an upregulation of PTHrP expression and a delayed onset of hypertrophic differentiation. Noggin treatment of limbs from these mice did not antagonize the effects of Ihh overexpression. Conversely, the promotion of chondrocyte maturation induced by cyclopamine, which blocks Ihh signaling, could not be rescued with BMP2. Thus BMP signaling does not act as a secondary signal of Ihh to induce PTHrP expression or to delay the onset of hypertrophic differentiation. Similar results were obtained using cultures of chick limbs. We further investigated the role of BMP signaling in regulating proliferation and hypertrophic differentiation of chondrocytes and identified three functions of BMP signaling in this process. First we found that maintaining a normal proliferation rate requires BMP and Ihh signaling acting in parallel. We further identified a role for BMP signaling in modulating the expression of IHH: Finally, the application of Noggin to mouse limb explants resulted in advanced differentiation of terminally hypertrophic cells, implicating BMP signaling in delaying the process of hypertrophic differentiation itself. This
Rochford, M. E.; Ibsen, P.; Jenerette, D.
Green infrastructure (GI) is greenery planted to absorb rainwater into the earth as an alternative to grey infrastructure, like storm drains. Not only does GI prevent flooding, but it also performs a number of ecosystem services, including increasing biodiversity, because it allows water to cycle through the environment naturally. Increased biodiversity in plant communities is said to help purify the air and improve the health and resilience of the plants themselves. I want to investigate these claims about GI's benefits by studying types of GI with slightly different functions. This will answer the questions 1) Are different types of green infrastructure's plant communities equally biodiverse in terms of functional trait diversity and species richness? 2) How does functional trait diversity and species richness differ along a temperature gradient in Southern California? To compare biodiversity, I must survey four different types of GI, urban parks, riparian zones, detention basins, and bioswales, in three cities in distinct climate regions. Detention basins are reservoirs lined with vegetation that collect water until it is absorbed into the soil. Bioswales are vegetated gutters that filter out pollutants in storm water. Unlike retention basins, they also add aesthetic value to an area. Even though parks are mainly for recreation and beatification rather than storm water management, they have plenty of permeable surface to absorb storm water. The types of GI that have high levels of interaction with humans should also have higher levels of maintenance. The results should follow the homogenization hypothesis and demonstrate that, regardless of climate, species richness should not differ much between highly maintained areas, like parks, in different cities. Otherwise, in GI that is not as manicured, species richness should be significantly different between cities and the different types of GI. Because types of GI selected vary in expected levels of human
Freitas, Rubens Moreno de; Spin-Neto, Rubens; Marcantonio Junior, Elcio; Pereira, Luís Antônio Violin Dias; Wikesjö, Ulf M E; Susin, Cristiano
The aim of this systematic review was to evaluate clinical and safety data for recombinant human bone morphogenetic protein-2 (rhBMP-2) in an absorbable collagen sponge (ACS) carrier when used for alveolar ridge/maxillary sinus augmentation in humans. Clinical studies/case series published 1980 through June 2012 using rhBMP-2/ACS were searched. Studies meeting the following criteria were considered eligible for inclusion: >10 subjects at baseline and maxillary sinus or alveolar ridge augmentation not concomitant with implant placement. Seven of 69 publications were eligible for review. rhBMP-2/ACS yielded clinically meaningful bone formation for maxillary sinus augmentation that would allow placement of regular dental implants without consistent differences between rhBMP-2 concentrations. Nevertheless, the statistical analysis showed that sinus augmentation following autogenous bone graft was significantly greater (mean bone height: 1.6 mm, 95% CI: 0.5-2.7 mm) than for rhBMP-2/ACS (rhBMP-2 at 1.5 mg/mL). In extraction sockets, rhBMP-2/ACS maintained alveolar ridge height while enhancing alveolar ridge width. Safety reports did not represent concerns for the proposed indications. rhBMP-2/ACS appears a promising alternative to autogenous bone grafts for alveolar ridge/maxillary sinus augmentation; dose and carrier optimization may expand its efficacy, use, and clinical application. © 2013 Wiley Periodicals, Inc.
Full Text Available Nodal and BMP signals are important for establishing left-right (LR asymmetry in vertebrates. In sea urchins, Nodal signaling prevents the formation of the rudiment on the right side. However, the opposing pathway to Nodal signaling during LR axis establishment is not clear. Here, we revealed that BMP signaling is activated in the left coelomic pouch, specifically in the veg2 lineage, but not in the small micromeres. By perturbing BMP activities, we demonstrated that BMP signaling is required for activating the expression of the left-sided genes and the formation of the left-sided structures. On the other hand, Nodal signals on the right side inhibit BMP signaling and control LR asymmetric separation and apoptosis of the small micromeres. Our findings show that BMP signaling is the positive signal for left-sided development in sea urchins, suggesting that the opposing roles of Nodal and BMP signals in establishing LR asymmetry are conserved in deuterostomes.
Kevin T Gobeske
Full Text Available Exposure to exercise or to environmental enrichment increases the generation of new neurons in the adult hippocampus and promotes certain kinds of learning and memory. While the precise role of neurogenesis in cognition has been debated intensely, comparatively few studies have addressed the mechanisms linking environmental exposures to cellular and behavioral outcomes. Here we show that bone morphogenetic protein (BMP signaling mediates the effects of exercise on neurogenesis and cognition in the adult hippocampus. Elective exercise reduces levels of hippocampal BMP signaling before and during its promotion of neurogenesis and learning. Transgenic mice with decreased BMP signaling or wild type mice infused with a BMP inhibitor both exhibit remarkable gains in hippocampal cognitive performance and neurogenesis, mirroring the effects of exercise. Conversely, transgenic mice with increased BMP signaling have diminished hippocampal neurogenesis and impaired cognition. Exercise exposure does not rescue these deficits, suggesting that reduced BMP signaling is required for environmental effects on neurogenesis and learning. Together, these observations show that BMP signaling is a fundamental mechanism linking environmental exposure with changes in cognitive function and cellular properties in the hippocampus.
Wang, Y.; Bakker, F.; Groot, de R.S.; Woertche, H.
The influence of urban green infrastructure on the indoor environment and the effects on human comfort and economic consequences are still unclear. This paper gives a systematic overview of the relationship, in terms of so-called ‘ecosystem services’, between urban green infrastructure and the
Thomas, J Terrig; Eric Dollins, D; Andrykovich, Kristin R; Chu, Tehyen; Stultz, Brian G; Hursh, Deborah A; Moos, Malcolm
The matricellular protein SMOC (Secreted Modular Calcium binding protein) is conserved phylogenetically from vertebrates to arthropods. We showed previously that SMOC inhibits bone morphogenetic protein (BMP) signaling downstream of its receptor via activation of mitogen-activated protein kinase (MAPK) signaling. In contrast, the most prominent effect of the Drosophila orthologue, pentagone ( pent ), is expanding the range of BMP signaling during wing patterning. Using SMOC deletion constructs we found that SMOC-∆EC, lacking the extracellular calcium binding (EC) domain, inhibited BMP2 signaling, whereas SMOC-EC (EC domain only) enhanced BMP2 signaling. The SMOC-EC domain bound HSPGs with a similar affinity to BMP2 and could expand the range of BMP signaling in an in vitro assay by competition for HSPG-binding. Together with data from studies in vivo we propose a model to explain how these two activities contribute to the function of Pent in Drosophila wing development and SMOC in mammalian joint formation.
Bozorgui, Behnaz; Teimouri, Hamid; Kolomeisky, Anatoly B.
We present a quantitative model that explains the scaling of BMP4 gradients during gastrulation and the recent experimental observation that geometric confinement of human embryonic stem cells is sufficient to recapitulate much of germ layer patterning. Based on a assumption that BMP4 diffusion rate is much smaller than the diffusion rate of it's inhibitor molecules, our results confirm that the length-scale which defines germ layer territories does not depend on system size.
Lintern, Katherine B; Guidato, Sonia; Rowe, Alison; Saldanha, José W; Itasaki, Nobue
Cross-talk of BMP and Wnt signaling pathways has been implicated in many aspects of biological events during embryogenesis and in adulthood. A secreted protein Wise and its orthologs (Sostdc1, USAG-1, and Ectodin) have been shown to modulate Wnt signaling and also inhibit BMP signals. Modulation of Wnt signaling activity by Wise is brought about by an interaction with the Wnt co-receptor LRP6, whereas BMP inhibition is by binding to BMP ligands. Here we have investigated the mode of action of Wise on Wnt and BMP signals. It was found that Wise binds LRP6 through one of three loops formed by the cystine knot. The Wise deletion construct lacking the LRP6-interacting loop domain nevertheless binds BMP4 and inhibits BMP signals. Moreover, BMP4 does not interfere with Wise-LRP6 binding, suggesting separate domains for the physical interaction. Functional assays also show that the ability of Wise to block Wnt1 activity through LRP6 is not impeded by BMP4. In contrast, the ability of Wise to inhibit BMP4 is prevented by additional LRP6, implying a preference of Wise in binding LRP6 over BMP4. In addition to the interaction of Wise with BMP4 and LRP6, the molecular characteristics of Wise, such as glycosylation and association with heparan sulfate proteoglycans on the cell surface, are suggested. This study helps to understand the multiple functions of Wise at the molecular level and suggests a possible role for Wise in balancing Wnt and BMP signals.
Full Text Available Bone morphogenetic proteins (BMPs regulate many aspects of skeletal development, including osteoblast and chondrocyte differentiation, cartilage and bone formation, and cranial and limb development. Among them, BMP-2, one of the most potent osteogenic signaling molecules, stimulates osteoblast differentiation, while it inhibits myogenic differentiation in C2C12 cells. To evaluate genes involved in BMP-2-induced osteoblast differentiation, we performed cDNA microarray analyses to compare BMP-2-treated and -untreated C2C12 cells. We focused on Alx3 (aristaless-like homeobox 3 which was clearly induced during osteoblast differentiation. Alx3, a homeobox gene related to the Drosophilaaristaless gene, has been linked to developmental functions in craniofacial structures and limb development. However, little is known about its direct relationship with bone formation. In the present study, we focused on the mechanisms of Alx3 gene expression and function during osteoblast differentiation induced by BMP-2. In C2C12 cells, BMP-2 induced increase of Alx3 gene expression in both time- and dose-dependent manners through the BMP receptors-mediated SMAD signaling pathway. In addition, silencing of Alx3 by siRNA inhibited osteoblast differentiation induced by BMP-2, as showed by the expressions of alkaline phosphatase (Alp, Osteocalcin, and Osterix, while over-expression of Alx3 enhanced osteoblast differentiation induced by BMP-2. These results indicate that Alx3 expression is enhanced by BMP-2 via the BMP receptors mediated-Smad signaling and that Alx3 is a positive regulator of osteoblast differentiation induced by BMP-2.
Plikus, Maksim V; Mayer, Julie Ann; de la Cruz, Damon; Baker, Ruth E; Maini, Philip K; Maxson, Robert; Chuong, Cheng-Ming
In the age of stem cell engineering it is critical to understand how stem cell activity is regulated during regeneration. Hairs are mini-organs that undergo cyclic regeneration throughout adult life, and are an important model for organ regeneration. Hair stem cells located in the follicle bulge are regulated by the surrounding microenvironment, or niche. The activation of such stem cells is cyclic, involving periodic beta-catenin activity. In the adult mouse, regeneration occurs in waves in a follicle population, implying coordination among adjacent follicles and the extrafollicular environment. Here we show that unexpected periodic expression of bone morphogenetic protein 2 (Bmp2) and Bmp4 in the dermis regulates this process. This BMP cycle is out of phase with the WNT/beta-catenin cycle, thus dividing the conventional telogen into new functional phases: one refractory and the other competent for hair regeneration, characterized by high and low BMP signalling, respectively. Overexpression of noggin, a BMP antagonist, in mouse skin resulted in a markedly shortened refractory phase and faster propagation of the regenerative wave. Transplantation of skin from this mutant onto a wild-type host showed that follicles in donor and host can affect their cycling behaviours mutually, with the outcome depending on the equilibrium of BMP activity in the dermis. Administration of BMP4 protein caused the competent region to become refractory. These results show that BMPs may be the long-sought 'chalone' inhibitors of hair growth postulated by classical experiments. Taken together, results presented in this study provide an example of hierarchical regulation of local organ stem cell homeostasis by the inter-organ macroenvironment. The expression of Bmp2 in subcutaneous adipocytes indicates physiological integration between these two thermo-regulatory organs. Our findings have practical importance for studies using mouse skin as a model for carcinogenesis, intra-cutaneous drug
Full Text Available Common approaches to mapping green infrastructure in urbanised landscapes invariably focus on measures of land use or land cover and associated functional or physical traits. However, such one-dimensional perspectives do not accurately capture the character and complexity of the landscapes in which urban inhabitants live. The new approach presented in this paper demonstrates how open-source, high spatial and temporal resolution data with global coverage can be used to measure and represent the landscape qualities of urban environments. Through going beyond simple metrics of quantity, such as percentage green and blue cover, it is now possible to explore the extent to which landscape quality helps to unpick the mixed evidence presented in the literature on the benefits of urban nature to human well-being. Here we present a landscape approach, employing remote sensing, GIS and data reduction techniques to map urban green infrastructure elements in a large U.K. city region. Comparison with existing urban datasets demonstrates considerable improvement in terms of coverage and thematic detail. The characterisation of landscapes, using census tracts as spatial units, and subsequent exploration of associations with social–ecological attributes highlights the further detail that can be uncovered by the approach. For example, eight urban landscape types identified for the case study city exhibited associations with distinct socioeconomic conditions accountable not only to quantities but also qualities of green and blue space. The identification of individual landscape features through simultaneous measures of land use and land cover demonstrated unique and significant associations between the former and indicators of human health and ecological condition. The approach may therefore provide a promising basis for developing further insight into processes and characteristics that affect human health and well-being in urban areas, both in the United
Chui, T. F. M.; Yang, Y.
Green infrastructures (GI) have been widely used to mitigate flood risk, improve surface water quality, and to restore predevelopment hydrologic regimes. Commonly-used GI include, bioretention system, porous pavement and green roof, etc. They are normally sized to fulfil different design criteria (e.g. providing certain storage depths, limiting peak surface flow rates) that are formulated for current climate conditions. While GI commonly have long lifespan, the sensitivity of their performance to climate change is however unclear. This study first proposes a method to formulate suitable design criteria to meet different management interests (e.g. different levels of first flush reduction and peak flow reduction). Then typical designs of GI are proposed. In addition, a high resolution stochastic design storm generator using copulas and random cascade model is developed, which is calibrated using recorded rainfall time series. Then, few climate change scenarios are generated by varying the duration and depth of design storms, and changing the parameters of the calibrated storm generator. Finally, the performance of GI with typical designs under the random synthesized design storms are then assessed using numerical modeling. The robustness of the designs is obtained by the comparing their performance in the future scenarios to the current one. This study overall examines the robustness of the current GI design criteria under uncertain future climate conditions, demonstrating whether current GI design criteria should be modified to account for climate change.
Full Text Available Urbanized areas of the southwestern/western United States are among the fastest growing in the nation and face multiple water resource challenges. Low impact development (LID/green infrastructure (GI practices are increasingly popular technologies for managing stormwater; however, LID is often not as common in the southwest/west due to the lack of regulatory and/or economic drivers. There is also a lack of performance evaluation of these practices, particularly at the field scale. This study focused on investigating the hydrologic and pollutant removal performance of field-scale LID/GI systems in arid/semi-arid climates. Nine typical practices were reviewed: rainwater harvest system, detention pond, retention pond, bioretention, media filter, porous pavement, vegetated swale/buffer/strip, green roof, and infiltration trench, as well as integrated LIDs. We evaluate these practices by a cost-effectiveness analysis and also recommend best practices for the arid/semi-arid area. The analysis provides data support and insights for future implementation of LID/GI in the southwest/west.
Lim, Theodore C.; Welty, Claire
Green infrastructure (GI) is an approach to stormwater management that promotes natural processes of infiltration and evapotranspiration, reducing surface runoff to conventional stormwater drainage infrastructure. As more urban areas incorporate GI into their stormwater management plans, greater understanding is needed on the effects of spatial configuration of GI networks on hydrological performance, especially in the context of potential subsurface and lateral interactions between distributed facilities. In this research, we apply a three-dimensional, coupled surface-subsurface, land-atmosphere model, ParFlow.CLM, to a residential urban sewershed in Washington DC that was retrofitted with a network of GI installations between 2009 and 2015. The model was used to test nine additional GI and imperviousness spatial network configurations for the site and was compared with monitored pipe-flow data. Results from the simulations show that GI located in higher flow-accumulation areas of the site intercepted more surface runoff, even during wetter and multiday events. However, a comparison of the differences between scenarios and levels of variation and noise in monitored data suggests that the differences would only be detectable between the most and least optimal GI/imperviousness configurations.
Tovar-Vidales, Tara; Fitzgerald, Ashley M; Clark, Abbot F
Glaucoma patients have elevated aqueous humor and trabecular meshwork (TM) levels of transforming growth factor-beta2 (TGF-β2). TGF-β2 has been associated with increased extracellular matrix (ECM) deposition (i.e. fibronectin), which is attributed to the increased resistance of aqueous humor outflow through the TM. We have previously demonstrated that bone morphogenetic protein (BMP) 4 selectively counteracts the profibrotic effect of TGF-β2 with respect to ECM synthesis in the TM, and this action is reversed by the BMP antagonist gremlin. Thus, the BMP and TGF-β signaling pathways antagonize each other's antifibrotic and profibrotic roles. The purpose of this study was to determine whether cultured human TM cells: (a) express other BMP antagonists including noggin, chordin, BMPER, BAMBI, Smurf1 and 2, and (b) whether expression of these proteins is regulated by exogenous TGF-β2 treatment. Primary human trabecular meshwork (TM) cells were grown to confluency and treated with TGF-β2 (5 ng/ml) for 24 or 48 h in serum-free medium. Untreated cell served as controls. qPCR and Western immunoblots (WB) determined that human TM cells expressed mRNAs and proteins for the BMP antagonist proteins: noggin, chordin, BMPER, BAMBI, and Smurf1/2. Exogenous TGF-β2 decreased chordin, BMPER, BAMBI, and Smurf1 mRNA and protein expression. In contrast, TGF-β2 increased secreted noggin and Smurf2 mRNA and protein levels. BMP antagonist members are expressed in the human TM. These molecules may be involved in the normal function of the TM as well as TM pathogenesis. Altered expression of BMP antagonist members may lead to functional changes in the human TM. Copyright © 2016 Elsevier Ltd. All rights reserved.
Kondo, Michelle C; Low, Sarah C; Henning, Jason; Branas, Charles C
We investigated the health and safety effects of urban green stormwater infrastructure (GSI) installments. We conducted a difference-in-differences analysis of the effects of GSI installments on health (e.g., blood pressure, cholesterol and stress levels) and safety (e.g., felonies, nuisance and property crimes, narcotics crimes) outcomes from 2000 to 2012 in Philadelphia, Pennsylvania. We used mixed-effects regression models to compare differences in pre- and posttreatment measures of outcomes for treatment sites (n=52) and randomly chosen, matched control sites (n=186) within multiple geographic extents surrounding GSI sites. Regression-adjusted models showed consistent and statistically significant reductions in narcotics possession (18%-27% less) within 16th-mile, quarter-mile, half-mile (P<.001), and eighth-mile (P<.01) distances from treatment sites and at the census tract level (P<.01). Narcotics manufacture and burglaries were also significantly reduced at multiple scales. Nonsignificant reductions in homicides, assaults, thefts, public drunkenness, and narcotics sales were associated with GSI installation in at least 1 geographic extent. Health and safety considerations should be included in future assessments of GSI programs. Subsequent studies should assess mechanisms of this association.
Jørgensen, Niklas Rye; Henriksen, Z; Sørensen, O H
. Osteoblast phenotypes were induced by either dexamethasone (Dex) or bone morphogenetic protein-2 (BMP-2). Bone marrow was obtained from biopsies at the posterior iliac spine. Cells were isolated by gradient centrifugation and grown to confluence. Cells were treated with 1 nM 1,25-dihydroxyvitamin D (vitamin...... activity was increased by Dex, but not by BMP-2 treatment. P1NP production was decreased after Dex treatment, while BMP-2 had no effect on P1NP levels. Osteocalcin production was low in cultures not stimulated with vitamin D. Dex or BMP-2 treatment alone did not affect the basic osteocalcin levels......, but in combination with vitamin D, BMP-2 increased the osteocalcin production, while Dex treatment completely suppressed osteocalcin production. Further, PTH-induced cAMP production was greatly enhanced by Dex treatment, whereas BMP-2 did not affect cAMP production. Finally, in vitro mineralization was greatly...
Full Text Available Gremlin-1, a bone morphogenetic protein (BMP antagonist, is overexpressed in various cancerous tissues but its role in carcinogenesis has not been established. Here, we report that gremlin-1 binds various cancer cell lines and this interaction is inhibited by our newly developed gremlin-1 antibody, GRE1. Gremlin-1 binding to cancer cells was unaffected by the presence of BMP-2, BMP-4, and BMP-7. In addition, the binding was independent of vascular endothelial growth factor receptor-2 (VEGFR2 expression on the cell surface. Addition of gremlin-1 to A549 cells induced a fibroblast-like morphology and decreased E-cadherin expression. In a scratch wound healing assay, A549 cells incubated with gremlin-1 or transfected with gremlin-1 showed increased migration, which was inhibited in the presence of the GRE1 antibody. Gremlin-1 transfected A549 cells also exhibited increased invasiveness as well as an increased growth rate. These effects were also inhibited by the addition of the GRE1 antibody. In conclusion, this study demonstrates that gremlin-1 directly interacts with cancer cells in a BMP- and VEGFR2-independent manner and can induce cell migration, invasion, and proliferation.
Azmi, Tengku Norsuhaila T.; Azma Abdullah, Nurul; Rahman, Nurul Hidayah Ab; Hamid, Isredza Rahmi A.; Chai Wen, Chuah
Image is one of the evidence component seek in digital forensics. Joint Photographic Experts Group (JPEG) format is most popular used in the Internet because JPEG files are very lossy and easy to compress that can speed up Internet transmitting processes. However, corrupted JPEG images are hard to recover due to the complexities of determining corruption point. Nowadays Bitmap (BMP) images are preferred in image processing compared to another formats because BMP image contain all the image information in a simple format. Therefore, in order to investigate the corruption point in JPEG, the file is required to be converted into BMP format. Nevertheless, there are many things that can influence the corrupting of BMP image such as the changes of image size that make the file non-viewable. In this paper, the experiment indicates that the size of BMP file influences the changes in the image itself through three conditions, deleting, replacing and insertion. From the experiment, we learnt by correcting the file size, it can able to produce a viewable file though partially. Then, it can be investigated further to identify the corruption point.
Qian, Dongyang; Bai, Bo; Yan, Guangbin; Zhang, Shujiang; Liu, Qi; Chen, Yi; Tan, Xiaobo; Zeng, Yanjun
The repairing of large segmental bone defects is difficult for clinical orthopedists at present. Gene therapy is regarded as a promising method for bone defects repair. The present study aimed to construct an effective and controllable Tet-On expression system for transferring hBMP-2 gene into bone marrow mesenchymal progenitor cells (BMSCs). Meanwhile, with combination of alginate-poly-L-lysine-alginate (APA) microencapsulation technology, we attempted to reduce the influence of immunologic rejection and examine the effect of the Tet-On expression system on osteogenesis of BMSCs. The adenovirus encoding hBMP-2 (ADV-hBMP2) was constructed using the means of molecular cloning. The ADV-hBMP2 and Adeno-X Tet-On virus was respectively transfected to the HEK293 for amplification and afterward BMSCs were co-infected with the virus of ADV-hBMP2 and the Adeno-X Tet-On. The expression of hBMP-2 was measured with induction by doxycycline (DOX) at different concentration by means of RT-PCR and ELISA. Combining Tet-On expression system and APA microcapsules with the use of the pulsed high-voltage electrostatic microcapsule instrument, we examined the expression level of hBMP-2 in APA microcapsules by ELISA as well as the osteogenesis by alizarin red S staining. An effective Tet-On expression system for transferring hBMP-2 gene into BMSCs was constructed successfully. Also, the expression of hBMP-2 could be regulated by concentration of DOX. The data exhibited that BMSCs in APA microcapsules maintained the capability of proliferation and differentiation. The combination of Tet-On expression system and APA microcapsules could promote the osteogenesis of BMSCs. According to the results, microencapsulated Tet-On expression system showed the effective characteristics of secreting hBMP-2 and enhancing osteogenesis, which would provide a promising way for bone repair.
Piscopo, A. N.; Detenbeck, N. E.
Managers of urban watersheds with excessive nutrient loads are more frequently turning to green infrastructure (GI) to manage their water quality impairments. The effectiveness of GI is dependent on a number of factors, including (1) the type and placement of GI within the watershed, (2) the specific nutrients to be treated, and (3) the uncertainty in future climates. Although many studies have investigated the effectiveness of individual GI units for different types of nutrients, relatively few have considered the effectiveness of GI on a watershed scale, the scale most relevant to management plans. At the watershed scale, endless combinations of GI type and location are possible, each with different effectiveness in reducing nutrient loads, minimizing costs, and maximizing co-benefits such as reducing runoff. To efficiently generate management plan options that balance the tradeoffs between these objectives, we simulate candidate options using EPA's Stormwater Management Model for multiple future climates and determine the Pareto optimal set of solution options using a multi-objective evolutionary algorithm. Our approach is demonstrated for an urban watershed in Rockville, Maryland.
Introduction: Urban roadside nature, an important component of ecosystem services, provides the opportunity for individuals to experience the natural world while going about their everyday lives. Despite mounting evidence that green space can improve health and health determinant...
Full Text Available Abstract Background Bone morphogenetic protein 4 gene (BMP4 plays a key role during maxillofacial development, since orofacial clefts are observed in animals when this gene is conditionally inactivated. We recently reported the existence of association between nonsyndromic cleft lip/palate (NSCLP and BMP4 polymorphisms by detecting transmission deviations for haplotypes that include a region containing a BMP4 promoter in case-parent trios. The aim of the present study was to search for possible causal mutations within BMP4 promoters (BMP4.1 and BMP4.2. Methods We analyzed the sequence of BMP4.1 and BMP4.2 in 167 Chilean NSCLP cases and 336 controls. Results We detected three novel variants in BMP4.1 (c.-5514G > A, c.-5365C > T and c.-5049C > T which could be considered as cleft risk factors due to their absence in controls. Additionally, rs2855530 G allele (BMP4.2 carriers showed an increased risk for NSCLP restricted to males (OR = 1.52; 95% C.I. = 1.07-2.15; p = 0.019. For this same SNP the dominant genotype model showed a higher frequency of G/G+G/C and a lower frequency of C/C in cases than controls in the total sample (p = 0.03 and in the male sample (p = 0.003. Bioinformatic prediction analysis showed that all the risk variants detected in this study could create new transcription factor binding motifs. Conclusions The sex-dependent association between rs2855530 and NSCLP could indirectly be related to the differential gene expression observed between sexes in animal models. We concluded that risk variants detected herein could potentially alter BMP4 promoter activity in NSCLP. Further functional and developmental studies are necessary to support this hypothesis.
Tucker, A S; Al Khamis, A; Sharpe, P T
Tooth development is regulated by a reciprocal series of epithelial-mesenchymal interactions. Bmp4 has been identified as a candidate signalling molecule in these interactions, initially as an epithelial signal and then later at the bud stage as a mesenchymal signal (Vainio et al.  Cell 75:45-58). A target gene for Bmp4 signalling is the homeobox gene Msx-1, identified by the ability of recombinant Bmp4 protein to induce expression in mesenchyme. There is, however, no evidence that Bmp4 is the endogenous inducer of Msx-1 expression. Msx-1 and Bmp-4 show dynamic, interactive patterns of expression in oral epithelium and ectomesenchyme during the early stages of tooth development. In this study, we compare the temporal and spatial expression of these two genes to determine whether the changing expression patterns of these genes are consistent with interactions between the two molecules. We show that changes in Bmp-4 expression precede changes in Msx-1 expression. At embryonic day (E)10.5-E11.0, expression patterns are consistent with BMP4 from the epithelium, inducing or maintaining Msx-1 in underlying mesenchyme. At E11.5, Bmp-4 expression shifts from epithelium to mesenchyme and is rapidly followed by localised up-regulation of Msx-1 expression at the sites of Bmp-4 expression. Using cultured explants of developing mandibles, we confirm that exogenous BMP4 is capable of replacing the endogenous source in epithelium and inducing Msx-1 gene expression in mesenchyme. By using noggin, a BMP inhibitor, we show that endogenous Msx-1 expression can be inhibited at E10.5 and E11.5, providing the first evidence that endogenous Bmp-4 from the epithelium is responsible for regulating the early spatial expression of Msx-1. We also show that the mesenchymal shift in Bmp-4 is responsible for up-regulating Msx-1 specifically at the sites of future tooth formation. Thus, we establish that a reciprocal series of interactions act to restrict expression of both genes to future
Follansbee, Taylor L; Gjelsvik, Kayla J; Brann, Courtney L; McParland, Aidan L; Longhurst, Colin A; Galko, Michael J; Ganter, Geoffrey K
Nociceptive sensitization is a common feature in chronic pain, but its basic cellular mechanisms are only partially understood. The present study used the Drosophila melanogaster model system and a candidate gene approach to identify novel components required for modulation of an injury-induced nociceptive sensitization pathway presumably downstream of Hedgehog. This study demonstrates that RNAi silencing of a member of the Bone Morphogenetic Protein (BMP) signaling pathway, Decapentaplegic (Dpp), specifically in the Class IV multidendritic nociceptive neuron, significantly attenuated ultraviolet injury-induced sensitization. Furthermore, overexpression of Dpp in Class IV neurons was sufficient to induce thermal hypersensitivity in the absence of injury. The requirement of various BMP receptors and members of the SMAD signal transduction pathway in nociceptive sensitization was also demonstrated. The effects of BMP signaling were shown to be largely specific to the sensitization pathway and not associated with changes in nociception in the absence of injury or with changes in dendritic morphology. Thus, the results demonstrate that Dpp and its pathway play a crucial and novel role in nociceptive sensitization. Because the BMP family is so strongly conserved between vertebrates and invertebrates, it seems likely that the components analyzed in this study represent potential therapeutic targets for the treatment of chronic pain in humans. SIGNIFICANCE STATEMENT This report provides a genetic analysis of primary nociceptive neuron mechanisms that promote sensitization in response to injury. Drosophila melanogaster larvae whose primary nociceptive neurons were reduced in levels of specific components of the BMP signaling pathway, were injured and then tested for nocifensive responses to a normally subnoxious stimulus. Results suggest that nociceptive neurons use the BMP2/4 ligand, along with identified receptors and intracellular transducers to transition to a
Wang, Jingxiao; Zheng, Yuanna; Zhao, Juan; Liu, Tie; Gao, Lixia; Gu, Zhiyuan; Wu, Gang
To delineate the dynamic micro-architectures of bone induced by low-dose bone morphogenetic protein (BMP)-2/7 heterodimer in peri-implant bone defects compared to BMP2 and BMP7 homodimer. Peri-implant bone defects (8 mm in diameter, 4 mm in depth) were created surrounding SLA-treated titanium implants (3.1 mm in diameter, 10 mm in length) in minipig's calvaria. We administrated collagen sponges with adsorbed low-dose (30 ng/mm(3) ) BMP2/7 to treat the defects using BMP2, BMP7 or no BMP as controls.2, 3 and 6 weeks after implantation, we adopted micro-computer tomography to evaluate the micro-architectures of new bone using the following parameters: relative bone volume (BV/TV), trabecular number (Tb.N), trabecular thickness (Tb.Th), trabecular separation (Tb.Sp), connectivity density, and structure mode index (SMI). Bone implant contact (BIC) was also revealed histologically. Consistent with 2 and 3 weeks, after 6 weeks post-operation, BMP2/7 resulted in significantly higher BV/TV (63.033 ± 2.055%) and significantly lower SMI (-4.405 ± 0.500) than BMP2 (BV/TV: 43.133 ± 2.001%; SMI: -0.086 ± 0.041) and BMP7 (BV/TV: 41.467 ± 1.850%; SMI: -0.044 ± 0.016) respectively. Significant differences were also found in Tb.N, Tb.Th and Tb.Sp at all time points. At 2 weeks, BMP2/7 resulted in significantly higher BIC than the controls. Low-dose BMP2/7 heterodimer facilitated more rapid bone regeneration in better quality in peri-implant bone defects than BMP2 and BMP7 homodimers. © 2011 John Wiley & Sons A/S.
Huang, Baolin; Yuan, Yuan; Ding, Sai; Li, Jianbo; Ren, Jie; Feng, Bo; Li, Tong; Gu, Yuantong; Liu, Changsheng
Highly efficient loading of bone morphogenetic protein-2 (BMP-2) onto carriers with desirable performance is still a major challenge in the field of bone regeneration. Till now, the nanoscaled surface-induced changes of the structure and bioactivity of BMP-2 remains poorly understood. Here, the effect of nanoscaled surface on the adsorption and bioactivity of BMP-2 was investigated with a series of hydroxyapatite surfaces (HAPs): HAP crystal-coated surface (HAP), HAP crystal-coated polished surface (HAP-Pol), and sintered HAP crystal-coated surface (HAP-Sin). The adsorption dynamics of recombinant human BMP-2 (rhBMP-2) and the accessibility of the binding epitopes of adsorbed rhBMP-2 for BMP receptors (BMPRs) were examined by a quartz crystal microbalance with dissipation. Moreover, the bioactivity of adsorbed rhBMP-2 and the BMP-induced Smad signaling were investigated with C2C12 model cells. A noticeably high mass-uptake of rhBMP-2 and enhanced recognition of BMPR-IA to adsorbed rhBMP-2 were found on the HAP-Pol surface. For the rhBMP-2-adsorbed HAPs, both ALP activity and Smad signaling increased in the order of HAP-Sinuses of rhBMP-2 in clinical applications and arouse broad interests among researchers in the fields of nano-biotechnology, biomaterials and bone tissue engineering. Copyright © 2015 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
Thomé, Antônio Márcio Tavares; Ceryno, Paula Santos; Scavarda, Annibal; Remmen, Arne
This paper proposes a taxonomy of themes and a research agenda on sustainable infrastructure, with a focus on sustainable buildings (SB) and green infrastructure (GI). The citation databases of Web of Science formed the basis for a novel strategic thematic analysis of co-citation and co-occurrence of keywords with a longitudinal identification of themes during the last two decades (from 1995 to 2015) of an emerging and ever growing research area. SI is a multidisciplinary endeavour, including a diversified array of disciplines as general engineering, environmental ecology, construction, architecture, urban planning, and geography. This paper traces that the number of publications in SI is growing exponentially since 2003. Over 80% of total citations are concentrated in less than 10% of papers spread over a large number of journals. Most publications originate from the United States, Europe, Australia, and Asia. The main research streams in SI are green infrastructure, sustainable buildings, and assessment methods. Emerging and prevailing research themes include methodological issues of cost-effectiveness, project management and assessment tools. Substantive issues complement the research agenda of emerging themes in the areas of integration of human, economic and corporate social responsibility values in environmental sustainability, urban landscape and sustainable drainage systems, interdisciplinary research in green material, integrated policy research in urbanization, agriculture and nature conservation, and extensions of Green Building (GB) and GI to cities of developing countries. Copyright © 2016 Elsevier Ltd. All rights reserved.
Calpe, Silvia; Correia, Ana C P; Sancho-Serra, Maria Del Carmen; Krishnadath, Kausilia K
Due to improved understanding of the role of bone morphogenetic protein 4 (BMP4) in an increasing number of diseases, the development of selective inhibitors of BMP4 is an attractive therapeutic option. The currently available BMP4 inhibitors are not suitable as therapeutics because of their low specificity and low effectiveness. Here, we compared newly generated anti-BMP4 llama-derived antibodies (VHHs) with 3 different types of commercially available BMP4 inhibitors, natural antagonists, small molecule BMPR inhibitors and conventional anti-BMP4 monoclonal antibodies. We found that the anti-BMP4 VHHs were as effective as the natural antagonist or small molecule inhibitors, but had higher specificity. We also showed that commercial anti-BMP4 antibodies were inferior in terms of both specificity and effectiveness. These findings might result from the fact that the VHHs C4C4 and C8C8 target a small region within the BMPR1 epitope of BMP4, whereas the commercial antibodies target other areas of the BMP4 molecule. Our results show that the newly developed anti-BMP4 VHHs are promising antibodies with better specificity and effectivity for inhibition of BMP4, making them an attractive tool for research and for therapeutic applications.
Wertheimer, Tobias; Velardi, Enrico; Tsai, Jennifer; Cooper, Kirsten; Xiao, Shiyun; Kloss, Christopher C.; Ottmüller, Katja J.; Mokhtari, Zeinab; Brede, Christian; deRoos, Paul; Kinsella, Sinéad; Palikuqi, Brisa; Ginsberg, Michael; Young, Lauren F.; Kreines, Fabiana; Lieberman, Sophia R.; Lazrak, Amina; Guo, Peipei; Malard, Florent; Smith, Odette M.; Shono, Yusuke; Jenq, Robert R.; Hanash, Alan M.; Nolan, Daniel J.; Butler, Jason M.; Beilhack, Andreas; Manley, Nancy R.; Rafii, Shahin; Dudakov, Jarrod A; van den Brink, Marcel RM
The thymus is extremely sensitive to damage but also has a remarkable ability to repair itself. However, the mechanisms underlying this endogenous regeneration remain poorly understood and this capacity diminishes considerably with age. Here we show that thymic endothelial cells (ECs) comprise a critical pathway of regeneration, via their production of BMP4. ECs increased their production of BMP4 after thymic damage, and abrogating BMP4 signalling or production by either pharmacologic or genetic inhibition impaired thymic repair. EC-derived BMP4 acted on thymic epithelial cells (TECs) to increase their expression of Foxn1, a key transcription factor involved in TEC development, maintenance and regeneration; and its downstream targets such as Dll4, itself a key mediator of thymocyte development and regeneration. These studies demonstrate the importance of the BMP4 pathway in endogenous tissue regeneration and offer a potential clinical approach to enhance T cell immunity. PMID:29330161
Duan, Junya; Wang, Yafei; Fan, Chen; Xia, Beicheng; de Groot, Rudolf
Cities face many challenging environmental problems that affect human well-being. Environmental risks can be reduced by Urban Green Infrastructures (UGIs). The effects of UGIs on the urban environment have been widely studied, but less attention has been given to the public perception of these effects. This paper presents the results of a study in Guangzhou, China, on UGI users' perceptions of these effects and their relationship with sociodemographic variables. A questionnaire survey was conducted in four public green spaces. Descriptive statistics, a binary logistic regression model and cross-tabulation analysis were applied on the data from 396 valid questionnaires. The results show that UGI users were more concerned about poor air quality and high temperature than about flooding events. Their awareness of environmental risks was partly in accordance with official records. Regarding the perception of the impacts of environmental risks on human well-being, elderly and female respondents with higher education levels were the most sensitive to these impacts. The respondents' perceptions of these impacts differed among the different green spaces. The effects of UGIs were well perceived and directly observed by the UGI users, but were not significantly influenced by most sociodemographic variables. Moreover, tourists had a lower perception of the impacts of environmental risks and the effects of UGI than residents did. This study provides strong support for UGIs as an effective tool to mitigate environmental risks. Local governments should consider the role of UGIs in environmental risk mitigation and human well-being with regard to urban planning and policy making.
Full Text Available Background/Aims: BMP9 is highly capable of promoting osteogenic differentiation of mesenchymal stem cells (MSCs although the molecular mechanism involved is largely unknown. Here, we explored the detail role of PKA/CREB signaling in BMP9-induced osteogenic differentiation. Methods: Activation status of PKA/CREB signaling is assessed by nonradioactive assay and Western blot. Using PKA inhibitors and a dominant negative protein of CREB (A-CREB, we investigated the effect of PKA/CREB signaling on BMP9-induced osteogenic differentiation. Results: We found that BMP9 promotes PKA activity and enhances CREB phosphorylation in MSCs. BMP9 is shown to down-regulate protein kinase A inhibitor γ (PKIγ expression. We demonstrated that PKA inhibitors suppress BMP9-induced early osteogenic marker alkaline phosphatase (ALP activity in MSCs as well as late osteogenic markers osteopontin (OPN, osteocalcin (OCN and matrix mineralization. We found that PKA inhibitor reduces BMP9-induced Runx2 activation and p38 phosphorylation in MSCs. Lastly, interference of CREB function by A-CREB decreased BMP9-induced osteogenic differentiation as well. Conclusion: Our results revealed that BMP9 may activate PKA/CREB signaling in MSCs through suppression of PKIγ expression. It is noteworthy that inhibition of PKA/CREB signaling may impair BMP9-induced osteogenic differentiation of MSCs, implying that activation of PKA/CREB signaling is required for BMP9 osteoinductive activity.
Tabisz, Barbara; Schmitz, Werner; Schmitz, Michael; Luehmann, Tessa; Heusler, Eva; Rybak, Jens-Christoph; Meinel, Lorenz; Fiebig, Juliane E; Mueller, Thomas D; Nickel, Joachim
The regenerative potential of bone is strongly impaired in pathological conditions, such as nonunion fractures. To support bone regeneration various scaffolds have been developed in the past, which have been functionalized with osteogenic growth factors such as bone morphogenetic proteins (BMPs). However, most of them required supra-physiological levels of these proteins leading to burst releases, thereby causing severe side effects. Site-specific, covalent coupling of BMP2 to implant materials might be an optimal strategy in order to overcome these problems. Therefore, we created a BMP-2 variant (BMP2-K3Plk) containing a noncanonical amino acid (propargyl-l-lysine) substitution introduced by genetic code expansion that allows for site-specific and covalent immobilization onto polymeric scaffold materials. To directly compare different coupling strategies, we also produced a BMP2 variant containing an additional cysteine residue (BMP2-A2C) allowing covalent coupling by thioether formation. The BMP2-K3Plk mutant was coupled to functionalized beads by a copper-catalyzed azide-alkyne cycloaddition (CuAAC) either directly or via a short biotin-PEG linker both with high specificity. After exposing the BMP-coated beads to C2C12 cells, ALP expression appeared locally restricted in close proximity to these beads, showing that both coupled BMP2 variants trigger cell differentiation. The advantage of our approach over non-site-directed immobilization techniques is the ability to produce fully defined osteogenic surfaces, allowing for lower BMP2 loads and concomitant higher bioactivities, for example, due to controlled orientation toward BMP2 receptors. Such products might provide superior bone healing capabilities with potential safety advantages as of homogeneous product outcome.
Bone morphogenetic protein (Bmp) signaling is vitally important in many aspects of cardiac development. These include cardiac induction and differentiation and establishing the L/R axis. In this thesis, we focus on the role of Bmp signaling in securing proper cardiac asymmetry, by (1) establishing
Gamer, Laura W; Cox, Karen; Carlo, Joelle M; Rosen, Vicki
Bone morphogenetic protein-3 (BMP) has been identified as a negative regulator in the skeleton as mice lacking BMP3 have increased bone mass. To further understand how BMP3 mediates bone formation, we created transgenic mice overexpressing BMP3 using the type I collagen promoter. BMP3 transgenic mice displayed spontaneous rib fractures that were first detected at E17.0. The fractures were due to defects in differentiation of the periosteum and late hypertrophic chondrocytes resulting in thinner cortical bone with decreased mineralization. As BMP3 modulates BMP and activin signaling through ActRIIB, we examined the ribs of ActRIIB receptor knockout mice and found they had defects in late chondrogenesis and mineralization similar to BMP3 transgenic mice. These data suggest that BMP3 exerts its effects in the skeleton by altering signaling through ActRIIB in chondrocytes and the periosteum, and this results in defects in bone collar formation and late hypertrophic chondrocyte maturation leading to decreased mineralization and less bone. 2009 Wiley-Liss, Inc.
Full Text Available Efficient osteogenetic differentiation and bone formation from muscle-derived stem cells (MDSCs should have potential clinical applications in treating nonunion fracture healing or bone defects. Here, we investigate osteogenetic differentiation ability of MDSCs induced by bone morphogenetic protein 9 (BMP9 in vitro and bone formation ability in rabbit radius defects repairing model. Rabbit's MDSCs were extracted by type I collagenase and trypsin methods, and BMP9 was introduced into MDSCs by infection with recombinant adenovirus. Effects of BMP9-induced osteogenetic differentiation of MDSCs were identified with alkaline phosphatase (ALP activity and expression of later marker. In stem-cell implantation assay, MDSCs have also shown valuable potential bone formation ability induced by BMP9 in rabbit radius defects repairing test. Taken together, our findings suggest that MDSCs are potentiated osteogenetic stem cells which can be induced by BMP9 to treat large segmental bone defects, nonunion fracture, and/or osteoporotic fracture.
Insulin-like growth factor-1 (IGF-1) enhances the osteogenic activity of bone morphogenetic protein-6 (BMP-6) in vitro and in vivo, and together have a stronger osteogenic effect than when IGF-1 is combined with BMP-2.
Rico-Llanos, Gustavo A; Becerra, Jose; Visser, Rick
Bone morphogenetic protein-2 (BMP-2) is widely used in orthopedic surgery and bone tissue engineering because of its strong osteogenic activity. However, BMP-2 treatments have several drawbacks and many groups are actively exploring alternatives. Since BMP-6 has been demonstrated to be more osteoinductive, its use, either alone or together with other growth factors, might be an interesting option. In this work, we have compared the effect of BMP-2, BMP-6, or insulin-like growth factor-1 (IGF-1), either alone or in combination. Murine preosteoblasts were treated with 15 nM IGF-1 and/or 6 nM BMP-2 or -6 and the expression of osteogenic marker genes, proliferation, and alkaline phosphatase (ALP) activity in vitro were analyzed. The results showed that IGF-1 greatly enhanced the BMP-induced osteogenic differentiation of these cells in general and that the ALP activity in the cultures was higher when the combination was made with BMP-6 than with BMP-2. Furthermore, we tested the osteogenic potential of these treatments in vivo by loading 25 pmoles of IGF-1 and/or 10 pmoles of BMP-2 or -6 onto absorbable collagen sponges and implanting them into an ectopic bone formation model in rats. This study revealed that only BMP-6 was able to induce bone formation at the used dose and that the addition of IGF-1 contributed to an increase of the mineralization in the implants. Hence, the combination of BMP-6 with IGF-1 might be a better alternative than BMP-2 for orthopedic surgery or bone tissue engineering approaches. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 1867-1875, 2017. © 2017 Wiley Periodicals, Inc.
Gilde, Flora; Fourel, Laure; Guillot, Raphael; Pignot-Paintrand, Isabelle; Okada, Takaharu; Fitzpatrick, Vincent; Boudou, Thomas; Albiges-Rizo, Corinne; Picart, Catherine
Surface coatings delivering BMP are a promising approach to render biomaterials osteoinductive. In contrast to soluble BMPs which can interact with their receptors at the dorsal side of the cell, BMPs presented as an insoluble cue physically bound to a biomimetic matrix, called here matrix-bound (bBMP-2), are presented to cells by their ventral side. To date, BMP-2 internalization and signaling studies in cell biology have always been performed by adding soluble (sBMP-2) to cells adhered on cell culture plates or glass slides, which will be considered here as a "reference" condition. However, whether and how matrix-bound BMP-2 can be internalized by cells and its relation to canonical (SMAD) and non-canonical signaling (ALP) remain open questions. In this study, we investigated the uptake and processing of BMP-2 by C2C12 myoblasts. This BMP-2 was presented either embedded in polyelectrolyte multilayer films (matrix-bound presentation) or as soluble form. Using fluorescently labeled BMP-2, we showed that the amount of matrix-bound BMP-2 internalized is dependent on the level of crosslinking of the polyelectrolyte films. Cav-1-mediated internalization is related to both SMAD and ALP signaling, while clathrin-mediated is only related to ALP signaling. BMP-2 internalization was independent of the presentation mode (sBMP-2 versus bBMP-2) for low crosslinked films (soft, EDC10) in striking contrast with high crosslinked (stiff, EDC70) films where internalization was much lower and slower for bBMP-2. As anticipated, internalization of sBMP-2 barely depended on the underlying matrix. Taken together, these results indicate that BMP-2 internalization can be tuned by the underlying matrix and activates downstream BMP-2 signaling, which is key for the effective formation of bone tissue. The presentation of growth factors from material surfaces currently presents significant challenges in academic research, clinics and industry. Being able to deliver efficiently these growth
Tribulo, Celeste; Aybar, Manuel J; Nguyen, Vu H; Mullins, Mary C; Mayor, Roberto
There is evidence in Xenopus and zebrafish embryos that the neural crest/neural folds are specified at the border of the neural plate by a precise threshold concentration of a Bmp gradient. In order to understand the molecular mechanism by which a gradient of Bmp is able to specify the neural crest, we analyzed how the expression of Bmp targets, the Msx genes, is regulated and the role that Msx genes has in neural crest specification. As Msx genes are directly downstream of Bmp, we analyzed Msx gene expression after experimental modification in the level of Bmp activity by grafting a bead soaked with noggin into Xenopus embryos, by expressing in the ectoderm a dominant-negative Bmp4 or Bmp receptor in Xenopus and zebrafish embryos, and also through Bmp pathway component mutants in the zebrafish. All the results show that a reduction in the level of Bmp activity leads to an increase in the expression of Msx genes in the neural plate border. Interestingly, by reaching different levels of Bmp activity in animal cap ectoderm, we show that a specific concentration of Bmp induces msx1 expression to a level similar to that required to induce neural crest. Our results indicate that an intermediate level of Bmp activity specifies the expression of Msx genes in the neural fold region. In addition, we have analyzed the role that msx1 plays on neural crest specification. As msx1 has a role in dorsoventral pattering, we have carried out conditional gain- and loss-of-function experiments using different msx1 constructs fused to a glucocorticoid receptor element to avoid an early effect of this factor. We show that msx1 expression is able to induce all other early neural crest markers tested (snail, slug, foxd3) at the time of neural crest specification. Furthermore, the expression of a dominant negative of Msx genes leads to the inhibition of all the neural crest markers analyzed. It has been previously shown that snail is one of the earliest genes acting in the neural crest
Pollitt, Rebecca C; Saraff, Vrinda; Dalton, Ann; Webb, Emma A; Shaw, Nick J; Sobey, Glenda J; Mughal, M Zulf; Hobson, Emma; Ali, Farhan; Bishop, Nicholas J; Arundel, Paul; Högler, Wolfgang; Balasubramanian, Meena
Osteogenesis Imperfecta (OI) is an inherited bone fragility disorder most commonly associated with autosomal dominant mutations in the type I collagen genes. Autosomal recessive mutations in a number of genes have also been described, including the BMP1 gene that encodes the mammalian Tolloid (mTLD) and its shorter isoform bone morphogenic protein-1 (BMP1). To date, less than 20 individuals with OI have been identified with BMP1 mutations, with skeletal phenotypes ranging from mild to severe and progressively deforming. In the majority of patients, bone fragility was associated with increased bone mineral density (BMD); however, the full range of phenotypes associated with BMP1 remains unclear. Here, we describe three children with mutations in BMP1 associated with a highly variable phenotype: a sibship homozygous for the c.2188delC mutation that affects only the shorter BMP1 isoform and a further patient who is compound heterozygous for a c.1293C>G nonsense mutation and a c.1148G>A missense mutation in the CUB1 domain. These individuals had recurrent fractures from early childhood, are hypermobile and have no evidence of dentinogenesis imperfecta. The homozygous siblings with OI had normal areal BMD by dual energy X-ray absorptiometry whereas the third patient presented with a high bone mass phenotype. Intravenous bisphosphonate therapy was started in all patients, but discontinued in two patients and reduced in another due to concerns about increasing bone stiffness leading to chalk-stick fractures. Given the association of BMP1-related OI with very high bone material density, concerns remain whether anti-resorptive therapy is indicated in this ultra-rare form of OI.© 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.
Kanomata, Kazuhiro; Kokabu, Shoichiro; Nojima, Junya; Fukuda, Toru; Katagiri, Takenobu
Bone morphogenetic proteins (BMPs) induce osteoblastic differentiation of myoblasts via binding to cell surface receptors. Repulsive guidance molecules (RGMs) have been identified as BMP co-receptors. We report here that DRAGON/RGMb, a member of the RGM family, suppressed BMP signaling in C2C12 myoblasts via a novel mechanism. All RGMs were expressed in C2C12 cells that were differentiated into myocytes and osteoblastic cells, but RGMc was not detected in immature cells. In C2C12 cells, only DRAGON suppressed ALP and Id1 promoter activities induced by BMP-4 or by constitutively activated BMP type I receptors. This inhibition by DRAGON was dependent on the secretory form of the von Willbrand factor type D domain. DRAGON even suppressed BMP signaling induced by constitutively activated Smad1. Over-expression of neogenin did not alter the inhibitory capacity of DRAGON. Taken together, these findings indicate that DRAGON may be an inhibitor of BMP signaling in C2C12 myoblasts. We also suggest that a novel molecule(s) expressed on the cell membrane may mediate the signal transduction of DRAGON in order to suppress BMP signaling in C2C12 myoblasts.
Full Text Available Bone morphogenetic proteins (BMPs are believed to be the most potent osteoinductive factors. However, BMPs are highly pleiotropic molecules and their supra-physiological high dose requirement leads to adverse side effects and inefficient bone formation. Thus, there is a need to develop alternative osteoinductive growth factor strategies that can effectively complement BMP activity. In this study, we intrinsically stimulated BMP signaling in adipose derived stem cells (ASCs by downregulating noggin, a potent BMP antagonist, using an RNAi strategy. ASCs transduced with noggin shRNA significantly enhanced osteogenic differentiation of cells. The potency of endogenous BMPs was subsequently enhanced by stimulating ASCs with exogenous BMPs at a significantly reduced dose. The level of mineralization in noggin shRNA treated ASCs when treated with BMP-2 was comparable to that of control shRNA treated cell treated with 10-fold more BMP-2. The complementary strategy of noggin suppression + BMP-2 to enhance osteogenesis was further confirmed in 3D in vitro environments using scaffolds consisting of chitosan (CH, chondroitin sulfate (CS, and apatite layer on their surfaces designed to slowly release BMP-2. This finding supports the novel therapeutic potential of this complementary strategy in bone regeneration.
DeCarlo Arthur A
Full Text Available Abstract Background Many growth factors, such as bone morphogenetic protein (BMP-2, have been shown to interact with polymers of sulfated disacharrides known as heparan sulfate (HS glycosaminoglycans (GAGs, which are found on matrix and cell-surface proteoglycans throughout the body. HS GAGs, and some more highly sulfated forms of chondroitin sulfate (CS, regulate cell function by serving as co-factors, or co-receptors, in GF interactions with their receptors, and HS or CS GAGs have been shown to be necessary for inducing signaling and GF activity, even in the osteogenic lineage. Unlike recombinant proteins, however, HS and CS GAGs are quite heterogenous due, in large part, to post-translational addition, then removal, of sulfate groups to various positions along the GAG polymer. We have, therefore, investigated whether it would be feasible to deliver a DNA pro-drug to generate a soluble HS/CS proteoglycan in situ that would augment the activity of growth-factors, including BMP-2, in vivo. Results Utilizing a purified recombinant human perlecan domain 1 (rhPln.D1 expressed from HEK 293 cells with HS and CS GAGs, tight binding and dose-enhancement of rhBMP-2 activity was demonstrated in vitro. In vitro, the expressed rhPln.D1 was characterized by modification with sulfated HS and CS GAGs. Dose-enhancement of rhBMP-2 by a pln.D1 expression plasmid delivered together as a lyophilized single-phase on a particulate tricalcium phosphate scaffold for 6 or more weeks generated up to 9 fold more bone volume de novo on the maxillary ridge in a rat model than in control sites without the pln.D1 plasmid. Using a significantly lower BMP-2 dose, this combination provided more than 5 times as much maxillary ridge augmentation and greater density than rhBMP-2 delivered on a collagen sponge (InFuse™. Conclusions A recombinant HS/CS PG interacted strongly and functionally with BMP-2 in binding and cell-based assays, and, in vivo, the pln.247 expression plasmid
Full Text Available The bone morphogenetic protein (BMP signaling cascade is aberrantly activated in human non-small cell lung cancer (NSCLC but not in normal lung epithelial cells, suggesting that blocking BMP signaling may be an effective therapeutic approach for lung cancer. Previous studies demonstrated that some BMP antagonists, which bind to extracellular BMP ligands and prevent their association with BMP receptors, dramatically reduced lung tumor growth. However, clinical application of protein-based BMP antagonists is limited by short half-lives, poor intra-tumor delivery as well as resistance caused by potential gain-of-function mutations in the downstream of the BMP pathway. Small molecule BMP inhibitors which target the intracellular BMP cascades would be ideal for anticancer drug development. In a zebrafish embryo-based structure and activity study, we previously identified a group of highly selective small molecule inhibitors specifically antagonizing the intracellular kinase domain of BMP type I receptors. In the present study, we demonstrated that DMH1, one of such inhibitors, potently reduced lung cell proliferation, promoted cell death, and decreased cell migration and invasion in NSCLC cells by blocking BMP signaling, as indicated by suppression of Smad 1/5/8 phosphorylation and gene expression of Id1, Id2 and Id3. Additionally, DMH1 treatment significantly reduced the tumor growth in human lung cancer xenograft model. In conclusion, our study indicates that small molecule inhibitors of BMP type I receptors may offer a promising novel strategy for lung cancer treatment.
Richards, Elliott G; El-Nashar, Sherif A; Schoolmeester, John K; Keeney, Gary L; Mariani, Andrea; Hopkins, Matthew R; Dowdy, Sean C; Daftary, Gaurang S; Famuyide, Abimbola O
Abnormal uterine bleeding (AUB), a common health concern of women, is a heterogeneous clinical entity that is traditionally categorized into organic and nonorganic causes. Despite varied pharmacologic treatments, few offer sustained efficacy, as most are empiric, unfocused, and do not directly address underlying dysregulated molecular mechanisms. Characterization of such molecular derangements affords the opportunity to develop and use novel, more successful treatments for AUB. Given its implication in other organ systems, we hypothesized that bone morphogenetic protein (BMP) expression is altered in patients with AUB and hence comprehensively investigated dysregulation of BMP signaling pathways by systematically screening 489 samples from 365 patients for differences in the expression of BMP2, 4, 6, and 7 ligands, BMPR1A and B receptors, and downstream SMAD4, 6, and 7 proteins. Expression analysis was correlated clinically with data abstracted from medical records, including bleeding history, age at procedure, ethnicity, body mass index, hormone treatment, and histological diagnosis of fibroids, polyps, adenomyosis, hyperplasia, and cancer. Expression of BMP7 ligand was significantly increased in patients with AUB (H-score: 18.0 vs 26.7; P bleeding (menorrhagia) as their specific AUB pattern demonstrated significantly higher BMP7 expression. Significantly, no differences in the expression of any other BMP ligands, receptors, or SMAD proteins were observed in this large patient cohort. However, expression of BMPR1A, BMPR1B, and SMAD4 was significantly decreased in cancer compared to benign samples. Our study demonstrates that BMP7 is a promising target for future investigation and pharmacologic treatment of AUB.
Li, Pengyao; Xiao, He; Li, Xiang; Hu, Wenhao; Gu, Shoubai; Yu, Zhenrong
Coping with various ecological risks caused by extreme weather events of global climate change has become an important issue in regional planning, and storm water management for sustainable development. In this paper, taking Shanghai, China as a case study, four potential ecological risks were identified including flood disaster, sea-source disaster, urban heat island effect, and land subsidence. Based on spatial database, the spatial variation of these four ecological risks was evaluated, and the planning area was divided into seven responding regions with different green infrastructure strategy. The methodology developed in this study combining ecological risk evaluation with spatial regionalization planning could contribute to coping with global climate change.
Klimas, C.; Montgomery, J.
Green infrastructure (GI) may be the most practical approach for reducing contaminated runoff, providing ecosystem services, mitigating food deserts and creating community open spaces in urban areas. This project was funded by the USEPA's People-Prosperity-Planet (P3) program and was a partnership between a team of DePaul University undergraduates (the P3 team) and high school interns (Green Teens) and staff from the Gary Comer Youth Center (GCYC). GCYC is located in a low-income African-American community on Chicago's south side characterized by high crime, abandoned buildings, lack of green space and a food desert. The overaching project goal was to develop a network of Green Teens qualified to conduct soil quality assessment using USDA-NRCS protocols in order to let them develop GI plans to minimize storm water runoff and contaminant loadings, improve community and environmental health, and provide more equitable access to green space. Working with a USDA-ARS soil scientist from Washington State University, the P3 team conducted soil quality assessment on 116 soil samples collected among four abandoned residential lots owned by GCYC. Analytes included infiltration, bulk density, texture, pH, conductivity, aggregate stability, available nutrients, and total and bioavailable (PBET) lead. Soil pH on all lots is greater than 8.0, are low in organic matter, have little microbial respiration activity, are enriched in available phosphorus, and have average total lead values ranging from 24-2,700 mg/kg. PBET lead was less than 40% on most lots. Regardless, these soils will need to be remediated by adding carbon-rich materials such as biosolids prior to GI installation. Students enrolled in a landscape design course at DePaul developed 3-D models representing potential GI designs for one of the vacant lots that include strategies for immobilizing heavy metals, reducing runoff, and which are tied into an educational module for neighborhood school children.
Full Text Available Background: Bone morphogenetic protein-15 (BMP15 is a maternal gene necessary for mammalian reproduction. BMP15 expression increased in oocytes accompanied by follicle growth and development. The function and regulation mechanism of BMP15 in porcine cumulus cell apoptosis process is still unclear now. Methods: In this study, flow cytometry (FCM was used to analyze the effects of BMP15 with different concentrations to cumulus cell apoptosis. High-throughput sequencing technology was carried out to screen regulatory genes linked closely with BMP15. In order to confirm the function of (MCP-1/CCL2 and FBN1 in cumulus cell apoptosis, RNA interference (RNAi method was used to inhibit the expression of (MCP-1/CCL2 and FBN1. Apoptosis and proliferation of cumulus cell treated with siRNA transfection technology were measured by FCM, 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide, quantitative real time-PCR (RT-qPCR and western blotting. Results: The results showed that the apoptosis levels of cumulus cell treated by BMP15 decreased significantly in a dose-dependent manner. The expression of related genes protein 1 (MCP-1/CCL2 and fibrillin1 (FBN1 were both regulated by BMP15. After transfection, the proliferation of porcine cumulus cells increased significantly and apoptosis of cumulus cells was prevented while FBN1 was silenced after BMP15 treatment. The proliferation of cumulus cells decreased significantly and apoptosis rate of cumulus cells increased significantly while CCL2 was silenced. Conclusion: The results obtained in this study firstly demonstrated that CCL2 and FBN1 are important regulatory factors of BMP15 in preventing cumulus cell apoptosis in porcine ovaries.
Background/Questions/MethodsA key environmental concern in managing urban ecosystems is controlling stormwater runoff to ameliorate pollution problems and sewage overflows. Vegetated green roofs have become an important green infrastructure tool to collect, store, and gradually r...
Yang, Wuchen; Guo, Dayong; Harris, Marie A.; Cui, Yong; Gluhak-Heinrich, Jelica; Wu, Junjie; Chen, Xiao-Dong; Skinner, Charles; Nyman, Jeffry S.; Edwards, James R.; Mundy, Gregory R.; Lichtler, Alex; Kream, Barbara E.; Rowe, David W.; Kalajzic, Ivo; David, Val; Quarles, Darryl L.; Villareal, Demetri; Scott, Greg; Ray, Manas; Liu, S.; Martin, James F.; Mishina, Yuji; Harris, Stephen E.
Summary We generated a new Bmp2 conditional-knockout allele without a neo cassette that removes the Bmp2 gene from osteoblasts (Bmp2-cKOob) using the 3.6Col1a1-Cre transgenic model. Bones of Bmp2-cKOob mice are thinner, with increased brittleness. Osteoblast activity is reduced as reflected in a reduced bone formation rate and failure to differentiate to a mature mineralizing stage. Bmp2 in osteoblasts also indirectly controls angiogenesis in the periosteum and bone marrow. VegfA production is reduced in Bmp2-cKOob osteoblasts. Deletion of Bmp2 in osteoblasts also leads to defective mesenchymal stem cells (MSCs), which correlates with the reduced microvascular bed in the periosteum and trabecular bones. Expression of several MSC marker genes (α-SMA, CD146 and Angiopoietin-1) in vivo, in vitro CFU assays and deletion of Bmp2 in vitro in α-SMA+ MSCs support our conclusions. Critical roles of Bmp2 in osteoblasts and MSCs are a vital link between bone formation, vascularization and mesenchymal stem cells. PMID:23843612
Full Text Available Bone morphogenetic proteins (BMPs are highly conserved signaling molecules that are part of the transforming growth factor (TGF-beta superfamily, and function in the patterning and morphogenesis of many organs including development of the dentition. The functions of the BMPs are controlled by certain classes of molecules that are recognized as BMP antagonists that inhibit BMP binding to their cognate receptors. In this study we tested the hypothesis that USAG-1 (uterine sensitization-associated gene-1 suppresses deciduous incisors by inhibition of BMP-7 function. We learned that USAG-1 and BMP-7 were expressed within odontogenic epithelium as well as mesenchyme during the late bud and early cap stages of tooth development. USAG-1 is a BMP antagonist, and also modulates Wnt signaling. USAG-1 abrogation rescued apoptotic elimination of odontogenic mesenchymal cells. BMP signaling in the rudimentary maxillary incisor, assessed by expressions of Msx1 and Dlx2 and the phosphorylation of Smad protein, was significantly enhanced. Using explant culture and subsequent subrenal capsule transplantation of E15 USAG-1 mutant maxillary incisor tooth primordia supplemented with BMP-7 demonstrated in USAG-1+/- as well as USAG-1-/- rescue and supernumerary tooth development. Based upon these results, we conclude that USAG-1 functions as an antagonist of BMP-7 in this model system. These results further suggest that the phenotypes of USAG-1 and BMP-7 mutant mice reported provide opportunities for regenerative medicine and dentistry.
Michelle T Poldervaart
Full Text Available The design of bioactive three-dimensional (3D scaffolds is a major focus in bone tissue engineering. Incorporation of growth factors into bioprinted scaffolds offers many new possibilities regarding both biological and architectural properties of the scaffolds. This study investigates whether the sustained release of bone morphogenetic protein 2 (BMP-2 influences osteogenicity of tissue engineered bioprinted constructs. BMP-2 loaded on gelatin microparticles (GMPs was used as a sustained release system, which was dispersed in hydrogel-based constructs and compared to direct inclusion of BMP-2 in alginate or control GMPs. The constructs were supplemented with goat multipotent stromal cells (gMSCs and biphasic calcium phosphate to study osteogenic differentiation and bone formation respectively. BMP-2 release kinetics and bioactivity showed continuous release for three weeks coinciding with osteogenicity. Osteogenic differentiation and bone formation of bioprinted GMP containing constructs were investigated after subcutaneous implantation in mice or rats. BMP-2 significantly increased bone formation, which was not influenced by the release timing. We showed that 3D printing of controlled release particles is feasible and that the released BMP-2 directs osteogenic differentiation in vitro and in vivo.
Barlow Linda A
Full Text Available Abstract Background Bone Morphogenetic Protein 4 (BMP4 is a diffusible factor which regulates embryonic taste organ development. However, the role of BMP4 in taste buds of adult mice is unknown. We utilized transgenic mice with LacZ under the control of the BMP4 promoter to reveal the expression of BMP4 in the tongues of adult mice. Further we evaluate the pattern of BMP4 expression with that of markers of specific taste bud cell types and cell proliferation to define and compare the cell populations expressing BMP4 in anterior (fungiform papillae and posterior (circumvallate papilla tongue. Results BMP4 is expressed in adult fungiform and circumvallate papillae, i.e., lingual structures composed of non-taste epithelium and taste buds. Unexpectedly, we find both differences and similarities with respect to expression of BMP4-driven ß-galactosidase. In circumvallate papillae, many fusiform cells within taste buds are BMP4-ß-gal positive. Further, a low percentage of BMP4-expressing cells within circumvallate taste buds is immunopositive for markers of each of the three differentiated taste cell types (I, II and III. BMP4-positive intragemmal cells also expressed a putative marker of immature taste cells, Sox2, and consistent with this finding, intragemmal cells expressed BMP4-ß-gal within 24 hours after their final mitosis, as determined by BrdU birthdating. By contrast, in fungiform papillae, BMP4-ß-gal positive cells are never encountered within taste buds. However, in both circumvallate and fungiform papillae, BMP4-ß-gal expressing cells are located in the perigemmal region, comprising basal and edge epithelial cells adjacent to taste buds proper. This region houses the proliferative cell population that gives rise to adult taste cells. However, perigemmal BMP4-ß-gal cells appear mitotically silent in both fungiform and circumvallate taste papillae, as we do not find evidence of their active proliferation using cell cycle immunomarkers
Nguyen, Ha M; Barlow, Linda A
Bone Morphogenetic Protein 4 (BMP4) is a diffusible factor which regulates embryonic taste organ development. However, the role of BMP4 in taste buds of adult mice is unknown. We utilized transgenic mice with LacZ under the control of the BMP4 promoter to reveal the expression of BMP4 in the tongues of adult mice. Further we evaluate the pattern of BMP4 expression with that of markers of specific taste bud cell types and cell proliferation to define and compare the cell populations expressing BMP4 in anterior (fungiform papillae) and posterior (circumvallate papilla) tongue. BMP4 is expressed in adult fungiform and circumvallate papillae, i.e., lingual structures composed of non-taste epithelium and taste buds. Unexpectedly, we find both differences and similarities with respect to expression of BMP4-driven ß-galactosidase. In circumvallate papillae, many fusiform cells within taste buds are BMP4-ß-gal positive. Further, a low percentage of BMP4-expressing cells within circumvallate taste buds is immunopositive for markers of each of the three differentiated taste cell types (I, II and III). BMP4-positive intragemmal cells also expressed a putative marker of immature taste cells, Sox2, and consistent with this finding, intragemmal cells expressed BMP4-ß-gal within 24 hours after their final mitosis, as determined by BrdU birthdating. By contrast, in fungiform papillae, BMP4-ß-gal positive cells are never encountered within taste buds. However, in both circumvallate and fungiform papillae, BMP4-ß-gal expressing cells are located in the perigemmal region, comprising basal and edge epithelial cells adjacent to taste buds proper. This region houses the proliferative cell population that gives rise to adult taste cells. However, perigemmal BMP4-ß-gal cells appear mitotically silent in both fungiform and circumvallate taste papillae, as we do not find evidence of their active proliferation using cell cycle immunomarkers and BrdU birthdating. Our data suggest that
Eaton, Timothy T
Urban stormwater control is an urgent concern in megacities where increased impervious surface has disrupted natural hydrology. Water managers are increasingly turning to more environmentally friendly ways of capturing stormwater, called Green Infrastructure (GI), to mitigate combined sewer overflow (CSO) that degrades local water quality. A rapid screening approach is described to evaluate how GI strategies can reduce the amount of stormwater runoff in a low-density residential watershed in New York City. Among multiple possible tools, the L-THIA LID online software package, using the SCS-CN method, was selected to estimate relative runoff reductions expected with different strategies in areas of different land uses in the watershed. Results are sensitive to the relative areas of different land uses, and show that bioretention and raingardens provide the maximum reduction (∼12%) in this largely residential watershed. Although commercial, industrial and high-density residential areas in the watershed are minor, larger runoff reductions from disconnection strategies and porous pavement in parking lots are also possible. Total stormwater reductions from various combinations of these strategies can reach 35-55% for individual land uses, and between 23% and 42% for the entire watershed. Copyright © 2017. Published by Elsevier Ltd.
Full Text Available Bone morphogenetic proteins (Bmp are major players in the formation of the vertebrate body plan due to their crucial role in patterning of the dorsal-ventral (DV axis. Despite the highly conserved nature of Bmp signalling in vertebrates, the consequences of changing this pathway can be species-specific. Here, we report that Bmp plays an important role in epiboly, yolk syncytial layer (YSL movements, and anterior-posterior (AP axis formation in embryos of the self-fertilizing mangrove killifish, Kryptolebias marmoratus. Stage and dose specific exposures of embryos to the Bmp inhibitor dorsomorphin (DM produced three distinctive morphologies, with the most extreme condition creating the splitbody phenotype, characterised by an extremely short AP axis where the neural tube, somites, and notochord were bilaterally split. In addition, parts of caudal neural tissues were separated from the main body and formed cell islands in the posterior region of the embryo. This splitbody phenotype, which has not been reported in other animals, shows that modification of Bmp may lead to significantly different consequences during development in other vertebrate species.
Roche C de Guzman
Full Text Available Hair-derived keratin biomaterials composed mostly of reduced keratin proteins (kerateines have demonstrated their utility as carriers of biologics and drugs for tissue engineering. Electrostatic forces between negatively-charged keratins and biologic macromolecules allow for effective drug retention; attraction to positively-charged growth factors like bone morphogenetic protein 2 (BMP-2 has been used as a strategy for osteoinduction. In this study, the intermolecular surface and bulk interaction properties of kerateines were investigated. Thiol-rich kerateines were chemisorbed onto gold substrates to form an irreversible 2-nm rigid layer for surface plasmon resonance analysis. Kerateine-to-kerateine cohesion was observed in pH-neutral water with an equilibrium dissociation constant (KD of 1.8 × 10(-4 M, indicating that non-coulombic attractive forces (i.e. hydrophobic and van der Waals were at work. The association of BMP-2 to kerateine was found to be greater (KD = 1.1 × 10(-7 M, within the range of specific binding. Addition of salts (phosphate-buffered saline; PBS shortened the Debye length or the electrostatic field influence which weakened the kerateine-BMP-2 binding (KD = 3.2 × 10(-5 M. BMP-2 in bulk kerateine gels provided a limited release in PBS (~ 10% dissociation in 4 weeks, suggesting that electrostatic intermolecular attraction was significant to retain BMP-2 within the keratin matrix. Complete dissociation between kerateine and BMP-2 occurred when the PBS pH was lowered (to 4.5, below the keratin isoelectric point of 5.3. This phenomenon can be attributed to the protonation of keratin at a lower pH, leading to positive-positive repulsion. Therefore, the dynamics of kerateine-BMP-2 binding is highly dependent on pH and salt concentration, as well as on BMP-2 solubility at different pH and molarity. The study findings may contribute to our understanding of the release kinetics of drugs from keratin biomaterials and allow for the
Green areas, also known as green infrastructure or urban vegetation, are vital to urbanites for their critical roles in mitigating urban heat island effects and climate change and for their provision of multiple ecosystem services and aesthetics. Here, I provide a high spatial resolution snapshot of the green cover distribution of the city of San Juan, Puerto Rico, by...
Olga M. Ramos-González
Full Text Available Green areas, also known as green infrastructure or urban vegetation, are vital to urbanites for their critical roles in mitigating urban heat island effects and climate change and for their provision of multiple ecosystem services and aesthetics. Here, I provide a high spatial resolution snapshot of the green cover distribution of the city of San Juan, Puerto Rico, by incorporating the use of morphological spatial pattern analysis (MSPA as a tool to describe the spatial pattern and connectivity of the city's urban green areas. Analysis of a previously developed IKONOS 4-m spatial resolution classification of the city of San Juan from 2002 revealed a larger area of vegetation (green areas or green infrastructure than previously estimated by moderate spatial resolution imagery. The city as a whole had approximately 42% green cover and 55% impervious surfaces. Although the city appeared greener in its southern upland sector compared to the northern coastal section, where most built-up urban areas occurred (66% impervious surfaces, northern San Juan had 677 ha more green area cover dispersed across the city than the southern component. MSPA revealed that most forest cover occurred as edges and cores, and green areas were most commonly forest cores, with larger predominance in the southern sector of the municipality. In dense, built-up, urban land, most of the green areas occurred in private yards as islets. When compared to other cities across the United States, San Juan was most similar in green cover features to Boston, Massachusetts, and Miami, Florida. Per capita green space for San Juan (122.2 m²/inhabitant was also comparable to these two U.S. cities. This study explores the intra-urban vegetation variation in the city of San Juan, which is generally overlooked by moderate spatial resolution classifications in Puerto Rico. It serves as a starting point for green infrastructure mapping and landscape pattern analysis of the urban green spaces
Dupont, Kenneth M; Boerckel, Joel D; Stevens, Hazel Y; Diab, Tamim; Kolambkar, Yash M; Takahata, Masahiko; Schwarz, Edward M; Guldberg, Robert E
Biomaterial scaffolds functionalized to stimulate endogenous repair mechanisms via the incorporation of osteogenic cues offer a potential alternative to bone grafting for the treatment of large bone defects. We first quantified the ability of a self-complementary adeno-associated viral vector encoding bone morphogenetic protein 2 (scAAV2.5-BMP2) to enhance human stem cell osteogenic differentiation in vitro. In two-dimensional culture, scAAV2.5-BMP2-transduced human mesenchymal stem cells (hMSCs) displayed significant increases in BMP2 production and alkaline phosphatase activity compared with controls. hMSCs and human amniotic-fluid-derived stem cells (hAFS cells) seeded on scAAV2.5-BMP2-coated three-dimensional porous polymer Poly(ε-caprolactone) (PCL) scaffolds also displayed significant increases in BMP2 production compared with controls during 12 weeks of culture, although only hMSC-seeded scaffolds displayed significantly increased mineral formation. PCL scaffolds coated with scAAV2.5-BMP2 were implanted into critically sized immunocompromised rat femoral defects, both with or without pre-seeding of hMSCs, representing ex vivo and in vivo gene therapy treatments, respectively. After 12 weeks, defects treated with acellular scAAV2.5-BMP2-coated scaffolds displayed increased bony bridging and had significantly higher bone ingrowth and mechanical properties compared with controls, whereas defects treated with scAAV2.5-BMP2 scaffolds pre-seeded with hMSCs failed to display significant differences relative to controls. When pooled, defect treatment with scAAV2.5-BMP2-coated scaffolds, both with or without inclusion of pre-seeded hMSCs, led to significant increases in defect mineral formation at all time points and increased mechanical properties compared with controls. This study thus presents a novel acellular bone-graft-free endogenous repair therapy for orthotopic tissue-engineered bone regeneration.
Full Text Available Background. The disruption of physiologic vascular smooth muscle cell (VSMC migration initiates atherosclerosis development. The biochemical mechanisms leading to dysfunctional VSMC motility remain unknown. Recently, cytokine BMP-2 has been implicated in various vascular physiologic and pathologic processes. However, whether BMP-2 has any effect upon VSMC motility, or by what manner, has never been investigated. Methods. VSMCs were adenovirally transfected to genetically overexpress BMP-2. VSMC motility was detected by modified Boyden chamber assay, confocal time-lapse video assay, and a colony wounding assay. Gene chip array and RT-PCR were employed to identify genes potentially regulated by BMP-2. Western blot and real-time PCR detected the expression of myosin Va and the phosphorylation of extracellular signal-regulated kinases 1/2 (Erk1/2. Immunofluorescence analysis revealed myosin Va expression locale. Intracellular Ca2+ oscillations were recorded. Results. VSMC migration was augmented in VSMCs overexpressing BMP-2 in a dose-dependent manner. siRNA-mediated knockdown of myosin Va inhibited VSMC motility. Both myosin Va mRNA and protein expression significantly increased after BMP-2 administration and were inhibited by Erk1/2 inhibitor U0126. BMP-2 induced Ca2+ oscillations, generated largely by a “cytosolic oscillator”. Conclusion. BMP-2 significantly increased VSMCs migration and myosin Va expression, via the Erk signaling pathway and intracellular Ca2+ oscillations. We provide additional insight into the pathophysiology of atherosclerosis, and inhibition of BMP-2-induced myosin Va expression may represent a potential therapeutic strategy.
Full Text Available Hematopoietic stem cells (HSC, the self-renewing cells of the adult blood differentiation hierarchy, are generated during embryonic stages. The first HSCs are produced in the aorta-gonad-mesonephros (AGM region of the embryo through endothelial to a hematopoietic transition. BMP4 and Hedgehog affect their production and expansion, but it is unknown whether they act to affect the same HSCs. In this study using the BRE GFP reporter mouse strain that identifies BMP/Smad-activated cells, we find that the AGM harbors two types of adult-repopulating HSCs upon explant culture: One type is BMP-activated and the other is a non-BMP-activated HSC type that is indirectly controlled by Hedgehog signaling through the VEGF pathway. Transcriptomic analyses demonstrate that the two HSC types express distinct but overlapping genetic programs. These results revealing the bifurcation in HSC types at early embryonic stages in the AGM explant model suggest that their development is dependent upon the signaling molecules in the microenvironment.
Wu, Gui; Wang, Hai; Qiu, Guixing; Yu, Xin; Su, Xinlin; Ma, Pei; Yin, Bo; Wu, Zhihong
To prepare rhBMP-2/chitosan microspheres (rhBMP-2 CMs) with vanilline as a cross-linking reagent and study the biocompatibility and drug release characteristic of microspheres in vitro. Emulsion cross-linking method was utilized to prepare rhBMP-2 CMs, Scanning electron microscope (SEM) was used to observe the microstructure of microspheres.Leaching solution of microspheres and blank culture medium were designated as experimental and control groups respectively. Both groups were cultured with human mesenchymal stem cells (hMSCs) to determine its cytotoxicity and its effect on the proliferation of hMSCs. Dynamic immersion method was used to examine the in vitro release characteristic of rhBMP-2. And the alkaline phosphatase (ALP) activity of hMSCs was determined to reveal the bioactivity of released rhBMP-2. The rhBMP-2 CMs were spherical under SEM.After treating with leaching solution for 24 and 48 h, there was no inter-group statistical difference in optical density (OD) values at both timepoints (24 h:0.72 ± 0.07 vs 0.73 ± 0.05, P > 0.05; 48 h:1.19 ± 0.11 vs 1.27 ± 0.06, P > 0.05). After culturing with leaching solution for 1, 3 and 7 days, the number of cells increased with time for both groups. And the OD values were not statistically different at each timepoint. Five milligram rhBMP-2 CMs soaked for 19 days with a gradual release of rhBMP-2. The concentration of rhBMP-2 was 216.1 ± 20.0 ng/ml at Day 19. At Days 3 and 7, the ALP activities of hMSCs were (0.50 ± 0.07) and (0.68 ± 0.06) µmol pNPP·min⁻¹·mg⁻¹ protein respectively and both were higher than that of blank culture medium group (0.14 ± 0.01) (P < 0.05). With an excellent biocompatibility, rhBMP-2 CMs may be an ideal carrier for control-released rhBMP-2 and encapsulated rhBMP-2 remains bioactive.
Filardo, Mary; Vincent, Jeffrey M.
To formulate a "systems-based" plan to address the PK-12 infrastructure crisis, in 2016, the 21st Century School Fund (21CSF) and the University of California-Berkeley's Center for Cities + Schools (CC+S), in partnership with the National Council on School Facilities and the Center for Green Schools at the U.S. Green Building Council,…
Ghimire, Santosh R; Johnston, John M
We propose a modified eco-efficiency (EE) framework and novel sustainability analysis methodology for green infrastructure (GI) practices used in water resource management. Green infrastructure practices such as rainwater harvesting (RWH), rain gardens, porous pavements, and green roofs are emerging as viable strategies for climate change adaptation. The modified framework includes 4 economic, 11 environmental, and 3 social indicators. Using 6 indicators from the framework, at least 1 from each dimension of sustainability, we demonstrate the methodology to analyze RWH designs. We use life cycle assessment and life cycle cost assessment to calculate the sustainability indicators of 20 design configurations as Decision Management Objectives (DMOs). Five DMOs emerged as relatively more sustainable along the EE analysis Tradeoff Line, and we used Data Envelopment Analysis (DEA), a widely applied statistical approach, to quantify the modified EE measures as DMO sustainability scores. We also addressed the subjectivity and sensitivity analysis requirements of sustainability analysis, and we evaluated the performance of 10 weighting schemes that included classical DEA, equal weights, National Institute of Standards and Technology's stakeholder panel, Eco-Indicator 99, Sustainable Society Foundation's Sustainable Society Index, and 5 derived schemes. We improved upon classical DEA by applying the weighting schemes to identify sustainability scores that ranged from 0.18 to 1.0, avoiding the nonuniqueness problem and revealing the least to most sustainable DMOs. Our methodology provides a more comprehensive view of water resource management and is generally applicable to GI and industrial, environmental, and engineered systems to explore the sustainability space of alternative design configurations. Integr Environ Assess Manag 2017;13:821-831. Published 2017. This article is a US Government work and is in the public domain in the USA. Integrated Environmental Assessment and
Tian, Aiguo; Jiang, Jin
Many adult organs including Drosophila adult midguts rely on resident stem cells to replenish damaged cells during tissue homeostasis and regeneration. Previous studies have shown that, upon injury, intestinal stem cells (ISCs) in the midguts can increase proliferation and lineage differentiation to meet the demand for tissue repair. Our recent study has demonstrated that, in response to certain injury, midguts can expand ISC population size as an additional regenerative mechanism. We found that injury elicited by bleomycin feeding or bacterial infection increased the production of two BMP ligands (Dpp and Gbb) in enterocytes (ECs), leading to elevated BMP signaling in progenitor cells that drove an expansion of ISCs by promoting their symmetric self-renewing division. Interestingly, we also found that BMP signaling in ECs inhibits the production of Dpp and Gbb, and that this negative feedback mechanism is required to reset ISC pool size to the homeostatic state. Our findings suggest that BMP signaling exerts two opposing influences on stem cell activity depending on where it acts: BMP signaling in progenitor cells promotes ISC self-renewal while BMP signaling in ECs restricts ISC self-renewal by preventing excessive production of BMP ligands. Our results further suggest that transient expansion of ISC population in conjunction with increasing ISC proliferation provides a more effective strategy for tissue regeneration.
Full Text Available Biomaterials are widely used as scaffolds for tissue engineering. We have developed a strategy for bone tissue engineering that entails application of immobilized anti-BMP-2 monoclonal antibodies (mAbs to capture endogenous BMPs in vivo and promote antibody-mediated osseous regeneration (AMOR. The purpose of the current study was to compare the efficacy of immobilization of a specific murine anti-BMP-2 mAb on three different types of biomaterials and to evaluate their suitability as scaffolds for AMOR. Anti-BMP-2 mAb or isotype control mAb was immobilized on titanium (Ti microbeads, alginate hydrogel, and ACS. The treated biomaterials were surgically implanted in rat critical-sized calvarial defects. After 8 weeks, de novo bone formation was assessed using micro-CT and histomorphometric analyses. Results showed de novo bone regeneration with all three scaffolds with immobilized anti-BMP-2 mAb, but not isotype control mAb. Ti microbeads showed the highest volume of bone regeneration, followed by ACS. Alginate showed the lowest volume of bone. Localization of BMP-2, -4, and -7 antigens was detected on all 3 scaffolds with immobilized anti-BMP-2 mAb implanted in calvarial defects. Altogether, these data suggested a potential mechanism for bone regeneration through entrapment of endogenous BMP-2, -4, and -7 proteins leading to bone formation using different types of scaffolds via AMOR.
Rankin, Scott A; McCracken, Kyle W; Luedeke, David M; Han, Lu; Wells, James M; Shannon, John M; Zorn, Aaron M
A small number of signaling pathways are used repeatedly during organogenesis, and they can have drastically different effects on the same population of cells depending on the embryonic stage. How cellular competence changes over developmental time is not well understood. Here we used Xenopus, mouse, and human pluripotent stem cells to investigate how the temporal sequence of Wnt, BMP, and retinoic acid (RA) signals regulates endoderm developmental competence and organ induction, focusing on respiratory fate. While Nkx2-1+ lung fate is not induced until late somitogenesis stages, here we show that lung competence is restricted by the gastrula stage as a result of Wnt and BMP-dependent anterior-posterior (A-P) patterning. These early Wnt and BMP signals make posterior endoderm refractory to subsequent RA/Wnt/BMP-dependent lung induction. We further mapped how RA modulates the response to Wnt and BMP in a temporal specific manner. In the gastrula RA promotes posterior identity, however in early somite stages of development RA regulates respiratory versus pharyngeal potential in anterior endoderm and midgut versus hindgut potential in posterior endoderm. Together our data suggest a dynamic and conserved response of vertebrate endoderm during organogenesis, wherein early Wnt/BMP/RA impacts how cells respond to later Wnt/BMP/RA signals, illustrating how reiterative combinatorial signaling can regulate both developmental competence and subsequent fate specification. Copyright © 2017 Elsevier Inc. All rights reserved.
Full Text Available Background. Gene therapeutic drug delivery approaches have been introduced to improve the efficiency of growth factors at the site of interest. This study investigated the efficacy and safety of a new nonviral copolymer-protected gene vector (COPROG for the stimulation of bone healing. Methods. In vitro, rat osteoblasts were transfected with COPROG + luciferase plasmid or COPROG + hBMP-2 plasmid. In vivo, rat tibial fractures were intramedullary stabilized with uncoated versus COPROG+hBMP-2-plasmid-coated titanium K-wires. The tibiae were prepared for biomechanical and histological analyses at days 28 and 42 and for transfection/safety study at days 2, 4, 7, 28, and 42. Results. In vitro results showed luciferase expression until day 21, and hBMP-2-protein was measured from day 2 – day 10. In vivo, the local application of hBMP-2-plasmid showed a significantly higher maximum load after 42 days compared to that in the control. The histomorphometric analysis revealed a significantly less mineralized periosteal callus area in the BMP-2 group compared to the control at day 28. The rt-PCR showed no systemic biodistribution of luciferase RNA. Conclusion. A positive effect on fracture healing by nonviral BMP-2 plasmid application from COPROG-coated implants could be shown in this study; however, the effect of the vector may be improved with higher plasmid concentrations. Transfection showed no biodistribution to distant organs and was considered to be safe.
Report on the technical assistance project to help Austin, TX, develop a vision for the South Central Waterfront that incorporates green infrastructure to manage stormwater runoff, makes streets safer, and spurs investment.
Yeung, Ching-Yan Chloé; Gossan, Nicole; Lu, Yinhui
knowledge of tendon gene regulation is essential for a complete understanding of FCT biology. Here we show autonomous circadian rhythms in mouse tendon and primary human tenocytes, controlled by an intrinsic molecular circadian clock. Time-series microarrays identified the first circadian transcriptome...... of murine tendon, revealing that 4.6% of the transcripts (745 genes) are expressed in a circadian manner. One of these genes was Grem2, which oscillated in antiphase to BMP signaling. Moreover, recombinant human Gremlin-2 blocked BMP2-induced phosphorylation of Smad1/5 and osteogenic differentiation...... of human tenocytes in vitro. We observed dampened Grem2 expression, deregulated BMP signaling, and spontaneously calcifying tendons in young CLOCKΔ19 arrhythmic mice and aged wild-type mice. Thus, disruption of circadian control, through mutations or aging, of Grem2/BMP signaling becomes a new focus...
Granoff, Ilmi; Hogarth, J. Ryan; Miller, Alan
Low-carbon, 'green' economic growth is necessary to simultaneously improve human welfare and avoid the worst impacts of climate change and environmental degradation. Infrastructure choices underpin both the growth and the carbon intensity of the economy. This Perspective explores the barriers to investing in low-carbon infrastructure and some of the policy levers available to overcome them. The barriers to decarbonizing infrastructure 'nest' within a set of barriers to infrastructure development more generally that cause spending on infrastructure--low-carbon or not--to fall more than 70% short of optimal levels. Developing countries face additional barriers such as currency and political risks that increase the investment gap. Low-carbon alternatives face further barriers, such as commercialization risk and financial and public institutions designed for different investment needs. While the broader barriers to infrastructure investment are discussed in other streams of literature, they are often disregarded in literature on renewable energy diffusion or climate finance, which tends to focus narrowly on the project costs of low- versus high-carbon options. We discuss how to overcome the barriers specific to low-carbon infrastructure within the context of the broader infrastructure gap.
Chaubey, I.; Cibin, R.; Sudheer, K.; Her, Y.
Use of computer simulation models have increased substantially to make watershed management decisions and to develop strategies for water quality improvements. These models are often used to evaluate potential benefits of various best management practices (BMPs) for reducing losses of pollutants from sources areas into receiving waterbodies. Similarly, use of simulation models in optimizing selection and placement of best management practices under single (maximization of crop production or minimization of pollutant transport) and multiple objective functions has increased recently. One of the limitations of the currently available assessment and optimization approaches is that the BMP strategies are considered deterministic. Uncertainties in input data (e.g. precipitation, streamflow, sediment, nutrient and pesticide losses measured, land use) and model parameters may result in considerable uncertainty in watershed response under various BMP options. We have developed and evaluated options to include uncertainty in BMP evaluation and optimization for watershed management. We have also applied these methods to evaluate uncertainty in ecosystem services from mixed land use watersheds. In this presentation, we will discuss methods to to quantify uncertainties in BMP assessment and optimization solutions due to uncertainties in model inputs and parameters. We have used a watershed model (Soil and Water Assessment Tool or SWAT) to simulate the hydrology and water quality in mixed land use watershed located in Midwest USA. The SWAT model was also used to represent various BMPs in the watershed needed to improve water quality. SWAT model parameters, land use change parameters, and climate change parameters were considered uncertain. It was observed that model parameters, land use and climate changes resulted in considerable uncertainties in BMP performance in reducing P, N, and sediment loads. In addition, climate change scenarios also affected uncertainties in SWAT
Badar Agung Nugroho
Full Text Available Green computing is a study and practice of designing, manufacturing, using, and disposing of information and communication devices efficiently and effectively with minimum impact on the environment. If the green computing concept was implemented, it will help the agencies or companies to reduce energy and capital cost from their IT infrastructure. The goal from this research is to explore the current condition about the efforts from local governments and IT companies at West Java to implement the green computing concept at their working environment. The primary data were collected by using focus group discussion by inviting the local governments and IT companies representatives who responsible to manage their IT infrastructure. And then, the secondary data were collected by doing brief observation in order to see the real effort of green computing implementation at each institution. The result shows that there are many different perspectives and efforts of green computing implementation between local governments and IT companies.
Full Text Available Background/Aims: Delayed graft function (DGF is associated with adverse outcomes after renal transplantation. Bone morphogenetic protein-2 (BMP-2 is involved in both endothelial function and immunological events. We compared expression of BMP-2 in epigastric artery of renal transplant recipients with immediate graft function (IGF and DGF. Methods: 79 patients were included in this prospective study. Patients were divided in IGF group (64 patients and DGF group (15 patients. BMP-2 expression in intima media (BMP2m and endothelium (BMP2e of epigastric artery was assessed by immunohistochemistry. Results: Lower intensity of BMP2e staining was recorded in DGF compared to IGF. In DGF patients, 93% had no expression of BMP2e and 7% had 1st grade expression, compared to 45% and 41% in IGF group, respectively (P=0.001 (Pst grade expression. Patients who had BMP2e staining positive had lower odds for DGF (OR 0.059 [0.007, 0.477] and this remained significant even after adjustment for donor and recipient variables, cold ischemia time, and immunological matching (OR 0.038 [0.003, 0.492]. Conclusions: Our results demonstrate that BMP-2 expression in endothelial cells of epigastric arteries may predict development of DGF.
Lee, Min Young; Lim, Hyun Woo; Lee, Sang Hun; Han, Ho Jae
It is known that bone morphogenetic protein 4 (BMP-4) has a diverse effect on ESCs. However, its precise mechanism in mouse ESCs is not fully understood. We evaluated the effect of BMP-4 on ESC proliferation and its related signal cascades in this study. BMP-4 significantly increased the level of [(3)H]-thymidine incorporation in time- (> or =8 hours) and dose- (> or =10 ng/ml) dependent manners. Additionally, BMP-4 increased cyclin D1 and decreased p27(kip1) expression values in a time-dependent manner. The increases in BMP-4-induced [(3)H]-thymidine incorporation and cyclin D1 expression were inhibited by the BMP-4 receptor antagonist noggin. BMP-4 increased Wnt1 expression. Wnt1 expression was attenuated by Smad4 small interfering RNA (siRNA), and BMP-4-induced cyclin D1 expression was inhibited by Smad4 and Wnt1 siRNAs. BMP-4 also activated beta-catenin, which was blocked by Smad4 and Wnt1 siRNAs. In addition, BMP-4 induced Akt phosphorylation. BMP-4-induced beta-catenin activation and cyclin D1 expression were attenuated by phosphatidyl inositol 3-kinase (PI3K) siRNA and Akt inhibitor. Additionally, downregulation of Smad4, Wnt1, and PI3K expression by siRNA decreased the levels of pluripotency marker mRNAs of ESCs, including Oct4, Sox2, and FoxD3. Our results suggested that BMP-4-induced [(3)H]-thymidine incorporation was significantly attenuated by Smad4, Wnt1, and PI3K knockdown. In conclusion, BMP-4 contributed to the maintenance of cell proliferation and the pluripotent state by Smad, PI3K/Akt, and Wnt1/beta-catenin in mouse ESCs.
Full Text Available Fertility rate is an economically important trait in sheep, which is influenced by genetic and environment. So far, three genes have been identified that affects this trait, one of them would be the BMP family, the most famous one is BMP15. Different mutations in the BMP15 gene, increases reproductive performance and growth rate in sheep. The aim of this study was to investigate the genetic and phylogenetic of BMP15 gene sequence in Iranian Sangsari sheep. For this purpose, the blood samples from 20 animal of Damghan station were collected. After DNA extracting, a segment of 222 bp of exon 2 of BMP15 gene was amplified using polymerase chain reaction. Then, all of the PCR products were sequenced. The results showed existence of four haplotypes and three significant mutations of the gene that which one of them was seen for first. In order to determine the genetic distance of Sansari sheep with other animals especially sheep breeds about 103 sequences were taken from Genebank, Then, phylogenetic trees were drawn. Genetic distances and nucleotide differences were calculated. The results showed that goat, cattle and buffalo have minimum genetic distance and monkey, human and mouse have maximum distance with Sangsari sheep and native Hindi and Kashmiri sheep have not any differences with Iranian Sangsari sheep.
Sato, Chieri; Iwasaki, Tsuyoshi; Kitano, Sachie; Tsunemi, Sachi; Sano, Hajime
Highlights: ► We investigated the role of S1P signaling for osteoblast differentiation. ► Both S1P and FTY enhanced BMP-2-stimulated osteoblast differentiation by C2C12 cells. ► S1P signaling enhanced BMP-2-stimulated Smad and ERK phosphorylation by C2C12 cells. ► MEK/ERK signaling is a pathway underlying S1P signaling for osteoblast differentiation. -- Abstract: We previously demonstrated that sphingosine 1-phosphate (S1P) receptor-mediated signaling induced proliferation and prostaglandin productions by synovial cells from rheumatoid arthritis (RA) patients. In the present study we investigated the role of S1P receptor-mediated signaling for osteoblast differentiation. We investigated osteoblast differentiation using C2C12 myoblasts, a cell line derived from murine satellite cells. Osteoblast differentiation was induced by the treatment of bone morphogenic protein (BMP)-2 in the presence or absence of either S1P or FTY720 (FTY), a high-affinity agonist of S1P receptors. Osteoblast differentiation was determined by osteoblast-specific transcription factor, Runx2 mRNA expression, alkaline phosphatase (ALP) activity and osteocalcin production by the cells. Smad1/5/8 and extracellular signal-regulated kinase (ERK) 1/2 phosphorylation was examined by Western blotting. Osteocalcin production by C2C12 cells were determined by ELISA. Runx2 expression and ALP activity by BMP-2-stimulated C2C12 cells were enhanced by addition of either S1P or FTY. Both S1P and FTY enhanced BMP-2-induced ERK1/2 and Smad1/5/8 phosphorylation. The effect of FTY was stronger than that of S1P. S1P receptor-mediated signaling on osteoblast differentiation was inhibited by addition of mitogen-activated protein kinase/ERK kinase (MEK) 1/2 inhibitor, indicating that the S1P receptor-mediated MEK1/2-ERK1/2 signaling pathway enhanced BMP-2-Smad signaling. These results indicate that S1P receptor-mediated signaling plays a crucial role for osteoblast differentiation.
Kanniah, K D; Sheikhi, A; Kang, C S
Development of cities has led to various environmental problems as a consequence of non sustaibale town planning. One of the strategies to make cities a livable place and to achieve low levels of CO 2 emissions (low carbon cities or LCC) is the integration of the blue and green infrastructure into the development and planning of new urban areas. Iskandar Malaysia (IM) located in the southern part of Malaysia is a special economic zone that has major urban centres. The planning of these urban centres will incorporate LCC strategies to achieve a sustainable development. The role of green (plants) and blue bodies (lakes and rivers) in moderating temperature in IM have been investigated in the current study. A remotely sensed satellite imagery was used to calculate the vegetation density and land surface temperature (LST). The effect of lakes in cooling the surrounding temperature was also investigated. Results show that increasing vegetation density by 1% can decrease the LST by 0.09°C. As for the water bodies we found as the distance increased from the lake side the temperature also increased about 1.7°C and the reduction in air humidity is 9% as the distance increased to 100 meter away from the lake
Full Text Available The present study was designed to determine the underlying mechanism of low-intensity pulsed ultrasound (LIPUS induced alveolar bone remodeling and the role of BMP-2 expression in a rat orthodontic tooth movement model. Orthodontic appliances were placed between the homonymy upper first molars and the upper central incisors in rats under general anesthesia, followed by daily 20-min LIPUS or sham LIPUS treatment beginning at day 0. Tooth movement distances and molecular changes were evaluated at each observation point. In vitro and in vivo studies were conducted to detect HGF (Hepatocyte growth factor/Runx2/BMP-2 signaling pathways and receptor activator of NFκB ligand (RANKL expression by quantitative real time PCR (qRT-PCR, Western blot and immunohistochemistry. At day 3, LIPUS had no effect on the rat orthodontic tooth movement distance and BMP-2-induced alveolar bone remodeling. However, beginning at day 5 and for the following time points, LIPUS significantly increased orthodontic tooth movement distance and BMP-2 signaling pathway and RANKL expression compared with the control group. The qRT-PCR and Western blot data in vitro and in vivo to study BMP-2 expression were consistent with the immunohistochemistry observations. The present study demonstrates that LIPUS promotes alveolar bone remodeling by stimulating the HGF/Runx2/BMP-2 signaling pathway and RANKL expression in a rat orthodontic tooth movement model, and LIPUS increased BMP-2 expression via Runx2 regulation.
Xiong, Long; Zeng, Jianhua; Yao, Aihua; Tu, Qiquan; Li, Jingtang; Yan, Liang; Tang, Zhiming
The regeneration of large bone defects is an osteoinductive, osteoconductive, and osteogenic process that often requires a bone graft for support. Limitations associated with naturally autogenic or allogenic bone grafts have demonstrated the need for synthetic substitutes. The present study investigates the feasibility of using novel hollow hydroxyapatite microspheres as an osteoconductive matrix and a carrier for controlled local delivery of bone morphogenetic protein 2 (BMP2), a potent osteogenic inducer of bone regeneration. Hollow hydroxyapatite microspheres (100±25 μm) with a core (60±18 μm) and a mesoporous shell (180±42 m(2)/g surface area) were prepared by a glass conversion technique and loaded with recombinant human BMP2 (1 μg/mg). There was a gentle burst release of BMP2 from microspheres into the surrounding phosphate-buffered saline in vitro within the initial 48 hours, and continued at a low rate for over 40 days. In comparison with hollow hydroxyapatite microspheres without BMP2 or soluble BMP2 without a carrier, BMP2-loaded hollow hydroxyapatite microspheres had a significantly enhanced capacity to reconstitute radial bone defects in rabbit, as shown by increased serum alkaline phosphatase; quick and complete new bone formation within 12 weeks; and great biomechanical flexural strength. These results indicate that BMP2-loaded hollow hydroxyapatite microspheres could be a potential new option for bone graft substitutes in bone regeneration.
Huang, Baolin; Tian, Yu; Zhang, Wenjing; Ma, Yifan; Yuan, Yuan; Liu, Changsheng
Preserving and improving osteogenic activity of bone morphogenetic protein-2 (BMP-2) upon implants remains one of the key limitations in bone regeneration. With calcium phosphate cement (CPC) as model, we have developed a series of strontium (Sr)-doped CPC (SCPC) to address this issue. The effects of fixed Sr on the bioactivity of recombinant human BMP-2 (rhBMP-2) as well as the underlying mechanism were investigated. The results suggested that the rhBMP-2-induced osteogenic activity was significantly promoted upon SCPCs, especially with a low amount of fixed Sr (SrCO 3 content IA (BMPR-IA) to rhBMP-2 and an increased expression of BMPR-IA in C2C12 model cells. As a result, the activations of BMP-induced signaling pathways were different in C2C12 cells incubated upon CPC/rhBMP-2 and SCPCs/rhBMP-2. These findings explicitly decipher the mechanism of SCPCs promoting osteogenic bioactivity of rhBMP-2 and signify the promising application of the SCPCs/rhBMP-2 matrix in bone regeneration implants. Copyright © 2017 Elsevier B.V. All rights reserved.
Lao, Lifeng; Cohen, Jeremiah R; Buser, Zorica; Brodke, Darrel S; Youssef, Jim A; Park, Jong-Beom; Yoon, S Tim; Wang, Jeffrey C; Meisel, Hans-Joerg
Retrospective study. Recombinant human bone morphogenetic protein-2 (rhBMP-2) has been widely used in spinal fusion surgery, but there is little information on rhBMP-2 utilization in single-level posterior lumbar interbody fusion (PLIF). The purpose of our study was to evaluate the trends and demographics of rhBMP-2 utilization in single-level PLIF. Patients who underwent single-level PLIF from 2005 to 2011 were identified by searching ICD-9 diagnosis and procedure codes in the PearlDiver Patient Records Database, a national database of orthopedic insurance records. The year of procedure, age, gender, and region of the United States were recorded for each patient. Results were reported for each variable as the incidence of procedures identified per 100 000 patients searched in the database. A total of 2735 patients had single-level PLIF. The average rate of single-level PLIF with rhBMP-2 maintained at a relatively stable level (28% to 31%) from 2005 to 2009, but decreased in 2010 (9.9%) and 2011 (11.8%). The overall incidence of single-level PLIF without rhBMP-2 (0.68 cases per 100 000 patients) was statistically higher ( P level PLIF with rhBMP-2 (0.21 cases per 100 000 patients). The average rate of single-level PLIF with rhBMP-2 utilization was the highest in West (30.1%), followed by Midwest (26.9%), South (20.5%), and Northeast (17.8%). The highest incidence of single-level PLIF with rhBMP-2 was observed in the age group level PLIF. There was a 3-fold increase in the rate of PLIF without rhBMP-2 compared to PLIF with rhBMP-2, with both procedures being mainly done in patients less than 65 years of age.
Basic-Jukic, Nikolina; Gulin, Marijana; Hudolin, Tvrtko; Kastelan, Zeljko; Katalinic, Lea; Coric, Marijana; Veda, Marija Varnai; Ivkovic, Vanja; Kes, Petar; Jelakovic, Bojan
Delayed graft function (DGF) is associated with adverse outcomes after renal transplantation. Bone morphogenetic protein-2 (BMP-2) is involved in both endothelial function and immunological events. We compared expression of BMP-2 in epigastric artery of renal transplant recipients with immediate graft function (IGF) and DGF. 79 patients were included in this prospective study. Patients were divided in IGF group (64 patients) and DGF group (15 patients). BMP-2 expression in intima media (BMP2m) and endothelium (BMP2e) of epigastric artery was assessed by immunohistochemistry. Lower intensity of BMP2e staining was recorded in DGF compared to IGF. In DGF patients, 93% had no expression of BMP2e and 7% had 1st grade expression, compared to 45% and 41% in IGF group, respectively (P=0.001) (P<0.001 for no expression and P = 0.015 for 1st grade expression). Patients who had BMP2e staining positive had lower odds for DGF (OR 0.059 [0.007, 0.477]) and this remained significant even after adjustment for donor and recipient variables, cold ischemia time, and immunological matching (OR 0.038 [0.003, 0.492]). Our results demonstrate that BMP-2 expression in endothelial cells of epigastric arteries may predict development of DGF. © 2016 The Author(s) Published by S. Karger AG, Basel.
He, Xi C; Zhang, Jiwang; Tong, Wei-Gang; Tawfik, Ossama; Ross, Jason; Scoville, David H; Tian, Qiang; Zeng, Xin; He, Xi; Wiedemann, Leanne M; Mishina, Yuji; Li, Linheng
In humans, mutations in BMPR1A, SMAD4 and PTEN are responsible for juvenile polyposis syndrome, juvenile intestinal polyposis and Cowden disease, respectively. The development of polyposis is a common feature of these diseases, suggesting that there is an association between BMP and PTEN pathways. The mechanistic link between BMP and PTEN pathways and the related etiology of juvenile polyposis is unresolved. Here we show that conditional inactivation of Bmpr1a in mice disturbs homeostasis of intestinal epithelial regeneration with an expansion of the stem and progenitor cell populations, eventually leading to intestinal polyposis resembling human juvenile polyposis syndrome. We show that BMP signaling suppresses Wnt signaling to ensure a balanced control of stem cell self-renewal. Mechanistically, PTEN, through phosphatidylinosital-3 kinase-Akt, mediates the convergence of the BMP and Wnt pathways on control of beta-catenin. Thus, BMP signaling may control the duplication of intestinal stem cells, thereby preventing crypt fission and the subsequent increase in crypt number.
Bielen, Holger; Houart, Corinne
Depletion of Wnt signaling is a major requirement for the induction of the anterior prosencephalon. However, the molecular events driving the differential regionalization of this area into eye-field and telencephalon fates are still unknown. Here we show that the BMP pathway is active in the anterior neural ectoderm during late blastula to early gastrula stage in zebrafish. Bmp2b mutants and mosaic loss-of-function experiments reveal that BMP acts as a repressor of eye-field fate through inhibition of its key transcription factor Rx3, thereby protecting the future telencephalon from acquiring eye identity. This BMP-driven mechanism initiates the establishment of the telencephalon prior to the involvement of Wnt antagonists from the anterior neural border. Furthermore, we demonstrate that Rx3 and BMP are respectively required to maintain and restrict the chemokine receptor cxcr4a, which in turn contributes to the morphogenetic separation of eye-field and telencephalic cells during early neurulation. Copyright © 2012 Elsevier Inc. All rights reserved.
Ren, Wei; Sun, Xiaoxiao; Wang, Ke; Feng, Honglei; Liu, Yuehong; Fei, Chang; Wan, Shaoheng; Wang, Wei; Luo, Jinyong; Shi, Qiong; Tang, Min; Zuo, Guowei; Weng, Yaguang; He, Tongchuan; Zhang, Yan
Bone morphogenetic proteins (BMPs), which belong to the transforming growth factor-β superfamily, regulate a wide range of cellular responses including cell proliferation, differentiation, adhesion, migration, and apoptosis. BMP9, the latest BMP to be discovered, is reportedly expressed in a variety of human carcinoma cell lines, but the role of BMP9 in breast cancer has not been fully clarified. In a previous study, BMP9 was found to inhibit the growth, migration, and invasiveness of MDA-MB-231 breast cancer cells. In the current study, the effect of BMP9 on the bone metastasis of breast cancer cells was investigated. After absent or low expression of BMP9 was detected in the MDA-MB-231 breast cancer cells and breast non-tumor adjacent tissues using Western blot and immunohistochemistry, In our previous study, BMP9 could inhibit the proliferation and invasiveness of breast cancer cells MDA-MB-231 in vitro and in vivo. This paper shows that BMP9 inhibit the bone metastasis of breast cancer cells by activating the BMP/Smad signaling pathway and downregulating connective tissue growth factor (CTGF); however, when CTGF expression was maintained, the inhibitory effect of BMP9 on the MDA-MB-231 cells was abolished. Together, these observations indicate that BMP9 is an important mediator of breast cancer bone metastasis and a potential therapeutic target for treating this deadly disease.
David Welsch; Roger Ryder; Tim Post
The specific purpose of the BMP protocol is to create an economical, standardized, and repeatable BMP monitoring process that is completely automated, from data gathering through report generation, in order to provide measured data, ease of use, and compatibility with State BMP programs.The protocol was developed to meet the following needs:? Document the use and...
Morikawa, Masato; Koinuma, Daizo; Mizutani, Anna; Kawasaki, Natsumi; Holmborn, Katarina; Sundqvist, Anders; Tsutsumi, Shuichi; Watabe, Tetsuro; Aburatani, Hiroyuki; Heldin, Carl-Henrik; Miyazono, Kohei
Bone morphogenetic protein (BMP) signaling exerts paradoxical roles in pluripotent stem cells (PSCs); it sustains self-renewal of mouse embryonic stem cells (ESCs), while it induces differentiation in other PSCs, including human ESCs. Here, we revisit the roles of BMP-4 using mouse ESCs (mESCs) in naive and primed states. SMAD1 and SMAD5, which transduce BMP signals, recognize enhancer regions together with KLF4 and KLF5 in naive mESCs. KLF4 physically interacts with SMAD1 and suppresses its activity. Consistently, a subpopulation of cells with active BMP-SMAD can be ablated without disturbing the naive state of the culture. Moreover, Smad1/5 double-knockout mESCs stay in the naive state, indicating that the BMP-SMAD pathway is dispensable for it. In contrast, the MEK5-ERK5 pathway mediates BMP-4-induced self-renewal of mESCs by inducing Klf2, a critical factor for the ground state pluripotency. Our study illustrates that BMP exerts its self-renewing effect through distinct functions of different Krüppel-like factors. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.
Suzuki, Kentaro; Adachi, Yasuha; Numata, Tomokazu; Nakada, Shoko; Yanagita, Motoko; Nakagata, Naomi; Evans, Sylvia M; Graf, Daniel; Economides, Aris; Haraguchi, Ryuma; Moon, Anne M; Yamada, Gen
Sirenomelia, also known as mermaid syndrome, is a developmental malformation of the caudal body characterized by leg fusion and associated anomalies of pelvic/urogenital organs including bladder, kidney, rectum and external genitalia. Most affected infants are stillborn, and the few born alive rarely survive beyond the neonatal period. Despite the many clinical studies of sirenomelia in humans, little is known about the pathogenic developmental mechanisms that cause the complex array of phenotypes observed. Here, we provide new evidences that reduced BMP (Bone Morphogenetic Protein) signaling disrupts caudal body formation in mice and phenocopies sirenomelia. Bmp4 is strongly expressed in the developing caudal body structures including the peri-cloacal region and hindlimb field. In order to address the function of Bmp4 in caudal body formation, we utilized a conditional Bmp4 mouse allele (Bmp4(flox/flox)) and the Isl1 (Islet1)-Cre mouse line. Isl1-Cre is expressed in the peri-cloacal region and the developing hindimb field. Isl1Cre;Bmp4(flox/flox) conditional mutant mice displayed sirenomelia phenotypes including hindlimb fusion and pelvic/urogenital organ dysgenesis. Genetic lineage analyses indicate that Isl1-expressing cells contribute to both the aPCM (anterior Peri-Cloacal Mesenchyme) and the hindlimb bud. We show Bmp4 is essential for the aPCM formation independently with Shh signaling. Furthermore, we show Bmp4 is a major BMP ligand for caudal body formation as shown by compound genetic analyses of Bmp4 and Bmp7. Taken together, this study reveals coordinated development of caudal body structures including pelvic/urogenital organs and hindlimb orchestrated by BMP signaling in Isl1-expressing cells. Our study offers new insights into the pathogenesis of sirenomelia.
Full Text Available Sirenomelia, also known as mermaid syndrome, is a developmental malformation of the caudal body characterized by leg fusion and associated anomalies of pelvic/urogenital organs including bladder, kidney, rectum and external genitalia. Most affected infants are stillborn, and the few born alive rarely survive beyond the neonatal period. Despite the many clinical studies of sirenomelia in humans, little is known about the pathogenic developmental mechanisms that cause the complex array of phenotypes observed. Here, we provide new evidences that reduced BMP (Bone Morphogenetic Protein signaling disrupts caudal body formation in mice and phenocopies sirenomelia. Bmp4 is strongly expressed in the developing caudal body structures including the peri-cloacal region and hindlimb field. In order to address the function of Bmp4 in caudal body formation, we utilized a conditional Bmp4 mouse allele (Bmp4(flox/flox and the Isl1 (Islet1-Cre mouse line. Isl1-Cre is expressed in the peri-cloacal region and the developing hindimb field. Isl1Cre;Bmp4(flox/flox conditional mutant mice displayed sirenomelia phenotypes including hindlimb fusion and pelvic/urogenital organ dysgenesis. Genetic lineage analyses indicate that Isl1-expressing cells contribute to both the aPCM (anterior Peri-Cloacal Mesenchyme and the hindlimb bud. We show Bmp4 is essential for the aPCM formation independently with Shh signaling. Furthermore, we show Bmp4 is a major BMP ligand for caudal body formation as shown by compound genetic analyses of Bmp4 and Bmp7. Taken together, this study reveals coordinated development of caudal body structures including pelvic/urogenital organs and hindlimb orchestrated by BMP signaling in Isl1-expressing cells. Our study offers new insights into the pathogenesis of sirenomelia.
This paper proposes a Green Cloud model for mobile Cloud computing. The proposed model leverage on the current trend of IaaS (Infrastructure as a Service), PaaS (Platform as a Service) and SaaS (Software as a Service), and look at new paradigm called "Network as a Service" (NaaS). The Green Cloud model proposes various Telco's revenue generating streams and services with the CaaS (Cloud as a Service) for the near future.
Wagner, Ines; Wang, Heng; Weissert, Philipp M; Straube, Werner L; Shevchenko, Anna; Gentzel, Marc; Brito, Goncalo; Tazaki, Akira; Oliveira, Catarina; Sugiura, Takuji; Shevchenko, Andrej; Simon, András; Drechsel, David N; Tanaka, Elly M
Limb amputation in the newt induces myofibers to dedifferentiate and re-enter the cell cycle to generate proliferative myogenic precursors in the regeneration blastema. Here we show that bone morphogenetic proteins (BMPs) and mature BMPs that have been further cleaved by serum proteases induce cell cycle entry by dedifferentiating newt muscle cells. Protease-activated BMP4/7 heterodimers that are present in serum strongly induced myotube cell cycle re-entry with protease cleavage yielding a 30-fold potency increase of BMP4/7 compared with canonical BMP4/7. Inhibition of BMP signaling via muscle-specific dominant-negative receptor expression reduced cell cycle entry in vitro and in vivo. In vivo inhibition of serine protease activity depressed cell cycle re-entry, which in turn was rescued by cleaved-mimic BMP. This work identifies a mechanism of BMP activation that generates blastema cells from differentiated muscle. Copyright © 2017 Elsevier Inc. All rights reserved.
von Laszewski, Gregor; Wang, Lizhe
In this paper we are introducing a framework towards the inclusion of Green IT metrics as part of service level agreements for future Grids and Clouds. As part of this effort we need to revisit Green IT metrics and proxies that we consider optimizing against in order to develop GreenIT as a Services (GaaS) that can be reused as part of a Software as a Service (SaaS) and Infrastructure Infrastructureas a service (IaaS) framework. We report on some of our ongoing efforts and demonstrate how we already achieve impact on the environment with our services.
Du, Guang-Yu; He, Sheng-Wei; Sun, Chuan-Xiu; Mi, Li-Dong
There is an increasing demand for formulations of silk fibroin (SF) scaffolds in biomedical applications. SF was crosslinked via glutaraldehyde with osteoinductive recombinant human bone morphogenic protein-2 (rhBMP2) of different ratios viz. (i) 3% SF with no rhBMP2 (SF), (ii) 3% SF with equal amount of rhBMP2 (SF+BMP2), and (iii) 12% SF with 3% of rhBMP2 (4SF+BMP2), and these solutions were used in electrospinning-based fabrication of nanoscaffolds for evaluating increased osteoinductive potential of SF scaffolds with rhBMP2. Stress-strain relationship suggested there is no loss in mechanical strength of fibers with addition of rhBMP2, and mechanical strength of scaffold was improved with increase in concentration of SF. rhBMP2 association increased the water retention capacity of scaffold as evident from swelling studies. Viability of hMSCs was found to be higher in conjugated scaffolds, and scaffolds do not exhibit any cytotoxicity towards guest cells. Cells were found to have higher alkaline phosphatase activity in conjugated scaffolds under in vitro and in vivo conditions which establishes the increased osteoinductivity of the novel construct. The scaffolds were found to be effective for in vivo bone formation as well.
Full Text Available Abstract Background Bone morphogenetic proteins (BMPs belong to the TGF-β superfamily and are secreted proteins with pleiotropic roles in many different cell types. A potential role of BMP-6 in the immune system has been implied by various studies of malignant and rheumatoid diseases. In the present study, we explored the role of BMP-6 in normal human peripheral blood B cells. Results The B cells were found to express BMP type I and type II receptors and BMP-6 rapidly induced phosphorylation of Smad1/5/8. Furthermore, Smad-phosphorylation was followed by upregulation of Id1 mRNA and Id1 protein, whereas Id2 and Id3 expression was not affected. Furthermore, we found that BMP-6 had an antiproliferative effect both in naïve (CD19+CD27- and memory B cells (CD19+CD27+ stimulated with anti-IgM alone or the combined action of anti-IgM and CD40L. Additionally, BMP-6 induced cell death in activated memory B cells. Importantly, the antiproliferative effect of BMP-6 in B-cells was completely neutralized by the natural antagonist, noggin. Furthermore, B cells were demonstrated to upregulate BMP-6 mRNA upon stimulation with anti-IgM. Conclusion In mature human B cells, BMP-6 inhibited cell growth, and rapidly induced phosphorylation of Smad1/5/8 followed by an upregulation of Id1.
Gill, Aman S; Lee, Angela; McGuire, Krista L
New York City (NYC) is pioneering green infrastructure with the use of bioswales and other engineered soil-based habitats to provide stormwater infiltration and other ecosystem functions. In addition to avoiding the environmental and financial costs of expanding traditional built infrastructure, green infrastructure is thought to generate cobenefits in the form of diverse ecological processes performed by its plant and microbial communities. Yet, although plant communities in these habitats are closely managed, we lack basic knowledge about how engineered ecosystems impact the distribution and functioning of soil bacteria. We sequenced amplicons of the 16S ribosomal subunit, as well as seven genes associated with functional pathways, generated from both total (DNA-based) and expressed (RNA) soil communities in the Bronx, NYC, NY, in order to test whether bioswale soils host characteristic bacterial communities with evidence for enriched microbial functioning, compared to nonengineered soils in park lawns and tree pits. Bioswales had distinct, phylogenetically diverse bacterial communities, including taxa associated with nutrient cycling and metabolism of hydrocarbons and other pollutants. Bioswale soils also had a significantly greater diversity of genes involved in several functional pathways, including carbon fixation ( cbbL-R [ cbbL gene, red-like subunit] and apsA ), nitrogen cycling ( noxZ and amoA ), and contaminant degradation ( bphA ); conversely, no functional genes were significantly more abundant in nonengineered soils. These results provide preliminary evidence that urban land management can shape the diversity and activity of soil communities, with positive consequences for genetic resources underlying valuable ecological functions, including biogeochemical cycling and degradation of common urban pollutants. IMPORTANCE Management of urban soil biodiversity by favoring taxa associated with decontamination or other microbial metabolic processes is a
Garcia-Cuerva, Laura; Berglund, Emily Zechman; Rivers, Louie
Increasing urbanization augments impervious surface area, which results in increased run off volumes and peak flows. Green Infrastructure (GI) approaches are a decentralized alternative for sustainable urban stormwater and provide an array of ecosystem services and foster community building by enhancing neighborhood aesthetics, increasing property value, and providing shared green spaces. While projects involving sustainability concepts and environmental design are favored in privileged communities, marginalized communities have historically been located in areas that suffer from environmental degradation. Underprivileged communities typically do not receive as many social and environmental services as advantaged communities. This research explores GI-based management strategies that are evaluated at the watershed scale to improve hydrological performance by mitigating storm water run off volumes and peak flows. GI deployment strategies are developed to address environmental justice issues by prioritizing placement in communities that are underprivileged and locations with high outreach potential. A hydrologic/hydraulic stormwater model is developed using the Storm Water Management Model (SWMM 5.1) to simulate the impacts of alternative management strategies. Management scenarios include the implementation of rain water harvesting in private households, the decentralized implementation of bioretention cells in private households, the centralized implementation of bioretention cells in municipally owned vacant land, and combinations of those strategies. Realities of implementing GI on private and public lands are taken into account to simulate various levels of coverage and routing for bioretention cell scenarios. The effects of these strategies are measured by the volumetric reduction of run off and reduction in peak flow; social benefits are not evaluated. This approach is applied in an underprivileged community within the Walnut Creek Watershed in Raleigh, North
R.M. Shaffer; H.L. Haney; E.G. Worrell; W.M. Aust
Forestry Best Management Practices (BMPs) are operational techniques used to protect water quality during timber harvesting operations. The implementation cost of BMPs is important to loggers, forest landowners, and the forest industry. This study provides an estimate of BMP implementation cost on a per harvested acre basis for the coastal plain, Piedmont, and...
Karlsson, Caroline; Kalantari, Zahra
With the ongoing urbanisation and increasing pressure for new housing and infrastructure, the nexus of developing compact, energy-efficient and yet liveable and sustainable cities is urgent to address. In this context, blue-green spaces and related ecosystem services (ES) are critical resources that need to be integrated in policy and planning of urban. Among the ES provided by blue-green spaces, regulating ES such as water retention and purification are particularly important in urban areas, affecting water supply and quality, related cultural ES and biodiversity, as well as cities potential to adapt to climate change. Blue-green infrastructure management is considered a sustainable way to reducing negative effects of urbanisation, such as decreasing flood risks, as well as adapting to climate change for example by controlling increasing flood and drought risks. Blue-green infrastructure management can for example create multifunctional surfaces with valuable environmental and social functions and generally handle greenways and ecological networks as important ecosystem service components, for example for stormwater regulation in a sustainable urban drainage system. The Norrström drainage basin (22,000 km2) is a large demonstrator for Blue-green infrastructure management. Both urbanisation and agriculture are extensive within this basin, which includes the Swedish capital Stockholm and is part of the fertile Swedish belt. Together, the relatively high population density combined with agricultural and industrial activities in this region imply large eutrophication and pollution pressures, not least transferred through storm runoff to both inland surface waters and the coastal waters of the Baltic Sea. The ecosystems of this basin provide highly valued but also threatened services. For example, Lake Mälaren is the single main freshwater supply for the Swedish capital Stockholm, as well as a key nutrient retention system that strongly mitigates waterborne nutrient
Full Text Available Abstract Background Glaucoma is a blinding disease usually associated with high intraocular pressure (IOP. In some families, abnormal anterior segment development contributes to glaucoma. The genes causing anterior segment dysgenesis and glaucoma in most of these families are not identified and the affected developmental processes are poorly understood. Bone morphogenetic proteins (BMPs participate in various developmental processes. We tested the importance of Bmp4 gene dosage for ocular development and developmental glaucoma. Results Bmp4+/- mice have anterior segment abnormalities including malformed, absent or blocked trabecular meshwork and Schlemm's canal drainage structures. Mice with severe drainage structure abnormalities, over 80% or more of their angle's extent, have elevated IOP. The penetrance and severity of abnormalities is strongly influenced by genetic background, being most severe on the C57BL/6J background and absent on some other backgrounds. On the C57BL/6J background there is also persistence of the hyaloid vasculature, diminished numbers of inner retinal cells, and absence of the optic nerve. Conclusions We demonstrate that heterozygous deficiency of BMP4 results in anterior segment dysgenesis and elevated IOP. The abnormalities are similar to those in human patients with developmental glaucoma. Thus, BMP4 is a strong candidate to contribute to Axenfeld-Rieger anomaly and other developmental conditions associated with human glaucoma. BMP4 also participates in posterior segment development and wild-type levels are usually critical for optic nerve development on the C57BL/6J background. Bmp4+/- mice are useful for studying various components of ocular development, and may allow identification of strain specific modifiers affecting a variety of ocular phenotypes.
Full Text Available From the theoretical context of Smart City various studies have emerged that adopt an analytical approach and description of urban phenomena based on the principles of “network design”; this line of research uses the network systems theory to define the principles that regulate the relationships among the various elements of urban sub-systems in order to optimize their functionality. From the same theoretical basis, urban greenspaces have also been studied as networks, by means of the creation of models capable of measuring the performance of the system in its entirety, posing the basis of a new multy-disciplinary research field called green network. This paper presents the results of research aimed at clarifying the meaning of green network from an urban planning perspective through a lexical analysis applied to a textual corpus of more than 300 abstracts of research papers that have dealt with this topic over the last twenty years. The results show that the concept of green network appears still fuzzy and unclear, due to the different meaning given to the term “green” and to an incorrect use of the term “network”, often referred to as a generic set of natural areas present in a city, without any reference to the network system theory or to the basic rules linking these elements together. For this reason, the paper proposes a unique definition of green network from an urban planning perspective that takes into account the contribution of other research areas to effective green infrastructure planning. This is the concept of “urban green network design” defined as “an urban planning practice, supported by decision support tools able to model green infrastructure as network, composed by natural and semi-natural areas, whose connections are modelled according to specific variables, in order to deliver an equal distribution of public services for enhancing the quality of life as well as a wide range of ecosystem services”.
Wang, J.; Zheng, Y.; Zhao, J.; Liu, T.; Gao, L.; Gu, Z.; Wu, G.
Objectives To delineate the dynamic micro-architectures of bone induced by low-dose bone morphogenetic protein (BMP)-2/7 heterodimer in peri-implant bone defects compared to BMP2 and BMP7 homodimer. Material and Methods Peri-implant bone defects (8 mm in diameter, 4 mm in depth) were created
The Green and Virtual Data Center sets aside the political aspects of what is or is not considered green to instead focus on the opportunities for organizations that want to sustain environmentally-friendly economical growth. If you are willing to believe that IT infrastructure resources deployed in a highly virtualized manner can be combined with other technologies to achieve simplified and cost-effective delivery of services in a green, profitable manner, this book is for you. Savvy industry veteran Greg Schulz provides real-world insight, addressing best practices, server, software, storag
J.F.M. Koppenjan (Joop)
markdownabstractRecently, the OECD has suggested to seek private investment to realize and accelerate the realization of low-carbon, climate-resilient (LCCR) infrastructure. One of the options explored was the use of Design, Build, Finance, Maintain and/or Operate (DBFMO) contracts. Since
Full Text Available Tendon bone healing of the rotator cuff is often associated with non-healing or recurrent defects, which seems to be influenced by the patient's age and sex. The present study aims to examine cellular biological characteristics of tenocyte-like cells that may contribute to this impaired rotator cuff healing. Moreover, a therapeutic approach using growth factors could possibly stimulate tendon bone healing. Therefore, our second aim was to identify patient groups who would particularly benefit from growth factor stimulation. Tenocyte-like cells isolated from supraspinatus tendons of female donors younger and older than 65 years of age were characterized with respect to different cellular biological parameters, such as cell density, cell count, marker expression, collagen-I protein synthesis, and stem cell potential. Furthermore, cells of the donor groups were stimulated with BMP-2 and BMP-7 (200 and 1000 ng/ml in 3D-culture and analyzed for cell count, marker expression and collagen-I protein synthesis. Female donors older than 65 years of age showed significantly decreased cell count and collagen-I protein synthesis compared to cells from donors younger than 65 years. Cellular biological parameters including cell count, collagen-I and -III expression, and collagen-I protein synthesis of cells from both donor groups were stimulated with BMP-2 and BMP-7. The cells from donors older than 65 years revealed a decreased stimulation potential for cell count compared to the younger group. Cells from female donors older than 65 years of age showed inferior cellular biological characteristics. This may be one reason for a weaker healing potential observed in older female patients and should be taken into consideration for tendon bone healing of the rotator cuff.
Das, Anusuya; Fishero, Brian A; Christophel, J Jared; Li, Ching-Ju; Kohli, Nikita; Lin, Yong; Dighe, Abhijit S; Cui, Quanjun
We have previously shown that the combined delivery of mesenchymal stem cells (MSCs), vascular endothelial growth factor (VEGF) and bone morphogenetic protein 6 (BMP-6) induces significantly more bone formation than that induced by the delivery of any single factor or a combination of any two factors. We now determine whether the exogenous addition of VEGF and BMP-6 is sufficient for bone healing when MSCs are not provided. Poly(lactic-co-glycolic acid) (PLAGA) microsphere-based three-dimensional scaffolds (P) were fabricated by thermal sintering of PLAGA microspheres. The scaffolds were chemically cross-linked with 200 ng recombinant human VEGF (P(VEGF)) or BMP-6 (P(BMP-6)) or both (P(VEGF+BMP-6)) by the EDC-NHS-MES method. Release of the proteins from the scaffolds was detected for 21 days in vitro which confirmed their comparable potential to supply the proteins in vivo. The scaffolds were delivered to a critical-sized mandibular defect created in 32 Sprague Dawley rats. Significant bone regeneration was observed only in rats with P(VEGF+BMP-6) scaffolds at weeks 2, 8 and 12 as revealed by micro-computer tomography. Vascular ingrowth was higher in the P(VEGF+BMP-6) group as seen by microfil imaging than in other groups. Trichrome staining revealed that a soft callus formed in P(VEGF), P(BMP-6) and P(VEGF+BMP-6) but not in P. MSCs isolated from rat femurs displayed expression of the bone-specific marker osteocalcin when cultured with P(VEGF), P(BMP-6), or P(VEGF+BMP-6) but not with P. Robust mineralization and increased alkaline phosphatase gene expression were seen in rat MSCs when cultured on P(VEGF+BMP-6) but not on P, P(VEGF), or P(BMP-6). Thus, unlike the delivery of VEGF or BMP-6 alone, the combined delivery of VEGF and BMP-6 to the bone defect significantly enhanced bone repair through the enhancement of angiogenesis and the differentiation of endogenously recruited MSCs into the bone repair site.
Liu, Jun; Ben, Qi-Wen; Yao, Wei-Yan; Zhang, Jian-Jun; Chen, Da-Fan; He, Xiang-Yi; Li, Lei; Yuan, Yao-Zong
The emerging roles of bone morphogenetic proteins (BMPs) in the initiation and progression of multiple cancers have drawn great attention in cancer research. We hypothesized that BMP2 promotes cancer metastasis by modulating MMP-2 secretion and activity through intracellular ROS regulation and ERK activation in human pancreatic cancer. Our data show that stimulation of PANC-1 cells with BMP2 induced MMP-2 secretion and activation, associated with decreased E-cadherin expression, resulting in epithelial-to-mesenchymal transformation (EMT) and cell invasion. Blockade of ROS by the ROS scavenger, 2-MPG, abolished cell invasion, inhibited the EMT process and decreased MMP-2 expression, suggesting ROS accumulation caused an increase in MMP-2 expression in BMP2-stimulated PANC-1 cell invasion. Furthermore, treatment of PANC-1 cells with 2-MPG or ERK inhibitor PD98059 reduced the phosphorylation of ERK, resulting in attenuation of BMP2-induced cell invasion and MMP-2 activation. Taken together, these results suggest that BMP2 induces the cell invasion of PANC-1 cells by enhancing MMP-2 secretion and acting through ROS accumulation and ERK activation.
Fuentealba, Luis C; Eivers, Edward; Ikeda, Atsushi; Hurtado, Cecilia; Kuroda, Hiroki; Pera, Edgar M; De Robertis, Edward M
BMP receptors determine the intensity of BMP signals via Smad1 C-terminal phosphorylations. Here we show that a finely controlled cell biological pathway terminates this activity. The duration of the activated pSmad1(Cter) signal was regulated by sequential Smad1 linker region phosphorylations at conserved MAPK and GSK3 sites required for its polyubiquitinylation and transport to the centrosome. Proteasomal degradation of activated Smad1 and total polyubiquitinated proteins took place in the centrosome. Inhibitors of the Erk, p38, and JNK MAPKs, as well as GSK3 inhibitors, prolonged the duration of a pulse of BMP7. Wnt signaling decreased pSmad1(GSK3) antigen levels and redistributed it from the centrosome to cytoplasmic LRP6 signalosomes. In Xenopus embryos, it was found that Wnts induce epidermis and that this required an active BMP-Smad pathway. Epistatic experiments suggested that the dorsoventral (BMP) and anteroposterior (Wnt/GSK3) patterning gradients are integrated at the level of Smad1 phosphorylations during embryonic pattern formation.
Sato, Chieri [Division of Rheumatology, Department of Internal Medicine, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo 663-8501 (Japan); Iwasaki, Tsuyoshi, E-mail: email@example.com [Division of Pharmacotherapy, Department of Pharmacy, School of Pharmacy, Hyogo University of Health Sciences, 1-3-6 Minatojima, Chuo-ku, Kobe 650-8530 (Japan); Kitano, Sachie; Tsunemi, Sachi; Sano, Hajime [Division of Rheumatology, Department of Internal Medicine, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo 663-8501 (Japan)
Highlights: Black-Right-Pointing-Pointer We investigated the role of S1P signaling for osteoblast differentiation. Black-Right-Pointing-Pointer Both S1P and FTY enhanced BMP-2-stimulated osteoblast differentiation by C2C12 cells. Black-Right-Pointing-Pointer S1P signaling enhanced BMP-2-stimulated Smad and ERK phosphorylation by C2C12 cells. Black-Right-Pointing-Pointer MEK/ERK signaling is a pathway underlying S1P signaling for osteoblast differentiation. -- Abstract: We previously demonstrated that sphingosine 1-phosphate (S1P) receptor-mediated signaling induced proliferation and prostaglandin productions by synovial cells from rheumatoid arthritis (RA) patients. In the present study we investigated the role of S1P receptor-mediated signaling for osteoblast differentiation. We investigated osteoblast differentiation using C2C12 myoblasts, a cell line derived from murine satellite cells. Osteoblast differentiation was induced by the treatment of bone morphogenic protein (BMP)-2 in the presence or absence of either S1P or FTY720 (FTY), a high-affinity agonist of S1P receptors. Osteoblast differentiation was determined by osteoblast-specific transcription factor, Runx2 mRNA expression, alkaline phosphatase (ALP) activity and osteocalcin production by the cells. Smad1/5/8 and extracellular signal-regulated kinase (ERK) 1/2 phosphorylation was examined by Western blotting. Osteocalcin production by C2C12 cells were determined by ELISA. Runx2 expression and ALP activity by BMP-2-stimulated C2C12 cells were enhanced by addition of either S1P or FTY. Both S1P and FTY enhanced BMP-2-induced ERK1/2 and Smad1/5/8 phosphorylation. The effect of FTY was stronger than that of S1P. S1P receptor-mediated signaling on osteoblast differentiation was inhibited by addition of mitogen-activated protein kinase/ERK kinase (MEK) 1/2 inhibitor, indicating that the S1P receptor-mediated MEK1/2-ERK1/2 signaling pathway enhanced BMP-2-Smad signaling. These results indicate that S1P
Full Text Available Background & objectives: BMP (bone morphogenetic protein-4/7 and bFGF (basic fibroblast growth factor significantly promote the osteogenic activity and the proliferation of rabbit BMSCs (bone marrow stromal cells, respectively. However, their synergistic effects on the proliferation and the differentiation of BMSCs remain unclear. In the present study, the effects of bFGF and BMP-4/7 were investigated on the proliferation and the differentiation of rat BMSCs in vitro. Methods: BMSCs were isolated from New Zealand white rabbits and cultured to the third passage. The samples were divided into five groups according to the material implanted: (A 80 ng/ml BMP-4/7; (B 80 ng/ml bFGF; (C 30 ng/ml BMP-4/7 and 30 ng/ml bFGF; (D 50 ng/ml BMP-4/7 and 50 ng/ml bFGF; and (E 80 ng/ml BMP-4/7 and 80 ng/ml bFGF. Cell proliferation was analyzed using methyl thiazolyl tetrazolium (MTT assay. Alkaline phosphatase activity and osteocalcin (OC dynamics were also measured. Results: BMP-4/7 alone significantly (P<0.05 promoted the proliferation of BMSCs. At the same time, it also promoted or inhibited the osteogenic differentiation of BMSCs. The synergistic effects of BMP-4/7 and bFGF significantly promoted both the proliferation and the osteogenic differentiation of BMSCs. The treatment of the synergistic effects was dose and time dependent. Interpretation & conclusions: A rational combination of BMP-4/7 and bFGF can promote the proliferation and the osteogenic differentiation of BMSCs. In addition, the synergistic functions are effective.
Miszuk, Jacob M; Xu, Tao; Yao, Qingqing; Fang, Fang; Childs, Josh D; Hong, Zhongkui; Tao, Jianning; Fong, Hao; Sun, Hongli
Bone morphogenic protein 2 (BMP2) is a key growth factor for bone regeneration, possessing FDA approval for orthopedic applications. BMP2 is often required in supratherapeutic doses clinically, yielding adverse side effects and substantial treatment costs. Considering the crucial role of materials for BMPs delivery and cell osteogenic differentiation, we devote to engineering an innovative bone-matrix mimicking niche to improve low dose of BMP2-induced bone formation. Our previous work describes a novel technique, named thermally induced nanofiber self-agglomeration (TISA), for generating 3D electrospun nanofibrous (NF) polycaprolactone (PCL) scaffolds. TISA process could readily blend PCL with PLA, leading to increased osteogenic capabilities in vitro , however, these bio-inert synthetic polymers produced limited BMP2-induced bone formation in vivo. We therefore hypothesize that functionalization of NF 3D PCL scaffolds with bone-like hydroxyapatite (HA) and BMP2 signaling activator phenamil will provide a favorable osteogenic niche for bone formation at low doses of BMP2. Compared to PCL-3D scaffolds, PCL/HA-3D scaffolds demonstrated synergistically enhanced osteogenic differentiation capabilities of C2C12 cells with phenamil. Importantly, in vivo studies showed this synergism was able to generate significantly increased new bone in an ectopic mouse model, suggesting PCL/HA-3D scaffolds act as a favorable synthetic extracellular matrix for bone regeneration.
Yeh, Lee-Chuan C; Ma, Xiuye; Ford, Jeffery J; Adamo, Martin L; Lee, John C
Bone morphogenetic proteins (BMPs) promote osteoblast differentiation and bone formation in vitro and in vivo. BMPs canonically signal through Smad transcription factors, but BMPs may activate signaling pathways traditionally stimulated by growth factor tyrosine kinase receptors. Of these, the mTOR pathway has received considerable attention because BMPs activate P70S6K, a downstream effector of mTOR, suggesting that BMP-induced osteogenesis is mediated by mTOR activation. However, contradictory effects of the mTOR inhibitor rapamycin (RAPA) on bone formation have been reported. Since bone formation is thought to be inversely related to lipid accumulation and mTOR is also important for lipid synthesis, we postulated that BMP-7 may stimulate lipogenic enzyme expression in a RAPA-sensitive mechanism. To test this hypothesis, we determined the effects of RAPA on BMP-7-stimulated expression of osteogenic and lipogenic markers in cultured fetal rat calvarial cells. Our study showed that BMP-7 promoted the expression of osteogenic and lipogenic markers. The effect of BMP-7 on osteogenic markers was greater in magnitude than on lipogenic markers and was temporally more sustained. RAPA inhibited basal and BMP-7-stimulated osteogenic and lipogenic marker expression and bone nodule mineralization. The acetyl CoA carboxylase inhibitor TOFA stimulated the expression of osteoblast differentiation markers, whereas palmitate suppressed their expression. We speculate that the BMP-7-stimulated adipogenesis is part of the normal anabolic response to BMPs, but that inappropriate activation of the lipid biosynthetic pathway by mTOR could have deleterious effects on bone formation and could explain paradoxical effects of RAPA to promote bone formation. Copyright © 2013 Wiley Periodicals, Inc.
Full Text Available Fibrillins are large extracellular macromolecules that polymerize to form the backbone structure of connective tissue microfibrils. Mutations in the gene for fibrillin-1 cause the Marfan syndrome, while mutations in the gene for fibrillin-2 cause Congenital Contractural Arachnodactyly. Both are autosomal dominant disorders, and both disorders affect musculoskeletal tissues. Here we show that Fbn2 null mice (on a 129/Sv background are born with reduced muscle mass, abnormal muscle histology, and signs of activated BMP signaling in skeletal muscle. A delay in Myosin Heavy Chain 8, a perinatal myosin, was found in Fbn2 null forelimb muscle tissue, consistent with the notion that muscle defects underlie forelimb contractures in these mice. In addition, white fat accumulated in the forelimbs during the early postnatal period. Adult Fbn2 null mice are already known to demonstrate persistent muscle weakness. Here we measured elevated creatine kinase levels in adult Fbn2 null mice, indicating ongoing cycles of muscle injury. On a C57Bl/6 background, Fbn2 null mice showed severe defects in musculature, leading to neonatal death from respiratory failure. These new findings demonstrate that loss of fibrillin-2 results in phenotypes similar to those found in congenital muscular dystrophies and that FBN2 should be considered as a candidate gene for recessive congenital muscular dystrophy. Both in vivo and in vitro evidence associated muscle abnormalities and accumulation of white fat in Fbn2 null mice with abnormally activated BMP signaling. Genetic rescue of reduced muscle mass and accumulation of white fat in Fbn2 null mice was accomplished by deleting a single allele of Bmp7. In contrast to other reports that activated BMP signaling leads to muscle hypertrophy, our findings demonstrate the exquisite sensitivity of BMP signaling to the fibrillin-2 extracellular environment during early postnatal muscle development. New evidence presented here suggests that
Raposo, F.; Fernández-Cegrí, V.; de la Rubia, M.A.
BACKGROUND: This paper describes results obtained for different participating research groups in an interlaboratory study related to biochemical methane potential (BMP). In this research work, all experimental conditions influencing the test such as inoculum, substrate characteristics and experim...... significantly according to the experimental approaches....
Piacentino, Michael L; Chung, Oliver; Ramachandran, Janani; Zuch, Daniel T; Yu, Jia; Conaway, Evan A; Reyna, Arlene E; Bradham, Cynthia A
Skeletal patterning in the sea urchin embryo requires coordinated signaling between the pattern-dictating ectoderm and the skeletogenic primary mesenchyme cells (PMCs); recent studies have begun to uncover the molecular basis for this process. Using an unbiased RNA-Seq-based screen, we have previously identified the TGF-ß superfamily ligand, LvBMP5-8, as a skeletal patterning gene in Lytechinus variegatus embryos. This result is surprising, since both BMP5-8 and BMP2/4 ligands have been implicated in sea urchin dorsal-ventral (DV) and left-right (LR) axis specification. Here, we demonstrate that zygotic LvBMP5-8 is required for normal skeletal patterning on the left side, as well as for normal PMC positioning during gastrulation. Zygotic LvBMP5-8 is required for expression of the left-side marker soxE, suggesting that LvBMP5-8 is required for left-side specification. Interestingly, we also find that LvBMP5-8 knockdown suppresses serotonergic neurogenesis on the left side. While LvBMP5-8 overexpression is sufficient to dorsalize embryos, we find that zygotic LvBMP5-8 is not required for normal DV specification or development. In addition, ectopic LvBMP5-8 does not dorsalize LvBMP2/4 morphant embryos, indicating that, in the absence of BMP2/4, BMP5-8 is insufficient to specify dorsal. Taken together, our data demonstrate that zygotic LvBMP5-8 signaling is essential for left-side specification, and for normal left-side skeletal and neural patterning, but not for DV specification. Thus, while both BMP2/4 and BMP5-8 regulate LR axis specification, BMP2/4 but not zygotic BMP5-8 regulates DV axis specification in sea urchin embryos. Copyright © 2016 Elsevier Inc. All rights reserved.
Schröder, C.; Mancosu, E.; Roerink, G.J.
Methodology proposal for estimation of carbon storage in urban green areas; final report. Subtitle: Final report of task Task 262-5-6 "Carbon sequestration in urban green infrastructure" Project manager Marie Cugny-Seguin. Date: 15-10-2013
Courtney M Tate
Full Text Available Bone morphogenetic proteins (BMPs, members of the TGF-β superfamily, have numerous biological activities including control of growth, differentiation, and vascular development. Using an in vitro co-culture endothelial cord formation assay, we investigated the role of a BMP7 variant (BMP7v in VEGF, bFGF, and tumor-driven angiogenesis. BMP7v treatment led to disruption of neo-endothelial cord formation and regression of existing VEGF and bFGF cords in vitro. Using a series of tumor cell models capable of driving angiogenesis in vitro, BMP7v treatment completely blocked cord formation. Pre-treatment of endothelial cells with BMP7v significantly reduced their cord forming ability, indicating a direct effect on endothelial cell function. BMP7v activated the canonical SMAD signaling pathway in endothelial cells but targeted gene knockdown using shRNA directed against SMAD4 suggests this pathway is not required to mediate the anti-angiogenic effect. In contrast to SMAD activation, BMP7v selectively decreased ERK and AKT activation, significantly decreased endothelial cell migration and down-regulated expression of critical RTKs involved in VEGF and FGF angiogenic signaling, VEGFR2 and FGFR1 respectively. Importantly, in an in vivo angiogenic plug assay that serves as a measurement of angiogenesis, BMP7v significantly decreased hemoglobin content indicating inhibition of neoangiogenesis. In addition, BMP7v significantly decreased angiogenesis in glioblastoma stem-like cell (GSLC Matrigel plugs and significantly impaired in vivo growth of a GSLC xenograft with a concomitant reduction in microvessel density. These data support BMP7v as a potent anti-angiogenic molecule that is effective in the context of tumor angiogenesis.
Tate, Courtney M; Mc Entire, Jacquelyn; Pallini, Roberto; Vakana, Eliza; Wyss, Lisa; Blosser, Wayne; Ricci-Vitiani, Lucia; D'Alessandris, Quintino Giorgio; Morgante, Liliana; Giannetti, Stefano; Larocca, Luigi Maria; Todaro, Matilde; Benfante, Antonina; Colorito, Maria Luisa; Stassi, Giorgio; De Maria, Ruggero; Rowlinson, Scott; Stancato, Louis
Bone morphogenetic proteins (BMPs), members of the TGF-β superfamily, have numerous biological activities including control of growth, differentiation, and vascular development. Using an in vitro co-culture endothelial cord formation assay, we investigated the role of a BMP7 variant (BMP7v) in VEGF, bFGF, and tumor-driven angiogenesis. BMP7v treatment led to disruption of neo-endothelial cord formation and regression of existing VEGF and bFGF cords in vitro. Using a series of tumor cell models capable of driving angiogenesis in vitro, BMP7v treatment completely blocked cord formation. Pre-treatment of endothelial cells with BMP7v significantly reduced their cord forming ability, indicating a direct effect on endothelial cell function. BMP7v activated the canonical SMAD signaling pathway in endothelial cells but targeted gene knockdown using shRNA directed against SMAD4 suggests this pathway is not required to mediate the anti-angiogenic effect. In contrast to SMAD activation, BMP7v selectively decreased ERK and AKT activation, significantly decreased endothelial cell migration and down-regulated expression of critical RTKs involved in VEGF and FGF angiogenic signaling, VEGFR2 and FGFR1 respectively. Importantly, in an in vivo angiogenic plug assay that serves as a measurement of angiogenesis, BMP7v significantly decreased hemoglobin content indicating inhibition of neoangiogenesis. In addition, BMP7v significantly decreased angiogenesis in glioblastoma stem-like cell (GSLC) Matrigel plugs and significantly impaired in vivo growth of a GSLC xenograft with a concomitant reduction in microvessel density. These data support BMP7v as a potent anti-angiogenic molecule that is effective in the context of tumor angiogenesis.
Full Text Available Formation of the dorsal-ventral axis of the sea urchin embryo relies on cell interactions initiated by the TGFbeta Nodal. Intriguingly, although nodal expression is restricted to the ventral side of the embryo, Nodal function is required for specification of both the ventral and the dorsal territories and is able to restore both ventral and dorsal regions in nodal morpholino injected embryos. The molecular basis for the long-range organizing activity of Nodal is not understood. In this paper, we provide evidence that the long-range organizing activity of Nodal is assured by a relay molecule synthesized in the ventral ectoderm, then translocated to the opposite side of the embryo. We identified this relay molecule as BMP2/4 based on the following arguments. First, blocking BMP2/4 function eliminated the long-range organizing activity of an activated Nodal receptor in an axis rescue assay. Second, we demonstrate that BMP2/4 and the corresponding type I receptor Alk3/6 functions are both essential for specification of the dorsal region of the embryo. Third, using anti-phospho-Smad1/5/8 immunostaining, we show that, despite its ventral transcription, the BMP2/4 ligand triggers receptor mediated signaling exclusively on the dorsal side of the embryo, one of the most extreme cases of BMP translocation described so far. We further report that the pattern of pSmad1/5/8 is graded along the dorsal-ventral axis and that two BMP2/4 target genes are expressed in nested patterns centered on the region with highest levels of pSmad1/5/8, strongly suggesting that BMP2/4 is acting as a morphogen. We also describe the very unusual ventral co-expression of chordin and bmp2/4 downstream of Nodal and demonstrate that Chordin is largely responsible for the spatial restriction of BMP2/4 signaling to the dorsal side. Thus, unlike in most organisms, in the sea urchin, a single ventral signaling centre is responsible for induction of ventral and dorsal cell fates. Finally
Schifman, L. A.; Herrmann, D. L.; Shuster, W. D.; Ossola, A.; Garmestani, A.; Hopton, M. E.
Management of urban hydrologic processes using green infrastructure (GI) has largely focused on storm water management. Thus, design and implementation of GI usually rely on physical site characteristics and local rainfall patterns, and do not typically account for human or social dimensions. This traditional approach leads to highly centralized storm water management in a disconnected urban landscape and can deemphasize additional benefits that GI offers, such as increased property value, greenspace aesthetics, heat island amelioration, carbon sequestration, and habitat for biodiversity. We propose the Framework for Adaptive Socio-Hydrology (FrASH) in which GI planning and implementation moves from a purely hydrology-driven perspective to an integrated sociohydrological approach. This allows for an iterative, multifaceted decision-making process that would enable a network of stakeholders to collaboratively set a dynamic, context-guided project plan for the installation of GI, rather than a "one-size-fits-all" installation. We explain how different sectors (e.g., governance, nongovernmental organizations, communities, academia, and industry) can create a connected network of organizations that work toward a common goal. Through a graphical Chambered Nautilus model, FrASH is experimentally applied to contrasting GI case studies and shows that this multistakeholder, connected, decentralized network with a coevolving decision-making project plan results in enhanced multifunctionality, potentially allowing for the management of resilience in urban systems at multiple scales.
Full Text Available Using the City of Roanoke, Virginia as a study site, this paper quantifies the forest structure, ecosystem services and values of vacant and residential land. Single family residential land had more trees (1,683,000 than vacant land (210,000 due largely to the differences in land area (32.44 km2 of vacant land vs. 57.94 km2 residential. While the percentage of tree coverage was almost identical across land uses (30.6% in vacant to 32.3% in residential, the number of trees per ha is greater on residential land (290.3 than on vacant land (63.4. The average healthy leaf surface area on individual trees growing on vacant land was greater than that of individual trees on residential land. The fact that trees in vacant land were found to provide more ecosystem services per tree than residential trees was attributed to this leaf area difference. Trees on vacant land are growing in more natural conditions and there are more large trees per ha. Assessing the forest structure and ecosystem services of Roanoke’s vacant and residential land provides a picture of the current extent and condition of the vacant and residential land. Understanding these characteristics provides the information needed for improved management and utilization of urban vacant land and estimating green infrastructure value.
Song, Liang-Li; Cui, Yan; Yu, Si-Jiu; Liu, Peng-Gang; Liu, Jun; Yang, Xue; He, Jun-Feng; Zhang, Qian
Bone morphogenetic protein 2 (BMP2), BMP receptor-IA (BMPR-IA), and the BMP2 antagonist Noggin are important proteins involved in regulating the hair follicle (HF) cycle in skin. In order to explore the expression profiles of BMP2, BMPR-IA, and Noggin in the HF cycle of yak skin, we collected adult yak skin in the telogen, proanagen, and midanagen phases of HFs and evaluated gene and protein expression by real-time quantitative polymerase chain reaction (qRT-PCR), western blotting, and immunohistochemistry. qRT-PCR and western blotting results showed that BMP2 and BMPR-IA expression levels were highest in the telogen of HFs and higher than that of Noggin in the same phase. The expression of Noggin was significantly higher in proanagen and midanagen phases of HFs than in the telogen phase, with the highest expression observed in the proanagen phase. Moreover, the expression of Noggin in the proanagen phase was significantly higher than those of BMP2 and BMPR-IA during the same phase. Immunohistochemistry results showed that BMP2, BMPR-IA, and Noggin were expressed in the skin epidermis, sweat glands, sebaceous glands, HF outer root sheath, and hair matrix. In summary, the characteristic expression profiles of BMP2, BMPR-IA, and Noggin suggested that BMP2 and BMPR-IA had inhibitory effects on the growth of HFs in yaks, whereas Noggin promoted the growth of yak HFs, mainly by affecting skin epithelial cell activity. These results provide a basis for further studies of HF development and cycle transition in yak skin. Copyright © 2017. Published by Elsevier Inc.
Full Text Available Abstract Background Axolotls have the unique ability, among vertebrates, to perfectly regenerate complex body parts, such as limbs, after amputation. In addition, axolotls pattern developing and regenerating autopods from the anterior to posterior axis instead of posterior to anterior like all tetrapods studied to date. Sonic hedgehog is important in establishing this anterior-posterior axis of limbs in all tetrapods including axolotls. Interestingly, its expression is conserved (to the posterior side of limb buds and blastemas in axolotl limbs as in other tetrapods. It has been suggested that BMP-2 may be the secondary mediator of sonic hedgehog, although there is mounting evidence to the contrary in mice. Since BMP-2 expression is on the anterior portion of developing and regenerating limbs prior to digit patterning, opposite to the expression of sonic hedgehog, we examined whether BMP-2 expression was dependent on sonic hedgehog signaling and whether it affects patterning of the autopod during regeneration. Results The expression of BMP-2 and SOX-9 in developing and regenerating axolotl limbs corresponded to the first digits forming in the anterior portion of the autopods. The inhibition of sonic hedgehog signaling with cyclopamine caused hypomorphic limbs (during development and regeneration but did not affect the expression of BMP-2 and SOX-9. Overexpression of BMP-2 in regenerating limbs caused a loss of digits. Overexpression of Noggin (BMP inhibitor in regenerating limbs also resulted in a loss of digits. Histological analysis indicated that the loss due to BMP-2 overexpression was the result of increased cell condensation and apoptosis while the loss caused by Noggin was due to a decrease in cell division. Conclusion The expression of BMP-2 and its target SOX-9 was independent of sonic hedgehog signaling in developing and regenerating limbs. Their expression correlated with chondrogenesis and the appearance of skeletal elements has
Childs, Andrew J; Kinnell, Hazel L; Collins, Craig S; Hogg, Kirsten; Bayne, Rosemary A L; Green, Samira J; McNeilly, Alan S; Anderson, Richard A
Primordial germ cells (PGCs) are the embryonic precursors of gametes in the adult organism, and their development, differentiation, and survival are regulated by a combination of growth factors collectively known as the germ cell niche. Although many candidate niche components have been identified through studies on mouse PGCs, the growth factor composition of the human PGC niche has not been studied extensively. Here we report a detailed analysis of the expression of components of the bone morphogenetic protein (BMP) signaling apparatus in the human fetal ovary, from postmigratory PGC proliferation to the onset of primordial follicle formation. We find developmentally regulated and reciprocal patterns of expression of BMP2 and BMP4 and identify germ cells to be the exclusive targets of ovarian BMP signaling. By establishing long-term cultures of human fetal ovaries in which PGCs are retained within their physiological niche, we find that BMP4 negatively regulates postmigratory PGC numbers in the human fetal ovary by promoting PGC apoptosis. Finally, we report expression of both muscle segment homeobox (MSX)1 and MSX2 in the human fetal ovary and reveal a selective upregulation of MSX2 expression in human fetal ovary in response to BMP4, suggesting this gene may act as a downstream effector of BMP-induced apoptosis in the ovary, as in other systems. These data reveal for the first time growth factor regulation of human PGC development in a physiologically relevant context and have significant implications for the development of cultures systems for the in vitro maturation of germ cells, and their derivation from pluripotent stem cells.
Pan, Hsin Chuan; Lee, Soonchul; Ting, Kang; Shen, Jia; Wang, Chenchao; Nguyen, Alan; Berthiaume, Emily A; Zara, Janette N; Turner, A Simon; Seim, Howard B; Kwak, Jin Hee; Zhang, Xinli; Soo, Chia
Multiple case reports using recombinant human bone morphogenetic protein-2 (rhBMP-2) have reported complications. However, the local adverse effects of rhBMP-2 application are not well documented. In this report we show that, in addition to promoting lumbar spinal fusion through potent osteogenic effects, rhBMP-2 augmentation promotes local cyst-like osteolytic formations in sheep trabecular bones that have undergone anterior lumbar interbody fusion. Three months after operation, conventional computed tomography showed that the trabecular bones of the rhBMP-2 application groups could fuse, whereas no fusion was observed in the control group. Micro-computed tomography analysis revealed that the core implant area's bone volume fraction and bone mineral density increased proportionately with rhBMP-2 dose. Multiple cyst-like bone voids were observed in peri-implant areas when using rhBMP-2 applications, and these sites showed significant bone mineral density decreases in relation to the unaffected regions. Biomechanically, these areas decreased in strength by 32% in comparison with noncystic areas. Histologically, rhBMP-2-affected void sites had an increased amount of fatty marrow, thinner trabecular bones, and significantly more adiponectin- and cathepsin K-positive cells. Despite promoting successful fusion, rhBMP-2 use in clinical applications may result in local adverse structural alterations and compromised biomechanical changes to the bone. Copyright © 2017 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.
Galeone, Antonio; Han, Seung Yeop; Huang, Chengcheng; Hosomi, Akira; Suzuki, Tadashi; Jafar-Nejad, Hamed
Mutations in the human N- glycanase 1 ( NGLY1 ) cause a rare, multisystem congenital disorder with global developmental delay. However, the mechanisms by which NGLY1 and its homologs regulate embryonic development are not known. Here we show that Drosophila Pngl encodes an N -glycanase and exhibits a high degree of functional conservation with human NGLY1. Loss of Pngl results in developmental midgut defects reminiscent of midgut-specific loss of BMP signaling. Pngl mutant larvae also exhibit a severe midgut clearance defect, which cannot be fully explained by impaired BMP signaling. Genetic experiments indicate that Pngl is primarily required in the mesoderm during Drosophila development. Loss of Pngl results in a severe decrease in the level of Dpp homodimers and abolishes BMP autoregulation in the visceral mesoderm mediated by Dpp and Tkv homodimers. Thus, our studies uncover a novel mechanism for the tissue-specific regulation of an evolutionarily conserved signaling pathway by an N -glycanase enzyme.
Egashira, Kazuhiro; Sumita, Yoshinori; Zhong, Weijian; I, Takashi; Ohba, Seigo; Nagai, Kazuhiro; Asahina, Izumi
Bone marrow concentrate (BMC), which is enriched in mononuclear cells (MNCs) and platelets, has recently attracted the attention of clinicians as a new optional means for bone engineering. We previously reported that the osteoinductive effect of bone morphogenetic protein-2 (BMP-2) could be enhanced synergistically by co-transplantation of peripheral blood (PB)-derived platelet-rich plasma (PRP). This study aims to investigate whether BMC can effectively promote bone formation induced by low-dose BMP-2, thereby reducing the undesirable side-effects of BMP-2, compared to PRP. Human BMC was obtained from bone marrow aspirates using an automated blood separator. The BMC was then seeded onto β-TCP granules pre-adsorbed with a suboptimal-dose (minimum concentration to induce bone formation at 2 weeks in mice) of recombinant human (rh) BMP-2. These specimens were transplanted subcutaneously to the dorsal skin of immunodeficient-mice and the induction of ectopic bone formation was assessed 2 and 4 weeks post-transplantation. Transplantations of five other groups [PB, PRP, platelet-poor plasma (PPP), bone marrow aspirate (BM), and BM-PPP] were employed as experimental controls. Then, to clarify the effects on vertical bone augmentation, specimens from the six groups were transplanted for on-lay placement on the craniums of mice. The results indicated that BMC, which contained an approximately 2.5-fold increase in the number of MNCs compared to PRP, could accelerate ectopic bone formation until 2 weeks post-transplantation. On the cranium, the BMC group promoted bone augmentation with a suboptimal-dose of rhBMP-2 compared to other groups. Particularly in the BMC specimens harvested at 4 weeks, we observed newly formed bone surrounding the TCP granules at sites far from the calvarial bone. In conclusion, the addition of BMC could reduce the amount of rhBMP-2 by one-half via its synergistic effect on early-phase osteoinduction. We propose here that BMC transplantation
Sansalone, John; Raje, Saurabh; Kertesz, Ruben; Maccarone, Kerrilynn; Seltzer, Karl; Siminari, Michele; Simms, Peter; Wood, Brandon
The built environs alter hydrology and water resource chemistry. Florida is subject to nutrient criteria and is promulgating "no-net-load-increase" criteria for runoff and constituents (nutrients and particulate matter, PM). With such criteria, green infrastructure, hydrologic restoration, indirect reuse and source control are potential design solutions. The study simulates runoff and constituent load control through urban source area re-design to provide long-term "no-net-load-increases". A long-term continuous simulation of pre- and post-development response for an existing surface parking facility is quantified. Retrofits include a biofiltration area reactor (BAR) for hydrologic and denitrification control. A linear infiltration reactor (LIR) of cementitious permeable pavement (CPP) provides infiltration, adsorption and filtration. Pavement cleaning provided source control. Simulation of climate and source area data indicates re-design achieves "no-net-load-increases" at lower costs compared to standard construction. The retrofit system yields lower cost per nutrient load treated compared to Best Management Practices (BMPs). Copyright © 2013 Elsevier Ltd. All rights reserved.
Chang, Hsun-Ming; Cheng, Jung-Chien; Klausen, Christian; Leung, Peter C K
In addition to somatic cell-derived growth factors, oocyte-derived growth differentiation factor (GDF)9 and bone morphogenetic protein (BMP)15 play essential roles in female fertility. However, few studies have investigated their effects on human ovarian steroidogenesis, and fewer still have examined their differential effects or underlying molecular determinants. In the present study, we used immortalized human granulosa cells (SVOG) and human granulosa cell tumor cells (KGN) to compare the effects of GDF9 and BMP15 on steroidogenic enzyme expression and investigate potential mechanisms of action. In SVOG cells, neither GDF9 nor BMP15 affects the mRNA levels of P450 side-chain cleavage enzyme or 3β-hydroxysteroid dehydrogenase. However, treatment with BMP15, but not GDF9, significantly decreases steroidogenic acute regulatory protein (StAR) mRNA and protein levels as well as progesterone production. These suppressive effects, along with the induction of Sma and Mad-related protein (SMAD)1/5/8 phosphorylation, are attenuated by cotreatment with 2 different BMP type I receptor inhibitors (dorsomorphin and DMH-1). Furthermore, depletion of activin receptor-like kinase (ALK)3 using small interfering RNA reverses the effects of BMP15 on SMAD1/5/8 phosphorylation and StAR expression. Similarly, knockdown of ALK3 abolishes BMP15-induced SMAD1/5/8 phosphorylation in KGN cells. These results provide evidence that oocyte-derived BMP15 down-regulates StAR expression and decreases progesterone production in human granulosa cells, likely via ALK3-mediated SMAD1/5/8 signaling. Our findings suggest that oocyte may play a critical role in the regulation of progesterone to prevent premature luteinization during the late stage of follicle development.
Sagomonyants, Karen; Mina, Mina
Odontoblast differentiation during physiological and reparative dentinogenesis is dependent upon multiple signaling molecules, including fibroblast growth factors (FGFs), bone morphogenetic proteins (BMPs) and Wingless/Integrated (Wnt) ligands. Recent studies in our laboratory showed that continuous exposure of primary dental pulp cultures to FGF2 exerted biphasic effects on the expression of markers of dentinogenesis. In the present study, we examined the possible involvement of the BMP and Wnt signaling pathways in mediating the effects of FGF2 on dental pulp cells. Our results showed that stimulatory effects of FGF2 on dentinogenesis during the proliferation phase of growth were associated with increased expression of the components of the BMP (Bmp2, Dlx5, Msx2, Osx) and Wnt (Wnt10a, Wisp2) pathways, and decreased expression of an inhibitor of the Wnt signaling, Nkd2. Further addition of FGF2 during the differentiation/mineralization phase of growth resulted in decreased expression of components of the BMP signaling (Bmp2, Runx2, Osx) and increased expression of inhibitors of the Wnt signaling (Nkd2, Dkk3). This suggests that both BMP and Wnt pathways may be involved in mediating the effects of FGF2 on dental pulp cells.
Full Text Available Abstract Background Adrenal chromaffin cells and sympathetic neurons both originate from the neural crest, yet signals that trigger chromaffin development remain elusive. Bone morphogenetic proteins (BMPs emanating from the dorsal aorta are important signals for the induction of a sympathoadrenal catecholaminergic cell fate. Results We report here that BMP-4 is also expressed by adrenal cortical cells throughout chick embryonic development, suggesting a putative role in chromaffin cell development. Moreover, bone morphogenetic protein receptor IA is expressed by both cortical and chromaffin cells. Inhibiting BMP-4 with noggin prevents the increase in the number of tyrosine hydroxylase positive cells in adrenal explants without affecting cell proliferation. Hence, adrenal BMP-4 is likely to induce tyrosine hydroxylase in sympathoadrenal progenitors. To investigate whether persistent BMP-4 exposure is able to induce chromaffin traits in sympathetic ganglia, we locally grafted BMP-4 overexpressing cells next to sympathetic ganglia. Embryonic day 8 chick sympathetic ganglia, in addition to principal neurons, contain about 25% chromaffin-like cells. Ectopic BMP-4 did not increase this proportion, yet numbers and sizes of 'chromaffin' granules were significantly increased. Conclusion BMP-4 may serve to promote specific chromaffin traits, but is not sufficient to convert sympathetic neurons into a chromaffin phenotype.
Bhavani S. Kowtharapu
Full Text Available In the cornea, healing of the wounded avascular surface is an intricate process comprising the involvement of epithelial, stromal and neuronal cell interactions. These interactions result to the release of various growth factors that play prominent roles during corneal wound healing response. Bone morphogenetic proteins (BMPs are unique multi-functional potent growth factors of the transforming growth factor-beta (TGF-β superfamily. Treatment of corneal epithelial cells with substance P and nerve growth factor resulted to an increase in the expression of BMP7 mRNA. Since BMP7 is known to modulate the process of corneal wound healing, in this present study, we investigated the influence of exogenous rhBMP7 on human corneal epithelial cell and stromal cell (SFs function. To obtain a high-fidelity expression profiling of activated biomarkers and pathways, transcriptome-wide gene-level expression profiling of epithelial cells in the presence of BMP7 was performed. Gene ontology analysis shows BMP7 stimulation activated TGF-β signaling and cell cycle pathways, whereas biological processes related to cell cycle, microtubule and intermediate filament cytoskeleton organization were significantly impacted in corneal epithelial cells. Scratch wound healing assay showed increased motility and migration of BMP7 treated epithelial cells. BMP7 stimulation studies show activation of MAPK cascade proteins in epithelial cells and SFs. Similarly, a difference in the expression of claudin, Zink finger E-box-binding homeobox 1 was observed along with phosphorylation levels of cofilin in epithelial cells. Stimulation of SFs with BMP7 activated them with increased expression of α-smooth muscle actin. In addition, an elevated phosphorylation of epidermal growth factor receptor following BMP7 stimulation was also observed both in corneal epithelial cells and SFs. Based on our transcriptome analysis data on epithelial cells and the results obtained in SFs, we
Full Text Available Recently a submicron particle of biphasic calcium phosphate ceramic (BCP with through-hole (donut-shaped BCP (d-BCP was developed for improving the osteoconductivity. This study was performed to examine the usefulness of d-BCP for the delivery of osteoinductive rhBMP2 and the effectiveness on cranial bone regeneration. The d-BCP was soaked in rhBMP2 solution and then freeze-dried. Scanning electron microscope (SEM, energy dispersive spectroscopy (EDS, and Raman spectroscopy analyses confirmed that rhBMP2 was well delivered onto the d-BCP surface and the through-hole. The bioactivity of the rhBMP2/d-BCP composite was validated in MC3T3-E1 cells as an in vitro model and in critical-sized cranial defects in C57BL/6 mice. When freeze-dried d-BCPs with rhBMP2 were placed in transwell inserts and suspended above MC3T3-E1, alkaline phosphatase activity and osteoblast-specific gene expression were increased compared to non-rhBMP2-containing d-BCPs. For evaluating in vivo effectiveness, freeze-dried d-BCPs with or without rhBMP2 were implanted into critical-sized cranial defects. Microcomputed tomography and histologic analysis showed that rhBMP2-containing d-BCPs significantly enhanced cranial bone regeneration compared to non-rhBMP2-containing control. These results suggest that a combination of d-BCP and rhBMP2 can accelerate bone regeneration, and this could be used to develop therapeutic strategies in hard tissue healing.
Jeong, Byung-Chul; Choi, Hyuck; Hur, Sung-Woong; Kim, Jung-Woo; Oh, Sin-Hye; Kim, Hyun-Seung; Song, Soo-Chang; Lee, Keun-Bae; Park, Kwang-Bum; Koh, Jeong-Tae
Recently a submicron particle of biphasic calcium phosphate ceramic (BCP) with through-hole (donut-shaped BCP (d-BCP)) was developed for improving the osteoconductivity. This study was performed to examine the usefulness of d-BCP for the delivery of osteoinductive rhBMP2 and the effectiveness on cranial bone regeneration. The d-BCP was soaked in rhBMP2 solution and then freeze-dried. Scanning electron microscope (SEM), energy dispersive spectroscopy (EDS), and Raman spectroscopy analyses confirmed that rhBMP2 was well delivered onto the d-BCP surface and the through-hole. The bioactivity of the rhBMP2/d-BCP composite was validated in MC3T3-E1 cells as an in vitro model and in critical-sized cranial defects in C57BL/6 mice. When freeze-dried d-BCPs with rhBMP2 were placed in transwell inserts and suspended above MC3T3-E1, alkaline phosphatase activity and osteoblast-specific gene expression were increased compared to non-rhBMP2-containing d-BCPs. For evaluating in vivo effectiveness, freeze-dried d-BCPs with or without rhBMP2 were implanted into critical-sized cranial defects. Microcomputed tomography and histologic analysis showed that rhBMP2-containing d-BCPs significantly enhanced cranial bone regeneration compared to non-rhBMP2-containing control. These results suggest that a combination of d-BCP and rhBMP2 can accelerate bone regeneration, and this could be used to develop therapeutic strategies in hard tissue healing.
Izawa, H.; Hachiya, Y.; Muramatsu, K.; Narita, Y.; Kawai, T.
Viral infection are an extremely serious in allogeneic bone transplantations. While it is essential to kill viruses such as HIV in allogeneic bone graft, the osteoinductive activity must be preserved. Heat treatment of allogeneic bone graft at 60 degree C for 10 hours is effective in killing viruses such as HIV, but it is unclear to what extent the activity of human bone morphogenetic protein (hBMP) is preserved. In this experiment crude hBMP was extracted from both heated and non-heated human bones which were decalcified by the Urist method. Gelatin capsules containing 5mg of crude hBMP were transplanted into the thigh muscles of 5 week old mice. Human bone samples heated in a water bath at 60 degree C for 10 hours and non-heated samples were each transplanted into 5 mice. At 20 days after transplantation, the heterotopic bone formation was compared by evaluation of X-ray and histologicic analysis. X-rays showed heterotopic bone formation in both heated and non-heated samples. Further, histologic analysis showed that peripheral osteoid tissue had developed into laminar bone formation and interlaminar bone marrow was observed. Heterotopic bone formation was induced by crude hBMP from heated bones in a similar way to crude hBMP from non-heated bones observed in X-ray. There was no significant difference in histologic analysis. The crude hBMP, extracted from bones which were heat-treated at 60 degree C for 10 hours induced heterotopic bone formation similar to that in non-heated bone observed by X-ray and histologic analysis at 20 days after transplantation. This demostrates that the heat-treated bone preserved osteoinduction
Cao, Lingyan [Key Laboratory for Ultrafine Materials of Ministry of Education, East China University of Science and Technology, Shanghai 200237 (China); Engineering Research Center for Biomedical Materials of Ministry of Education, East China University of Science and Technology, Shanghai 200237 (China); CSIRO Manufacturing, Bayview Avenue, Clayton, Victoria 3168 (Australia); Department of Prosthodontics, College of Stomatology, Ninth People' s Hospital, School of Medicine, Shanghai Jiao Tong University, 639 Zhizaoju Road, Shanghai 200011 (China); Yu, Yuanman [Key Laboratory for Ultrafine Materials of Ministry of Education, East China University of Science and Technology, Shanghai 200237 (China); Engineering Research Center for Biomedical Materials of Ministry of Education, East China University of Science and Technology, Shanghai 200237 (China); Wang, Jing, E-mail: firstname.lastname@example.org [Key Laboratory for Ultrafine Materials of Ministry of Education, East China University of Science and Technology, Shanghai 200237 (China); Engineering Research Center for Biomedical Materials of Ministry of Education, East China University of Science and Technology, Shanghai 200237 (China); Werkmeister, Jerome A [CSIRO Manufacturing, Bayview Avenue, Clayton, Victoria 3168 (Australia); McLean, Keith M, E-mail: Keith.McLean@csiro.au [CSIRO Manufacturing, Bayview Avenue, Clayton, Victoria 3168 (Australia); Liu, Changsheng, E-mail: email@example.com [Key Laboratory for Ultrafine Materials of Ministry of Education, East China University of Science and Technology, Shanghai 200237 (China); Engineering Research Center for Biomedical Materials of Ministry of Education, East China University of Science and Technology, Shanghai 200237 (China)
The aim of this study was to develop a 2-N, 6-O-sulfated chitosan (26SCS) modified electrospun fibrous PCL scaffold for bone morphogenetic protein-2 (BMP-2) delivery to improve osteoinduction. The PCL scaffold was modified by an aminolysis reaction using ethylenediamine (ED) and 26SCS was immobilized via electrostatic interactions (PCL-N-S). Scaffolds were characterized by scanning electron microscopy (SEM), atomic force microscopy (AFM), X-ray photoelectron spectroscopy (XPS) and contact angle measurements. In vitro BMP-2 adsorption and release kinetics indicated that modified PCL-N-S scaffolds showed higher levels of binding of BMP-2 (about 30–100 times), moderative burst release (about one third), and prolonged releasing time compared to the unmodified PCL scaffold. The bioactivity of released BMP-2 determined by alkaline phosphatase (ALP) activity assay was maintained and improved 8– 12 times with increasing concentration of immobilized 26SCS on the scaffolds. In vitro studies demonstrated that bone marrow mesenchymal stem cells (BMSCs) attached more readily to the PCL-N-S scaffolds with increased spreading. In conclusion, 26SCS modified PCL scaffolds can be a potent system for the sustained and bioactive delivery of BMP-2. - Graphical abstract: Limited self-regenerating capacity of human body makes the reconstruction of critical size bone defect a significant challenge. Although bone morphogenetic protein-2 (BMP-2) is an important differentiation factor inducing bone regeneration, it's short half-life in vivo and potent side effect at high dosage still show lots of concerns in the clinical use. Herein, modification of electrospun PCL scaffolds was presented through immobilizing of sulfated chitosan (26SCS). The modified scaffolds effectively improve the binding capacity of BMP-2 and exhibited an enhanced bioactivity and sustained release in vitro. Thus, the use of 26SCS modified PCL scaffolds combined with BMP-2 could be a useful scaffold for tissue
Markus D Schofer
Full Text Available Adequate migration and differentiation of mesenchymal stem cells is essential for regeneration of large bone defects. To achieve this, modern graft materials are becoming increasingly important. Among them, electrospun nanofiber scaffolds are a promising approach, because of their high physical porosity and potential to mimic the extracellular matrix (ECM.The objective of the present study was to examine the impact of electrospun PLLA nanofiber scaffolds on bone formation in vivo, using a critical size rat calvarial defect model. In addition we analyzed whether direct incorporation of bone morphogenetic protein 2 (BMP-2 into nanofibers could enhance the osteoinductivity of the scaffolds. Two critical size calvarial defects (5 mm were created in the parietal bones of adult male Sprague-Dawley rats. Defects were either (1 left unfilled, or treated with (2 bovine spongiosa, (3 PLLA scaffolds alone or (4 PLLA/BMP-2 scaffolds. Cranial CT-scans were taken at fixed intervals in vivo. Specimens obtained after euthanasia were processed for histology, histomorphometry and immunostaining (Osteocalcin, BMP-2 and Smad5.PLLA scaffolds were well colonized with cells after implantation, but only showed marginal ossification. PLLA/BMP-2 scaffolds showed much better bone regeneration and several ossification foci were observed throughout the defect. PLLA/BMP-2 scaffolds also stimulated significantly faster bone regeneration during the first eight weeks compared to bovine spongiosa. However, no significant differences between these two scaffolds could be observed after twelve weeks. Expression of osteogenic marker proteins in PLLA/BMP-2 scaffolds continuously increased throughout the observation period. After twelve weeks osteocalcin, BMP-2 and Smad5 were all significantly higher in the PLLA/BMP-2 group than in all other groups.Electrospun PLLA nanofibers facilitate colonization of bone defects, while their use in combination with BMP-2 also increases bone
Haris, H.; Chow, M. F.; Usman, F.; Sidek, L. M.; Roseli, Z. A.; Norlida, M. D.
Urbanization is growing rapidly in Malaysia. Rapid urbanization has known to have several negative impacts towards hydrological cycle due to decreasing of pervious area and deterioration of water quality in stormwater runoff. One of the negative impacts of urbanization is the congestion of the stormwater drainage system and this situation leading to flash flood problem and water quality degradation. There are many urban stormwater management softwares available in the market such as Storm Water Drainage System design and analysis program (DRAINS), Urban Drainage and Sewer Model (MOUSE), InfoWorks River Simulation (InfoWork RS), Hydrological Simulation Program-Fortran (HSPF), Distributed Routing Rainfall-Runoff Model (DR3M), Storm Water Management Model (SWMM), XP Storm Water Management Model (XPSWMM), MIKE-SWMM, Quality-Quantity Simulators (QQS), Storage, Treatment, Overflow, Runoff Model (STORM), and Hydrologic Engineering Centre-Hydrologic Modelling System (HEC-HMS). In this paper, we are going to discuss briefly about several softwares and their functionality, accessibility, characteristics and components in the quantity analysis of the hydrological design software and compare it with MSMA Design Aid and Database. Green Infrastructure (GI) is one of the main topics that has widely been discussed all over the world. Every development in the urban area is related to GI. GI can be defined as green area build in the develop area such as forest, park, wetland or floodway. The role of GI is to improve life standard such as water filtration or flood control. Among the twenty models that have been compared to MSMA SME, ten models were selected to conduct a comprehensive review for this study. These are known to be widely accepted by water resource researchers. These ten tools are further classified into three major categories as models that address the stormwater management ability of GI in terms of quantity and quality, models that have the capability of conducting the
Hansen, Rieke; Pauleit, Stephan
Green infrastructure (GI) and ecosystem services (ES) are promoted as concepts that have potential to improve environmental planning in urban areas based on a more holistic understanding of the complex interrelations and dynamics of social-ecological systems. However, the scientific discourses around both concepts still lack application-oriented frameworks that consider such a holistic perspective and are suitable to mainstream GI and ES in planning practice. This literature review explores how multifunctionality as one important principle of GI planning can be operationalized by approaches developed and tested in ES research. Specifically, approaches developed in ES research can help to assess the integrity of GI networks, balance ES supply and demand, and consider trade-offs. A conceptual framework for the assessment of multifunctionality from a social-ecological perspective is proposed that can inform the design of planning processes and support stronger exchange between GI and ES research.
Farooq, Muhammad Junaid; Ghazzai, Hakim; Yaacoub, Elias; Kadri, Abdullah; Alouini, Mohamed-Slim
This paper proposes and investigates a green virtualization framework for infrastructure sharing among multiple cellular operators whose networks are powered by a combination of conventional and renewable sources of energy. Under the proposed
Comparative expression analyses of bone morphogenetic protein 4 (BMP4) expressions in muscles of tilapia and common carp indicate that BMP4 plays a role in the intermuscular bone distribution in a dose-dependent manner.
Su, Shengyan; Dong, Zaijie
Intermuscular bones in fish negatively influence both meet processing and attractiveness to consumers. Tilapia (Oreochromis niloticus) and common carp (Cyprinus carpio) are both major farmed fish species globally, but whereas the former does not possess intermuscular bones, the latter does. Therefore, these two species might present a good model to study the genetic control of distribution of intermuscular bones in fish. Bone morphogenetic protein 4 (BMP4) gene is associated with tissue ossification and bone regeneration in mammals, but in fish its role in ossification remains understudied. To study the relationship between BMP4 and bone distribution in fish, we determined the expression of BMP4 in muscle tissues of common carp and tilapia on transcriptional and translational levels. As the gene has been merely predicted in silico from the genome of common carp, we have cloned and characterized it. The gene (GenBank: HQ446455) contains one intron and two exons, which encode a 400-amino acid protein with high homology to other known BMP4 protein sequences. Phylogenetic analysis showed that common carp clustered within the Cypriniformes clade (zebrafish was the closest ortholog) and tilapia within the Percomorpha clade. Using microCT scanning, we confirmed that intermuscular bones could be observed only in common carp (none in tilapia), but only in dorsal and caudal muscles (none in the ventral muscle). Expression levels of BMP4 in the muscles of common carp were in agreement with this observation both on transcriptional (qPCR) and translational (immunohistochemistry) level: higher in dorsal and caudal muscles, and lower in the ventral muscle. In tilapia, expression of BMP4 gene was also detectable in all three muscles, but expression levels in all three muscles were comparable to the one observed in the ventral muscle of carp, i.e., very low. Therefore, among the six studied muscles, the expression of BMP4 was high only in the two that possess intermuscular bones
Feng, Jian Q; Xing, Lianping; Zhang, Jiang-Hong; Zhao, Ming; Horn, Diane; Chan, Jeannie; Boyce, Brendan F; Harris, Stephen E; Mundy, Gregory R; Chen, Di
Bone morphogenetic protein-2 (BMP-2) regulates growth plate chondrogenesis during development and postnatal bone growth, but the control mechanisms of BMP-2 expression in growth plate chondrocytes are unknown. Here we have used both in vitro and in vivo approaches to demonstrate that transcription factor, NF-kappaB, regulates BMP-2 gene expression in chondrocytes. Two putative NF-kappaB response elements were found in the -2712/+165 region of the BMP-2 gene. Cotransfection of mutant I-kappaBalpha expression plasmids with BMP-2 promoter-luciferase reporters into TMC-23 chondrocyte cell line suppressed BMP-2 transcription. Mutations in NF-kappaB response elements in the BMP-2 gene lead to decreases in BMP-2 promoter activity. Electrophoretic mobility shift assay using nuclear extracts from TMC-23 chondrocytic cells revealed that the NF-kappaB subunits p50 and p65 bound to the NF-kappaB response elements of the BMP-2 gene. Thus, NF-kappaB may positively regulate BMP-2 gene transcription. Consistent with these findings, expression of BMP-2 mRNA was significantly reduced in growth plate chondrocytes in NF-kappaB p50/p52 dKO mice, which associated with decreased numbers of 5-bromo-2'-deoxyuridine (BrdUrd)-positive cells in the proliferating zone of growth plate in these mice. Therefore, in postnatal growth plate chondrocytes, expression of BMP-2 is regulated by NF-kappaB, which may play an important role in chondrogenesis.
Andersson, Therese; Duckworth, Joshua K; Fritz, Nicolas
levels, that in turn exerted a concentration-dependent inhibition of BMP4-mediated mesenchymal differentiation of NSCs. Instead, BMP4 exposure of NSCs induced neuronal differentiation in mesenchyme-preventing conditions, whereas treatment with recombinant noggin alone did not. Wnt signaling is known...... to be essential for the development of neurons derived from the dorsal telencephalon, and co-stimulation of NSCs with BMP4+Wnt3a resulted in a synergistic effect yielding significantly increased number of mature neurons compared to stimulation with each factor alone. Thus whereas only a subset of BMP4-induced...... neurons derived from telencephalic NSCs, responded to glutamate receptor (GluR) agonists, over 80% of BMP4+Wnt3a-induced neurons responded appropriately to GluR-agonists. Our results increase the understanding of the role for BMP4 in differentiation of telencephalic multipotent progenitors, and reveal...
Raposo, Francisco; Fernández-Cegrí, V.; De la Rubia, M.A.
This paper describes the results obtained for different participating research groups in an interlaboratory study related to the biochemical methane potential (BMP). In this research work, the full experimental conditions influencing the test such as inoculum, substrate characteristics and experi...
Song, Yang; Tang, Yinhong; Song, Jinlin; Lei, Mingxing; Liang, Panpan; Fu, Tiwei; Su, Xudong; Zhou, Pengfei; Yang, Li; Huang, Enyi
The purpose of this study was to investigate whether mechanical stretch can enhance the bone morphogenetic protein 9 (BMP9)-induced osteogenic differentiation in MSCs. Recombinant adenoviruses were used to overexpress the BMP9 in C3H10T1/2 MSCs. Cells were seeded onto six-well BioFlex collagen I-coated plates and subjected to cyclic mechanical stretch [6% elongation at 60 cycles/minute (1 Hz)] in a Flexercell FX-4000 strain unit for up to 12 hours. Immunostaining and confocal microscope were used to detect cytoskeleton organization. Cell cycle progression was checked by flow cytometry. Alkaline phosphatase activity was measured with a Chemiluminescence Assay Kit and was quantified with a histochemical staining assay. Matrix mineralization was examined by Alizarin Red S Staining. Mechanical stretch induces cytoskeleton reorganization and inhibits cell proliferation by preventing cells entry into S phase of the cell cycle. Although mechanical stretch alone does not induce the osteogenic differentiation of C3H10T1/2 MSCs, co-stimulation with mechanical stretch and BMP9 enhances alkaline phosphatase activity. The expression of key lineage-specific regulators (e.g., osteocalcin (OCN), SRY-related HMG-box 9, and runt-related transcription factor 2) is also increased after the co-stimulation, compared to the mechanical stretch stimulation along. Furthermore, mechanical stretch augments the BMP9-mediated bone matrix mineralization of C3H10T1/2 MSCs. Our results suggest that mechanical stretch enhances BMP9-induced osteoblastic lineage specification in C3H10T1/2 MSCs.
He, Xiaoning; Liu, Yang; Yuan, Xue; Lu, Li
In this study, we designed a chitosan/alginate/hydroxyapatite scaffold as a carrier for recombinant BMP-2 (CAH/B2), and evaluated the release kinetics of BMP-2. We evaluated the effect of the CAH/B2 scaffold on the viability and differentiation of bone marrow mesenchymal stem cells (MSCs) by scanning electron microscopy, MTS, ALP assay, alizarin-red staining and qRT-PCR. Moreover, MSCs were seeded on scaffolds and used in a 8 mm rat calvarial defect model. New bone formation was assessed by radiology, hematoxylin and eosin staining 12 weeks postoperatively. We found the release kinetics of BMP-2 from the CAH/B2 scaffold were delayed compared with those from collagen gel, which is widely used for BMP-2 delivery. The BMP-2 released from the scaffold increased MSC differentiation and did not show any cytotoxicity. MSCs exhibited greater ALP activity as well as stronger calcium mineral deposition, and the bone-related markers Col1α, osteopontin, and osteocalcin were upregulated. Analysis of in vivo bone formation showed that the CAH/B2 scaffold induced more bone formation than other groups. This study demonstrates that CAH/B2 scaffolds might be useful for delivering osteogenic BMP-2 protein and present a promising bone regeneration strategy. PMID:25084008
Jarrin, Miguel; Pandit, Tanushree; Gunhaga, Lena
In embryonic and adult lenses, a balance of cell proliferation, cell cycle exit, and differentiation is necessary to maintain physical function. The molecular mechanisms regulating the transition of proliferating lens epithelial cells to differentiated primary lens fiber cells are poorly characterized. To investigate this question, we used gain- and loss-of-function analyses to modulate fibroblast growth factor (FGF) and/or bone morphogenetic protein (BMP) signals in chick lens/retina explants. Here we show that FGF activity plays a key role for proliferation independent of BMP signals. Moreover, a balance of FGF and BMP signals regulates cell cycle exit and the expression of Ccdc80 (also called Equarin), which is expressed at sites where differentiation of lens fiber cells occurs. BMP activity promotes cell cycle exit and induces Equarin expression in an FGF-dependent manner. In contrast, FGF activity is required but not sufficient to induce cell cycle exit or Equarin expression. Furthermore, our results show that in the absence of BMP activity, lens cells have increased cell cycle length or are arrested in the cell cycle, which leads to decreased cell cycle exit. Taken together, these findings suggest that proliferation, cell cycle exit, and early differentiation of primary lens fiber cells are regulated by counterbalancing BMP and FGF signals. PMID:22718906
Full Text Available Background: Alveolar bone defects in children still have a high incidence. Conventional bone graft technique that has been used as a defect therapy is still not effective, so new techniques with tissue engineering approach are needed. Bone Morphogenetic Protein 4 (BMP4 as one of the indicators of osteogenic differentiation has not been widely studied, especially in the transplantation with combination of Stem Cells from Human Exfoliated Deciduous (SHED and carbonate apatite. Aim and Objectives: This research aimed to determine the expression of BMP4 after SHED and carbonate apatite transplantation on Rattus norvegicus. Material and Methods: The combinations of SHED and carbonate apatite were transplanted on alveolar bone defects of 4 rats (Rattus norvegicus as the treatment groups and another 4 rats were transplanted with carbonate apatite as the control groups. After 21 days, staining with Hematoxylin Eosin (HE and Immunohistochemistry (IHC BMP4 was performed. Results: BMP4 expression in the treatment groups was significantly higher when compared to the control groups. Discussion: Carbonate apatite has low crystallization rate and high osteoconductivity that produce more osteoblasts and increased BMP4 expression. Conclusion: The transplantation of SHED and carbonate apatite increased BMP4 expression as an indicator of osteogenic differentiation in rats.
Hurlbert, R John; Alexander, David; Bailey, Stewart; Mahood, James; Abraham, Ed; McBroom, Robert; Jodoin, Alain; Fisher, Charles
Multicenter randomized controlled trial. To evaluate the effect of recombinant human bone morphogenetic protein (rhBMP-2) on radiographical fusion rate and clinical outcome for surgical lumbar arthrodesis compared with iliac crest autograft. In many types of spinal surgery, radiographical fusion is a primary outcome equally important to clinical improvement, ensuring long-term stability and axial support. Biologic induction of bone growth has become a commonly used adjunct in obtaining this objective. We undertook this study to objectify the efficacy of rhBMP-2 compared with traditional iliac crest autograft in instrumented posterolateral lumbar fusion. Patients undergoing 1- or 2-level instrumented posterolateral lumbar fusion were randomized to receive either autograft or rhBMP-2 for their fusion construct. Clinical and radiographical outcome measures were followed for 2 to 4 years postoperatively. One hundred ninety seven patients were successfully randomized among the 8 participating institutions. Adverse events attributable to the study drug were not significantly different compared with controls. However, the control group experienced significantly more graft-site complications as might be expected. 36-Item Short Form Health Survey, Oswestry Disability Index, and leg/back pain scores were comparable between the 2 groups. After 4 years of follow-up, radiographical fusion rates remained significantly higher in patients treated with rhBMP-2 (94%) than those who received autograft (69%) (P = 0.007). The use of rhBMP-2 for instrumented posterolateral lumbar surgery significantly improves the chances of radiographical fusion compared with the use of autograft. However, there is no associated improvement in clinical outcome within a 4-year follow-up period. These results suggest that use of rhBMP-2 should be considered in cases where lumbar arthrodesis is of primary concern.
Feng, Y.; Burian, S. J.; Pardyjak, E.; Pomeroy, C. A.
Green infrastructure (GI) measures have been well established as part of low-impact development approaches for stormwater (SW) management. The origin of the concepts, practices and the preponderance of research have taken place in humid climates. Recent work has begun to explore and adapt GI to subhumid and semi-arid climates, which experience warmer and drier periods. But much remains unknown about effects of GI on the water cycle and how to effectively implement to maximize ecosystem benefits. This research synthesizes observation and modeling to address questions related to changes in evapotranspiration (ET), SW runoff volume, and other water cycle processes from GI introduction in Salt Lake City, Utah, USA. First, the water budget of green roofs is being studied via weighing lysimeter systems on two rooftop gardens on the University of Utah campus. ET, outflow, and soil moisture have been measured for approximately one year. Up to this early summer, average ET rates for lysimeters of pure medium, Sedums, and Bluegrass are 1.85±1.01, 1.97±0.94, and 2.31±0.91 mm/d respectively; the maximum ET rate could reach 6.11 mm/d from Sedums. Over 2/3 of total rainfall and irrigation were slowly consumed via ET from green roof. Second, the observation studies are leading to new ET modeling techniques that are being incorporated into the U.S. EPA Storm Water Management Model (SWMM). The modified SWMM has been used to simulate ET, SW runoff volume, and overall water budget changes from GI implementation. Preliminary result shows that ET could account for 10% of the total inflows into bioretentions, and 25% of the inflows into landscapes; potential ET rates could vary up to 0.95 mm/hr across 53 subcatchments in the 29 acres catchment. The influence of various design factors for GI on SW runoff reduction and the water budget is also to be estimated. The application of the research is to analyze the water budget of the Red Butte Creek Watershed in Salt Lake City and to
Gode, Funda; Gulekli, Bulent; Dogan, Erbil; Korhan, Peyda; Dogan, Seda; Bige, Ozgur; Cimrin, Dilek; Atabey, Nese
To evaluate the association between follicular fluid levels of propeptide and mature forms of growth differentiation factor (GDF) 9 and bone morphogenetic protein (BMP) 15 with subsequent oocyte and embryo quality. Prospective clinical study. University hospital. Eighty-one infertile patients who underwent in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI). The expression levels of the propeptide and mature forms of follicular fluid GDF9 and BMP15 were determined by western blot analysis. The levels of follicular fluid hormones (FSH, E2, and P) were measured with automated chemiluminescent enzyme immunoassays. The relationships between the levels of GDF9 and BMP15, hormones, oocyte maturation, and embryo quality. Mature GDF9 levels were significantly correlated with the nuclear maturation of oocytes. The mean mature GDF9 level was 4.87±0.60 in the high-embryo-quality group and 1.45±0.81 in the low-embryo-quality group. There were no statistically significant differences in embryo quality among the patients regarding propeptide GDF9 and BMP15 expression status. There was a negative correlation between follicular fluid levels of P and the mature form of GDF9. Higher mature GDF9 levels in the follicular fluid were significantly correlated with oocyte nuclear maturation and embryo quality. Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.
Full Text Available Current clinical delivery of recombinant human bone morphogenetic proteins (rhBMPs utilises freeze-dried collagen. Despite effective new bone generation, rhBMP via collagen can be limited by significant complications due to inflammation and uncontrolled bone formation. This study aimed to produce an alternative rhBMP local delivery system to permit more controllable and superior rhBMP-induced bone formation. Cylindrical porous poly(lactic-co-glycolic acid (PLGA scaffolds were manufactured by thermally-induced phase separation. Scaffolds were encapsulated with anabolic rhBMP-2 (20 µg ± anti-resorptive agents: zoledronic acid (5 µg ZA, ZA pre-adsorbed onto hydroxyapatite microparticles, (5 µg ZA/2 % HA or IkappaB kinase (IKK inhibitor (10 µg PS-1145. Scaffolds were inserted in a 6-mm critical-sized femoral defect in Wistar rats, and compared against rhBMP-2 via collagen. The regenerate region was examined at 6 weeks by 3D microCT and descriptive histology. MicroCT and histology revealed rhBMP-induced bone was more restricted in the PLGA scaffolds than collagen scaffolds (-92.3 % TV, p < 0.01. The regenerate formed by PLGA + rhBMP-2/ZA/HA showed comparable bone volume to rhBMP-2 via collagen, and bone mineral density was +9.1 % higher (p < 0.01. Local adjunct ZA/HA or PS-1145 significantly enhanced PLGA + rhBMP-induced bone formation by +78.2 % and +52.0 %, respectively (p ≤ 0.01. Mechanistically, MG-63 human osteoblast-like cells showed cellular invasion and proliferation within PLGA scaffolds. In conclusion, PLGA scaffolds enabled superior spatial control of rhBMP-induced bone formation over clinically-used collagen. The PLGA scaffold has the potential to avoid uncontrollable bone formation-related safety issues and to customise bone shape by scaffold design. Moreover, local treatment with anti-resorptive agents incorporated within the scaffold further augmented rhBMP-induced bone formation.
Naroznova, Irina; Møller, Jacob; Scheutz, Charlotte
This study is dedicated to characterising the chemical composition and biochemical methane potential (BMP) of individual material fractions in untreated Danish source-separated organic household waste (SSOHW). First, data on SSOHW in different countries, available in the literature, were evaluated and then, secondly, laboratory analyses for eight organic material fractions comprising Danish SSOHW were conducted. No data were found in the literature that fully covered the objectives of the present study. Based on laboratory analyses, all fractions were assigned according to their specific properties in relation to BMP, protein content, lipids, lignocellulose biofibres and easily degradable carbohydrates (carbohydrates other than lignocellulose biofibres). The three components in lignocellulose biofibres, i.e. lignin, cellulose and hemicellulose, were differentiated, and theoretical BMP (TBMP) and material degradability (BMP from laboratory incubation tests divided by TBMP) were expressed. Moreover, the degradability of lignocellulose biofibres (the share of volatile lignocellulose biofibre solids degraded in laboratory incubation tests) was calculated. Finally, BMP for average SSOHW composition in Denmark (untreated) was calculated, and the BMP contribution of the individual material fractions was then evaluated. Material fractions of the two general waste types, defined as "food waste" and "fibre-rich waste," were found to be anaerobically degradable with considerable BMP. Material degradability of material fractions such as vegetation waste, moulded fibres, animal straw, dirty paper and dirty cardboard, however, was constrained by lignin content. BMP for overall SSOHW (untreated) was 404 mL CH4 per g VS, which might increase if the relative content of material fractions, such as animal and vegetable food waste, kitchen tissue and dirty paper in the waste, becomes larger. Copyright © 2016 Elsevier Ltd. All rights reserved.
Rici, Rose Eli Grassi; Alcântara, Dayane; Fratini, Paula; Wenceslau, Cristiane Valverde; Ambrósio, Carlos Eduardo; Miglino, Maria Angelica; Maria, Durvanei Augusto
The bone morphogenetic proteins (BMPs) belong to a unique group of proteins that includes the growth factor TGF-β. BMPs play important roles in cell differentiation, cell proliferation, and inhibition of cell growth. They also participate in the maturation of several cell types, depending on the microenvironment and interactions with other regulatory factors. Depending on their concentration gradient, the BMPs can attract various types of cells and act as chemotactic, mitogenic, or differentiation agents. BMPs can interfere with cell proliferation and the formation of cartilage and bone. In addition, BMPs can induce the differentiation of mesenchymal progenitor cells into various cell types, including chondroblasts and osteoblasts. The aim of this study was to analyze the effects of treatment with rhBMP-2 on the proliferation of canine mesenchymal stem cells (cMSCs) and the tumor suppression properties of rhBMP-2 in canine osteocarcoma (OST) cells. Osteosarcoma cell lines were isolated from biopsies and excisions of animals with osteosarcoma and were characterized by the Laboratory of Biochemistry and Biophysics, Butantan Institute. The mesenchymal stem cells were derived from the bone marrow of canine fetuses (cMSCs) and belong to the University of São Paulo, College of Veterinary Medicine (FMVZ-USP) stem cell bank. After expansion, the cells were cultured in a 12-well Transwell system; cells were treated with bone marrow mesenchymal stem cells associated with rhBMP2. Expression of the intracytoplasmic and nuclear markers such as Caspase-3, Bax, Bad, Bcl-2, Ki-67, p53, Oct3/4, Nanog, Stro-1 were performed by flow citometry. We evaluated the regenerative potential of in vitro treatment with rhBMP-2 and found that both osteogenic induction and tumor regression occur in stem cells from canine bone marrow. rhBMP-2 inhibits the proliferation capacity of OST cells by mechanisms of apoptosis and tumor suppression mediated by p53. We propose that rhBMP-2 has great
Full Text Available Our previous studies demonstrated that bone morphogenetic protein 4 (BMP4 mediated, elevated expression of canonical transient receptor potential (TRPC largely accounts for the enhanced proliferation in pulmonary arterial smooth muscle cells (PASMCs. In the present study, we sought to determine the signaling pathway through which BMP4 up-regulates TRPC expression.We employed recombinant human BMP4 (rhBMP4 to determine the effects of BMP4 on NADPH oxidase 4 (NOX4 and reactive oxygen species (ROS production in rat distal PASMCs. We also designed small interfering RNA targeting NOX4 (siNOX4 and detected whether NOX4 knockdown affects rhBMP4-induced ROS, TRPC1 and 6 expression, cell proliferation and intracellular Ca2+ determination in PASMCs.In rhBMP4 treated rat distal PASMCs, NOX4 expression was (226.73±11.13 %, and the mean ROS level was (123.65±1.62 % of that in untreated control cell. siNOX4 transfection significantly reduced rhBMP4-induced elevation of the mean ROS level in PASMCs. Moreover, siNOX4 transfection markedly reduced rhBMP4-induced elevation of TRPC1 and 6 proteins, basal [Ca2+]i and SOCE. Furthermore, compared with control group (0.21±0.001, the proliferation of rhBMP4 treated cells was significantly enhanced (0.41±0.001 (P<0.01. However, such increase was attenuated by knockdown of NOX4. Moreover, external ROS (H2O2 100 µM, 24 h rescued the effects of NOX4 knockdown, which included the declining of TRPC1 and 6 expression, basal intracellular calcium concentration ([Ca2+]i and store-operated calcium entry (SOCE, suggesting that NOX4 plays as an important mediator in BMP4-induced proliferation and intracellular calcium homeostasis.These results suggest that BMP4 may increase ROS level, enhance TRPC1 and 6 expression and proliferation by up-regulating NOX4 expression in PASMCs.
Full Text Available We investigate the bone generation capacity of recombinant human bone morphogenetic protein-2 (rhBMP-2 immobilized Medpor surface through acrylic acid plasma-polymerization. Plasma-polymerization was carried out at a 20 W at an acrylic acid flow rate of 7 sccm for 5 min. The plasma-polymerized Medpor surface showed hydrophilic properties and possessed a high density of carboxyl groups. The rhBMP-2 was immobilized with covalently attached carboxyl groups using 1-ethyl-3-(3-dimethylaminopropyl carbodiimide and N-hydroxysuccinimide. Carboxyl groups and rhBMP-2 immobilization on the Medpor surface were identified by Fourier transform infrared spectroscopy. The activity of Medpor with rhBMP-2 immobilized was examined using an alkaline phosphatase assay on MC3T3-E1 cultured Medpor. These results showed that the rhBMP-2 immobilized Medpor increased the level of MC3T3-E1 cell differentiation. These results demonstrated that plasma surface modification has the potential to immobilize rhBMP-2 on polymer implant such as Medpor and can be used for the binding of bioactive nanomolecules in bone tissue engineering.
Arjunan, Pachiappan; Gnanaprakasam, Jaya P; Ananth, Sudha; Romej, Michelle A; Rajalakshmi, Veeranan-Karmegam; Prasad, Puttur D; Martin, Pamela M; Gurusamy, Mariappan; Thangaraju, Muthusamy; Bhutia, Yangzom D; Ganapathy, Vadivel
Hemochromatosis, an iron-overload disease, occurs as adult and juvenile types. Mutations in hemojuvelin (HJV), an iron-regulatory protein and a bone morphogenetic protein (BMP) coreceptor, underlie most of the juvenile type. Hjv(-/-) mice accumulate excess iron in retina and exhibit aberrant vascularization and angiomas. A succinate receptor, GPR91, is pro-angiogenic in retina. We hypothesized that Hjv(-/-) retinas have increased BMP signaling and increased GPR91 expression as the basis of angiomas. Expression of GPR91 was examined by qPCR, immunofluorescence, and Western blot in wild-type and Hjv(-/-) mouse retinas and pRPE cells. Influence of excess iron and BMP6 on GPR91 expression was investigated in ARPE-19 cells, and wild-type and Hjv(-/-) pRPE cells. Succinate was used to activate GPR91 and determine the effects of GPR91 signaling on VEGF expression. Signaling of BMP6 was studied by the expression of Smad1/5/8 and pSmad4, and the BMP-target gene Id1. The interaction of pSmad4 with GPR91 promoter was studied by ChIP. Expression of GPR91 was higher in Hjv(-/-) retinas and RPE than in wild-type counterparts. Unexpectedly, BMP signaling was increased, not decreased, in Hjv(-/-) retinas and RPE. Bone morphogenetic protein 6 induced GPR91 in RPE, suggesting that increased BMP signaling in Hjv(-/-) retinas was likely responsible for GPR91 upregulation. Exposure of RPE to excess iron and succinate as well as BMP6 and succinate increased VEGF expression. Bone morphogenetic protein 6 promoted the interaction of pSmad4 with GPR91 promoter in RPE. G-protein-coupled receptor 91 is a BMP6 target and Hjv deletion enhances BMP signaling in retina, thus underscoring a role for excess iron and hemochromatosis in abnormal retinal vascularization.
Bao, Li-Rong; Zhao, Wen-Qing; Lin, Tian; Lu, Yan-Ling; Wu, Yu
To screen and verify the differentially expressed microRNAs (miRNAs) during the differentiation of human dental pulp cells (hDPCs) to odontoblasts induced by BMP-2. The isolated hDPCs were cultured in vitro and induced by BMP-2. The levels of ALP, DMP-1 and DSPP were quantified by quantitative real-time polymerase chain reaction (qRT-PCR). The potential characteristics of hDPCs were investigated by miRNA microarray and highly expressed miRNAs were selected with bio-information software for predicting target genes and their biological functions. Then the results were validated using qRT-PCR analysis for the selected miRNAs. Statistical analysis was performed using SPSS 18.0 software package. The expression of ALP, DSPP, and DMP-1 showed significantly higher levels in BMP-2 induced groups compared to the control group(Pfunction(33%), while the function of other 0.2% genes remained unknown. This study identified differential expression of miRNAs in BMP-2-induced odontoblastic differentiation of hDPCs, thus contributing to further investigations of regulatory mechanisms and biological effect of target genes in BMP-2-induced odontoblastic differentiation of hDPCs.
Huang, Peide; Chen, Anan; He, Weiyi
Bone morphogenetic protein 2 (BMP-2) has been reported to facilitate epithelial-to-mesenchymal transition (EMT) and bone metastasis in breast cancer xenograft models. To investigate the role of BMP-2 in the development of breast cancer stem cells (BCSCs), and to further elucidate the mechanisms u...... then contribute to breast cancer metastasis. These findings may be helpful for developing new strategies for the treatment and prognosis of advanced breast cancer....
North Kathryn N
Full Text Available Abstract Background Osteoblasts are considered to primarily arise from osseous progenitors within the periosteum or bone marrow. We have speculated that cells from local soft tissues may also take on an osteogenic phenotype. Myoblasts are known to adopt a bone gene program upon treatment with the osteogenic bone morphogenetic proteins (BMP-2,-4,-6,-7,-9, but their osteogenic capacity relative to other progenitor types is unclear. We further hypothesized that the sensitivity of cells to BMP-2 would correlate with BMP receptor expression. Methods We directly compared the BMP-2 sensitivity of myoblastic murine cell lines and primary cells with osteoprogenitors from osseous tissues and fibroblasts. Fibroblasts forced to undergo myogenic conversion by transduction with a MyoD-expressing lentiviral vector (LV-MyoD were also examined. Outcome measures included alkaline phosphatase expression, matrix mineralization, and expression of osteogenic genes (alkaline phosphatase, osteocalcin and bone morphogenetic protein receptor-1A as measured by quantitative PCR. Results BMP-2 induced a rapid and robust osteogenic response in myoblasts and osteoprogenitors, but not in fibroblasts. Myoblasts and osteoprogenitors grown in osteogenic media rapidly upregulated Bmpr-1a expression. Chronic BMP-2 treatment resulted in peak Bmpr-1a expression at day 6 before declining, suggestive of a negative feedback mechanism. In contrast, fibroblasts expressed low levels of Bmpr-1a that was only weakly up-regulated by BMP-2 treatment. Bioinformatics analysis confirmed the presence of myogenic responsive elements in the proximal promoter region of human and murine BMPR-1A/Bmpr-1a. Forced myogenic gene expression in fibroblasts was associated with a significant increase in Bmpr-1a expression and a synergistic increase in the osteogenic response to BMP-2. Conclusion These data demonstrate the osteogenic sensitivity of muscle progenitors and provide a mechanistic insight into the
Lawrence, James P; Waked, Walid; Gillon, Thomas J; White, Andrew P; Spock, Christopher R; Biswas, Debdut; Rosenberger, Patricia; Troiano, Nancy; Albert, Todd J; Grauer, Jonathan N
The study design consisted of a New Zealand white rabbit model of pseudarthrosis repair. Study groups consisting of no graft, autograft, or recombinant human bone morphogenetic protein-2 (rhBMP-2) with absorbable collagen sponge (ACS) or compression resistant matrix (CRM) were evaluated. To evaluate the relative efficacy of bone graft materials (autograft, ACS, and CRM). rhBMP-2 has been shown to have a 100% fusion rate in a primary rabbit fusion model, even in the presence of nicotine, which is known to inhibit fusion. Seventy-two New Zealand white rabbits underwent posterolateral lumbar fusion with iliac crest autograft. To establish pseudarthroses, nicotine was administered to all animals. At 5 weeks, the spines were explored and all pseudarthroses were redecorticated and implanted with no graft, autograft, rhBMP-2/ACS, or rhBMP-2/CRM. At 10 weeks, fusions were assessed by manual palpation and histology. Eight rabbits (11%) were lost to complications. At 5 weeks, 66 (97%) had pseudarthroses. At 10 weeks, attempted pseudarthrosis repairs were fused in 1 of 16 of no graft rabbits (6%), 5 of 17 autograft rabbits (29%), and 31 of 31 rhBMP-2 rabbits (with ACS or CRM) (100%). Histologic analysis demonstrated more mature bone formation in the rhBMP-2 groups. The 2 rhBMP-2 formulations led to significantly higher fusion rates and histologic bone formation than no graft and autograft controls in this pseudarthrosis repair model.
Graef, Jennifer L; Rendina-Ruedy, Elizabeth; Crockett, Erica K; Ouyang, Ping; King, Jarrod B; Cichewicz, Robert H; Lucas, Edralin A; Smith, Brenda J
Dried plum supplementation has been shown to enhance bone formation while suppressing bone resorption. Evidence from previous studies has demonstrated that these responses can be attributed in part to the fruit's polyphenolic compounds. The purpose of this study was to identify the most bioactive polyphenolic fractions of dried plum with a focus on their osteogenic activity and to investigate their mechanisms of action under normal and inflammatory conditions. Utilizing chromatographic techniques, six fractions of polyphenolic compounds were prepared from a crude extract of dried plum. Initial screening assays revealed that two fractions (DP-FrA and DP-FrB) had the greatest osteogenic potential. Subsequent experiments using primary bone-marrow-derived osteoblast cultures demonstrated these two fractions enhanced extracellular alkaline phosphatase (ALP), an indicator of osteoblast activity, and mineralized nodule formation under normal conditions. Both fractions enhanced bone morphogenetic protein (BMP) signaling, as indicated by increased Bmp2 and Runx2 gene expression and protein levels of phosphorylated Smad1/5. DP-FrB was most effective at up-regulating Tak1 and Smad1, as well as protein levels of phospho-p38. Under inflammatory conditions, TNF-α suppressed ALP and tended to decrease nodule formation (P=.0674). This response coincided with suppressed gene expression of Bmp2 and the up-regulation of Smad6, an inhibitor of BMP signaling. DP-FrA and DP-FrB partially normalized these responses. Our results show that certain fractions of polyphenolic compounds in dried plum up-regulate osteoblast activity by enhancing BMP signaling, and when this pathway is inhibited by TNF-α, the osteogenic response is attenuated. Copyright © 2017 Elsevier Inc. All rights reserved.
Xiao Caiwen; Zhou Huifang; Fu Yao; Gu Ping; Fan Xianqun; Liu Guangpeng; Zhang Peng; Hou Hongliang; Tang Tingting
Bone graft substitutes with osteogenic factors alone often exhibit poor bone regeneration due to inadequate vascularization. Combined delivery of osteogenic and angiogenic factors from biodegradable scaffolds may enhance bone regeneration. We evaluated the effects of bone morphogenetic protein 2 (BMP2) and vascular endothelial growth factor (VEGF), combined with natural coral scaffolds, on the repair of critical-sized bone defects in rabbit orbits. In vitro expanded rabbit bone marrow stromal cells (BMSCs) were transfected with human BMP2 and VEGF165 genes. Target protein expression and osteogenic differentiation were confirmed after gene transduction. Rabbit orbital defects were treated with a coral scaffold loaded with BMP2-transduced and VEGF-transduced BMSCs, BMP2-expressing BMSCs, VEGF-expressing BMSCs, or BMSCs without gene transduction. Volume and density of regenerated bone were determined by micro-computed tomography at 4, 8, and 16 weeks after implantation. Neovascularity, new bone deposition rate, and new bone formation were measured by immunostaining, tetracycline and calcein labelling, and histomorphometric analysis at different time points. The results showed that VEGF increased blood vessel formation relative to groups without VEGF. Combined delivery of BMP2 and VEGF increased new bone deposition and formation, compared with any single factor. These findings indicate that mimicking the natural bone development process by combined BMP2 and VEGF delivery improves healing of critical-sized orbital defects in rabbits.
Persada, C.; Sitorus, S. R. P.; Marimin; Djakapermana, R. D.
Infrastructure development does not only affect the economic aspect, but also social and environmental, those are the main dimensions of sustainable development. Many aspects and actors involved in urban infrastructure development requires a comprehensive and integrated policy towards sustainability. Therefore, it is necessary to formulate an infrastructure development policy that considers various dimensions of sustainable development. The main objective of this research is to formulate policy of sustainable infrastructure development. In this research, urban infrastructure covers transportation, water systems (drinking water, storm water, wastewater), green open spaces and solid waste. This research was conducted in Bandarlampung City. This study use a comprehensive modeling, namely the Multi Dimensional Scaling (MDS) with Rapid Appraisal of Infrastructure (Rapinfra), it uses of Analytic Network Process (ANP) and it uses system dynamics model. The findings of the MDS analysis showed that the status of Bandarlampung City infrastructure sustainability is less sustainable. The ANP analysis produces 8 main indicators of the most influential in the development of sustainable infrastructure. The system dynamics model offered 4 scenarios of sustainable urban infrastructure policy model. The best scenario was implemented into 3 policies consist of: the integrated infrastructure management, the population control, and the local economy development.
Lao, Lifeng; Cohen, Jeremiah R; Buser, Zorica; Brodke, Darrel S; Yoon, S Tim; Youssef, Jim A; Park, Jong-Beom; Meisel, Hans-Joerg; Wang, Jeffrey C
Retrospective case study. To evaluate the trends and demographics of recombinant human bone morphogenetic protein 2 (rhBMP2) utilization in single-level anterior lumbar interbody fusion (ALIF) in the United States. Patients who underwent single-level ALIF from 2005 to 2011 were identified by searching ICD-9 diagnosis and procedure codes in the PearlDiver Patient Records Database (PearlDiver Technologies, Fort Wayne, IN), a national database of orthopedic insurance records. The year of procedure, age, gender, and region of the United States were analyzed for each patient. A total of 921 patients were identified who underwent a single-level ALIF in this study. The average rate of single-level ALIF with rhBMP2 utilization increased (35%-48%) from 2005 to 2009, but sharply decreased to 16.7% in 2010 and 15.0% in 2011. The overall incidence of single-level ALIF without rhBMP2 (0.20 cases per 100 000 patients) was more than twice of the incidence of single-level ALIF with rhBMP2 (0.09 cases per 100 000 patients). The average rate of single-level ALIF with rhBMP2 utilization is highest in West (41.4%), followed by Midwest (33.3%), South (26.5%) and Northeast (22.2%). The highest incidence of single-level ALIF with rhBMP2 was observed in the group aged less than 65 years (compared with any other age groups, P level ALIF increased from 2006 to 2009, but decreased in 2010 and 2011. The Northeast region had the lowest incidence of rhBMP2 utilization. The group aged less than 65 years trended to have the higher incidence of single-level ALIF with rhBMP2 utilization.
Urban infrastructure - broadly defined to include the systems that provide water, energy, food, shelter, transportation-communication, sanitation and green/public spaces in cities - have tremendous impact on the environment and on human well-being (Ramaswami et al., 2016; Ramaswami et al., 2012). Aggregated globally, these sectors contribute 90% of global greenhouse gas (GHG) emissions and 96% of global water withdrawals. Urban infrastructure contributions to such impacts are beginning to dominate. Cities are therefore becoming the action arena for infrastructure transformations that can achieve high levels of service delivery while reducing environmental impacts and enhancing human well-being. Achieving sustainable urban infrastructure transitions requires: information about the engineered infrastructure, and its interaction with the natural (ecological-environmental) and the social sub-systems In this paper, we apply a multi-sector, multi-scalar Social-Ecological-Infrastructural Systems framework that describes the interactions among biophysical engineered infrastructures, the natural environment and the social system in a systems-approach to inform urban infrastructure transformations. We apply the SEIS framework to inform water and energy sector transformations in cities to achieve environmental and human health benefits realized at multiple scales - local, regional and global. Local scales address pollution, health, wellbeing and inequity within the city; regional scales address regional pollution, scarcity, as well as supply risks in the water-energy sectors; global impacts include greenhouse gas emissions and climate impacts. Different actors shape infrastructure transitions including households, businesses, and policy actors. We describe the development of novel cross-sectoral strategies at the water-energy nexus in cities, focusing on water, waste and energy sectors, in a case study of Delhi, India. Ramaswami, A.; Russell, A.G.; Culligan, P.J.; Sharma, K
Sehgal, Rachna; Sheibani, Nader; Rhodes, Simon J; Belecky Adams, Teri L
Pax2 is essential for development of the neural tube, urogenital system, optic vesicle, optic cup and optic tract. In the eye, Pax2 deficiency is associated with coloboma, a loss of astrocytes in the optic nerve and retina, and abnormal axonal pathfinding of the ganglion cell axons at the optic chiasm. Thus, appropriate expression of Pax2 is essential for astrocyte determination and differentiation. Although BMP7 and SHH have been shown to regulate Pax2 expression, the molecular mechanism by which this regulation occurs is not well understood. In this study, we determined that BMP7 and SHH activate Pax2 expression in mouse retinal astrocyte precursors in vitro. SHH appeared to play a dual role in Pax2 regulation; 1) SHH may regulate BMP7 expression, and 2) the SHH pathway cooperates with the BMP pathway to regulate Pax2 expression. BMP and SHH pathway members can interact separately or together with TLX, a repressor protein in the tailless transcription factor family. Here we show that the interaction of both pathways with TLX relieves the repression of Pax2 expression in mouse retinal astrocytes. Together these data reveal a new mechanism for the cooperative actions of signaling pathways in astrocyte determination and differentiation and suggest interactions of regulatory pathways that are applicable to other developmental programs.
Deng, Zhili; Lei, Xiaohua; Zhang, Xudong; Zhang, Huishan; Liu, Shuang; Chen, Qi; Hu, Huimin; Wang, Xinyue; Ning, Lina; Cao, Yujing; Zhao, Tongbiao; Zhou, Jiaxi; Chen, Ting; Duan, Enkui
Hair follicles (HFs) undergo cycles of degeneration (catagen), rest (telogen), and regeneration (anagen) phases. Anagen begins when the hair follicle stem cells (HFSCs) obtain sufficient activation cues to overcome suppressive signals, mainly the BMP pathway, from their niche cells. Here, we unveil that mTOR complex 1 (mTORC1) signaling is activated in HFSCs, which coincides with the HFSC activation at the telogen-to-anagen transition. By using both an inducible conditional gene targeting strategy and a pharmacological inhibition method to ablate or inhibit mTOR signaling in adult skin epithelium before anagen initiation, we demonstrate that HFs that cannot respond to mTOR signaling display significantly delayed HFSC activation and extended telogen. Unexpectedly, BMP signaling activity is dramatically prolonged in mTOR signaling-deficient HFs. Through both gain- and loss-of-function studies in vitro, we show that mTORC1 signaling negatively affects BMP signaling, which serves as a main mechanism whereby mTORC1 signaling facilitates HFSC activation. Indeed, in vivo suppression of BMP by its antagonist Noggin rescues the HFSC activation defect in mTORC1-null skin. Our findings reveal a critical role for mTOR signaling in regulating stem cell activation through counterbalancing BMP-mediated repression during hair regeneration. © The Author (2015). Published by Oxford University Press on behalf of Journal of Molecular Cell Biology, IBCB, SIBS, CAS. All rights reserved.
Cohen, J. S.; McGarity, A. E.
The ability for mass deployment of green stormwater infrastructure (GSI) to intercept significant amounts of urban runoff has the potential to reduce the frequency of a city's combined sewer overflows (CSOs). This study was performed to aid in the Overbrook Environmental Education Center's vision of applying this concept to create a Green Commercial Corridor in Philadelphia's Overbrook Neighborhood, which lies in the Mill Creek Sewershed. In an attempt to further implement physical and social reality into previous work using simulation-optimization techniques to produce GSI deployment strategies (McGarity, et al., 2016), this study's models incorporated land use types and a specific neighborhood in the sewershed. The low impact development (LID) feature in EPA's Storm Water Management Model (SWMM) was used to simulate various geographic configurations of GSI in Overbrook. The results from these simulations were used to obtain formulas describing the annual CSO reduction in the sewershed based on the deployed GSI practices. These non-linear hydrologic response formulas were then implemented into the Storm Water Investment Strategy Evaluation (StormWISE) model (McGarity, 2012), a constrained optimization model used to develop optimal stormwater management practices on the watershed scale. By saturating the avenue with GSI, not only will CSOs from the sewershed into the Schuylkill River be reduced, but ancillary social and economic benefits of GSI will also be achieved. The effectiveness of these ancillary benefits changes based on the type of GSI practice and the type of land use in which the GSI is implemented. Thus, the simulation and optimization processes were repeated while delimiting GSI deployment by land use (residential, commercial, industrial, and transportation). The results give a GSI deployment strategy that achieves desired annual CSO reductions at a minimum cost based on the locations of tree trenches, rain gardens, and rain barrels in specified land
Ponizy, Lidia; Majchrzak, Weronika; Zwierzchowska, Iwona
The quality of life of big city dwellers depends on the use of green infrastructure. The idea of a compact city, opposed to urban sprawl, can lead to reduced access to green areas and increased demand for cultural services provided through urban green infrastructure. Considering the above, the aim of the paper was to identify the supply of and demand for cultural ecosystem services related to the urban green spaces in densely built-up urban areas. To find out how important the ability to use green areas for dwellers of the densely built-up areas is, the questionnaire interviews with the residents of the area of the Old Town of Poznan were conducted. Questions in the survey concerned the amount of green spaces and their availability, the way of use, types of activity, factors limiting the use and factors encouraging to visit green spaces and the motives for using green areas away from inhabitants’ place of residence. Respondents claim that there is not enough greenery, especially associated with housing and street side greenery; the amount of parks (which they use most) is slightly higher, in their opinion. Limitations that influence utilising green spaces concern both greenery itself (e.g. insufficient recreational infrastructure, neglected green areas) as well as respondent’s issues (e.g. lack of free time). Improvements to recreational infrastructure and more well-kept green spaces would encourage respondents to utilise it more often. Active participation of inhabitants in developing and maintaining their closest neighbourhood would allow to enlarge green spaces in housing areas and make them more customized to the residents’ needs and requirements in terms of functionality and aesthetic.
Effect of bone morphogenetic protein-7 (BMP-7 on in vitro survival of caprine preantral follicles Efeito da proteína morfogenética óssea 7 (BMP-7 para a sobrevivência in vitro de folículos pré-antrais caprinos
Valdevane R. Araújo
Full Text Available This study was conducted in order to verify the effect of different concentrations of BMP-7 in the in vitro survival and development of caprine preantral follicles. Fragments of caprine ovarian cortical tissue were cultured for 1 or 7 days in Minimum Essential Medium (MEM+ supplemented with different concentrations of BMP-7 (1, 10, 50 or 100ng/ml. Non-cultured fragments or those cultured for 1 or 7 days were processed for classical histology and transmission electron microscopy (TEM. Parameters such as follicular survival, activation and growth were evaluated. The results showed that, after 1 or 7 days of culture, the percentage of morphologically normal follicles was significantly reduced in all treatments when compared with fresh control, except at 1ng/ml of BMP-7 for 1 day. In addition, the concentration of 10ng/ml of BMP-7 significantly increases follicular diameter from day 1 to 7 of culture. There was no influence of the other concentrations of BMP-7 regarding to the follicular and oocyte diameter. Ultrastructure studies confirmed follicular integrity after 7 days of culture in 1ng/ml BMP-7. In conclusion, small concentrations of BMP-7 can improve the survival and growth of caprine preantral follicles during in vitro culture.O presente trabalho foi conduzido de modo a se verificar o efeito de diferentes concentrações da BMP-7 no desenvolvimento in vitro de folículos pré-antrais caprinos. Fragmentos de tecido cortical ovariano caprino foram cultivados por 1 ou 7 dias em Minimum Essential Medium (MEM+ suplementado com diferentes concentrações de BMP-7 (1, 10, 50 ou 100ng/ml. Os fragmentos não cultivados ou aqueles cultivados por 1 ou 7 dias foram processados para histologia clássica e microscopia eletrônica de transmissão (TEM, sendo avaliados parâmetros morfológicos indicativos de viabilidade, ativação e crescimento. Os resultados mostraram que o percentual de folículos morfologicamente normais diminuiu significativamente em
Levine, Ariel J.; Levine, Zachary J.; Brivanlou, Ali H.
Within the TGF-β superfamily, there are approximately forty ligands divided into two major branches: the TGF-β/Activin/Nodal ligands and the BMP/GDF ligands. We studied the ligand GDF3 and found that it inhibits signaling by its co-family members, the BMPs; however, GDF3 has been described by others to have Nodal-like activity. Here, we show that GDF3 can activate Nodal signaling, but only at very high doses and only upon mRNA over-expression. In contrast, GDF3 inhibits BMP signaling upon over-expression of GDF3 mRNA, as recombinant protein, and regardless of its dose. We therefore further characterized the mechanism through which GDF3 protein acts as a specific BMP inhibitor and found that the BMP inhibitory activity of GDF3 resides redundantly in the unprocessed, predominant form and in the mature form of the protein. These results confirm and extend the activity that we described for GDF3 and illuminate the experimental basis for the different observations of others. We suggest that GDF3 is either a bi-functional TGF-β ligand, or, more likely, that it is a BMP inhibitor that can artificially activate Nodal signaling under non-physiological conditions. PMID:18823971
Peng, Xiaochun; Chen, Yunsu; Li, Yamin; Wang, Yiming
We explored a novel poly(3-hydroxybutyrate) (PHB) nanoparticle loaded with hydrophilic recombinant human BMP-2 with amphiphilic phospholipid (BPC-PHB NP) for a rapid-acting and long-acting delivery system of BMP-2 for osteogenic differentiation. The BPC-PHB NPs were prepared by a solvent evaporation method and showed a spherical particle with a mean particle size of 253.4 nm, mean zeta potential of −22.42 mV, and high entrapment efficiency of 77.18%, respectively. For BPC-PHB NPs, a short initial burst release of BMP-2 from NPs in 24 h was found and it has steadily risen to reach about 80% in 20 days for in vitro test. BPC-PHB NPs significantly reduced the burst release of BMP-2, as compared to that of PHB NPs loading BMP-2 without PL (B-PHB NPs). BPC-PHB NPs maintained the content of BMP-2 for a long-term osteogenic differentiation. The OCT-1 cells with BPC-PHB NPs have high ALP activity in comparison with others. The gene markers for osteogenic differentiation were significantly upregulated for sample with BPC-PHB NPs, implying that BPC-PHB NPs can be used as a rapid-acting and long-acting BMP-2 delivery system for osteogenic differentiation. PMID:27379249
Full Text Available Abstract Background Both bone morphogenetic proteins (BMPs and histone deacetylases (HDACs have previously been established to play a role in the development of the three major cell types of the central nervous system: neurons, astrocytes, and oligodendrocytes. We have previously established a connection between these two protein families, showing that HDACs suppress BMP-promoted astrogliogenesis in the embryonic striatum. Since HDACs act in the nucleus to effect changes in transcription, an unbiased analysis of their transcriptional targets could shed light on their downstream effects on BMP-signaling. Results Using neurospheres from the embryonic striatum as an in vitro system to analyze this phenomenon, we have performed microarray expression profiling on BMP2- and TSA-treated cultures, followed by validation of the findings with quantitative RT-PCR and protein analysis. In BMP-treated cultures we first observed an upregulation of genes involved in cell-cell communication and developmental processes such as members of BMP and canonical Wnt signaling pathways. In contrast, in TSA-treated cultures we first observed an upregulation of genes involved in chromatin modification and transcription. Interestingly, we could not record direct changes in the protein levels of canonical members of BMP2 signaling, but we did observe an upregulation of both the transcription factor STAT3 and its active isoform phospho-STAT3 at the protein level. Conclusions STAT3 and SMAD1/5/8 interact synergistically to promote astrogliogenesis, and thus we show for the first time that HDACs act to suppress BMP-promoted astrogliogenesis by suppression of the crucial partner STAT3.
Yin Jinbo; Ma Yuxin; Yin Qing; Xu Haiwei; An Ning; Liu Shiyong; Fan Xiaotang; Yang Hui
The dentate gyrus (DG) of the hippocampus is one of a few regions in the adult mammalian brain characterized by ongoing neurogenesis. Proliferation of neural precursors in the granule cell layer of the DG has been identified in pentylenetetrazol (PTZ) kindling epilepsy model, however, little is known about the molecular mechanism. We previously reported that the expression pattern of bone morphogenetic proteins-4 (BMP4) mRNA in the hippocampus was developmentally regulated and mainly localized in the DG of the adult. To explore the role of BMP4 in epileptic activity, we detected BMP4 expression in the DG during PTZ kindling process and explore its correlation with cell proliferation combined with bromodeoxyuridine (BrdU) labeling technique. We found that dynamic changes in BMP4 level and BrdU labeled cells dependent on the kindling stage of PTZ induced seizure-prone state. The number of BMP4 mRNA-positive cells and BrdU labeled cells reached the top level 1 day after PTZ kindled, then declined to base level 2 months later. Furthermore, there was a significant correlation between increased BMP4 mRNA expression and increased number of BrdU labeled cells. After effectively blocked expression of BMP4 with antisense oligodeoxynucleotides(ASODN), the BrdU labeled cells in the dentate gyrus subgranular zone(DG-SGZ) and hilus were significantly decreased 16d after First PTZ injection and 1, 3, 7, 14d after kindled respectively. These findings suggest that increased proliferation in the DG of the hippocampus resulted from kindling epilepsy elicited by PTZ maybe be modulated by BMP4 over-expression
Full Text Available The effects of retinoids, the structural derivatives of vitamin A (retinol, on post-natal peak bone density acquisition and skeletal remodeling are complex and compartment specific. Emerging data indicates that retinoids, such as all trans retinoic acid (ATRA and its precursor all trans retinaldehyde (Rald, exhibit distinct and divergent transcriptional effects in metabolism. Despite these observations, the role of enzymes that control retinoid metabolism in bone remains undefined. In this study, we examined the skeletal phenotype of mice deficient in retinaldehyde dehydrogenase 1 (Aldh1a1, the enzyme responsible for converting Rald to ATRA in adult animals. Bone densitometry and micro-computed tomography (µCT demonstrated that Aldh1a1-deficient (Aldh1a1(-/- female mice had higher trabecular and cortical bone mass compared to age and sex-matched control C57Bl/6 wild type (WT mice at multiple time points. Histomorphometry confirmed increased cortical bone thickness and demonstrated significantly higher bone marrow adiposity in Aldh1a1(-/- mice. In serum assays, Aldh1a1(-/- mice also had higher serum IGF-1 levels. In vitro, primary Aldh1a1(-/- mesenchymal stem cells (MSCs expressed significantly higher levels of bone morphogenetic protein 2 (BMP2 and demonstrated enhanced osteoblastogenesis and adipogenesis versus WT MSCs. BMP2 was also expressed at higher levels in the femurs and tibias of Aldh1a1(-/- mice with accompanying induction of BMP2-regulated responses, including expression of Runx2 and alkaline phosphatase, and Smad phosphorylation. In vitro, Rald, which accumulates in Aldh1a1(-/- mice, potently induced BMP2 in WT MSCs in a retinoic acid receptor (RAR-dependent manner, suggesting that Rald is involved in the BMP2 increases seen in Aldh1a1 deficiency in vivo. Collectively, these data implicate Aldh1a1 as a novel determinant of cortical bone density and marrow adiposity in the skeleton in vivo through modulation of BMP signaling.
Nallamshetty, Shriram; Wang, Hong; Rhee, Eun-Jung; Kiefer, Florian W; Brown, Jonathan D; Lotinun, Sutada; Le, Phuong; Baron, Roland; Rosen, Clifford J; Plutzky, Jorge
The effects of retinoids, the structural derivatives of vitamin A (retinol), on post-natal peak bone density acquisition and skeletal remodeling are complex and compartment specific. Emerging data indicates that retinoids, such as all trans retinoic acid (ATRA) and its precursor all trans retinaldehyde (Rald), exhibit distinct and divergent transcriptional effects in metabolism. Despite these observations, the role of enzymes that control retinoid metabolism in bone remains undefined. In this study, we examined the skeletal phenotype of mice deficient in retinaldehyde dehydrogenase 1 (Aldh1a1), the enzyme responsible for converting Rald to ATRA in adult animals. Bone densitometry and micro-computed tomography (µCT) demonstrated that Aldh1a1-deficient (Aldh1a1(-/-) ) female mice had higher trabecular and cortical bone mass compared to age and sex-matched control C57Bl/6 wild type (WT) mice at multiple time points. Histomorphometry confirmed increased cortical bone thickness and demonstrated significantly higher bone marrow adiposity in Aldh1a1(-/-) mice. In serum assays, Aldh1a1(-/-) mice also had higher serum IGF-1 levels. In vitro, primary Aldh1a1(-/-) mesenchymal stem cells (MSCs) expressed significantly higher levels of bone morphogenetic protein 2 (BMP2) and demonstrated enhanced osteoblastogenesis and adipogenesis versus WT MSCs. BMP2 was also expressed at higher levels in the femurs and tibias of Aldh1a1(-/-) mice with accompanying induction of BMP2-regulated responses, including expression of Runx2 and alkaline phosphatase, and Smad phosphorylation. In vitro, Rald, which accumulates in Aldh1a1(-/-) mice, potently induced BMP2 in WT MSCs in a retinoic acid receptor (RAR)-dependent manner, suggesting that Rald is involved in the BMP2 increases seen in Aldh1a1 deficiency in vivo. Collectively, these data implicate Aldh1a1 as a novel determinant of cortical bone density and marrow adiposity in the skeleton in vivo through modulation of BMP signaling.
Full Text Available Background/Aims: Periapical periodontitis is a common oral disease caused by bacterial invasion of the tooth pulp, which usually leads to local release of pro-inflammatory cytokines and osteolytic lesion. This study is intended to examine the effect of TNF-α on BMP9-induced osteogenic differentiation of the stem cells of dental apical papilla (SCAPs. Methods: Rat model of periapical periodontitis was established. TNF-α expression was assessed. Osteogenic markers and ectopic bone formation in iSCAPs were analyzed upon BMP9 and TNF-α treatment. Results: Periapical periodontitis was successfully established in rat immature permanent teeth with periapical lesions, in which TNF-α was shown to release during the inflammatory phase. BMP9-induced alkaline phosphatase activity, the expression of osteocalcin and osteopontin, and matrix mineralization in iSCAPs were inhibited by TNF-α in a dose-dependent fashion, although increased AdBMP9 partially overcame TNF-α inhibition. Furthermore, high concentration of TNF-α effectively inhibited BMP9-induced ectopic bone formation in vivo. Conclusion: TNF-α plays an important role in periapical bone defect during the inflammatory phase and inhibits BMP9-induced osteoblastic differentiation of iSCAPs, which can be partially reversed by high levels of BMP9. Therefore, BMP9 may be further explored as a potent osteogenic factor to improve osteo/odontogenic differentiation in tooth regeneration in chronic inflammation conditions.
Chang Yan; Xue Yilong; Luo Yun; Tian Lei; Pan Jingkun; Cui Xin
The cholinergic-inducing effect of BMP4 on isolated and cultivated rat's cerebral neural stem cells (NSC) was examined. NSC isolated from two months old rat's brain region like hippocampus and striatum was cultivated in a DMEM/F12 medium containing EGF and bFGF, and was identified with morphological character and nestin immunocytochemistry test. After 24 hours, cultivating the NSC with the BMP4-added medium for 7-8 days, then the microscopical change were observed, ChAT and nestin double-labelling immunocytochemistry test was done. Results showed that about 34% NSC of neuron-like character was observed by microscope in the paper. That ChAT-positive cells coexist with nestin-positive cells was found by immunocytochemistry test. There were 28% ChAT-positive cells and 38% nestin-positive cells in the study. Cholinergic neurons differentiated from NSC could be induced by adding BMP4 to the medium
Grassi Rici Rose
Full Text Available Abstract Background The bone morphogenetic proteins (BMPs belong to a unique group of proteins that includes the growth factor TGF-β. BMPs play important roles in cell differentiation, cell proliferation, and inhibition of cell growth. They also participate in the maturation of several cell types, depending on the microenvironment and interactions with other regulatory factors. Depending on their concentration gradient, the BMPs can attract various types of cells and act as chemotactic, mitogenic, or differentiation agents. BMPs can interfere with cell proliferation and the formation of cartilage and bone. In addition, BMPs can induce the differentiation of mesenchymal progenitor cells into various cell types, including chondroblasts and osteoblasts. The aim of this study was to analyze the effects of treatment with rhBMP-2 on the proliferation of canine mesenchymal stem cells (cMSCs and the tumor suppression properties of rhBMP-2 in canine osteocarcoma (OST cells. Osteosarcoma cell lines were isolated from biopsies and excisions of animals with osteosarcoma and were characterized by the Laboratory of Biochemistry and Biophysics, Butantan Institute. The mesenchymal stem cells were derived from the bone marrow of canine fetuses (cMSCs and belong to the University of São Paulo, College of Veterinary Medicine (FMVZ-USP stem cell bank. After expansion, the cells were cultured in a 12-well Transwell system; cells were treated with bone marrow mesenchymal stem cells associated with rhBMP2. Expression of the intracytoplasmic and nuclear markers such as Caspase-3, Bax, Bad, Bcl-2, Ki-67, p53, Oct3/4, Nanog, Stro-1 were performed by flow citometry. Results We evaluated the regenerative potential of in vitro treatment with rhBMP-2 and found that both osteogenic induction and tumor regression occur in stem cells from canine bone marrow. rhBMP-2 inhibits the proliferation capacity of OST cells by mechanisms of apoptosis and tumor suppression mediated by p
Diane Pataki; Margaret Carreiro; Jennifer Cherrier; Nancy Grulke; Viniece Jennings; Stephanie Pincetl; Richard Pouyat; Thomas Whitlow; Wayne. Zipperer
Urban green space is purported to offset greenhouse-gas (GHG) emissions, remove air and water pollutants, cool local climate, and improve public health. To use these services, municipalities have focused efforts on designing and implementing ecosystem-services-based "green infrastructure" in urban environments. In some cases the environmental benefits of this...
Ogura-Ochi, Kanako; Fujisawa, Satoshi; Iwata, Nahoko; Komatsubara, Motoshi; Nishiyama, Yuki; Tsukamoto-Yamauchi, Naoko; Inagaki, Kenichi; Wada, Jun; Otsuka, Fumio
The effects of melatonin on prolactin production and its regulatory mechanism remain uncertain. We investigated the regulatory role of melatonin in prolactin production using rat pituitary lactotrope GH3 cells by focusing on the bone morphogenetic protein (BMP) system. Melatonin receptor activation, induced by melatonin and its receptor agonist ramelteon, significantly suppressed basal and forskolin-induced prolactin secretion and prolactin mRNA expression in GH3 cells. The melatonin MT2 receptor was predominantly expressed in GH3 cells, and the inhibitory effects of melatonin on prolactin production were reversed by treatment with the receptor antagonist luzindole, suggesting functional involvement of MT2 action in the suppression of prolactin release. Melatonin receptor activation also suppressed BMP-4-induced prolactin expression by inhibiting phosphorylation of Smad and transcription of the BMP-target gene Id-1, while BMP-4 treatment upregulated MT2 expression. Melatonin receptor activation suppressed basal, BMP-4-induced and forskolin-induced cAMP synthesis; however, BtcAMP-induced prolactin mRNA expression was not affected by melatonin or ramelteon, suggesting that MT2 activation leads to inhibition of prolactin production through the suppression of Smad signaling and cAMP synthesis. Experiments using intracellular signal inhibitors revealed that the ERK pathway is, at least in part, involved in prolactin induction by GH3 cells. Thus, a new regulatory role of melatonin involving BMP-4 in prolactin secretion was uncovered in lactotrope GH3 cells. Copyright © 2017 Elsevier Inc. All rights reserved.
Esfandiari, Fereshteh; Ashtiani, Mohammad Kazemi; Sharifi-Tabar, Mehdi; Saber, Maryam; Daemi, Hamed; Ghanian, Mohammad Hossein; Shahverdi, Abdolhossein; Baharvand, Hossein
Producing meiosis-competent germ cells (GCs) from embryonic stem cells (ESCs) is essential for developing advanced therapies for infertility. Here, a novel approach is presented for generation of GCs from ESCs. In this regard, microparticles (MPs) have been developed from alginate sulfate loaded with bone morphogenetic protein 4 (BMP4). The results here show that BMP4 release from alginate sulfate MPs is significantly retarded by the sulfated groups compared to neat alginate. Then, BMP4-laden MPs are incorporated within the aggregates during differentiation of GCs from ESCs. It is observed that BMP4-laden MPs increase GC differentiation from ESCs at least twofold compared to the conventional soluble delivery method. Interestingly, following meiosis induction, Dazl, an intrinsic factor that enables GCs to enter meiosis, and two essential meiosis genes (Stra8 and Smc1b) are upregulated significantly in MP-induced aggregates compared to aggregates, which are formed by the conventional method. Together, these data show that controlled delivery of BMP4 during ESC differentiation into GC establish meiosis-competent GCs which can serve as an attractive GC source for reproductive medicine. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Kondratenko, Yuriy; Kacprzyk, Janusz
This book presents modern approaches to improving the energy efficiency, safety and environmental performance of industrial processes and products, based on the application of advanced trends in Green Information Technologies (IT) Engineering to components, networks and complex systems (software, programmable and hardware components, communications, Cloud and IoT-based systems, as well as IT infrastructures). The book’s 16 chapters, prepared by authors from Greece, Malaysia, Russia, Slovakia, Ukraine and the United Kingdom, are grouped into four sections: (1) The Green Internet of Things, Cloud Computing and Data Mining, (2) Green Mobile and Embedded Control Systems, (3) Green Logic and FPGA Design, and (4) Green IT for Industry and Smart Grids. The book will motivate researchers and engineers from different IT domains to develop, implement and propagate green values in complex systems. Further, it will benefit all scientists and graduate students pursuing research in computer science with a focus on green ...
Diniz, Ivana M A; Carreira, Ana C O; Sipert, Carla R; Uehara, Cindi M; Moreira, Maria S N; Freire, Laila; Pelissari, Cibele; Kossugue, Patrícia M; de Araújo, Daniele R; Sogayar, Mari C; Marques, Márcia M
Photobiomodulation (PBM) therapy displays relevant properties for tissue healing and regeneration, which may be of interest for the tissue engineering field. Here, we show that PBM is able to improve cell survival and to interact with recombinant human Bone Morphogenetic Protein 4 (rhBMP4) to direct and accelerate odonto/osteogenic differentiation of dental derived mesenchymal stem cells (MSCs). MSCs were encapsulated in an injectable and thermo-responsive cell carrier (Pluronic ® F-127) loaded with rhBMP4 and then photoactivated. PBM improved MSCs self-renewal and survival upon encapsulation in the Pluronic ® F-127. In the presence of rhBMP4, cell odonto/osteogenic differentiation was premature and markedly improved in the photoactivated MSCs. An in vivo calvarial critical sized defect model demonstrated significant increase in bone formation after PBM treatment. Finally, a balance in the reactive oxygen species levels may be related to the favorable results of PBM and rhBMP4 association. PBM may act in synergism with rhBMP4 and is a promise candidate to direct and accelerate hard tissue bioengineering. © 2017 Wiley Periodicals, Inc.
M. Crisan (Mihaela); P. Solaimani Kartalaei (Parham); C.S. Vink (Chris); T. Yamada-Inagawa (Tomoko); K. Bollerot (Karine); W.F.J. van IJcken (Wilfred); R. Van Der Linden (Reinier); S.C. de Sousa Lopes (Susana Chuva); R. Monteiro (Rui); C.L. Mummery (Christine); E.A. Dzierzak (Elaine)
textabstractAdult haematopoiesis is the outcome of distinct haematopoietic stem cell (HSC) subtypes with self-renewable repopulating ability, but with different haematopoietic cell lineage outputs. The molecular basis for this heterogeneity is largely unknown. BMP signalling regulates HSCs as they
Muzdalifah, Aji Uhfatun; Maryono
Park is one of the spot green infrastructure. There are two major characteristic of park, first Active parks and second passive park. Those of two open spaces have been significant on the fulfillment of urban environment. To maintenance the urban park, it is very importance to identify the characteristic of active and passive park. The identification also needs to fostering stakeholder effort to increase quality of urban park infrastructure. This study aims to explore and assess the characteristic of urban park infrastructure in Semarang City, Central Java. Data collection methods conduct by review formal document, field observation and interview with key government officer. The study founded that urban active parks infrastructure resilience could be defined by; Park Location, Garden Shape, Vegetation, Support Element, Park Function, and Expected Benefit from Park Existence. Moreover, the vegetation aspect and the supporting elements are the most importance urban park infrastructure in Semarang.
Full Text Available Hyperglycemia induced reactive oxygen species (ROS generation is believed as major factors leading to diabetic nephropathy (DN. DangGui (Angelica sinensis is mentioned to show renal protective effect in combination with other herbs. Bone morphogenetic proteins-7 (BMP-7 is produced merit in protection of DN. The role of BMP-7 in DangGui-induced renal improvement is not clear. The present study investigated the effects of DangGui on renal functions, BMP-7 expression and the levels of ROS in streptozotocin (STZ-induced diabetic rats and high glucose-exposed rat mesangial cells (RMCs. After 1- or 4-week treatment, DangGui improved renal functions and increased renal BMP-7 expression in diabetic rats. The BMP-7 expression in RMCs was reduced by high glucose treatment and this could be reversed by DangGui. Moreover, RMCs exposed to high glucose were expired by BMP-7 RNAi transfection but those cells remained alive by scramble transfection. Thus, we employed regular RMCs to knock down BMP-7 with RNAi and we found that DangGui increased BMP-7 expression in these RMCs. Direct activation of BMP-7 expression by DangGui could be considered. The results of DPPH assay, DHE stain and lucigenin assay indicated that DangGui could inhibit high glucose-induced ROS in RMCs. These results suggest that DangGui has an ability to improve renal functions in STZ-diabetic rats through increasing endogenous BMP-7 expression and decreasing oxidative stress in kidney. The present study suggest that DangGui could be applied to improve renal functions in diabetic disorders.
Chen, Zhuoyue; Zhang, Zhen; Feng, Juantao; Guo, Yayuan; Yu, Yuan; Cui, Jihong; Li, Hongmin; Shang, Lijun
Osteoinductive activity of the implant in bone healing and regeneration is still a challenging research topic. Therapeutic application of recombinant human bone morphogenetic protein-2 (BMP-2) is a promising approach to enhance osteogenesis. However, high dose and uncontrolled burst release of BMP-2 may introduce edema, bone overgrowth, cystlike bone formation, and inflammation. In this study, low-dose BMP-2 of 1 μg was used to design PLA-PD-BMP for functionalization of polylactic acid (PLA) implants via mussel-inspired polydopamine (PD) assist. For the first time, the binding property and efficiency of the PD coating with BMP-2 were directly demonstrated and analyzed using an antigen-antibody reaction. The obtained PLA-PD-BMP surface immobilized with this low BMP-2 dose can endow the implants with abilities of introducing strong stem cell adhesion and enhanced osteogenicity. Furthermore, in vivo osteoinduction of the PLA-PD-BMP-2 scaffolds was confirmed by a rat ectopic bone model, which is marked as the "gold standard" for the evidence of osteoinductive activity. The microcomputed tomography, Young's modulus, and histology analyses were also employed to demonstrate that PLA-PD-BMP grafted with 1 μg of BMP-2 can induce bone formation. Therefore, the method in this study can be used as a model system to immobilize other growth factors onto various different types of polymer substrates. The highly biomimetic mussel-derived strategy can therefore improve the clinical outcome of polymer-based medical implants in a facile, safe, and effective way.
Full Text Available This study was undertaken to evaluate the effect of 3D printed polycaprolactone (PCL/β-tricalcium phosphate (β-TCP scaffold containing bone demineralized and decellularized extracellular matrix (bdECM and human recombinant bone morphogenetic protein-2 (rhBMP-2 on bone regeneration. Scaffolds were divided into PCL/β-TCP, PCL/β-TCP/bdECM, and PCL/β-TCP/bdECM/BMP groups. In vitro release kinetics of rhBMP-2 were determined with respect to cell proliferation and osteogenic differentiation. These three reconstructive materials were implanted into 8 mm diameter calvarial bone defect in male Sprague-Dawley rats. Animals were sacrificed four weeks after implantation for micro-CT, histologic, and histomorphometric analyses. The findings obtained were used to calculate new bone volumes (mm3 and new bone areas (%. Excellent cell bioactivity was observed in the PCL/β-TCP/bdECM and PCL/β-TCP/bdECM/BMP groups, and new bone volume and area were significantly higher in the PCL/β-TCP/bdECM/BMP group than in the other groups (p<.05. Within the limitations of this study, bdECM printed PCL/β-TCP scaffolds can reproduce microenvironment for cells and promote adhering and proliferating the cells onto scaffolds. Furthermore, in the rat calvarial defect model, the scaffold which printed rhBMP-2 loaded bdECM stably carries rhBMP-2 and enhances bone regeneration confirming the possibility of bdECM as rhBMP-2 carrier.
Li, Chen-Shuang; Tian, Haijun; Zou, Min; Zhao, Ke-Wei; Li, Yawei; Lao, Lifeng; Brochmann, Elsa J.; Duarte, M. Eugenia L.; Daubs, Michael D.; Zhou, Yan-Heng; Murray, Samuel S.; Wang, Jeffrey C.
The emerging role of bone morphogenetic proteins (BMPs) in the initiation and progression of multiple cancers has drawn great attention in cancer research. In this study, we report that BMP-2 can promote the proliferation of the pancreatic tumor cell line, PANC-1. Secreted phosphoprotein 24 kD (Spp24), a BMP binding protein, did not affect the proliferation of the cells but promoted the apoptosis of the cells in vitro. In a xeneograft tumor model using PANC-1 cells, BMP-2 dramatically promoted tumor growth, while Spp24 not only abolished the effect of BMP-2, but also dramatically induced tumor shrinking when used alone. Activation of Smad1/5/8 participated in this process as demonstrated by immunohistochemical staining of phosphorylated Smad 1/5/8. We conclude that Spp24 can be developed into a therapeutic agent that could be employed in clinical situations where the inhibition of BMPs and related proteins is advantageous. - Highlights: • Spp24 effectively inhibited the in vivo tumor growth of PANC-1. • BMP-2 dramatically promoted tumor growth by promoting PANC-1 proliferation. • Spp24 abolished the tumor growth effect of BMP-2 by promoting PANC-1 apoptosis. • Spp24 may be a candidate as a therapeutic agent of pancreatic cancer.
Li, Chen-Shuang [Department of Orthodontics, Peking University School and Hospital of Stomatology, Beijing (China); Tian, Haijun, E-mail: firstname.lastname@example.org [Department of Orthopaedic Surgery, Changzheng Hospital, Second Military Medical University, Shanghai (China); Department of Orthopaedic Surgery, University of California, Los Angeles, Los Angeles, CA (United States); Department of Surgery, Bethune School of Medics, Shijiazhuang (China); Zou, Min [Department of Orthodontics, School and Hospital of Stomatology, Xi' an Jiaotong University, Xi' an (China); Zhao, Ke-Wei [Research Service, VA Greater Los Angeles Healthcare System, North Hills, CA (United States); Li, Yawei; Lao, Lifeng [Department of Orthopaedic Surgery, University of California, Los Angeles, Los Angeles, CA (United States); Brochmann, Elsa J. [Research Service, VA Greater Los Angeles Healthcare System, North Hills, CA (United States); Geriatric Research, Education and Clinical Center, VA Greater Los Angeles Healthcare System, North Hills, CA (United States); Department of Medicine, University of California, Los Angeles, Los Angeles, CA (United States); Duarte, M. Eugenia L. [National Institute of Traumatology and Orthopaedics, Rio de Janeiro (Brazil); Daubs, Michael D. [Division of Orthopaedic Surgery, Department of Surgery, University of Nevada School of Medicine, Las Vegas, NV (United States); Zhou, Yan-Heng, E-mail: email@example.com [Department of Orthodontics, Peking University School and Hospital of Stomatology, Beijing (China); Murray, Samuel S. [Research Service, VA Greater Los Angeles Healthcare System, North Hills, CA (United States); Geriatric Research, Education and Clinical Center, VA Greater Los Angeles Healthcare System, North Hills, CA (United States); Department of Medicine, University of California, Los Angeles, Los Angeles, CA (United States); Wang, Jeffrey C. [Department of Orthopaedic Surgery, University of Southern California, Los Angeles, CA (United States)
The emerging role of bone morphogenetic proteins (BMPs) in the initiation and progression of multiple cancers has drawn great attention in cancer research. In this study, we report that BMP-2 can promote the proliferation of the pancreatic tumor cell line, PANC-1. Secreted phosphoprotein 24 kD (Spp24), a BMP binding protein, did not affect the proliferation of the cells but promoted the apoptosis of the cells in vitro. In a xeneograft tumor model using PANC-1 cells, BMP-2 dramatically promoted tumor growth, while Spp24 not only abolished the effect of BMP-2, but also dramatically induced tumor shrinking when used alone. Activation of Smad1/5/8 participated in this process as demonstrated by immunohistochemical staining of phosphorylated Smad 1/5/8. We conclude that Spp24 can be developed into a therapeutic agent that could be employed in clinical situations where the inhibition of BMPs and related proteins is advantageous. - Highlights: • Spp24 effectively inhibited the in vivo tumor growth of PANC-1. • BMP-2 dramatically promoted tumor growth by promoting PANC-1 proliferation. • Spp24 abolished the tumor growth effect of BMP-2 by promoting PANC-1 apoptosis. • Spp24 may be a candidate as a therapeutic agent of pancreatic cancer.
Hogan, Dianna M.; Shapiro, Carl D.; Karp, David N.; Wachter, Susan M.
Traditional approaches to urban development often do not account for, or recognize, the role of ecosystem services and the benefits these services provide to the health and well-being of city residents. Without such accounting, urban ecosystem services are likely to be degraded over time, with negative consequences for the sustainability of cities and the well-being of their residents (Millennium Ecosystem Assessment, 2005; Hirsch, 2008). On May 23, 2013, the Spatial Integration Laboratory for Urban Systems (SILUS), a collaboration between the U.S. Geological Survey (USGS) Science and Decisions Center and the Wharton GIS Lab, convened a one-day symposium—Urban Ecosystem Services and Decision Making: A Green Philadelphia—at the University of Pennsylvania in Philadelphia, Pennsylvania, to examine the role of green infrastructure in the environmental, economic, and social well-being of cities. Cosponsored by the USGS and the Penn Institute for Urban Research (Penn IUR), the symposium brought together policymakers, practitioners, and researchers from a range of disciplines to advance a research agenda on the use of science in public decision making to inform investment in green infrastructure and ecosystem services in urban areas. The city of Philadelphia has recently implemented a program designed to sustain urban ecosystem services and advance the use of green infrastructure. In 2009, the Philadelphia Mayor’s Office of Sustainability launched its Greenworks plan, establishing a citywide sustainability strategy. Major contributions towards its goals are being implemented in coordination with the Philadelphia Water Department (PWD). The Green City, Clean Waters initiative, the city’s nationally recognized stormwater management plan, was signed into action with the U.S. Environmental Protection Agency (EPA) in April 2012. The plan outlines a 25-year strategy to use green infrastructure to protect and improve the city’s watershed.