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Sample records for biomethane potential bmp

  1. Biomethane yield of energy crops and prediction of their biochemical methane potential (BMP) with near infrared spectroscopy (NIRS)

    OpenAIRE

    Mayer, Frédéric

    2015-01-01

    Anaerobic digestion process produces biomethane as a renewable energy source. To optimize the energy production, energy crops with a high biomethane yield per hectare should be identified. A large number of samples of maize, tall fescue, sorghum, spelt, miscanthus, immature rye, switchgrass, sunflower and hemp was cropped. The fresh biomass yield per hectare, the volatile solid (VS) content, the biochemical composition and the biochemical methane potential (BMP) were measured. Maize (annual p...

  2. Defining the biomethane potential (BMP) of solid organic wastes and energy crops

    DEFF Research Database (Denmark)

    Angelidaki, Irini; Alves, M.; Bolzonella, D.;

    2009-01-01

    The application of anaerobic digestion technology is growing worldwide because of its economic and environmental benefits. As a consequence, a number of studies and research activities dealing with the determination of the biogas potential of solid organic substrates have been carrying out in the...... Specialist Group of the International Water Association. This is the first step for the definition of a standard protocol....

  3. Biomethanation and Its Potential

    DEFF Research Database (Denmark)

    Angelidaki, Irini; Karakashev, Dimitar Borisov; Batstone, Damien J.;

    2011-01-01

    Biomethanation is a process by which organic material is microbiologically converted under anaerobic conditions to biogas. Three main physiological groups of microorganisms are involved: fermenting bacteria, organic acid oxidizing bacteria, and methanogenic archaea. Microorganisms degrade organic...

  4. Biomethanation and its potential

    NARCIS (Netherlands)

    Angelidaki, I.; Karakashev, D.; Batstone, D.J.; Plugge, C.M.; Stams, A.J.M.

    2011-01-01

    Biomethanation is a process by which organic material is microbiologically converted under anaerobic conditions to biogas. Three main physiological groups of microorganisms are involved: fermenting bacteria, organic acid oxidizing bacteria, and methanogenic archaea. Microorganisms degrade organic ma

  5. Testing the Biomethane Yield of Degradable Wastes of Meat Industry by BMP Test

    OpenAIRE

    Imamović, I.; Goletić, Š.

    2014-01-01

    The optimal mix of solid waste from the meat industry (MI) for anaerobic digestion (AD) treatment can be selected by defining the biomethane potential (BMP test) of the waste in relation to the unit value of chemical oxygen demand (COD). In this paper, the BMP test of biodegradable wastes from MI has been performed. For the purposes of the experiment, two types of input substrates have been defined: manure (manure from cattle depots and transport vehicles for cattle transport) labeled as O1 a...

  6. Defining the biomethane potential (BMP) of solid organic wastes and energy crops : a proposed protocol for batch assays

    OpenAIRE

    Angelidaki, I.; Alves, M.M.; Bolzonella, D.; Borzacconi, L.; Campos, J. L.; Guwy, A. J.; Kalyuzhnyi, S.; Jenicek, P.; van Lier, J B

    2009-01-01

    The application of anaerobic digestion technology is growing worldwide because of its economic and environmental benefits. As a consequence, a number of studies and research activities dealing with the determination of the biogas potential of solid organic substrates have been carrying out in the recent years. Therefore, it is of particular importance to define a protocol for the determination of the ultimate methane potential for a given solid substrates. In fact, this paramet...

  7. The biomethane potential in Chile

    International Nuclear Information System (INIS)

    Within the last decade natural gas gained considerable importance in Chile. The contribution of natural gas within the energy system will increase in the future by predicted 3.6% annually until the year 2015. Due to limited resources within its own country, the energy system of Chile depends on natural gas imports preferential from Argentina. Therefore, the aim of several stakeholders from policy and industry is to reduce the share of imported primary energy within the overall energy system. In order to reach this goal, the use of domestic resources and particularly the utilisation of biomass as one of the most important renewable sources of energy in Chile could play an important role. Against this background, the goal of this paper is the analysis of the technical potentials of biomethane as a substitute for natural gas. For the production of biomethane the anaerobic or bio-chemical (i.e. Biogas) as well as the thermo-chemical conversion pathways (i.e. Bio-SNG) are considered. The results of this analysis show that biomass converted to biomethane is a promising energy provision option for Chile and it contributes to the reduction of greenhouse gas emissions

  8. Biomethane as transport fuel : a study on upgrading technologies and biomethane potential in Finland

    OpenAIRE

    Cui, Nan

    2015-01-01

    Due to the negative environmental impact caused by fossil fuels usage, the focus on bioenergy has been raised in recent years. Biogas produced from an anaerobic process is good enough to produce electricity and heat, but after upgrading to biomethane, it also has a great potential to act as vehicle fuel. This Bachelor’s thesis starts with a theoretical background of the benefits of using biomethane as transport fuel. It reviews and compares five current upgrading technologies: membrane separa...

  9. Screening of biomethane production potential from dominant microalgae.

    Science.gov (United States)

    Fermoso, Fernando G; Beltran, Carolina; Jimenez, Antonia; Fernández, María José; Rincón, Bárbara; Borja, Rafael; Jeison, David

    2016-10-14

    The use of microalgae for biomethane production has been considerably increasing during the recent years. In this study, four dominant species belonging to the genera Scenedesmus, Chlorella, Dunaliella and Nostoc were selected. The influence of different genera with several morphological, structural and physicochemical characteristics on methane production was assessed in biochemical methane potential (BMP) tests. The ultimate methane yield values were 332 ± 24, 211 ± 2, 63 ± 17 and 28 ± 10 mL CH4/g VSadded for Scenedesmus obliquus, Chlorella sorokiniana, Dunaliella salina and Nostoc sp., respectively. The highest methane production was achieved by microalga species that had no complex cell wall or wall basically composed by proteins and simple sugars such as in S. obliquus, whereas lower methane yields were found for D. salina and Nostoc sp., due to the salinity effects and cell wall composition in terms of complex polysaccharide and glycolipid layers, respectively. Kinetic constant values obtained in the BMP tests ranged between 1.00 ± 0.08 and 0.097 ± 0.005 days(-1) for D. salina and S. obliquus, respectively. PMID:27409043

  10. Status and potential of bio-methane fuel

    International Nuclear Information System (INIS)

    This document first indicates and describes the various bio-methane production processes which can be implemented on a short term (use of organic wastes or effluents), on a medium term (from energetic crops) and on a longer term (gasification). It discusses and assesses the potential production of bio-methane fuel from different sources and processes. It describes the steps of the production of bio-methane fuel from biogas, with notably biogas refinement to produce bio-methane through three processes (de-carbonation, desulfurization, dehydration). Cost productions are assessed. Expected technology advances are evoked. Finally, the authors outline the contribution of bio-methane in the limitation of greenhouse gas emissions in the transport sector

  11. Determining the regional potential for a grass biomethane industry

    International Nuclear Information System (INIS)

    Research highlights: → We identified assessment criteria for determining the regional potential for grass biomethane. → Grass biomethane is distributed via the natural gas grid. → The criteria include: land use; grass yields; gas grid coverage; availability of co-substrates. → The county with the highest potential can fuel 50% of cars or supply 130% of domestic gas consumption. - Abstract: Grass biogas/biomethane has been put forward as a renewable energy solution and it has been shown to perform well in terms of energy balance, greenhouse gas emissions and policy constraints. Biofuel and energy crop solutions are country-specific and grass biomethane has strong potential in countries with temperate climates and a high proportion of grassland, such as Ireland. For a grass biomethane industry to develop in a country, suitable regions (i.e. those with the highest potential) must be identified. In this paper, factors specifically related to the assessment of the potential of a grass biogas/biomethane industry are identified and analysed. The potential for grass biogas and grass biomethane is determined on a county-by-county basis using multi-criteria decision analysis. Values are assigned to each county and ratings and weightings applied to determine the overall county potential. The potential for grass biomethane with co-digestion of slaughter waste (belly grass) is also determined. The county with the highest potential (Limerick) is analysed in detail and is shown to have ready potential for production of gaseous biofuel to meet either 50% of the vehicle fleet or 130% of the domestic natural gas demand, through 25 facilities at a scale of ca. 30 kt yr-1 of feedstock. The assessment factors developed in this paper can be used in other resource studies into grass biomethane or other energy crops.

  12. Effect of enzymatic pretreatment of various lignocellulosic substrates on production of phenolic compounds and biomethane potential.

    Science.gov (United States)

    Schroyen, Michel; Vervaeren, Han; Vandepitte, Hanne; Van Hulle, Stijn W H; Raes, Katleen

    2015-09-01

    Pretreatment of lignocellulosic biomass is necessary to enhance the hydrolysis, which is the rate-limiting step in biogas production. Laccase and versatile peroxidase are enzymes known to degrade lignin. Therefore, the impact of enzymatic pretreatment was studied on a variety of biomass. A significant higher release in total phenolic compounds (TPC) was observed, never reaching the inhibiting values for anaerobic digestion. The initial concentration of TPC was higher in the substrates containing more lignin, miscanthus and willow. The anaerobic digestion of these two substrates resulted in a significant lower biomethane production (68.8-141.7 Nl/kg VS). Other substrates, corn stover, flax, wheat straw and hemp reached higher biomethane potential values (BMP), between 241 and 288 Nl/kg VS. Ensilaged maize reached 449 Nl/kg VS, due to the ensilation process, which can be seen as a biological and acid pretreatment. A significant relation (R(2) = 0.89) was found between lignin content and BMP. PMID:26094196

  13. Biomethanation of Carpet Grass (Axonopus fissifolius)

    OpenAIRE

    Chima Ngumah; Jude Ogbulie; Justina Orji; Ekperechi Amadi

    2013-01-01

    Axonopus fissifolius commonly called “carpet grass” was subjected to anaerobic digestion for 30 days. Anaerobic digestion was carried out in a batch-fed process at the ambient temperature of 27-290C. Biomethane measurements were obtained by measuring the volume displacement of a saturated filtered calcium hydroxide solution in a transparent calibrated vessel.  42.7g of fresh carpet grass clippings yielded 1.955 L of biomethane. Biomethane potential (BMP) of carpet grass for a 30 day anaerobic...

  14. Biochemicalmethane potential (BMP) of solid organic substrates

    DEFF Research Database (Denmark)

    Raposo, F.; Fernández-Cegrí, V.; de la Rubia, M.A.;

    2011-01-01

    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......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...

  15. The potential for biomethane from grass and slurry to satisfy renewable energy targets.

    Science.gov (United States)

    Wall, David M; O'Kiely, Padraig; Murphy, Jerry D

    2013-12-01

    A biomethane potential (BMP) assessment of grass silage yielded 107 m(3)CH4 t(-1). Long term mono-digestion of grass silage can suffer due to a deficiency in essential nutrients; this may be overcome by co-digesting with slurry. Mono-digestion of slurry achieved a low yield of 16 m(3)CH4 t(-1). BMP assessments at a range of co-digestion ratios indicated methane yields were between 4% and 11% lower than the values calculated from mono-digestion. This paper suggests that co-digestion of the majority of slurry produced from dairy cows in Ireland with grass silage quantities equivalent to 1.1% of grassland on a 50:50 volatile solids basis would generate over 10% renewable energy supply in transport (RES-T). The industry proposed would equate to 170 digesters each treating 10,000 t a(-1) of grass silage and 40,000 t a(-1) of slurry from dairy cows.

  16. Status and potential of bio-methane fuel; Etat des lieux et potentiel du biomethane carburant Etude ADEME, AFGNV, ATEE Club Biogaz, GDF SUEZ, IFP, MEEDDAT

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2008-07-01

    This document first indicates and describes the various bio-methane production processes which can be implemented on a short term (use of organic wastes or effluents), on a medium term (from energetic crops) and on a longer term (gasification). It discusses and assesses the potential production of bio-methane fuel from different sources and processes. It describes the steps of the production of bio-methane fuel from biogas, with notably biogas refinement to produce bio-methane through three processes (de-carbonation, desulfurization, dehydration). Cost productions are assessed. Expected technology advances are evoked. Finally, the authors outline the contribution of bio-methane in the limitation of greenhouse gas emissions in the transport sector

  17. Bio-hydrogen and bio-methane potentials of skim latex serum in batch thermophilic two-stage anaerobic digestion.

    Science.gov (United States)

    Jariyaboon, Rattana; O-Thong, Sompong; Kongjan, Prawit

    2015-12-01

    Anaerobic digestion by two-stage process, containing hydrogen-producing (acidogenic) first stage and methanogenic second stage, has been proposed to degrade substrates which are difficult to be treated by single stage anaerobic digestion process. This research was aimed to evaluate the bio-hydrogen and the bio-methane potentials (BHP and BMP) of skim latex serum (SLS) by using sequential batch hydrogen and methane cultivations at thermophilic conditions (55°C) and with initial SLS concentrations of 37.5-75.0% (v/v). The maximal 1.57 L H2/L SLS for BHP and 12.2L CH4/L SLS for BMP were both achieved with 60% (v/v) SLS. The dominant hydrogen-producing bacteria in the H2 batch reactor were Thermoanaerobacterium sp. and Clostrdium sp. Meanwhile, the CH4 batch reactor was dominated by the methanogens Methanosarcina mazei and Methanothermobacter defluvii. The results demonstrate that SLS can be degraded by conversion to form hydrogen and methane, waste treatment and bioenergy production are thus combined. PMID:26386423

  18. Biomethanation of Carpet Grass (Axonopus fissifolius

    Directory of Open Access Journals (Sweden)

    Chima Ngumah

    2014-01-01

    Full Text Available Axonopus fissifolius commonly called “carpet grass” was subjected to anaerobic digestion for 30 days. Anaerobic digestion was carried out in a batch-fed process at the ambient temperature of 27-290C. Biomethane measurements were obtained by measuring the volume displacement of a saturated filtered calcium hydroxide solution in a transparent calibrated vessel.  42.7g of fresh carpet grass clippings yielded 1.955 L of biomethane. Biomethane potential (BMP of carpet grass for a 30 day anaerobic digestion was 0.05 m3 CH4 kg-1 TS. The rates of biomethane potentials for the first, second, third, fourth and fifth six-day intervals were 1.5mL g-1 TS (2.81%, 6.4mL g-1 TS (14.58%, 16.1mL g-1 TS (30.18%, 17.74mL g-1 TS (33.25%, and 10.23mL g-1 TS (19.81% respectively. The total solids, volatile solids and pH of feedstock and digestate were 85.80% and 85.56%, 90.91% and 87.58%, 6.6 (27oC and 6.9 (27oC respectively.  The relatively high biomethane potential of carpet grass at the ambient temperature presented in this paper depicts anaerobic digestion as a viable means of profitably treating grass waste for both sanitation and generating biomethane especially in the tropics where the ambient temperatures are usually favourable for optimum biomethanation for most part of the year, thus making the process affordable and less cumbersome.DOI http://dx.doi.org/10.5755/j01.erem.66.4.5228

  19. Biomethanation of Carpet Grass (Axonopus fissifolius

    Directory of Open Access Journals (Sweden)

    Chima Ngumah

    2013-12-01

    Full Text Available Axonopus fissifolius commonly called “carpet grass” was subjected to anaerobic digestion for 30 days. Anaerobic digestion was carried out in a batch-fed process at the ambient temperature of 27-290C. Biomethane measurements were obtained by measuring the volume displacement of a saturated filtered calcium hydroxide solution in a transparent calibrated vessel. 42.7g of fresh carpet grass clippings yielded 1.955 L of biomethane. Biomethane potential (BMP of carpet grass for a 30 day anaerobic digestion was 0.05 m3 CH4 kg-1 TS. The rates of biomethane potentials for the first, second, third, fourth and fifth six-day intervals were 1.5mL g-1 TS (2.81%, 6.4mL g-1 TS (14.58%, 16.1mL g-1 TS (30.18%, 17.74mL g-1 TS (33.25%, and 10.23mL g-1 TS (19.81% respectively. The total solids, volatile solids and pH of feedstock and digestate were 85.80% and 85.56%, 90.91% and 87.58%, 6.6 (27oC and 6.9 (27oC respectively. The relatively high biomethane potential of carpet grass at the ambient temperature presented in this paper depicts anaerobic digestion as a viable means of profitably treating grass waste for both sanitation and generating biomethane especially in the tropics where the ambient temperatures are usually favourable for optimum biomethanation for most part of the year, thus making the process affordable and less cumbersome.

  20. Biochemical methane potential (BMP) of solid organic materials

    DEFF Research Database (Denmark)

    Raposo, Francisco; Fernández-Cegrí, V.; De la Rubia, M.A.;

    2010-01-01

    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...

  1. The biostimulation of anaerobic digestion with (semi)conductive ferric oxides: their potential for enhanced biomethanation.

    Science.gov (United States)

    Baek, Gahyun; Kim, Jaai; Cho, Kyungjin; Bae, Hyokwan; Lee, Changsoo

    2015-12-01

    The effect of biostimulation with ferric oxides, semiconductive ferric oxyhydroxide, and conductive magnetite on the anaerobic digestion of dairy wastewater was examined in a batch mode. The reactors supplemented with ferric oxyhydroxide (R2) and magnetite (R3) showed significantly enhanced biomethanation performance compared with the control (R1). The removal of chemical oxygen demand (COD) after 30 days was 31.9, 59.3, and 82.5% in R1, R2, and R3, respectively. The consumed COD was almost fully recovered as biogas in R2 and R3, while only 79% was recovered in R1. The total energy production as biogas was accordingly 32.2, 71.0, and 97.7 kJ in R1, R2, and R3, respectively. The reactors also differed in the acid formation profile with more propionate and butyrate found in R1 and more acetate found in R3. The enhanced biomethanation seems to be associated with variations in the bacterial community structure supposedly induced by the ferric oxides added. In contrast, no evident variation was observed in the archaeal community structure among the reactors. The potential electric syntrophy formed between Methanosaeta concilii-like methanogens and electroactive iron-reducing bacteria, particularly Trichococcus, was likely responsible for the enhanced performance. The stimulated growth of fermentative iron reducers may also have contributed by altering the metabolic characteristics of the bacterial communities to produce more favorable acidogenic products for methanogenesis. The overall results suggest the potential of biostimulation with (semi)conductive ferric oxides to enhance the rate and efficiency of the biomethanation of organic wastes. This seems to be potentially attractive, as increasing attention is being paid to the energy self-sufficiency of waste/wastewater treatment processes today. PMID:26272096

  2. Assessment of the potential of biomethane produced from the French municipal sludge. Synthesis

    International Nuclear Information System (INIS)

    To achieve the goals of renewable energy production by 23% in 2020 and by 32% in 2030 (Law project on energy transition), the French Government is committed to strongly support all the local renewable energy sectors and in particular the anaerobic digestion. This sector can recycle organic waste into renewable energy while respecting local needs and issues. The objective of this study is to consider the potential of biomethane injectable into the gas grid from Waste Water Treatment Plant (WWTP) sludge in 2020 and in 2050. Wastewater is all sewage from the population but also industrial and commercial activities. The wastewater treatment can be achieved collectively in a wastewater treatment plant or individually (independent sanitation). The organic pollution in wastewater is usually expressed in Population Equivalent. Metropolitan France has 19,521 active wastewater treatment plants (data from portal sanitation, 2014) out of which 85 currently have an anaerobic digestion plant on site for sludge treatment. The entire theoretical methanogenic potential from all the sludge WWTP is 2.13 TWh/year. To estimate the wastewater treatment plants liable to digest sludge, the approach used in this study is to determine the breakeven points of an anaerobic digestion plant installed on different sectors-types of wastewater treatment. The different ways of biogas recovery are sized and compared. It is considered that a case is profitable if its internal rate of return is at least 10 % (compared to a reference case). This approach is characterized by: - A literature review of technical and economic characteristics of the various treatments found at a WWTP including anaerobic digestion and biogas recovery associated, - A return of experience and collect of opinions from various experts in the field of sanitation, - A technical and economic analysis of the various defined cases in relation to a reference case (without anaerobic digestion plant). According to the technical and

  3. Evaluation of the biomethane potential of solid fish waste

    OpenAIRE

    Eiroa, M.; Costa, J. C.; Alves, M.M.; Kennes, C.; Veiga, M. C.

    2012-01-01

    Manufacturing processes in fish canning industries generate a considerable amount of solid waste that can be digested anaerobically. The aim of this research was to study the biochemical methane potential of different solid fish waste. For tuna, sardine and needle fish waste, around 0.47 g COD–CH4/g CODadded was obtained in batch experiments with 1%TS; whereas for mackerel waste, the methane production attained 0.59 g COD–CH4/g CODadded. The increase in the waste/inoculum ratio, f...

  4. Determination of lab-scale biomethane potential of wheat straw pellets and their influence on anaerobic digestion

    OpenAIRE

    Kolbl, Sabina; Stres, Blaž

    2015-01-01

    Laboratory scale degradation of wheat straw pellets as an additional substrate for methane production was monitored as an example of controlled usage of unconventional substrates. In the laboratory biomethane potential of input feedstock from biogas plant (BGP) Organica Nova to which pellets were added in different proportions was determined. Organic loading (volatile solids, VS) was 5 g VS/L in all cases. Measurements were carried out by AMPTS I (Bioprocess Control, Sweden). Amou...

  5. Determination of lab-scale biomethane potential of wheat straw pellets and their influence on anaerobic digestion

    OpenAIRE

    Kolbl, Sabina; Stres, Blaž

    2013-01-01

    Laboratory scale degradation of wheat straw pellets as an additional substrate for methane production was monitored as an example of controlled usage of unconventional substrates. In the laboratory biomethane potential of input feedstock from biogas plant (BGP) Organica Nova to which pellets were added in different proportions was determined. Organic loading (volatile solids, VS) was 5 g VS/L in all cases. Measurements were carried out by AMPTS I (Bioprocess Control, Sweden). Amount of produc...

  6. Thermo-Acidic Pretreatment of Beach Macroalgae from Rügen to Optimize Biomethane Production—Double Benefit with Simultaneous Bioenergy Production and Improvement of Local Beach and Waste Management

    Directory of Open Access Journals (Sweden)

    Yann Nicolas Barbot

    2015-09-01

    Full Text Available Eutrophication is a phenomenon which can rapidly generate masses of marine macroalgae, particularly in areas with high nutrient pollution. Washed ashore, this biomass impairs coastal tourism and negatively affects the coastal ecosystem. The present study evaluates the biochemical methane potential (BMP of a macroalgae mix (Rügen-Mix, RM (RM = Rügen-Mix originating from Rügen, Germany. To improve biomethane recovery, thermo-acidic pretreatment was applied to the biomass prior to biomethanation to disintegrate the biomass macrostructure. Acid hydrolysis was successfully triggered with 0.2 M industry-grade HCl at 80 °C for a 2 h period, increasing biomethane recovery by +39%, with a maximum BMP of 121 mL·g−1 volatile solids (VS. To reduce the necessity for input material, HCl was replaced by the acidic waste product flue gas condensate (FGC. Improved performance was achieved by showing an increase in biomethane recovery of +24% and a maximum BMP of 108 mL·g−1 VS. Continuous anaerobic digestion trials of RM were conducted for three hydraulic retention times, showing the feasibility of monodigestion. The biomethane recovery was 60 mL and 65 mL·g−1 VS·d−1 for thermophilic and mesophilic operation, respectively. The quality of biomethanation performance aligned to the composition of the source material which exhibited a low carbon/nitrogen ratio and an increased concentration of sulfur compounds.

  7. Thermo-Acidic Pretreatment of Beach Macroalgae from Rügen to Optimize Biomethane Production--Double Benefit with Simultaneous Bioenergy Production and Improvement of Local Beach and Waste Management.

    Science.gov (United States)

    Barbot, Yann Nicolas; Thomsen, Laurenz; Benz, Roland

    2015-09-01

    Eutrophication is a phenomenon which can rapidly generate masses of marine macroalgae, particularly in areas with high nutrient pollution. Washed ashore, this biomass impairs coastal tourism and negatively affects the coastal ecosystem. The present study evaluates the biochemical methane potential (BMP) of a macroalgae mix (Rügen-Mix, RM (RM = Rügen-Mix)) originating from Rügen, Germany. To improve biomethane recovery, thermo-acidic pretreatment was applied to the biomass prior to biomethanation to disintegrate the biomass macrostructure. Acid hydrolysis was successfully triggered with 0.2 M industry-grade HCl at 80 °C for a 2 h period, increasing biomethane recovery by +39%, with a maximum BMP of 121 mL·g(-1) volatile solids (VS). To reduce the necessity for input material, HCl was replaced by the acidic waste product flue gas condensate (FGC). Improved performance was achieved by showing an increase in biomethane recovery of +24% and a maximum BMP of 108 mL·g(-1) VS. Continuous anaerobic digestion trials of RM were conducted for three hydraulic retention times, showing the feasibility of monodigestion. The biomethane recovery was 60 mL and 65 mL·g(-1) VS·d(-1) for thermophilic and mesophilic operation, respectively. The quality of biomethanation performance aligned to the composition of the source material which exhibited a low carbon/nitrogen ratio and an increased concentration of sulfur compounds. PMID:26404327

  8. Thermo-Acidic Pretreatment of Beach Macroalgae from Rügen to Optimize Biomethane Production—Double Benefit with Simultaneous Bioenergy Production and Improvement of Local Beach and Waste Management

    Science.gov (United States)

    Barbot, Yann Nicolas; Thomsen, Laurenz; Benz, Roland

    2015-01-01

    Eutrophication is a phenomenon which can rapidly generate masses of marine macroalgae, particularly in areas with high nutrient pollution. Washed ashore, this biomass impairs coastal tourism and negatively affects the coastal ecosystem. The present study evaluates the biochemical methane potential (BMP) of a macroalgae mix (Rügen-Mix, RM (RM = Rügen-Mix)) originating from Rügen, Germany. To improve biomethane recovery, thermo-acidic pretreatment was applied to the biomass prior to biomethanation to disintegrate the biomass macrostructure. Acid hydrolysis was successfully triggered with 0.2 M industry-grade HCl at 80 °C for a 2 h period, increasing biomethane recovery by +39%, with a maximum BMP of 121 mL·g−1 volatile solids (VS). To reduce the necessity for input material, HCl was replaced by the acidic waste product flue gas condensate (FGC). Improved performance was achieved by showing an increase in biomethane recovery of +24% and a maximum BMP of 108 mL·g−1 VS. Continuous anaerobic digestion trials of RM were conducted for three hydraulic retention times, showing the feasibility of monodigestion. The biomethane recovery was 60 mL and 65 mL·g−1 VS·d−1 for thermophilic and mesophilic operation, respectively. The quality of biomethanation performance aligned to the composition of the source material which exhibited a low carbon/nitrogen ratio and an increased concentration of sulfur compounds. PMID:26404327

  9. Comparison of osteogenic potentials of human rat BMP4 and BMP6 gene therapy using [E1-] and [E1-,E2b-] adenoviral vectors

    Directory of Open Access Journals (Sweden)

    Hongwei Li, Jin Zhong Li, Debra D. Pittman, Andy Amalfitano, Gerald R. Hankins, Gregory A. Helm

    2006-01-01

    Full Text Available Osteogenic potentials of some recombinant human bone morphogenetic protein (BMP first-generation adenoviral vectors (ADhBMPs are significantly limited in immunocompetent animals. It is unclear what role expression of viral proteins and foreign proteins transduced by adenoviral vectors play in the host immune response and in ectopic bone formation. In this study two sets of experiments were designed and performed. First, rat BMP6 cDNA were amplified, sequenced, and recombined in first-generation adenoviral vector (ADrBMP6. A comparison of human and rat BMP6 adenoviral vectors demonstrated identical osteogenic activities in both immunodeficient and immunocompetent rats. Second, the activities of recombinant human BMP6 in E1- (ADhBMP6 and [E1-,E2b-] ( [E1-,E2b-]ADGFP&hBMP6, and [E1-,E2b-]ADhBMP6 adenoviral vectors were compared in both in vitro and in vivo models. Similar activities of these two generations of BMP adenoviral vectors were found in all models. These results indicate that the amount of viral gene expression and the source of the BMP cDNA are not major factors in the interruption of osteogenic potentials of recombinant BMP6 adenoviral vectors in immunocompetent animals.

  10. Environmental assessment of two different crop systems in terms of biomethane potential production

    Energy Technology Data Exchange (ETDEWEB)

    Bacenetti, Jacopo; Fusi, Alessandra, E-mail: alessandra.fusi@unimi.it; Negri, Marco; Guidetti, Riccardo; Fiala, Marco

    2014-01-01

    The interest in renewable energy sources has gained great importance in Europe due to the need to reduce fossil energy consumption and greenhouse gas emissions, as required by the Renewable Energy Directive (RED) of the European Parliament. The production of energy from energy crops appears to be consistent with RED. The environmental impact related to this kind of energy primarily originates from crop cultivation. This research aimed to evaluate the environmental impact of different crop systems for biomass production: single and double crop. The environmental performances of maize and maize plus wheat were assessed from a life cycle perspective. Two alternative scenarios considering different yields, crop management, and climatic conditions, were also addressed. One normal cubic metre of potential methane was chosen as a functional unit. Methane potential production data were obtained through lab experimental tests. For both of the crop systems, the factors that have the greatest influence on the overall environmental burden are: fertilizer emissions, diesel fuel emissions, diesel fuel production, and pesticide production. Notwithstanding the greater level of methane potential production, the double crop system appears to have the worse environmental performance with respect to its single crop counterpart. This result is due to the bigger quantity of inputs needed for the double crop system. Therefore, the greater amount of biomass (silage) obtained through the double crop system is less than proportional to the environmental burden that results from the bigger quantity of inputs requested for double crop. - Highlights: • Environmental impact of two crop systems was evaluated • Biomethane specific production tests were carried out • Alternative scenarios (different yields and crop management) were assessed • Maize single crop obtains the better environmental performance • Critical factors are: fertilizer and diesel fuel emissions and diesel fuel

  11. Environmental assessment of two different crop systems in terms of biomethane potential production

    International Nuclear Information System (INIS)

    The interest in renewable energy sources has gained great importance in Europe due to the need to reduce fossil energy consumption and greenhouse gas emissions, as required by the Renewable Energy Directive (RED) of the European Parliament. The production of energy from energy crops appears to be consistent with RED. The environmental impact related to this kind of energy primarily originates from crop cultivation. This research aimed to evaluate the environmental impact of different crop systems for biomass production: single and double crop. The environmental performances of maize and maize plus wheat were assessed from a life cycle perspective. Two alternative scenarios considering different yields, crop management, and climatic conditions, were also addressed. One normal cubic metre of potential methane was chosen as a functional unit. Methane potential production data were obtained through lab experimental tests. For both of the crop systems, the factors that have the greatest influence on the overall environmental burden are: fertilizer emissions, diesel fuel emissions, diesel fuel production, and pesticide production. Notwithstanding the greater level of methane potential production, the double crop system appears to have the worse environmental performance with respect to its single crop counterpart. This result is due to the bigger quantity of inputs needed for the double crop system. Therefore, the greater amount of biomass (silage) obtained through the double crop system is less than proportional to the environmental burden that results from the bigger quantity of inputs requested for double crop. - Highlights: • Environmental impact of two crop systems was evaluated • Biomethane specific production tests were carried out • Alternative scenarios (different yields and crop management) were assessed • Maize single crop obtains the better environmental performance • Critical factors are: fertilizer and diesel fuel emissions and diesel fuel

  12. Biomethane technology

    OpenAIRE

    Ogejo, Jactone Arogo; Wen, Zhiyou; Ignosh, John; Bendfeldt, Eric S.; Collins, Eldridge, 1940-

    2009-01-01

    This publication provides a general overview of anaerobic digestion and the current status of biomethane technology on livestock farms in the United States. It is part of the Bioenergy Engineering Education Program (BEEP) of the Biological Systems Engineering Department at Virginia Tech. Most of the discussion uses dairy manure as an example of feedstock for an anaerobic digester.

  13. Inhibition of Histone Deacetylases Potentiates BMP9-Induced Osteogenic Signaling in Mouse Mesenchymal Stem Cells

    Directory of Open Access Journals (Sweden)

    Ning Hu

    2013-08-01

    Full Text Available Background/Aims: We have demonstrated that bone morphogenetic protein 9 (BMP9 is one of the most potent BMPs in regulating osteoblast differentiation of mesenchymal stem cells (MSCs although the molecular mechanism underlying BMP9-induced osteogenesis remains to be fully elucidated. It is known that epigenetic regulations play an important role in regulating the stem cell potency and lineage commitment. Here, we investigate if the inhibition of histone deacetylases (Hdacs affects BMP9-induced osteogenic differentiation of MSCs. Methods: Using the Hdac inhibitor trichostatin A (TSA, we assess that TSA enhances BMP9-mediated osteogenic markers and matrix mineralization in MSCs, and bone formation in mouse embryonic limb explants. Results: We find that the endogenous expression of most of the 11 Hdacs is readily detectable in MSCs. BMP9 is shown to induce most Hdacs in MSCs. We demonstrate that TSA potentiates BMP9-induced early osteogenic marker alkaline phosphatase (ALP activity in MSCs, as well as late osteogenic markers osteopontin (OPN and osteocalcin (OCN and matrix mineralization. Fetal limb explant culture studies reveal that TSA potentiates BMP9-induced endochondral bone formation, possibly by expanding hypertrophic chondrocyte zone of growth plate. Conclusion: Our findings strongly suggest histone deacetylases may play an important role in fine-tuning BMP9-mediated osteogenic signaling through a negative feedback network in MSCs. Thus, Hdac inhibitors may be used as novel therapeutics for bone fracture healing.

  14. Biomethane obtained from micro-algae. Assessment of the production potential in France by 2020 and 2050. Final report - February 2013. Study performed on behalf of GrDF by the GDF SUEZ's CRIGEN

    International Nuclear Information System (INIS)

    After a presentation of the technical aspects of microalgae processing, and comments on its integration within third-generation biomethane production sector, the authors describe the methodological framework of their study: scope and identification of economic sectors potentially in charge of 3. generation biomethane production, characterization of technological scenarios and technical hypotheses, aggregation and sensitivity analysis on the biomethane production potential. Results are commented in terms of potential of deployment of the microalgae technology within each identified sector, of production of third-generation biomethane by the identified sectors, and of third-generation biomethane production by 2020 and by 2050. Appendices notably give examples of microalgae production technologies, and give sheets of analysis of the potential of implementation of microalgae technologies for different sectors: chemistry-refinery-petro chemistry, agro-food industries, paper, rubber, textile, plastics engineering, metallurgy, materials, farming, crops, thermal power stations, gas infrastructures, etc.

  15. State of the art and potential of biomethane vehicle fuel Joint study by ADEME, AFGNV, ATEE Club Biogaz, GDF SUEZ, IFP, MEEDDAT

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2008-11-15

    This document presents approaches to producing biomethane vehicle fuel and the resources involved. The potential of each type of resource and the production costs are described in this report. Lastly, the contribution of this gaseous biofuel to reducing greenhouse gas emissions is evaluated. (author)

  16. State of the art and potential of biomethane vehicle fuel Joint study by ADEME, AFGNV, ATEE Club Biogaz, GDF SUEZ, IFP, MEEDDAT

    International Nuclear Information System (INIS)

    This document presents approaches to producing biomethane vehicle fuel and the resources involved. The potential of each type of resource and the production costs are described in this report. Lastly, the contribution of this gaseous biofuel to reducing greenhouse gas emissions is evaluated. (author)

  17. The effect of storage conditions on microbial community composition and biomethane potential in a biogas starter culture.

    Science.gov (United States)

    Hagen, Live Heldal; Vivekanand, Vivekanand; Pope, Phillip B; Eijsink, Vincent G H; Horn, Svein J

    2015-07-01

    A new biogas process is initiated by adding a microbial community, typically in the form of a sample collected from a functional biogas plant. This inoculum has considerable impact on the initial performance of a biogas reactor, affecting parameters such as stability, biogas production yields and the overall efficiency of the anaerobic digestion process. In this study, we have analyzed changes in the microbial composition and performance of an inoculum during storage using barcoded pyrosequencing of bacterial and archaeal 16S ribosomal RNA (rRNA) genes, and determination of the biomethane potential, respectively. The inoculum was stored at room temperature, 4 and -20 °C for up to 11 months and cellulose was used as a standard substrate to test the biomethane potential. Storage up to 1 month resulted in similar final methane yields, but the rate of methane production was reduced by storage at -20 °C. Longer storage times resulted in reduced methane yields and slower production kinetics for all storage conditions, with room temperature and frozen samples consistently giving the best and worst performance, respectively. Both storage time and temperature affected the microbial community composition and methanogenic activity. In particular, fluctuations in the relative abundance of Bacteroidetes were observed. Interestingly, a shift from hydrogenotrophic methanogens to methanogens with the capacity to perform acetoclastic methanogensis was observed upon prolonged storage. In conclusion, this study suggests that biogas inocula may be stored up to 1 month with low loss of methanogenic activity, and identifies bacterial and archaeal species that are affected by the storage. PMID:25947246

  18. The effect of storage conditions on microbial community composition and biomethane potential in a biogas starter culture.

    Science.gov (United States)

    Hagen, Live Heldal; Vivekanand, Vivekanand; Pope, Phillip B; Eijsink, Vincent G H; Horn, Svein J

    2015-07-01

    A new biogas process is initiated by adding a microbial community, typically in the form of a sample collected from a functional biogas plant. This inoculum has considerable impact on the initial performance of a biogas reactor, affecting parameters such as stability, biogas production yields and the overall efficiency of the anaerobic digestion process. In this study, we have analyzed changes in the microbial composition and performance of an inoculum during storage using barcoded pyrosequencing of bacterial and archaeal 16S ribosomal RNA (rRNA) genes, and determination of the biomethane potential, respectively. The inoculum was stored at room temperature, 4 and -20 °C for up to 11 months and cellulose was used as a standard substrate to test the biomethane potential. Storage up to 1 month resulted in similar final methane yields, but the rate of methane production was reduced by storage at -20 °C. Longer storage times resulted in reduced methane yields and slower production kinetics for all storage conditions, with room temperature and frozen samples consistently giving the best and worst performance, respectively. Both storage time and temperature affected the microbial community composition and methanogenic activity. In particular, fluctuations in the relative abundance of Bacteroidetes were observed. Interestingly, a shift from hydrogenotrophic methanogens to methanogens with the capacity to perform acetoclastic methanogensis was observed upon prolonged storage. In conclusion, this study suggests that biogas inocula may be stored up to 1 month with low loss of methanogenic activity, and identifies bacterial and archaeal species that are affected by the storage.

  19. Comparison of osteogenic potentials of human rat BMP4 and BMP6 gene therapy using [E1-] and [E1-,E2b-] adenoviral vectors

    OpenAIRE

    Li, Hongwei; Li, Jin Zhong; D. Pittman, Debra; Amalfitano, Andy; Hankins, Gerald R.; Helm, Gregory A.

    2006-01-01

    Osteogenic potentials of some recombinant human bone morphogenetic protein (BMP) first-generation adenoviral vectors (ADhBMPs) are significantly limited in immunocompetent animals. It is unclear what role expression of viral proteins and foreign proteins transduced by adenoviral vectors play in the host immune response and in ectopic bone formation. In this study two sets of experiments were designed and performed. First, rat BMP6 cDNA were amplified, sequenced, and recombined in first-genera...

  20. Early assessment of a rapid alternative method for the estimation of the biomethane potential of sewage sludge.

    Science.gov (United States)

    Bellaton, Solenn; Guérin, Sabrina; Pautremat, Nathalie; Bernier, Jean; Muller, Mathieu; Motellet, Stéphane; Azimi, Sam; Pauss, André; Rocher, Vincent

    2016-04-01

    This short communication briefly presents a rapid method using a fluorescent redox indicator, similar to resazurin, in order to estimate the biodegradability of sewage sludge during anaerobic digestion (AD). The biodegradability and by extension the Biochemical Methane Potential (BMP) of nineteen municipal sludge samples (primary, biological and tertiary) were investigated and estimated in only 48 h. Results showed the relevance to follow the metabolic activity of anaerobic sludge by the kinetic of probe reduction. The extended lag phase of inoculum indicated an impact of pre-treatments on enzyme activity. The comparison with Automatic Methane Potential Test System II (AMPTS) confirmed the estimated values of BMP according to an uncertainty limit of 25%. These first results highlight the interest of this rapid assay as a preliminary tool of the biodegradability of sewage sludge in anaerobic digestion. PMID:26869069

  1. Modelling a demand driven biogas system for production of electricity at peak demand and for production of biomethane at other times.

    Science.gov (United States)

    O'Shea, R; Wall, D; Murphy, J D

    2016-09-01

    Four feedstocks were assessed for use in a demand driven biogas system. Biomethane potential (BMP) assays were conducted for grass silage, food waste, Laminaria digitata and dairy cow slurry. Semi-continuous trials were undertaken for all feedstocks, assessing biogas and biomethane production. Three kinetic models of the semi-continuous trials were compared. A first order model most accurately correlated with gas production in the pulse fed semi-continuous system. This model was developed for production of electricity on demand, and biomethane upgrading. The model examined a theoretical grass silage digester that would produce 435kWe in a continuous fed system. Adaptation to demand driven biogas required 187min to produce sufficient methane to run a 2MWe combined heat and power (CHP) unit for 60min. The upgrading system was dispatched 71min following CHP shutdown. Of the biogas produced 21% was used in the CHP and 79% was used in the upgrading system. PMID:27240240

  2. Effect of ultrasonic pretreatment on biomethane potential of two-phase olive mill solid waste: kinetic approach and process performance.

    Science.gov (United States)

    Rincón, B; Bujalance, L; Fermoso, F G; Martín, A; Borja, R

    2014-01-01

    The effect of ultrasound (US) pretreatment on two-phase olive mil solid waste (OMSW) composition and subsequent anaerobic biodegradation was evaluated by chemical oxygen demand solubilization and biochemical methane potential (BMP) tests. OMSW was ultrasonically pretreated at a power of 200 W and frequency of 24 kHz for time periods of 20, 40, 60, 90, 120, and 180 minutes, corresponding to specific energies of 11367, 21121, 34072, 51284, 68557, and 106003 kJ/kg total solids, respectively. In order to evaluate the US pretreatment, a low, medium, and high exposure time, that is, 20, 90, and 180 min, were selected for BMP tests. Methane yields of 311 ± 15, 393 ± 14, and 370 ± 20 mL CH₄/g VSadded (VS: volatile solids) were obtained for 20, 90, and 180 minutes, respectively, while the untreated OMSW gave 373 ± 4 mL CH₄/g VSadded. From a kinetic point of view, the BMP tests showed a first exponential stage and a second sigmoidal stage. In the first stage, the kinetic constant obtained for US pretreated OMSW at 20 minutes was 46% higher than those achieved for the pretreated OMSW at 90 and 180 minutes and 48% higher than that for untreated OMSW. The maximum methane production rate achieved was 12% higher than that obtained for untreated OMSW.

  3. Effect of Ultrasonic Pretreatment on Biomethane Potential of Two-Phase Olive Mill Solid Waste: Kinetic Approach and Process Performance

    Directory of Open Access Journals (Sweden)

    B. Rincón

    2014-01-01

    Full Text Available The effect of ultrasound (US pretreatment on two-phase olive mil solid waste (OMSW composition and subsequent anaerobic biodegradation was evaluated by chemical oxygen demand solubilization and biochemical methane potential (BMP tests. OMSW was ultrasonically pretreated at a power of 200 W and frequency of 24 kHz for time periods of 20, 40, 60, 90, 120, and 180 minutes, corresponding to specific energies of 11367, 21121, 34072, 51284, 68557, and 106003 kJ/kg total solids, respectively. In order to evaluate the US pretreatment, a low, medium, and high exposure time, that is, 20, 90, and 180 min, were selected for BMP tests. Methane yields of 311±15, 393±14, and 370±20 mL CH4/g VSadded (VS: volatile solids were obtained for 20, 90, and 180 minutes, respectively, while the untreated OMSW gave 373±4 mL CH4/g VSadded. From a kinetic point of view, the BMP tests showed a first exponential stage and a second sigmoidal stage. In the first stage, the kinetic constant obtained for US pretreated OMSW at 20 minutes was 46% higher than those achieved for the pretreated OMSW at 90 and 180 minutes and 48% higher than that for untreated OMSW. The maximum methane production rate achieved was 12% higher than that obtained for untreated OMSW.

  4. Effect of Ultrasonic Pretreatment on Biomethane Potential of Two-Phase Olive Mill Solid Waste: Kinetic Approach and Process Performance

    Science.gov (United States)

    Rincón, B.; Bujalance, L.; Fermoso, F. G.; Martín, A.

    2014-01-01

    The effect of ultrasound (US) pretreatment on two-phase olive mil solid waste (OMSW) composition and subsequent anaerobic biodegradation was evaluated by chemical oxygen demand solubilization and biochemical methane potential (BMP) tests. OMSW was ultrasonically pretreated at a power of 200 W and frequency of 24 kHz for time periods of 20, 40, 60, 90, 120, and 180 minutes, corresponding to specific energies of 11367, 21121, 34072, 51284, 68557, and 106003 kJ/kg total solids, respectively. In order to evaluate the US pretreatment, a low, medium, and high exposure time, that is, 20, 90, and 180 min, were selected for BMP tests. Methane yields of 311 ± 15, 393 ± 14, and 370 ± 20 mL CH4/g VSadded (VS: volatile solids) were obtained for 20, 90, and 180 minutes, respectively, while the untreated OMSW gave 373 ± 4 mL CH4/g VSadded. From a kinetic point of view, the BMP tests showed a first exponential stage and a second sigmoidal stage. In the first stage, the kinetic constant obtained for US pretreated OMSW at 20 minutes was 46% higher than those achieved for the pretreated OMSW at 90 and 180 minutes and 48% higher than that for untreated OMSW. The maximum methane production rate achieved was 12% higher than that obtained for untreated OMSW. PMID:25197705

  5. Evaluation and modeling of biochemical methane potential (BMP) of landfilled solid waste: a pilot scale study

    DEFF Research Database (Denmark)

    Bilgili, M Sinan; Demir, Ahmet; Varank, Gamze

    2009-01-01

    The main goal of this study was to present a comparison of landfill performance with respect to solids decomposition. Biochemical methane potential (BMP) test was used to determine the initial and the remaining CH(4) potentials of solid wastes during 27 months of landfilling operation in two pilot...

  6. Statistical prediction of biomethane potentials based on the composition of lignocellulosic biomass

    DEFF Research Database (Denmark)

    Thomsen, Sune Tjalfe; Spliid, Henrik; Østergård, Hanne

    2014-01-01

    linear and quadratic mixture models. The full model to predict BMP (R2>0.96), including the four biomass components cellulose (xC), hemicellulose (xH), lignin (xL) and residuals (xR=1-xC-xH-xL) had highly significant regression coefficients. It was possible to reduce the model without substantially...... affecting the quality of the prediction, as the regression coefficients for xC, xH and xR were not significantly different based on the dataset. The model was extended with an effect of different methods of analysing the biomass constituents content (DA) which had a significant impact. In conclusion...

  7. Effect of Ultrasonic Pretreatment on Biomethane Potential of Two-Phase Olive Mill Solid Waste: Kinetic Approach and Process Performance

    OpenAIRE

    B. Rincón; Bujalance, L.; Fermoso, F.G.; Martín, A.; R. Borja

    2014-01-01

    © 2014 B. Rincón et al. The effect of ultrasound (US) pretreatment on two-phase olive mil solid waste (OMSW) composition and subsequent anaerobic biodegradation was evaluated by chemical oxygen demand solubilization and biochemical methane potential (BMP) tests. OMSW was ultrasonically pretreated at a power of 200 W and frequency of 24 kHz for time periods of 20, 40, 60, 90, 120, and 180 minutes, corresponding to specific energies of 11367, 21121, 34072, 51284, 68557, and 106003 kJ/kg total s...

  8. Thermo-Acidic Pretreatment of Beach Macroalgae from Rügen to Optimize Biomethane Production—Double Benefit with Simultaneous Bioenergy Production and Improvement of Local Beach and Waste Management

    OpenAIRE

    Yann Nicolas Barbot; Laurenz Thomsen; Roland Benz

    2015-01-01

    Eutrophication is a phenomenon which can rapidly generate masses of marine macroalgae, particularly in areas with high nutrient pollution. Washed ashore, this biomass impairs coastal tourism and negatively affects the coastal ecosystem. The present study evaluates the biochemical methane potential (BMP) of a macroalgae mix (Rügen-Mix, RM (RM = Rügen-Mix)) originating from Rügen, Germany. To improve biomethane recovery, thermo-acidic pretreatment was applied to the biomass prior to biomethanat...

  9. Towards eliminating systematic errors caused by the experimental conditions in Biochemical Methane Potential (BMP) tests

    Energy Technology Data Exchange (ETDEWEB)

    Strömberg, Sten, E-mail: sten.stromberg@biotek.lu.se [Department of Biotechnology, Lund University, Getingevägen 60, 221 00 Lund (Sweden); Nistor, Mihaela, E-mail: mn@bioprocesscontrol.com [Bioprocess Control, Scheelevägen 22, 223 63 Lund (Sweden); Liu, Jing, E-mail: jing.liu@biotek.lu.se [Department of Biotechnology, Lund University, Getingevägen 60, 221 00 Lund (Sweden); Bioprocess Control, Scheelevägen 22, 223 63 Lund (Sweden)

    2014-11-15

    Highlights: • The evaluated factors introduce significant systematic errors (10–38%) in BMP tests. • Ambient temperature (T) has the most substantial impact (∼10%) at low altitude. • Ambient pressure (p) has the most substantial impact (∼68%) at high altitude. • Continuous monitoring of T and p is not necessary for kinetic calculations. - Abstract: The Biochemical Methane Potential (BMP) test is increasingly recognised as a tool for selecting and pricing biomass material for production of biogas. However, the results for the same substrate often differ between laboratories and much work to standardise such tests is still needed. In the current study, the effects from four environmental factors (i.e. ambient temperature and pressure, water vapour content and initial gas composition of the reactor headspace) on the degradation kinetics and the determined methane potential were evaluated with a 2{sup 4} full factorial design. Four substrates, with different biodegradation profiles, were investigated and the ambient temperature was found to be the most significant contributor to errors in the methane potential. Concerning the kinetics of the process, the environmental factors’ impact on the calculated rate constants was negligible. The impact of the environmental factors on the kinetic parameters and methane potential from performing a BMP test at different geographical locations around the world was simulated by adjusting the data according to the ambient temperature and pressure of some chosen model sites. The largest effect on the methane potential was registered from tests performed at high altitudes due to a low ambient pressure. The results from this study illustrate the importance of considering the environmental factors’ influence on volumetric gas measurement in BMP tests. This is essential to achieve trustworthy and standardised results that can be used by researchers and end users from all over the world.

  10. Evaluating the biochemical methane potential (BMP) of low-organic waste at Danish landfills

    DEFF Research Database (Denmark)

    Mou, Zishen; Scheutz, Charlotte; Kjeldsen, Peter

    2014-01-01

    The biochemical methane potential (BMP) is an essential parameter when using first order decay (FOD) landfill gas (LFG) generation models to estimate methane (CH4) generation from landfills. Different categories of waste (mixed, shredder and sludge waste) with a low-organic content and temporaril...... for the first time, which is important and valuable for using current FOD LFG generation models to estimate realistic CH4 emissions from modern landfills receiving low-organic waste.......The biochemical methane potential (BMP) is an essential parameter when using first order decay (FOD) landfill gas (LFG) generation models to estimate methane (CH4) generation from landfills. Different categories of waste (mixed, shredder and sludge waste) with a low-organic content and temporarily...... content (DOCC) was in the range of 0.44–0.70% of total weight (wet waste). Numeric values of both parameters were much lower than values of traditional municipal solid waste (MSW), as well as default numeric values in current FOD models. The sludge waste and temporarily stored combustible waste showed BMP...

  11. Characteristics and Stimulation Potential with BMP-2 and BMP-7 of Tenocyte-Like Cells Isolated from the Rotator Cuff of Female Donors

    Science.gov (United States)

    Klatte-Schulz, Franka; Pauly, Stephan; Scheibel, Markus; Greiner, Stefan; Gerhardt, Christian; Hartwig, Jelka; Schmidmaier, Gerhard; Wildemann, Britt

    2013-01-01

    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. PMID:23825642

  12. Characteristics and stimulation potential with BMP-2 and BMP-7 of tenocyte-like cells isolated from the rotator cuff of female donors.

    Directory of Open Access Journals (Sweden)

    Franka Klatte-Schulz

    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.

  13. Potential of wastewater-treating anaerobic granules for biomethanation of synthesis gas.

    Science.gov (United States)

    Guiot, Serge R; Cimpoia, Ruxandra; Carayon, Gaël

    2011-03-01

    Gasification of biomass produces a mixture of gas (mainly carbon monoxide (CO), carbon dioxide (CO(2)), and hydrogen (H(2))) called synthesis gas, or syngas, by thermal degradation without combustion. Syngas can be used for heat or electricity production by thermochemical processes. This project aims at developing an alternative way to bioupgrade syngas into biogas (mainly methane), via anaerobic fermentation. Nonacclimated industrial granular sludge to be used as reactor inoculum was initially evaluated for mesophilic carboxydotrophic methanogenesis potential in batch tests at 4 and 8 mmol CO/g VSS.d, in the absence and presence of H(2) and CO(2), respectively. Granular sludge was then introduced into a 30 L gas-lift reactor and supplied with CO, to study the production of methane and other metabolites, at different gas dilutions as well as feeding and recirculation rates. A maximal CO conversion efficiency of 75%, which was gas-liquid mass transfer limited, occurred at a CO partial pressure of 0.6 atm combined with a gas recirculation ratio of 20:1. The anaerobic granule potential for methanogenesis from CO was likely hydrogenotrophic, combined with CO-dependent H(2) formation, either under mesophilic or thermophilic conditions. Thermophilic conditions provide the anaerobic granules with a CO-bioconversion potential significantly larger (5-fold) than under mesophilic conditions, so long as the gas-liquid transfer is alleviated.

  14. Enhanced biomethane potential from wheat straw by low temperature alkaline calcium hydroxide pre-treatment.

    Science.gov (United States)

    Reilly, Matthew; Dinsdale, Richard; Guwy, Alan

    2015-08-01

    A factorially designed experiment to examine the effectiveness of Ca(OH)2 pre-treatment, enzyme addition and particle size, on the mesophilic (35 °C) anaerobic digestion of wheat straw was conducted. Experiments used a 48 h pre-treatment with Ca(OH)2 7.4% (w/w), addition of Accellerase®-1500, with four particle sizes of wheat straw (1.25, 2, 3 and 10mm) and three digestion time periods (5, 15 and 30 days). By combining particle size reduction and Ca(OH)2 pre-treatment, the average methane potential was increased by 315% (from 48 NmL-CH4 g-VS(-1) to 202 NmL-CH4 g-VS(-1)) after 5 days of anaerobic digestion compared to the control. Enzyme addition or Ca(OH)2 pre-treatment with 3, 2 and 1.25 mm particle sizes had 30-day batch yields of between 301 and 335 NmL-CH4 g-VS(-1). Alkali pre-treatment of 3mm straw was shown to have the most potential as a cost effective pre-treatment and achieved 290 NmL-CH4 g-VS(-1), after only 15 days of digestion. PMID:25898087

  15. Potential CO2 savings through biomethane generation from municipal waste biogas

    International Nuclear Information System (INIS)

    An alternative source of methane that can also reduce the greenhouse gas effect is one that comes from the upgrading of biogas. This paper studies eight technologies through life cycle assessment (LCA). Six of the technologies are ones that are already on the market and the two others are novel technologies that use carbon mineralization to store CO2 upon their removal. The two novel technologies include alkaline with regeneration (AwR) and bottom ash upgrading (BABIU). These technologies use waste rich in calcium, from municipal solid waste incinerators (MSWI), to store the CO2 from biogas. Among all conventional technologies, high pressure water scrubbing and chemical scrubbing with amine had the lowest CO2 impacts. Of the novel technologies BABIU saves 10% more CO2 than AwR. An uncertainty analysis and a material flow analysis demonstrated that proximity to a MSWI is an important factor to consider. As well, it was seen that while the technology is promising it cannot be applied to an entire country if the proper infrastructure is not in place. - Highlights: • The CO2 savings of using CO2 capture technologies in biogas upgrading was studied. • 6 marketed and 2 novel technologies were studied using LCA. • A novel carbon mineralization process has the highest CO2 savings. • Limited waste management infrastructure can hinder the potential CO2 savings

  16. Influence of composition on the biomethanation potential of restaurant waste at mesophilic temperatures.

    Science.gov (United States)

    Neves, L; Gonçalo, E; Oliveira, R; Alves, M M

    2008-01-01

    A synthetic waste was used to study the effect of waste composition on anaerobic degradation of restaurant waste. It was made by blending melted pork lard, white cabbage, chicken breast, and potato flakes, to simulate lipids, cellulose, protein, and carbohydrates, respectively. Four blends of the four constituents with an excess of each component were assayed and compared with a fifth blend containing an equal amount of chemical oxygen demand (COD) of each of the four components. The methane production and the time course of soluble COD and volatile fatty acids were assessed in batch assays. A high reduction of volatile solids (between 94% and 99.6%) was obtained in all the assays. The methane yield was between 0.40 m(3) CH(4)/kg VS(initial) (excess of carbohydrates) and 0.49 m(3) CH(4)/kg VS(initial) (excess of lipids). The degradation of the lipid-rich assays differed from the others. Fifty percent of the biochemical methane potential was obtained after 3-6 days for all of the assays, except for the one with excess of lipids which achieved 50% methanation only after 14.7 days of incubation. In the assay with excess of lipids, a considerable fraction of COD remained in the liquid phase, suggesting an inhibition of the methanogenic process that was likely due to the accumulation of long chain fatty acids. The hydrolysis rate constants, assuming first order kinetics, over the first 6 days were between 0.12d(-1) (excess of lipids) and 0.32 d(-1) (excess of carbohydrates). The results indicate that anaerobic digestion facilities with large variations in lipid input could have significant changes in process performance that merit further examination. PMID:17601723

  17. Characterisation of the biochemical methane potential (BMP) of individual material fractions in Danish source-separated organic household waste

    DEFF Research Database (Denmark)

    Naroznova, Irina; Møller, Jacob; Scheutz, Charlotte

    2016-01-01

    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 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...

  18. Potential development of compressed bio-methane gas production from pig farms and elephant grass silage for transportation in Thailand.

    Science.gov (United States)

    Dussadee, Natthawud; Reansuwan, Kamoldara; Ramaraj, Rameshprabu

    2014-03-01

    This research project evaluated biogas production using anaerobic co-digestion of pig manure and elephant grass silage in large scale to delivered transportation directly for cars. Anaerobic co-digestion was estimated in three full-scale continuously stirred tank reactors (CSTRs) at 40°C. In the form of compressed bio-methane gas (CBG) production was 14,400m(3)/day (CH4 60-70%) amount of CBG was 9600m(3)/day. The procedure was enhanced by using molecular sieve, activated carbon for removal of moisture and CO2 membrane H2S and CO2 respectively. The results were demonstrated the amount of CO2, H2S gas was reduced along with CH4 was improved up to 90% by volume and compressed to 250bar tank pressure gauge to the fuel for cars. The CBG production, methane gas improvement and performance were evaluated before entering the delivered systems according to the energy standards. The production of CBG is advantageous to strengthen the Thailand biogas market.

  19. Modelling and control of biomethanization for energy production

    OpenAIRE

    Hess, Jonathan

    2007-01-01

    Anaerobic digestion involves a complex ecosystem that progressively degrades the organic matter into carbon dioxide and (bio)methane. The biomethane is an highly energetic environmental friendly biofuel which can replace natural gas in the perspective of sustainable development. However biogas is still valorised below its potential. This is mainly due to a lack of dedicated methods that would ensure the anaerobic plant durability and the stability of the biogas composition. Two approaches are...

  20. Biomethane to Natural Gas Grid Injection : A Technological Innovation System Analysis

    OpenAIRE

    Singhal, Ankit

    2012-01-01

    Biomethane (upgraded form of biogas) holds unlocked potential as a substitute to fossil natural gas, in terms of achieving climate reduction targets as well as developing a locally secured fuel supply. Biomethane is fully compatible with the existing natural gas grid infrastructure. Currently, nine countries in European Union are practicing natural gas grid injection. Remaining countries are in various phases of development concerning production and utilisation of biomethane. Successful deplo...

  1. Evaluation of anaerobic co-digestion of dairy manure with food wastes via bio-methane potential assay and CSTR reactor.

    Science.gov (United States)

    Ye, Yulin; Zamalloa, Carlos; Lin, Hongjian; Yan, Mi; Schmidt, David; Hu, Bo

    2015-01-01

    The introduction of food wastes into anaerobic digestion (AD) brings a promising scenario of increasing feedstock availability and overall energy production from AD. This study evaluated the biodegradability and methane potential from co-digestion of two typical food wastes, kitchen waste and chicken fat, with dairy manure. For single substrate, the bio-methane potential assays showed that kitchen waste had the highest methane yield of 352 L-CH4 kg(-1)-VS added, 92% more than dairy manure alone. Chicken fat at the same Volatile Solid (VS) level (2 g L(-1)) inhibited bio-methane production. Addition of kitchen waste and chicken fat to a VS percentage of up to 40% improved overall methane yield by 44% and 34%, respectively. Synergistic effect was observed when either combining two or three substrates as AD feedstock, possibly as a result of increased biodegradability of organic materials in chicken fat and kitchen waste compared with dairy manure. Addition of chicken fat improved methane yield more than kitchen waste. However, addition of chicken fat VS over 0.8 g L(-1) should be cautiously done because it may cause reactor failure due to decrease in pH. The maximum methane yield was 425 L-CH4 kg(-1)-VS, achieved at a VS ratio of 2:2:1 for kitchen waste, chicken fat, and dairy manure. Results from batch AD experiment demonstrated that supplementing dairy manure to chicken fat and/or kitchen waste improved alkalinity of substrate due to the inclusion of more titratable bases in dairy manure, and therefore stabilized the methanogenesis and substantially improved biogas yield. A mixture of substrates of kitchen waste, chicken fat, and dairy manure at a ratio of 1:1:3 was fed to a continuously stirred tank reactor operated at organic loading rates of 3.28, 6.55, and 2.18 g-COD L(-1)-day (hydraulic retention time of 20, 10, and 30 days, respectively) under mesophilic condition, and methane production rate reached 0.65, 0.95, and 0.34 L-CH4 L(-1)-reactor-day.

  2. Enhancement of the Regenerative Potential of Anorganic Bovine Bone Graft Utilizing a Polyglutamate-Modified BMP2 Peptide with Improved Binding to Calcium-Containing Materials.

    Science.gov (United States)

    Bain, Jennifer L; Bonvallet, Paul P; Abou-Arraj, Ramzi V; Schupbach, Peter; Reddy, Michael S; Bellis, Susan L

    2015-09-01

    Autogenous bone is the gold standard material for bone grafting in craniofacial and orthopedic regenerative medicine. However, due to complications associated with harvesting donor bone, clinicians often use commercial graft materials that may lose their osteoinductivity due to processing. This study was aimed to functionalize one of these materials, anorganic bovine bone (ABB), with osteoinductive peptides to enhance regenerative capacity. Two peptides known to induce osteoblastic differentiation of mesenchymal stem cells were evaluated: (1) DGEA, an amino acid motif within collagen I and (2) a biomimetic peptide derived from bone morphogenic protein 2 (BMP2pep). To achieve directed coupling of the peptides to the graft surface, the peptides were engineered with a heptaglutamate domain (E7), which confers specific binding to calcium moieties within bone mineral. Peptides with the E7 domain exhibited greater anchoring to ABB than unmodified peptides, and E7 peptides were retained on ABB for at least 8 weeks in vivo. To assess the osteoinductive potential of the peptide-conjugated ABB, ectopic bone formation was evaluated utilizing a rat subcutaneous pouch model. ABB conjugated with full-length recombinant BMP2 (rBMP2) was also implanted as a model for current clinical treatments utilizing rBMP2 passively adsorbed to carriers. These studies showed that E7BMP2pep/ABB samples induced more new bone formation than all other peptides, and an equivalent amount of new bone as compared with rBMP2/ABB. A mandibular defect model was also used to examine intrabony healing of peptide-conjugated ABB. Bone healing was monitored at varying time points by positron emission tomography imaging with (18)F-NaF, and it was found that the E7BMP2pep/ABB group had greater bone metabolic activity than all other groups, including rBMP2/ABB. Importantly, animals implanted with rBMP2/ABB exhibited complications, including inflammation and formation of cataract-like lesions in the eye, whereas

  3. Experimental and computational investigation of the effect of hydrophobicity on aggregation and osteoinductive potential of BMP-2-derived peptide in a hydrogel matrix.

    Science.gov (United States)

    Moeinzadeh, Seyedsina; Barati, Danial; Sarvestani, Samaneh K; Karimi, Tahereh; Jabbari, Esmaiel

    2015-01-01

    An attractive approach to reduce the undesired side effects of bone morphogenetic proteins (BMPs) in regenerative medicine is to use osteoinductive peptide sequences derived from BMPs. Although the structure and function of BMPs have been studied extensively, there is limited data on structure and activity of BMP-derived peptides immobilized in hydrogels. The objective of this work was to investigate the effect of concentration and hydrophobicity of the BMP-2 peptide, corresponding to residues 73-92 of the knuckle epitope of BMP-2 protein, on peptide aggregation and osteogenic differentiation of human mesenchymal stem cells encapsulated in a polyethylene glycol (PEG) hydrogel. The peptide hydrophobicity was varied by capping PEG chain ends with short lactide segments. The BMP-2 peptide with a positive index of hydrophobicity had a critical micelle concentration (CMC) and formed aggregates in aqueous solution. Based on simulation results, there was a slight increase in the concentration of free peptide in solution with 1000-fold increase in peptide concentration. The dose-osteogenic response curve of the BMP-2 peptide was in the 0.0005-0.005 mM range, and osteoinductive potential of the BMP-2 peptide was significantly less than that of BMP-2 protein even at 1000-fold higher concentrations, which was attributed to peptide aggregation. Further, the peptide or PEG-peptide aggregates had significantly higher interaction energy with the cell membrane compared with the free peptide, which led to a higher nonspecific interaction with the cell membrane and loss of osteoinductive potential. Conjugation of the BMP-2 peptide to PEG increased CMC and osteoinductive potential of the peptide whereas conjugation to lactide-capped PEG reduced CMC and osteoinductive potential of the peptide. Experimental and simulation results revealed that osteoinductive potential of the BMP-2 peptide is correlated with its CMC and the free peptide concentration in aqueous medium and not the

  4. Experimental and computational investigation of the effect of hydrophobicity on aggregation and osteoinductive potential of BMP-2-derived peptide in a hydrogel matrix.

    Science.gov (United States)

    Moeinzadeh, Seyedsina; Barati, Danial; Sarvestani, Samaneh K; Karimi, Tahereh; Jabbari, Esmaiel

    2015-01-01

    An attractive approach to reduce the undesired side effects of bone morphogenetic proteins (BMPs) in regenerative medicine is to use osteoinductive peptide sequences derived from BMPs. Although the structure and function of BMPs have been studied extensively, there is limited data on structure and activity of BMP-derived peptides immobilized in hydrogels. The objective of this work was to investigate the effect of concentration and hydrophobicity of the BMP-2 peptide, corresponding to residues 73-92 of the knuckle epitope of BMP-2 protein, on peptide aggregation and osteogenic differentiation of human mesenchymal stem cells encapsulated in a polyethylene glycol (PEG) hydrogel. The peptide hydrophobicity was varied by capping PEG chain ends with short lactide segments. The BMP-2 peptide with a positive index of hydrophobicity had a critical micelle concentration (CMC) and formed aggregates in aqueous solution. Based on simulation results, there was a slight increase in the concentration of free peptide in solution with 1000-fold increase in peptide concentration. The dose-osteogenic response curve of the BMP-2 peptide was in the 0.0005-0.005 mM range, and osteoinductive potential of the BMP-2 peptide was significantly less than that of BMP-2 protein even at 1000-fold higher concentrations, which was attributed to peptide aggregation. Further, the peptide or PEG-peptide aggregates had significantly higher interaction energy with the cell membrane compared with the free peptide, which led to a higher nonspecific interaction with the cell membrane and loss of osteoinductive potential. Conjugation of the BMP-2 peptide to PEG increased CMC and osteoinductive potential of the peptide whereas conjugation to lactide-capped PEG reduced CMC and osteoinductive potential of the peptide. Experimental and simulation results revealed that osteoinductive potential of the BMP-2 peptide is correlated with its CMC and the free peptide concentration in aqueous medium and not the

  5. A role for BMP-induced homeobox gene MIXL1 in acute myelogenous leukemia and identification of type I BMP receptor as a potential target for therapy.

    Science.gov (United States)

    Raymond, Aaron; Liu, Bin; Liang, Hong; Wei, Caimiao; Guindani, Michele; Lu, Yue; Liang, Shoudan; St John, Lisa S; Molldrem, Jeff; Nagarajan, Lalitha

    2014-12-30

    Mesoderm Inducer in Xenopus Like1 (MIXL1), a paired-type homeobox transcription factor induced by TGF-β family of ligands is required for early embryonic specification of mesoderm and endoderm. Retrovirally transduced Mixl1 is reported to induce acute myelogenous leukemia (AML) with a high penetrance. But the mechanistic underpinnings of MIXL1 mediated leukemogenesis are unknown. Here, we establish the protooncogene c-REL to be a transcriptional target of MIXL1 by genome wide chromatin immune precipitation. Accordingly, expression of c-REL and its downstream targets BCL2L1 and BCL2A2 are elevated in MIXL1 expressing cells. Notably, MIXL1 regulates c-REL through a zinc finger binding motif, potentially by a MIXL1-Zinc finger protein transcriptional complex. Furthermore, MIXL1 expression is detected in the cancer genome atlas (TCGA) AML samples in a pattern mutually exclusive from that of HOXA9, CDX2 and HLX suggesting the existence of a core, yet distinct HOX transcriptional program. Finally, we demonstrate MIXL1 to be induced by BMP4 and not TGF-β in primary human hematopoietic stem and progenitor cells. Consequently, MIXL1 expressing AML cells are preferentially sensitive to the BMPR1 kinase inhibitor LDN-193189. These findings support the existence of a novel MIXL1-c REL mediated survival axis in AML that can be targeted by BMPR1 inhibitors. (MIXL1- human gene, Mixl1- mouse ortholog, MIXL1- protein). PMID:25544748

  6. Bio-methane obtained by gasification. Assessment of the production potential in France by 2020 and 2050. Final report - February 2013. Study performed on behalf of GrDF by the GDF SUEZ's CRIGEN

    International Nuclear Information System (INIS)

    This study aims at determining the bio-methane production potential by using so-called second-generation technologies in France in order to inject it into the natural gas network by 2020 or 2050. The second-generation production process is described: gasification, cleaning, methanation, compliance with specifications. Energetic and environmental performances of these processes are also addressed. Different biomass are considered (forest biomass, sawmill by-products, wood wastes, paper sludge, crops, energetic cops, agro-food industry by-products) within three prospective scenarios

  7. The impact of inocula carryover and inoculum dilution on the methane yields in batch methane potential tests.

    Science.gov (United States)

    Reilly, Matthew; Dinsdale, Richard; Guwy, Alan

    2016-05-01

    Batch studies are used to benchmark biohydrogen potential (BHP) and biomethane potential (BMP) yields from feed substrates, digestates residues and different process configurations. This study shows that BMP yields using cellulose can be biased positively by not diluting the initial sewage sludge inoculum and the bias is independent of starting inoculum volatile solids (VS) concentration. The carryover of BHP inoculum also increased the BMP yields when using cellulose as a substrate by up to 18.8%. Furthermore it was also observed that the dilution of BMP inoculum with deionised H2O reduced methane yields from cellulose by up to 132±26 N mL-CH4 g-VS(-1). Therefore it is proposed that inoculum and standard substrate controls (as used in this study) should be included in methane batch methodologies, particularly when using a pre-fermentation stage such as dark fermentation. PMID:26938808

  8. Gene delivery nanocarriers of bioactive glass with unique potential to load BMP2 plasmid DNA and to internalize into mesenchymal stem cells for osteogenesis and bone regeneration

    Science.gov (United States)

    Kim, Tae-Hyun; Singh, Rajendra K.; Kang, Min Sil; Kim, Joong-Hyun; Kim, Hae-Won

    2016-04-01

    The recent development of bioactive glasses with nanoscale morphologies has spurred their specific applications in bone regeneration, for example as drug and gene delivery carriers. Bone engineering with stem cells genetically modified with this unique class of nanocarriers thus holds great promise in this avenue. Here we report the potential of the bioactive glass nanoparticle (BGN) system for the gene delivery of mesenchymal stem cells (MSCs) targeting bone. The composition of 15% Ca-added silica, proven to be bone-bioactive, was formulated into surface aminated mesoporous nanospheres with enlarged pore sizes, to effectively load and deliver bone morphogenetic protein-2 (BMP2) plasmid DNA. The enlarged mesopores were highly effective in loading BMP2-pDNA with an efficiency as high as 3.5 wt% (pDNA w.r.t. BGN), a level more than twice than for small-sized mesopores. The BGN nanocarriers released the genetic molecules in a highly sustained manner (for as long as 2 weeks). The BMP2-pDNA/BGN complexes were effectively internalized to rat MSCs with a cell uptake level of ~73%, and the majority of cells were transfected to express the BMP2 protein. Subsequent osteogenesis of the transfected MSCs was demonstrated by the expression of bone-related genes, including bone sialoprotein, osteopontin, and osteocalcin. The MSCs transfected with BMP2-pDNA/BGN were locally delivered inside a collagen gel to the target calvarium defects. The results showed significantly improved bone regeneration, as evidenced by the micro-computed tomographic, histomorphometric and immunohistochemical analyses. This study supports the excellent capacity of the BGN system as a pDNA-delivery nanocarrier in MSCs, and the engineered system, BMP2-pDNA/BGN with MSCs, may be considered a new promising candidate to advance the therapeutic potential of stem cells through genetic modification, targeting bone defects and diseases.The recent development of bioactive glasses with nanoscale morphologies has

  9. Improving the osteogenic potential of BMP-2 with hyaluronic acid hydrogel modified with integrin-specific fibronectin fragment

    NARCIS (Netherlands)

    Kisiel, M.; Martino, M.M.; Ventura, M.; Hubbell, J.A.; Hilborn, J.; Ossipov, D.A.

    2013-01-01

    While human bone morphogenetic protein-2 (rhBMP-2) is a promising growth factor for bone regeneration, its clinical efficacy has recently shown to be below expectation. In order to improve the clinical translation of rhBMP-2, there exists strong motivation to engineer better delivery systems. Hyalur

  10. Feasibility study on combining anaerobic digestion and biomass gasification to increase the production of biomethane

    International Nuclear Information System (INIS)

    Highlights: • Anaerobic digestion and biomass gasification are integrated. • The novel concept can produce much more biomethane. • The novel concept can improve the exergy efficiency. • The novel concept demonstrates a big potential of income increase. - Abstract: There is a rapid growing interest in using biomethane as fuel for transport applications. A new concept is proposed to combine anaerobic digestion and biomass gasification to produce biomethane. H2 is separated from the syngas generated by biomass gasification in a membrane system, and then is used to upgrade raw biogas from anaerobic digestion. Simulations have been conducted based on the real operation data of one full scale biogas plant and one full scale biomass gasification plant in order to investigate the feasibility of the new concept. Results show that although less power and heat are generated compared to the gasification plant, which results in a lower overall efficiency, much more biomethane can be produced than the biogas plant; and the new concept can achieve a higher exergy efficiency. Due to the increasing price of biomethane, the novel concept demonstrates a big potential of income increase. For example, at a biomethane price of 12.74SEK/kg, the annual income can be increased by 5.3% compared to the total income of the biogas and gasification plant

  11. Manipulation of Fgf and Bmp signaling in teleost fishes suggests potential pathways for the evolutionary origin of multicuspid teeth.

    Science.gov (United States)

    Jackman, William R; Davies, Shelby H; Lyons, David B; Stauder, Caitlin K; Denton-Schneider, Benjamin R; Jowdry, Andrea; Aigler, Sharon R; Vogel, Scott A; Stock, David W

    2013-01-01

    Teeth with two or more cusps have arisen independently from an ancestral unicuspid condition in a variety of vertebrate lineages, including sharks, teleost fishes, amphibians, lizards, and mammals. One potential explanation for the repeated origins of multicuspid teeth is the existence of multiple adaptive pathways leading to them, as suggested by their different uses in these lineages. Another is that the addition of cusps required only minor changes in genetic pathways regulating tooth development. Here we provide support for the latter hypothesis by demonstrating that manipulation of the levels of Fibroblast growth factor (Fgf) or Bone morphogenetic protein (Bmp) signaling produces bicuspid teeth in the zebrafish (Danio rerio), a species lacking multicuspid teeth in its ancestry. The generality of these results for teleosts is suggested by the conversion of unicuspid pharyngeal teeth into bicuspid teeth by similar manipulations of the Mexican Tetra (Astyanax mexicanus). That these manipulations also produced supernumerary teeth in both species supports previous suggestions of similarities in the molecular control of tooth and cusp number. We conclude that despite their apparent complexity, the evolutionary origin of multicuspid teeth is positively constrained, likely requiring only slight modifications of a pre-existing mechanism for patterning the number and spacing of individual teeth.

  12. Retrieving the Bioenergy Potential from Maize Crops Using Hyperspectral Remote Sensing

    Directory of Open Access Journals (Sweden)

    Miriam Machwitz

    2013-01-01

    Full Text Available Biogas production from energy crops by anaerobic digestion is becoming increasingly important. The amount of biogas that can be produced per unit of biomass is referred to as the biomethane potential (BMP. For energy crops, the BMP varies among varieties and with crop state during the vegetation period. Traditional ways of analytical BMP determination are based on fermentation trials and require a minimum of 30 days. Here, we present a faster method for BMP retrievals using near infrared spectroscopy and partial least square regression (PLSR. PLSR prediction models were developed based on two different sets of spectral reflectance data: (i laboratory spectra of silage samples and (ii airborne imaging spectra (HyMap of maize canopies under field (in situ conditions. Biomass was sampled from 35 plots covering different maize varieties and the BMP was determined as BMP per mass (BMPFM, Nm3 biogas/t fresh matter (Nm3/t FM and BMP per area (BMParea, Nm3 biogas/ha (Nm3/ha. We found that BMPFM significantly differs among maize varieties; it could be well retrieved from silage samples in the laboratory approach (Rcv2 = 0.82, n = 35, especially at levels >190 Nm3/t. In the in situ approach PLSR prediction quality declined (Rcv2 = 0.50, n = 20. BMParea, on the other hand, was found to be strongly correlated with total biomass, but could not be satisfactorily predicted using airborne HyMap imaging data and PLSR.

  13. Biomethane production from grass silage: laboratory assessment to maximise yields

    OpenAIRE

    Wall, David M.

    2015-01-01

    On-farm biogas production is typically associated with forage maize as the biomass source. Digesters are designed and operated with the focus of optimising the conditions for this feedstock. Thus, such systems may not be ideally suited to the digestion of grass. Ireland has ca. 3.85 million ha of grassland. Annual excess grass, surplus to livestock requirements, could potentially fuel an anaerobic digestion industry. Biomethane associated with biomass from 1.1 % of grassland in Ireland, could...

  14. Inoculum selection influences the biochemical methane potential of agro-industrial substrates.

    Science.gov (United States)

    De Vrieze, Jo; Raport, Linde; Willems, Bernard; Verbrugge, Silke; Volcke, Eveline; Meers, Erik; Angenent, Largus T; Boon, Nico

    2015-09-01

    Obtaining a reliable estimation of the methane potential of organic waste streams in anaerobic digestion, for which a biochemical methane potential (BMP) test is often used, is of high importance. Standardization of this BMP test is required to ensure inter-laboratory repeatability and accuracy of the BMP results. Therefore, guidelines were set out; yet, these do not provide sufficient information concerning origin of and the microbial community in the test inoculum. Here, the specific contribution of the methanogenic community on the BMP test results was evaluated. The biomethane potential of four different substrates (molasses, bio-refinery waste, liquid manure and high-rate activated sludge) was determined by means of four different inocula from full-scale anaerobic digestion plants. A significant effect of the selected inoculum on the BMP result was observed for two out of four substrates. This inoculum effect could be attributed to the abundance of methanogens and a potential inhibiting effect in the inoculum itself, demonstrating the importance of inoculum selection for BMP testing. We recommend the application of granular sludge as an inoculum, because of its higher methanogenic abundance and activity, and protection from bulk solutions, compared with other inocula. PMID:25756301

  15. Comparison on batch anaerobic digestion of five different livestock manures and prediction of biochemical methane potential (BMP) using different statistical models.

    Science.gov (United States)

    Kafle, Gopi Krishna; Chen, Lide

    2016-02-01

    There is a lack of literature reporting the methane potential of several livestock manures under the same anaerobic digestion conditions (same inoculum, temperature, time, and size of the digester). To the best of our knowledge, no previous study has reported biochemical methane potential (BMP) predicting models developed and evaluated by solely using at least five different livestock manure tests results. The goal of this study was to evaluate the BMP of five different livestock manures (dairy manure (DM), horse manure (HM), goat manure (GM), chicken manure (CM) and swine manure (SM)) and to predict the BMP using different statistical models. Nutrients of the digested different manures were also monitored. The BMP tests were conducted under mesophilic temperatures with a manure loading factor of 3.5g volatile solids (VS)/L and a feed to inoculum ratio (F/I) of 0.5. Single variable and multiple variable regression models were developed using manure total carbohydrate (TC), crude protein (CP), total fat (TF), lignin (LIG) and acid detergent fiber (ADF), and measured BMP data. Three different kinetic models (first order kinetic model, modified Gompertz model and Chen and Hashimoto model) were evaluated for BMP predictions. The BMPs of DM, HM, GM, CM and SM were measured to be 204, 155, 159, 259, and 323mL/g VS, respectively and the VS removals were calculated to be 58.6%, 52.9%, 46.4%, 81.4%, 81.4%, respectively. The technical digestion time (T80-90, time required to produce 80-90% of total biogas production) for DM, HM, GM, CM and SM was calculated to be in the ranges of 19-28, 27-37, 31-44, 13-18, 12-17days, respectively. The effluents from the HM showed the lowest nitrogen, phosphorus and potassium concentrations. The effluents from the CM digesters showed highest nitrogen and phosphorus concentrations and digested SM showed highest potassium concentration. Based on the results of the regression analysis, the model using the variable of LIG showed the best (R(2

  16. Influence of headspace pressure on methane production in Biochemical Methane Potential (BMP) tests.

    Science.gov (United States)

    Valero, David; Montes, Jesús A; Rico, José Luis; Rico, Carlos

    2016-02-01

    The biochemical methane potential test is the most commonly applied method to determine methane production from organic wastes. One of the parameters measured is the volume of biogas produced which can be determined manometrically by keeping the volume constant and measuring increases in pressure. In the present study, the effect of pressure accumulation in the headspace of the reactors has been studied. Triplicate batch trials employing cocoa shell, waste coffee grounds and dairy manure as substrates have been performed under two headspace pressure conditions. The results obtained in the study showed that headspace overpressures higher than 600mbar affected methane production for waste coffee grounds. On the contrary, headspace overpressures within a range of 600-1000mbar did not affect methane production for cocoa shell and dairy manure. With the analyses performed in the present work it has not been possible to determine the reasons for the lower methane yield value obtained for the waste coffee grounds under high headspace pressures.

  17. Bio-methane. Challenges and technical solutions

    International Nuclear Information System (INIS)

    Among the new energy sectors in development, biogas has many benefits: several valorization possibilities (bio-methane, electricity and heat), continuous production, easy storage. In Europe, and particularly in France, the bio-methane market will be in the next years a driver for the improvement of the economic, environmental and social performance of the actors of the value chain of biogas. ENEA releases a report on the current state of the bio-methane market in Europe. This publication mainly describes: An outlook of the market evolution and the corresponding stakes for the actors of this sector, the technical and economic characteristics, maturity level and specificities of each biogas upgrading process, An analysis of the French regulatory framework for bio-methane injection into the grid

  18. Biogas upgrading to biomethane. Proceedings; Biogasaufbereitung zu Biomethan. Tagungsband

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2008-12-05

    Within the 6th Hanauer Dialogue 'Biogas upgrading to biomethane' at 21st February, 2008, the following lectures were held: (a) Processing of biogas - an introduction (Michael Beil); (b) The climate protecting targets of the Federal Republic of Germany: Which role will play the upgrading of biogas, and which legal boundary conditions are created by the Federal Government? (Uwe Holzhammer); (c) Future strategy: CH{sub 4} grids (Juergen Schmid); (d) Biogas upgrading and biomethane utilization in Sweden (Anneli Petersson); (e) Biogas upgrading and utilization of bio methane in Switzerland (Arthur Wellinger); (f) Biogas upgrading by means of pressure swing adsorption (Alfons Schulte-Schulze Berndt); (g) Biogas upgrading by means of pressurized water washing (Ulf Richter); (h) Biogas upgrading for feeding in public grids. The case of biogas plant Bruck a.d. Leitha (Michael Harasek); (i) Biogas upgrading by means of chemical absorption according to the LP Cooab process (Jerome van Beek); (j) Practical experiences in unpressurized amine washing MT bio methane (Karsten Wuensche); (k) Biogas upgrading by means of organic physical washing with HAASE biogas amplifiers (Roland Kahn); (l) Upgrading using cryogenic technology; the GPP registered -system (Jeroen de Pater); (m) Micro Gas Distribution Systems: Alternatives to biogas upgrading and grid injection (Michael Beil, Bernd Krautkremer); (n) Feeding of exchange gas. The case of project Straelen and Kerpen (Frank Schaefer); (o) Feeding of biogas from the view of grid operators (Norbert Nordmeyer); BIOGASMAX: Biogas as Vehicle Fuel - Market Expansion to 2020 Air Quality (Michael Beil, Uwe Hoffstede); (p) Study: Feeding of biogas into the natural gas distribution system (Fachagentur Nachwachsende Rohstoffe).

  19. Biomethane in the transport sector-An appraisal of the forgotten option

    International Nuclear Information System (INIS)

    The last 20 years efforts to find a long-term and large-scale biofuel alternative to petrol and diesel for the transport sector have been intensified with a focus on liquid biofuels, such as ethanol, methanol and Fischer-Tropsh diesel derived from wood. The large-scale production of biomethane has so far largely been overlooked in comparative studies that focus on the long-term renewable options. The aim of this article fills this gap and to provide a broad and systematic assessment of the future potential of biomethane compared to other biofuels. In order to become a large-scale option, biomethane production from woody biomass via gasification needs to be developed and commercialized. However, biomethane exhibits a clear development path with relatively low financial and technical risks starting with local solutions utilizing wet biomass resources towards medium and eventually large-scale gasification with economics similar to liquid second generation biofuels. The disadvantage of being a gaseous fuel is not insurmountable and can furthermore be relaxed by the integration and dual-use of the existing distribution system for natural gas. This assessment concludes that more emphasize should be given to biomethane as a large-scale option given the opportunity to use woody biomass from gasification.

  20. Power-to-Gas coupling to biomethane production. A feasibility study

    Energy Technology Data Exchange (ETDEWEB)

    Saric, M.; Dijkstra, J.W.; Walspurger, S. [ECN Biomass and Energy Efficiency, Petten (Netherlands)

    2013-09-15

    This preliminary feasibility study on coupling 'Power-to-gas' conversion chain to the bio-methane from producer gas shows a promising potential for efficient and cost effective operation. The production capacity of the biomethane plant can be doubled, while cold gas efficiency remains the same as compared to a standalone biomethane plant. The specifications of the natural gas grid can be reached at the condition that the allowed H2 content is not too strict. The study showed that such coupling implies that both methanation and SNG upgrade sections need to be designed to withstand variable operation conditions and part-load. The methanation section would have to deal with a turndown factor of 2 when switching from E-demand to E-excess operating mode while the CO2 removal section must work efficiently in part-load and respond well in shutdown/start-up operations.

  1. Development strategy of efficient bio-methane system by focused utilization of distributed biomass

    Institute of Scientific and Technical Information of China (English)

    Ouyang Pingkai

    2014-01-01

    Bio-methane,as a promising renewable green energy,the component and thermal value of which are very close to that of natural gas,indicates an enormous resource potential and could be employed as the al-ternative of fossil energy through the development of agro-industrial integration and efficient bio-methane sys-tem. Establishment of high efficient agro-industrial integrated bio-methane system is an important component of the renewable energy system and also a significant way of emission reduction.

  2. A model-based analysis of biomethane production in the Netherlands and the effectiveness of the subsidization policy under uncertainty

    International Nuclear Information System (INIS)

    Biomethane is a renewable alternative to natural gas. It has the potential to increase the sustainability of the energy system and to help deal with supply problems. However, several factors make the future of biomethane production complex and uncertain, such as resource availability, demand, capacity installation, profitability and the competition between the biomethane and electricity sectors for sharing the available biogas and biomass resources. In this research, we study the dynamics of the Dutch biomethane production and analyze the effects of subsidization policy with a system dynamics model. The policy is tested under uncertainty with respect to three conflicting objectives, namely maximizing production and emission reduction, and minimizing costs. According to the results, the subsidization is crucial to develop biomethane production, and the performance of the policy is enhanced in terms of robustness and of meeting all three objectives satisfactorily when the policy is implemented for a long time, with relatively low subsidy prices. Besides, the subsidization policy is found to be most vulnerable to the producers’ uncertain investment response to profitability. In future research, different policy options such as subsidizing other biomass-based renewable energy options and policies affecting the biomethane demand can be tested

  3. Assessment of GHG emissions of biomethane from energy cereal crops in Umbria, Italy

    International Nuclear Information System (INIS)

    Highlights: • GHG emissions of biomethane from energy crops cultivated in a central Italian farm were investigated. • Electricity consumption of the biogas plant was monitored. • Current scenario does not allow to achieve a GHG saving according to Renewable Energy Directive. • GHG emissions could be reduced by covering the storage tanks of digestate and installing a CHP plant. - Abstract: Biomethane from energy crops is a renewable energy carrier and therefore it potentially contributes to climate change mitigation. However, significant greenhouse gas (GHG) emissions resulting from cultivation and processing must be considered. Among those, the production and use of nitrogen fertilizers, the resulting nitrous oxide (N2O) emissions, the methane emissions from digestate storage and the energy consumption of the biogas plant are crucial factors. In the present paper an integrated life cycle assessment (LCA) of GHG emissions from biomethane production is carried out, taking into account own measurements and experience data from a modern biogas plant located in Umbria, Italy. The study is also focused on the electricity consumption of the biogas plant, assessing the specific absorption power of each machinery. The analysis is based on the methodology defined by the European Union Renewable Energy Directive 2009/28/EC (RED). The main result is that the biomethane chain exceeds the minimum value of GHG saving (35%) mainly due to the open storage of digestate. However by varying the system, using heat and electricity from a biogas CHP plant and covering digestate storage tank, a reduction of 68.9% could be obtained

  4. Alkaline Pretreatment of Sugarcane Bagasse and Filter Mud Codigested to Improve Biomethane Production

    Science.gov (United States)

    Mehryar, Esmaeil; Bi, Jinhua

    2016-01-01

    To enhance the codigestion of degradation and improve biomethane production potential, sugarcane bagasse and filter mud were pretreated by sodium hydroxide NaOH 1 N at 100°C for 15, 30, and 45 minutes, respectively. Biomethane generation from 1-liter batch reactor was studied at mesophilic temperature (37 ± 1)°C, solid concentrations of 6%, and five levels of mixing proportion with and without pretreatment. The results demonstrate that codigestion of filter mud with bagasse produces more biomethane than fermentation of filter mud as single substrate; even codigested substrate composition presented a better balance of nutrients (C/N ratio of 24.70) when codigestion ratio between filter mud and bagasse was 25 : 75 in comparison to filter mud as single substrate (C/N ratio 9.68). All the pretreatments tested led to solubilization of the organic matter, with a maximum lignin reduction of 86.27% and cumulative yield of biomethane (195.8 mL·gVS−1, digestion of pretreated bagasse as single substrate) obtained after 45 minutes of cooking by NaOH 1 N at 100°C. Under this pretreatment condition, significant increase in cumulative methane yield was observed (126.2 mL·gVS−1) at codigestion ratio of 25 : 75 between filter mud and bagasse by increase of 81.20% from untreated composition.

  5. Durable titania films for solar treatment of biomethanated spent wash

    Science.gov (United States)

    Akbarzadeh, Rokhsareh; S. Ghole, Vikram; Javadpour, Sirus

    2016-10-01

    The use of TiO2 films for treatment of biomethanated spent wash is reported. The films of TiO2 were formed and photocatalytic performance of the prepared films in degradation of methylene blue and biomethanated spent wash were studied. Photocatalytic use of these films was found to be effective for degradation of biomethanated spent wash. The photocatalyst was used up for 20 cycles without significant reduction in activities showing long life of the catalyst.

  6. Biomethane: Status and Factors Affecting Market Development and Trade

    OpenAIRE

    Thrän, Daniela; Persson, Tobias; Daniel-Gromke, Jaqueline; PONITKA Jens; Seiffert, Michael; Baldwin, John; Kranzl, Lukas; SCHIPFER Fabian; MATZENBERGER Julian; Devriendt, Nathalie; Dumont, Mathieu; Dahl, Jonas; BOCHMANN Günther

    2014-01-01

    This publication focusses on the status of biomethane (which includes upgraded biogas and bio-SNG) production, grid injection and use in different IEA countries. It also illustrates the options and needs for the development of biomethane supply strategies with the focus of improved trade. Further an overview of expected future development of the biomethane sector is given. As part of of the study, results from a dedicated questionnaire were assessed to get an insight into the opportunities an...

  7. Model based sustainable production of biomethane

    OpenAIRE

    Biernacki, Piotr

    2014-01-01

    The main intention of this dissertation was to evaluate sustainable production of biomethane with use of mathematical modelling. To achieve this goal, widely acknowledged models like Anaerobic Digestion Model No.1 (ADM1), describing anaerobic digestion, and electrolyte Non-Random Two Liquid Model (eNRTL), for gas purification, were utilized. The experimental results, batch anaerobic digestion of different substrates and carbon dioxide solubility in 2-(Ethylamino)ethanol, were used to determin...

  8. The effect of feedstock cost on biofuel cost as exemplified by biomethane production from grass silage.

    OpenAIRE

    McEniry, J.; O’Kiely, P.; Crosson, P.; Groom, Elaine; Murphy, J. D.

    2011-01-01

    Abstract: The potential variance in feedstock costs can have signifi cant implications for the cost of a biofuel and the fi nancial viability of a biofuel facility. This paper employs the Grange Feed Costing Model to assess the cost of on-farm biomethane production using grass silages produced under a range of management scenarios. These costs were compared with the cost of wheat grain and sugarbeet roots for ethanol production at an industrial scale. Of the three feedstocks examined, grass s...

  9. Biomethane production from food waste and organic residues

    OpenAIRE

    Browne, James D.

    2014-01-01

    Anaerobic digestion (AD) of biodegradable waste is an environmentally and economically sustainable solution which incorporates waste treatment and energy recovery. The organic fraction of municipal solid waste (OFMSW), which comprises mostly of food waste, is highly degradable under anaerobic conditions. Biogas produced from OFMSW, when upgraded to biomethane, is recognised as one of the most sustainable renewable biofuels and can also be one of the cheapest sources of biomethane if a gate fe...

  10. Validation and Recommendation of Methods to Measure Biogas Production Potential of Animal Manure

    Science.gov (United States)

    Pham, C. H.; Triolo, J. M.; Cu, T. T. T.; Pedersen, L.; Sommer, S. G.

    2013-01-01

    In developing countries, biogas energy production is seen as a technology that can provide clean energy in poor regions and reduce pollution caused by animal manure. Laboratories in these countries have little access to advanced gas measuring equipment, which may limit research aimed at improving local adapted biogas production. They may also be unable to produce valid estimates of an international standard that can be used for articles published in international peer-reviewed science journals. This study tested and validated methods for measuring total biogas and methane (CH4) production using batch fermentation and for characterizing the biomass. The biochemical methane potential (BMP) (CH4 NL kg−1 VS) of pig manure, cow manure and cellulose determined with the Moller and VDI methods was not significantly different in this test (p>0.05). The biodegradability using a ratio of BMP and theoretical BMP (TBMP) was slightly higher using the Hansen method, but differences were not significant. Degradation rate assessed by methane formation rate showed wide variation within the batch method tested. The first-order kinetics constant k for the cumulative methane production curve was highest when two animal manures were fermented using the VDI 4630 method, indicating that this method was able to reach steady conditions in a shorter time, reducing fermentation duration. In precision tests, the repeatability of the relative standard deviation (RSDr) for all batch methods was very low (4.8 to 8.1%), while the reproducibility of the relative standard deviation (RSDR) varied widely, from 7.3 to 19.8%. In determination of biomethane concentration, the values obtained using the liquid replacement method (LRM) were comparable to those obtained using gas chromatography (GC). This indicates that the LRM method could be used to determine biomethane concentration in biogas in laboratories with limited access to GC. PMID:25049861

  11. Smad8/9 Is Regulated Through the BMP Pathway.

    Science.gov (United States)

    Katakawa, Yuko; Funaba, Masayuki; Murakami, Masaru

    2016-08-01

    Members of the transforming growth factor-β (TGF-β) family function through Smad-dependent and Smad-independent pathways. The Smad-dependent pathway is stimulated through the phosphorylation of receptor-regulated Smad (R-Smad) and inhibited through the dephosphorylation of R-Smad or the gene induction of inhibitory Smad (I-Smad). Little information is available on the regulation of R-Smad gene expression. BMP4 potentiated the up-regulation of Smad8/9 expression in C2C12, H9c2, 3T3-L1, HepG2, B16, and primary fibroblasts. BMP4-induced Smad8/9 expression was cycloheximide-insensitive and LDN-193189-sensitive, suggesting a direct event mediated through BMP type I receptors. BMP4 transcriptionally stimulated the Smad8/9 gene, and BMP-responsive elements (BREs) spanning nt -121 to nt -44 are involved in the up-regulation of Smad8/9 expression in response to BMP4. Phosphorylated Smad1/5/8/9 specifically bound to the BREs of Smad8/9 gene. The present study reveals that Smad8/9 is a unique R-Smad regulated through the BMP pathway at the mRNA level. J. Cell. Biochem. 117: 1788-1796, 2016. © 2016 Wiley Periodicals, Inc. PMID:26748560

  12. Identification of small molecule activators of BMP signaling.

    Directory of Open Access Journals (Sweden)

    Karen Vrijens

    Full Text Available Bone Morphogenetic Proteins (BMPs are morphogens that play a major role in regulating development and homeostasis. Although BMPs are used for the treatment of bone and kidney disorders, their clinical use is limited due to the supra-physiological doses required for therapeutic efficacy causing severe side effects. Because recombinant BMPs are expensive to produce, small molecule activators of BMP signaling would be a cost-effective alternative with the added benefit of being potentially more easily deliverable. Here, we report our efforts to identify small molecule activators of BMP signaling. We have developed a cell-based assay to monitor BMP signaling by stably transfecting a BMP-responsive human cervical carcinoma cell line (C33A with a reporter construct in which the expression of luciferase is driven by a multimerized BMP-responsive element from the Id1 promoter. A BMP-responsive clone C33A-2D2 was used to screen a bioactive library containing ∼5,600 small molecules. We identified four small molecules of the family of flavonoids all of which induced luciferase activity in a dose-dependent manner and ventralized zebrafish embryos. Two of the identified compounds induced Smad1, 5 phosphorylation (P-Smad, Id1 and Id2 expression in a dose-dependent manner demonstrating that our assays identified small molecule activators of BMP signaling.

  13. Analysis of BMP4 and BMP7 signaling in breast cancer cells unveils time-dependent transcription patterns and highlights a common synexpression group of genes

    Directory of Open Access Journals (Sweden)

    Rodriguez-Martinez Alejandra

    2011-11-01

    Full Text Available Abstract Background Bone morphogenetic proteins (BMPs are members of the TGF-beta superfamily of growth factors. They are known for their roles in regulation of osteogenesis and developmental processes and, in recent years, evidence has accumulated of their crucial functions in tumor biology. BMP4 and BMP7, in particular, have been implicated in breast cancer. However, little is known about BMP target genes in the context of tumor. We explored the effects of BMP4 and BMP7 treatment on global gene transcription in seven breast cancer cell lines during a 6-point time series, using a whole-genome oligo microarray. Data analysis included hierarchical clustering of differentially expressed genes, gene ontology enrichment analyses and model based clustering of temporal data. Results Both ligands had a strong effect on gene expression, although the response to BMP4 treatment was more pronounced. The cellular functions most strongly affected by BMP signaling were regulation of transcription and development. The observed transcriptional response, as well as its functional outcome, followed a temporal sequence, with regulation of gene expression and signal transduction leading to changes in metabolism and cell proliferation. Hierarchical clustering revealed distinct differences in the response of individual cell lines to BMPs, but also highlighted a synexpression group of genes for both ligands. Interestingly, the majority of the genes within these synexpression groups were shared by the two ligands, probably representing the core molecular responses common to BMP4 and BMP7 signaling pathways. Conclusions All in all, we show that BMP signaling has a remarkable effect on gene transcription in breast cancer cells and that the functions affected follow a logical temporal pattern. Our results also uncover components of the common cellular transcriptional response to BMP4 and BMP7. Most importantly, this study provides a list of potential novel BMP target

  14. Conference on the role of biomethane in the energy transition in France and in Germany

    International Nuclear Information System (INIS)

    The French-German office for Renewable energies (OFAEnR) organised a conference on the role of biomethane in the energy transition in France and in Germany. In the framework of this French-German exchange of experience, about 110 participants exchanged views on the status of the legal framework and of the development of biomethane industry in the French and German energy transitions. This document brings together the available presentations (slides) made during this event: 1 - Biomethane injection in France - elaboration and implementation of the price structure (Stanislas Reizine); 2 - Biomethane framework conditions in Germany 3 - German Road-map for Biomethane (Matthias Edel); 4 - A vision for biomethane in France in 2030 - purified biogas injection in the natural gas network (Olivier Theobald); 5 - Biomethane produced by the Strasbourg-la Wantzenau waste water plant and injected into the GDS natural gas network (Frederic Pierre); 6 - Biomethane fuel in Lille city: 1995-2015 100% clean and renewable energy in transportation (Jean Marc Mestrel); 7 - Biomethane from organic waste and its utilisation (Johan Grope); 8 - Marketing of Biomethane to end consumers (Jens Eberlein); 9 - Developing new approaches to promote injection into the grid (Suzanne Renard); 10 - Demand driven power supply from Bioenergy - a balancing option for power distribution networks (Marcus Trommler); 11 - Flexible biogas production and its integration to power and gas grids (Tatiana Demeusy); 12 - A partnership for the development of Agricultural methanization plants around a single injection point (Nicolas Chapelat); 13 - Keynotes: biomethane development paths to favour (Mathieu Lefebvre)

  15. Bmp2 and Bmp4 accelerate alveolar bone development.

    Science.gov (United States)

    Ou, Mingming; Zhao, Yibing; Zhang, Fangming; Huang, Xiaofeng

    2015-06-01

    Alveolar bone remodeling is a continuous process that takes place during development and in response to various physiological and pathological stimuli. However, detailed knowledge regarding the underlying mechanisms involved in alveolar bone development is still lacking. This study aims at improving our understanding of alveolar bone formation and the role of bone morphogenetic proteins (Bmps) in this process. Mice at embryonic (E) day 13.5 to postnatal (PN) day 15.5 were selected to observe the process of alveolar bone development. Alveolar bone development was found to be morphologically observable at E14.5. Molar teeth isolated from mice at PN7.5 were pretreated with Bmp2, Bmp4, Noggin, or BSA, and grafted subcutaneously into mice. The subcutaneously implanted tooth germs formed alveolar bone indicating the role of the dental follicle in alveolar bone development. Alveolar bone formation was increased after pretreatment with Bmp2 and Bmp4, but not with Noggin. Gene expression levels in dental follicle cells from murine molars were also determined by real-time RT-PCR. The expression levels of Runx2, Bsp, and Ocn were significantly higher in dental follicle cells cultured with Bmp2 or Bmp4, and significantly lower in those cultured with Noggin when compared with that of the BSA controls. Our results suggest that the dental follicle participates in alveolar bone formation and Bmp2/4 appears to accelerate alveolar bone development.

  16. Emission and operating performance of a biomethane tractor with dual fuel engine; Emissions- und Betriebsverhalten eines Biomethan-Traktors mit Zuendstrahlmotor

    Energy Technology Data Exchange (ETDEWEB)

    Mautner, Sebastian [Technologie- und Foerderzentrum (TFZ), Straubing (Germany); Emberger, Peter; Thuneke, Klaus; Remmele, Edgar

    2016-08-01

    The use of biomethane as fuel for agricultural machinery with dual fuel technology is contributing to climate protection and ensures safe fuel supply. So far, hardly any documented operational experiences are known. The aim of the project, funded by the Bavarian Ministry of Economic Affairs and Media, Energy and Technology, was to investigate practicability for daily use and the emission behaviour of a Valtra N101 prototype tractor (exhaust stage IIIA). The retrofitted dual-fuel technology of the former conventional diesel tractor simultaneously uses biomethane or natural gas and diesel as ignition fuel. During the field test over 590 working hours, the tractor showed overall high reliability. On average the operating range in dual-fuel mode with one complete filling of the gas tanks was about 11.5 hours. On the tractor test bench a significant improvement of the exhaust emissions could be observed, since the gas ECU had been optimized and changed by the manufacturer. For dual-fuel operation, nitrogen oxides (NO{sub x}) are lower, whereas carbon monoxide (CO), hydrocarbons (HC) and particulate matter emissions (PM) are higher compared to solely diesel operation. In particular, HC emissions exceed the proposed limiting value, submitted by the European Commission. This is due to incomplete gas combustion and insufficient conversion by the exhaust after-treatment-system (methane slip). A big potential for optimization is expected by adjusting the operating point-specific gasdiesel ratio and improving the exhaust gas aftertreatment system.

  17. Biomethane Production as an Alternative Bioenergy Source from Codigesters Treating Municipal Sludge and Organic Fraction of Municipal Solid Wastes

    OpenAIRE

    M. Evren Ersahin; Cigdem Yangin Gomec; R. Kaan Dereli; Osman Arikan; Izzet Ozturk

    2010-01-01

    Energy recovery potential of a mesophilic co-digester treating OFMSW and primary sludge at an integrated biomethanization plant was investigated based on feasibility study results. Since landfilling is still the main solid waste disposal method in Turkey, land scarcity will become one of the most important obstacles. Restrictions for biodegradable waste disposal to sanitary landfills in EU Landfill Directive and uncontrolled long-term contamination with gas emissions and leachate necessitate ...

  18. The Role of natural gas and biomethane in the fuel mix of the future in Germany. Required action and potential solutions to accelerate adoption in transport applications; Erdgas und Biomethan im kuenftigen Kraftstoffmix. Handlungsbedarf und Loesungsansaetze fuer eine beschleunigte Etablierung im Verkehr

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2011-09-15

    The contribution under consideration reports on the need of action and on solution attempts for an accelerated establishment of natural gas and bio methane in the future fuel mix. The authors come to the following conclusions: The energy situation and climatic situation require a stronger diversification of fuels and drives. The targets for the amount of natural gas and bio methane as a fuel are not reached yet. The characteristics of natural gas speak for an accelerated establishment in the traffic sector. The admixture of bio methane can increase the climatic, environmental and resources advantages. In order to penetrate the market all participants involved must commit themselves to a concrete 'roadmap'. The contribution shows which measures must be converted by the participants involved in order to be able to utilize fully the potentials of the employment of natural gas and bio methane in the traffic sector.

  19. DMH1, a small molecule inhibitor of BMP type i receptors, suppresses growth and invasion of lung cancer.

    Directory of Open Access Journals (Sweden)

    Jijun Hao

    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.

  20. Which is the preferable transport fuel on a greenhouse gas basis; biomethane or ethanol?

    Energy Technology Data Exchange (ETDEWEB)

    Power, Niamh M. [Department of Civil, Structural and Environmental Engineering, Cork Institute of Technology, Cork (Ireland); Murphy, Jerry D. [Department of Civil and Environmental Engineering, University College Cork, Cork (Ireland)

    2009-10-15

    Biomethane and ethanol are both biofuels which are generated from agricultural crops that can be utilised to meet the Biofuels Directive. In Ireland with the demise of the sugar industry 48,000 Ha of land is readily available for biofuel production, without unduly effecting food production. Which biofuel should dominate? This paper investigates biofuel production for three different crop rotations: wheat, barley and sugar beet; wheat, wheat and sugar beet; wheat only. A greenhouse gas balance is performed to determine under what conditions each biofuel is preferable. For both biofuels, the preferred crop on a weight basis is wheat, while on an area basis the preferred crop is sugar beet. Biomethane scenarios produce more gross energy than ethanol scenarios. Under the base assumption (7.41% biogas losses, and biomethane utilised in a converted petrol engine, such as a bi-fuel car, and thus underperforming on a km/MJ basis) ethanol generated more net greenhouse gas savings than biomethane. This was unexpected as biomethane produces twice the net energy per hectare as ethanol. If either biogas losses were reduced or biomethane was utilised in a vehicular engine optimised for biomethane (such as a bus powered solely on gaseous biofuel) then biomethane would generate significantly more net greenhouse gas savings than ethanol. It was found that if biogas losses were eliminated and the biomethane was used in a vehicle optimised for biomethane, then the net greenhouse gas savings are 2.4 times greater than those from ethanol generated from the same feedstock. (author)

  1. Which is the preferable transport fuel on a greenhouse gas basis; biomethane or ethanol?

    International Nuclear Information System (INIS)

    Biomethane and ethanol are both biofuels which are generated from agricultural crops that can be utilised to meet the Biofuels Directive. In Ireland with the demise of the sugar industry 48,000 Ha of land is readily available for biofuel production, without unduly effecting food production. Which biofuel should dominate? This paper investigates biofuel production for three different crop rotations: wheat, barley and sugar beet; wheat, wheat and sugar beet; wheat only. A greenhouse gas balance is performed to determine under what conditions each biofuel is preferable. For both biofuels, the preferred crop on a weight basis is wheat, while on an area basis the preferred crop is sugar beet. Biomethane scenarios produce more gross energy than ethanol scenarios. Under the base assumption (7.41% biogas losses, and biomethane utilised in a converted petrol engine, such as a bi-fuel car, and thus underperforming on a km/MJ basis) ethanol generated more net greenhouse gas savings than biomethane. This was unexpected as biomethane produces twice the net energy per hectare as ethanol. If either biogas losses were reduced or biomethane was utilised in a vehicular engine optimised for biomethane (such as a bus powered solely on gaseous biofuel) then biomethane would generate significantly more net greenhouse gas savings than ethanol. It was found that if biogas losses were eliminated and the biomethane was used in a vehicle optimised for biomethane, then the net greenhouse gas savings are 2.4 times greater than those from ethanol generated from the same feedstock.

  2. Biomethane production in an AnSBBR treating wastewater from biohydrogen process.

    Science.gov (United States)

    Lullio, T G; Souza, L P; Ratusznei, S M; Rodrigues, J A D; Zaiat, M

    2014-11-01

    An anaerobic sequencing batch reactor containing immobilized biomass (AnSBBR) was used to produce biomethane by treating the effluent from another AnSBBR used to produce biohydrogen from glucose- (AR-EPHG) and sucrose-based (AR-EPHS) wastewater. In addition, biomethane was also produced from sucrose-based synthetic wastewater (AR-S) in a single AnSBBR to compare the performance of biomethane production in two steps (acidogenic and methanogenic) in relation to a one-step operation. The system was operated at 30 °C and at a fixed stirring rate of 300 rpm. For AR-EPHS treatment, concentrations were 1,000, 2,000, 3,000, and 4,000 mg chemical oxygen demand (COD) L(-1) and cycle lengths were 6 and 8 h. The applied volumetric organic loads were 2.15, 4.74, 5.44, and 8.22 g COD L(-1) day(-1). For AR-EPHG treatment, concentration of 4,000 mg COD L(-1) and 4-h cycle length (7.21 g COD L(-1) day(-1)) were used. For AR-S treatment, concentration was 4,000 mg COD L(-1) day(-1) and cycle lengths were 8 (7.04 g COD L(-1) day(-1)) and 12 h (4.76 g COD L(-1) day(-1)). The condition of 8.22 g COD L(-1) day(-1) (AR-EPHS) showed the best performance with respect to the following parameters: applied volumetric organic load of 7.56 g COD L(-1) day(-1), yield between produced methane and removed organic material of 0.016 mol CH4 g COD(-1), CH4 content in the produced biogas of 85 %, and molar methane productivity of 127.9 mol CH4 m(-3) day(-1). In addition, a kinetic study of the process confirmed the trend that, depending on the biodegradability characteristics of the wastewaters used, the two-step treatment (acidogenic for biohydrogen production and methanogenic for biomethane production) has potential advantages over the single-step process. PMID:25149460

  3. Biomethane production in an AnSBBR treating wastewater from biohydrogen process.

    Science.gov (United States)

    Lullio, T G; Souza, L P; Ratusznei, S M; Rodrigues, J A D; Zaiat, M

    2014-11-01

    An anaerobic sequencing batch reactor containing immobilized biomass (AnSBBR) was used to produce biomethane by treating the effluent from another AnSBBR used to produce biohydrogen from glucose- (AR-EPHG) and sucrose-based (AR-EPHS) wastewater. In addition, biomethane was also produced from sucrose-based synthetic wastewater (AR-S) in a single AnSBBR to compare the performance of biomethane production in two steps (acidogenic and methanogenic) in relation to a one-step operation. The system was operated at 30 °C and at a fixed stirring rate of 300 rpm. For AR-EPHS treatment, concentrations were 1,000, 2,000, 3,000, and 4,000 mg chemical oxygen demand (COD) L(-1) and cycle lengths were 6 and 8 h. The applied volumetric organic loads were 2.15, 4.74, 5.44, and 8.22 g COD L(-1) day(-1). For AR-EPHG treatment, concentration of 4,000 mg COD L(-1) and 4-h cycle length (7.21 g COD L(-1) day(-1)) were used. For AR-S treatment, concentration was 4,000 mg COD L(-1) day(-1) and cycle lengths were 8 (7.04 g COD L(-1) day(-1)) and 12 h (4.76 g COD L(-1) day(-1)). The condition of 8.22 g COD L(-1) day(-1) (AR-EPHS) showed the best performance with respect to the following parameters: applied volumetric organic load of 7.56 g COD L(-1) day(-1), yield between produced methane and removed organic material of 0.016 mol CH4 g COD(-1), CH4 content in the produced biogas of 85 %, and molar methane productivity of 127.9 mol CH4 m(-3) day(-1). In addition, a kinetic study of the process confirmed the trend that, depending on the biodegradability characteristics of the wastewaters used, the two-step treatment (acidogenic for biohydrogen production and methanogenic for biomethane production) has potential advantages over the single-step process.

  4. Bone regeneration by implantation of adipose-derived stromal cells expressing BMP-2

    International Nuclear Information System (INIS)

    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

  5. Heating and cooking with methane; Heizen und kochen mit Biomethan

    Energy Technology Data Exchange (ETDEWEB)

    Sieg, K.

    2008-09-15

    Biomethane is a climate-friendly alternative to natural gas. In the meantime it is being fed into the public gas grid, and in some regions of Germany consumers can opt for so-called ''bio-natural-gas'' tariffs.

  6. Biomethane as an Environment-Friendly Fuel for Municipal Transport

    Science.gov (United States)

    Papacz, Władysław J.

    2012-09-01

    An idea to replace the conventional engine fuel with biomethane has been described. The effects of such a swap have been analysed for municipal transport buses in Warsaw. The replacement has been shown to result in a significant reduction of toxic exhaust emissions and in economic savings. The analysis results have been presented in the form of tables and graphs.

  7. Biomethane production and physicochemical characterization of anaerobically digested teff (Eragrostis tef) straw pretreated by sodium hydroxide.

    Science.gov (United States)

    Chufo, Akiber; Yuan, Hairong; Zou, Dexun; Pang, Yunzhi; Li, Xiujin

    2015-04-01

    The biogas production potential and biomethane content of teff straw through pretreatment by NaOH was investigated. Different NaOH concentrations (1%, 2%, 4% and 6%) were used for each four solid loadings (50, 65, 80 and 95 g/L). The effects of NaOH as pretreatment factor on the biodegradability of teff straw, changes in main compositions and enhancement of anaerobic digestion were analyzed. The result showed that, using 4% NaOH for pretreatment in 80 g/L solid loading produced 40.0% higher total biogas production and 48.1% higher biomethane content than the untreated sample of teff straw. Investigation of changes in chemical compositions and physical microstructure indicated that there was 4.3-22.1% total lignocellulosic compositions removal after three days pretreatment with NaOH. The results further revealed that NaOH pretreatment changed the structural compositions and lignin network, and improved biogas production from teff straw. PMID:25656865

  8. BMP7 retards peripheral myelination by activating p38 MAPK in Schwann cells.

    Science.gov (United States)

    Liu, Xiaoyu; Zhao, Yahong; Peng, Su; Zhang, Shuqiang; Wang, Meihong; Chen, Yeyue; Zhang, Shan; Yang, Yumin; Sun, Cheng

    2016-01-01

    Schwann cell (SC) myelination is pivotal for the proper physiological functioning of the nervous system, but the underlying molecular mechanism remains less well understood. Here, we showed that the expression of bone morphogenetic protein 7 (BMP7) inversely correlates with myelin gene expression during peripheral myelination, which suggests that BMP7 is likely a negative regulator for myelin gene expression. Our experiments further showed that the application of BMP7 attenuates the cAMP induced myelin gene expression in SCs. Downstream pathway analysis suggested that both p38 MAPK and SMAD are activated by exogenous BMP7 in SCs. The pharmacological intervention and gene silence studies revealed that p38 MAPK, not SMAD, is responsible for BMP7-mediated suppression of myelin gene expression. In addition, c-Jun, a potential negative regulator for peripheral myelination, was up-regulated by BMP7. In vivo experiments showed that BMP7 treatment greatly impaired peripheral myelination in newborn rats. Together, our results established that BMP7 is a negative regulator for peripheral myelin gene expression and that p38 MAPK/c-Jun axis might be the main downstream target of BMP7 in this process. PMID:27491681

  9. Two-phase anaerobic digestion of mixed waste streams to separate generation of bio-hydrogen and bio-methane

    Energy Technology Data Exchange (ETDEWEB)

    Siddiqui, Z.; Horam, N.J. [Leeds Univ. (United Kingdom). School of Civil Engineering

    2010-07-01

    The purpose of this study was to investigate the net energy potential of single stage mesophilic reactor and two phase mesophilic reactor (hydrogeniser followed by methaniser) using the mix of process industrial food waste (IFW) and sewage sludge (SS). Two-phase reactor efficiency was analysed based on individual optimum influent/environmental (C:N and pH) and reactor/engineering (HRT and OLR) conditions achieved using the batch and continuous reactor study for the hydrogen and methane. Optimum C:N 20 and pH 5.5{+-}0.5 was observed using the Bio-H{sub 2} potential (BHP) and C:N 15 and pH 6.5{+-}0.3 for the biochemical methane potential (BMP) test. The maximum hydrogen content of 47% (v/v) was achieved using OLR 6 g VS/L/d and HRT of 5 days. Increase in hydrogen yield was noticed with consistent decrease in OLR. The volatile solids (VS) removal and hydrogen yield was observed in range 41.3 to 47% and 112.3 to 146.7 mL/ gVS{sub removed}. The specific hydrogen production rate improved at low OLR, 0.2 to 0.4 L/(L.d) using OLR 7.1 and 6 g VS/L/d respectively was well corroborated comparable to previous reported results at OLR 6 gVS/L/d using the enriched carbohydrate waste stream in particular to food wastes. A significant increase in VFA concentrations were noticed shifting OLR higher from 6 g VS/L/d thereby unbalancing the reactor pH and the biogas yield respectively. In similar, maximum methane content of 70% (v/v) was achieved using OLR of 3.3 gVS/L/d and HRT of 10 days. Slight decrease in methane content was noticed thereby increasing HRT to 12 and 15 days respectively. The volatile solids (VS) removal and specific methane production rate was observed in range 57.6 to 68.7 and 0.22 to 1.19 L/(L.d). The specific methane production potential improved thereby reducing the HRT and optimum yield was recorded as 476.6 mL/gVS{sub removed} using OLR 3.3 gVS/L/d. The energy potential of optimum condition in single stage hydorgeniser is 2.27 MW/tonne VS{sub fed}. Using the

  10. Wood to Bio-Methane demonstration project in the Netherlands

    Energy Technology Data Exchange (ETDEWEB)

    Van der Meijden, C.M.; Van der Drift, A.; Rietveld, G. [ECN Biomass and Energy Efficiency, Petten (Netherlands); Koenemann, J.W. [Dahlman Renewable Technology, P.O. Box 438, 3140 AK Maassluis (Netherlands); Sierhuis, W. [HVCgroup, P.O. Box 9199, 1800 GD, Alkmaar (Netherlands)

    2013-06-15

    The Energy research Centre of the Netherlands (ECN) has developed a biomass gasification technology, called the MILENA technology. The Milena gasification technology has a high cold gas efficiency and high methane yield, making it very suitable for gas engine and turbine applications as well as upgrading of the gas into Bio-Methane. An overall efficiency from biomass to power of over 30% is possible, whereas 70% efficiency is achievable from biomass to gas grid quality methane. HVC Group (situated in Alkmaar, North Holland) is a modern public service waste company. HVC converts waste streams which cannot be recycled into usable forms of energy. HVC has a 75 MWth waste wood boiler in operation which produces heat and electricity, and an anaerobic digester which converts domestic fruit, vegetable and garden waste into Bio-Methane. HVC expects an important role for Bio-Methane in the future and HVC has decided to join ECN with the development, demonstration and implementation of the MILENA Bio-Methane technology. Linked to the Bio-Methane demonstration project is the Netherlands Expertise Centre for Biomass Gasification. The MILENA demonstration project and the Gasification Expert Centre are supported by the following companies and organizations: HVC, TAQA, Gasunie, Dahlman, province of North Holland, the Alkmaar municipality and ECN. In 2010 and 2012 extensive lab-scale and pilot scale tests have been executed by ECN and HVC to proof that the gasification and gas cleaning technology is ready for commercial application. The final step in this test program was a duration test in the 800 kWth MILENA pilot plant coupled to the OLGA tar removal unit. The goal was to show high availability. The result of the test was an availability of the gasifier of 96% and an overall availability (including gas cooling and gas cleaning) of 85%. The results of the duration tests convinced HVC and the other partners that the technology is ready for scale-up. The results produced in the

  11. Life cycle assessment of biomethane use in Argentina.

    Science.gov (United States)

    Morero, Betzabet; Groppelli, Eduardo; Campanella, Enrique A

    2015-04-01

    Renewable substitutes for natural gas, such as biogas, require adequate treatment to remove impurities. This paper presents the life cycle and environmental impact of upgrading biogas using absorption-desorption process with three different solvents: water, diglycolamine and polyethylene glycol dimethyl ether. The results showed that water produces a minor impact in most of the considered categories, and an economic analysis showed that water is the most feasible solvent for obtaining the lowest payback period. This analysis includes three different sources for biogas production and two end uses for biomethane. The use of different wastes as sources results in different environmental impacts depending on the type of energy used in the anaerobic digestion. The same situation occurs when considering the use of biomethane as a domestic fuel or for power generation. Using energy from biogas to replace conventional energy sources in production and upgrading biogas significantly reduce the environmental impacts of processes. PMID:25700340

  12. Biomethanation of white rotted and brown rotted rice straw

    Energy Technology Data Exchange (ETDEWEB)

    Ghosh, A.; Bhattacharyya, B.C. [Chemical Engineeringg Dept., Biotechnology Unit, IIT Kharagpur, (India)

    1999-04-01

    Biomethanation of white rotted and brown rotted rice straw was taken for the present investigation and their efficiency on biomethanation has been tested. Rice straw was treated with white rot fungus Phanerochaete chrysosporium (P{sub C}) and brown rot fungus Polyporus ostreiformis (P{sub O}). Biogas and methane production was increased by about 34.73% and 46.19% in P{sub C}-treated straw and 21.12% and 31.94% in P{sub O}-treated straw respectively. VFA production has also been increased in P{sub C} and P{sub O} treated straw compared to control straw which were 76.73% and 30.69% respectively. Reduction of COD has also been found during biomethanation. The rate of reduction of COD during the initial period of digestion was 59.01%, 55.55% and 26.00% in P{sub C}-treated, P{sub O}-treated and control straw respectively after 21 days of digestion. (orig.) With 12 figs., 3 tabs., 14 refs.

  13. Risk variants in BMP4 promoters for nonsyndromic cleft lip/palate in a Chilean population

    Directory of Open Access Journals (Sweden)

    Suazo José

    2011-12-01

    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.

  14. Economic Assessment of Biomethane Supply System Based on Natural Gas Infrastructure

    OpenAIRE

    Paturska, A; Rēpele, M; Bažbauers, G

    2014-01-01

    Upgraded biogas injected into a natural gas grid provide considerable increase of renewable energy share within the natural gas-fired systems. The costs of biomethane produced in distributed biogas plants and injected into the natural gas grid were determined. The results show that under the most favorable scenario, biomethane production is more expensive than natural gas by approximately 35%.

  15. Expression of active hBMP2 in transgenic tobacco plants.

    Science.gov (United States)

    Suo, Guangli; Chen, Bing; Zhang, Jingyu; Gao, Yuan; Wang, Xia; He, Zhengquan; Dai, Jianwu

    2006-12-01

    Bone morphogenetic protein 2 (BMP2) is important for bone tissue repair. The goal of this research is to construct a high level human BMP2 (hBMP2) expression system using transgenic tobacco plants as a bioreactor. Cauliflower mosaic virus (CaMV) 35S promoter, alfalfa mosaic virus (AMV) enhancer, tobacco mosaic virus (TMV) enhancer, matrix attachment regions (MARs) sequence, and "Kozak" sequence were used to construct recombinant expression vectors and the high-expression vectors were screened out through GUS-fusions assay. The promoter is the most important factor; double-CaMV 35S promoter is more effective than single promoter. The AMV or TMV enhancer is able to promote the foreign protein expression. After four-step purification, the activated hBMP2 (0.02% total soluble protein) was obtained. Our results suggested that the transgenic tobacco has great potential to be used as a bioreactor to produce hBMP2. PMID:16819603

  16. Biokerosene from biomethane via GtL-processes. A technical and economic analysis; Biokerosin aus Biomethan ueber GtL-Prozesse. Eine technische und oekonomische Analyse

    Energy Technology Data Exchange (ETDEWEB)

    Gebauer, Jan Peer; Wagner, Hannes; Kaltschmitt, Martin [Technische Univ. Hamburg-Harburg, Hamburg (Germany). Inst. fuer Umwelttechnik und Energiewirtschaft

    2013-02-15

    To protect climate, the aviation industry is asked to reduce GHG emissions. A possible measure to achieve this goal is the increased use of biokerosene. One possible way to provide biokerosene is through liquefaction of biomethane. This biomethane can be produced by anaerobic fermentation from large variety of organic waste streams. Considering this background, an overview of the overall process chain for the production of biokerosene from biomethane is given. The starting point for the analysis is the Gasto-Liquid-process (GtL). This process is described in detail focusing on the differences between autothermal and steam reforming of biomethane. Based on this, two reference concepts are designed, modeled, and simulated. The results of this simulation are then evaluated according to predefined technical parameters. Finally, the defined concepts are analyzed economically, i.e. the production costs are assessed and the key parameters defining the results are identified.

  17. Bio methane in the cogeneration market and heating market. Status quo, potentials and recommendations for an accelerated market penetration; Biomethan im KWK- und Waermemarkt. Status Quo, Potenziale und Handlungsempfehlungen fuer eine beschleunigte Marktdurchdringung

    Energy Technology Data Exchange (ETDEWEB)

    Herr, Michael; Rostek, Sandra (comps.)

    2010-07-15

    The current contribution of the German Energy Agency (Berlin, Federal Republic of Germany) reports on the present sale situation of bio methane on the coupled and uncoupled heating market. The contribution clarifies, why the existing support measures do not stimulate the demand for bio methane in the necessary order of magnitude. Without adjustment of the legal framework neither the considerable sales potentials can be established, nor the targets for the development of the biogas feeding can be achieved approximately. The low demand on bio methane led to a planning stop on the producer side. Direct need for action is required.

  18. EU-Project REDUBAR. National and international biomethane networks; Das EU-Projekt REDUBAR. Nationale und internationale Biomethan-Netzwerke

    Energy Technology Data Exchange (ETDEWEB)

    Oettel, Eberhard; Rickert, Ingo [Foerdergesellschaft Erneuerbare Energien e.V. (FEE), Berlin (Germany); Albring, Peter [ILK Inst. fuer Luft- und Kaeltetechnikgemeinnuetzige GmbH, Dresden (Germany); Schrum, Peter; Tuaschke, Martin [BBK Bundesverband Biogene und RegenerativeKraft- und Treibstoffe e.V., Erkner (Germany)

    2009-07-01

    In an unprecedented appeal to the G8 Energy Ministers at their meeting 24./25.05.2009 at Rome, Italy, the Executive Secretary of the IEA International Energy Agency called for immediate and appropriate measures to counterbalance the effects of the global financial crisis. He demanded to invest substantially more in renewable energy sources (RES), energy efficiency (EE) and decarbonisation. Otherwise a long-lasting energy crisis could menace already by 2012 /2013 with far-reaching consequences for energy security and climate protection. The crisis could even lead to energy poverty. [1] The 16{sup th} European Biomass Conference ''From Research to Industry and Markets'' (02 - 06 June 2008, Valencia, Spain) approved that biomass is becoming a scarce commodity and urged decision-makers from politics, industry, transport, agriculture and forestry to increase exergy, decrease energy and augment substantially the energy efficiency of use of biomass in cascades from cultivation to polygeneration. Biomass is the only renewable carbon and energy carrier made by human beings. [2] Biogas produced by digestion from biological secondary raw materials and industrial crops would offer just these properties in its combustion in combined heat and power (CHP) plants to generate electricity and heat, and convert the heat into cold. But because of the location of the plant sites far away from heat sinks about half of its chemically bound energy is wasted. Just in this regard biomethane and in future bio-SNG are commodities with outstanding properties. As a natural gas substitute biomethane can be injected into the natural gas grid, used as automotive fuel or as a secondary renewable energy carrier utilised in high temperature industrial processes with high efficiency far away from the producing plants. Resulting from a study, several research institutes summarized that given well-defined conditions theoretically and under ideal assumptions all natural gas imported

  19. Differential expression of Bmp2, Bmp4 and Bmp3 in embryonic development of mouse anterior and posterior palate

    Institute of Scientific and Technical Information of China (English)

    NIE Xu-guang

    2005-01-01

    Background The palate is differently regulated and developed along the anterior-posterior axis. The Bmp signal pathway plays a crucial role in palatogenesis. Conditioned-inactivation of Bmp type I receptor Alk2 or Alk3 in the neural crest or craniofacial region leads to palatal cleft in mice. However, how different Bmp members are involved in palatogenesis remains to be elucidated. In the present study, mRNA expression patterns of Bmp2, Bmp3 and Bmp4 in the developing anterior and posterior palates were examined and compared, focusing on the fusion stage. Methods To detect the expression of Bmp mRNA, antisense riboprobes were synthesized by in vitro transcription. Radioactive in situ hybridization was performed on sagital and coronal sections of mice head from E13 to E18. Results The expression of these Bmps were developmentally regulated in the anterior and posterior palates prior to, during and after palatal fusion. During palatal fusion, Bmp4 expression shifted from the anterior to the posterior palate, Bmp2 was highly expressed in both the anterior and posterior palates in this process, whereas Bmp3 was only localized in the posterior palate. They showed generally non-overlapping pattern in their expression domains. Thereafter, their expression was detected in both the anterior and posterior palates regulating osteogenesis and myogenesis respectively. Conclusions Bmp signalling is involved in palatogenesis in multiple stages and has multiple roles in regulating anterior and posterior palatal development. Disturbances of Bmp signalling during palatogenesis might be a possible mechanism of cleft palate.

  20. Bone Morphogenetic Protein (BMP-4 and BMP-7 regulate differentially Transforming Growth Factor (TGF-β1 in normal human lung fibroblasts (NHLF

    Directory of Open Access Journals (Sweden)

    Lloyd Clare M

    2010-06-01

    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

  1. Fibrin Hydrogel Based Bone Substitute Tethered with BMP-2 and BMP-2/7 Heterodimers

    Directory of Open Access Journals (Sweden)

    Lindsay S. Karfeld-Sulzer

    2015-03-01

    Full Text Available Current clinically used delivery methods for bone morphogenetic proteins (BMPs are collagen based and require large concentrations that can lead to dangerous side effects. Fibrin hydrogels can serve as osteoinductive bone substitute materials in non-load bearing bone defects in combination with BMPs. Two strategies to even further optimize such a fibrin based system include employing more potent BMP heterodimers and engineering growth factors that can be covalently tethered to and slowly released from a fibrin matrix. Here we present an engineered BMP-2/BMP-7 heterodimer where an N-terminal transglutaminase substrate domain in the BMP-2 portion provides covalent attachment to fibrin together with a central plasmin substrate domain, a cleavage site for local release of the attached BMP-2/BMP-7 heterodimer under the influence of cell-activated plasmin. In vitro and in vivo results revealed that the engineered BMP-2/BMP-7 heterodimer induces significantly more alkaline phosphatase activity in pluripotent cells and bone formation in a rat calvarial model than the engineered BMP-2 homodimer. Therefore, the engineered BMP-2/BMP-7 heterodimer could be used to reduce the amount of BMP needed for clinical effect.

  2. BMP12 induces tenogenic differentiation of adipose-derived stromal cells.

    Directory of Open Access Journals (Sweden)

    Hua Shen

    Full Text Available Adipose-derived stromal cells (ASCs are pluripotent cells that have the capacity to differentiate into tendon fibroblasts (TFs. They are abundant in adults, easy to access, and are therefore an ideal cell source for tendon tissue engineering. Despite this potential, the molecular cues necessary for tenogenic differentiation of ASCs are unknown. Unlike other bone morphogenetic proteins (BMPs, BMP12, BMP13, and BMP14 have been reported to be less osteo-chondrogenic and to induce tendon rather than bone formation in vivo. This study investigated the effects of BMP12 and BMP14 on ASC differentiation in vitro. In canine ASCs, BMP12 effectively increased the expression of the tendon markers scleraxis and tenomodulin at both mRNA and protein levels. Consistent with these results, BMP12 induced scleraxis promoter driven-GFP and tenomodulin protein expression in mouse ASCs. Although BMP12 also enhanced the expression of the cartilage matrix gene aggrecan in ASCs, the resulting levels remained considerably lower than those detected in tendon fibroblasts. In addition, BMP12 reduced expression of the bone marker osteocalcin, but not the osteogenic transcription factor runx-2. BMP14 exhibited similar, but marginally less potent and selective effects, compared to BMP12. BMPs are known to signal through the canonical Smad pathway and the non-canonical mitogen-activated protein kinase (MAPK pathway. BMP12 triggered robust phosphorylation of Smad1/5/8 but not Smad2/3 or p38 MAPK in ASCs. The effect was likely conveyed by type I receptors ALK2/3/6, as phosphorylation of Smad1/5/8 was blocked by the ALK2/3/6 inhibitor LDN-193189 but not by the ALK4/5/7 inhibitor SB-505124. Moreover, ALK6 was found to be the most abundant type I receptor in ASCs, with mRNA expression 100 to 10,000 times that of any other type I receptor. Collectively, results support the conclusion that BMP12 induces tenogenic differentiation of ASCs via the Smad1/5/8 pathway.

  3. BMP-2 Overexpression Augments Vascular Smooth Muscle Cell Motility by Upregulating Myosin Va via Erk Signaling

    Directory of Open Access Journals (Sweden)

    Ming Zhang

    2014-01-01

    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.

  4. Characterization of anaerobic consortia coupled lignin depolymerization with biomethane generation.

    Science.gov (United States)

    Wu, Yi-Rui; He, Jianzhong

    2013-07-01

    Two sediment-free microbial consortia (LI3 and LP3) were established to depolymerize lignin under anaerobic conditions. During depolymerizing high molecular weight lignin to low molecular weight molecules, the two cultures produced biomethane up to 151.7 and 113.0 mL g(-1) total lignin. Furthermore, LI3 and LP3 could also utilize the biomass - oil palm empty fruit bunch fiber (OPEFB) to produce 190.6 and 195.6 mL methaneg(-1) total lignin in OPEFB, and at the same time improve the bioavailability of lignocellulosic matters for further enzymatic hydrolysis. The microbial community analysis by denature gradient gel electrophoresis (DGGE) and the high-density 16S rDNA gene microarray (PhyloChip) exhibited that Methanomethylovorans sp. (LI3) and Methanoculleus sp. (LP3) were the main methanogens present, and phylum Firmicutes and Bacteroidetes were mainly involved in the lignin depolymerization. The established microbial consortia with both lignin depolymerization and biomethane production provide profound application on the environmental friendly pretreatment of lignocellulosic materials. PMID:23639408

  5. Studies on biomethanation of water hyacinth (eichhornia crassipes) using biocatalyst

    Energy Technology Data Exchange (ETDEWEB)

    Sarkar, Santanu [Department of Chemical Engineering, Jadavpur University, Kolkata-700032 (India); Banerjee, Saikat [Department of Chemical Engineering, Salalah College of Technology, Salalah (Oman)

    2013-07-01

    Water hyacinth is a huge source of biomass in tropical countries. That can be used for biogas production. The aim of this conversion process is to improve the quality, specific energy content, transportability, etc. of the raw biomass source or to capture gases which are naturally produced as biomass is micro biologically degraded. An experimental study on catalytic biomethanation of Water Hyacinth has been carried out in a semi batch digester at different substrate concentration using cow urine as an organic catalyst under controlled pH with in the range of 6.9 to 7.2. The rate of bio gas production varies with different conditions and parameters like temperature, stirring speed, feed concentration, catalyst concentration, etc. It has been found that the catalyst mainly increases the production rate of biogas from water hyacinth. Mathematical analysis of the experimental data on catalytic biomethanation has been done in the present study. Mathematical equations relating maximum specific growth rate and kinetic parameter at different substrate and catalyst concentration have been developed.

  6. Biomethane production system: Energetic analysis of various scenarios.

    Science.gov (United States)

    Wu, Bin; Zhang, Xiangping; Bao, Di; Xu, Yajing; Zhang, Suojiang; Deng, Liyuan

    2016-04-01

    The energy consumption models of biomethane production system were established, which are more rigorous and universal than the empirical data reported by previous biomethane system energetic assessment work. The energy efficiencies of different scenarios considering factors such as two digestion modes, two heating modes of digester, with or without heat exchange between slurry and feedstock, and four crude biogas upgrading technologies were evaluated. Results showed the scenario employing thermophilic digestion and high pressure water scrubbing technology, with heat exchange between feedstock and slurry, and heat demand of digester supplied by the energy source outside the system has the highest energy efficiency (46.5%) and lowest energy consumption (13.46 MJth/Nm(3) CH4), while scenario employing mesophilic digestion and pressure swing adsorption technology, without heat exchange and heat demand of digester supplied by combusting the biogas produced inside the system has the lowest energy efficiency (15.8%) and highest energy consumption (34.90 MJth/Nm(3) CH4). PMID:26855289

  7. Studies on biomethanation of water hyacinth (eichhornia crassipes using biocatalyst

    Directory of Open Access Journals (Sweden)

    Santanu Sarkar, Saikat Banerjee

    2013-01-01

    Full Text Available Water hyacinth is a huge source of biomass in tropical countries. That can be used for biogas production. The aim of this conversion process is to improve the quality, specific energy content, transportability, etc. of the raw biomass source or to capture gases which are naturally produced as biomass is micro biologically degraded. An experimental study on catalytic biomethanation of Water Hyacinth has been carried out in a semi batch digester at different substrate concentration using cow urine as an organic catalyst under controlled pH with in the range of 6.9 to 7.2. The rate of bio gas production varies with different conditions and parameters like temperature, stirring speed, feed concentration, catalyst concentration, etc. It has been found that the catalyst mainly increases the production rate of biogas from water hyacinth. Mathematical analysis of the experimental data on catalytic biomethanation has been done in the present study. Mathematical equations relating maximum specific growth rate and kinetic parameter at different substrate and catalyst concentration have been developed.

  8. BMP2-loaded hollow hydroxyapatite microspheres exhibit enhanced osteoinduction and osteogenicity in large bone defects.

    Science.gov (United States)

    Xiong, Long; Zeng, Jianhua; Yao, Aihua; Tu, Qiquan; Li, Jingtang; Yan, Liang; Tang, Zhiming

    2015-01-01

    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. PMID:25609957

  9. Repressive BMP2 gene regulatory elements near the BMP2 promoter

    International Nuclear Information System (INIS)

    The level of bone morphogenetic protein 2 (BMP2) profoundly influences essential cell behaviors such as proliferation, differentiation, apoptosis, and migration. The spatial and temporal pattern of BMP2 synthesis, particular in diverse embryonic cells, is highly varied and dynamic. We have identified GC-rich sequences within the BMP2 promoter region that strongly repress gene expression. These elements block the activity of a highly conserved, osteoblast enhancer in response to FGF2 treatment. Both positive and negative gene regulatory elements control BMP2 synthesis. Detecting and mapping the repressive motifs is essential because they impede the identification of developmentally regulated enhancers necessary for normal BMP2 patterns and concentration.

  10. Repressive BMP2 gene regulatory elements near the BMP2 promoter

    Energy Technology Data Exchange (ETDEWEB)

    Jiang, Shan [Department of Biochemistry and Molecular Biology, University of Medicine and Dentistry (UMDNJ), New Jersey Medical School (NJMS), Newark, NJ (United States); Chandler, Ronald L. [Department of Molecular Physiology and Biophysics, Center for Human Genetics Research, Vanderbilt University School of Medicine, Nashville, TN (United States); Fritz, David T. [Department of Biochemistry and Molecular Biology, University of Medicine and Dentistry (UMDNJ), New Jersey Medical School (NJMS), Newark, NJ (United States); Mortlock, Douglas P. [Department of Molecular Physiology and Biophysics, Center for Human Genetics Research, Vanderbilt University School of Medicine, Nashville, TN (United States); Rogers, Melissa B., E-mail: rogersmb@umdnj.edu [Department of Biochemistry and Molecular Biology, University of Medicine and Dentistry (UMDNJ), New Jersey Medical School (NJMS), Newark, NJ (United States)

    2010-02-05

    The level of bone morphogenetic protein 2 (BMP2) profoundly influences essential cell behaviors such as proliferation, differentiation, apoptosis, and migration. The spatial and temporal pattern of BMP2 synthesis, particular in diverse embryonic cells, is highly varied and dynamic. We have identified GC-rich sequences within the BMP2 promoter region that strongly repress gene expression. These elements block the activity of a highly conserved, osteoblast enhancer in response to FGF2 treatment. Both positive and negative gene regulatory elements control BMP2 synthesis. Detecting and mapping the repressive motifs is essential because they impede the identification of developmentally regulated enhancers necessary for normal BMP2 patterns and concentration.

  11. Biomethane Production as an Alternative Bioenergy Source from Codigesters Treating Municipal Sludge and Organic Fraction of Municipal Solid Wastes

    Directory of Open Access Journals (Sweden)

    M. Evren Ersahin

    2011-01-01

    Full Text Available Energy recovery potential of a mesophilic co-digester treating OFMSW and primary sludge at an integrated biomethanization plant was investigated based on feasibility study results. Since landfilling is still the main solid waste disposal method in Turkey, land scarcity will become one of the most important obstacles. Restrictions for biodegradable waste disposal to sanitary landfills in EU Landfill Directive and uncontrolled long-term contamination with gas emissions and leachate necessitate alternative management strategies due to rapid increase in MSW production. Moreover, since energy contribution from renewable resources will be required more in the future with increasing oil prices and dwindling supplies of conventional energy sources, the significance of biogas as a renewable fuel has been increased in the last decade. Results indicated that almost 93% of annual total cost can be recovered if 100% renewable energy subsidy is implemented. Besides, considering the potential revenue when replacing transport fuels, about 26 heavy good vehicles or 549 cars may be powered per year by the biogas produced from the proposed biomethanization plant (PE = 100,000; XPS = 61 g TS/PE⋅day; XSS-OFMSW=50 g TS/PE⋅day.

  12. Biomethane production as an alternative bioenergy source from codigesters treating municipal sludge and organic fraction of municipal solid wastes.

    Science.gov (United States)

    Ersahin, M Evren; Gomec, Cigdem Yangin; Dereli, R Kaan; Arikan, Osman; Ozturk, Izzet

    2011-01-01

    Energy recovery potential of a mesophilic co-digester treating OFMSW and primary sludge at an integrated biomethanization plant was investigated based on feasibility study results. Since landfilling is still the main solid waste disposal method in Turkey, land scarcity will become one of the most important obstacles. Restrictions for biodegradable waste disposal to sanitary landfills in EU Landfill Directive and uncontrolled long-term contamination with gas emissions and leachate necessitate alternative management strategies due to rapid increase in MSW production. Moreover, since energy contribution from renewable resources will be required more in the future with increasing oil prices and dwindling supplies of conventional energy sources, the significance of biogas as a renewable fuel has been increased in the last decade. Results indicated that almost 93% of annual total cost can be recovered if 100% renewable energy subsidy is implemented. Besides, considering the potential revenue when replacing transport fuels, about 26 heavy good vehicles or 549 cars may be powered per year by the biogas produced from the proposed biomethanization plant (PE = 100,000; X(PS) = 61 g TS/PE·day; X(SS-OFMSW) = 50 g TS/PE·day). PMID:21274432

  13. KlimaCH4. Climate effects of biomethane economy; KlimaCH4. Klimaeffekte von Biomethan

    Energy Technology Data Exchange (ETDEWEB)

    Westerkamp, Tanja; Reinelt, Torsten; Oehmichen, Katja; Ponitka, Jens; Naumann, Karin

    2014-07-01

    Within the project ''Climate effects of biomethane economy'' (KlimaCH4) of the German Biomass Research Centre two methods for measurement of direct greenhouse gas emissions were analyzed for their applicability and comparability. In the context of concrete measurements direct emissions, mainly of methane, three biogas plants with methane treatment for feeding into the natural gas grid were quantified. These tests were carried out on the one hand directly on-site by using leak detection, enclosures and ''open chamber'' measurements, but also indirectly by optical remote sensing with tunable diode laser absorption spectrometry (TDLAS) and reverse dispersion modelling by inverse dispersion modeling. The on-site method offers the possibility, to investigate the influences of plant operation on emissions of known diffuse sources, inter alia, through the balance of the operating status with the timeline of a specific emission source (e.g. as increased release of methane due to stirring intervals). This is particularly useful for deriving appropriate measures to reduce emissions. The quantification of individual, diffuse emission sources is metrologically possibly only very costly to implement. The effort is depending to a considerable extent by the design and the size of the examined biogas plant. In order to detect the influence seasonal changing of environmental conditions recurring emission measurements were realized. The use of optical telemetry showed as an advantageous alternative to on-site method, because it can significantly reduce time required for emission measurements particularly at large biogas plants or plants with numerous individual sources. With only one measurement sequence all emission sources are covered, without consuming individual measurements. In addition, in comparision to the on-site method, the emission situation of the entire system can be better reproduced, since all individual sources are included in

  14. KlimaCH4. Climate effects of biomethane economy; KlimaCH4. Klimaeffekte von Biomethan

    Energy Technology Data Exchange (ETDEWEB)

    Westerkamp, Tanja; Reinelt, Torsten; Oehmichen, Katja; Ponitka, Jens; Naumann, Karin

    2014-07-01

    Within the project ''Climate effects of biomethane economy'' (KlimaCH4) of the German Biomass Research Centre two methods for measurement of direct greenhouse gas emissions were analyzed for their applicability and comparability. In the context of concrete measurements direct emissions, mainly of methane, three biogas plants with methane treatment for feeding into the natural gas grid were quantified. These tests were carried out on the one hand directly on-site by using leak detection, enclosures and ''open chamber'' measurements, but also indirectly by optical remote sensing with tunable diode laser absorption spectrometry (TDLAS) and reverse dispersion modelling by inverse dispersion modeling. The on-site method offers the possibility, to investigate the influences of plant operation on emissions of known diffuse sources, inter alia, through the balance of the operating status with the timeline of a specific emission source (e.g. as increased release of methane due to stirring intervals). This is particularly useful for deriving appropriate measures to reduce emissions. The quantification of individual, diffuse emission sources is metrologically possibly only very costly to implement. The effort is depending to a considerable extent by the design and the size of the examined biogas plant. In order to detect the influence seasonal changing of environmental conditions recurring emission measurements were realized. The use of optical telemetry showed as an advantageous alternative to on-site method, because it can significantly reduce time required for emission measurements particularly at large biogas plants or plants with numerous individual sources. With only one measurement sequence all emission sources are covered, without consuming individual measurements. In addition, in comparision to the on-site method, the emission situation of the entire system can be better reproduced, since all individual sources are included in

  15. Mouse bone marrow stromal cells differentiate to neuron-like cells upon inhibition of BMP signaling.

    Science.gov (United States)

    Saxena, Monika; Prashar, Paritosh; Yadav, Prem Swaroop; Sen, Jonaki

    2016-01-01

    Bone marrow stromal cells (BMSCs) are a source of autologous stem cells that have the potential for undergoing differentiation into multiple cell types including neurons. Although the neuronal differentiation of mesenchymal stem cells has been studied for a long time, the molecular players involved are still not defined. Here we report that the genetic deletion of two members of the bone morphogenetic protein (Bmp) family, Bmp2 and Bmp4 in mouse BMSCs causes their differentiation into cells with neuron-like morphology. Surprisingly these cells expressed certain markers characteristic of both neuronal and glial cells. Based on this observation, we inhibited BMP signaling in mouse BMSCs through a brief exposure to Noggin protein which also led to their differentiation into cells expressing both neuronal and glial markers. Such cells seem to have the potential for further differentiation into subtypes of neuronal and glial cells and thus could be utilized for cell-based therapeutic applications.

  16. Profitability Analysis for Biomethane: A Strategic Role in the Italian Transport Sector

    OpenAIRE

    Federica Cucchiella; Idiano D’Adamo; Massimo Gastaldi

    2015-01-01

    Biomethane is an interesting source for sustainable energy systems, featuring great flexibility that translates into multiple possible applications (vehicle fuel, combined production of thermal and electrical energy, injection in the gas grid). Compared to biogas, biomethane permits greater efficiency. Its use is not limited to the immediate area of the plant and purification of the raw methane means greater lifespans for the equipment. This paper analyses its use in the transport sector in l...

  17. Analyzing the Dynamics of the Bio-methane Production Chain and the Effectiveness of Subsidization Schemes under Uncertainty

    OpenAIRE

    Eker, S.; Van Daalen, C.

    2014-01-01

    Bio-methane is a renewable gas option that can be injected to the natural gas grids to increase the sustainability of the energy system and to deal with natural gas supply problems. However, being based on several factors such as resource availability, competition between bio-methane and electricity sectors for biogas and biomass supply, demand, capacity installation and profitability, the future dynamics of bio-methane production is uncertain. In this study, we investigated the dynamics of b...

  18. A MATHEMATICAL STUDY OF THE IMPACT OF METHANOGENIC AND HYDROGENOTROPHIC STEPS ON BIOMETHANE PRODUCTION FROM ORGANIC WASTES

    OpenAIRE

    Simeonov, Ivan; Kroumov, Alexander

    2012-01-01

    Anaerobic digestion is an effective biotechnological process for treatment of different organic waste with production of biogas. In this paper the performed mathematical analysis of the behavior of a bacterial consortium during biomethane synthesis is presented. A new pathway of biomethane production was studied based on the metabolism of hydrogenotrophic bacteria where up to 30% of biometane can be synthesized. The other group involved in biomethane synthesis were recognised as acidoclastic ...

  19. BMP7 Activates Brown Adipose Tissue and Reduces Diet-Induced Obesity Only at Subthermoneutrality

    Science.gov (United States)

    Boon, Mariëtte R.; van den Berg, Sjoerd A. A.; Wang, Yanan; van den Bossche, Jan; Karkampouna, Sofia; Bauwens, Matthias; De Saint-Hubert, Marijke; van der Horst, Geertje; Vukicevic, Slobodan; de Winther, Menno P. J.; Havekes, Louis M.; Jukema, J. Wouter; Tamsma, Jouke T.; van der Pluijm, Gabri; van Dijk, Ko Willems; Rensen, Patrick C. N.

    2013-01-01

    Background/Aims Brown adipose tissue (BAT) dissipates energy stored in triglycerides as heat via the uncoupling protein UCP-1 and is a promising target to combat hyperlipidemia and obesity. BAT is densely innervated by the sympathetic nervous system, which increases BAT differentiation and activity upon cold exposure. Recently, Bone Morphogenetic Protein 7 (BMP7) was identified as an inducer of BAT differentiation. We aimed to elucidate the role of sympathetic activation in the effect of BMP7 on BAT by treating mice with BMP7 at varying ambient temperature, and assessed the therapeutic potential of BMP7 in combating obesity. Methods and Results High-fat diet fed lean C57Bl6/J mice were treated with BMP7 via subcutaneous osmotic minipumps for 4 weeks at 21°C or 28°C, the latter being a thermoneutral temperature in which sympathetic activation of BAT is largely diminished. At 21°C, BMP7 increased BAT weight, increased the expression of Ucp1, Cd36 and hormone-sensitive lipase in BAT, and increased total energy expenditure. BMP7 treatment markedly increased food intake without affecting physical activity. Despite that, BMP7 diminished white adipose tissue (WAT) mass, accompanied by increased expression of genes related to intracellular lipolysis in WAT. All these effects were blunted at 28°C. Additionally, BMP7 resulted in extensive ‘browning’ of WAT, as evidenced by increased expression of BAT markers and the appearance of whole clusters of brown adipocytes via immunohistochemistry, independent of environmental temperature. Treatment of diet-induced obese C57Bl6/J mice with BMP7 led to an improved metabolic phenotype, consisting of a decreased fat mass and liver lipids as well as attenuated dyslipidemia and hyperglycemia. Conclusion Together, these data show that BMP7-mediated recruitment and activation of BAT only occurs at subthermoneutral temperature, and is thus likely dependent on sympathetic activation of BAT, and that BMP7 may be a promising tool to

  20. Optimization of biomethanation focusing on high ammonia loaded processes

    DEFF Research Database (Denmark)

    Wang, Han

    , could theoretically mitigate the ammonia inhibition problem (Angelidaki et al., 1999). Therefore, the effect of co-digestion of cattle manure with lipids (i.e. glycerol trioleate (GTO)) under high ammonia levels (5 g NH4+-N·L-1) in anaerobic continuous stirred tank (CSTR) reactors (RGTO) was assessed......” was observed, which caused a deterioration of the inhibition effect in anaerobic digestion process. On contrary, the reactor where glucose was co-digested demonstrated higher tolerance to ammonia toxicity compared with the reactor where GTO was used. Secondly, the problem of ammonia inhibition during...... in continuous reactors. Furthermore, bioaugmentation with an ammonia tolerant methanogen to alleviate ammonia toxicity could be applied for improving the efficiency of biomethanation process in full-scale continuous reactors. Finally, an innovative method, where hydrogen is injected in the anaerobic reactor...

  1. Bacillus thuringiensis metalloproteinase Bmp1 functions as a nematicidal virulence factor.

    Science.gov (United States)

    Luo, Xiaoxia; Chen, Ling; Huang, Qiong; Zheng, Jinshui; Zhou, Wei; Peng, Donghai; Ruan, Lifang; Sun, Ming

    2013-01-01

    Some Bacillus thuringiensis strains have high toxicity to nematodes. Nematicidal activity has been found in several families of crystal proteins, such as Cry5, Cry6, and Cry55. The B. thuringiensis strain YBT-1518 has three cry genes that have high nematicidal activity. The whole genome sequence of this strain contains multiple potential virulence factors. To evaluate the pathogenic potential of virulence factors, we focused on a metalloproteinase called Bmp1. It encompasses a consecutive N-terminal signal peptide, an FTP superfamily domain, an M4 neutral protease GluZincin superfamily, two Big-3 superfamily motifs, and a Gram-positive anchor superfamily motif as a C-terminal domain. Here, we showed that purified Bmp1 protein showed metalloproteinase activity and toxicity against Caenorhabditis elegans (the 50% lethal concentration is 610 ± 9.37 μg/ml). In addition, mixing Cry5Ba with Bmp1 protein enhanced the toxicity 7.9-fold (the expected toxicity of the two proteins calculated from their separate toxicities) against C. elegans. Confocal microscopic observation revealed that Bmp1 protein was detected from around the mouth and esophagus to the intestine. Striking microscopic images revealed that Bmp1 degrades intestine tissues, and the Cry5Ba causes intestinal shrinkage from the body wall. Thus, the B. thuringiensis Bmp1 metalloproteinase is a nematicidal virulence factor. These findings give a new insight into the relationship between B. thuringiensis and its host nematodes.

  2. Osteogenesis Capacity of a Novel BMP/α-TCP Bioactive Composite Bone Cement

    Institute of Scientific and Technical Information of China (English)

    YANG Wei-zhong; ZHOU Da-li; YIN Shao-ya; YIN Guang-fu; GAO Li-da; ZHANG Yun

    2004-01-01

    To improve the osteogenesis ability of α-tricalcium phosphate (α-TCP) bone cement,a novel BMP/α-TCP composite bone cement was prepared.By measuring the setting time and compressive strength,the hydration characteristic of bone cement was evaluated.Animal experiments including histological observation,radiographic investigation as well as digital image analyses reveal the difference of osteogenesis ability among BMP,α-TCP bone cement and BMP/α-TCP composite bone cement.Results show that α-TCP bone cement possesses excellent hydration and setting properties as well as high mechanical property.Comparison experiments show that BMP/α-TCP composite bone cement has a stronger osteogenesis ability.The gross observation of the implant site does not exhibit any inflammation or necrosis.Histological analyses reveal that the material has good osteointegration with host bone,and new bone formation is detected within the materials,which are degrading.Strong osteogenesis ability of the composite is due to not only the excellent osteoconductive potential but also the osteoinductive potential contributed by active BMP releasing and the material degradation.Large skull defect could be well-healed by filling BMP/α-TCP composite bone cement.This novel material proves itself to be an absorbable and bioactive bone cement with an osteogenesis ability.

  3. Simultaneous gene transfer of bone morphogenetic protein (BMP -2 and BMP-7 by in vivo electroporation induces rapid bone formation and BMP-4 expression

    Directory of Open Access Journals (Sweden)

    Miyazaki Jun-ichi

    2006-08-01

    Full Text Available Abstract Background Transcutaneous in vivo electroporation is expected to be an effective gene-transfer method for promoting bone regeneration using the BMP-2 plasmid vector. To promote enhanced osteoinduction using this method, we simultaneously transferred cDNAs for BMP-2 and BMP-7, as inserts in the non-viral vector pCAGGS. Methods First, an in vitro study was carried out to confirm the expression of BMP-2 and BMP-7 following the double-gene transfer. Next, the individual BMP-2 and BMP-7 plasmids or both together were injected into rat calf muscles, and transcutaneous electroporation was applied 8 times at 100 V, 50 msec. Results In the culture system, the simultaneous transfer of the BMP-2 and BMP-7 genes led to a much higher ALP activity in C2C12 cells than did the transfer of either gene alone. In vivo, ten days after the treatment, soft X-ray analysis showed that muscles that received both pCAGGS-BMP-2 and pCAGGS-BMP-7 had better-defined opacities than those receiving a single gene. Histological examination showed advanced ossification in calf muscles that received the double-gene transfer. BMP-4 mRNA was also expressed, and RT-PCR showed that its level increased for 3 days in a time-dependent manner in the double-gene transfer group. Immunohistochemistry confirmed that BMP-4-expressing cells resided in the matrix between muscle fibers. Conclusion The simultaneous transfer of BMP-2 and BMP-7 genes using in vivo electroporation induces more rapid bone formation than the transfer of either gene alone, and the increased expression of endogenous BMP-4 suggests that the rapid ossification is related to the induction of BMP-4.

  4. Bone Morphogenetic Protein (BMP-7 expression is decreased in human hypertensive nephrosclerosis

    Directory of Open Access Journals (Sweden)

    Cohen Clemens D

    2010-11-01

    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.

  5. How can we improve biomethane production per unit of feedstock in biogas plants?

    International Nuclear Information System (INIS)

    Biogas production is one of the number of tools that may be used to alleviate the problems of global warming, energy security and waste management. Biogas plants can be difficult to sustain from a financial perspective. The facilities must be financially optimized through use of substrates with high biogas potential, low water content and low retention requirement. This research carried out in laboratory scale batch digesters assessed the biogas potential of energy crops (maize and grass silage) and solid manure fractions from manure separation units. The ultimate methane productivity in terms of volatile solids (VS) was determined as 330, 161, 230, 236, 361 L/kg VS from raw pig slurry, filter pressed manure fiber (FPMF), chemically precipitated manure fiber (CPMF), maize silage and grass silage respectively. Methane productivity based on mass (L/kg substrate) was significantly higher in FPMF (55 L/kg substrate), maize silage (68 L/kg substrate) and grass silage (45-124 L/kg substrate (depending on dry solids of feedstock)) as in comparison to raw pig slurry (10 L/kg substrate). The use of these materials as co-substrates with raw pig slurry will increase significantly the biomethane yield per unit feedstock in the biogas plant.

  6. Rat adipose-derived stromal cells expressing BMP4 induce ectopic bone formation in vitro and in vivo

    Institute of Scientific and Technical Information of China (English)

    Lin LIN; Xin FU; Xin ZHANG; Lian-xu CHEN; Ji-ying ZHANG; Chang-long YU; Kang-tao MA; Chun-yan ZHOU

    2006-01-01

    Aim: Bone morphogenetic protein 4 (BMP4) is one of the main local contributing factors in callus formation in the early phase of fracture healing. Adipose-derived stromal cells (ADSC) are multipotent cells. The present study was conducted to investigate the osteogenic potential of ADSC when exposed to adenovirus containing BMP4 cDNA (Ad-BMP4). Methods: ADSC were harvested from Sprague-Dawley rats. After exposure to Ad-BMP4, ADSC were assessed by alkaline phos-phatase activity (ALP) assay, RT-PCR and von Kossa staining. BMP4 expression was assessed by RT-PCR, immunofluorescence and Western blot analysis. ADSC transduced with Ad-BMP4 were directly injected into the hind limb muscles of athymic mice. ADSC Ad-EGFP(enhanced green fluorescence protein) served as controls. All animals were examined by X-ray film and histological analysis. Results: The expression of BMP4 was confirmed at both mRNA and protein levels. The expression of the osteoblastic gene, ALP activity and von Kossa staining confirmed that ADSC transduced with Ad-BMP4 underwent rapid and marked osteoblast differentiation, whereas ADSC transduced with Ad-EGFP and cells left alone displayed no osteogenic differentiation. X-ray and histological examination confirmed new bone formation in athymic mice transplanted with ADSC transduced with Ad-BMP4. Conclusion: Our data demonstrated successful osteogenic differentiation of ADSC transduced with Ad-BMP4 in vitro and in vivo. ADSC may be an ideal source of mesenchyme lineage stem cells for gene therapy and tissue engineering.

  7. Analyzing the Dynamics of the Bio-methane Production Chain and the Effectiveness of Subsidization Schemes under Uncertainty

    NARCIS (Netherlands)

    Eker, S.; Van Daalen, C.

    2014-01-01

    Bio-methane is a renewable gas option that can be injected to the natural gas grids to increase the sustainability of the energy system and to deal with natural gas supply problems. However, being based on several factors such as resource availability, competition between bio-methane and electricity

  8. Emerging roles of BMP9 and BMP10 in hereditary hemorrhagic telangiectasia

    Directory of Open Access Journals (Sweden)

    Emmanuelle eTillet

    2015-01-01

    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.

  9. Simultaneous gene transfer of bone morphogenetic protein (BMP) -2 and BMP-7 by in vivo electroporation induces rapid bone formation and BMP-4 expression

    OpenAIRE

    Kawai, Mariko; Bessho, Kazuhisa; Maruyama, Hiroki; Miyazaki, Jun-ichi; Yamamoto, Toshio

    2006-01-01

    Background: Transcutaneous in vivo electroporation is expected to be an effective gene-transfer method for promoting bone regeneration using the BMP-2 plasmid vector. To promote enhanced osteoinduction using this method, we simultaneously transferred cDNAs for BMP-2 and BMP-7, as inserts in the non-viral vector pCAGGS.

  10. A Review on the Valorization of Macroalgal Wastes for Biomethane Production

    Science.gov (United States)

    Barbot, Yann Nicolas; Al-Ghaili, Hashem; Benz, Roland

    2016-01-01

    The increased use of terrestrial crops for biofuel production and the associated environmental, social and ethical issues have led to a search for alternative biomass materials. Terrestrial crops offer excellent biogas recovery, but compete directly with food production, requiring farmland, fresh water and fertilizers. Using marine macroalgae for the production of biogas circumvents these problems. Their potential lies in their chemical composition, their global abundance and knowledge of their growth requirements and occurrence patterns. Such a biomass industry should focus on the use of residual and waste biomass to avoid competition with the biomass requirements of the seaweed food industry, which has occurred in the case of terrestrial biomass. Overabundant seaweeds represent unutilized biomass in shallow water, beach and coastal areas. These eutrophication processes damage marine ecosystems and impair local tourism; this biomass could serve as biogas feedstock material. Residues from biomass processing in the seaweed industry are also of interest. This is a rapidly growing industry with algae now used in the comestible, pharmaceutical and cosmetic sectors. The simultaneous production of combustible biomethane and disposal of undesirable biomass in a synergistic waste management system is a concept with environmental and resource-conserving advantages. PMID:27338422

  11. A Review on the Valorization of Macroalgal Wastes for Biomethane Production.

    Science.gov (United States)

    Barbot, Yann Nicolas; Al-Ghaili, Hashem; Benz, Roland

    2016-01-01

    The increased use of terrestrial crops for biofuel production and the associated environmental, social and ethical issues have led to a search for alternative biomass materials. Terrestrial crops offer excellent biogas recovery, but compete directly with food production, requiring farmland, fresh water and fertilizers. Using marine macroalgae for the production of biogas circumvents these problems. Their potential lies in their chemical composition, their global abundance and knowledge of their growth requirements and occurrence patterns. Such a biomass industry should focus on the use of residual and waste biomass to avoid competition with the biomass requirements of the seaweed food industry, which has occurred in the case of terrestrial biomass. Overabundant seaweeds represent unutilized biomass in shallow water, beach and coastal areas. These eutrophication processes damage marine ecosystems and impair local tourism; this biomass could serve as biogas feedstock material. Residues from biomass processing in the seaweed industry are also of interest. This is a rapidly growing industry with algae now used in the comestible, pharmaceutical and cosmetic sectors. The simultaneous production of combustible biomethane and disposal of undesirable biomass in a synergistic waste management system is a concept with environmental and resource-conserving advantages. PMID:27338422

  12. Use of a marine microbial community as inoculum for biomethane production.

    Science.gov (United States)

    Fistarol, Giovana O; Rosato, Mario; Thompson, Fabiano L; do Valle, Rogerio de A B; Garcia-BlairsyReina, Guillermo; Salomon, Paulo S

    2016-01-01

    Marine substrates are prominent candidates for the production of biofuels, especially for biogas, which is a well-established technology that accepts different types of substrates for its production. However, the use of marine substrates in bioreactors may cause inhibition of methanogenic bacteria due to the addition of seasalts. Here, we explore a simple and economically viable way to circumvent the problem of inoculum inhibition. Based on the current knowledge of the diversity of microorganisms in marine sediments, we tested the direct use of methanogenic bacteria from an anoxic marine environment as inoculum for biomethane production. Both marine and freshwater substrates were added to this inoculum. No pretreatment (that may have enhanced methane production, but would have made the process more expensive) was applied either to the inoculum or to the substrates. For comparison, the same substrates were added to a standard inoculum (cow manure). Both the marine inoculum and cow manure produced methane by anaerobic digestion of the substrates added. The highest methane production (0.299 m(3) kg VS(-1)) was obtained by adding marine microalgae biomass (Chlorella sp. and Synechococcus sp.) to the marine inoculum. No inhibitory effects were observed due to differences in salinity between the inocula and substrates. Our results indicate the potential of using both marine inoculum and substrates for methane production. PMID:26227555

  13. A Review on the Valorization of Macroalgal Wastes for Biomethane Production

    Directory of Open Access Journals (Sweden)

    Yann Nicolas Barbot

    2016-06-01

    Full Text Available The increased use of terrestrial crops for biofuel production and the associated environmental, social and ethical issues have led to a search for alternative biomass materials. Terrestrial crops offer excellent biogas recovery, but compete directly with food production, requiring farmland, fresh water and fertilizers. Using marine macroalgae for the production of biogas circumvents these problems. Their potential lies in their chemical composition, their global abundance and knowledge of their growth requirements and occurrence patterns. Such a biomass industry should focus on the use of residual and waste biomass to avoid competition with the biomass requirements of the seaweed food industry, which has occurred in the case of terrestrial biomass. Overabundant seaweeds represent unutilized biomass in shallow water, beach and coastal areas. These eutrophication processes damage marine ecosystems and impair local tourism; this biomass could serve as biogas feedstock material. Residues from biomass processing in the seaweed industry are also of interest. This is a rapidly growing industry with algae now used in the comestible, pharmaceutical and cosmetic sectors. The simultaneous production of combustible biomethane and disposal of undesirable biomass in a synergistic waste management system is a concept with environmental and resource-conserving advantages.

  14. Ecoengineering high rate anaerobic digestion systems: analysis of improved syntrophic biomethanation catalysts.

    Science.gov (United States)

    Thiele, J H; Wu, W M; Jain, M K; Zeikus, J G

    1990-04-25

    High performance biomethanation granules with operational specific COD removal rates of 7 kg COD removed/kg SS/d were obtained by ecoengineering conventional, granular, UASB digester sludge using a designed protocol of starvation and selection on a defined volatile fatty acid (VFA) based mineral medium. Addition of low (0.15 mM) sulfate levels to this VFA medium increased the maximum shock-load COD removal rate of the ecoengineered biomethanation granules to 9 kg COD/kg SS/d with specific acetate, propionate, and butyrate removal rates of 111, 28, and 64 mol/g SS/d. Addition of moderate (26 mM) calcium levels inhibited growth and altered the structure of granules. The general cellular, growth, stability, and performance features of these ecoengineered granules are described and discussed in relation to their use as improved biomethanation starter cultures. PMID:18588244

  15. A Critical Assessment of Microbiological Biogas to Biomethane Upgrading Systems.

    Science.gov (United States)

    Rittmann, Simon K-M R

    2015-01-01

    Microbiological biogas upgrading could become a promising technology for production of methane (CH(4)). This is, storage of irregular generated electricity results in a need to store electricity generated at peak times for use at non-peak times, which could be achieved in an intermediate step by electrolysis of water to molecular hydrogen (H(2)). Microbiological biogas upgrading can be performed by contacting carbon dioxide (CO(2)), H(2) and hydrogenotrophic methanogenic Archaea either in situ in an anaerobic digester, or ex situ in a separate bioreactor. In situ microbiological biogas upgrading is indicated to require thorough bioprocess development, because only low volumetric CH(4) production rates and low CH(4) fermentation offgas content have been achieved. Higher volumetric production rates are shown for the ex situ microbiological biogas upgrading compared to in situ microbiological biogas upgrading. However, the ex situ microbiological biogas upgrading currently suffers from H(2) gas liquid mass transfer limitation, which results in low volumetric CH(4) productivity compared to pure H(2)/CO(2) conversion to CH(4). If waste gas utilization from biological and industrial sources can be shown without reduction in volumetric CH(4) productivity, as well as if the aim of a single stage conversion to a CH(4) fermentation offgas content exceeding 95 vol% can be demonstrated, ex situ microbiological biogas upgrading with pure or enrichment cultures of methanogens could become a promising future technology for almost CO(2)-neutral biomethane production. PMID:26337846

  16. A Critical Assessment of Microbiological Biogas to Biomethane Upgrading Systems.

    Science.gov (United States)

    Rittmann, Simon K-M R

    2015-01-01

    Microbiological biogas upgrading could become a promising technology for production of methane (CH(4)). This is, storage of irregular generated electricity results in a need to store electricity generated at peak times for use at non-peak times, which could be achieved in an intermediate step by electrolysis of water to molecular hydrogen (H(2)). Microbiological biogas upgrading can be performed by contacting carbon dioxide (CO(2)), H(2) and hydrogenotrophic methanogenic Archaea either in situ in an anaerobic digester, or ex situ in a separate bioreactor. In situ microbiological biogas upgrading is indicated to require thorough bioprocess development, because only low volumetric CH(4) production rates and low CH(4) fermentation offgas content have been achieved. Higher volumetric production rates are shown for the ex situ microbiological biogas upgrading compared to in situ microbiological biogas upgrading. However, the ex situ microbiological biogas upgrading currently suffers from H(2) gas liquid mass transfer limitation, which results in low volumetric CH(4) productivity compared to pure H(2)/CO(2) conversion to CH(4). If waste gas utilization from biological and industrial sources can be shown without reduction in volumetric CH(4) productivity, as well as if the aim of a single stage conversion to a CH(4) fermentation offgas content exceeding 95 vol% can be demonstrated, ex situ microbiological biogas upgrading with pure or enrichment cultures of methanogens could become a promising future technology for almost CO(2)-neutral biomethane production.

  17. Molecular characterization, expression and methylation status analysis of BMP4 gene in skin tissue of Liaoning cashmere goat during hair follicle cycle.

    Science.gov (United States)

    Bai, Wen L; Dang, Yun L; Wang, Jiao J; Yin, Rong H; Wang, Ze Y; Zhu, Yu B; Cong, Yu Y; Xue, Hui L; Deng, Liang; Guo, Dan; Wang, Shi Q; Yang, Shu H

    2016-08-01

    Bone morphogenetic protein 4 (BMP4) is a member of the bone morphogenetic protein family (BMPs). It is involved in the development and cycle of hair follicle, as well as, is thought to be a potential candidate gene for cashmere traits in goats. In the present study, we isolated and characterized a full-length open reading frame (ORF) of BMP4 cDNA from the skin tissue of Liaoning cashmere goat, and investigated the transcriptional pattern and methylation status of BMP4 gene in skin tissue of this breed during different stages of hair follicle cycle. The sequence analysis indicated that the isolated cDNA was 1264-bp in length containing a complete ORF of 1230-bp. It encoded a precursor peptide of 409 amino acids with a signal peptide of 19 amino acids. The structural analysis indicated that goat BMP4 contains typical TGF-β propeptide and TGF-β domains. In skin tissue, BMP4 is generally transcribed in an ascendant pattern from anagen to telogen. The methylation level of 5' flanking regulatory region of BMP4 gene might be involved in its mRNA expression in skin tissue: a higher BMP4 methylation level in skin coincides with a lower expression of BMP4 mRNA. These results from the present work provided a foundation for further insight into the functional and regulatory characteristics of BMP4 in the development and cycle of hair follicle in Liaoning Cashmere goat. PMID:27406581

  18. Molecular characterization, expression and methylation status analysis of BMP4 gene in skin tissue of Liaoning cashmere goat during hair follicle cycle.

    Science.gov (United States)

    Bai, Wen L; Dang, Yun L; Wang, Jiao J; Yin, Rong H; Wang, Ze Y; Zhu, Yu B; Cong, Yu Y; Xue, Hui L; Deng, Liang; Guo, Dan; Wang, Shi Q; Yang, Shu H

    2016-08-01

    Bone morphogenetic protein 4 (BMP4) is a member of the bone morphogenetic protein family (BMPs). It is involved in the development and cycle of hair follicle, as well as, is thought to be a potential candidate gene for cashmere traits in goats. In the present study, we isolated and characterized a full-length open reading frame (ORF) of BMP4 cDNA from the skin tissue of Liaoning cashmere goat, and investigated the transcriptional pattern and methylation status of BMP4 gene in skin tissue of this breed during different stages of hair follicle cycle. The sequence analysis indicated that the isolated cDNA was 1264-bp in length containing a complete ORF of 1230-bp. It encoded a precursor peptide of 409 amino acids with a signal peptide of 19 amino acids. The structural analysis indicated that goat BMP4 contains typical TGF-β propeptide and TGF-β domains. In skin tissue, BMP4 is generally transcribed in an ascendant pattern from anagen to telogen. The methylation level of 5' flanking regulatory region of BMP4 gene might be involved in its mRNA expression in skin tissue: a higher BMP4 methylation level in skin coincides with a lower expression of BMP4 mRNA. These results from the present work provided a foundation for further insight into the functional and regulatory characteristics of BMP4 in the development and cycle of hair follicle in Liaoning Cashmere goat.

  19. Life cycle greenhouse gas impacts of ethanol, biomethane and limonene production from citrus waste

    Science.gov (United States)

    Pourbafrani, Mohammad; McKechnie, Jon; MacLean, Heather L.; Saville, Bradley A.

    2013-03-01

    The production of biofuel from cellulosic residues can have both environmental and financial benefits. A particular benefit is that it can alleviate competition for land conventionally used for food and feed production. In this research, we investigate greenhouse gas (GHG) emissions associated with the production of ethanol, biomethane, limonene and digestate from citrus waste, a byproduct of the citrus processing industry. The study represents the first life cycle-based evaluations of citrus waste biorefineries. Two biorefinery configurations are studied—a large biorefinery that converts citrus waste into ethanol, biomethane, limonene and digestate, and a small biorefinery that converts citrus waste into biomethane, limonene and digestate. Ethanol is assumed to be used as E85, displacing gasoline as a light-duty vehicle fuel; biomethane displaces natural gas for electricity generation, limonene displaces acetone in solvents, and digestate from the anaerobic digestion process displaces synthetic fertilizer. System expansion and two allocation methods (energy, market value) are considered to determine emissions of co-products. Considerable GHG reductions would be achieved by producing and utilizing the citrus waste-based products in place of the petroleum-based or other non-renewable products. For the large biorefinery, ethanol used as E85 in light-duty vehicles results in a 134% reduction in GHG emissions compared to gasoline-fueled vehicles when applying a system expansion approach. For the small biorefinery, when electricity is generated from biomethane rather than natural gas, GHG emissions are reduced by 77% when applying system expansion. The life cycle GHG emissions vary substantially depending upon biomethane leakage rate, feedstock GHG emissions and the method to determine emissions assigned to co-products. Among the process design parameters, the biomethane leakage rate is critical, and the ethanol produced in the large biorefinery would not meet EISA

  20. Anaerobic digestion for simultaneous sewage sludge treatment and CO biomethanation: process performance and microbial ecology

    DEFF Research Database (Denmark)

    Luo, Gang; Wang, Wen; Angelidaki, Irini

    2013-01-01

    Syngas is produced by thermal gasification of both non-renewable and renewable sources including biomass and coal, and it consists mainly of CO, CO2 and H2. In this paper we aim to bio-convert CO in the syngas to CH4. A novel technology for simultaneous sewage sludge treatment and CO biomethanation...... biomethanation. However, the two species were distributed differently in the liquid phase and in the biofilm. Although carboxidotrophic activities test showed that CO was converted by both archaea and bacteria, the bacterial species responsible for CO conversion are unknown....

  1. Life cycle greenhouse gas impacts of ethanol, biomethane and limonene production from citrus waste

    International Nuclear Information System (INIS)

    The production of biofuel from cellulosic residues can have both environmental and financial benefits. A particular benefit is that it can alleviate competition for land conventionally used for food and feed production. In this research, we investigate greenhouse gas (GHG) emissions associated with the production of ethanol, biomethane, limonene and digestate from citrus waste, a byproduct of the citrus processing industry. The study represents the first life cycle-based evaluations of citrus waste biorefineries. Two biorefinery configurations are studied—a large biorefinery that converts citrus waste into ethanol, biomethane, limonene and digestate, and a small biorefinery that converts citrus waste into biomethane, limonene and digestate. Ethanol is assumed to be used as E85, displacing gasoline as a light-duty vehicle fuel; biomethane displaces natural gas for electricity generation, limonene displaces acetone in solvents, and digestate from the anaerobic digestion process displaces synthetic fertilizer. System expansion and two allocation methods (energy, market value) are considered to determine emissions of co-products. Considerable GHG reductions would be achieved by producing and utilizing the citrus waste-based products in place of the petroleum-based or other non-renewable products. For the large biorefinery, ethanol used as E85 in light-duty vehicles results in a 134% reduction in GHG emissions compared to gasoline-fueled vehicles when applying a system expansion approach. For the small biorefinery, when electricity is generated from biomethane rather than natural gas, GHG emissions are reduced by 77% when applying system expansion. The life cycle GHG emissions vary substantially depending upon biomethane leakage rate, feedstock GHG emissions and the method to determine emissions assigned to co-products. Among the process design parameters, the biomethane leakage rate is critical, and the ethanol produced in the large biorefinery would not meet EISA

  2. hBMP-7 induces the differentiation of adipose-derived mesenchymal stem cells into osteoblast-like cells.

    Science.gov (United States)

    Ren, Y; Han, C; Wang, J; Jia, Y; Kong, L; Eerdun, T; Wu, L; Jiang, D

    2016-01-01

    The aim of this study was to investigate the differentiation potential of adipose-derived mesenchymal stem cells (ADMSCs) into osteoblasts by human bone morphogenetic protein-7 (hBMP-7) induction. ADMSCs were isolated from the subcutaneous adipose tissue of a rabbit, and then transfected with the pcDNA3.1 vector alone and pcDNA3.1-hBMP-7 (hBMP-7), respectively. Untransfected ADMSCs were used as the control group. After transfection, the morphology and green fluorescent protein (GFP) fluorescence intensity of ADMSCs were observed by fluorescent microscopy. The 3-(4,5-dimethylthiazol- 2-yl)-2,5-diphenyltetrazolium bromide assay was performed to detect the growth of ADMSCs at 1, 3, and 5 days, respectively. Transmission electron microscopy was performed to observe the ultrastructural morphology of ADMSCs. In addition, ADMSCs were stained with quinalizarin and toluidine blue to reflect the content of osteoblasts and chondrocytes, respectively. Finally, the expression of collagen I and osteocalcin in ADMSCs was detected by western blot. ADMSCs were successfully isolated. Obvious GFP fluorescence and high expression of hBMP-7 demonstrated the successful transfection of hBMP-7. Specific morphological characters with a metabolically active ultrastructure were exhibited on the ADMSCs transfected with hBMP- 7. In addition, the growth rate of ADMSCs transfected with hBMP-7 was significantly higher than that of the cells in the vector and control groups. Successfully induced osteoblast-like cells were identified by an obvious erythrine area and high expression of collagen I and osteocalcin in ADMSCs transfected with hBMP-7. Thus, ADMSCs can be successfully differentiated into osteoblast-like cells by hBMP-7 induction in vitro. PMID:27525862

  3. The effects of 3D bioactive glass scaffolds and BMP-2 on bone formation in rat femoral critical size defects and adjacent bones

    International Nuclear Information System (INIS)

    Reconstruction of critical size defects in the load-bearing area has long been a challenge in orthopaedics. In the past, we have demonstrated the feasibility of using a biodegradable load-sharing scaffold fabricated from poly(propylene fumarate)/tricalcium phosphate (PPF/TCP) loaded with bone morphogenetic protein-2 (BMP-2) to successfully induce healing in those defects. However, there is limited osteoconduction observed with the PPF/TCP scaffold itself. For this reason, 13-93 bioactive glass scaffolds with local BMP-2 delivery were investigated in this study for inducing segmental defect repairs in a load-bearing region. Furthermore, a recent review on BMP-2 revealed greater risks in radiculitis, ectopic bone formation, osteolysis and poor global outcome in association with the use of BMP-2 for spinal fusion. We also evaluated the potential side effects of locally delivered BMP-2 on the structures of adjacent bones. Therefore, cylindrical 13-93 glass scaffolds were fabricated by indirect selective laser sintering with side holes on the cylinder filled with dicalcium phosphate dehydrate as a BMP-2 carrier. The scaffolds were implanted into critical size defects created in rat femurs with and without 10 μg of BMP-2. The x-ray and micro-CT results showed that a bridging callus was found as soon as three weeks and progressed gradually in the BMP group while minimal bone formation was observed in the control group. Degradation of the scaffolds was noted in both groups. Stiffness, peak load and energy to break of the BMP group were all higher than the control group. There was no statistical difference in bone mineral density, bone area and bone mineral content in the tibiae and contralateral femurs of the control and BMP groups. In conclusion, a 13-93 bioactive glass scaffold with local BMP-2 delivery has been demonstrated for its potential application in treating large bone defects. (paper)

  4. Anaerobic digestion of solid waste in RAS: Effect of reactor type on the biochemical acidogenic potential (BAP) and assessment of the biochemical methane potential (BMP) by a batch assay

    DEFF Research Database (Denmark)

    Suhr, Karin Isabel; Letelier-Gordo, Carlos Octavio; Lund, Ivar

    2015-01-01

    Anaerobic digestion is a way to utilize the potential energy contained in solid waste produced in recirculating aquaculture systems (RASs), either by providing acidogenic products for driving heterotrophic denitrification on site or by directly producing combustive methane. In this study the bioc...

  5. Review of the integrated process for the production of grass biomethane.

    Science.gov (United States)

    Nizami, Abdul-Sattar; Korres, Nicholas E; Murphy, Jerry D

    2009-11-15

    Production of grass biomethane is an integrated process which involves numerous stages with numerous permutations. The grass grown can be of numerous species, and it can involve numerous cuts. The lignocellulosic content of grass increases with maturity of grass; the first cut offers more methane potential than the later cuts. Water-soluble carbohydrates (WSC) are higher (and as such methane potential is higher) for grass cut in the afternoon as opposed to that cut in the morning. The method of ensiling has a significant effect on the dry solids content of the grass silage. Pit or clamp silage in southern Germany and Austria has a solids content of about 40%; warm dry summers allow wilting of the grass before ensiling. In temperate oceanic climates like Ireland, pit silage has a solids content of about 21% while bale silage has a solids content of 32%. Biogas production is related to mass of volatile solids rather than mass of silage; typically one ton of volatile solid produces 300 m(3) of methane. The dry solids content of the silage has a significant impact on the biodigester configuration. Silage with a high solids content would lend itself to a two-stage process; a leach bed where volatile solids are converted to a leachate high in chemical oxygen demand (COD), followed by an upflow anaerobic sludge blanket where the COD can be converted efficiently to CH(4). Alternative configurations include wet continuous processes such as the ubiquitous continuously stirred tank reactor; this necessitates significant dilution of the feedstock to effect a solids content of 12%. Various pretreatment methods may be employed especially if the hydrolytic step is separated from the methanogenic step. Size reduction, thermal, and enzymatic methodologies are used. Good digester design is to seek to emulate the cow, thus rumen fluid offers great potential for hydrolysis.

  6. Functional cardiomyocytes derived from Isl1 cardiac progenitors via Bmp4 stimulation.

    Directory of Open Access Journals (Sweden)

    Esra Cagavi

    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

  7. BMP pathway regulation of and by macrophages.

    Directory of Open Access Journals (Sweden)

    Megha Talati

    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.

  8. From pre-treatment toward inter-treatment. Getting some clues from sewage sludge biomethanation.

    Science.gov (United States)

    Ortega-Martinez, Eduardo; Sapkaite, Ieva; Fdz-Polanco, Fernando; Donoso-Bravo, Andres

    2016-07-01

    The conventional application of thermal pretreatment of sewage sludge has been to apply it prior to the anaerobic digestion. In this study, the thermal treatment of the digestate was assessed at lab-scale under several temperature and time conditions. Biochemical methane potential (BMP) tests were set up to evaluate the methane production kinetic by using the Gompertz modified and the first order equation. A full-scale digester evaluation was done by using the ADM1 model under different scenarios and by using the parameters drawn from the BMP tests. The best results were obtained at 180°C and 200°C both at 30min where an improvement of 50% in the methane yield in regards to raw digestate. Full-scale simulations show that a scenario with two anaerobic reactors with thermal inter-treatment would improve the methane production by 45% and 20% compared to conventional anaerobic digestion and pretreatments followed by anaerobic digestion, respectively. PMID:27107339

  9. BMP4 was associated with NSCL/P in an Asian population.

    Directory of Open Access Journals (Sweden)

    Qianqian Chen

    Full Text Available BACKGROUND: The Bone Morphogenetic Protein 4 gene (BMP4 is located in chromosome 14q22-q23 which has shown evidence of linkage for isolated nonsyndromic cleft lip with or without cleft palate (NSCL/P in a genome wide linkage analysis of human multiplex families. BMP4 has been shown to play crucial roles in lip and palatal development in animal models. Several candidate gene association analyses also supported its potential risk for NSCL/P, however, results across these association studies have been inconsistent. The aim of the current study was to test for possible association between markers in and around the BMP4 gene and NSCL/P in Asian and Maryland trios. METHODOLOGY/PRINCIPAL FINDINGS: Family Based Association Test was used to test for deviation from Mendelian assortment for 12 SNPs in and around BMP4. Nominal significant evidence of linkage and association was seen for three SNPs (rs10130587, rs2738265 and rs2761887 in 221 Asian trios and for one SNP (rs762642 in 76 Maryland trios. Statistical significance still held for rs10130587 after Bonferroni correction (corrected p = 0.019 among the Asian group. Estimated odds ratio for carrying the apparent high risk allele at this SNP was 1.61 (95%CI = 1.20, 2.18. CONCLUSIONS: Our results provided further evidence of association between BMP4 and NSCL/P.

  10. Effects of codon modification on human BMP2 gene expression in tobacco plants.

    Science.gov (United States)

    Suo, Guangli; Chen, Bing; Zhang, Jingyu; Duan, Ziyuan; He, Zhengquan; Yao, Wei; Yue, Chaoyin; Dai, Jianwu

    2006-07-01

    Bone morphogenetic protein 2 (BMP2) has great potential in therapeutic applications. We are working on generating transgenic plants as a bioreactor to produce BMP2. We have studied the effects of codon optimization on the expression of human BMP2 (hBMP2) in tobacco plants. Three modified hBMP2 genes were transformed into tobacco under the control of either cauliflower mosaic virus 35S (CaMV35S) promoter or double-CaMV35S promoter plus alfalfa mosaic virus (AMV) enhancer. The fused beta-glucuronidase (GUS) reporter gene was used to facilitate the assay of protein expression. The results indicated that codon optimization could increase the protein expression level obviously under CaMV35S promoter. However, under relatively stronger initiation condition (double-CaMV35S promoter plus AMV enhancer), only the gene with the lowest degree of codon optimization could increase the protein expression level. Our findings suggest that the action of codon optimization may be influenced by the factors of promoter strength and A+T content in tobacco plants. PMID:16491379

  11. A Receptor Tyrosine Kinase Inhibitor, Dovitinib (TKI-258), Enhances BMP-2-Induced Osteoblast Differentiation In Vitro

    Science.gov (United States)

    Lee, Yura; Bae, Kyoung Jun; Chon, Hae Jung; Kim, Seong Hwan; Kim, Soon Ae; Kim, Jiyeon

    2016-01-01

    Dovitinib (TKI258) is a small molecule multi-kinase inhibitor currently in clinical phase I/II/III development for the treatment of various types of cancers. This drug has a safe and effective pharmacokinetic/pharmacodynamic profile. Although dovitinib can bind several kinases at nanomolar concentrations, there are no reports relating to osteoporosis or osteoblast differentiation. Herein, we investigated the effect of dovitinib on human recombinant bone morphogenetic protein (BMP)-2-induced osteoblast differentiation in a cell culture model. Dovitinib enhanced the BMP-2-induced alkaline phosphatase (ALP) induction, which is a representative marker of osteoblast differentiation. Dovitinib also stimulated the translocation of phosphorylated Smad1/5/8 into the nucleus and phosphorylation of mitogen-activated protein kinases, including ERK1/2 and p38. In addition, the mRNA expression of BMP-4, BMP-7, ALP, and OCN increased with dovitinib treatment. Our results suggest that dovitinib has a potent stimulating effect on BMP-2-induced osteoblast differentiation and this existing drug has potential for repositioning in the treatment of bone-related disorders. PMID:27025387

  12. Effect of lipase addition on hydrolysis and biomethane production of Chinese food waste.

    Science.gov (United States)

    Meng, Ying; Li, Sang; Yuan, Hairong; Zou, Dexun; Liu, Yanping; Zhu, Baoning; Li, Xiujin

    2015-03-01

    The lipase obtained from Aspergillums niger was applied to promote the hydrolysis of food waste for achieving high biomethane production. Two strategies of lipase additions were investigated. One (Group A) was to pre-treat food waste to pre-decompose lipid to fatty acids before anaerobic digestion, and another one (Group B) was to add lipase to anaerobic digester directly to degrade lipid inside digester. The lipase was used at the concentrations of 0.1%, 0.5%, and 1.0% (w/v). The results showed that Group A achieved higher biomethane production, TS and VS reductions than those of Group B. At 0.5% lipase concentration, Group A obtained experimental biomethane yield of 500.1 mL/g VS(added), 4.97-26.50% higher than that of Group B. The maximum Bd of 73.8% was also achieved in Group A. Therefore, lipase pre-treatment strategy is recommended. This might provide one of alternatives for efficient biomethane production from food waste and mitigating environmental impact associated. PMID:25575204

  13. Greenhouse gas emissions from biomethane plants. Measurement results and cause analysis

    International Nuclear Information System (INIS)

    Biomethane gained importance in the past years. Nevertheless the sustainability of an increasing biomethane production is an important issue. In the meantime the methane loss from biogas upgrading units can be minimized reliably. Henceforth, the diffuse greenhouse gas (GHG) emissions from the biogas-producing plant components and the digestate storage are brought into focus. By two different measurement methods (on-site and remote sensing method) GHG emissions from three biomethane plants were quantified. The on-site method measured methane emissions in the amount of 0.12 to 0. 88 % CH4 and the remote sensing method in the amount of 0.19 to 2.84% CH4. Ammonia and nitrogen dioxide emissions were irrelevant in particular if the systems engineering was completely gastight. At every plant the biogas upgrading was carried out by chemical scrubbing so that methane emissions were emitted in particular by not gastight digestate storage, diffuse leakages and pressure relief vents. Both measurement methods gave similar estimations about the GHG-emissions from the biomethane plants while differences in the exact amount of the measured GHG-emissions occurred.

  14. E. coli-Produced BMP-2 as a Chemopreventive Strategy for Colon Cancer: A Proof-of-Concept Study

    Directory of Open Access Journals (Sweden)

    Saravanan Yuvaraj

    2012-01-01

    Full Text Available Colon cancer is a serious health problem, and novel preventive and therapeutical avenues are urgently called for. Delivery of proteins with anticancer activity through genetically modified bacteria provides an interesting, potentially specific, economic and effective approach here. Interestingly, bone morphogenetic protein 2 (BMP-2 is an important and powerful tumour suppressor in the colon and is thus an attractive candidate protein for delivery through genetically modified bacteria. It has not been shown, however, that BMP production in the bacterial context is effective on colon cancer cells. Here we demonstrate that transforming E. coli with a cDNA encoding an ileal-derived mature human BMP-2 induces effective apoptosis in an in vitro model system for colorectal cancer, whereas the maternal organism was not effective in this respect. Furthermore, these effects were sensitive to cotreatment with the BMP inhibitor Noggin. We propose that prevention and treatment of colorectal cancer using transgenic bacteria is feasible.

  15. Vergleich von BMP-4 versus BMP-2 für die osteogene Differenzierung von Periostzellen

    OpenAIRE

    Klumpp, Florian (Alexander Stephan)

    2010-01-01

    Es ist heute bekannt, dass humane periostale mesenchymale Stammzellen (PMSCs) eine aussichtsreiche Grundlage für ein erfolgreiches Knochen Tissue Engineering darstellen. Dennoch ist die osteogene Differenzierung noch nicht vollständig be-schrieben. Da BMP-2 und BMP-4 nachweislich Regulatoren der Osteogenese sind, bestand die Aufgabe der vorliegenden Arbeit darin, die Wirkung derer auf die osteo-gene Differenzierung humaner PMSCs zu untersuchen. Isolierte humane PMSCs wurden mit Hilfe von o...

  16. Effects of Cadmium on BMP Induced Bone Formation

    Institute of Scientific and Technical Information of China (English)

    陈秋生; 徐顺清

    2003-01-01

    To demonstrate the direct effects of cadmium on activities of bone morphogenetic protein (BMP), a complex containing BMP and cadmium chloride (CdCl2) was implanted beneath the abdominal skin of young male Wistar rats. The activity of BMP was studied by observing the histological changes, and measuring the activity of alkaline phosphatase (ALP) and acid phosphatase (ACP) and calcium content of the implants at different time points. Our results showed that during bone formation induced by BMP, cadmium inhibited the activities of osteoblasts and osteoclasts, and slowed the deposition of calcium. It is concluded that cadmium can directly affect biological activities of BMP directly.

  17. Endoplasmic reticulum (ER stress inducible factor cysteine-rich with EGF-like domains 2 (Creld2 is an important mediator of BMP9-regulated osteogenic differentiation of mesenchymal stem cells.

    Directory of Open Access Journals (Sweden)

    Jiye Zhang

    Full Text Available Mesenchymal stem cells (MSCs are multipotent progenitors that can undergo osteogenic differentiation under proper stimuli. We demonstrated that BMP9 is one of the most osteogenic BMPs. However, the molecular mechanism underlying BMP9-initiated osteogenic signaling in MSCs remains unclear. Through gene expression profiling analysis we identified several candidate mediators of BMP9 osteogenic signaling. Here, we focus on one such signaling mediator and investigate the functional role of cysteine-rich with EGF-like domains 2 (Creld2 in BMP9-initiated osteogenic signaling. Creld2 was originally identified as an ER stress-inducible factor localized in the ER-Golgi apparatus. Our genomewide expression profiling analysis indicates that Creld2 is among the top up-regulated genes in BMP9-stimulated MSCs. We confirm that Creld2 is up-regulated by BMP9 in MSCs. ChIP analysis indicates that Smad1/5/8 directly binds to the Creld2 promoter in a BMP9-dependent fashion. Exogenous expression of Creld2 in MSCs potentiates BMP9-induced early and late osteogenic markers, and matrix mineralization. Conversely, silencing Creld2 expression inhibits BMP9-induced osteogenic differentiation. In vivo stem cell implantation assay reveals that exogenous Creld2 promotes BMP9-induced ectopic bone formation and matrix mineralization, whereas silencing Creld2 expression diminishes BMP9-induced bone formation and matrix mineralization. We further show that Creld2 is localized in ER and the ER stress inducers potentiate BMP9-induced osteogenic differentiation. Our results strongly suggest that Creld2 may be directly regulated by BMP9 and ER stress response may play an important role in regulating osteogenic differentiation.

  18. The effect of SDF-1α on low dose BMP-2 mediated bone regeneration by release from heparinized mineralized collagen type I matrix scaffolds in a murine critical size bone defect model.

    Science.gov (United States)

    Zwingenberger, Stefan; Langanke, Robert; Vater, Corina; Lee, Geoffrey; Niederlohmann, Eik; Sensenschmidt, Markus; Jacobi, Angela; Bernhardt, Ricardo; Muders, Michael; Rammelt, Stefan; Knaack, Sven; Gelinsky, Michael; Günther, Klaus-Peter; Goodman, Stuart B; Stiehler, Maik

    2016-09-01

    The treatment of critical size bone defects represents a challenge. The growth factor bone morphogenetic protein 2 (BMP-2) is clinically established but has potentially adverse effects when used at high doses. The aim of this study was to evaluate if stromal derived factor-1 alpha (SDF-1α) and BMP-2 released from heparinized mineralized collagen type I matrix (MCM) scaffolds have a cumulative effect on bone regeneration. MCM scaffolds were functionalized with heparin, loaded with BMP-2 and/or SDF-1α and implanted into a murine critical size femoral bone defect (control group, low dose BMP-2 group, low dose BMP-2 + SDF-1α group, and high dose BMP-2 group). After 6 weeks, both the low dose BMP-2 + SDF-1α group (5.8 ± 0.6 mm³, p = 0.0479) and the high dose BMP-2 group (6.5 ± 0.7 mm³, p = 0.008) had a significantly increased regenerated bone volume compared to the control group (4.2 ± 0.5 mm³). There was a higher healing score in the low dose BMP-2 + SDF-1α group (median grade 8; Q1-Q3 7-9; p = 0.0357) than in the low dose BMP-2 group (7; Q1-Q3 5-9) histologically. This study showed that release of BMP-2 and SDF-1α from heparinized MCM scaffolds allows for the reduction of the applied BMP-2 concentration since SDF-1α seems to enhance the osteoinductive potential of BMP-2. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 2126-2134, 2016. PMID:27060915

  19. Twisted gastrulation, a BMP antagonist, exacerbates podocyte injury.

    Directory of Open Access Journals (Sweden)

    Sachiko Yamada

    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.

  20. KlimaCH4. Climate effects of biomethane economy

    International Nuclear Information System (INIS)

    Within the project ''Climate effects of biomethane economy'' (KlimaCH4) of the German Biomass Research Centre two methods for measurement of direct greenhouse gas emissions were analyzed for their applicability and comparability. In the context of concrete measurements direct emissions, mainly of methane, three biogas plants with methane treatment for feeding into the natural gas grid were quantified. These tests were carried out on the one hand directly on-site by using leak detection, enclosures and ''open chamber'' measurements, but also indirectly by optical remote sensing with tunable diode laser absorption spectrometry (TDLAS) and reverse dispersion modelling by inverse dispersion modeling. The on-site method offers the possibility, to investigate the influences of plant operation on emissions of known diffuse sources, inter alia, through the balance of the operating status with the timeline of a specific emission source (e.g. as increased release of methane due to stirring intervals). This is particularly useful for deriving appropriate measures to reduce emissions. The quantification of individual, diffuse emission sources is metrologically possibly only very costly to implement. The effort is depending to a considerable extent by the design and the size of the examined biogas plant. In order to detect the influence seasonal changing of environmental conditions recurring emission measurements were realized. The use of optical telemetry showed as an advantageous alternative to on-site method, because it can significantly reduce time required for emission measurements particularly at large biogas plants or plants with numerous individual sources. With only one measurement sequence all emission sources are covered, without consuming individual measurements. In addition, in comparision to the on-site method, the emission situation of the entire system can be better reproduced, since all individual sources are included in

  1. Power requirements of biogas upgrading by water scrubbing and biomethane compression: comparative analysis of various plant configurations

    OpenAIRE

    Budzianowski, Wojciech; Wylock, Christophe; Marciniak, Przemysław

    2016-01-01

    Biogas upgrading by water scrubbing followed by biomethane compression is an environmentally benign process. It may be achieved using various plant configurations characterised by various power requirements with associated effects on biomethane sustainability. Therefore, the current study has been undertaken to systematically investigate the power requirements of a range of water scrubbing options. Two groups of water scrubbing are analysed: (1) high pressure water scrubbing (HPWS) and (2) ne...

  2. BMP7在非酒精性脂肪性肝病的作用机制探讨%Mechanism of BMP7 in non-alcoholic fatty liver disease

    Institute of Scientific and Technical Information of China (English)

    许敏; 张淑文; 李异玲

    2016-01-01

    骨形成蛋白7(bone morphogenetic protein 7,BMP7),又称成骨蛋白1(OP1),是一个35 KD的同型二聚体蛋白质。近年来研究发现,BMP7在改善代谢类疾病、促进棕色脂肪组织( brown adipose tissue,BAT)分化、抑制炎症、抑制肝纤维化等方面发挥着重要作用,且与肝癌预后相关,同时BMP7在非酒精性脂肪性肝病( non-alcoholic fatty liver disease,NAFLD)的发生及进展中发挥着重要作用,可能成为诊断及治疗NAFLD的新靶点。%Bone morphogenetic protein 7 (BMP7), also called OP1, is a 35 KD homodimer protein. Recently, studies have shown that BMP7 contributes to improve metabolic dysfunction, promote differentiation of brown adipose tis-sue ( BAT) , inhibit inflammation and liver fibrosis, and is associated with prognosis of hepatic carcinoma. BMP7 is also associated with occurrence and development of non-alcoholic fatty liver disease ( NAFLD) , and may be a potential target for diagnosing and treating NAFLD.

  3. Enhancing the production of biomethane : A comparison between GoBiGas process and new process of combining anaerobic digestion and biomass gasification

    OpenAIRE

    Mehmood, Daheem

    2016-01-01

    In recent years, there is a rapid growing interest in the use of biomethane for the transport sector. A new method of combining anaerobic digestion and biomass gasification is proposed.The feasibility study shows that more biomethane can be produced; resulting in an increase in the revenue compared to individual biogas plants. The GoBiGas project,which is initiated by Göteborg Energi, adopted another method based on gasification, water gas shift and methanation to enable biomethane production...

  4. Plasma Treated High-Density Polyethylene (HDPE Medpor Implant Immobilized with rhBMP-2 for Improving the Bone Regeneration

    Directory of Open Access Journals (Sweden)

    Jin-Su Lim

    2014-01-01

    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.

  5. Opportunities and challenges for the future utilization of bio methane in regional energy supply structures; Chancen und Herausforderungen fuer die zukuenftige Nutzung von Biomethan in regionalen Energieversorgungsstrukturen

    Energy Technology Data Exchange (ETDEWEB)

    Scholwin, Frank; Nelles, Michael [Rostock Univ. (Germany). Professur Biogas/Bioenergie

    2013-10-01

    In fact, that the transition of the energy system needs a decentralisation of energy supply. Energy from biomass will play an important role for stabilisation of energy supply and compensation of fluctuating energy demand and energy supply from solar and wind power. Especially biomethane what can be stored in the natural gas grid allows high flexibility in its use. Therefore the following options are analysed: - Integration of biomethane/biogas driven CHP units in local heat supply structures - Flexible operation of biomethane/biogas driven CHP units - Synergies through utilisation of biomethane as vehicle fuel. (orig.)

  6. BMP2 Transfer to Neighboring Cells and Activation of Signaling.

    Science.gov (United States)

    Alborzinia, Hamed; Shaikhkarami, Marjan; Hortschansky, Peter; Wölfl, Stefan

    2016-09-01

    Morphogen gradients and concentration are critical features during early embryonic development and cellular differentiation. Previously we reported the preparation of biologically active, fluorescently labeled BMP2 and quantitatively analyzed their binding to the cell surface and followed BMP2 endocytosis over time on the level of single endosomes. Here we show that this internalized BMP2 can be transferred to neighboring cells and, moreover, also activates downstream BMP signaling in adjacent cells, indicated by Smad1/5/8 phosphorylation and activation of the downstream target gene id1. Using a 3D matrix to modulate cell-cell contacts in culture we could show that direct cell-cell contact significantly increased BMP2 transfer. Using inhibitors of vesicular transport, transfer was strongly inhibited. Interestingly, cotreatment with the physiological BMP inhibitor Noggin increased BMP2 uptake and transfer, albeit activation of Smad signaling in neighboring cells was completely suppressed. Our findings present a novel and interesting mechanism by which morphogens such as BMP2 can be transferred between cells and how this is modulated by BMP antagonists such as Noggin, and how this influences activation of Smad signaling by BMP2 in neighboring cells. PMID:27306974

  7. Arsenite suppression of BMP signaling in human keratinocytes

    Energy Technology Data Exchange (ETDEWEB)

    Phillips, Marjorie A.; Qin, Qin [Department of Environmental Toxicology, University of California, Davis, CA 95616-8588 (United States); Hu, Qin; Zhao, Bin [State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085 (China); Rice, Robert H., E-mail: rhrice@ucdavis.edu [Department of Environmental Toxicology, University of California, Davis, CA 95616-8588 (United States)

    2013-06-15

    Arsenic, a human skin carcinogen, suppresses differentiation of cultured keratinocytes. Exploring the mechanism of this suppression revealed that BMP-6 greatly increased levels of mRNA for keratins 1 and 10, two of the earliest differentiation markers expressed, a process prevented by co-treatment with arsenite. BMP also stimulated, and arsenite suppressed, mRNA for FOXN1, an important transcription factor driving early keratinocyte differentiation. Keratin mRNAs increased slowly after BMP-6 addition, suggesting they are indirect transcriptional targets. Inhibition of Notch1 activation blocked BMP induction of keratins 1 and 10, while FOXN1 induction was largely unaffected. Supporting a requirement for Notch1 signaling in keratin induction, BMP increased levels of activated Notch1, which was blocked by arsenite. BMP also greatly decreased active ERK, while co-treatment with arsenite maintained active ERK. Inhibition of ERK signaling mimicked BMP by inducing keratin and FOXN1 mRNAs and by increasing active Notch1, effects blocked by arsenite. Of 6 dual-specificity phosphatases (DUSPs) targeting ERK, two were induced by BMP unless prevented by simultaneous exposure to arsenite and EGF. Knockdown of DUSP2 or DUSP14 using shRNAs greatly reduced FOXN1 and keratins 1 and 10 mRNA levels and their induction by BMP. Knockdown also decreased activated Notch1, keratin 1 and keratin 10 protein levels, both in the presence and absence of BMP. Thus, one of the earliest effects of BMP is induction of DUSPs, which increases FOXN1 transcription factor and activates Notch1, both required for keratin gene expression. Arsenite prevents this cascade by maintaining ERK signaling, at least in part by suppressing DUSP expression. - Highlights: • BMP induces FOXN1 transcription. • BMP induces DUSP2 and DUSP14, suppressing ERK activation. • Arsenite suppresses levels of phosphorylated Smad1/5 and FOXN1 and DUSP mRNA. • These actions rationalize arsenite suppression of keratinocyte

  8. BMP signaling in the nephron progenitor niche

    OpenAIRE

    Oxburgh, Leif; Brown, Aaron C.; Fetting, Jennifer; Hill, Beth

    2011-01-01

    Bone morphogenic proteins (BMPs) play diverse roles in embryonic kidney development, regulating essential aspects of both ureteric bud and nephron development. In this review, we provide an overview of reported expression patterns and functions of BMP signaling components within the nephrogenic zone or nephron progenitor niche of the developing kidney. Reported in situ hybridization results are relatively challenging to interpret and sometimes conflicting. Comparing these with high-resolution...

  9. Application of biomethane for new buildings according to the German renewable heat act. A barrier and profitability analysis; Einsatz von Biomethan in Neubauten nach EEWaermeG. Eine Hemmnis- und Wirtschaftlichkeitsanalyse

    Energy Technology Data Exchange (ETDEWEB)

    Lossner, Martin [Leipzig Univ. (Germany). Inst. fuer Infrastruktur und Ressourcenmanagement; Gawel, Erik [Leipzig Univ. (Germany). Inst. fuer Infrastruktur und Ressourcenmanagement; Helmholtz-Zentrum fuer Umweltforschung GmbH - UFZ, Leipzig (Germany); Herbes, Carsten [Hochschule fuer Wirtschaft und Umwelt Nuertingen-Geislingen, Nuertingen (Germany)

    2012-12-15

    The German Federal Government aims at increasing the use of biomethane to 6 billion cubic meters per year by 2020. The German Act on the Promotion of Renewable Energies in the Heat Sector (Renewable Heat Act - EEWaermeG) of 2009 has paved the way for renewable energies in the heating market with 14 % in 2020 being the ultimate goal. Biomethane is one of the options provided in the EEWaermeG. Building owners can choose between different renewable energy sources as well as a range of compensatory measures such as district heating, insulation or combined heat and power. However, they do not make this decision independently but together with other members of a buying center that comprises architects, specialist consultants and installers. These other members are pursuing their own interests, which includes maximizing their contract volume. Moreover the owner takes his decision under incomplete information. Both factors are detrimental to an optimal decision. Biomethane is chosen for only 3 % of newly constructed buildings. For a better understanding of why the use of biomethane for heating purposes is so limited, the authors have developed an economic calculation method that compares different renewable energy sources as well as compensatory measures. For a single-family home, biomethane is the least attractive option from a financial perspective; for a multi-family house, on the other hand, it ranks third. In order to promote the utilization of biomethane and to achieve the 6 billion cubic meter/year goal by 2020, the Federal Government needs to open up the options for biomethane beyond the now mandatory cogeneration solution. Moreover, the EEWaermeG, which applies to newly built houses only, should be expanded to existing buildings. (orig.)

  10. Improvement of gaseous energy recovery from sugarcane bagasse by dark fermentation followed by biomethanation process.

    Science.gov (United States)

    Kumari, Sinu; Das, Debabrata

    2015-10-01

    The aim of the present study was to enhance the gaseous energy recovery from sugarcane bagasse. The two stage (biohydrogen and biomethanation) batch process was considered under mesophilic condition. Alkali pretreatment (ALP) was used to remove lignin from sugarcane bagasse. This enhanced the enzymatic digestibility of bagasse to a great extent. The maximum lignin removal of 60% w/w was achieved at 0.25 N NaOH concentration (50°C, 30 min). The enzymatic hydrolysis efficiency was increased to about 2.6-folds with alkali pretreated sugarcane bagasse as compared to untreated one. The maximum hydrogen and methane yields from the treated sugarcane bagasse by biohydrogen and biomethanation processes were 93.4 mL/g-VS and 221.8 mL/g-VS respectively. This process resulted in significant increase in energy conversion efficiency (44.8%) as compared to single stage hydrogen production process (5.4%). PMID:26210150

  11. Waste-to-biomethane Concept Application: A Case Study of Valmiera City in Latvia

    Directory of Open Access Journals (Sweden)

    Barisa Aiga

    2015-12-01

    Full Text Available The current needs of sustainable urban development are rising. As the transport sector expands, emissions continue to rise. Due to their negative impact on human health and the environment, air quality requirements are becoming more and more stringent. At the same time, the amount of waste is increasing. Europe Union policies attempt to relieve the pressure that these two stressors place on urban systems as they themselves expand. Today different solutions are available to decrease greenhouse gas emissions, increase air quality and improve waste management systems. Among them, waste-to-biomethane for use in urban systems deserves more attention. The paper focuses on application of the concept of waste-to-biomethane and the case study of Valmiera is evaluated. The results show that the application of the waste-to-biomethane strategy can contribute to a complete substitution of diesel fuel in urban buses and gives savings of around 1,000 tCO2/year. The price of the biomethane was found to be the most sensitive input factor. It is suggested that it should not exceed 0.40 EUR/Nm3 for a fuel conversion project of a fleet of 10 vehicles. Such a price can be ensured, if dry fermentation technology is chosen for biogas production. However, from the sustainability perspective, wet fermentation is more preferable due to the introduction of a source-separated organic waste management system in the region and higher gas yields. Introduction of this alternative requires additional funds which is a question of policy-level decisions.

  12. Vehicular Quality Biomethane Production from Biogas by Using an Automated Water Scrubbing System

    OpenAIRE

    Chandra, R; Vijay, V. K.; Subbarao, P. M. V.

    2012-01-01

    This paper presents the results of an automated water scrubbing system used for enrichment of methane content in the biogas, to produce vehicular grade biomethane fuel. Incorporation of automatic control systems for precisely regulating the water level and maintaining constant operating pressure in the packed bed absorption column of water scrubbing system resulted in steady-state operation of the scrubbing system and a consistent supply of methane-enriched biogas from the gas outlet. The imp...

  13. Waste-to-biomethane Concept Application: A Case Study of Valmiera City in Latvia

    Science.gov (United States)

    Barisa, Aiga; Dzene, Ilze; Rosa, Marika; Dobraja, Kristine

    2015-12-01

    The current needs of sustainable urban development are rising. As the transport sector expands, emissions continue to rise. Due to their negative impact on human health and the environment, air quality requirements are becoming more and more stringent. At the same time, the amount of waste is increasing. Europe Union policies attempt to relieve the pressure that these two stressors place on urban systems as they themselves expand. Today different solutions are available to decrease greenhouse gas emissions, increase air quality and improve waste management systems. Among them, waste-to-biomethane for use in urban systems deserves more attention. The paper focuses on application of the concept of waste-to-biomethane and the case study of Valmiera is evaluated. The results show that the application of the waste-to-biomethane strategy can contribute to a complete substitution of diesel fuel in urban buses and gives savings of around 1,000 tCO2/year. The price of the biomethane was found to be the most sensitive input factor. It is suggested that it should not exceed 0.40 EUR/Nm3 for a fuel conversion project of a fleet of 10 vehicles. Such a price can be ensured, if dry fermentation technology is chosen for biogas production. However, from the sustainability perspective, wet fermentation is more preferable due to the introduction of a source-separated organic waste management system in the region and higher gas yields. Introduction of this alternative requires additional funds which is a question of policy-level decisions.

  14. Bmp2 Is Required for Odontoblast Differentiation and Pulp Vasculogenesis

    OpenAIRE

    Yang, W; Harris, M.A.; Y. Cui; Mishina, Y; Harris, S.E.; Gluhak-Heinrich, J.

    2012-01-01

    Using the Bmp2 floxed/3.6Col1a1-Cre (Bmp2-cKOod) mouse model, we have observed severe defects in odontogenesis and dentin formation with the removal of the Bmp2 gene in early-polarizing odontoblasts. The odontoblasts in the Bmp2-cKOod do not mature properly and fail to form proper dentin with normal dentinal tubules and activate terminal differentiation, as reflected by decreased Osterix, Col1a1, and Dspp expression. There is less dentin, and the dentin is hypomineralized and patchy. We also ...

  15. Comparison of different pretreatments for the production of bioethanol and biomethane from corn stover and switchgrass.

    Science.gov (United States)

    Papa, G; Rodriguez, S; George, A; Schievano, A; Orzi, V; Sale, K L; Singh, S; Adani, F; Simmons, B A

    2015-05-01

    In this study the efficiency of mild ionic liquid (IL) pretreatment and pressurized hot water (PHW) is evaluated and compared in terms of bioethanol and biomethane yields, with corn stover (CS) and switchgrass (SG) as model bioenergy crops. Both feedstocks pretreated with the IL 1-ethyl-3-methylimidazolium acetate [C2C1Im][OAc] at 100°C for 3h exhibited lower glucose yield that those treated with harsher pretreatment conditions previously used. Compared to PHW, IL pretreatment demonstrated higher bioethanol yields; moreover IL pretreatment enhanced biomethane production. Taking into consideration both bioethanol and biomethane productions, results indicated that when using IL pretreatment, the total energy produced per kg of total solids was higher compared to untreated biomasses. Specifically energy produced from CS and SG was +18.6% and +34.5% respectively, as compared to those obtained by hot water treatment, i.e. +2.3% and +23.4% for CS and SG, respectively. PMID:25725408

  16. Wheat straw pretreatment with KOH for enhancing biomethane production and fertilizer value in anaerobic digestion☆

    Institute of Scientific and Technical Information of China (English)

    Muhammad Jaffar; Yunzhi Pang; Hairong Yuan; Dexun Zou; Yanping Liu; Baoning Zhu; Rashid Mustafa Korai; Xiujin Li

    2016-01-01

    Wheat straw biodegradability during anaerobic digestion was improved by treatment with potassium hydroxide (KOH) to decrease digestion time and enhance biomethane production and fertility value. KOH concentrations of 1%(K1), 3%(K2), 6%(K3) and 9%(K4) were tested for wheat straw pretreatment at ambient temperature with a C:N ratio of 25:1. 86%of total solids (TS), 89%of volatile solids (VS) and 22%of lignocel ulose, cellulose and hemi-cellulose (LCH) (22%) were decomposed effectively with the wheat straw pretreated by 6%KOH. Enhanced bio-gas production and cumulative biomethane yield of 258 ml·(g VS)−1 were obtained increased by 45%and 41%respectively, compared with untreated wheat straw. Pretreated wheat straw digestion also yielded a digestate with higher fertilizer values potassium (138%), calcium (22%) and magnesium (16%). These results show that TS, VS and LCH can be effectively removed from wheat straw pretreated with KOH, improving biodegradability biomethane production and fertilizer value.

  17. Studies on acidification in two-phase biomethanation process of municipal solid waste.

    Science.gov (United States)

    Bhattacharyya, J K; Kumar, Sunil; Devotta, Sukumar

    2008-01-01

    Biomethanation of municipal solid waste (MSW) is a slow process and the yield of biogas is usually low. Enhancement of acidification is necessary to increase the biogas yield in biomethanation of MSW. MSW contains a significant fraction of ligno-cellulosic material. The acidification of these materials influences the biogas yield. In the present study, hydrolysis and acidification have been considered as a combined phase. Experiments have been conducted to study the effect of recirculation of leachate on the acidification stage of the two-phase biomethanation process. Chemical oxygen demand (COD) and volatile fatty acid (VFA) were considered as indicator parameters. The study was also conducted to investigate the effect of using acid and alkali solution of 0.1% concentration in the acidification study. It was observed that daily recirculation of leachate does not have any major impact on the acidification process. It was also observed that treatment of MSW with sodium hydroxide yields leachate of significantly higher COD and VFA values compared to others. PMID:17276666

  18. Mesenchymal stem cells with rhBMP-2 inhibits the growth of canine osteosarcoma cells

    Directory of Open Access Journals (Sweden)

    Grassi Rici Rose

    2012-02-01

    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

  19. Laboratory investigations on continuous bio-methanization of energy crops as mono-substrate without supplementation

    Energy Technology Data Exchange (ETDEWEB)

    Demirel, Burak [Hamburg University of Applied Sciences (HAW Hamburg), Lifetec Process Engineering, Lohbruegger Kirchstrasse 65, 21033 Hamburg-Bergedorf (Germany); Bogazici University, Institute of Environmental Sciences, Bebek, 34342 Istanbul (Turkey)

    2009-06-15

    Continuous bio-methanization of an energy crop, namely the beet silage, was investigated in this laboratory-scale work as mono-substrate, using a mesophilic biogas digester controlled by a fuzzy logic control (FLC) technique and without using any supplementing or buffering agent, despite the low pH of the substrate around 3.80. The temperature, pH, redox potential (ORP), daily biogas production and composition of digester biogas were continuously measured online. During the operation, the hydraulic retention time (HRT) varied between 24.8 and 9 days, as the organic loading rate (OLR) ranged from 2.6 to 4.7 g L{sup -1} d{sup -1}. The average pH, specific gas production rate (spec. GPR) and volumetric gas production rate (vol. GPR) were determined to be 7.12, 0.31 L g VS{sup -1} d{sup -1} and 1.084 L L{sup -1} d{sup -1}, respectively. The average methane (CH{sub 4}) content of digester biogas was about 56%. The FLC technique, which was developed at HAW Hamburg for anaerobic conversion of acidic energy crops to methane, determined the daily feeding volume ({proportional_to} OLR/HRT) for the biogas digester, depending on the feedback from online pH and methane measurements, and on the calculation of the spec. GPR. The spec. GPR was calculated by the corrected daily biogas production. Through online monitoring of pH, biogas production rate and composition, and by use of the FLC technique, the acidic beet silage could continuously be converted to biogas, without using manure or any other kind of buffering or supplementing agent(s). The lab-scale anaerobic biogas digester performed stable and safe, without encountering any problems of instability, as indicated by an adequate amount of buffering capacity, a VFA content below 0.5 g L{sup -1} and a neutral pH range throughout the study. (author)

  20. THE IMPACT OF EXTRUSION ON THE BIOGAS AND BIOMETHANE YIELD OF PLANT SUBSTRATES

    Directory of Open Access Journals (Sweden)

    Krzysztof Pilarski

    2016-09-01

    Full Text Available The objective of the present work was to determine the effect of pretreatment by extrusion on the biogas and biomethane yield of lignocellulosic substrates such as maize silage and maize straw silage. The biogas yields of the substrates before and after treatment were compared. Moreover, energy efficiency of pretreatment by extrusion was analyzed in order to assess the applicability of the process in an agricultural biogas plant. Extrusion tests were carried out in a short single-screw extruder KZM-2 in which the length-to-diameter ratio of the screw was 6:1 and rotational speed was 200 rpm. The biogas yield tests of the plant substrates after extrusion were carried out in a laboratory scale, using 15 biofermenters operated in a periodic manner, at a constant temperature of 39°C (mesophilic digestion and controlled pH conditions. The gas-emission analysis was performed using a certified gas analyzer from Geotech GA5000. Pretreatment by extrusion was observed to improve the quantity of methane generated: in terms of fresh matter for maize silage subjected to extrusion, the methane yield was 16.48% higher than that of the non-extruded silage. On the other hand, maize straw silage after extrusion gave 35.30% more methane than did the same, non-extruded, material. Differences in yields relative to dry organic matter are also described in this paper. Taking into account the amount of energy that is spent on pretreatment and the generated amount of methane, the energy balance for the process gives an idea of the economics of the operation. For maize silage, energy efficiency was lower by 13.21% (-553.2 kWh/Mg, in contrast to maize straw silage, where the increase in energy was 33.49% (678.4 kWh/Mg. The obtained results indicate that more studies on the pretreatment and digestion of maize silage are required in order to improve the efficiency of its use for making biogas. To fully utilize its potential, it is necessary to know thoroughly the effect of

  1. Changes with Age and the Effect of Recombinant Human BMP-2 on Proteoglycan and Collagen Gene Expression in Rabbit Anulus Fibrosus Cells

    Institute of Scientific and Technical Information of China (English)

    Qin-Ming FEI; Xiao-Xing JIANG; Tong-Yi CHEN; Jun LI; Hideki MURAKAMI; Kai-Jow TSAI; William C. HUTTON

    2006-01-01

    In order to compare the difference between young and old intervertebral disc cells and their responsiveness to recombinant human bone morphogenetic protein-2 (rhBMP-2), disc cells were isolated from the anulus fibrosus (AF) and transition zones of lumbar discs from eight old and eight young New Zealand white rabbits. Compared with the cells from the young rabbits, cells from old rabbits respond less to rhBMP-2 treatment with respect to sulfated-glycosaminoglycan (sGAG) synthesis and aggrecan gene expression. But in collagen Ⅰ and collagen Ⅱ gene expressions, there are no significant differences between the old and the young. When comparing sGAG content, aggrecan, and collagen Ⅱ gene expression of the old AF cells after rhBMP-2 treatment with that of the young AF cells without rhBMP-2 treatment, the old AF cells with rhBMP-2 treatment have a greater capacity to synthesize sGAG bound in the cells and to release sGAG in the media, as well as to express aggrecan and collagen Ⅱ gene. It can be concluded that old AF cells after rhBMP-2 treatment have a greater capacity to synthesize sGAG and express aggrecan and collagen Ⅱ as compared to young AF cells without rhBMP-2 treatment. Thus rhBMP-2 can reverse the decline in the anabolic capacity of the disc cells with ageing. So it seems that rhBMP-2 has potential for use as an agent to retard a key component of disc degeneration and loss of disc matrix.

  2. A feasibility study on the bioconversion of CO2 and H2 to biomethane by gas sparging through polymeric membranes.

    Science.gov (United States)

    Díaz, I; Pérez, C; Alfaro, N; Fdz-Polanco, F

    2015-06-01

    In this study, the potential of a pilot hollow-fiber membrane bioreactor for the conversion of H2 and CO2 to CH4 was evaluated. The system transformed 95% of H2 and CO2 fed at a maximum loading rate of 40.2 [Formula: see text] and produced 0.22m(3) of CH4 per m(3) of H2 fed at thermophilic conditions. H2 mass transfer to the liquid phase was identified as the limiting step for the conversion, and kLa values of 430h(-1) were reached in the bioreactor by sparging gas through the membrane module. A simulation showed that the bioreactor could upgrade biogas at a rate of 25m(3)/mR(3)d, increasing the CH4 concentration from 60 to 95%v. This proof-of-concept study verified that gas sparging through a membrane module can efficiently transfer H2 from gas to liquid phase and that the conversion of H2 and CO2 to biomethane is feasible on a pilot scale at noteworthy load rates.

  3. A feasibility study on the bioconversion of CO2 and H2 to biomethane by gas sparging through polymeric membranes.

    Science.gov (United States)

    Díaz, I; Pérez, C; Alfaro, N; Fdz-Polanco, F

    2015-06-01

    In this study, the potential of a pilot hollow-fiber membrane bioreactor for the conversion of H2 and CO2 to CH4 was evaluated. The system transformed 95% of H2 and CO2 fed at a maximum loading rate of 40.2 [Formula: see text] and produced 0.22m(3) of CH4 per m(3) of H2 fed at thermophilic conditions. H2 mass transfer to the liquid phase was identified as the limiting step for the conversion, and kLa values of 430h(-1) were reached in the bioreactor by sparging gas through the membrane module. A simulation showed that the bioreactor could upgrade biogas at a rate of 25m(3)/mR(3)d, increasing the CH4 concentration from 60 to 95%v. This proof-of-concept study verified that gas sparging through a membrane module can efficiently transfer H2 from gas to liquid phase and that the conversion of H2 and CO2 to biomethane is feasible on a pilot scale at noteworthy load rates. PMID:25770473

  4. BMP-2 and titanium particles synergistically activate osteoclast formation

    Energy Technology Data Exchange (ETDEWEB)

    Sun, S.X. [Affiliated Hospital of Ningxia Medical University, Department of Orthopedics, Yinchuan, Ningxia Hui Autonomous Region, China, Department of Orthopedics, Affiliated Hospital of Ningxia Medical University, Yinchuan, Ningxia Hui Autonomous Region (China); Guo, H.H. [Ningxia Medical University, Yinchuan, Ningxia Hui Autonomous Region, China, Ningxia Medical University, Yinchuan, Ningxia Hui Autonomous Region (China); Zhang, J. [Institute of Pathology, Xi' an Jiaotong University, Xi' an Shaanxi, China, Institute of Pathology, Xi' an Jiaotong University, Xi' an Shaanxi (China); Yu, B. [Ningxia Medical University, Yinchuan, Ningxia Hui Autonomous Region, China, Ningxia Medical University, Yinchuan, Ningxia Hui Autonomous Region (China); Sun, K.N.; Jin, Q.H. [Affiliated Hospital of Ningxia Medical University, Department of Orthopedics, Yinchuan, Ningxia Hui Autonomous Region, China, Department of Orthopedics, Affiliated Hospital of Ningxia Medical University, Yinchuan, Ningxia Hui Autonomous Region (China)

    2014-05-09

    A previous study showed that BMP-2 (bone morphogenetic protein-2) and wear debris can separately support osteoclast formation induced by the receptor activator of NF-κB ligand (RANKL). However, the effect of BMP-2 on wear debris-induced osteoclast formation is unclear. In this study, we show that neither titanium particles nor BMP-2 can induce osteoclast formation in RAW 264.7 mouse leukemic monocyte macrophage cells but that BMP-2 synergizes with titanium particles to enhance osteoclast formation in the presence of RANKL, and that at a low concentration, BMP-2 has an optimal effect to stimulate the size and number of multinuclear osteoclasts, expression of osteoclast genes, and resorption area. Our data also clarify that the effects caused by the increase in BMP-2 on phosphorylated SMAD levels such as c-Fos expression increased throughout the early stages of osteoclastogenesis. BMP-2 and titanium particles stimulate the expression of p-JNK, p-P38, p-IkB, and P50 compared with the titanium group. These data suggested that BMP-2 may be a crucial factor in titanium particle-mediated osteoclast formation.

  5. Bmp indicator mice reveal dynamic regulation of transcriptional response.

    Directory of Open Access Journals (Sweden)

    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.

  6. BMP signaling pathway is required for commitment of C3H10T1/2 pluripotent stem cells to the adipocyte lineage

    OpenAIRE

    Huang, Haiyan; Song, Tan-Jing; Li, Xi; Hu, Lingling; He, Qun; Liu, Mei; Lane, M. Daniel; Tang, Qi-Qun

    2009-01-01

    Obesity is accompanied by an increase in both adipocyte number and size. The increase in adipocyte number is the result of recruitment to the adipocyte lineage of pluripotent stem cells present in the vascular stroma of adipose tissue. These pluripotent cells have the potential to undergo commitment and then differentiate into adipocytes, as well as myocytes, osteocytes, and chondrocytes. In this article, we show that both bone morphogenetic protein (BMP)2 and BMP4 can induce commitment of C3...

  7. Using feature objects aided strategy to evaluate the biomethane production of food waste and corn stalk anaerobic co-digestion.

    Science.gov (United States)

    Zhou, Qi; Yuan, Hairong; Liu, Yanping; Zou, Dexun; Zhu, Baoning; Chufo, Wachemo A; Jaffar, Muhammad; Li, Xiujin

    2015-03-01

    Feature objects aided strategy was used to predict and evaluate the biomethane production of food waste and corn stalk anaerobic co-digestion. The kinetics of co-digestion and mono-digestion of food waste and/or corn stalk was also analyzed. The results indicated that the compositions of food waste and corn stalk were significantly different. The anaerobic digestion of three feature objects at different mixing ratios showed the different biomethane yields and kinetic constants. Food waste and corn stalk co-digestion enhanced the digestion rate and achieved 22.48% and 41.55% higher biomethane production than those of food waste and corn stalk mono-digestion, respectively. PMID:25575585

  8. BMP7 enhances the effect of BMSCs on extracellular matrix remodeling in a rabbit model of intervertebral disc degeneration.

    Science.gov (United States)

    Xu, Jun; E, Xiao-Qiang; Wang, Nan-Xiang; Wang, Mo-Nan; Xie, Huan-Xin; Cao, Yan-Hui; Sun, Li-Hua; Tian, Jun; Chen, Hua-Jiang; Yan, Jing-Long

    2016-05-01

    Intervertebral discs (IVDs) provide stability and flexibility to the spinal column; however, IVDs, and in particular the nucleus pulposus (NP), undergo a degenerative process characterized by changes in the disc extracellular matrix (ECM), decreased cell viability, and reduced synthesis of proteoglycan and type II collagen. Here, we investigated the efficacy and feasibility of stem cell therapy using bone marrow mesenchymal stem cells (BMSCs) over-expressing bone morphogenetic protein 7 (BMP7) to promote ECM remodeling of degenerated IVDs. Lentivirus-mediated BMP7 over-expression induced differentiation of BMSCs into an NP phenotype, as indicated by expression of the NP markers collagen type II, aggrecan, SOX9 and keratins 8 and 19, increased the content of glycosaminoglycan, and up-regulated β-1,3-glucuronosyl transferase 1, a regulator of chondroitin sulfate synthesis in NP cells. These effects were suppressed by Smad1 silencing, indicating that the effect of BMP7 on ECM remodeling was mediated by the Smad pathway. In vivo analysis in a rabbit model of disc degeneration showed that implantation of BMSCs over-expressing BMP7 promoted cell differentiation and proliferation in the NP, as well as their own survival, and these effects were mediated by the Smad pathway. The results of the present study indicate the beneficial effects of BMP7 on restoring ECM homeostasis in NP cells, and suggest potential strategies for improving cell therapy for the treatment of disc diseases. PMID:26929154

  9. BMP-2 Is Involved in Scleral Remodeling in Myopia Development.

    Directory of Open Access Journals (Sweden)

    Honghui Li

    Full Text Available The development of myopia is associated with scleral remodeling, but it is unclear which factors regulate this process. This study investigated bone morphogenetic protein-2 (BMP-2 expression in the sclera of guinea pigs with lens-induced myopia (LIM and after recovery from myopia and evaluated the effect of BMP-2 on extracellular matrix (ECM synthesis in human scleral fibroblasts (HSFs cultured in vitro. Lens-induced myopia was brought about in two groups of guinea pigs (the lens-induced myopia and myopia recovery groups by placing -4.00 D lenses on the right eye for three weeks. The left eye served as a contralateral control. In the recovery group, the lenses were removed after one week. The refractive power and axial length of the eyes were measured, and the BMP-2 expression levels in the sclera were measured. After three weeks, the lens-induced eyes acquired relative myopia in both groups of guinea pigs. Immunostaining of the eyeballs revealed significantly decreased BMP-2 expression in the posterior sclera of the myopic eyes compared to the contralateral eyes. One week after lens removal, BMP-2 expression recovered, and no differences were observed between the experimental and contralateral eyes in the recovery group. HSFs were cultured with BMP-2 or transforming growth factor-β1 (TGF-β1. Type I and type III collagen synthesis was significantly up-regulated following BMP-2 treatment in culture after one and two weeks, but the ratio of type III to type I collagen mRNA was not increased. Biosynthesis of glycosaminoglycan (GAG and aggrecan was increased in HSFs treated with BMP-2. Some chondrogenesis-associated genes expression increased in HSFs treated with BMP-2. From this study, we concluded that BMP-2 is involved in scleral remodeling in the development and recovery of lens-induced myopia.

  10. BMP-2 Is Involved in Scleral Remodeling in Myopia Development

    Science.gov (United States)

    Li, Honghui; Cui, Dongmei; Zhao, Feng; Huo, Lijun; Hu, Jianmin; Zeng, Junwen

    2015-01-01

    The development of myopia is associated with scleral remodeling, but it is unclear which factors regulate this process. This study investigated bone morphogenetic protein-2 (BMP-2) expression in the sclera of guinea pigs with lens-induced myopia (LIM) and after recovery from myopia and evaluated the effect of BMP-2 on extracellular matrix (ECM) synthesis in human scleral fibroblasts (HSFs) cultured in vitro. Lens-induced myopia was brought about in two groups of guinea pigs (the lens-induced myopia and myopia recovery groups) by placing -4.00 D lenses on the right eye for three weeks. The left eye served as a contralateral control. In the recovery group, the lenses were removed after one week. The refractive power and axial length of the eyes were measured, and the BMP-2 expression levels in the sclera were measured. After three weeks, the lens-induced eyes acquired relative myopia in both groups of guinea pigs. Immunostaining of the eyeballs revealed significantly decreased BMP-2 expression in the posterior sclera of the myopic eyes compared to the contralateral eyes. One week after lens removal, BMP-2 expression recovered, and no differences were observed between the experimental and contralateral eyes in the recovery group. HSFs were cultured with BMP-2 or transforming growth factor-β1 (TGF-β1). Type I and type III collagen synthesis was significantly up-regulated following BMP-2 treatment in culture after one and two weeks, but the ratio of type III to type I collagen mRNA was not increased. Biosynthesis of glycosaminoglycan (GAG) and aggrecan was increased in HSFs treated with BMP-2. Some chondrogenesis-associated genes expression increased in HSFs treated with BMP-2. From this study, we concluded that BMP-2 is involved in scleral remodeling in the development and recovery of lens-induced myopia. PMID:25965995

  11. Immunohistological Localization of BMP-2, BMP-7, and Their Receptors in Knee Joints with Focal Cartilage Lesions

    Directory of Open Access Journals (Sweden)

    Hagen Schmal

    2012-01-01

    Full Text Available Introduction. Although it is well known that BMP-2 and BMP-7 play significant roles in cartilage metabolism, data about intra-articular expression and localization of these proteins and their receptors in humans are rare. Methods. Biopsies of synovia and debrided cartilage were taken in patients undergoing autologous chondrocyte implantation. Expression of BMP-2, BMP-7, and their receptors BMPR-1A, BMPR-1B and BMPR-2 were semiquantitatively evaluated by immunohistological staining. Results. BMP-7 was equally highly expressed in all cartilage and synovial biopsies. Increased levels of BMPR-1A, but not of BMPR-1B, and BMPR-2, were found in all synovial and 47% of all cartilage samples (P=0.002. BMP-2 was positively scored in 47% of all cartilage and 40% of all synovial specimens. Defect size, KOSS, Henderson or Kellgren-Lawrence score did not statistically significant correlate with the expression of the analyzed proteins or Mankin and Pritzker scores. Duration of symptoms and localization of lesions were associated with KOSS (P<0.02, but there was no influence of these parameters on protein expression. Conclusions. BMP-2, BMP-7, and BMPR-1A were expressed in cartilage and synovia of knees with focal cartilage lesions. Although defect localization and duration of symptoms decisively influence KOSS, there was no associated alteration of protein expression observed.

  12. NOX4 mediates BMP4-induced upregulation of TRPC1 and 6 protein expressions in distal pulmonary arterial smooth muscle cells.

    Directory of Open Access Journals (Sweden)

    Qian Jiang

    Full Text Available RATIONALE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: These results suggest that BMP4 may increase ROS level, enhance TRPC1 and 6 expression and proliferation by up-regulating NOX4 expression in PASMCs.

  13. Improving Biomethane Production and Mass Bioconversion of Corn Stover Anaerobic Digestion by Adding NaOH Pretreatment and Trace Elements

    OpenAIRE

    ChunMei Liu; HaiRong Yuan; DeXun Zou; YanPing Liu; BaoNing Zhu; XiuJin Li

    2015-01-01

    This research applied sodium hydroxide (NaOH) pretreatment and trace elements to improve biomethane production when using corn stover for anaerobic digestion. Full-factor experimental tests identified the best combination of trace elements with the NaOH pretreatment, indicating that the best combination was with 1.0, 0.4, and 0.4 mg·L−1·d−1 of elements Fe, Co, and Ni, respectively. The cumulative biomethane production adding NaOH pretreatment and trace elements was 11,367 mL; total solid bioc...

  14. BMP2 gene delivery to bone mesenchymal stem cell by chitosan-g-PEI nonviral vector

    Science.gov (United States)

    Yue, Jianhui; Wu, Jun; Liu, Di; Zhao, Xiaoli; Lu, William W.

    2015-04-01

    Nanotechnology has made a significant impact on the development of nanomedicine. Nonviral vectors have been attracting more attention for the advantage of biosafety in gene delivery. Polyethylenimine (PEI)-conjugated chitosan (chitosan-g-PEI) emerged as a promising nonviral vector and has been demonstrated in many tumor cells. However, there is a lack of study focused on the behavior of this vector in stem cells which hold great potential in regenerative medicine. Therefore, in this study, in vitro gene delivering effect of chitosan-g-PEI was investigated in bone marrow stem cells. pIRES2-ZsGreen1-hBMP2 dual expression plasmid containing both the ZsGreen1 GFP reporter gene and the BMP2 functional gene was constructed for monitoring the transgene expression level. Chitosan-g-PEI-mediated gene transfer showed 17.2% of transfection efficiency and more than 80% of cell viability in stem cells. These values were higher than that of PEI. The expression of the delivered BMP2 gene in stem cells enhanced the osteogenic differentiation. These results demonstrated that chitosan-g-PEI is capable of applying in delivering gene to stem cells and providing potential applications in stem cell-based gene therapy.

  15. Integration of nodal and BMP signals in the heart requires FoxH1 to create left-right differences in cell migration rates that direct cardiac asymmetry.

    Directory of Open Access Journals (Sweden)

    Kari F Lenhart

    Full Text Available Failure to properly establish the left-right (L/R axis is a major cause of congenital heart defects in humans, but how L/R patterning of the embryo leads to asymmetric cardiac morphogenesis is still unclear. We find that asymmetric Nodal signaling on the left and Bmp signaling act in parallel to establish zebrafish cardiac laterality by modulating cell migration velocities across the L/R axis. Moreover, we demonstrate that Nodal plays the crucial role in generating asymmetry in the heart and that Bmp signaling via Bmp4 is dispensable in the presence of asymmetric Nodal signaling. In addition, we identify a previously unappreciated role for the Nodal-transcription factor FoxH1 in mediating cell responsiveness to Bmp, further linking the control of these two pathways in the heart. The interplay between these TGFβ pathways is complex, with Nodal signaling potentially acting to limit the response to Bmp pathway activation and the dosage of Bmp signals being critical to limit migration rates. These findings have implications for understanding the complex genetic interactions that lead to congenital heart disease in humans.

  16. Greenhouse gas emissions from biomethane plants. Measurement results and cause analysis; Treibhausgasemissionen aus Biomethananlagen. Messergebnisse und Ursachenanalyse

    Energy Technology Data Exchange (ETDEWEB)

    Reinelt, Torsten; Westerkamp, Tanja [DBFZ Deutsches Biomasseforschungszentrum gemeinnuetzige GmbH, Leipzig (Germany). Bereich Thermochemische Konversion

    2014-08-01

    Biomethane gained importance in the past years. Nevertheless the sustainability of an increasing biomethane production is an important issue. In the meantime the methane loss from biogas upgrading units can be minimized reliably. Henceforth, the diffuse greenhouse gas (GHG) emissions from the biogas-producing plant components and the digestate storage are brought into focus. By two different measurement methods (on-site and remote sensing method) GHG emissions from three biomethane plants were quantified. The on-site method measured methane emissions in the amount of 0.12 to 0. 88 % CH{sub 4} and the remote sensing method in the amount of 0.19 to 2.84% CH{sub 4}. Ammonia and nitrogen dioxide emissions were irrelevant in particular if the systems engineering was completely gastight. At every plant the biogas upgrading was carried out by chemical scrubbing so that methane emissions were emitted in particular by not gastight digestate storage, diffuse leakages and pressure relief vents. Both measurement methods gave similar estimations about the GHG-emissions from the biomethane plants while differences in the exact amount of the measured GHG-emissions occurred.

  17. What type of digester configurations should be employed to produce biomethane from grass silage?

    Energy Technology Data Exchange (ETDEWEB)

    Nizami, Abdul-Sattar; Murphy, Jerry D. [Department of Civil and Environmental Engineering, University College Cork, Cork (Ireland); Environmental Research Institute, University College Cork (Ireland)

    2010-08-15

    Grass is an excellent energy crop; it may be classified as a high yielding, low energy input, perennial crop. Over 90% of Irish agricultural land is under grass; thus farmers are familiar with, and comfortable with, this crop as opposed to a ''new energy crop'' such as Miscanthus. Of issue therefore is not the crop, but the methodology of generating energy from the crop. Numerous farmers across Europe (in particular Germany and Austria) use grass silage as a feedstock for biogas production; in a number of cases the produced biogas is scrubbed to biomethane and used as a transport fuel or injected into the natural gas grid. Many Irish farmers are considering converting from conventional farming such as beef production to grass biomethane production. Numerous technologies and combinations of such technologies are available; from one-stage batch dry systems to two-stage wet continuous systems; from one-stage continuous wet systems to two-stage systems incorporating a batch dry reactor coupled with a second stage high-rate reactor. This paper reviews work carried out both in the scientific literature and in practice at commercial scale. (author)

  18. BMP4 density gradient in disk-shaped confinement

    Science.gov (United States)

    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.

  19. BMP-2 Is Involved in Scleral Remodeling in Myopia Development

    OpenAIRE

    Honghui Li; Dongmei Cui; Feng Zhao; Lijun Huo; Jianmin Hu; Junwen Zeng

    2015-01-01

    The development of myopia is associated with scleral remodeling, but it is unclear which factors regulate this process. This study investigated bone morphogenetic protein-2 (BMP-2) expression in the sclera of guinea pigs with lens-induced myopia (LIM) and after recovery from myopia and evaluated the effect of BMP-2 on extracellular matrix (ECM) synthesis in human scleral fibroblasts (HSFs) cultured in vitro. Lens-induced myopia was brought about in two groups of guinea pigs (the lens-induced ...

  20. 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

    Directory of Open Access Journals (Sweden)

    C. Oleskovicz

    2004-08-01

    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.

  1. Hepcidin regulation by BMP signaling in macrophages is lipopolysaccharide dependent.

    Directory of Open Access Journals (Sweden)

    Xinggang Wu

    Full Text Available Hepcidin is an antimicrobial peptide, which also negatively regulates iron in circulation by controlling iron absorption from dietary sources and iron release from macrophages. Hepcidin is synthesized mainly in the liver, where hepcidin is regulated by iron loading, inflammation and hypoxia. Recently, we have demonstrated that bone morphogenetic protein (BMP-hemojuvelin (HJV-SMAD signaling is central for hepcidin regulation in hepatocytes. Hepcidin is also expressed by macrophages. Studies have shown that hepcidin expression by macrophages increases following bacterial infection, and that hepcidin decreases iron release from macrophages in an autocrine and/or paracrine manner. Although previous studies have shown that lipopolysaccharide (LPS can induce hepcidin expression in macrophages, whether hepcidin is also regulated by BMPs in macrophages is still unknown. Therefore, we examined the effects of BMP signaling on hepcidin expression in RAW 264.7 and J774 macrophage cell lines, and in primary peritoneal macrophages. We found that BMP4 or BMP6 alone did not have any effect on hepcidin expression in macrophages although they stimulated Smad1/5/8 phosphorylation and Id1 expression. In the presence of LPS, however, BMP4 and BMP6 were able to stimulate hepcidin expression in macrophages, and this stimulation was abolished by the NF-κB inhibitor Ro1069920. These results suggest that hepcidin expression is regulated differently in macrophages than in hepatocytes, and that BMPs regulate hepcidin expression in macrophages in a LPS-NF-κB dependent manner.

  2. Apc bridges Wnt/{beta}-catenin and BMP signaling during osteoblast differentiation of KS483 cells

    Energy Technology Data Exchange (ETDEWEB)

    Miclea, Razvan L., E-mail: R.L.Miclea@lumc.nl [Department of Pediatrics, Leiden University Medical Centre (LUMC), Leiden (Netherlands); Horst, Geertje van der, E-mail: G.van_der_Horst@lumc.nl [Department of Urology, LUMC, Leiden (Netherlands); Robanus-Maandag, Els C., E-mail: E.C.Robanus@lumc.nl [Department of Human Genetics, LUMC, Leiden (Netherlands); Loewik, Clemens W.G.M., E-mail: C.W.G.M.Lowik@lumc.nl [Department of Endocrinology and Metabolic Diseases, LUMC, Leiden (Netherlands); Oostdijk, Wilma, E-mail: W.Oostdijk@lumc.nl [Department of Pediatrics, Leiden University Medical Centre (LUMC), Leiden (Netherlands); Wit, Jan M., E-mail: J.M.Wit@lumc.nl [Department of Pediatrics, Leiden University Medical Centre (LUMC), Leiden (Netherlands); Karperien, Marcel, E-mail: H.B.J.Karperien@tnw.utwente.nl [MIRA Institute for Biomedical Technology and Technical Medicine, Department of Tissue Regeneration, University of Twente, Zuidhorst Room ZH 144, Drienerlolaan 5, 7522 NB Enschede (Netherlands)

    2011-06-10

    The canonical Wnt signaling pathway influences the differentiation of mesenchymal cell lineages in a quantitative and qualitative fashion depending on the dose of {beta}-catenin signaling. Adenomatous polyposis coli (Apc) is the critical intracellular regulator of {beta}-catenin turnover. To better understand the molecular mechanisms underlying the role of Apc in regulating the differentiation capacity of skeletal progenitor cells, we have knocked down Apc in the murine mesenchymal stem cell-like KS483 cells by stable expression of Apc-specific small interfering RNA. In routine culture, KSFrt-Apc{sub si} cells displayed a mesenchymal-like spindle shape morphology, exhibited markedly decreased proliferation and increased apoptosis. Apc knockdown resulted in upregulation of the Wnt/{beta}-catenin and the BMP/Smad signaling pathways, but osteogenic differentiation was completely inhibited. This effect could be rescued by adding high concentrations of BMP-7 to the differentiation medium. Furthermore, KSFrt-Apc{sub si} cells showed no potential to differentiate into chondrocytes or adipocytes. These results demonstrate that Apc is essential for the proliferation, survival and differentiation of KS483 cells. Apc knockdown blocks the osteogenic differentiation of skeletal progenitor cells, a process that can be overruled by high BMP signaling.

  3. Apc bridges Wnt/β-catenin and BMP signaling during osteoblast differentiation of KS483 cells

    International Nuclear Information System (INIS)

    The canonical Wnt signaling pathway influences the differentiation of mesenchymal cell lineages in a quantitative and qualitative fashion depending on the dose of β-catenin signaling. Adenomatous polyposis coli (Apc) is the critical intracellular regulator of β-catenin turnover. To better understand the molecular mechanisms underlying the role of Apc in regulating the differentiation capacity of skeletal progenitor cells, we have knocked down Apc in the murine mesenchymal stem cell-like KS483 cells by stable expression of Apc-specific small interfering RNA. In routine culture, KSFrt-Apcsi cells displayed a mesenchymal-like spindle shape morphology, exhibited markedly decreased proliferation and increased apoptosis. Apc knockdown resulted in upregulation of the Wnt/β-catenin and the BMP/Smad signaling pathways, but osteogenic differentiation was completely inhibited. This effect could be rescued by adding high concentrations of BMP-7 to the differentiation medium. Furthermore, KSFrt-Apcsi cells showed no potential to differentiate into chondrocytes or adipocytes. These results demonstrate that Apc is essential for the proliferation, survival and differentiation of KS483 cells. Apc knockdown blocks the osteogenic differentiation of skeletal progenitor cells, a process that can be overruled by high BMP signaling.

  4. Constitutive activation of BMP signalling abrogates experimental metastasis of OVCA429 cells via reduced cell adhesion

    Directory of Open Access Journals (Sweden)

    Shepherd Trevor G

    2010-02-01

    Full Text Available Abstract Background Activation of bone morphogenetic protein (BMP4 signalling in human ovarian cancer cells induces a number of phenotypic changes in vitro, including altered cell morphology, adhesion, motility and invasion, relative to normal human ovarian surface epithelial cells. From these in vitro analyses, we had hypothesized that active BMP signalling promotes the metastatic potential of ovarian cancer. Methods To test this directly, we engineered OVCA429 human ovarian cancer cells possessing doxycycline-inducible expression of a constitutively-active mutant BMP receptor, ALK3QD, and administered these cells to immunocompromised mice. Further characterization was performed in vitro to address the role of activated BMP signalling on the EOC phenotype, with particular emphasis on epithelial-mesenchymal transition (EMT and cell adhesion. Results Unexpectedly, doxycycline-induced ALK3QD expression in OVCA429 cells reduced tumour implantation on peritoneal surfaces and ascites formation when xenografted into immunocompromised mice by intraperitoneal injection. To determine the potential mechanisms controlling this in vivo observation, we followed with several cell culture experiments. Doxycycline-induced ALK3QD expression enhanced the refractile, spindle-shaped morphology of cultured OVCA429 cells eliciting an EMT-like response. Using in vitro wound healing assays, we observed that ALK3QD-expressing cells migrated with long, cytoplasmic projections extending into the wound space. The phenotypic alterations of ALK3QD-expressing cells correlated with changes in specific gene expression patterns of EMT, including increased Snail and Slug and reduced E-cadherin mRNA expression. In addition, ALK3QD signalling reduced β1- and β3-integrin expression, critical molecules involved in ovarian cancer cell adhesion. The combination of reduced E-cadherin and β-integrin expression correlates directly with the reduced EOC cell cohesion in spheroids and

  5. The origin of bmp16, a novel Bmp2/4 relative, retained in teleost fish genomes

    Directory of Open Access Journals (Sweden)

    Meyer Axel

    2009-12-01

    Full Text Available Abstract Background Whole genome sequences have allowed us to have an overview of the evolution of gene repertoires. The target of the present study, the TGFβ superfamily, contains many genes involved in vertebrate development, and provides an ideal system to explore the relationships between evolution of gene repertoires and that of developmental programs. Results As a result of a bioinformatic survey of sequenced vertebrate genomes, we identified an uncharacterized member of the TGFβ superfamily, designated bmp16, which is confined to teleost fish species. Our molecular phylogenetic study revealed a high affinity of bmp16 to the Bmp2/4 subfamily. Importantly, further analyses based on the maximum-likelihood method unambiguously ruled out the possibility that this teleost-specific gene is a product of teleost-specific genome duplication. This suggests that the absence of a bmp16 ortholog in tetrapods is due to a secondary loss. In situ hybridization showed embryonic expression of the zebrafish bmp16 in the developing swim bladder, heart, tail bud, and ectoderm of pectoral and median fin folds in pharyngula stages, as well as gut-associated expression in 5-day embryos. Conclusion Comparisons of expression patterns revealed (1 the redundancy of bmp16 expression with its homologs in presumably plesiomorphic expression domains, such as the fin fold, heart, and tail bud, which might have permitted its loss in the tetrapod lineage, and (2 the loss of craniofacial expression and gain of swim bladder expression of bmp16 after the gene duplication between Bmp2, -4 and -16. Our findings highlight the importance of documenting secondary changes of gene repertoires and expression patterns in other gene families.

  6. Single-molecule imaging of BMP4 dimerization on human periodontal ligament cells.

    Science.gov (United States)

    Mi, H-W; Lee, M-C; Chiang, Y-C; Chow, L-P; Lin, C-P

    2011-11-01

    We expressed bone morphogenetic protein 4 (BMP4) fused with enhanced green fluorescent protein (BMP4-EGFP) in the secretory pathways of producer cells. Fluorescent EGFP was acquired only after we interrupted the transport of BMP4-EGFP by culturing cells at a lower temperature (20°C), and the dynamics of BMP4-EGFP could be monitored by single-molecule microscopy. Western blotting analysis confirmed that exposure to low temperature helped the integrated formation of BMP4-EGFP fusion proteins. In this study, for the first time, we could image the fluorescently labeled BMP4 molecules localized on the plasma membrane of living hPDL cells. The one-step photobleaching with EGFP and the "blinking" behavior of quantum dots suggest that the fluorescent spots represent the events of single BMP4 molecules. Single-molecule tracking showed that the BMP receptors (BMPR) dimerize after BMP4 stimulation, or that a complex of one BMP4 molecule and a pre-formed BMPR dimer develops first, followed by the binding of the second BMP4 molecule. Furthermore, BMP4-EGFP enhanced the osteogenic differentiation of hPDL cells via signal transduction involving BMP receptors. This single-molecule imaging technique might be a valuable tool for the future development of BMP4 gene therapy and regenerative medicine mediated by hPDLs. PMID:21841042

  7. Abrogation of epithelial BMP2 and BMP4 causes Amelogenesis Imperfecta by reducing MMP20 and KLK4 expression

    Science.gov (United States)

    Xie, Xiaohua; Liu, Chao; Zhang, Hua; Jani, Priyam H.; Lu, Yongbo; Wang, Xiaofang; Zhang, Bin; Qin, Chunlin

    2016-01-01

    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;Bmp2f/f;Bmp4f/fameloblasts, suggesting that the reduced MMP20 and KLK4 expression may be due to the attenuated epithelial BMP/Smad4 signaling. PMID:27146352

  8. Defining BMP functions in the hair follicle by conditional ablation of BMP receptor IA

    OpenAIRE

    Kobielak, Krzysztof; Pasolli, H. Amalia; Alonso, Laura; Polak, Lisa; Fuchs, Elaine

    2003-01-01

    Using conditional gene targeting in mice, we show that BMP receptor IA is essential for the differentiation of progenitor cells of the inner root sheath and hair shaft. Without BMPRIA activation, GATA-3 is down-regulated and its regulated control of IRS differentiation is compromised. In contrast, Lef1 is up-regulated, but its regulated control of hair differentiation is still blocked, and BMPRIA-null follicles fail to activate Lef1/β-catenin–regulated genes, including keratin genes. Wnt-medi...

  9. Villification in the mouse: Bmp signals control intestinal villus patterning.

    Science.gov (United States)

    Walton, Katherine D; Whidden, Mark; Kolterud, Åsa; Shoffner, Suzanne K; Czerwinski, Michael J; Kushwaha, Juhi; Parmar, Nishita; Chandhrasekhar, Deepa; Freddo, Andrew M; Schnell, Santiago; Gumucio, Deborah L

    2016-02-01

    In the intestine, finger-like villi provide abundant surface area for nutrient absorption. During murine villus development, epithelial Hedgehog (Hh) signals promote aggregation of subepithelial mesenchymal clusters that drive villus emergence. Clusters arise first dorsally and proximally and spread over the entire intestine within 24 h, but the mechanism driving this pattern in the murine intestine is unknown. In chick, the driver of cluster pattern is tensile force from developing smooth muscle, which generates deep longitudinal epithelial folds that locally concentrate the Hh signal, promoting localized expression of cluster genes. By contrast, we show that in mouse, muscle-induced epithelial folding does not occur and artificial deformation of the epithelium does not determine the pattern of clusters or villi. In intestinal explants, modulation of Bmp signaling alters the spatial distribution of clusters and changes the pattern of emerging villi. Increasing Bmp signaling abolishes cluster formation, whereas inhibiting Bmp signaling leads to merged clusters. These dynamic changes in cluster pattern are faithfully simulated by a mathematical model of a Turing field in which an inhibitor of Bmp signaling acts as the Turing activator. In vivo, genetic interruption of Bmp signal reception in either epithelium or mesenchyme reveals that Bmp signaling in Hh-responsive mesenchymal cells controls cluster pattern. Thus, unlike in chick, the murine villus patterning system is independent of muscle-induced epithelial deformation. Rather, a complex cocktail of Bmps and Bmp signal modulators secreted from mesenchymal clusters determines the pattern of villi in a manner that mimics the spread of a self-organizing Turing field. PMID:26721501

  10. Defining BMP functions in the hair follicle by conditional ablation of BMP receptor IA.

    Science.gov (United States)

    Kobielak, Krzysztof; Pasolli, H Amalia; Alonso, Laura; Polak, Lisa; Fuchs, Elaine

    2003-11-10

    Using conditional gene targeting in mice, we show that BMP receptor IA is essential for the differentiation of progenitor cells of the inner root sheath and hair shaft. Without BMPRIA activation, GATA-3 is down-regulated and its regulated control of IRS differentiation is compromised. In contrast, Lef1 is up-regulated, but its regulated control of hair differentiation is still blocked, and BMPRIA-null follicles fail to activate Lef1/beta-catenin-regulated genes, including keratin genes. Wnt-mediated transcriptional activation can be restored by transfecting BMPRIA-null keratinocytes with a constitutively activated beta-catenin. This places the block downstream from Lef1 expression but upstream from beta-catenin stabilization. Because mice lacking the BMP inhibitor Noggin fail to express Lef1, our findings support a model, whereby a sequential inhibition and then activation of BMPRIA is necessary to define a band of hair progenitor cells, which possess enough Lef1 and stabilized beta-catenin to activate the hair specific keratin genes and generate the hair shaft.

  11. Trehalose maintains bioactivity and promotes sustained release of BMP-2 from lyophilized CDHA scaffolds for enhanced osteogenesis in vitro and in vivo.

    Directory of Open Access Journals (Sweden)

    Jun Zhao

    Full Text Available Calcium phosphate (Ca-P scaffolds have been widely employed as a supportive matrix and delivery system for bone tissue engineering. Previous studies using osteoinductive growth factors loaded Ca-P scaffolds via passive adsorption often experience issues associated with easy inactivation and uncontrolled release. In present study, a new delivery system was fabricated using bone morphogenetic protein-2 (BMP-2 loaded calcium-deficient hydroxyapatite (CDHA scaffold by lyophilization with addition of trehalose. The in vitro osteogenesis effects of this formulation were compared with lyophilized BMP-2/CDHA construct without trehalose and absorbed BMP-2/CDHA constructs with or without trehalose. The release characteristics and alkaline phosphatase (ALP activity analyses showed that addition of trehalose could sufficiently protect BMP-2 bioactivity during lyophilization and achieve sustained BMP-2 release from lyophilized CDHA construct in vitro and in vivo. However, absorbed BMP-2/CDHA constructs with or without trehalose showed similar BMP-2 bioactivity and presented a burst release. Quantitative real-time PCR (RT-qPCR and enzyme-linked immunosorbent assay (ELISA demonstrated that lyophilized BMP-2/CDHA construct with trehalose (lyo-tre-BMP-2 promoted osteogenic differentiation of bone marrow stromal cells (bMSCs significantly and this formulation could preserve over 70% protein bioactivity after 5 weeks storage at 25°C. Micro-computed tomography, histological and fluorescent labeling analyses further demonstrated that lyo-tre-BMP-2 formulation combined with bMSCs led to the most percentage of new bone volume (38.79% ± 5.32% and area (40.71% ± 7.14% as well as the most percentage of fluorochrome stained bone area (alizarin red S: 2.64% ± 0.44%, calcein: 6.08% ± 1.37% and mineral apposition rate (4.13 ± 0.62 µm/day in critical-sized rat cranial defects healing. Biomechanical tests also indicated the maximum stiffness (118.17 ± 15.02 Mpa and

  12. Negative and positive auto-regulation of BMP expression in early eye development.

    Science.gov (United States)

    Huang, Jie; Liu, Ying; Filas, Benjamen; Gunhaga, Lena; Beebe, David C

    2015-11-15

    Previous results have shown that Bone Morphogenetic Protein (BMP) signaling is essential for lens specification and differentiation. How BMP signals are regulated in the prospective lens ectoderm is not well defined. To address this issue we have modulated BMP activity in a chicken embryo pre-lens ectoderm explant assay, and also studied transgenic mice, in which the type I BMP receptors, Bmpr1a and Acvr1, are deleted from the prospective lens ectoderm. Our results show that chicken embryo pre-lens ectoderm cells express BMPs and require BMP signaling for lens specification in vitro, and that in vivo inhibition of BMP signals in the mouse prospective lens ectoderm interrupts lens placode formation and prevents lens invagination. Furthermore, our results provide evidence that BMP expression is negatively auto-regulated in the lens-forming ectoderm, decreasing when the tissue is exposed to exogenous BMPs and increasing when BMP signaling is prevented. In addition, eyes lacking BMP receptors in the prospective lens placode develop coloboma in the adjacent wild type optic cup. In these eyes, Bmp7 expression increases in the ventral optic cup and the normal dorsal-ventral gradient of BMP signaling in the optic cup is disrupted. Pax2 becomes undetectable and expression of Sfrp2 increases in the ventral optic cup, suggesting that increased BMP signaling alter their expression, resulting in failure to close the optic fissure. In summary, our results suggest that negative and positive auto-regulation of BMP expression is important to regulate early eye development.

  13. Enhanced biomethanation of kitchen waste by different pre-treatments.

    Science.gov (United States)

    Ma, Jingxing; Duong, Thu Hang; Smits, Marianne; Verstraete, Willy; Carballa, Marta

    2011-01-01

    Five different pre-treatments were investigated to enhance the solubilisation and anaerobic biodegradability of kitchen waste (KW) in thermophilic batch and continuous tests. In the batch solubilisation tests, the highest and the lowest solubilisation efficiency were achieved with the thermo-acid and the pressure-depressure pre-treatments, respectively. However, in the batch biodegradability tests, the highest cumulative biogas production was obtained with the pressure-depressure method. In the continuous tests, the best performance in terms of an acceptable biogas production efficiency of 60% and stable in-reactor CODs and VFA concentrations corresponded to the pressure-depressure reactor, followed by freeze-thaw, acid, thermo-acid, thermo and control. The maximum OLR (5 g COD L(-1) d(-1)) applied in the pressure-depressure and freeze-thaw reactors almost doubled the control reactor. From the overall analysis, the freeze-thaw pre-treatment was the most profitable process with a net potential profit of around 11.5 € ton(-1) KW.

  14. Biohydrogen and biomethane production sustained by untreated matrices and alternative application of compost waste.

    Science.gov (United States)

    Arizzi, Mariaconcetta; Morra, Simone; Pugliese, Massimo; Gullino, Maria Lodovica; Gilardi, Gianfranco; Valetti, Francesca

    2016-10-01

    Biohydrogen and biomethane production offers many advantages for environmental protection over the fossil fuels or the existing physical-chemical methods for hydrogen and methane synthesis. The aim of this study is focused on the exploitation of several samples from the composting process: (1) a mixture of waste vegetable materials ("Mix"); (2) an unmatured compost sample (ACV15); and (3) three types of green compost with different properties and soil improver quality (ACV1, ACV2 and ACV3). These samples were tested for biohydrogen and biomethane production, thus obtaining second generation biofuels and resulting in a novel possibility to manage renewable waste biomasses. The ability of these substrates as original feed during dark fermentation was assayed anaerobically in batch, in glass bottles, in order to determine the optimal operating conditions for hydrogen and/or methane production using "Mix" or ACV1, ACV2 or ACV3 green compost and a limited amount of water. Hydrogen could be produced with a fast kinetic in the range 0.02-2.45mLH2g(-1)VS, while methane was produced with a slower kinetic in the range 0.5-8mLCH4g(-1)VS. It was observed that the composition of each sample influenced significantly the gas production. It was also observed that the addition of different water amounts play a crucial role in the development of hydrogen or methane. This parameter can be used to push towards the alternative production of one or another gas. Hydrogen and methane production was detected spontaneously from these matrices, without additional sources of nutrients or any pre-treatment, suggesting that they can be used as an additional inoculum or feed into single or two-stage plants. This might allow the use of compost with low quality as soil improver for alternative and further applications. PMID:27422046

  15. Biohydrogen and biomethane production sustained by untreated matrices and alternative application of compost waste.

    Science.gov (United States)

    Arizzi, Mariaconcetta; Morra, Simone; Pugliese, Massimo; Gullino, Maria Lodovica; Gilardi, Gianfranco; Valetti, Francesca

    2016-10-01

    Biohydrogen and biomethane production offers many advantages for environmental protection over the fossil fuels or the existing physical-chemical methods for hydrogen and methane synthesis. The aim of this study is focused on the exploitation of several samples from the composting process: (1) a mixture of waste vegetable materials ("Mix"); (2) an unmatured compost sample (ACV15); and (3) three types of green compost with different properties and soil improver quality (ACV1, ACV2 and ACV3). These samples were tested for biohydrogen and biomethane production, thus obtaining second generation biofuels and resulting in a novel possibility to manage renewable waste biomasses. The ability of these substrates as original feed during dark fermentation was assayed anaerobically in batch, in glass bottles, in order to determine the optimal operating conditions for hydrogen and/or methane production using "Mix" or ACV1, ACV2 or ACV3 green compost and a limited amount of water. Hydrogen could be produced with a fast kinetic in the range 0.02-2.45mLH2g(-1)VS, while methane was produced with a slower kinetic in the range 0.5-8mLCH4g(-1)VS. It was observed that the composition of each sample influenced significantly the gas production. It was also observed that the addition of different water amounts play a crucial role in the development of hydrogen or methane. This parameter can be used to push towards the alternative production of one or another gas. Hydrogen and methane production was detected spontaneously from these matrices, without additional sources of nutrients or any pre-treatment, suggesting that they can be used as an additional inoculum or feed into single or two-stage plants. This might allow the use of compost with low quality as soil improver for alternative and further applications.

  16. Expression of Human BMP-2 Gene in Different Tissues of Tobacco Plants%重组人BMP-2在烟草不同组织中的表达

    Institute of Scientific and Technical Information of China (English)

    高原; 索广力; 韩津; 何正权; 姚伟; 戴建武

    2006-01-01

    骨形态发生蛋白(BMPs)是一类调节骨组织发育的生长因子.BMP-2是BMP家族中诱骨活性最强的.在骨组织工程研究和临床应用中需要大量的BMP-2.因此,研究出一种能够有效地大量生产BMP-2的方法是十分必要的.随着植物分子生物学的进展,转基因植物被用作一种生物反应器来生产目的蛋白.以gus作为报告基因,研究了重组人bmp-2基因在烟草中的表达.通过GUS活性检测、半定量PCR和Western blotting分析了根、茎、叶组织中基因表达的水平,结果显示融合蛋白在根和茎组织中表达量显著高于叶组织.由于根和茎组织中蛋白组成与叶组织相比相对简单,提示其更易于进行目的蛋白的纯化.%The bone morphogenetic proteins (BMPs) are a family of growth factors that regulate the development of bone. BMP-2 is the most effective in the induction of bone tissue. A large amount of BMP-2 is needed for both bone tissue engineering research and clinical application. Thus, an effective way is necessary to produce sufficient BMP-2 protein. With the advance in plant biotechnology, transgenic plants have been targeted as a bioreactor to produce desired recombinant proteins. Here, the expression of recombinant human bmp-2 gene (rhbmp-2) was studied in tobacco plants using gus as a reporter gene. The difference of expression levels in root, stem and leaf tissues was analyzed by GUS activity assay, semi-quantitive RT-PCR and westem blotting.The results indicated that the expression levels of fusion protein in root and stem tissues were significantly higher than those in leaf tissue. For the protein compositions in root and stem tissues were simpler than those in leaf tissue,this suggested that the purification process with root and stem tissues would potentially be easier.

  17. Effect of maize silage addition on biomethane recovery from mesophilic co-digestion of chicken and cattle manure to suppress ammonia inhibition

    International Nuclear Information System (INIS)

    Highlights: • Daily biomethane and total energy productions improved 1.2 fold when maize silage is co-digested with the animal wastes. • Heat produced is sufficient for successful mesophilic co-digestion with an energy saving ∼36 × 103 kW h with maize silage. • Excess heat up to 16 × 103 kW h can be utilized elsewhere in the premises of the biogas plant. • Biogas plants including co-digestion of manure with a suitable co-substrate are becoming net producers of renewable energy. • pH values above 7.4 may cause severe inhibition of methanogenic cultures for an unadapted process to NH3. - Abstract: The aim of this study is to evaluate the biogas recovery potential if mesophilic (35 ± 2 °C) anaerobic co-digestion of two different types of manure sources (from chicken and cattle) is applied at a biogas plant. In order to evaluate the improvement in biogas production in the presence of the co-substrate, maize silage is digested together with the animal manure. Results indicated that daily biomethane and total energy (power + heat) productions improved about 1.2 fold when maize silage is co-digested with cattle and chicken wastes. The heat and power energy potentials from the produced biogas were determined using the conversion rates of a CHP unit. Significant energy recovery could be achieved for both cases; i.e. total methane productions were calculated as 5800 and 6580 m3/day corresponding to total energy productions of some 45.05 × 103 and 51.06 × 103 kW h without and with maize silage addition, respectively. A heat analysis was also performed where the resulting biomethane productions were the basis of the heat requirements. Results indicated that the major part of the heating requirements consisted of slurry heating to the operating temperature (in this study 35 °C). When the overall heat requirements are compared to the heat potential from a CHP unit, it is clear that the heat produced is sufficient for successful mesophilic co-digestion giving

  18. BMP2-loaded hollow hydroxyapatite microspheres exhibit enhanced osteoinduction and osteogenicity in large bone defects

    Directory of Open Access Journals (Sweden)

    Xiong L

    2015-01-01

    Full Text Available Long Xiong,1 Jianhua Zeng,1 Aihua Yao,2 Qiquan Tu,3 Jingtang Li,1 Liang Yan,4 Zhiming Tang1 1Department of Osteology, People’s Hospital of Jiangxi Province, Nanchang, Jiangxi, People’s Republic of China; 2School of Materials Science and Engineering, Tongji University, Shanghai, People’s Republic of China; 3Department of Osteology, People’s Hospital of Jiujiang County, Jiujiang, Jiangxi, People’s Republic of China; 4Department of Osteology, The Third Hospital of Nanchang City, Nanchang, Jiangxi, People’s Republic of China Abstract: 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 m2/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

  19. Anaerobic Digestion of Laminaria japonica Waste from Industrial Production Residues in Laboratory- and Pilot-Scale

    OpenAIRE

    Yann Nicolas Barbot; Claudia Thomsen; Laurenz Thomsen; Roland Benz

    2015-01-01

    The cultivation of macroalgae to supply the biofuel, pharmaceutical or food industries generates a considerable amount of organic residue, which represents a potential substrate for biomethanation. Its use optimizes the total resource exploitation by the simultaneous disposal of waste biomaterials. In this study, we explored the biochemical methane potential (BMP) and biomethane recovery of industrial Laminaria japonica waste (LJW) in batch, continuous laboratory and pilot-scale trials. Therm...

  20. In silico Mechano-Chemical Model of Bone Healing for the Regeneration of Critical Defects: The Effect of BMP-2.

    Directory of Open Access Journals (Sweden)

    Frederico O Ribeiro

    Full Text Available The healing of bone defects is a challenge for both tissue engineering and modern orthopaedics. This problem has been addressed through the study of scaffold constructs combined with mechanoregulatory theories, disregarding the influence of chemical factors and their respective delivery devices. Of the chemical factors involved in the bone healing process, bone morphogenetic protein-2 (BMP-2 has been identified as one of the most powerful osteoinductive proteins. The aim of this work is to develop and validate a mechano-chemical regulatory model to study the effect of BMP-2 on the healing of large bone defects in silico. We first collected a range of quantitative experimental data from the literature concerning the effects of BMP-2 on cellular activity, specifically proliferation, migration, differentiation, maturation and extracellular matrix production. These data were then used to define a model governed by mechano-chemical stimuli to simulate the healing of large bone defects under the following conditions: natural healing, an empty hydrogel implanted in the defect and a hydrogel soaked with BMP-2 implanted in the defect. For the latter condition, successful defect healing was predicted, in agreement with previous in vivo experiments. Further in vivo comparisons showed the potential of the model, which accurately predicted bone tissue formation during healing, bone tissue distribution across the defect and the quantity of bone inside the defect. The proposed mechano-chemical model also estimated the effect of BMP-2 on cells and the evolution of healing in large bone defects. This novel in silico tool provides valuable insight for bone tissue regeneration strategies.

  1. Potential of biomethane for energy supply in the transport sector in Portugal

    OpenAIRE

    Marques, C.; Remígio, R.; Alves, M.M.

    2008-01-01

    Use of renewable fuels in the transport sector is being promoted worldwide. Although new conversion technologies for efficient biofuel production from lignocellulosic materials are currently being developed, some bioethanol and biodiesel production routes have limitations with regard to resource efficiency and reduction of greenhouse gases. Compared with other vehicle biofuels available presently, biogas has several advantages from an environmental and resource-efficiency persp...

  2. Influence of composition on the biomethanation potential of restaurant waste at mesophilic temperatures

    OpenAIRE

    L. Neves; Gonçalo, E.; Oliveira, Rosário; Alves, M. M.

    2008-01-01

    A synthetic waste was used to study the effect of waste composition on anaerobic degradation of restaurant waste. It was made by blending melted pork lard, white cabbage, chicken breast, and potato flakes, to simulate lipids, cellulose, protein, and carbohydrates, respectively. Four blends of the four constituents with an excess of each component were assayed and compared with a fifth blend containing an equal amount of chemical oxygen demand (COD) of each of the four components. The methane ...

  3. Anaerobic Digestion of Wastewaters from Pulp and Paper Mills : A Substantial Source for Biomethane Production in Sweden

    OpenAIRE

    Larsson, Madeleine

    2015-01-01

    The Swedish pulp and paper industry is the third largest exporter of pulp and paper products worldwide. It is a highly energy-demanding and water-utilising industry, which generates large volumes of wastewater rich in organic material. These organic materials are to different extents suitable for anaerobic digestion (AD) and production of energy-rich biomethane. The implementation of an AD process within the wastewater treatment plant of a mill would increase the treatment capacity and decrea...

  4. A BMP regulatory network controls ectodermal cell fate decisions at the neural plate border.

    Science.gov (United States)

    Reichert, Sabine; Randall, Rebecca A; Hill, Caroline S

    2013-11-01

    During ectodermal patterning the neural crest and preplacodal ectoderm are specified in adjacent domains at the neural plate border. BMP signalling is required for specification of both tissues, but how it is spatially and temporally regulated to achieve this is not understood. Here, using a transgenic zebrafish BMP reporter line in conjunction with double-fluorescent in situ hybridisation, we show that, at the beginning of neurulation, the ventral-to-dorsal gradient of BMP activity evolves into two distinct domains at the neural plate border: one coinciding with the neural crest and the other abutting the epidermis. In between is a region devoid of BMP activity, which is specified as the preplacodal ectoderm. We identify the ligands required for these domains of BMP activity. We show that the BMP-interacting protein Crossveinless 2 is expressed in the BMP activity domains and is under the control of BMP signalling. We establish that Crossveinless 2 functions at this time in a positive-feedback loop to locally enhance BMP activity, and show that it is required for neural crest fate. We further demonstrate that the Distal-less transcription factors Dlx3b and Dlx4b, which are expressed in the preplacodal ectoderm, are required for the expression of a cell-autonomous BMP inhibitor, Bambi-b, which can explain the specific absence of BMP activity in the preplacodal ectoderm. Taken together, our data define a BMP regulatory network that controls cell fate decisions at the neural plate border.

  5. Improving Biomethane Production and Mass Bioconversion of Corn Stover Anaerobic Digestion by Adding NaOH Pretreatment and Trace Elements

    Directory of Open Access Journals (Sweden)

    ChunMei Liu

    2015-01-01

    Full Text Available This research applied sodium hydroxide (NaOH pretreatment and trace elements to improve biomethane production when using corn stover for anaerobic digestion. Full-factor experimental tests identified the best combination of trace elements with the NaOH pretreatment, indicating that the best combination was with 1.0, 0.4, and 0.4 mg·L−1·d−1 of elements Fe, Co, and Ni, respectively. The cumulative biomethane production adding NaOH pretreatment and trace elements was 11,367 mL; total solid bioconversion rate was 55.7%, which was 41.8%–62.2% higher than with NaOH-pretreatment alone and 22.2%–56.3% higher than with untreated corn stover. The best combination was obtained 5–9 days shorter than T90 and maintained good system operation stability. Only a fraction of the trace elements in the best combination was present in the resulting solution; more than 85% of the total amounts added were transferred into the solid fraction. Adding 0.897 g of Fe, 0.389 g of Co, and 0.349 g of Ni satisfied anaerobic digestion needs and enhanced biological activity at the beginning of the operation. The results showed that NaOH pretreatment and adding trace elements improve corn stover biodegradability and enhance biomethane production.

  6. Improving Biomethane Production and Mass Bioconversion of Corn Stover Anaerobic Digestion by Adding NaOH Pretreatment and Trace Elements.

    Science.gov (United States)

    Liu, ChunMei; Yuan, HaiRong; Zou, DeXun; Liu, YanPing; Zhu, BaoNing; Li, XiuJin

    2015-01-01

    This research applied sodium hydroxide (NaOH) pretreatment and trace elements to improve biomethane production when using corn stover for anaerobic digestion. Full-factor experimental tests identified the best combination of trace elements with the NaOH pretreatment, indicating that the best combination was with 1.0, 0.4, and 0.4 mg·L(-1)·d(-1) of elements Fe, Co, and Ni, respectively. The cumulative biomethane production adding NaOH pretreatment and trace elements was 11,367 mL; total solid bioconversion rate was 55.7%, which was 41.8%-62.2% higher than with NaOH-pretreatment alone and 22.2%-56.3% higher than with untreated corn stover. The best combination was obtained 5-9 days shorter than T90 and maintained good system operation stability. Only a fraction of the trace elements in the best combination was present in the resulting solution; more than 85% of the total amounts added were transferred into the solid fraction. Adding 0.897 g of Fe, 0.389 g of Co, and 0.349 g of Ni satisfied anaerobic digestion needs and enhanced biological activity at the beginning of the operation. The results showed that NaOH pretreatment and adding trace elements improve corn stover biodegradability and enhance biomethane production.

  7. Improving Biomethane Production and Mass Bioconversion of Corn Stover Anaerobic Digestion by Adding NaOH Pretreatment and Trace Elements.

    Science.gov (United States)

    Liu, ChunMei; Yuan, HaiRong; Zou, DeXun; Liu, YanPing; Zhu, BaoNing; Li, XiuJin

    2015-01-01

    This research applied sodium hydroxide (NaOH) pretreatment and trace elements to improve biomethane production when using corn stover for anaerobic digestion. Full-factor experimental tests identified the best combination of trace elements with the NaOH pretreatment, indicating that the best combination was with 1.0, 0.4, and 0.4 mg·L(-1)·d(-1) of elements Fe, Co, and Ni, respectively. The cumulative biomethane production adding NaOH pretreatment and trace elements was 11,367 mL; total solid bioconversion rate was 55.7%, which was 41.8%-62.2% higher than with NaOH-pretreatment alone and 22.2%-56.3% higher than with untreated corn stover. The best combination was obtained 5-9 days shorter than T90 and maintained good system operation stability. Only a fraction of the trace elements in the best combination was present in the resulting solution; more than 85% of the total amounts added were transferred into the solid fraction. Adding 0.897 g of Fe, 0.389 g of Co, and 0.349 g of Ni satisfied anaerobic digestion needs and enhanced biological activity at the beginning of the operation. The results showed that NaOH pretreatment and adding trace elements improve corn stover biodegradability and enhance biomethane production. PMID:26137469

  8. Interplay between self-assembled structure of bone morphogenetic protein-2 (BMP-2) and osteoblast functions in three-dimensional titanium alloy scaffolds: Stimulation of osteogenic activity.

    Science.gov (United States)

    Nune, K C; Kumar, A; Murr, L E; Misra, R D K

    2016-02-01

    Three-dimensional cellular scaffolds are receiving significant attention in bone tissue engineering to treat segmental bone defects. However, there are indications of lack of significant osteoinductive ability of three-dimensional cellular scaffolds. In this regard, the objective of the study is to elucidate the interplay between bone morphogenetic protein (BMP-2) and osteoblast functions on 3D mesh structures with different porosities and pore size that were fabricated by electron beam melting. Self-assembled dendritic microstructure with interconnected cellular-type morphology of BMP-2 on 3D scaffolds stimulated osteoblast functions including adhesion, proliferation, and mineralization, with prominent effect on 2-mm mesh. Furthermore, immunofluorescence studies demonstrated higher density and viability of osteoblasts on lower porosity mesh structure (2 mm) as compared to 3- and 4-mm mesh structures. Enhanced filopodia cellular extensions with extensive cell spreading was observed on BMP-2 treated mesh structures, a behavior that is attributed to the unique self-assembled structure of BMP-2 that effectively communicates with the cells. The study underscores the potential of BMP-2 in imparting osteoinductive capability to the 3D printed scaffolds.

  9. BMP type I receptor ALK2 is required for angiotensin II-induced cardiac hypertrophy.

    Science.gov (United States)

    Shahid, Mohd; Spagnolli, Ester; Ernande, Laura; Thoonen, Robrecht; Kolodziej, Starsha A; Leyton, Patricio A; Cheng, Juan; Tainsh, Robert E T; Mayeur, Claire; Rhee, David K; Wu, Mei X; Scherrer-Crosbie, Marielle; Buys, Emmanuel S; Zapol, Warren M; Bloch, Kenneth D; Bloch, Donald B

    2016-04-15

    Bone morphogenetic protein (BMP) signaling contributes to the development of cardiac hypertrophy. However, the identity of the BMP type I receptor involved in cardiac hypertrophy and the underlying molecular mechanisms are poorly understood. By using quantitative PCR and immunoblotting, we demonstrated that BMP signaling increased during phenylephrine-induced hypertrophy in cultured neonatal rat cardiomyocytes (NRCs), as evidenced by increased phosphorylation of Smads 1 and 5 and induction of Id1 gene expression. Inhibition of BMP signaling with LDN193189 or noggin, and silencing of Smad 1 or 4 using small interfering RNA diminished the ability of phenylephrine to induce hypertrophy in NRCs. Conversely, activation of BMP signaling with BMP2 or BMP4 induced hypertrophy in NRCs. Luciferase reporter assay further showed that BMP2 or BMP4 treatment of NRCs repressed atrogin-1 gene expression concomitant with an increase in calcineurin protein levels and enhanced activity of nuclear factor of activated T cells, providing a mechanism by which BMP signaling contributes to cardiac hypertrophy. In a model of cardiac hypertrophy, C57BL/6 mice treated with angiotensin II (A2) had increased BMP signaling in the left ventricle. Treatment with LDN193189 attenuated A2-induced cardiac hypertrophy and collagen deposition in left ventricles. Cardiomyocyte-specific deletion of BMP type I receptor ALK2 (activin-like kinase 2), but not ALK1 or ALK3, inhibited BMP signaling and mitigated A2-induced cardiac hypertrophy and left ventricular fibrosis in mice. The results suggest that BMP signaling upregulates the calcineurin/nuclear factor of activated T cell pathway via BMP type I receptor ALK2, contributing to cardiac hypertrophy and fibrosis. PMID:26873969

  10. Increased iron loading induces Bmp6 expression in the non-parenchymal cells of the liver independent of the BMP-signaling pathway.

    Directory of Open Access Journals (Sweden)

    Caroline A Enns

    Full Text Available Bone morphogenetic protein 6 (BMP6 is an essential cytokine for the expression of hepcidin, an iron regulatory hormone secreted predominantly by hepatocytes. Bmp6 expression is upregulated by increased iron-levels in the liver. Both hepatocytes and non-parenchymal liver cells have detectable Bmp6 mRNA. Here we showed that induction of hepcidin expression in hepatocytes by dietary iron is associated with an elevation of Bmp6 mRNA in the non-parenchymal cells of the liver. Consistently, incubation with iron-saturated transferrin induces Bmp6 mRNA expression in isolated hepatic stellate cells, but not in hepatocytes. These observations suggest an important role of the non-parenchymal liver cells in regulating iron-homeostasis by acting as a source of Bmp6.

  11. A new class of small molecule inhibitor of BMP signaling.

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    Caroline E Sanvitale

    Full Text Available Growth factor signaling pathways are tightly regulated by phosphorylation and include many important kinase targets of interest for drug discovery. Small molecule inhibitors of the bone morphogenetic protein (BMP receptor kinase ALK2 (ACVR1 are needed urgently to treat the progressively debilitating musculoskeletal disease fibrodysplasia ossificans progressiva (FOP. Dorsomorphin analogues, first identified in zebrafish, remain the only BMP inhibitor chemotype reported to date. By screening an assay panel of 250 recombinant human kinases we identified a highly selective 2-aminopyridine-based inhibitor K02288 with in vitro activity against ALK2 at low nanomolar concentrations similar to the current lead compound LDN-193189. K02288 specifically inhibited the BMP-induced Smad pathway without affecting TGF-β signaling and induced dorsalization of zebrafish embryos. Comparison of the crystal structures of ALK2 with K02288 and LDN-193189 revealed additional contacts in the K02288 complex affording improved shape complementarity and identified the exposed phenol group for further optimization of pharmacokinetics. The discovery of a new chemical series provides an independent pharmacological tool to investigate BMP signaling and offers multiple opportunities for pre-clinical development.

  12. Sonic Hedgehog Promotes Cementoblastic Differentiation via Activating the BMP Pathways.

    Science.gov (United States)

    Bae, Won-Jung; Auh, Q-Schick; Lim, Hyun-Chang; Kim, Gyu-Tae; Kim, Hyun-Soo; Kim, Eun-Cheol

    2016-10-01

    Although sonic hedgehog (SHH), an essential molecule in embryogenesis and organogenesis, stimulates proliferation of human periodontal ligament (PDL) stem cells, the effects of recombinant human SHH (rh-SHH) on osteoblastic differentiation are unclear. To reveal the role of SHH in periodontal regeneration, expression of SHH in mouse periodontal tissues and its effects on the osteoblastic/cementoblastic differentiation in human cementoblasts were investigated. SHH is immunolocalized to differentiating cementoblasts, PDL cells, and osteoblasts of the developing mouse periodontium. Addition of rh-SHH increased cell growth, ALP activity, and mineralization nodule formation, and upregulated mRNA expression of osteoblastic and cementoblastic markers. The osteoblastic/cementoblastic differentiation of rh-SHH was abolished by the SHH inhibitor cyclopamine (Cy) and the BMP antagonist noggin. rh-SHH increased the expression of BMP-2 and -4 mRNA, as well as levels of phosphorylated Akt, ERK, p38, and JNK, and of MAPK and NF-κB activation, which were reversed by noggin, Cy, and BMP-2 siRNA. Collectively, this study is the first to demonstrate that SHH can promote cell growth and cell osteoblastic/cementoblastic differentiation via BMP pathway. Thus, SHH plays important roles in the development of periodontal tissue, and might represent a new therapeutic target for periodontitis and periodontal regeneration. PMID:27289556

  13. Biological activity of a genetically modified BMP-2 variant with inhibitory activity

    Directory of Open Access Journals (Sweden)

    Kübler Alexander C

    2009-02-01

    Full Text Available Abstract Background Alterations of the binding epitopes of bone morphogenetic protein-2 (BMP-2 lead to a modified interaction with the ectodomains of BMP receptors. In the present study the biological effect of a BMP-2 double mutant with antagonistic activity was evaluated in vivo. Methods Equine-derived collagenous carriers were loaded with recombinant human BMP-2 (rhBMP-2 in a well-known dose to provide an osteoinductive stimulus. The study was performed in a split animal design: carriers only coupled with rhBMP-2 (control were implanted into prepared cavities of lower limb muscle of rats, specimens coupled with rhBMP-2 as well as BMP-2 double mutant were placed into the opposite limb in the same way. After 28 days the carriers were explanted, measured radiographically and characterized histologically. Results As expected, the BMP-2 loaded implants showed a typical heterotopic bone formation. The specimens coupled with both proteins showed a significant decreased bone formation in a dose dependent manner. Conclusion The antagonistic effect of a specific BMP-2 double mutant could be demonstrated in vivo. The dose dependent influence on heterotopic bone formation by preventing rhBMP-2 induced osteoinduction suggests a competitive receptor antagonism.

  14. Transforming growth factor β1 inhibits bone morphogenic protein (BMP-2 and BMP-7 signaling via upregulation of Ski-related novel protein N (SnoN: possible mechanism for the failure of BMP therapy?

    Directory of Open Access Journals (Sweden)

    Ehnert Sabrina

    2012-09-01

    Full Text Available Abstract Background Bone morphogenic proteins (BMPs play a key role in bone formation. Consequently, it was expected that topical application of recombinant human (rhBMP-2 and rhBMP-7 would improve the healing of complex fractures. However, up to 36% of fracture patients do not respond to this therapy. There are hints that a systemic increase in transforming growth factor β1 (TGFβ1 interferes with beneficial BMP effects. Therefore, in the present work we investigated the influence of rhTGFβ1 on rhBMP signaling in primary human osteoblasts, with the aim of more specifically delineating the underlying regulatory mechanisms. Methods BMP signaling was detected by adenoviral Smad-binding-element-reporter assays. Gene expression was determined by reverse transcription polymerase chain reaction (RT-PCR and confirmed at the protein level by western blot. Histone deacetylase (HDAC activity was determined using a test kit. Data sets were compared by one-way analysis of variance. Results Our findings showed that Smad1/5/8-mediated rhBMP-2 and rhBMP-7 signaling is completely blocked by rhTGFβ1. We then investigated expression levels of genes involved in BMP signaling and regulation (for example, Smad1/5/8, TGFβ receptors type I and II, noggin, sclerostin, BMP and activin receptor membrane bound inhibitor (BAMBI, v-ski sarcoma viral oncogene homolog (Ski, Ski-related novel protein N (SnoN and Smad ubiquitination regulatory factors (Smurfs and confirmed the expression of regulated genes at the protein level. Smad7 and SnoN were significantly induced by rhTGFβ1 treatment while expression of Smad1, Smad6, TGFβRII and activin receptor-like kinase 1 (Alk1 was reduced. Elevated SnoN expression was accompanied by increased HDAC activity. Addition of an HDAC inhibitor, namely valproic acid, fully abolished the inhibitory effect of rhTGFβ1 on rhBMP-2 and rhBMP-7 signaling. Conclusions rhTGFβ1 effectively blocks rhBMP signaling in osteoblasts. As possible

  15. Tsukushi modulates Xnr2, FGF and BMP signaling: regulation of Xenopus germ layer formation.

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    Samantha A Morris

    Full Text Available BACKGROUND: Cell-cell communication is essential in tissue patterning. In early amphibian development, mesoderm is formed in the blastula-stage embryo through inductive interactions in which vegetal cells act on overlying equatorial cells. Members of the TGF-beta family such as activin B, Vg1, derrière and Xenopus nodal-related proteins (Xnrs are candidate mesoderm inducing factors, with further activity to induce endoderm of the vegetal region. TGF-beta-like ligands, including BMP, are also responsible for patterning of germ layers. In addition, FGF signaling is essential for mesoderm formation whereas FGF signal inhibition has been implicated in endoderm induction. Clearly, several signaling pathways are coordinated to produce an appropriate developmental output; although intracellular crosstalk is known to integrate multiple pathways, relatively little is known about extracellular coordination. METHODOLOGY/PRINCIPAL FINDINGS: Here, we show that Xenopus Tsukushi (X-TSK, a member of the secreted small leucine rich repeat proteoglycan (SLRP family, is expressed in ectoderm, endoderm, and the organizer during early development. We have previously reported that X-TSK binds to and inhibits BMP signaling in cooperation with chordin. We now demonstrate two novel interactions: X-TSK binds to and inhibits signaling by FGF8b, in addition to binding to and enhancement of Xnr2 signaling. This signal integration by X-TSK at the extracellular level has an important role in germ layer formation and patterning. Vegetally localized X-TSK potentiates endoderm formation through coordination of BMP, FGF and Xnr2 signaling. In contrast, X-TSK inhibition of FGF-MAPK signaling blocks ventrolateral mesoderm formation, while BMP inhibition enhances organizer formation. These actions of X-TSK are reliant upon its expression in endoderm and dorsal mesoderm, with relative exclusion from ventrolateral mesoderm, in a pattern shaped by FGF signals. CONCLUSIONS

  16. New Strategy for a Suitable Fast Stabilization of the Biomethanization Performance

    Directory of Open Access Journals (Sweden)

    L. A. Fernández-Güelfo

    2012-01-01

    Full Text Available The start-up strategies for thermophilic anaerobic reactors usually consist of an initial mesophilic stage (35°C, with an approximate duration of 185 days, and a subsequent thermophilic stage (55°C, which normally requires around 60 days to achieve the system stabilizatio. During the first 8–10 days of the mesophilic stage, the reactor is not fed so that the inoculum, which is generally a mesophilic anaerobic sludge, may be adapted to the organic solid waste. Between mesophilic and thermophilic conditions the reactor is still not fed in an effort to prevent possible imbalances in the proces. As a consequence, the start-up and stabilization of the biomethanization performance described in the literature require, at least, around 245 days. In this sense, a new strategy for the start-up and stabilization phases is presented in this study. This approach allows an important reduction in the overall time necessary for these stages in an anaerobic continuous stirred tank reactor (CSTR operated at thermophilic-dry conditions for treating the organic fraction of the municipal solid waste (OFMSW: 60 days versus 245 days of conventional strategies. The new strategy uses modified SEBAC technology to adapt an inoculum to the OFMSW and the operational conditions prior to seeding the CSTR.

  17. Enhanced biohydrogen and subsequent biomethane production from sugarcane bagasse using nano-titanium dioxide pretreatment.

    Science.gov (United States)

    Jafari, Omid; Zilouei, Hamid

    2016-08-01

    Nano-titanium dioxide (nanoTiO2) under ultraviolet irradiation (UV) followed by dilute sulfuric acid hydrolysis of sugarcane bagasse was used to enhance the production of biohydrogen and biomethane in a consecutive dark fermentation and anaerobic digestion. Different concentrations of 0.001, 0.01, 0.1 and 1g nanoTiO2/L under different UV times of 30, 60, 90 and 120min were used. Sulfuric acid (2%v/v) at 121°C was used for 15, 30 and 60min to hydrolyze the pretreated bagasse. For acidic hydrolysis times of 15, 30 and 60min, the highest total free sugar values were enhanced by 260%, 107%, and 189%, respectively, compared to samples without nanoTiO2 pretreatment. The highest hydrogen production samples for the same acidic hydrolysis times showed 88%, 127%, and 25% enhancement. The maximum hydrogen production of 101.5ml/g VS (volatile solids) was obtained at 1g nanoTiO2/L and 120min UV irradiation followed by 30min acid hydrolysis. PMID:27208737

  18. Co-digestion of Whey with Glycerin in an AnSBBR for Biomethane Production.

    Science.gov (United States)

    Lovato, G; Ratusznei, S M; Rodrigues, J A D; Zaiat, M

    2016-01-01

    This study aimed to evaluate the co-digestion of cheese whey and glycerin in an anaerobic sequencing batch biofilm reactor (AnSBBR) with recirculation of the liquid phase applied to biomethane production. The applied volumetric organic load (AVOL) in all conditions was 7.5 kgCOD m(-3) day(-1). The feeding time was equal to half of the cycle time. The best condition for co-digestion was the wastewater with 75 % of cheese whey and 25 % of glycerin (chemical oxygen demand (COD) basis); it achieved a productivity of 101.8 molCH4 m(-3) day(-1) and a yield of 13.3 molCH4 kgCOD(-1) with 89 % of COD removal. This represents an increase of productivity of almost 9 and 30 % when compared to the anaerobic digestion of cheese whey and glycerin alone, respectively. The co-digestion proposed is a promising solution for both pollutants with the advantage of high energy production. A first-order kinetic model was fitted efficiently to the process. PMID:26400495

  19. Anaerobic Co-Digestion of Microalgae Scenedesmus sp. and TWAS for Biomethane Production.

    Science.gov (United States)

    Garoma, Temesgen; Nguyen, Don

    2016-01-01

    The paper investigated the feasibility of biomethane (bio-CH4) production from the anaerobic co-digestion of the microalgae Scenedesmus quadricauda (S. quadricauda) and thickened waste activated sludge (TWAS). The concept was tested in bench-scale anaerobic digesters by varying the proportions of volatile solids (VS) loading from S. quadricauda and TWAS and two critical operational parameters, temperature and alkalinity. The CH(4) production for the various S. quadricauda and TWAS proportions ranged from 234 to 318 mL/g of chemical oxygen demand (COD) digested and 329 to 530 mL/g of VS digested at 35 °C. The reductions in total solids (TS), COD, and VS ranged from 25 to 44%, 46 to 53%, and 40 to 53%, respectively. Temperature had a significant effect on CH(4) production, lower temperatures greatly reduced CH(4) production. No significant difference in CH(4) production was observed for experiments conducted at alkalinity levels of 70, 1630, and 3200 mg/L as CaCO(3). PMID:26803022

  20. Enhanced biohydrogen and subsequent biomethane production from sugarcane bagasse using nano-titanium dioxide pretreatment.

    Science.gov (United States)

    Jafari, Omid; Zilouei, Hamid

    2016-08-01

    Nano-titanium dioxide (nanoTiO2) under ultraviolet irradiation (UV) followed by dilute sulfuric acid hydrolysis of sugarcane bagasse was used to enhance the production of biohydrogen and biomethane in a consecutive dark fermentation and anaerobic digestion. Different concentrations of 0.001, 0.01, 0.1 and 1g nanoTiO2/L under different UV times of 30, 60, 90 and 120min were used. Sulfuric acid (2%v/v) at 121°C was used for 15, 30 and 60min to hydrolyze the pretreated bagasse. For acidic hydrolysis times of 15, 30 and 60min, the highest total free sugar values were enhanced by 260%, 107%, and 189%, respectively, compared to samples without nanoTiO2 pretreatment. The highest hydrogen production samples for the same acidic hydrolysis times showed 88%, 127%, and 25% enhancement. The maximum hydrogen production of 101.5ml/g VS (volatile solids) was obtained at 1g nanoTiO2/L and 120min UV irradiation followed by 30min acid hydrolysis.

  1. Future combustion methods for biomethane powered tractor engines; Zukuenftige Brennverfahren fuer biomethanbetriebene Traktormotoren

    Energy Technology Data Exchange (ETDEWEB)

    Prehn, Sascha; Harndorf, Horst [Rostock Univ. (Germany). Lehrstuhl fuer Kolbenmaschinen und Verbrennungsmotoren; Wichmann, Volker [Rostock Univ. (Germany). Maschinenlabor; Beberdick, Wolfgang

    2016-08-01

    Biomethane represents an alternative to fossil fuels (petrol, diesel), not only in the on-road sector. Methane-based fuels come in focus of farmers in the agriculture sector, due to cost constraints, increasing regulation of pollutant emissions and reduction of carbondioxid. To represent a monovalent gas operation, a functional model is derived from a series diesel engine for agricultural use. On the test engine, systematic studies on the combustion process are carried out by cylinder pressure indication and exhaust-emission measurement. Combustion under stoichiometric conditions (with or without exhaust gas recirculation) as well as the conversion of fuel from excess air is observed. The study shows that with a natural-gas engine, a complex post-treatment system of exhaust gas (DOC + DPF + SCR) that is typically for diesel engines can be dispensed with. The exhaust gas limits in force since 2014 and a limitation of methane on 0,5 g/kWh can be met with a stoichiometric combustion concept and a three way catalytic converter optimized for the methane oxidation.

  2. Regulation of the BMP Signaling-Responsive Transcriptional Network in the Drosophila Embryo.

    Science.gov (United States)

    Deignan, Lisa; Pinheiro, Marco T; Sutcliffe, Catherine; Saunders, Abbie; Wilcockson, Scott G; Zeef, Leo A H; Donaldson, Ian J; Ashe, Hilary L

    2016-07-01

    The BMP signaling pathway has a conserved role in dorsal-ventral axis patterning during embryonic development. In Drosophila, graded BMP signaling is transduced by the Mad transcription factor and opposed by the Brinker repressor. In this study, using the Drosophila embryo as a model, we combine RNA-seq with Mad and Brinker ChIP-seq to decipher the BMP-responsive transcriptional network underpinning differentiation of the dorsal ectoderm during dorsal-ventral axis patterning. We identify multiple new BMP target genes, including positive and negative regulators of EGF signaling. Manipulation of EGF signaling levels by loss- and gain-of-function studies reveals that EGF signaling negatively regulates embryonic BMP-responsive transcription. Therefore, the BMP gene network has a self-regulating property in that it establishes a balance between its activity and that of the antagonistic EGF signaling pathway to facilitate correct patterning. In terms of BMP-dependent transcription, we identify key roles for the Zelda and Zerknüllt transcription factors in establishing the resulting expression domain, and find widespread binding of insulator proteins to the Mad and Brinker-bound genomic regions. Analysis of embryos lacking the BEAF-32 insulator protein shows reduced transcription of a peak BMP target gene and a reduction in the number of amnioserosa cells, the fate specified by peak BMP signaling. We incorporate our findings into a model for Mad-dependent activation, and discuss its relevance to BMP signal interpretation in vertebrates. PMID:27379389

  3. Complexation and sequestration of BMP-2 from an ECM mimetic hyaluronan gel for improved bone formation.

    Directory of Open Access Journals (Sweden)

    Marta Kisiel

    Full Text Available Bone morphogenetic protein-2 (BMP-2 is considered a promising adjuvant for the treatment of skeletal non-union and spinal fusion. However, BMP-2 delivery in a conventional collagen scaffold necessitates a high dose to achieve an efficacious outcome. To lower its effective dose, we precomplexed BMP-2 with the glycosaminoglycans (GAGs dermatan sulfate (DS or heparin (HP, prior to loading it into a hyaluronic acid (HA hydrogel. In vitro release studies showed that BMP-2 precomplexed with DS or HP had a prolonged delivery compared to without GAG. BMP-2-DS complexes achieved a slightly faster release in the first 24 h than HP; however, both delivered BMP-2 for an equal duration. Analysis of the kinetic interaction between BMP-2 and DS or HP showed that HP had approximately 10 times higher affinity for BMP-2 than DS, yet it equally stabilized the protein, as determined by alkaline phosphatase activity. Ectopic bone formation assays at subcutaneous sites in rats demonstrated that HA hydrogel-delivered BMP-2 precomplexed with GAG induced twice the volume of bone compared with BMP-2 delivered uncomplexed to GAG.

  4. BMP-2 induces versican and hyaluronan that contribute to post-EMT AV cushion cell migration.

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    Kei Inai

    Full Text Available Distal outgrowth and maturation of mesenchymalized endocardial cushions are critical morphogenetic events during post-EMT atrioventricular (AV valvuloseptal morphogenesis. We explored the role of BMP-2 in the regulation of valvulogenic extracellular matrix (ECM components, versican and hyaluronan (HA, and cell migration during post-EMT AV cushion distal outgrowth/expansion. We observed intense staining of versican and HA in AV cushion mesenchyme from the early cushion expansion stage, Hamburger and Hamilton (HH stage-17 to the cushion maturation stage, HH stage-29 in the chick. Based on this expression pattern we examined the role of BMP-2 in regulating versican and HA using 3D AV cushion mesenchymal cell (CMC aggregate cultures on hydrated collagen gels. BMP-2 induced versican expression and HA deposition as well as mRNA expression of versican and Has2 by CMCs in a dose dependent manner. Noggin, an antagonist of BMP, abolished BMP-2-induced versican and HA as well as mRNA expression of versican and Has2. We further examined whether BMP-2-promoted cell migration was associated with expression of versican and HA. BMP-2- promoted cell migration was significantly impaired by treatments with versican siRNA and HA oligomer. In conclusion, we provide evidence that BMP-2 induces expression of versican and HA by AV CMCs and that these ECM components contribute to BMP-2-induced CMC migration, indicating critical roles for BMP-2 in distal outgrowth/expansion of mesenchymalized AV cushions.

  5. BMP is an important regulator of proepicardial identity in the chick embryo.

    Science.gov (United States)

    Schlueter, Jan; Männer, Jörg; Brand, Thomas

    2006-07-15

    The proepicardium (PE) is a transient structure formed by pericardial coelomic mesothelium at the venous pole of the embryonic heart and gives rise to several cell types of the mature heart. In order to study PE development in chick embryos, we have analyzed the expression pattern of the marker genes Tbx18, Wt1, and Cfc. During PE induction, the three marker genes displayed a left-right asymmetric expression pattern. In each case, expression on the right side was stronger than on the left side. The left-right asymmetric gene expression observed here is in accord with the asymmetric formation of the proepicardium in the chick embryo. While initially the marker genes were expressed in the primitive sinus horn, subsequently, expression became confined to the PE mesothelium. In order to search for signaling factors involved in PE development, we studied Bmp2 and Bmp4 expression. Bmp2 was bilaterally expressed in the sinus venosus. In contrast, Bmp4 expression was initially expressed unilaterally in the right sinus horn and subsequently in the PE. In order to assess its functional role, BMP signaling was experimentally modulated by supplying exogenous BMP2 and by inhibiting endogenous BMP signaling through the addition of Noggin. Both supplying BMP and blocking BMP signaling resulted in a loss of PE marker gene expression. Surprisingly, both experimental situations lead to cardiac myocyte formation in the PE cultures. Careful titration experiments with exogenously added BMP2 or Noggin revealed that PE-specific marker gene expression depends on a low level of BMP signaling. Implantation of BMP2-secreting cells or beads filled with Noggin protein into the right sinus horn of HH stage 11 embryos resulted in downregulation of Tbx18 expression, corresponding to the results of the explant assay. Thus, a distinct level of BMP signaling is required for PE formation in the chick embryo. PMID:16677627

  6. Threshold-dependent BMP-mediated repression: a model for a conserved mechanism that patterns the neuroectoderm.

    Directory of Open Access Journals (Sweden)

    Claudia Mieko Mizutani

    2006-10-01

    Full Text Available Subdivision of the neuroectoderm into three rows of cells along the dorsal-ventral axis by neural identity genes is a highly conserved developmental process. While neural identity genes are expressed in remarkably similar patterns in vertebrates and invertebrates, previous work suggests that these patterns may be regulated by distinct upstream genetic pathways. Here we ask whether a potential conserved source of positional information provided by the BMP signaling contributes to patterning the neuroectoderm. We have addressed this question in two ways: First, we asked whether BMPs can act as bona fide morphogens to pattern the Drosophila neuroectoderm in a dose-dependent fashion, and second, we examined whether BMPs might act in a similar fashion in patterning the vertebrate neuroectoderm. In this study, we show that graded BMP signaling participates in organizing the neural axis in Drosophila by repressing expression of neural identity genes in a threshold-dependent fashion. We also provide evidence for a similar organizing activity of BMP signaling in chick neural plate explants, which may operate by the same double negative mechanism that acts earlier during neural induction. We propose that BMPs played an ancestral role in patterning the metazoan neuroectoderm by threshold-dependent repression of neural identity genes.

  7. Performance and microbial community analysis of the anaerobic reactor with coke oven gas biomethanation and in situ biogas upgrading

    DEFF Research Database (Denmark)

    Wang, Wen; Xie, Li; Luo, Gang;

    2013-01-01

    (HFM). With pH control at 8.0, the added H2 and CO were fully consumed and no negative effects on the anaerobic degradation of sewage sludge were observed. The maximum CH4 content in the biogas was 99%. The addition of SCOG resulted in enrichment and dominance of homoacetogenetic genus Treponema......A new method for simultaneous coke oven gas (COG) biomethanation and in situ biogas upgrading in anaerobic reactor was developed in this study. The simulated coke oven gas (SCOG) (92% H2 and 8% CO) was injected directly into the anaerobic reactor treating sewage sludge through hollow fiber membrane...

  8. A robust fuzzy-logic-based controller for bio-methane production in anaerobic fixed-film reactors

    OpenAIRE

    Robles Martinez, Angel; Latrille, Eric; Ruano, M.V.; Steyer, Jean-Philippe

    2015-01-01

    The main objective of this work was to develop a robust controller for bio-methane production in continuous anaerobic fixed-bed reactors. To this aim, a fuzzy-logic-based control system was developed, tuned and validated in an anaerobic fixed-bed reactor at pilot scale that treated raw winery wastewater. The proposed controller regulated the flow-rate of wastewater entering the system as a function of the gaseous outflow rate of methane and the effluent Volatile Fatty Acids (VFA) concentratio...

  9. A feasibility study of using Biomethane as an alternative fuel for taxis in the Reykjavík capital area

    OpenAIRE

    Hannes Arnórsson

    2011-01-01

    Price of gasoline at the dispenser in Iceland has never been higher than today. This paper investigates the economic feasibility of using biomethane as an alternative fuel for the taxi fleet in the Reykjavík capital area. Cases of different groups of taxis were set up on the basis of existing data of the fleet and the financial feasibility evaluated. The cases were divided into separate groups based on the emission classes and various scenarios and sensitivity analysis applied. The research l...

  10. Hepcidin Regulation by BMP Signaling in Macrophages Is Lipopolysaccharide Dependent

    OpenAIRE

    Wu, Xinggang; Yung, Lai-Ming; Cheng, Wai-Hang; Yu, Paul B.; Babitt, Jodie L.; Lin, Herbert Yih-Fuu; Xia, Yin

    2012-01-01

    Hepcidin is an antimicrobial peptide, which also negatively regulates iron in circulation by controlling iron absorption from dietary sources and iron release from macrophages. Hepcidin is synthesized mainly in the liver, where hepcidin is regulated by iron loading, inflammation and hypoxia. Recently, we have demonstrated that bone morphogenetic protein (BMP)-hemojuvelin (HJV)-SMAD signaling is central for hepcidin regulation in hepatocytes. Hepcidin is also expressed by macrophages. Studies ...

  11. Immortalization and characterization of mouse floxed Bmp2/4 osteoblasts

    International Nuclear Information System (INIS)

    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.

  12. Immortalization and characterization of mouse floxed Bmp2/4 osteoblasts

    Energy Technology Data Exchange (ETDEWEB)

    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: chens0@uthscsa.edu [Department of Pediatric Dentistry, The University of Texas Health Science Center at San Antonio, TX (United States)

    2009-08-14

    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.

  13. Biohydrogen, biomethane and bioelectricity as crucial components of biorefinery of organic wastes: a review.

    Science.gov (United States)

    Poggi-Varaldo, Héctor M; Munoz-Paez, Karla M; Escamilla-Alvarado, Carlos; Robledo-Narváez, Paula N; Ponce-Noyola, M Teresa; Calva-Calva, Graciano; Ríos-Leal, Elvira; Galíndez-Mayer, Juvencio; Estrada-Vázquez, Carlos; Ortega-Clemente, Alfredo; Rinderknecht-Seijas, Noemí F

    2014-05-01

    the inverse cascade. Finally, biohydrogen, biomethane and bioelectricity could contribute to significant improvements for solid organic waste management in agricultural regions, as well as in urban areas. PMID:24742981

  14. Biohydrogen, biomethane and bioelectricity as crucial components of biorefinery of organic wastes: a review.

    Science.gov (United States)

    Poggi-Varaldo, Héctor M; Munoz-Paez, Karla M; Escamilla-Alvarado, Carlos; Robledo-Narváez, Paula N; Ponce-Noyola, M Teresa; Calva-Calva, Graciano; Ríos-Leal, Elvira; Galíndez-Mayer, Juvencio; Estrada-Vázquez, Carlos; Ortega-Clemente, Alfredo; Rinderknecht-Seijas, Noemí F

    2014-05-01

    the inverse cascade. Finally, biohydrogen, biomethane and bioelectricity could contribute to significant improvements for solid organic waste management in agricultural regions, as well as in urban areas.

  15. Biomethane production from vinasse in upflow anaerobic sludge blanket reactors inoculated with granular sludge.

    Science.gov (United States)

    Barros, Valciney Gomes de; Duda, Rose Maria; Oliveira, Roberto Alves de

    2016-01-01

    The main objective of this study was to evaluate the anaerobic conversion of vinasse into biomethane with gradual increase in organic loading rate (OLR) in two upflow anaerobic sludge blanket (UASB) reactors, R1 and R2, with volumes of 40.5 and 21.5L in the mesophilic temperature range. The UASB reactors were operated for 230 days with a hydraulic detection time (HDT) of 2.8d (R1) and 2.8-1.8d (R2). The OLR values applied in the reactors were 0.2-7.5gtotalCOD (Ld)(-1) in R1 and 0.2-11.5gtotalCOD (Ld)(-1) in R2. The average total chemical oxygen demand (totalCOD) removal efficiencies ranged from 49% to 82% and the average conversion efficiencies of the removed totalCOD into methane were 48-58% in R1 and 39-65% in R2. The effluent recirculation was used for an OLR above 6gtotalCOD (Ld)(-1) in R1 and 8gtotalCOD (Ld)(-1) in R2 and was able to maintain the pH of the influent in R1 and R2 in the range from 6.5 to 6.8. However, this caused a decrease for 53-39% in the conversion efficiency of the removed totalCOD into methane in R2 because of the increase in the recalcitrant COD in the influent. The largest methane yield values were 0.181 and 0.185 (L) CH4 (gtotalCOD removed)(-1) in R1 and R2, respectively. These values were attained after 140 days of operation with an OLR of 5.0-7.5gtotalCOD (Ld)(-1) and totalCOD removal efficiencies around 70 and 80%. PMID:27289246

  16. Analysis of process related factors to increase volumetric productivity and quality of biomethane with Methanothermobacter marburgensis

    International Nuclear Information System (INIS)

    Highlights: • Biological methanogenesis with M. marburgensis was identified to be gas limited. • Volumetric productivity was increased by improving gas/liquid mass transfer. • Quantitative analysis of key parameters in gas/liquid mass transfer was demonstrated. • A systematic strategy for maximising productivity without quality loss is suggested. - Abstract: The biological conversion of H2 and CO2 into CH4, using methanogenic archaea is an interesting technology for CO2 conversion, energy storage and biogas upgrading. For an industrial application of this process however, the optimization of the volumetric productivity and the product quality is an important issue. Since the reactants in this fermentation process are, unlike in most microbial fermentations, solely gasses, the gas liquid mass transfer is supposed to play an important role on the way to a higher volumetric productivity. This work aimed at investigating the effects of the gassing rate, the reactor pressure, as well as reactor design issues on the performance of Methanothermobactermarburgensis by using continuous cultures. Our results show that biological methanogenesis with M. marburgensis is gas limited. Maximum physiological capacity is not reached yet. The gassing rate influenced mainly the volumetric methane production rate (MER), the reactor pressure influenced mainly the offgas quality. Based on this information, we demonstrated how a combination of increased gas flow rate and increased reactor pressure can be used to reach high volumetric productivity at high offgas quality. Maximum MER was 950 mmol L−1 h−1 at a CH4 concentration of 60 Vol.-%, maximum CH4 concentration reached was 85 Vol.-% at a MER of 255 mmol L−1 h−1. The reactor design currently limits further increase in gas flow rate and reactor pressure. Therefore Interdisciplinary bridges from bioprocessing to chemical reactor design must be followed in the future to boot this promising bioprocess to gain biomethane via

  17. Potential Biogas Production from Artichoke Byproducts in Sardinia, Italy

    OpenAIRE

    Fabio Menna; Remo Alessio Malagnino; Matteo Vittuari; Giovanni Molari; Giovanna Seddaiu; Paola A. Deligios; Stefania Solinas; Luigi Ledda

    2016-01-01

    The paper aims at evaluating the potential biogas production, both in terms of CH4 and theoretical energy potential, from globe artichoke agricultural byproducts in Sardinia. Field data about the productivity of byproducts were collected on five artichoke varieties cultivated in Sardinia, to assess the biomethane production of their aboveground non-food parts (excluding the head). Moreover, secondary data from previous studies and surveys at regional scale were collected to evaluate the poten...

  18. Regulation of Pancreatic Alpha Cell Function and Proliferation by Bone Morphogenetic Protein 4 (BMP4) in vitro

    DEFF Research Database (Denmark)

    Nielsen, Sofie Sylvest; Christensen, Gitte Lund; Holst, Jens Juul;

    2016-01-01

    Increased expression of Bone Morphogenetic Proteins (BMPs) in several tissues is associated with inflammation and Type II Diabetes Mellitus. BMP2 and BMP4 mRNA expression is increased in pancreatic islets from db/db mice and beta cell proliferation and function are inhibited by BMP4. The effect...... incubation with BMP4 in mouse islets, but not in human islets. The percentage of proliferating alpha cells was reduced from 7.3 to 0.2 % in mouse islets incubated with BMP4. Alpha cell proliferation in human islets ranged from 0 to 11.8 %, and BMP4 was found to inhibit proliferation of alpha cells from all...

  19. Conditional Deletion of BMP7 from the Limb Skeleton Does Not Affect Bone Formation or Fracture Repair

    OpenAIRE

    Tsuji, Kunikazu; Cox, Karen; Gamer, Laura; Graf, Daniel; Economides, Aris; Rosen, Vicki

    2010-01-01

    While the osteoinductive activity of recombinant bone morphogenetic protein 7 (BMP7) is well established, evaluation of the role of endogenous BMP7 in bone formation and fracture healing has been hampered by perinatal lethality in BMP7 knockout mice. Here we employ conditional deletion of BMP7 from the embryonic limb prior to the onset of skeletogenesis to create limb bones lacking BMP7. We find that the absence of locally produced BMP7 has no effect on postnatal limb growth, articular cartil...

  20. BMP signaling requires retromer-dependent recycling of the type I receptor

    OpenAIRE

    Gleason, Ryan J; Akintobi, Adenrele M.; Barth D Grant; Padgett, Richard W.

    2014-01-01

    The mechanisms that mediate bone morphogenetic protein (BMP) receptor recycling, and the importance of such recycling for signaling in vivo, have remained poorly understood. We find that the retromer complex functions as a linchpin in the recycling of the BMP type I receptor SMA-6 (small-6). In the absence of retromer-dependent recycling, retromer mutants result in the missorting of SMA-6 to lysosomes and a loss of BMP-mediated signaling. Surprisingly, we find that the BMP type II receptor, D...

  1. Signaling Crosstalk between PPARγ and BMP2 in Mesenchymal Stem Cells

    Directory of Open Access Journals (Sweden)

    Ichiro Takada

    2012-01-01

    Full Text Available Recent studies have revealed that PPARγ’s transactivation function is regulated by extracellular signals. In particular, cytokines and Wnt family proteins suppress the ligand-inducible transactivation function of PPARγ and attenuate adipogenesis/osteoblastogenesis switching in mesenchymal stem cells (MSCs. For example, Wnt5a suppresses PPARγ transcriptional activity through the NLK/SETDB1/CHD7 pathway. Among these factors, BMP2 strongly induces bone formation, but the effect of BMP2 on PPARγ function remains unclear. We examined the effect of BMP2 and PPARγ in ST2 cells and found that PPARγ activation affected BMP2’s signaling pathway through epigenetic regulation. Although BMP2 did not interfere with PPARγ-mediated adipogenesis, BMP2 increased mRNA expression levels of PPARγ target genes (such as Fabp4 and Nr1h3 when cells were first treated with troglitazone (TRO. Moreover, PPARγ activation affected BMP2 through enhancement of histone activation markers (acetylated histone H3 and trimethylated Lys4 of histone H3 on the Runx2 promoter. After TRO treatment for three hours, BMP2 enhanced the levels of active histone marks on the promoter of a PPARγ target gene. These results suggest that the order of treatment with BMP2 and a PPARγ ligand is critical for adipogenesis and osteoblastogenesis switching in MSCs.

  2. Bmp2 deletion causes an amelogenesis imperfecta phenotype via regulating enamel gene expression.

    Science.gov (United States)

    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

    2015-08-01

    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.

  3. Cell saver filtering of extravasated rhBMP-2 after degenerative scoliosis reconstruction

    Directory of Open Access Journals (Sweden)

    Gabriel Liu, MBBCh, MSc, FRCS, FAMS (Orth

    2015-06-01

    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.

  4. Study on Z-H/BMP Toughened Compound Artificial Bone and Its Osteogenesis

    Institute of Scientific and Technical Information of China (English)

    XU Wei-guo; CHEN An-min; SUN Shu-zhen

    2003-01-01

    The purpose of this study was to find a kind of new artificial bone for anterior spinal fusion.ZrO2 stabilized by Y2O3 ( Y- PSZ), porous hydroxyapatite ( HA ) and bone morphogenetic protein (BMP) were used to make artificial compound bone ( Y2O3 ) ZrO2 -HA/ BMP( Z-H/ BMP ) , whose function was tested, microstructure and mineralogic composition constitution were analysised by SEM and XRD , and the corresponding animal tests were porformed. Osteogenesis of the material was observed by eyes, histology and SEM. Experimental results show that the component and ossific activity of Z-H/BMP were satisfactory.

  5. Factors Affecting Pollutant Load Reduction with Uncertainty Analysis in Urban Stormwater BMP Systems

    Science.gov (United States)

    Park, D.

    2015-12-01

    This study incorporates uncertainty analysis into a model of the performance of stormwater best management practices (BMPs) to characterize the uncertainty in stormwater BMP effluent load that results from uncertainty in the BMP performance modeling in an urban stormwater system. Detention basins are used as BMPs in the urban stormwater systems, and the total suspended solids (TSS) are used as an urban nonpoint source pollutant in Los Angeles, CA. The k-C* model, which incorporates uncertainty analysis, is applied to the uncertainty of the stormwater effluent concentration in urban stormwater systems. This study presents a frequency analysis of the runoff volume and BMP overflows to characterize the uncertainty of BMP effluent loads, and the load frequency curve (LFC) is simulated with and without BMP conditions and verified using the observed TSS load. Finally, the effects of imperviousness, BMP volume, and BMP surface area are investigated using a reliability analysis. The results of this study can be used to determine the appropriate BMP size to achieve a specific watershed runoff pollutant load. The result of this evaluation method can support the adequate sizing of a BMP to meet the defined nonpoint source pollutant regulations. Acknowlegments This research was supported by a grant (14AWMP-B082564-01) from Advanced Water Management Research Program funded by Ministry of Land, Infrastructure and Transport of Korean government.

  6. Impact of biological treatments of bio-waste for nutrients, energy and bio-methane recovery in a life cycle perspective.

    Science.gov (United States)

    Di Maria, Francesco; Micale, Caterina; Contini, Stefano; Morettini, Emanuela

    2016-06-01

    Composting of the source-segregated organic fraction of municipal solid waste was compared in a life cycle perspective with conventional anaerobic digestion (AD), aimed at electricity substitution, and with AD aimed at biogas upgrading into bio-methane. Three different uses of the bio-methane were considered: injection in the natural gas grid for civil heating needs; use as fuel for high efficiency co-generation; use as fuel for vehicles. Scenarios with biogas upgrading showed quite similar impact values, generally higher than those of composting and conventional AD, for which there was a lower impact. A decisive contribution to the higher impact of the scenarios with bio-methane production was by the process for biogas upgrading. In any case the substitution of natural gas with bio-methane resulted in higher avoided impacts compared to electricity substitution by conventional AD. The uncertainty analysis confirmed the positive values for eutrophication, acidification and particulate matter. Large uncertainty was determined for global warming and photochemical ozone formation.

  7. Impact of biological treatments of bio-waste for nutrients, energy and bio-methane recovery in a life cycle perspective.

    Science.gov (United States)

    Di Maria, Francesco; Micale, Caterina; Contini, Stefano; Morettini, Emanuela

    2016-06-01

    Composting of the source-segregated organic fraction of municipal solid waste was compared in a life cycle perspective with conventional anaerobic digestion (AD), aimed at electricity substitution, and with AD aimed at biogas upgrading into bio-methane. Three different uses of the bio-methane were considered: injection in the natural gas grid for civil heating needs; use as fuel for high efficiency co-generation; use as fuel for vehicles. Scenarios with biogas upgrading showed quite similar impact values, generally higher than those of composting and conventional AD, for which there was a lower impact. A decisive contribution to the higher impact of the scenarios with bio-methane production was by the process for biogas upgrading. In any case the substitution of natural gas with bio-methane resulted in higher avoided impacts compared to electricity substitution by conventional AD. The uncertainty analysis confirmed the positive values for eutrophication, acidification and particulate matter. Large uncertainty was determined for global warming and photochemical ozone formation. PMID:27095293

  8. Calcium phosphate nanoparticles carrying BMP-7 plasmid DNA induce an osteogenic response in MC3T3-E1 pre-osteoblasts.

    Science.gov (United States)

    Hadjicharalambous, Chrystalleni; Kozlova, Diana; Sokolova, Viktoriya; Epple, Matthias; Chatzinikolaidou, Maria

    2015-12-01

    Functionalized calcium phosphate nanoparticles with osteogenic activity were prepared. Polyethyleneimine-stabilized calcium phosphate nanoparticles were coated with a shell of silica and covalently functionalized by silanization with thiol groups. Between the calcium phosphate surface and the outer silica shell, plasmid DNA which encoded either for bone morphogenetic protein 7 (BMP-7) or for enhanced green fluorescent protein was incorporated as cargo. The plasmid DNA-loaded calcium phosphate nanoparticles were used for the transfection of the pre-osteoblastic MC3T3-E1 cells. The cationic nanoparticles showed high transfection efficiency together with a low cytotoxicity. Their potential to induce an osteogenic response by transfection was demonstrated by measuring the alkaline phosphatase (ALP) activity and calcium deposition with alizarin red staining. The expression of the osteogenic markers Alp, Runx2, ColIa1 and Bsp was investigated by means of real-time quantitative polymerase chain reaction. It was shown that phBMP-7-loaded nanoparticles can provide a means of transient transfection and localized production of BMP-7 in MC3T3-E1 cells, with a subsequent increase of two osteogenic markers, specifically ALP activity and calcium accumulation in the extracellular matrix. Future strategies to stimulate bone regeneration focus into enhancing transfection efficiency and achieving higher levels of BMP-7 produced by the transfected cells.

  9. Influence of lignin on biochemical methane potential of biomass for biogas production

    DEFF Research Database (Denmark)

    Triolo, J M; Sommer, S G; Møller, H B;

    2011-01-01

    Biochemical methane potential (BMP) of biomass is of great importance in assessing biodegradability as well as predicting biogas yield for biogas production. Since the current BMP determination methods are costly and time-consuming, innovative techniques for predicting BMP are needed. The objective...... of this study was to examine the influence of fibrous fractions of biomass on BMP to develop an economical and easy-to-use predicting model of BMP, and hence the biodegradability of organic materials for biogas production. The model was developed either for energy crops or for animal manures, or as a...... combined model for these two biomass groups. Validation of the combined model was carried out using datasets from the literature. This study showed that lignin was not degraded during anaerobic digestion. Furthermore, lignin concentration in organic materials was the strongest predictor of BMP for all the...

  10. TGF-β1刺激下损伤的前交叉韧带和内侧副韧带中BMP-1基因的表达%Differential BMP-1 expression in injured anterior cruciate ligament and medial collateral ligament fibroblasts induced by TGF-β1

    Institute of Scientific and Technical Information of China (English)

    尹琳; 谢静; 蒋稼欢; 王春莉; 张艳君; 许春明; KL Paul Sung

    2012-01-01

    Objective To investigate the differential expression of bone morphogenetic protein-1 (BMP-1) in injured anterior cruciate ligament ( ACL) and medial collateral ligament ( MCL) fibroblasts induced by TGF-p,, and to find out the differences between the poorly self-healing ACL and well functionally self-healing MCL fibroblasts. Methods Fibroblasts were primarily cultured from clinical ACL and MCL samples, and then given 12% mechanical stretch injury and treated by 1, 5 and 50 ng/ml TGF-β1 for 2 h, or by 5 ng/ml TGF-β,1 for 2, 6, 12 and 24 h respectively at the same time. The expression of BMP-1 in the above treated and untreated fibroblasts were detected by reversed-transcript PCR and real-time quantitative PCR. Western blotting was used to detect the expression of BMP-1 in the injured fibroblasts induced by 5 ng/ml TGF-p, for 48 h. Results TGF-p, treatment resulted in an increased mRNA expression of BMP-1 in the injured fibroblasts in a dose-depended manner, especially in the cells from MCL than in those from ACL (about 1 times higher, P <0. 05). Compared with the fibroblasts without TGF-p, treatment, 5 ng/ml TGF-p, treatment for 24 h made the expression of BMP-1 reach the summit in ACL (6.1 folds higher, P <0.05) and in MCL (9.84 folds higher, P <0.05). Compared with the control, the protein expression of BMP-1 were elevated to 2. 32 and 3. 84 folds higher in ACL and MCL respectively after 5 ng/ml TGF-p, treatment for 48 h (P <0.01). Conclusion TGF-p, affects the expression of BMP-1 in the injured fibroblasts, and then directly affects activities of lysyl oxiadse in the extracellular matrix, implying its potential significant value and clinical usage in repair of injured ACL.%目的 观察在转化生长因子-β1(transforming growth factor betal,TGF-β1)作用下,损伤的前交叉韧带(anterior cruciate ligament,ACL)和内侧副韧带(medial collateral ligament,MCL)中骨形态发生蛋白-1(bone morphogenetic protein-1,BMP-1)基因的表达,找出TGF-31、BMP

  11. Recovering biomethane and nutrients from anaerobic digestion of water hyacinth (Eichhornia crassipes) and its co-digestion with fruit and vegetable waste.

    Science.gov (United States)

    Hernández-Shek, M A; Cadavid-Rodríguez, L S; Bolaños, I V; Agudelo-Henao, A C

    2016-01-01

    The potential to recover bioenergy from anaerobic digestion of water hyacinth (WH) and from its co-digestion with fruit and vegetable waste (FVW) was investigated. Initially, biogas and methane production were studied using the biochemical methane potential (BMP) test at 2 g volatile solids (VS) L(-1) of substrate concentration, both in the digestion of WH alone and in its co-digestion with FVW (WH-FVW ratio of 70:30). Subsequently, the biogas production was optimized in terms of total solids (TS) concentration, testing 4 and 6% of TS. The BMP test showed a biogas yield of 0.114 m(3) biogas kg(-1) VSadded for WH alone. On the other hand, the biogas potential from the WH-FVW co-digestion was 0.141 m(3) biogas kg(-1) VSadded, showing an increase of 23% compared to that of WH alone. Maximum biogas production of 0.230 m(3) biogas kg(-1) VSadded was obtained at 4% of TS in the co-digestion of WH-FVW. Using semi-continuously stirred tank reactors, 1.3 m(3) biogas yield kg(-1) VSadded was produced using an organic loading rate of 2 kg VS m(-3) d(-1) and hydraulic retention time of 15 days. It was also found that a WH-FVW ratio of 80:20 improved the process in terms of pH stability. Additionally, it was found that nitrogen can be recovered in the liquid effluent with a potential for use as a liquid fertilizer. PMID:26819391

  12. BMP-2 Induced Expression of Alx3 That Is a Positive Regulator of Osteoblast Differentiation.

    Directory of Open Access Journals (Sweden)

    Takashi Matsumoto

    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.

  13. Potential bone-inducing activity in vitro of recombinant human bone morphogenetic protein-7 from a CHO expression system

    Institute of Scientific and Technical Information of China (English)

    LI Xiao-yan; SHI Wei-wei; WANG Hao; LI Bo-hua; YANG Yang; TAN Min; XUE Jing-ya; GUO Ya-jun

    2005-01-01

    Objective: To express the recombinant human bone morphogenetic protein-7 (rhBMP-7) in Chinese hamster ovary(CHO) cells, and to establish the in vitro biological activity assay of rhBMP-7.Methods: Human BMP-7 cDNA was subcloned into p114 mammalian expression vector and transfected to CHO cells by using the Lipofectamine2000 transfection method. CHO cell supernatants were harvested and analyzed to identify the molecule mass of secreted rhBMP-7 and examine its biological activity in vitro to stimulate the synthesis of alkaline phophatase(ALP), a characteristic of osteoblast phenotypes. Results:rhBMP-7 was produced stably in CHO cells, as a processed mature disulfide-linked homodimer, with an apparent molecular mass of 36 000. Examination of the rhBMP-7 biological activity showed that rhBMP-7 specifically stimulated the production of ALP(4-fold increase at 100 ng of rhBMP-7/ml). Conclusion: The rhBMP-7 from CHO expression system has significant biological activity in induction of osteoblast phenotype, which demonstrates rhBMP-7 has the potential bone regeneration activity.

  14. Genetic analysis reveals an unexpected role of BMP7 in initiation of ureteric bud outgrowth in mouse embryos.

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    Alexandre Gonçalves

    Full Text Available BACKGROUND: Genetic analysis in the mouse revealed that GREMLIN1 (GREM1-mediated antagonism of BMP4 is essential for ureteric epithelial branching as the disruption of ureteric bud outgrowth and renal agenesis in Grem1-deficient embryos is restored by additional inactivation of one Bmp4 allele. Another BMP ligand, BMP7, was shown to control the proliferative expansion of nephrogenic progenitors and its requirement for nephrogenesis can be genetically substituted by Bmp4. Therefore, we investigated whether BMP7 in turn also participates in inhibiting ureteric bud outgrowth during the initiation of metanephric kidney development. METHODOLOGY/PRINCIPAL FINDINGS: Genetic inactivation of one Bmp7 allele in Grem1-deficient mouse embryos does not alleviate the bilateral renal agenesis, while complete inactivation of Bmp7 restores ureteric bud outgrowth and branching. In mouse embryos lacking both Grem1 and Bmp7, GDNF/WNT11 feedback signaling and the expression of the Etv4 target gene, which regulates formation of the invading ureteric bud tip, are restored. In contrast to the restoration of ureteric bud outgrowth and branching, nephrogenesis remains aberrant as revealed by the premature loss of Six2 expressing nephrogenic progenitor cells. Therefore, very few nephrons develop in kidneys lacking both Grem1 and Bmp7 and the resulting dysplastic phenotype is indistinguishable from the one of Bmp7-deficient mouse embryos. CONCLUSIONS/SIGNIFICANCE: Our study reveals an unexpected inhibitory role of BMP7 during the onset of ureteric bud outgrowth. As BMP4, BMP7 and GREM1 are expressed in distinct mesenchymal and epithelial domains, the localized antagonistic interactions of GREM1 with BMPs could restrict and guide ureteric bud outgrowth and branching. The robustness and likely significant redundancy of the underlying signaling system is evidenced by the fact that global reduction of Bmp4 or inactivation of Bmp7 are both able to restore ureteric bud outgrowth

  15. A Bmp/Admp regulatory circuit controls maintenance and regeneration of dorsal-ventral polarity in planarians

    OpenAIRE

    Gaviño, Michael A; Reddien, Peter W.

    2011-01-01

    Animal embryos have diverse anatomy and vary greatly in size. It is therefore remarkable that a common signaling pathway – BMP signaling – controls development of the dorsoventral (DV) axis throughout the Bilateria [1-8]. In vertebrates, spatially opposed expression of the BMP-family signaling proteins Bmp4 and Admp (anti-dorsalizing morphogenetic protein) can promote restoration of DV pattern following tissue removal [9-11]. bmp4 orthologs have been identified in all three groups of the Bila...

  16. An evolutionarily conserved enhancer regulates Bmp4 expression in developing incisor and limb bud.

    Directory of Open Access Journals (Sweden)

    Dolrudee Jumlongras

    Full Text Available To elucidate the transcriptional regulation of Bmp4 expression during organogenesis, we used phylogenetic footprinting and transgenic reporter analyses to identify Bmp4 cis-regulatory modules (CRMs. These analyses identified a regulatory region located ∼46 kb upstream of the mouse Bmp4 transcription start site that had previously been shown to direct expression in lateral plate mesoderm. We refined this regulatory region to a 396-bp minimal enhancer, and show that it recapitulates features of endogenous Bmp4 expression in developing mandibular arch ectoderm and incisor epithelium during the initiation-stage of tooth development. In addition, this enhancer directs expression in the apical ectodermal ridge (AER of the developing limb and in anterior and posterior limb mesenchyme. Transcript profiling of E11.5 mouse incisor dental lamina, together with protein binding microarray (PBM analyses, allowed identification of a conserved DNA binding motif in the Bmp4 enhancer for Pitx homeoproteins, which are also expressed in the developing mandibular and incisor epithelium. In vitro electrophoretic mobility shift assays (EMSA and in vivo transgenic reporter mutational analyses revealed that this site supports Pitx binding and that the site is necessary to recapitulate aspects of endogenous Bmp4 expression in developing craniofacial and limb tissues. Finally, Pitx2 chromatin immunoprecipitation (ChIP demonstrated direct binding of Pitx2 to this Bmp4 enhancer site in a dental epithelial cell line. These results establish a direct molecular regulatory link between Pitx family members and Bmp4 gene expression in developing incisor epithelium.

  17. Effect of rhBMP-2 on tibial plateau fractures in a canine model.

    Science.gov (United States)

    Schaefer, Susan L; Lu, Yan; Seeherman, Howard; Li, X Jian; Lopez, Mandi J; Markel, Mark D

    2009-04-01

    This study was to determine the efficacy of recombinant human bone morphogenetic protien-2 (rhBMP-2)/calcium phosphate matrix (CPX) paste to accelerate healing in a canine articular fracture model with associated subchondral defect. rhBMP-2/CPX (BMP), CPX alone (CPX) or autogenous bone graft (ABG) was administered to a canine articular tibial plateau osteotomy with a subchondral defect in each of 21 female dogs. The unoperated contralateral limbs served as controls. Ground reaction forces, synovial fluid, radiographic changes, mechanical testing, bone density, and histology of bone and synovium were analyzed at 6 weeks after surgery. Radiographic analysis demonstrated that the BMP and CPX groups showed improved bony healing compared to the ABG group at week 6. Histomorphometric analysis demonstrated that the BMP group had significantly increased trabecular bone volume compared to the CPX and ABG groups. Mechanical testing revealed that the BMP group had significantly greater maximum failure loads than the ABG group. Histological analysis demonstrated that the BMP group had significantly less sub-synovial inflammation than CPX group. This study demonstrated that rhBMP-2/CPX accelerated healing of articular fractures with subchondral defect compared to ABG in most of the parameters evaluated, and had less subsynovial inflammation than the CPX alone in a canine model.

  18. BMP4 signaling is involved in the generation of inner ear sensory epithelia

    Directory of Open Access Journals (Sweden)

    Wang Yucheng

    2005-08-01

    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.

  19. Delayed BMP4 exposure increases germ cell differentiation in mouse embryonic stem cells.

    Science.gov (United States)

    Talaei-Khozani, Tahereh; Zarei Fard, Nehleh; Bahmanpour, Soghra; Jaberipour, Mansoureh; Hosseini, Ahmah; Esmaeilpour, Tahereh

    2014-01-01

    Fate mapping studies have revealed that bone morphogenetic protein 4 (BMP4) signaling has a key role in segregation of primordial germ cells from proximal epiblast. Adding BMP4 to the culture media of embryonic stem (ES) cells could induce expression of germ cell markers; however, to provide a desired number of germ cells has remained a challenge. In the current study, we intended to establish an in vitro system to obtain reliable germ cells derived from ES cells. Differentiation was induced in ES cells via embryoid body (EB) and monolayer culture system. Cells were cultured with BMP4 from the beginning (++BMP4) or after 48 hours (+BMP4) of culturing for five days. The cultures were assessed for alkaline phosphatase (ALP) activity, expression of Oct4, Mvh and c-kit. In EB culture protocol, the expression of Mvh, Oct4 and ALP activity significantly increased in +BMP4 culture condition, but a significant down-regulation in the expression of germ cell markers was shown in ++BMP4 condition compared with the control group. Parallel differentiation experiments using monolayer culture system indicated the number of putative germ cells did not change. In the current study, we compared two differentiation methods (EB and monolayer) to achieve an optimal germ cell production. The EBs with a short exposure time period to BMP4, showing typical characteristics of germ cells. Therefore, our approach provides a strategy for the production of germline cells from ES cells. PMID:24969978

  20. Gremlin-2 is a BMP antagonist that is regulated by the circadian clock

    DEFF Research Database (Denmark)

    Yeung, Ching-Yan Chloé; Gossan, Nicole; Lu, Yinhui;

    2014-01-01

    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...

  1. Whole-Farm Evaluation of Phosphorus Crystallization as a Dairy Farm BMP

    Science.gov (United States)

    A recently proven method for precipitating significant phosphorus from dairy lagoons was incorporated to the Integrated Farm System Model. A whole-farm analysis of this BMP, including environmental and economical effects, were evaluated for an organic dairy farm in Washington. The BMP provides a non...

  2. TGF-b/BMP signaling and other molecular events:regulation of osteoblastogenesis and bone formation

    Institute of Scientific and Technical Information of China (English)

    Md Shaifur Rahman; Naznin Akhtar; Hossen Mohammad Jamil; Rajat Suvra Banik; Sikder M Asaduzzaman

    2015-01-01

    Transforming growth factor-beta (TGF-b)/bone morphogenetic protein (BMP) plays a fundamental role in the regulation of bone organogenesis through the activation of receptor serine/threonine kinases. Perturbations of TGF-b/BMP activity are almost invariably linked to a wide variety of clinical outcomes, i.e., skeletal, extra skeletal anomalies, autoimmune, cancer, and cardiovascular diseases. Phosphorylation of TGF-b (I/II) or BMP receptors activates intracellular downstream Smads, the transducer of TGF-b/BMP signals. This signaling is modulated by various factors and pathways, including transcription factor Runx2. The signaling network in skeletal development and bone formation is overwhelmingly complex and highly time and space specific. Additive, positive, negative, or synergistic effects are observed when TGF-b/BMP interacts with the pathways of MAPK, Wnt, Hedgehog (Hh), Notch, Akt/mTOR, and miRNA to regulate the effects of BMP-induced signaling in bone dynamics. Accumulating evidence indicates that Runx2 is the key integrator, whereas Hh is a possible modulator, miRNAs are regulators, and b-catenin is a mediator/regulator within the extensive intracellular network. This review focuses on the activation of BMP signaling and interaction with other regulatory components and pathways highlighting the molecular mechanisms regarding TGF-b/BMP function and regulation that could allow understanding the complexity of bone tissue dynamics.

  3. Matrix-immobilized BMP-2 on microcontact printed fibronectin as in vitro tool to study BMP-mediated signaling and cell migration

    Directory of Open Access Journals (Sweden)

    Kristin eHauff

    2015-05-01

    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

  4. BMP2 Regulation of CXCL12 Cellular, Temporal, and Spatial Expression is Essential During Fracture Repair

    Science.gov (United States)

    Myers, Timothy J; Longobardi, Lara; Willcockson, Helen; Temple, Joseph D; Tagliafierro, Lidia; Ye, Ping; Li, Tieshi; Esposito, Alessandra; Moats-Staats, Billie M; Spagnoli, Anna

    2016-01-01

    The cellular and humoral responses that orchestrate fracture healing are still elusive. Here we report that bone morphogenic protein 2 (BMP2)-dependent fracture healing occurs through a tight control of chemokine C-X-C motif-ligand-12 (CXCL12) cellular, spatial, and temporal expression. We found that the fracture repair process elicited an early site-specific response of CXCL12+-BMP2+ endosteal cells and osteocytes that was not present in unfractured bones and gradually decreased as healing progressed. Absence of a full complement of BMP2 in mesenchyme osteoprogenitors (BMP2cKO/+) prevented healing and led to a dysregulated temporal and cellular upregulation of CXCL12 expression associated with a deranged angiogenic response. Healing was rescued when BMP2cKO/+ mice were systemically treated with AMD3100, an antagonist of CXCR4 and agonist for CXCR7 both receptors for CXCL12. We further found that mesenchymal stromal cells (MSCs), capable of delivering BMP2 at the endosteal site, restored fracture healing when transplanted into BMP2cKO/+ mice by rectifying the CXCL12 expression pattern. Our in vitro studies showed that in isolated endosteal cells, BMP2, while inducing osteoblastic differentiation, stimulated expression of pericyte markers that was coupled with a decrease in CXCL12. Furthermore, in isolated BMP2cKO/cKO endosteal cells, high expression levels of CXCL12 inhibited osteoblastic differentiation that was restored by AMD3100 treatment or coculture with BMP2-expressing MSCs that led to an upregulation of pericyte markers while decreasing platelet endothelial cell adhesion molecule (PECAM). Taken together, our studies show that following fracture, a CXCL12+-BMP2+ perivascular cell population is recruited along the endosteum, then a timely increase of BMP2 leads to downregulation of CXCL12 that is essential to determine the fate of the CXCL12+-BMP2+ to osteogenesis while departing their supportive role to angiogenesis. Our findings have far

  5. BMP signaling protects telencephalic fate by repressing eye identity and its Cxcr4-dependent morphogenesis.

    Science.gov (United States)

    Bielen, Holger; Houart, Corinne

    2012-10-16

    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.

  6. Activin A inhibits BMP-signaling by binding ACVR2A and ACVR2B

    DEFF Research Database (Denmark)

    Olsen, Oddrun Elise; Wader, Karin Fahl; Hella, Hanne;

    2015-01-01

    BACKGROUND: Activins are members of the TGF-β family of ligands that have multiple biological functions in embryonic stem cells as well as in differentiated tissue. Serum levels of activin A were found to be elevated in pathological conditions such as cachexia, osteoporosis and cancer. Signaling...... by activin A through canonical ALK4-ACVR2 receptor complexes activates the transcription factors SMAD2 and SMAD3. Activin A has a strong affinity to type 2 receptors, a feature that they share with some of the bone morphogenetic proteins (BMPs). Activin A is also elevated in myeloma patients with advanced...... disease and is involved in myeloma bone disease. RESULTS: In this study we investigated effects of activin A binding to receptors that are shared with BMPs using myeloma cell lines with well-characterized BMP-receptor expression and responses. Activin A antagonized BMP-6 and BMP-9, but not BMP-2 and BMP-4...

  7. The p38/MK2/Hsp25 pathway is required for BMP-2-induced cell migration.

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    Cristina Gamell

    Full Text Available BACKGROUND: Bone morphogenetic proteins (BMPs have been shown to participate in the patterning and specification of several tissues and organs during development and to regulate cell growth, differentiation and migration in different cell types. BMP-mediated cell migration requires activation of the small GTPase Cdc42 and LIMK1 activities. In our earlier report we showed that activation of LIMK1 also requires the activation of PAKs through Cdc42 and PI3K. However, the requirement of additional signaling is not clearly known. METHODOLOGY/PRINCIPAL FINDINGS: Activation of p38 MAPK has been shown to be relevant for a number of BMP-2's physiological effects. We report here that BMP-2 regulation of cell migration and actin cytoskeleton remodelling are dependent on p38 activity. BMP-2 treatment of mesenchymal cells results in activation of the p38/MK2/Hsp25 signaling pathway downstream from the BMP receptors. Moreover, chemical inhibition of p38 signaling or genetic ablation of either p38α or MK2 blocks the ability to activate the downstream effectors of the pathway and abolishes BMP-2-induction of cell migration. These signaling effects on p38/MK2/Hsp25 do not require the activity of either Cdc42 or PAK, whereas p38/MK2 activities do not significantly modify the BMP-2-dependent activation of LIMK1, measured by either kinase activity or with an antibody raised against phospho-threonine 508 at its activation loop. Finally, phosphorylated Hsp25 colocalizes with the BMP receptor complexes in lamellipodia and overexpression of a phosphorylation mutant form of Hsp25 is able to abolish the migration of cells in response to BMP-2. CONCLUSIONS: These results indicate that Cdc42/PAK/LIMK1 and p38/MK2/Hsp25 pathways, acting in parallel and modulating specific actin regulatory proteins, play a critical role in integrating responses during BMP-induced actin reorganization and cell migration.

  8. Bmp7 functions via a polarity mechanism to promote cloacal septation.

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    Kun Xu

    Full Text Available BACKGROUND: During normal development in human and other placental mammals, the embryonic cloacal cavity separates along the axial longitudinal plane to give rise to the urethral system, ventrally, and the rectum, dorsally. Defects in cloacal development are very common and present clinically as a rectourethral fistula in about 1 in 5,000 live human births. Yet, the cellular mechanisms of cloacal septation remain poorly understood. METHODOLOGY/PRINCIPAL FINDINGS: We previously detected Bone morphogenetic protein 7 (Bmp7 expression in the urorectal mesenchyme (URM, and have shown that loss of Bmp7 function results in the arrest of cloacal septation. Here, we present evidence that cloacal partitioning is driven by Bmp7 signaling in the cloacal endoderm. We performed TUNEL and immunofluorescent analysis on cloacal sections from Bmp7 null and control littermate embryos. We found that loss of Bmp7 results in a dramatic decrease in the endoderm survival and a delay in differentiation. We used immunological methods to show that Bmp7 functions by activating the c-Jun N-terminal kinase (JNK pathway. We carried out confocal and 3D imaging analysis of mitotic chromosome bundles to show that during normal septation cells in the cloacal endoderm divide predominantly in the apical-basal direction. Loss of Bmp7/JNK signaling results in randomization of mitotic angles in the cloacal endoderm. We also conducted immunohistochemical analysis of human fetal sections to show that BMP/phospho-SMAD and JNK pathways function in the human cloacal region similar as in the mouse. CONCLUSION/SIGNIFICANCE: Our results strongly indicate that Bmp7/JNK signaling regulates remodeling of the cloacal endoderm resulting in a topological separation of the urinary and digestive systems. Our study points to the importance of Bmp and JNK signaling in cloacal development and rectourethral malformations.

  9. BMP2, 4 and 6 and BMPR1B are altered from early stages of bovine cystic ovarian disease development.

    Science.gov (United States)

    Díaz, Pablo U; Hein, Gustavo J; Belotti, Eduardo M; Rodríguez, Fernanda M; Rey, Florencia; Amweg, Ayelén N; Matiller, Valentina; Baravalle, María E; Ortega, Hugo H; Salvetti, Natalia R

    2016-10-01

    Cystic ovarian disease (COD) is an important cause of subfertility in dairy cattle. Bone morphogenetic proteins (BMPs), mainly BMP2, BMP4 and BMP6, play a key role in female fertility. In this study, we hypothesized that an altered BMP system is associated with ovarian alterations contributing to COD pathogenesis. Therefore, we examined the expression of BMP2, BMP4 and BMP6 and BMP receptor 1B (BMPR1B) in the ovaries of animals with spontaneous or ACTH-induced COD, as well as during the development of the disease, in a model of follicular persistence induced by low doses of progesterone (at 5, 10 and 15 days of follicular persistence). Results showed changes in BMP2, BMP4 and BMP6 expression during folliculogenesis, in granulosa and theca cells in the COD groups, as well as at different stages of follicular persistence. Results also showed changes in BMPR1B expression in developing follicles in animals with COD, and at the initial stages of follicular persistence (P5). Comparison between groups showed significant differences, mainly in BMP4 and BMP6 expression, in granulosa and theca cells of different follicular categories. The expression of these BMPs also increased in cystic and persistent follicles, in relation to antral follicles of the control group. BMPR1B showed high expression in cystic follicles. Together, these results may indicate an alteration in BMPs, especially in BMP4 and BMP6, as well as in BMPR1B, which occurs early in folliculogenesis and incipiently during the development of COD, which could be a major cause of recurrence of this disease in cattle.Free Spanish abstract: A Spanish translation of this abstract is freely available at http://www.reproduction-online.org/content/early/2016/08/01/REP-15-0315/suppl/DC1. PMID:27486268

  10. Biochemical methane potential and anaerobic biodegradability of non-herbaceous and herbaceous phytomass in biogas production

    DEFF Research Database (Denmark)

    Triolo, Jin Mi; Pedersen, Lene; Qu, Haiyan;

    2012-01-01

    The suitability of municipal plant waste for anaerobic digestion was examined using 57 different herbaceous and non-herbaceous samples. Biochemical methane potential (BMP) and anaerobic biodegradability were related to the degree of lignification and crystallinity of cellulose. The BMP of...

  11. Effect of cobalt supplementation and fractionation on the biological response in the biomethanization of Olive Mill Solid Waste.

    Science.gov (United States)

    Pinto-Ibieta, F; Serrano, A; Jeison, D; Borja, R; Fermoso, F G

    2016-07-01

    Due to the low trace metals concentration in the Olive Mill Solid Waste (OMSW), a proposed strategy to improve its biomethanization is the supplementation of key metals to enhance the microorganism activity. Among essential trace metals, cobalt has been reported to have a crucial role in anaerobic degradation. This study evaluates the effect of cobalt supplementation to OMSW, focusing on the connection between fractionation of cobalt in the system and the biological response. The highest biological responses was found in a range from 0.018 to 0.035mg/L of dissolved cobalt (0.24-0.65mg total cobalt/L), reaching improvements up to 23% and 30% in the methane production rate and the methane yield coefficient, respectively. It was found that the dissolved cobalt fraction is more accurately related with the biological response than the total cobalt. The total cobalt is distorted by the contribution of dissolved and non-dissolved inert fractions.

  12. GHG emission factors for bioelectricity, biomethane, and bioethanol quantified for 24 biomass substrates with consequential life-cycle assessment

    DEFF Research Database (Denmark)

    Tonini, Davide; Hamelin, Lorie; Alvarado-Morales, Merlin;

    2016-01-01

    factors (EFs) for bioelectricity, biomethane, and bioethanol produced from twenty-four biomasses (from dedicated crops to residues of different origin) under a fossil and a non-fossil energy system. Accounting for numerous variations in the pathways, a total of 554 GHG EFs were quantified. The results...... showed that, important GHG savings were obtained with residues and seaweed, both under fossil and non-fossil energy systems. For high-yield perennial crops (e.g. willow and Miscanthus), GHG savings were achieved only under fossil energy systems. Biofuels from annual crops and residues that are today used...... in the feed sector should be discouraged, as LUC GHG emissions exceeded any GHG savings from displacing conventional energy sources. (C) 2016 Elsevier Ltd. All rights reserved....

  13. A Bmp/Admp regulatory circuit controls maintenance and regeneration of dorsal-ventral polarity in planarians.

    Science.gov (United States)

    Gaviño, Michael A; Reddien, Peter W

    2011-02-22

    Animal embryos have diverse anatomy and vary greatly in size. It is therefore remarkable that a common signaling pathway, BMP signaling, controls development of the dorsoventral (DV) axis throughout the Bilateria. In vertebrates, spatially opposed expression of the BMP family proteins Bmp4 and Admp (antidorsalizing morphogenetic protein) can promote restoration of DV pattern following tissue removal. bmp4 orthologs have been identified in all three groups of the Bilateria (deuterostomes, ecdysozoans, and lophotrochozoans). By contrast, the absence of admp orthologs in ecdysozoans such as Drosophila and C. elegans has suggested that a regulatory circuit of oppositely expressed bmp4 and admp genes represents a deuterostome-specific innovation. Here we describe the existence of spatially opposed bmp and admp expression in a protostome. An admp ortholog (Smed-admp) is expressed ventrally and laterally in adult Schmidtea mediterranea planarians, opposing the dorsal-pole expression of Smed-bmp4. Smed-admp is required for regeneration following parasagittal amputation. Furthermore, Smed-admp promotes Smed-bmp4 expression and Smed-bmp4 inhibits Smed-admp expression, generating a regulatory circuit that buffers against perturbations of Bmp signaling. These results suggest that a Bmp/Admp regulatory circuit is a central feature of the Bilateria, used broadly for the establishment, maintenance, and regeneration of the DV axis. PMID:21295483

  14. Effect of rhBMP-2 Immobilized Anorganic Bovine Bone Matrix on Bone Regeneration

    Directory of Open Access Journals (Sweden)

    Jung-Bo Huh

    2015-07-01

    Full Text Available Anorganic bovine bone matrix (Bio-Oss® has been used for a long time for bone graft regeneration, but has poor osteoinductive capability. The use of recombinant human bone morphogenetic protein-2 (rhBMP-2 has been suggested to overcome this limitation of Bio-Oss®. In the present study, heparin-mediated rhBMP-2 was combined with Bio-Oss® in animal experiments to investigate bone formation performance; heparin was used to control rhBMP-2 release. Two calvarial defects (8 mm diameter were formed in a white rabbit model and then implanted or not (controls with Bio-Oss® or BMP-2/Bio-Oss®. The Bio-Oss® and BMP-2/Bio-Oss® groups had significantly greater new bone areas (expressed as percentages of augmented areas than the non-implanted controls at four and eight weeks after surgery, and the BMP-2/Bio-Oss® group (16.50 ± 2.87 (n = 6 had significantly greater new bone areas than the Bio-Oss® group (9.43 ± 3.73 (n = 6 at four weeks. These findings suggest that rhBMP-2 treated heparinized Bio-Oss® markedly enhances bone regeneration.

  15. Endocardial to myocardial notch-wnt-bmp axis regulates early heart valve development.

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    Yidong Wang

    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.

  16. BMP9 protects septal neurons from axotomy-evoked loss of cholinergic phenotype.

    Directory of Open Access Journals (Sweden)

    Ignacio Lopez-Coviella

    Full Text Available BACKGROUND: Cholinergic projection from the septum to the hippocampus is crucial for normal cognitive function and degeneration of cells and nerve fibers within the septohippocampal pathway contributes to the pathophysiology of Alzheimer's disease. Bone morphogenetic protein (BMP 9 is a cholinergic differentiating factor during development both in vivo and in vitro. METHODOLOGY/PRINCIPAL FINDINGS: To determine whether BMP9 could protect the adult cholinergic septohippocampal pathway from axotomy-evoked loss of the cholinergic phenotype, we performed unilateral fimbria-fornix transection in mice and treated them with a continuous intracerebroventricular infusion of BMP9 for six days. The number of choline acetyltransferase (CHAT-positive cells was reduced by 50% in the medial septal nucleus ipsilateral to the lesion as compared to the intact, contralateral side, and BMP9 infusion prevented this loss in a dose-dependent manner. Moreover, BMP9 prevented most of the decline of hippocampal acetylcholine levels ipsilateral to the lesion, and markedly increased CHAT, choline transporter CHT, NGF receptors p75 (NGFR-p75 and TrkA (NTRK1, and NGF protein content in both the lesioned and unlesioned hippocampi. In addition, BMP9 infusion reduced bilaterally hippocampal levels of basic FGF (FGF2 protein. CONCLUSIONS/SIGNIFICANCE: These data indicate that BMP9 administration can prevent lesion-evoked impairment of the cholinergic septohippocampal neurons in adult mice and, by inducing NGF, establishes a trophic environment for these cells.

  17. BMP signaling mediates effects of exercise on hippocampal neurogenesis and cognition in mice.

    Directory of Open Access Journals (Sweden)

    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.

  18. BMP antagonists enhance myogenic differentiation and ameliorate the dystrophic phenotype in a DMD mouse model.

    Science.gov (United States)

    Shi, SongTing; Hoogaars, Willem M H; de Gorter, David J J; van Heiningen, Sandra H; Lin, Herbert Y; Hong, Charles C; Kemaladewi, Dwi U; Aartsma-Rus, Annemieke; ten Dijke, Peter; 't Hoen, Peter A C

    2011-02-01

    Duchenne Muscular Dystrophy (DMD) is an X-linked lethal muscle wasting disease characterized by muscle fiber degeneration and necrosis. The progressive pathology of DMD can be explained by an insufficient regenerative response resulting in fibrosis and adipose tissue formation. BMPs are known to inhibit myogenic differentiation and in a previous study we found an increased expression of a BMP family member BMP4 in DMD myoblasts. The aim of the current study was therefore to investigate whether inhibition of BMP signaling could be beneficial for myoblast differentiation and muscle regeneration processes in a DMD context. All tested BMP inhibitors, Noggin, dorsomorphin and LDN-193189, were able to accelerate and enhance myogenic differentiation. However, dorsomorphin repressed both BMP and TGFβ signaling and was found to be toxic to primary myoblast cell cultures. In contrast, Noggin was found to be a potent and selective BMP inhibitor and was therefore tested in vivo in a DMD mouse model. Local adenoviral-mediated overexpression of Noggin in muscle resulted in an increased expression of the myogenic regulatory genes Myog and Myod1 and improved muscle histology. In conclusion, our results suggest that repression of BMP signaling may constitute an attractive adjunctive therapy for DMD patients. PMID:20940052

  19. BMP signaling and cellular dynamics during regeneration of airway epithelium from basal progenitors.

    Science.gov (United States)

    Tadokoro, Tomomi; Gao, Xia; Hong, Charles C; Hotten, Danielle; Hogan, Brigid L M

    2016-03-01

    The pseudostratified epithelium of the lung contains ciliated and secretory luminal cells and basal stem/progenitor cells. To identify signals controlling basal cell behavior we screened factors that alter their self-renewal and differentiation in a clonal organoid (tracheosphere) assay. This revealed that inhibitors of the canonical BMP signaling pathway promote proliferation but do not affect lineage choice, whereas exogenous Bmp4 inhibits proliferation and differentiation. We therefore followed changes in BMP pathway components in vivo in the mouse trachea during epithelial regeneration from basal cells after injury. The findings suggest that BMP signaling normally constrains proliferation at steady state and this brake is released transiently during repair by the upregulation of endogenous BMP antagonists. Early in repair, the packing of epithelial cells along the basal lamina increases, but density is later restored by active extrusion of apoptotic cells. Systemic administration of the BMP antagonist LDN-193189 during repair initially increases epithelial cell number but, following the shedding phase, normal density is restored. Taken together, these results reveal crucial roles for both BMP signaling and cell shedding in homeostasis of the respiratory epithelium. PMID:26811382

  20. Effect of rhBMP-2 Immobilized Anorganic Bovine Bone Matrix on Bone Regeneration.

    Science.gov (United States)

    Huh, Jung-Bo; Yang, June-Jip; Choi, Kyung-Hee; Bae, Ji Hyeon; Lee, Jeong-Yeol; Kim, Sung-Eun; Shin, Sang-Wan

    2015-01-01

    Anorganic bovine bone matrix (Bio-Oss®) has been used for a long time for bone graft regeneration, but has poor osteoinductive capability. The use of recombinant human bone morphogenetic protein-2 (rhBMP-2) has been suggested to overcome this limitation of Bio-Oss®. In the present study, heparin-mediated rhBMP-2 was combined with Bio-Oss® in animal experiments to investigate bone formation performance; heparin was used to control rhBMP-2 release. Two calvarial defects (8 mm diameter) were formed in a white rabbit model and then implanted or not (controls) with Bio-Oss® or BMP-2/Bio-Oss®. The Bio-Oss® and BMP-2/Bio-Oss® groups had significantly greater new bone areas (expressed as percentages of augmented areas) than the non-implanted controls at four and eight weeks after surgery, and the BMP-2/Bio-Oss® group (16.50 ± 2.87 (n = 6)) had significantly greater new bone areas than the Bio-Oss® group (9.43 ± 3.73 (n = 6)) at four weeks. These findings suggest that rhBMP-2 treated heparinized Bio-Oss® markedly enhances bone regeneration. PMID:26184187

  1. Bmp signaling mediates endoderm pouch morphogenesis by regulating Fgf signaling in zebrafish.

    Science.gov (United States)

    Lovely, C Ben; Swartz, Mary E; McCarthy, Neil; Norrie, Jacqueline L; Eberhart, Johann K

    2016-06-01

    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

  2. Low dose BMP-2 treatment for bone repair using a PEGylated fibrinogen hydrogel matrix.

    Science.gov (United States)

    Ben-David, Dror; Srouji, Samer; Shapira-Schweitzer, Keren; Kossover, Olga; Ivanir, Eran; Kuhn, Gisela; Müller, Ralph; Seliktar, Dror; Livne, Erella

    2013-04-01

    Bone repair strategies utilizing resorbable biomaterial implants aim to stimulate endogenous cells in order to gradually replace the implant with functional repair tissue. These biomaterials should therefore be biodegradable, osteoconductive, osteoinductive, and maintain their integrity until the newly formed host tissue can contribute proper function. In recent years there has been impressive clinical outcomes for this strategy when using osteoconductive hydrogel biomaterials in combination with osteoinductive growth factors such as human recombinant bone morphogenic protein (hrBMP-2). However, the success of hrBMP-2 treatments is not without risks if the factor is delivered too rapidly and at very high doses because of a suboptimal biomaterial. Therefore, the aim of this study was to evaluate the use of a PEGylated fibrinogen (PF) provisional matrix as a delivery system for low-dose hrBMP-2 treatment in a critical size maxillofacial bone defect model. PF is a semi-synthetic hydrogel material that can regulate the release of physiological doses of hrBMP-2 based on its controllable physical properties and biodegradation. hrBMP-2 release from the PF material and hrBMP-2 bioactivity were validated using in vitro assays and a subcutaneous implantation model in rats. Critical size calvarial defects in mice were treated orthotopically with PF containing 8 μg/ml hrBMP-2 to demonstrate the capacity of these bioactive implants to induce enhanced bone formation in as little as 6 weeks. Control defects treated with PF alone or left empty resulted in far less bone formation when compared to the PF/hrBMP-2 treated defects. These results demonstrate the feasibility of using a semi-synthetic biomaterial containing small doses of osteoinductive hrBMP-2 as an effective treatment for maxillofacial bone defects. PMID:23375953

  3. BMP15 Prevents Cumulus Cell Apoptosis Through CCL2 and FBN1 in Porcine Ovaries

    Directory of Open Access Journals (Sweden)

    Bo Zhai

    2013-07-01

    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.

  4. TGF-βand BMP signaling in osteoblast, skeletal development, and bone formation, homeostasis and disease

    Institute of Scientific and Technical Information of China (English)

    Mengrui Wu; Guiqian Chen; and Yi-Ping Li

    2016-01-01

    Transforming growth factor-beta (TGF-β) and bone morphogenic protein (BMP) signaling has fundamental roles in both embryonic skeletal development and postnatal bone homeostasis. TGF-βs and BMPs, acting on a tetrameric receptor complex, transduce signals to both the canonical Smad-dependent signaling pathway (that is, TGF-β/BMP ligands, receptors, and Smads) and the non-canonical-Smad-independent signaling pathway (that is, p38 mitogen-activated protein kinase/p38 MAPK) to regulate mesenchymal stem cell differentiation during skeletal development, bone formation and bone homeostasis. Both the Smad and p38 MAPK signaling pathways converge at transcription factors, for example, Runx2 to promote osteoblast differentiation and chondrocyte differentiation from mesenchymal precursor cells. TGF-βand BMP signaling is controlled by multiple factors, including the ubiquitin–proteasome system, epigenetic factors, and microRNA. Dysregulated TGF-βand BMP signaling result in a number of bone disorders in humans. Knockout or mutation of TGF-βand BMP signaling-related genes in mice leads to bone abnormalities of varying severity, which enable a better understanding of TGF-β/BMP signaling in bone and the signaling networks underlying osteoblast differentiation and bone formation. There is also crosstalk between TGF-β/BMP signaling and several critical cytokines’ signaling pathways (for example, Wnt, Hedgehog, Notch, PTHrP, and FGF) to coordinate osteogenesis, skeletal development, and bone homeostasis. This review summarizes the recent advances in our understanding of TGF-β/BMP signaling in osteoblast differentiation, chondrocyte differentiation, skeletal development, cartilage formation, bone formation, bone homeostasis, and related human bone diseases caused by the disruption of TGF-β/BMP signaling.

  5. BIOMETHANIZATION OF SOLID URBAN WASTE URBAN: LABORATORY SCALEAND PILOT SCALE = BIOMETANIZACIÓN DE RESIDUO SÓLIDO URBANO: ESCALA DE LABORATORIO Y PLANTA PILOTO

    OpenAIRE

    Luis Isidoro Romero García; Montserrat Perez Garcia; Tânia Forster Carneiro

    2007-01-01

    The general objective of the present work has been to establish an appropriate protocol to carry out the start up and stabilization of the process of biomethanization of municipal solid waste (MSW), under dry (20-30 % total solid) and thermophilic (55ºC temperature) conditions, and transferable to industrial scale. The first study was conducted to develop and apply the different technical analytic for the appropriate characterization of the MSW. The second objective was defined to propose a s...

  6. Hybridizing concentrated solar power (CSP) with biogas and biomethane as an alternative to natural gas: Analysis of environmental performance using LCA

    OpenAIRE

    San Miguel Alfaro, Guillermo; Corona Bellostas, Blanca

    2014-01-01

    Concentrating Solar Power (CSP) plants typically incorporate one or various auxiliary boilers operating in parallel to the solar field to facilitate start up operations, provide system stability, avoid freezing of heat transfer fluid (HTF) and increase generation capacity. The environmental performance of these plants is highly influenced by the energy input and the type of auxiliary fuel, which in most cases is natural gas (NG). Replacing the NG with biogas or biomethane (BM) in commercial C...

  7. Effect of rhBMP-2 Immobilized Anorganic Bovine Bone Matrix on Bone Regeneration

    OpenAIRE

    Jung-Bo Huh; June-Jip Yang; Kyung-Hee Choi; Ji Hyeon Bae; Jeong-Yeol Lee; Sung-Eun Kim; Sang-Wan Shin

    2015-01-01

    Anorganic bovine bone matrix (Bio-Oss®) has been used for a long time for bone graft regeneration, but has poor osteoinductive capability. The use of recombinant human bone morphogenetic protein-2 (rhBMP-2) has been suggested to overcome this limitation of Bio-Oss®. In the present study, heparin-mediated rhBMP-2 was combined with Bio-Oss® in animal experiments to investigate bone formation performance; heparin was used to control rhBMP-2 release. Two calvarial defects (8 mm diameter) were fo...

  8. Transcriptional repression of Bmp2 by p21(Waf1/Cip1) links quiescence to neural stem cell maintenance.

    Science.gov (United States)

    Porlan, Eva; Morante-Redolat, José Manuel; Marqués-Torrejón, María Ángeles; Andreu-Agulló, Celia; Carneiro, Carmen; Gómez-Ibarlucea, Esther; Soto, Atenea; Vidal, Anxo; Ferrón, Sacri R; Fariñas, Isabel

    2013-11-01

    Relative quiescence and self renewal are defining features of adult stem cells, but their potential coordination remains unclear. Subependymal neural stem cells (NSCs) lacking cyclin-dependent kinase (CDK) inhibitor (CKI) 1a (p21) exhibit rapid expansion that is followed by their permanent loss later in life. Here we demonstrate that transcription of the gene encoding bone morphogenetic protein 2 (Bmp2) in NSCs is under the direct negative control of p21 through actions that are independent of CDK. Loss of p21 in NSCs results in increased levels of secreted BMP2, which induce premature terminal differentiation of multipotent NSCs into mature non-neurogenic astrocytes in an autocrine and/or paracrine manner. We also show that the cell-nonautonomous p21-null phenotype is modulated by the Noggin-rich environment of the subependymal niche. The dual function that we describe here provides a physiological example of combined cell-autonomous and cell-nonautonomous functions of p21 with implications in self renewal, linking the relative quiescence of adult stem cells to their longevity and potentiality.

  9. Evaluating biomethane production from anaerobic mono- and co-digestion of food waste and floatable oil (FO) skimmed from food waste.

    Science.gov (United States)

    Meng, Ying; Li, Sang; Yuan, Hairong; Zou, Dexun; Liu, Yanping; Zhu, Baoning; Chufo, Akiber; Jaffar, Muhammad; Li, Xiujin

    2015-06-01

    Batch anaerobic digestion was employed to investigate the performance of the floatable oil (FO) skimmed from food waste (FW) and the effect of different FO concentrations (5, 10, 20, 30, 40 and 50g/L) on biomethane production and system stability. FO and FO+FW were mono-digested and co-digested. The results showed that FO and FO+FW could be well anaerobically converted to biomethane in appropriate loads. For the mono-digestions of FO, the biomethane yield, TS and VS reduction achieved 607.7-846.9mL/g, 69.7-89% and 84.5-92.8%, respectively, when FO concentration was 5-40g/L. But the mono-digestion appeared instability when FO concentration was 50g/L. For the co-digestions of FW+FO, TS and VS reductions reached 70.7-86.1% and 87.5-91.4%, respectively, when FO concentration was 5-30g/L. However, the inhibition occurred when FO concentrations increased to 40-50g/L. The maximal FO loads of 40g/L and 30g/L were hence suggested for efficient mono-digestions and co-digestions of FO and FO+FW. PMID:25746472

  10. Dexamethasone, BMP-2, and 1,25-dihydroxyvitamin D enhance a more differentiated osteoblast phenotype

    DEFF Research Database (Denmark)

    Jørgensen, Niklas Rye; Henriksen, Z; Sørensen, O H;

    2004-01-01

    D), 100 nM Dex, and/or 100 ng/ml BMP-2. The osteoblast phenotype was assessed as alkaline phosphatase (AP) activity/staining, production of osteocalcin and procollagen type 1 (P1NP), parathyroid hormone (PTH)-induced cyclic adenosine mono-phosphate (cAMP) production, and in vitro mineralization. AP...... 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...... osteoblastic cells with different phenotypic characteristics, and a selective activation of some of the most important genes and functions of the mature osteoblast can thus be performed in vitro....

  11. Crystallization of BMP receptor type IA bound to the antibody Fab fragment AbD1556

    International Nuclear Information System (INIS)

    The crystallization of BMP receptor type IA bound to the neutralizing antibody Fab fragment AbD1556 obtained by phage-display selection is reported. An antibody Fab fragment, AbD1556, was selected against the extracellular domain of BMP receptor type IA, which blocks the binding of BMP-2 to BMPR-IA and thereby neutralizes BMP-2 activity. To study the mechanism by which BMPR-IA is recognized and bound by the Fab fragment, the complex of AbD1556 bound to BMPR-IA was prepared and crystallized. Crystals of this binary complex belonged to the monoclinic space group P21, with unit-cell parameters a = 89.32, b = 129.25, c = 100.24 Å, β = 92.27°

  12. Bone induction at physiological doses of BMP through localization by clay nanoparticle gels.

    Science.gov (United States)

    Gibbs, D M R; Black, C R M; Hulsart-Billstrom, G; Shi, P; Scarpa, E; Oreffo, R O C; Dawson, J I

    2016-08-01

    Bone Morphogenic Protein 2 (BMP2) can induce ectopic bone. This ability, which first motivated the widespread application of BMP2 in fracture healing and spinal arthrodesis has, more recently, been indicated as one of several serious adverse effects associated with the supra-physiological doses of BMP2 relied upon for clinical efficacy. Key to harnessing BMPs and other agents safely and effectively will be the ability to localize activity at a target site at substantially reduced doses. Clay (Laponite) nanoparticles can self assemble into gels under physiological conditions and bind growth factors for enhanced and localized efficacy. Here we show the ability to localize and enhance the activity of BMP2 to achieve ectopic bone formation at doses within the sub-microgram per ml range of concentrations sufficient to induce differentiation of responsive cell populations in vitro and at approximately 3000 fold lower than those employed in clinical practice. PMID:27209259

  13. Sustained and promoter dependent bone morphogenetic protein expression by rat mesenchymal stem cells after BMP-2 transgene electrotransfer

    Directory of Open Access Journals (Sweden)

    E Ferreira

    2012-07-01

    Full Text Available Transplantation of mesenchymal stem cells (MSCs with electrotransferred bone morphogenetic protein-2 (BMP-2 transgene is an attractive therapeutic modality for the treatment of large bone defects: it provides both stem cells with the ability to form bone and an effective bone inducer while avoiding viral gene transfer. The objective of the present study was to determine the influence of the promoter driving the human BMP-2 gene on the level and duration of BMP-2 expression after transgene electrotransfer into rat MSCs. Cytomegalovirus, elongation factor-1α, glyceraldehyde 3-phosphate dehydrogenase, and beta-actin promoters resulted in a BMP-2 secretion rate increase of 11-, 78-, 66- and 36-fold over respective controls, respectively. In contrast, the osteocalcin promoter had predictable weak activity in undifferentiated MSCs but induced the strongest BMP-2 secretion rates in osteoblastically-differentiated MSCs. Regardless of the promoter driving the transgene, a plateau of maximal BMP-2 secretion persisted for at least 21 d after the hBMP-2 gene electrotransfer. The present study demonstrates the feasibility of gene electrotransfer for efficient BMP-2 transgene delivery into MSCs and for a three-week sustained BMP-2 expression. It also provides the first in vitro evidence for a safe alternative to viral methods that permit efficient BMP-2 gene delivery and expression in MSCs but raise safety concerns that are critical when considering clinical applications.

  14. 我国碳减排模式探讨——CCS路线与生物甲烷路线的比较%Carbon reduction pattern in China: comparison of CCS and biomethane route

    Institute of Scientific and Technical Information of China (English)

    刘畅; 陆小华

    2013-01-01

    CCS (carbon capture and storage) route and biomethane route are very important methods to reduce CO2 emission. But the high cost for CO2 capture in CCS route, and the small scale in biomethane route limit their widespread application. In this work, CCS route and biomethane route were compared in terms of economics and technology. It was found that theoretical energy consumption of biomethane route was only half of that of CCS route. The mild condition to capture CO2 in biomethane route was beneficial to increasing adsorption capacity and then reducing capture cost. Thus biomethane route was better to reduce CO2 emission. In order to solve the problems in CCS route and biomethane route, a new idea to boost biomethane route by coupling of CCS route and biomethane route was proposed.%碳捕获和封存路线(carbon capture and storage,简称CCS)和生物甲烷路线是实现二氧化碳减排的两种重要途径.但CCS路线存在捕集成本高的难题,而生物甲烷路线规模小、尚处于起步阶段.本文从经济和技术角度对比了两种路线减排二氧化碳的优缺点,发现生物甲烷路线理论捕集能耗仅为CCS路线的一半,且捕集条件温和,更有利于提高吸附剂材料的容量、降低捕集成本,因而生物甲烷路线更具有减排潜力.为了解决CCS和生物甲烷路线目前存在的困境,提出了CCS与生物甲烷耦合、借助CCS加速发展生物甲烷过程的新思路.

  15. Cyclic dermal BMP signalling regulates stem cell activation during hair regeneration.

    Science.gov (United States)

    Plikus, Maksim V; Mayer, Julie Ann; de la Cruz, Damon; Baker, Ruth E; Maini, Philip K; Maxson, Robert; Chuong, Cheng-Ming

    2008-01-17

    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

  16. Advanced BMP Gene Therapies for Temporal and Spatial Control of Bone Regeneration

    OpenAIRE

    Wilson, C.G.; Martín-Saavedra, F.M.; Vilaboa, N.; Franceschi, R.T.

    2013-01-01

    Spatial and temporal patterns of bone morphogenetic protein (BMP) signaling are crucial to the assembly of appropriately positioned and shaped bones of the face and head. This review advances the hypothesis that reconstitution of such patterns with cutting-edge gene therapies will transform the clinical management of craniofacial bone defects attributed to trauma, disease, or surgical resection. Gradients in BMP signaling within developing limbs and orofacial primordia regulate proliferation ...

  17. BMP signaling turns up in fragile X syndrome: FMRP represses BMPR2.

    Science.gov (United States)

    Broihier, Heather T

    2016-01-01

    Fragile X syndrome is the most common inherited form of intellectual disability and results from a loss of function of the translational repressor FMRP. In this issue of Science Signaling, Kashima et al find that FMRP binds to and represses a specific isoform of BMPR2, a type II bone morphogenetic protein (BMP) receptor. Reducing signaling through this BMP pathway reverses neuroanatomical defects observed in fragile X models. PMID:27273094

  18. Sustained release of BMP-2 in bioprinted alginate for osteogenicity in mice and rats.

    Directory of Open Access Journals (Sweden)

    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.

  19. Effect of a Novel Nonviral Gene Delivery of BMP-2 on Bone Healing

    Directory of Open Access Journals (Sweden)

    P. Schwabe

    2012-01-01

    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.

  20. Scorpion Toxin, BmP01, Induces Pain by Targeting TRPV1 Channel

    Directory of Open Access Journals (Sweden)

    Md Abdul Hakim

    2015-09-01

    Full Text Available The intense pain induced by scorpion sting is a frequent clinical manifestation. To date, there is no established protocol with significant efficacy to alleviate the pain induced by scorpion envenomation. One of the important reasons is that, little information on pain-inducing compound from scorpion venoms is available. Here, a pain-inducing peptide (BmP01 has been identified and characterized from the venoms of scorpion (Mesobuthus martensii. In an animal model, intraplantar injection of BmP01 in mouse hind paw showed significant acute pain in wild type (WT mice but not in TRPV1 knock-out (TRPV1 KO mice during 30 min recording. BmP01 evoked currents in WT dorsal root ganglion (DRG neurons but had no effect on DRG neurons of TRPV1 KO mice. Furthermore, OPEN ACCESS Toxins 2015, 7 3672 BmP01 evoked currents on TRPV1-expressed HEK293T cells, but not on HEK293T cells without TRPV1. These results suggest that (1 BmP01 is one of the pain-inducing agents in scorpion venoms; and (2 BmP01 induces pain by acting on TRPV1. To our knowledge, this is the first report about a scorpion toxin that produces pain by targeting TRPV1. Identification of a pain-inducing compound may facilitate treating pain induced by scorpion envenomation.

  1. Scorpion Toxin, BmP01, Induces Pain by Targeting TRPV1 Channel.

    Science.gov (United States)

    Hakim, Md Abdul; Jiang, Wenbin; Luo, Lei; Li, Bowen; Yang, Shilong; Song, Yuzhu; Lai, Ren

    2015-09-01

    The intense pain induced by scorpion sting is a frequent clinical manifestation. To date, there is no established protocol with significant efficacy to alleviate the pain induced by scorpion envenomation. One of the important reasons is that, little information on pain-inducing compound from scorpion venoms is available. Here, a pain-inducing peptide (BmP01) has been identified and characterized from the venoms of scorpion (Mesobuthus martensii). In an animal model, intraplantar injection of BmP01 in mouse hind paw showed significant acute pain in wild type (WT) mice but not in TRPV1 knock-out (TRPV1 KO) mice during 30 min recording. BmP01 evoked currents in WT dorsal root ganglion (DRG) neurons but had no effect on DRG neurons of TRPV1 KO mice. Furthermore, OPEN ACCESS Toxins 2015, 7 3672 BmP01 evoked currents on TRPV1-expressed HEK293T cells, but not on HEK293T cells without TRPV1. These results suggest that (1) BmP01 is one of the pain-inducing agents in scorpion venoms; and (2) BmP01 induces pain by acting on TRPV1. To our knowledge, this is the first report about a scorpion toxin that produces pain by targeting TRPV1. Identification of a pain-inducing compound may facilitate treating pain induced by scorpion envenomation. PMID:26389953

  2. A feed-forward loop coupling extracellular BMP transport and morphogenesis in Drosophila wing.

    Directory of Open Access Journals (Sweden)

    Shinya Matsuda

    2013-03-01

    Full Text Available A variety of extracellular factors regulate morphogenesis during development. However, coordination between extracellular signaling and dynamic morphogenesis is largely unexplored. We address the fundamental question by studying posterior crossvein (PCV development in Drosophila as a model, in which long-range BMP transport from the longitudinal veins plays a critical role during the pupal stages. Here, we show that RhoGAP Crossveinless-C (Cv-C is induced at the PCV primordial cells by BMP signaling and mediates PCV morphogenesis cell-autonomously by inactivating members of the Rho-type small GTPases. Intriguingly, we find that Cv-C is also required non-cell-autonomously for BMP transport into the PCV region, while a long-range BMP transport is guided toward ectopic wing vein regions by loss of the Rho-type small GTPases. We present evidence that low level of ß-integrin accumulation at the basal side of PCV epithelial cells regulated by Cv-C provides an optimal extracellular environment for guiding BMP transport. These data suggest that BMP transport and PCV morphogenesis are tightly coupled. Our study reveals a feed-forward mechanism that coordinates the spatial distribution of extracellular instructive cues and morphogenesis. The coupling mechanism may be widely utilized to achieve precise morphogenesis during development and homeostasis.

  3. Cell-mediated BMP-2 liberation promotes bone formation in a mechanically unstable implant environment.

    Science.gov (United States)

    Hägi, Tobias T; Wu, Gang; Liu, Yuelian; Hunziker, Ernst B

    2010-05-01

    The flexible alloplastic materials that are used in bone-reconstruction surgery lack the mechanical stability that is necessary for sustained bone formation, even if this process is promoted by the application of an osteogenic agent, such as BMP-2. We hypothesize that if BMP-2 is delivered gradually, in a cell-mediated manner, to the surgical site, then the scaffolding material's lack of mechanical stability becomes a matter of indifference. Flexible discs of Ethisorb were functionalized with BMP-2, which was either adsorbed directly onto the material (rapid release kinetics) or incorporated into a calcium-phosphate coating (slow release kinetics). Unstabilized and titanium-plate-stabilized samples were implanted subcutaneously in rats and retrieved up to 14 days later for a histomorphometric analysis of bone and cartilage volumes. On day 14, the bone volume associated with titanium-plate-stabilized discs bearing an adsorbed depot of BMP-2 was 10-fold higher than that associated with their mechanically unstabilized counterparts. The bone volume associated with discs bearing a coating-incorporated depot of BMP-2 was similar in the mechanically unstabilized and titanium-plate-stabilized groups, and comparable to that associated with the titanium-plate-stabilized discs bearing an adsorbed depot of BMP-2. Hence, if an osteogenic agent is delivered in a cell-mediated manner (via coating degradation), ossification can be promoted even within a mechanically unstable environment.

  4. The toxic effects of Tris-(2,3-dibromopropyl)isocyanurate(TBC) on genes expression of bmp2b and bmp4 of zebrafish embryos

    Institute of Scientific and Technical Information of China (English)

    JIA Wan-jun

    2016-01-01

    We exposed zebrafish embryos to Tris-(2,3-dibromopropyl)isocyanurate(TBC)at the concentration of 20ppb, 100ppb, 400ppb, 1000ppb for 120h and 0.1%DMSO was set as the control group. Bmp2b and bmp4 were chosen perform RT-PCR to determine their genes expression level. The results showed that, TBC influenced their genes expression level in some extent and it significantly raised the genes expression level at the concentration of 20ppb.

  5. BMP-2 and BMP-2/7 Heterodimers Conjugated to a Fibrin/Hyaluronic Acid Hydrogel in a Large Animal Model of Mild Intervertebral Disc Degeneration.

    Science.gov (United States)

    Peeters, Mirte; Detiger, Suzanne E L; Karfeld-Sulzer, Lindsay S; Smit, Theo H; Yayon, Avner; Weber, Franz E; Helder, Marco N

    2015-01-01

    Intervertebral disc (IVD) degeneration is etiologically associated with low back pain and is currently only treated in severe cases with spinal fusion. Regenerative medicine attempts to restore degenerated tissue by means of cells, hydrogels, and/or growth factors and can therefore be used to slow, halt, or reverse the degeneration of the IVD in a minimally invasive manner. Previously, the growth factors bone morphogenetic proteins 2 and 7 (BMP-2, -7) were shown to enhance disc regeneration, in vitro and in vivo. Since BMPs have only a short in vivo half-life, and to prevent heterotopic ossification, we evaluated the use of a slow release system for BMP-2 homodimers and BMP-2/7 heterodimers for IVD regeneration. BMP growth factors were conjugated to a fibrin/hyaluronic acid (FB/HA) hydrogel and intradiscally injected in a goat model of mild IVD degeneration to study safety and efficacy. Mild degeneration was induced in five lumbar discs of seven adult Dutch milk goats, by injections with the enzyme chondroitinase ABC. After 12 weeks, discs were treated with either FB/HA-hydrogel only or supplemented with 1 or 5 μg/mL of BMP-2 or BMP-2/7. BMPs were linked to the FB/HA hydrogels using a transglutaminase moiety, to be released through an incorporated plasmin cleavage site. After another 12 weeks, goats were sacrificed and discs were assessed using radiography, MRI T2* mapping, and biochemical and histological analyses. All animals maintained weight throughout the study and no heterotopic bone formation or other adverse effects were noted during follow-up. Radiographs showed significant disc height loss upon induction of mild degeneration. MRI T2* mapping showed strong and significant correlations with biochemistry and histology as shown before. Surprisingly, no differences could be demonstrated in any parameter between intervention groups. To our knowledge, this is the first large animal study evaluating BMPs conjugated to an FB/HA-hydrogel for the treatment of

  6. Implant Composed of Demineralized Bone and Mesenchymal Stem Cells Genetically Modified with AdBMP2/AdBMP7 for the Regeneration of Bone Fractures in Ovis aries

    Science.gov (United States)

    Hernandez-Hurtado, Adelina A.; Lara-Arias, Jorge; Romero-Diaz, Viktor J.; Abrego-Guerra, Adalberto; Vilchez-Cavazos, Jose F.; Elizondo-Riojas, Guillermo; Martinez-Rodriguez, Herminia G.; Espinoza-Juarez, Marcela A.; Mendoza Lemus, Oscar F.

    2016-01-01

    Adipose-derived mesenchymal stem cells (ADMSCs) are inducible to an osteogenic phenotype by the bone morphogenetic proteins (BMPs). This facilitates the generation of implants for bone tissue regeneration. This study evaluated the in vitro osteogenic differentiation of ADMSCs transduced individually and in combination with adenoviral vectors expressing BMP2 and BMP7. Moreover, the effectiveness of the implant containing ADMSCs transduced with the adenoviral vectors AdBMP2/AdBMP7 and embedded in demineralized bone matrix (DBM) was tested in a model of tibial fracture in sheep. This graft was compared to ewes implanted with untransduced ADMSCs embedded in the same matrix and with injured but untreated animals. In vivo results showed accelerated osteogenesis in the group treated with the AdBMP2/AdBMP7 transduced ADMSC graft, which also showed improved restoration of the normal bone morphology.

  7. Differential expression of a BMP4 reporter allele in anterior fungiform versus posterior circumvallate taste buds of mice

    Directory of Open Access Journals (Sweden)

    Barlow Linda A

    2010-10-01

    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

  8. BMP treatment of C3H10T1/2 mesenchymal stem cells induces both chondrogenesis and osteogenesis.

    Science.gov (United States)

    Shea, Colleen M; Edgar, Cory M; Einhorn, Thomas A; Gerstenfeld, Louis C

    2003-12-15

    The molecular mechanisms by which bone morphogenetic proteins (BMPs) promote skeletal cell differentiation were investigated in the murine mesenchymal stem cell line C3H10T1/2. Both BMP-7 and BMP-2 induced C3H10T1/2 cells to undergo a sequential pattern of chondrogenic followed by osteogenic differentiation that was dependent on both the concentration and the continuous presence of BMP in the growth media. Differentiation was determined by the expression of chondrogenesis and osteogenesis associated matrix genes. Subsequent experiments using BMP-7 demonstrated that withdrawal of BMP from the growth media led to a complete loss of skeletal cell differentiation accompanied by adipogenic differentiation of these cells. Continuous treatment with BMP-7 increased the expression of Sox9, Msx 2, and c-fos during the periods of chondrogenic differentiation after which point their expression decreased. In contrast, Dlx 5 expression was induced by BMP-7 treatment and remained elevated throughout the time-course of skeletal cell differentiation. Runx2/Cbfa1 was not detected by ribonuclease protection assay (RPA) and did not appear to be induced by BMP-7. The sequential nature of differentiation of chondrocytic and osteoblastic cells and the necessity for continuous BMP treatment to maintain skeletal cell differentiation suggests that the maintenance of selective differentiation of the two skeletal cell lineages might be dependent on BMP-7-regulated expression of other morphogenetic factors. An examination of the expression of Wnt, transforming growth factor-beta (TGF-beta), and the hedgehog family of morphogens showed that Wnt 5b, Wnt 11, BMP-4, growth and differentiation factor-1 (GDF-1), Sonic hedgehog (Shh), and Indian hedgehog (Ihh) were endogenously expressed by C3H10T1/2 cells. Wnt 11, BMP-4, and GDF-1 expression were inhibited by BMP-7 treatment in a dose-dependent manner while Wnt 5b and Shh were selectively induced by BMP-7 during the period of chondrogenic

  9. Combination therapy with BMP-2 and a systemic RANKL inhibitor enhances bone healing in a mouse critical-sized femoral defect.

    Science.gov (United States)

    Bougioukli, Sofia; Jain, Ashish; Sugiyama, Osamu; Tinsley, Brian A; Tang, Amy H; Tan, Matthew H; Adams, Douglas J; Kostenuik, Paul J; Lieberman, Jay R

    2016-03-01

    Recombinant human BMP-2 (rhBMP-2) is a potent osteoinductive agent, but has been associated not only with bone formation, but also osteoclastogenesis and bone resorption. Osteoprotegerin (OPG) is a RANKL inhibitor that blocks differentiation and function of osteoclasts. We hypothesized that the combination of local BMP-2 (recombinant protein or a product of gene therapy) plus systemic OPG-Fc is more effective than BMP-2 alone in promoting bone repair. To test this hypothesis we used a mouse critical-sized femoral defect model. Col2.3eGFP (osteoblastic marker) male mice were treated with rhBMP-2 (group I), rhBMP-2 and systemic OPG (group II), rhBMP-2 and delayed administration of OPG (group III), mouse BM cells transduced with a lentiviral vector containing the BMP-2 gene (LV-BMP-2; group IV), LV-BMP-2 and systemic OPG (group V), a carrier alone (group VI) and administration of OPG alone (group VII). All bone defects treated with BMP-2 (alone or combined with OPG) healed, whereas minimal bone formation was noted in animals treated with the carrier alone or OPG alone. MicroCT analysis showed that bone volume (BV) in rhBMP-2+OPG and LV-BMP-2+OPG groups was significantly higher compared to rhBMP-2 alone (p<0.01) and LV-BMP-2 alone (p<0.001). Similar results were observed in histomorphometry, with rhBMP-2 alone defects exhibiting significantly lower bone area (B.Ar) compared to rhBMP-2+OPG defects (p<0.005) and LV-BMP-2 defects having a significantly lower B.Ar compared to all BMP-2+OPG treated groups (p≤0.01). TRAP staining demonstrated a major osteoclast response in the groups that did not receive OPG (rhBMP-2, LV-BMP-2 and sponge alone) beginning as early as 7days post-operatively. In conclusion, we demonstrated that locally delivered BMP-2 (recombinant protein or gene therapy) in combination with systemically administered OPG improved bone healing compared to BMP-2 alone in a mouse critical-sized bone defect. These data indicate that osteoclasts can diminish

  10. Handbook methane potential; Handbok metanpotential

    Energy Technology Data Exchange (ETDEWEB)

    Carlsson, My (AnoxKaldnes AB (Sweden)); Schnurer, Anna (Swedish Univ. of Agricultural Sciences, Uppsala (Sweden))

    2011-07-15

    Before using a organic material for biogas production it is essential to evaluate the methane production potential. The methane potential is one important tool possible to use during planning of new plants but also when new materials are considered for already running biogas plants. The chemical composition of different organic material varies extensively and this will have an impact on both the degradability and the methane potential. Information about the methane potential of a specific material can sometimes be found in the literature or can be calculated after a chemical/ physical or biological characterization. Here, the BMP test (Biochemical Methane Potential) is a commonly used method. Today the BMP test is a commonly used method to determine the methane potential. Many national and international research groups, consultants as well as personal at biogas plants are using this method and there is a lot of data available in the literature from such tests. In addition there are several protocols giving guidelines on how to execute a BMP-test. The BMP-test is performed in many different ways, not always under optimized conditions, and there is a lack of information on how to interpret the obtained data. This report summarizes knowledge from the literature and the experience from a Swedish referee group, consisting of persons being active performers of BMP-tests. The report does not include a standardized protocol as the procedure can be performed in different ways depending on available equipment and on the type of material to be tested. Instead the report discusses different factors of great importance for a successful test giving reliable results. The report also summarizes important information concerning the interpretation and how to present results in order to allow comparison of data from different test.

  11. Zygotic LvBMP5-8 is required for skeletal patterning and for left-right but not dorsal-ventral specification in the sea urchin embryo.

    Science.gov (United States)

    Piacentino, Michael L; Chung, Oliver; Ramachandran, Janani; Zuch, Daniel T; Yu, Jia; Conaway, Evan A; Reyna, Arlene E; Bradham, Cynthia A

    2016-04-01

    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.

  12. BMP4-mediated brown fat-like changes in white adipose tissue alter glucose and energy homeostasis

    OpenAIRE

    Qian, Shu-Wen; Tang, Yan; Li, Xi; Liu, Yuan; Zhang, You-you; Huang, Hai-yan; Xue, Rui-Dan; Yu, Hao-Yong; Guo, Liang; Gao, Hui-Di; Liu, Yan; Sun, Xia; Li, Yi-ming; Jia, Wei-Ping; Tang, Qi-Qun

    2013-01-01

    Expression of bone morphogenetic protein 4 (BMP4) in adipocytes of white adipose tissue (WAT) produces “white adipocytes” with characteristics of brown fat and leads to a reduction of adiposity and its metabolic complications. Although BMP4 is known to induce commitment of pluripotent stem cells to the adipocyte lineage by producing cells that possess the characteristics of preadipocytes, its effects on the mature white adipocyte phenotype and function were unknown. Forced expression of a BMP...

  13. Smad1 and its target gene Wif1 coordinate BMP and Wnt signaling activities to regulate fetal lung development

    OpenAIRE

    Xu, Bing; Chen, Cheng; Chen, Hui; Zheng, Song-Guo; Bringas, Pablo; Xu, Min; Zhou, Xianghong; Chen, Di; Umans, Lieve; Zwijsen, An; SHI, Wei

    2011-01-01

    Bone morphogenetic protein 4 (Bmp4) is essential for lung development. To define the intracellular signaling mechanisms by which Bmp4 regulates lung development, BMP-specific Smad1 or Smad5 was selectively knocked out in fetal mouse lung epithelial cells. Abrogation of lung epithelial-specific Smad1, but not Smad5, resulted in retardation of lung branching morphogenesis and reduced sacculation, accompanied by altered distal lung epithelial cell proliferation and differentiation and, consequen...

  14. Reduced BMP signaling results in hindlimb fusion with lethal pelvic/urogenital organ aplasia: a new mouse model of sirenomelia.

    Directory of Open Access Journals (Sweden)

    Kentaro Suzuki

    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.

  15. Algal wastewater treatment and biomass producing potential: nutrient removal efficiency and cell physiological responses

    OpenAIRE

    Samorì, Giulia

    2012-01-01

    Microalgae are sun - light cell factories that convert carbon dioxide to biofuels, foods, feeds, and other bioproducts. The concept of microalgae cultivation as an integrated system in wastewater treatment has optimized the potential of the microalgae - based biofuel production. These microorganisms contains lipids, polysaccharides, proteins, pigments and other cell compounds, and their biomass can provide different kinds of biofuels such as biodiesel, biomethane and ethanol. The algal biomas...

  16. Biomethanation of vegetable market waste in an anaerobic baffled reactor: Effect of effluent recirculation and carbon mass balance analysis.

    Science.gov (United States)

    Gulhane, Madhuri; Khardenavis, Anshuman A; Karia, Sneha; Pandit, Prabhakar; Kanade, Gajanan S; Lokhande, Satish; Vaidya, Atul N; Purohit, Hemant J

    2016-09-01

    In the present study, feasibility of biomethanation of vegetable market waste in a 4-chambered anaerobic baffled reactor (ABR) was investigated at 30d hydraulic retention time and organic loading rate of 0.5gVS/L/d for one year. Indicators of process stability viz., butyrate/acetate and propionate/acetate ratios were consistent with phase separation in the different chambers, which remained unaltered even during recirculation of effluent. Chemical oxygen demand (COD) and volatile solids (VS) removal efficiencies were observed to be consistently high (above 90%). Corresponding biogas and methane yields of 0.7-0.8L/g VS added/d and 0.42-52L/g VS added/d respectively were among the highest reported in case of AD of vegetable waste in an ABR. Process efficiency of the ABR for vegetable waste methanation, which is indicated by carbon recovery factor showed that, nearly 96.7% of the input carbon considered for mass balance was accounted for in the product. PMID:27133362

  17. Performance and microbial community analysis of the anaerobic reactor with coke oven gas biomethanation and in situ biogas upgrading.

    Science.gov (United States)

    Wang, Wen; Xie, Li; Luo, Gang; Zhou, Qi; Angelidaki, Irini

    2013-10-01

    A new method for simultaneous coke oven gas (COG) biomethanation and in situ biogas upgrading in anaerobic reactor was developed in this study. The simulated coke oven gas (SCOG) (92% H2 and 8% CO) was injected directly into the anaerobic reactor treating sewage sludge through hollow fiber membrane (HFM). With pH control at 8.0, the added H2 and CO were fully consumed and no negative effects on the anaerobic degradation of sewage sludge were observed. The maximum CH4 content in the biogas was 99%. The addition of SCOG resulted in enrichment and dominance of homoacetogenetic genus Treponema and hydrogenotrophic genus Methanoculleus in the liquid, which indicated that H2 were converted to methane by both direct (hydrogenotrophic methanogenesis) and indirect (homoacetogenesis+aceticlastic methanogenesis) pathways in the liquid. However, the aceticlasitic genus Methanosaeta was dominant for archaea in the biofilm on the HFM, which indicated indirect (homoacetogenesis+aceticlastic methanogenesis) H2 conversion pathway on the biofilm. PMID:23941705

  18. The effect of seasonal variation on biomethane production from seaweed and on application as a gaseous transport biofuel.

    Science.gov (United States)

    Tabassum, Muhammad Rizwan; Xia, Ao; Murphy, Jerry D

    2016-06-01

    Biomethane produced from seaweed may be used as a transport biofuel. Seasonal variation will have an effect on this industry. Laminaria digitata, a typical Irish brown seaweed species, shows significant seasonal variation both in proximate, ultimate and biochemical composition. The characteristics in August were optimal with the lowest level of ash (20% of volatile solids), a C:N ratio of 32 and the highest specific methane yield measured at 327LCH4kgVS(-1), which was 72% of theoretical yield. The highest yield per mass collected of 53m(3)CH4t(-1) was achieved in August, which is 4.5 times higher than the lowest value, obtained in December. A seaweed cultivation area of 11,800ha would be required to satisfy the 2020 target for advanced biofuels in Ireland, of 1.25% renewable energy supply in transport (RES-T) based on the optimal gross energy yield obtained in August (200GJha(-1)yr(-1)). PMID:26970924

  19. GHG emission factors for bioelectricity, biomethane, and bioethanol quantified for 24 biomass substrates with consequential life-cycle assessment.

    Science.gov (United States)

    Tonini, Davide; Hamelin, Lorie; Alvarado-Morales, Merlin; Astrup, Thomas Fruergaard

    2016-05-01

    Greenhouse gas (GHG) emission savings from biofuels dramatically depend upon the source of energy displaced and the effects induced outside the energy sector, for instance land-use changes (LUC). Using consequential life-cycle assessment and including LUC effects, this study provides GHG emission factors (EFs) for bioelectricity, biomethane, and bioethanol produced from twenty-four biomasses (from dedicated crops to residues of different origin) under a fossil and a non-fossil energy system. Accounting for numerous variations in the pathways, a total of 554 GHG EFs were quantified. The results showed that, important GHG savings were obtained with residues and seaweed, both under fossil and non-fossil energy systems. For high-yield perennial crops (e.g. willow and Miscanthus), GHG savings were achieved only under fossil energy systems. Biofuels from annual crops and residues that are today used in the feed sector should be discouraged, as LUC GHG emissions exceeded any GHG savings from displacing conventional energy sources. PMID:26938807

  20. Interactions between BMP-7 and USAG-1 (uterine sensitization-associated gene-1 regulate supernumerary organ formations.

    Directory of Open Access Journals (Sweden)

    Honoka Kiso

    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.

  1. CONSTRUCTION OF RECOMBINANT PLASMID pcDNA3.1/BMP-2 AND ITS INVOLVEMENT IN DIFFERENTIATION OF HUMAN DENTAL PULP-DERIVED CELLS INTO AN ODONTOBLASTIC LINEAGE

    Directory of Open Access Journals (Sweden)

    Boy M. Bachtiar

    2009-06-01

    Full Text Available Experimental studies have shown that dental pulp tissue has potential to regenerate dentine in response to adverse stimuli, such as caries and associated operative procedures. However, the potential of dental pulp regeneration seems to be limited by regenerative capacity of the cell involved. In this study, we report the effect of transfection of a recombinant plasmid containing human BMP-2 gene in proliferation and differentiation of dental pulp tissue in vitro. The regenerative capacity was analyzed by ALP production and calcium content. Results showed that the transfected dental pulp cell was able to differentiate into the odontoblast phenotype, indicating the presence of odontoblast progentitor cells in dental pulp tissue.

  2. Regulating the osteogenic function of rhBMP 2 by different titanium surface properties.

    Science.gov (United States)

    Xiao, Ming; Biao, Meina; Chen, Yangmei; Xie, Meiju; Yang, Bangcheng

    2016-08-01

    Bone morphogenetic protein 2 (BMP-2) is important for regulating the osteogenic differentiation of mesenchymal stem cells and the response of bone tissue. It adsorbs on the surface of biomedical implants immediately and plays a role of mediator between the materials surfaces and the host cells. Studies usually connect the material surface properties and the new bone formation directly. However, interaction between the adsorbed BMP-2 on the implant surface and the cells in the tissue is the key to explaining the osteogenic properties of the material. So, in this article, we investigated the conformational and functional changes induced by the surface modified titanium metals. We found that the α-helix and β-sheet structure of rhBMP-2 can be well maintained on the anodic oxidation treated titanium surface. The osteogenic function of rhBMP-2 can sustain for a relatively long time even though there is less amount adhere to the surface compared with that on the acid alkali treated titanium. Surface properties, especially the morphology enable a larger amount of rhBMP-2 to adsorb to the surface of the acid alkali treated titanium, but the conformation of the protein is severely influenced. The percentage of α-helix structure is also significantly decreased so that the efficacy of rhBMP-2 is only maintained in the early time. This study indicated that different surface modification of the surface could regulate the structure of rhBMP-2 and then further influence its osteogenic function. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 1882-1893, 2016. PMID:26991341

  3. Induction of chondrogenesis and expression of superficial zone protein (SZP)/lubricin by mesenchymal progenitors in the infrapatellar fat pad of the knee joint treated with TGF-beta1 and BMP-7.

    Science.gov (United States)

    Lee, Sang Yang; Nakagawa, Toshiyuki; Reddi, A Hari

    2008-11-01

    Superficial zone protein (SZP) is a key mediator of boundary lubrication of articular cartilage in joints. In this investigation, we made the unexpected discovery that SZP was expressed in infrapatellar fat pad (IFP) from bovine knee. Quantitative analysis of secreted proteins in the medium of the IFP stromal cells demonstrated a significant stimulation by TGF-beta1 and BMP-7. Real-time PCR analysis revealed the SZP expression was up-regulated by TGF-beta1 and BMP-7. Chondrogenically differentiated IFP progenitor cells were stimulated by TGF-beta1 and BMP-7 to synthesize and secrete SZP. SZP mRNA was significantly up-regulated by chondrogenic induction for 21 days. These findings indicate that the stimulation of SZP expression by TGF-beta and BMP-7 may lead to functional improvement of damaged intraarticular tissues and that IFP progenitor cells may be a potential useful source for inducing superficial zone of articular cartilage by tissue engineering for regeneration of damaged articular cartilage due to osteoarthritis.

  4. Binding Interactions of Keratin-Based Hair Fiber Extract to Gold, Keratin, and BMP-2.

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    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

  5. No advantage to rhBMP-2 in addition to autogenous graft for fracture nonunion.

    Science.gov (United States)

    Takemoto, Richelle; Forman, Jordanna; Taormina, David P; Egol, Kenneth A

    2014-06-01

    Bone morphogenetic proteins are a necessary component of the fracture healing cascade. Few studies have delineated the efficacy of iliac crest bone graft and recombinant human bone morphogenetic protein 2 (rhBMP-2), especially, in comparison with the gold standard treatment of nonunion, which is autogenous bone graft alone. This study compared the outcome of patients with fracture nonunion treated with autogenous bone graft plus rhBMP-2 adjuvant vs patients treated with autogenous bone graft alone. A total of 118 consecutive patients who were to undergo long bone nonunion surgery with autogenous bone graft (50) or autogenous bone graft plus rhBMP-2 (68) were identified. Surgical intervention included either harvested iliac autogenous bone graft or autogenous bone graft plus 1.5 mg/mL of rhBMP-2 placed in and around the site of nonunion. No differences were found in the distribution of nonunion sites included within each group. Twelve-month follow-up was obtained on 100 of 118 patients (84.7%). Analyses of demographic characteristics (including tobacco), medical comorbidities, previous surgeries, and nonunion type (atrophic vs hypertrophic) did not differ. Postoperative complication rates did not differ. The percentage of patients who progressed to union did not differ. Mean time to union in the autogenous bone graft plus rhBMP-2 group was 6.6 months (±3.9) vs 5.4 (±2.7) months in the autogenous bone graft-only group (P=.06). Rates of revision (16.2% for rhBMP-2 plus autogenous bone graft vs 8% for autogenous bone graft) did not differ statistically (P=.19), nor did 12-month scores of pain and functional assessment. Although rhBMP-2 is a safe adjuvant, there was no benefit seen when rhBMP-2 was added to autogenous bone graft in the treatment of long bone nonunion. Given its high cost, rhBMP-2 should be reconsidered as an aid to autogenous bone graft in the treatment of nonunion. PMID:24972432

  6. High-purity magnesium interference screws promote fibrocartilaginous entheses regeneration in the anterior cruciate ligament reconstruction rabbit model via accumulation of BMP-2 and VEGF.

    Science.gov (United States)

    Cheng, Pengfei; Han, Pei; Zhao, Changli; Zhang, Shaoxiang; Wu, Hongliu; Ni, Jiahua; Hou, Peng; Zhang, Yuanzhuang; Liu, Jingyi; Xu, Haidong; Liu, Shen; Zhang, Xiaonong; Zheng, Yufeng; Chai, Yimin

    2016-03-01

    Interference screw in the fixation of autologous tendon graft to the bone tunnel is widely accepted for the reconstruction of anterior cruciate ligament (ACL), but the regeneration of fibrocartilaginous entheses could hardly be achieved with the traditional interference screw. In the present work, biodegradable high-purity magnesium (HP Mg) showed good cytocompatibility and promoted the expression of bone morphogenetic protein-2 (BMP-2) and vascular endothelial growth factor (VEGF), fibrocartilage markers (Aggrecan, COL2A1 and SOX-9), and glycosaminoglycan (GAG) production in vitro. The HP Mg screw was applied to fix the semitendinosus autograft to the femoral tunnel in a rabbit model of ACL reconstruction with titanium (Ti) screw as the control. The femur-tendon graft-tibia complex was retrieved at 3, 6, 9 and 12 weeks. Gross observation and range of motion (ROM) of the animal model reached normal levels at 12 weeks. No sign of host reaction was found in the X-ray scanning. The HP Mg group was comparable to the Ti group with respect to biomechanical properties of the reconstructed ACL, and the ultimate load to failure and stiffness increased 12 weeks after surgery. In the histological analysis, the HP Mg group formed distinct fibrocartilage transition zones at the tendon-bone interface 12 weeks after surgery, whereas a disorganized fibrocartilage layer was found in the Ti group. In the immunohistochemical analysis, highly positive staining of BMP-2, VEGF and the specific receptor for BMP-2 (BMPR1A) was shown at the tendon-bone interface of the HP Mg group compared with the Ti group. Furthermore, the HP Mg group had significantly higher expression of BMP-2 and VEGF than the Ti group in the early phase of tendon-bone healing, followed by enhanced expression of fibrocartilage markers and GAG production. Therefore we proposed that the stimulation of BMP-2 and VEGF by Mg ions was responsible for the fibrochondrogenesis of Mg materials. HP Mg was promising as a

  7. Cooperative inputs of Bmp and Fgf signaling induce tail regeneration in urodele amphibians.

    Science.gov (United States)

    Makanae, Aki; Mitogawa, Kazumasa; Satoh, Akira

    2016-02-01

    Urodele amphibians have remarkable organ regeneration ability. They can regenerate not only limbs but also a tail throughout their life. It has been demonstrated that the regeneration of some organs are governed by the presence of neural tissues. For instance, limb regeneration cannot be induced without nerves. Thus, identifying the nerve factors has been the primary focus in amphibian organ regeneration research. Recently, substitute molecules for nerves in limb regeneration, Bmp and Fgfs, were identified. Cooperative inputs of Bmp and Fgfs can induce limb regeneration in the absence of nerves. In the present study, we investigated whether similar or same regeneration mechanisms control another neural tissue governed organ regeneration, i.e., tail regeneration, in Ambystoma mexicanum. Neural tissues in a tail, which is the spinal cord, could transform wound healing responses into organ regeneration responses, similar to nerves in limb regeneration. Furthermore, the identified regeneration inducer Fgf2+Fgf8+Bmp7 showed similar inductive effects. However, further analysis revealed that the blastema cells induced by Fgf2+Fgf8+Bmp7 could participate in the regeneration of several tissues, but could not organize a patterned tail. Regeneration inductive ability of Fgf2+Fgf8+Bmp7 was confirmed in another urodele, Pleurodeles waltl. These results suggest that the organ regeneration ability in urodele amphibians is controlled by a common mechanism. PMID:26703427

  8. Cooperative inputs of Bmp and Fgf signaling induce tail regeneration in urodele amphibians.

    Science.gov (United States)

    Makanae, Aki; Mitogawa, Kazumasa; Satoh, Akira

    2016-02-01

    Urodele amphibians have remarkable organ regeneration ability. They can regenerate not only limbs but also a tail throughout their life. It has been demonstrated that the regeneration of some organs are governed by the presence of neural tissues. For instance, limb regeneration cannot be induced without nerves. Thus, identifying the nerve factors has been the primary focus in amphibian organ regeneration research. Recently, substitute molecules for nerves in limb regeneration, Bmp and Fgfs, were identified. Cooperative inputs of Bmp and Fgfs can induce limb regeneration in the absence of nerves. In the present study, we investigated whether similar or same regeneration mechanisms control another neural tissue governed organ regeneration, i.e., tail regeneration, in Ambystoma mexicanum. Neural tissues in a tail, which is the spinal cord, could transform wound healing responses into organ regeneration responses, similar to nerves in limb regeneration. Furthermore, the identified regeneration inducer Fgf2+Fgf8+Bmp7 showed similar inductive effects. However, further analysis revealed that the blastema cells induced by Fgf2+Fgf8+Bmp7 could participate in the regeneration of several tissues, but could not organize a patterned tail. Regeneration inductive ability of Fgf2+Fgf8+Bmp7 was confirmed in another urodele, Pleurodeles waltl. These results suggest that the organ regeneration ability in urodele amphibians is controlled by a common mechanism.

  9. BMP13 Prevents the Effects of Annular Injury in an Ovine Model

    Directory of Open Access Journals (Sweden)

    Aiqun Wei, Lisa A Williams, Divya Bhargav, Bojiang Shen, Thomas Kishen, Neil Duffy, Ashish D Diwan

    2009-01-01

    Full Text Available Chronic back pain is a global health problem affecting millions of people worldwide and carries significant economic and social morbidities. Intervertebral disc damage and degeneration is a major cause of back pain, characterised by histological and biochemical changes that have been well documented in animal models. Recently there has been intense interest in early intervention in disc degeneration using growth factors or stem cell transplantation, to replenish the diseased tissues. Bone Morphogenetic Proteins (BMPs have been approved for clinical use in augmenting spinal fusions, and may represent candidate molecules for intervertebral disc regeneration. BMP13 has an important role in embryonic development and recent genetic evidence shows a role in the development of the human spine. This study explores the effect of BMP13 on a damaged intervertebral disc in an ovine model of discal degeneration. We found that, when injected at the time of injury, BMP13 reversed or arrested histological changes that occurred in the control discs such as loss of extracellular matrix proteins. In addition, BMP13 injected discs retained greater hydration after 4months, and possessed more cells in the NP. Taken together, BMP13 may be a potent clinical therapeutic agent when used early in the degeneration cascade to promote healthy disc tissue.

  10. Tracheal cartilage regeneration and new bone formation by slow release of bone morphogenetic protein (BMP)-2.

    Science.gov (United States)

    Igai, Hitoshi; Chang, Sung Soo; Gotoh, Masashi; Yamamoto, Yasumichi; Yamamoto, Masaya; Tabata, Yasuhiko; Yokomise, Hiroyasu

    2008-01-01

    We investigated the efficiency of bone morphogenetic protein (BMP)-2 released slowly from gelatin sponge for tracheal cartilage regeneration. A 1-cm gap was made in the mid-ventral portion of each of 10 consecutive tracheal cartilages. In the control group (n = 4), the resulting gap was left untreated. In the gelatin group (n = 4), plain gelatin was implanted in the gap. In the BMP-2 group (n = 4), gelatin containing 100 microg BMP-2 was implanted. We euthanatized all dogs in each group at 1, 3, 6, and 12 months after the implantation, respectively, and then examined the implant site macro- and microscopically. In the BMP-2 group, regenerated fibrous cartilage and newly formed bone were observed at 1 and 12 months. Regenerated cartilage was observed at the ends of the host cartilage stumps, with newly formed bone in the middle portion. The gaps were filled with regenerated cartilage and newly formed bone. At 3 and 6 months, regenerated cartilage, but not newly formed bone, was evident. The regenerated cartilage was covered with perichondrium and showed continuity with the host cartilage. We succeeded in inducing cartilage regeneration and new bone formation in canine trachea by slow release of 100 microg BMP-2 from gelatin. PMID:18204324

  11. A late role for bmp2b in the morphogenesis of semicircular canal ducts in the zebrafish inner ear.

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    Katherine L Hammond

    Full Text Available The Bone Morphogenetic Protein (BMP genes bmp2 and bmp4 are expressed in highly conserved patterns in the developing vertebrate inner ear. It has, however, proved difficult to elucidate the function of BMPs during ear development as mutations in these genes cause early embryonic lethality. Previous studies using conditional approaches in mouse and chicken have shown that Bmp4 has a role in semicircular canal and crista development, but there is currently no direct evidence for the role of Bmp2 in the developing inner ear.We have used an RNA rescue strategy to test the role of bmp2b in the zebrafish inner ear directly. Injection of bmp2b or smad5 mRNA into homozygous mutant swirl (bmp2b(-/- embryos rescues the early patterning defects in these mutants and the fish survive to adulthood. As injected RNA will only last, at most, for the first few days of embryogenesis, all later development occurs in the absence of bmp2b function. Although rescued swirl adult fish are viable, they have balance defects suggestive of vestibular dysfunction. Analysis of the inner ears of these fish reveals a total absence of semicircular canal ducts, structures involved in the detection of angular motion. All other regions of the ear, including the ampullae and cristae, are present and appear normal. Early stages of otic development in rescued swirl embryos are also normal.Our findings demonstrate a critical late role for bmp2b in the morphogenesis of semicircular canals in the zebrafish inner ear. This is the first demonstration of a developmental role for any gene during post-embryonic stages of otic morphogenesis in the zebrafish. Despite differences in the early stages of semicircular canal formation between zebrafish and amniotes, the role of Bmp2 in semicircular canal duct outgrowth is likely to be conserved between different vertebrate species.

  12. An FGF3-BMP Signaling Axis Regulates Caudal Neural Tube Closure, Neural Crest Specification and Anterior-Posterior Axis Extension.

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    Matthew J Anderson

    2016-05-01

    Full Text Available During vertebrate axis extension, adjacent tissue layers undergo profound morphological changes: within the neuroepithelium, neural tube closure and neural crest formation are occurring, while within the paraxial mesoderm somites are segmenting from the presomitic mesoderm (PSM. Little is known about the signals between these tissues that regulate their coordinated morphogenesis. Here, we analyze the posterior axis truncation of mouse Fgf3 null homozygotes and demonstrate that the earliest role of PSM-derived FGF3 is to regulate BMP signals in the adjacent neuroepithelium. FGF3 loss causes elevated BMP signals leading to increased neuroepithelium proliferation, delay in neural tube closure and premature neural crest specification. We demonstrate that elevated BMP4 depletes PSM progenitors in vitro, phenocopying the Fgf3 mutant, suggesting that excessive BMP signals cause the Fgf3 axis defect. To test this in vivo we increased BMP signaling in Fgf3 mutants by removing one copy of Noggin, which encodes a BMP antagonist. In such mutants, all parameters of the Fgf3 phenotype were exacerbated: neural tube closure delay, premature neural crest specification, and premature axis termination. Conversely, genetically decreasing BMP signaling in Fgf3 mutants, via loss of BMP receptor activity, alleviates morphological defects. Aberrant apoptosis is observed in the Fgf3 mutant tailbud. However, we demonstrate that cell death does not cause the Fgf3 phenotype: blocking apoptosis via deletion of pro-apoptotic genes surprisingly increases all Fgf3 defects including causing spina bifida. We demonstrate that this counterintuitive consequence of blocking apoptosis is caused by the increased survival of BMP-producing cells in the neuroepithelium. Thus, we show that FGF3 in the caudal vertebrate embryo regulates BMP signaling in the neuroepithelium, which in turn regulates neural tube closure, neural crest specification and axis termination. Uncovering this FGF3

  13. Good practice examples for the management and logistics of organic urban waste: Urban waste for biomethane grid injection and transport in urban areas

    OpenAIRE

    Niklass, M.; Pubule, J.; Hahn, H.; Rutz, D.; Günert, D.; Surowiec, D.; Ribic, B.; Schinnerl, D.

    2012-01-01

    This report was elaborated in the framework of the UrbanBiogas project (Urban waste for biomethane grid injection and transport in urban areas). The objective of this report is to show in short factsheets 11 examples of the management and logistics of organic urban waste in different European countries. This should provide input to the UrbanBiogas target cities City of Zagreb (Croatia), Municipality of Abrantes (Portugal), City of Graz (Austria), City of Rzeszów (Poland), and North Vidzeme Re...

  14. Methane from CO₂: Influence of different CO₂ concentrations in the flush gas on the methane production in BMP tests.

    Science.gov (United States)

    Koch, Konrad; Huber, Bettina; Fernández, Yadira Bajón; Drewes, Jörg E

    2016-03-01

    The influence of carbon dioxide (CO2) in the headspace gas on the specific methane (CH4) production of blank samples with just inoculum during Biochemical Methane Potential (BMP) tests was studied. The headspace of the bottles had been flushed with 15 different ratios of CO2 and N2 prior to incubation, while they were treated otherwise identically. The results revealed that the CH4 yield increased linearly with higher ratio of CO2 in the flush gas reaching a 30% higher yield at pure CO2 relative to pure N2 headspace conditions. However, a slightly distinct lag is noticeable during the initial phase of the degradation process at high ratios of CO2, hypothesizing a reversible disturbance of the biocenosis. Further experiments and analyses need to be performed to elucidate the underlying mechanisms. PMID:26818184

  15. Overexpression of MyrAkt1 in endothelial cells leads to erythropoietin- and BMP4-independent splenic erythropoiesis in mice.

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    Rebekah K O'Donnell

    Full Text Available Under steady state conditions, erythropoiesis occurs in the bone marrow. However, in mice, stress or tissue hypoxia results in increased erythropoiesis in the spleen. There is increasing evidence that the hematopoietic microenvironment, including endothelial cells, plays an important role in regulating erythropoiesis. Here, we show that short-term expression of constitutively active Akt in the endothelium of mice results in non-anemic stress erythropoiesis in the spleen. The initiation of this stress response was independent of erythropoietin and BMP4, and was observed in endothelial myrAkt1 mice reconstituted with wild-type bone marrow. Together, these data suggest that endothelial cell hyperactivation is a potentially novel pathway of inducing red cell production under stress.

  16. Does Recombinant Human Bone Morphogenetic Protein-2 (rhBMP-2) Use in Adult Spinal Deformity (ASD) Increase Complications and Are Complications Associated With Location of rhBMP-2 Use?: A Prospective, Multicenter Study of 279 Consecutive Patients.

    Science.gov (United States)

    Bess, Shay; Line, Breton G; Lafarge, Virginie; Schwab, Frank; Shaffrey, Christopher I; Hart, Robert A; Boachie-Adjei, Oheneba; Akbarnia, Behrooz A; Ames, Christopher P; Burton, Douglas C; Deverin, Vedat; Fu, Kai-Ming G; Gupta, Munish; Hostin, Richard; Kebaish, Khaled; Klineberg, Eric; Mundis, Gregory; O'Brien, Michael; Shelokov, Alexis; Smith, Justin S

    2013-11-18

    Study Design. Multi-center, prospective analysis of consecutive ASD patients.Objective. Evaluate complications associated with rhBMP-2 use in ASDSummary of Background Data. Off-label rhBMP-2 use is common, however under-reporting of rhBMP-2 associated complications has been recently scrutinized.Methods. ASD patients consecutively enrolled into a prospective, multicenter database, were evaluated for type and timing of acute perioperative complications. Inclusion criteria: age ≥ 18 years, ASD, spinal arthrodesis >4 levels, and ≥3 months follow-up. Patients divided into those receiving rhBMP-2 (BMP) or no rhBMP-2 (NOBMP). BMP divided into location of use: posterior (PBMP), interbody (IBMP), and interbody + posterior spine (I+PBMP). Correlations between acute perioperative complications and rhBMP-2 use including total dose, dose/level and location of use were evaluated.Results. 279 patients (mean age 57 years, mean spinal levels fused 12.0, mean follow-up 28.8 months) met inclusion criteria. BMP (n = 172; average posterior dose = 2.5 mg/level, average interbody dose = 5 mg/level) had similar age, smoking history, previous spine surgery, total spinal levels fused, estimated blood loss, and duration of hospital stay as NOBMP (n = 107; p>0.05). BMP had greater Charlson Comorbidity Index (1.9 vs. 1.2), greater scoliosis (43° vs. 38°), longer operative time (488.2 vs. 414.6 minutes), more osteotomies/patient (4.0 vs. 1.6) and greater percentage of anteroposterior fusion (APSF; 20.9% vs. 8.4%) than NOBMP, respectively (p0.05). Multivariate analysis demonstrated small to non-existent correlations between rhBMP-2 use and complications.Conclusions. RhBMP-2 use and location of rhBMP-2 use in ASD surgery, at reported doses, does not increase acute major, neurological or wound complications. Research is needed for higher rhBMP-2 dosing and long-term follow-up.

  17. Circadian period integrates network information through activation of the BMP signaling pathway.

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    Esteban J Beckwith

    2013-12-01

    Full Text Available Living organisms use biological clocks to maintain their internal temporal order and anticipate daily environmental changes. In Drosophila, circadian regulation of locomotor behavior is controlled by ∼150 neurons; among them, neurons expressing the PIGMENT DISPERSING FACTOR (PDF set the period of locomotor behavior under free-running conditions. To date, it remains unclear how individual circadian clusters integrate their activity to assemble a distinctive behavioral output. Here we show that the BONE MORPHOGENETIC PROTEIN (BMP signaling pathway plays a crucial role in setting the circadian period in PDF neurons in the adult brain. Acute deregulation of BMP signaling causes period lengthening through regulation of dClock transcription, providing evidence for a novel function of this pathway in the adult brain. We propose that coherence in the circadian network arises from integration in PDF neurons of both the pace of the cell-autonomous molecular clock and information derived from circadian-relevant neurons through release of BMP ligands.

  18. BMP4-mediated brown fat-like changes in white adipose tissue alter glucose and energy homeostasis.

    Science.gov (United States)

    Qian, Shu-Wen; Tang, Yan; Li, Xi; Liu, Yuan; Zhang, You-You; Huang, Hai-Yan; Xue, Rui-Dan; Yu, Hao-Yong; Guo, Liang; Gao, Hui-Di; Liu, Yan; Sun, Xia; Li, Yi-Ming; Jia, Wei-Ping; Tang, Qi-Qun

    2013-02-26

    Expression of bone morphogenetic protein 4 (BMP4) in adipocytes of white adipose tissue (WAT) produces "white adipocytes" with characteristics of brown fat and leads to a reduction of adiposity and its metabolic complications. Although BMP4 is known to induce commitment of pluripotent stem cells to the adipocyte lineage by producing cells that possess the characteristics of preadipocytes, its effects on the mature white adipocyte phenotype and function were unknown. Forced expression of a BMP4 transgene in white adipocytes of mice gives rise to reduced WAT mass and white adipocyte size along with an increased number of a white adipocyte cell types with brown adipocyte characteristics comparable to those of beige or brite adipocytes. These changes correlate closely with increased energy expenditure, improved insulin sensitivity, and protection against diet-induced obesity and diabetes. Conversely, BMP4-deficient mice exhibit enlarged white adipocyte morphology and impaired insulin sensitivity. We identify peroxisome proliferator-activated receptor gamma coactivator 1-α (PGC1α) as the target of BMP signaling required for these brown fat-like changes in WAT. This effect of BMP4 on WAT appears to extend to human adipose tissue, because the level of expression of BMP4 in WAT correlates inversely with body mass index. These findings provide a genetic and metabolic basis for BMP4's role in altering insulin sensitivity by affecting WAT development.

  19. Local expression and role of BMP-2/4 in injured spinal cord.

    Science.gov (United States)

    Cui, Z S; Zhao, P; Jia, C X; Liu, H J; Qi, R; Cui, J W; Cui, J H; Peng, Q; Lin, B; Rao, Y J

    2015-08-07

    We investigated local changes in BMP-2/4 expression in rat spinal cords 1 week following injury to study the damage effects of BMP-2/4 in spinal cord injury (SCI). Sprague Dawley rats (45, 4 months old) were randomized into three groups comprising 15 rats each: a SHAM group, an SCI without noggin group (SCIO), and an SCI with noggin group (SCID). The SCIO and SCID groups were subjected to spinal cord hemisection, and motor activity was assessed using the BBB score. Expression of BMP-2/4 in each injured spinal cord section was examined by hematoxylin and eosin staining, immunohistochemistry, and western blot. There were no significant differences in BBB scores among the three groups (P > 0.05). Following hemisection, the BBB score in the SHAM group was significantly higher than in the other two groups on the 1st day after modeling (P 0.05). Seven days after modeling, the BBB score in the SHAM group was significantly higher than in the other two groups (P < 0.05), and the BBB score in the SCID group was obviously higher than in the SCIO group (P < 0.05). The expression of BMP-2/4 was highest in the SCIO group and lowest in the SHAM group (P < 0.05). SCI can cause severe impairment of motor activity in rats. Seven days after SCI, the local expression of BMP-2/4 had obviously increased; noggin can effectively inhibit the expression of BMP-2/4 and reduce impairment.

  20. BMP signaling is essential in neonatal surfactant production during respiratory adaptation.

    Science.gov (United States)

    Luo, Yongfeng; Chen, Hui; Ren, Siying; Li, Nan; Mishina, Yuji; Shi, Wei

    2016-07-01

    Deficiency in pulmonary surfactant results in neonatal respiratory distress, and the known genetic mutations in key components of surfactant only account for a small number of cases. Therefore, determining the regulatory mechanisms of surfactant production and secretion, particularly during the transition from prenatal to neonatal stages, is essential for better understanding of the pathogenesis of human neonatal respiratory distress. We have observed significant increase of bone morphogenetic protein (BMP) signaling in neonatal mouse lungs immediately after birth. Using genetically manipulated mice, we then studied the relationship between BMP signaling and surfactant production in neonates. Blockade of endogenous BMP signaling by deleting Bmpr1a (Alk3) or Smad1 in embryonic day 18.5 in perinatal lung epithelial cells resulted in severe neonatal respiratory distress and death, accompanied by atelectasis in histopathology and significant reductions of surfactant protein B and C, as well as Abca3, whereas prenatal lung development was not significantly affected. We then identified a new BMP-Smad1 downstream target, Nfatc3, which is known as an important transcription activator for surfactant proteins and Abca3. Furthermore, activation of BMP signaling in cultured lung epithelial cells was able to promote endogenous Nfatc3 expression and also stimulate the activity of an Nfatc3 promoter that contains a Smad1-binding site. Therefore, our study suggests that the BMP-Alk3-Smad1-Nfatc3 regulatory loop plays an important role in enhancing surfactant production in neonates, possibly helping neonatal respiratory adaptation from prenatal amniotic fluid environment to neonatal air breathing. PMID:27190064

  1. Abnormal Activation of BMP Signaling Causes Myopathy in Fbn2 Null Mice.

    Science.gov (United States)

    Sengle, Gerhard; Carlberg, Valerie; Tufa, Sara F; Charbonneau, Noe L; Smaldone, Silvia; Carlson, Eric J; Ramirez, Francesco; Keene, Douglas R; Sakai, Lynn Y

    2015-06-01

    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 fibrillin-2 can

  2. Abnormal Activation of BMP Signaling Causes Myopathy in Fbn2 Null Mice.

    Directory of Open Access Journals (Sweden)

    Gerhard Sengle

    2015-06-01

    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

  3. BMP7 transfection induces in-vitro osteogenic differentiation of dental pulp mesenchymal stem cells

    Directory of Open Access Journals (Sweden)

    Ka Po John Yau

    2013-01-01

    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.

  4. Identification of bone morphogenetic protein 9 (BMP9) as a novel profibrotic factor in vitro.

    Science.gov (United States)

    Muñoz-Félix, José M; Cuesta, Cristina; Perretta-Tejedor, Nuria; Subileau, Mariela; López-Hernández, Francisco J; López-Novoa, José M; Martínez-Salgado, Carlos

    2016-09-01

    Upregulated synthesis of extracellular matrix (ECM) proteins by myofibroblasts is a common phenomenon in the development of fibrosis. Although the role of TGF-β in fibrosis development has been extensively studied, the involvement of other members of this superfamily of cytokines, the bone morphogenetic proteins (BMPs) in organ fibrosis has given contradictory results. BMP9 is the main ligand for activin receptor-like kinase-1 (ALK1) TGF-β1 type I receptor and its effect on fibrosis development is unknown. Our purpose was to study the effect of BMP9 in ECM protein synthesis in fibroblasts, as well as the involved receptors and signaling pathways. In cultured mice fibroblasts, BMP9 induces an increase in collagen, fibronectin and connective tissue growth factor expression, associated with Smad1/5/8, Smad2/3 and Erk1/2 activation. ALK5 inhibition with SB431542 or ALK1/2/3/6 with dorsomorphin-1, inhibition of Smad3 activation with SIS3, and inhibition of the MAPK/Erk1/2 with U0126, demonstrates the involvement of these pathways in BMP9-induced ECM synthesis in MEFs. Whereas BMP9 induced Smad1/5/8 phosphorylation through ALK1, it also induces Smad2/3 phosphorylation through ALK5 but only in the presence of ALK1. Summarizing, this is the first study that accurately identifies BMP9 as a profibrotic factor in fibroblasts that promotes ECM protein expression through ALK1 and ALK5 receptors. PMID:27208502

  5. Deficiency of retinaldehyde dehydrogenase 1 induces BMP2 and increases bone mass in vivo.

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    Shriram Nallamshetty

    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.

  6. Effect of heat treatment at 600 degree C for 10 hours on human BMP

    International Nuclear Information System (INIS)

    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

  7. Perlecan domain 1 recombinant proteoglycan augments BMP-2 activity and osteogenesis

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    DeCarlo Arthur A

    2012-09-01

    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

  8. EXPRESSION OF rhBMP-7 GENE IN TRANSDUCED BONE MARROW DERIVED STROMAL CELLS

    Institute of Scientific and Technical Information of China (English)

    段德宇; 杜靖远; 王洪; 刘勇; 郭晓东

    2002-01-01

    Objective. To explore the possibility of expression of exogenous gene in transduced bone marrow derived stromal cells(BMSCs). Methods. The marker gene , pbLacZ, was transferred into cultured BMSCs and the expression of transduced gene by X-gal staining was examined. Then plasmid pcDNA3-rhBMP7 was delivered to cultured BMSCs. Through immunohistochemical staining and RT-PCR assay, the expression of rhBMP7 gene was detected. Results. The exogenous gene could be expressed efficiently in transduced BMSCs. Conculsion. The present study provided a theoretical basis to gene therapy on the problems of bone and cartilage tissue.

  9. A BMP7 Variant Inhibits Tumor Angiogenesis In Vitro and In Vivo through Direct Modulation of Endothelial Cell Biology.

    Directory of Open Access Journals (Sweden)

    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.

  10. Leap-forward development strategy of China's biomethane industry based on new developments of chemical engineering%化工新视野下中国生物甲烷跨越式发展策略

    Institute of Scientific and Technical Information of China (English)

    刘畅; 陆小华; 杨祝红; 朱育丹; 冯新

    2013-01-01

    生物甲烷作为战略资源和可再生能源已在德国和瑞典等发达国家得到快速发展,我国尚处于起步阶段.目前,对生物甲烷物质高效转化和能量有效利用机制缺乏深入了解仍然是制约其大规模应用的瓶颈.本文从化学工程前沿理论出发,分析生物甲烷高效转化存在的关键科学问题,认为基于中国国情的生物甲烷工业,可以在化工界面传递新理论、纳微尺度新材料和系统优化方法介入下,获得物质转化和能量利用方面的突破,实现生物甲烷产业的跨越式发展.%Biomethane has developed rapidly in western countries, such as Germany and Sweden, but it is still in its infancy in China though biomethane is an important renewable energy made from organic sources. At present, the bottleneck limiting its large-scale application is unclear mechanisms of high efficiency conversion and effective energy utilization in biomethane process. In this work, the key problems in biomethane process were discussed based on new theory of chemical engineering. It was concluded that that rapid progress can be made in biomethane industry in China with the help of new theory of interface transport, new micro and nano materials and system optimization methods.

  11. Experimental Research on Ectopic Osteogenesis of BMP2-derived Peptide P24 Combined with PLGA Copolymers

    Institute of Scientific and Technical Information of China (English)

    DUAN Zhixia; ZHENG Qixin; GUO Xiaodong; YUAN Quan; CHEN Shunguang

    2007-01-01

    To experimentally evaluate the ectopic osteogenetic capacity of synthesized BMP2-derived peptide P24 combined with poly lactic-co-glycolic acid (PLGA), Wistar rats were divided into two groups: group A, in which BMP2-derived peptide P24/PLGA complex was implanted,and group B which received simple PLGA implant. The complex was respectively implanted into the back muscles of rats. Samples were taken the 1 st, 4 th, 8 th, and the 12 th week after the implantation.Their bone formation was detected by X-ray examination, and tissue response was histologically observed. Western blotting was used for the detection of the expression of collagen Ⅰ (Col- Ⅰ ) and osteopontin (OPN). There was acute inflammation in the tissue around both types of implants at early stage. The cartilage was found around implant areas 4 weeks after the implantation of BMP2-derived peptide p24/PLGA complex, 8 weeks after the implantation, osteoblasts were found, and 12 weeks after the implantation, typical trabecular bone structure was observed. In group B, after 12 weeks, no osteoblasts were found. It is concluded that PLGA is an ideal scaffold material for bone tissue engineering. BMP2-derived peptide can start endochondral ossification and is more effective in inducing ectopic osteogenesis.

  12. cDNA library Table: BmP [KAIKOcDNA[Archive

    Lifescience Database Archive (English)

    Full Text Available BmP NA Qingsong-Haoyue whole body pupal stage mixed pHelix Site_1 Hind II M13 Forwa...rd DN236876-DN237878, DN591076-DN591089,DN985172-DN985373,DY230449-DY231514 EST[number] whole pupae body but for the skin ...

  13. Biodegradable Chitosan Nanoparticle Coatings on Titanium for the Delivery of BMP-2

    Directory of Open Access Journals (Sweden)

    Nils Poth

    2015-01-01

    Full Text Available A simple method for the functionalization of a common implant material (Ti6Al4V with biodegradable, drug loaded chitosan-tripolyphosphate (CS-TPP nanoparticles is developed in order to enhance the osseointegration of endoprostheses after revision operations. The chitosan used has a tailored degree of acetylation which allows for a fast biodegradation by lysozyme. The degradability of chitosan is proven via viscometry. Characteristics and degradation of nanoparticles formed with TPP are analyzed using dynamic light scattering. The particle degradation via lysozyme displays a decrease in particle diameter of 40% after 4 days. Drug loading and release is investigated for the nanoparticles with bone morphogenetic protein 2 (BMP-2, using ELISA and the BRE luciferase test for quantification and bioactivity evaluation. Furthermore, nanoparticle coatings on titanium substrates are created via spray-coating and analyzed by ellipsometry, scanning electron microscopy and X-ray photoelectron spectroscopy. Drug loaded nanoparticle coatings with biologically active BMP-2 are obtained in vitro within this work. Additionally, an in vivo study in mice indicates the dose dependent induction of ectopic bone growth through CS-TPP-BMP-2 nanoparticles. These results show that biodegradable CS-TPP coatings can be utilized to present biologically active BMP-2 on common implant materials like Ti6Al4V.

  14. BMP and Hedgehog Regulate Distinct AGM Hematopoietic Stem Cells Ex Vivo.

    Science.gov (United States)

    Crisan, Mihaela; Solaimani Kartalaei, Parham; Neagu, Alex; Karkanpouna, Sofia; Yamada-Inagawa, Tomoko; Purini, Caterina; Vink, Chris S; van der Linden, Reinier; van Ijcken, Wilfred; Chuva de Sousa Lopes, Susana M; Monteiro, Rui; Mummery, Christine; Dzierzak, Elaine

    2016-03-01

    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. PMID:26923823

  15. BMP and Hedgehog Regulate Distinct AGM Hematopoietic Stem Cells Ex Vivo

    Directory of Open Access Journals (Sweden)

    Mihaela Crisan

    2016-03-01

    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.

  16. Signaling cross-talk between TGF-β/BMP and other path-ways

    Institute of Scientific and Technical Information of China (English)

    Xing Guo; Xiao-Fan Wang

    2009-01-01

    Transforming growth factor-beta(TGF-β)/bone morphogenic protein(BMP)signaling is involved in the vast majority of cellular processes and is fundamentally important during the entire life of alI metazoans.Deregulation of TGF-β/BMP activity almost invariably leads to developmental defects and/or diseases.including cancer.The proper functioning of the TGF-β/BMP pathway depends on its constitutive and extensive communication with other signaling pathways,leading to synergistic or antagonistic effects and eventually desirable biological outcomes.The nature of such signaling cross-talk iS overwhelmingly complex and highly context-dependent.Here we review the difierent modes of cross-talk between TGF-β/BMP and the signaling pathways of Mitogen-activated protein kinase,phosphatidyIinositoI-3 kinase/Akt,Wnt,Hedgehog,Notch,and the interleukin/interferon-gamma/tumor necrosis factor-alpha cytokines,with an emphasis on the underlying molecular mechanisms.

  17. In Search of Biomarkers for Idiopathic Scoliosis: Leptin and BMP4 Functional Polymorphisms

    Directory of Open Access Journals (Sweden)

    Svetla Nikolova

    2015-01-01

    Full Text Available Idiopathic scoliosis (IS is the most common spinal disorder in children and adolescents. The current consensus on IS maintains that it has a multifactorial etiology with genetic predisposition factors. In the present study the association of two functional polymorphisms of leptin (rs7799039 and BMP4 (rs4898820 with susceptibility to IS and curve severity was investigated in a Bulgarian population sample. The molecular detection of the genotypes was performed by amplification followed by restriction technology. The statistical analysis was performed by Pearson’s chi-squared test. This case-control study revealed no statistically significant association between the functional polymorphisms of leptin and BMP4 and susceptibility to IS or curve progression (p>0.05. On the basis of these results the examined polymorphic variants of leptin and BMP4 could not be considered as genetic variants with predisposition effect or as risk factors for the progression of the curve. In addition, these results do not exclude a synergistic effect of the promoter polymorphisms of leptin and BMP4 in the etiology and pathogenesis of IS. The identification of molecular markers for IS could be useful for early detection and prognosis of the risk for a rapid progression of the curve. That would permit early stage treatment of the patient with the least invasive procedures.

  18. CLONING AND SEQUENCING OF MATURE FRAGMENT OF HUMAN BMP4 GENE

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Objective To study the cloning and sequencing of mature fragment of human bone morphogenetic protein-4 gene. Methods The template DNA was obtained from the human osteosarcoma cell line U2OS. By using RT- PCR method, the cDNA coding for the mature fragment of BMP-4 was amplified, cloned into the vector pUC19, and sequenced by Sanger Dideoxy-mediated Chain Termination method. Results The mature fragment of BMP4 cDNA was obtained by RT-PCR and determined by sequencing. Through the computer search on Genebank, the analysis showed that the homology of nucleotides and amino acids between cDNA of rhBMP4 mature fragment of this study and the published sequence was 99%. Sequence analysis showed that there were two differences, one was at base 1154 (201): G→C, which had no influence on the corresponding amino acids (Val). Another was at basel222 (269):C→T, the mutation at the base 1222 had the change of Ala to Val. Conclusion The mature fragment of BMP4 gene has been cloned. The results will be of great significance in treatment of skeletal injuries and diseases.

  19. Discovery of a Small-Molecule BMP Sensitizer for Human Embryonic Stem Cell Differentiation

    Directory of Open Access Journals (Sweden)

    Lingling Feng

    2016-05-01

    Full Text Available Sorely missing from the “toolkit” for directed differentiation of stem/progenitor cells are agonists of the BMP-signaling pathway. Using a high-throughput chemical screen, we discovered that PD407824, a checkpoint kinase 1 (CHK1 inhibitor, increases the sensitivity of cells to sub-threshold amounts of BMP4. We show utility of the compound in the directed differentiation of human embryonic stem cells toward mesoderm or cytotrophoblast stem cells. Blocking CHK1 activity using pharmacological compounds or CHK1 knockout using single guide RNA (sgRNA confirmed that CHK1 inhibition increases the sensitivity to BMP4 treatment. Additional mechanistic studies indicate that CHK1 inhibition depletes p21 levels, thereby activating CDK8/9, which then phosphorylates the SMAD2/3 linker region, leading to decreased levels of SMAD2/3 protein and enhanced levels of nuclear SMAD1. This study provides insight into mechanisms controlling the BMP/transforming growth factor beta (TGF-β signaling pathways and a useful pharmacological reagent for directed differentiation of stem cells.

  20. Bio-methane & Bio-hydrogen. Status and perspectives of biological methane and hydrogen production

    NARCIS (Netherlands)

    Wijffels, R.H.; Janssen, M.G.J.

    2003-01-01

    Eerst wordt het kader geschetst voor de potentiële rol van bio-methaan en bio-waterstof in de energiehuishouding en de invloeden daarop van de ontwikkeling van eindgebruikstechnologie en infrastructuur, en het energiebeleid. Daarna wordt uitvoerig ingegaan op de technieken voor bio-methaan en bio-wa

  1. Genetic predisposition to fracture non-union: a case control study of a preliminary single nucleotide polymorphisms analysis of the BMP pathway

    Directory of Open Access Journals (Sweden)

    Giannoudis Peter V

    2011-02-01

    Full Text Available Abstract Background Despite the known multi-factorial nature of atrophic fracture non-unions, a possible genetic predisposition for the development of this complication after long bone fractures remains unknown. This pilot study aimed to address this issue by performing a preliminary SNP analysis of specific genes known to regulate fracture healing. Methods A total of fifteen SNPs within four genes of the Bone Morphogenetic Protein (BMP pathway (BMP-2, BMP-7, NOGGIN and SMAD6 were examined, in 109 randomly selected patients with long bone fractures as a result of motor vehicle accident, fall or direct blow. There were sixty-two patients with atrophic non-union and forty-seven patients (54 fractures with uneventful fracture union. Overall SNPs frequencies were computed with respect to patient's age, gender, smoking habits, fracture-associated parameters and the use of nonsteroidal anti-inflammatory drugs (NSAIDs, and tested for their association to the impaired bone healing process, using binary logistic regression (STATA 11.1; StataCorp, Texas USA. Results Statistical analysis revealed age to be an important covariate in the development of atrophic non-union (p = 0.01, OR 1.05 [per year], and two specific genotypes (G/G genotype of the rs1372857 SNP, located on NOGGIN and T/T genotype of the rs2053423 SNP, located on SMAD6 to be associated with a greater risk of fracture non-union (p = 0.02, OR 4.56 and p = 0.04, OR 10.27, respectively, after adjustment for age. Conclusions This is the first clinical study to investigate the potential existence of genetic susceptibility to fracture non-union. Even though no concrete conclusions can be obtained from this pilot study, our results indicate the existence of a potential genetically predetermined impairment within the BMP signalling cascade, initiated after a fracture and when combined with other risk factors could synergistically increase the susceptibility of a patient to develop non-union. Further

  2. Bone formation of a porous Gelatin-Pectin-biphasic calcium phosphate composite in presence of BMP-2 and VEGF.

    Science.gov (United States)

    Amirian, Jhaleh; Linh, Nguyen Thuy Ba; Min, Young Ki; Lee, Byong-Taek

    2015-05-01

    A composite scaffold of gelatin (Gel)-pectin (Pec)-biphasic calcium phosphate (BCP) was fabricated for the successful delivery of growth factors. Bone morphogenetic protein-2 (BMP-2) and vascular endothelial growth factor (VEGF) were coated on the Gel-Pec-BCP surface to investigate of effect of them on bone healing. Surface morphology was investigated by scanning electron microscopy, and BCP dispersion in the hydrogel scaffolds was measured by energy dispersive X-ray spectroscopy. The results obtained from Fourier transform infrared spectroscopy showed that BMP-2 and VEGF were successfully coated on Gel-Pec-BCP hydrogel scaffolds. MC3T3-E1 preosteoblasts were cultivated on the scaffolds to investigate the effect of BMP-2 and VEGF on cell viability and proliferation. VEGF and BMP-2 loaded on Gel-Pec-BCP scaffold facilitated increased cell spreading and proliferation compared to Gel-Pec-BCP scaffolds. In vivo, bone formation was examined using rat models. Bone formation was observed in Gel-Pec-BCP/BMP-2 and Gel-Pec-BCP/VEGF scaffolds within 4 weeks, and was greatest with Gel-Pec-BCP/BMP-2 scaffolds. In vitro and in vivo results suggest that Gel-Pec-BCP/BMP-2 and Gel-Pec-BCP/VEGF scaffolds could enhance bone regeneration.

  3. Preconditioning Human Mesenchymal Stem Cells with a Low Concentration of BMP2 Stimulates Proliferation and Osteogenic Differentiation In Vitro

    DEFF Research Database (Denmark)

    Lysdahl, Helle; Baatrup, Anette; Foldager, Casper Bindzus;

    2014-01-01

    treatment strategy in which human bone marrow-derived mesenchymal stem cells (hMSCs) are preconditioned with low concentrations of BMP2 for a short time in vitro. hMSCs in suspension were stimulated for 15 min with 10 and 20 ng/mL of BMP2. After the BMP2 was removed, the cells were seeded and cultured...... in osteogenesis was validated by findings of increased gene expression of SMAD1 and an increase in dual phosphorylation of ser 463 and ser 465 in the SMAD 1/5/8 pathway. We concluded that preconditioning hMSCs with BMP2 stimulates osteogenesis: proliferation with matrix secretion and matrix maturation of h......MSCs. This implies that preconditioning with BMP2 might be more effective at inducing proliferation and osteogenic differentiation of hMSCs than continuous stimulation. Preconditioning with BMP2 could benefit the clinical application of BMP2 since side effects from high-dose treatments could be avoided....

  4. Study of the association between the BMP4 gene and congenital anomalies of the kidney and urinary tract

    Directory of Open Access Journals (Sweden)

    Geisilaine Soares dos Reis

    2014-01-01

    Full Text Available OBJECTIVE: To determine the frequency of different phenotypes for congenital anomalies of the kidney and urinary tract (CAKUT in a Brazilian sample, and to evaluate the association between the CAKUT phenotypes and the BMP4 gene. METHODS: In this study, 457 Brazilian individuals were analyzed in an attempt to establish the association between the BMP4 gene and the CAKUT diagnosis. A case-control sample was genotyped for three BMP4 gene polymorphisms. RESULTS: Association data was established with CAKUT sample as a whole and with the three most important CAKUT phenotypes: multicystic dysplastic kidney disease (MDK, ureteropelvic junction obstruction (UPJO and vesicoureteral reflux (VUR. When the sample was segregated in these three phenotypes, associations between the BMP4 gene were observed with UPJO and with MDK. Conversely, VUR was not associated to the polymorphisms of the BMP4 gene. CONCLUSIONS: The present data suggest that Brazilian individuals with polymorphisms of the BMP4 gene have a higher risk to develop CAKUT, especially the malformations related to nephrogenesis and initial branching such as MDK and UPJO. Conversely, VUR appeared not to be related to BMP4 gene.

  5. Wnt/β-catenin regulates the activity of Epiprofin/Sp6, SHH, FGF and BMP to coordinate the stages of odontogenesis

    Directory of Open Access Journals (Sweden)

    Maitane Aurrekoetxea

    2016-03-01

    Full Text Available Background: We used an in vitro tooth development model to investigate the effects of overactivation of the Wnt/β-catenin pathway during odontogenesis by bromoindirubin oxime reagent (BIO, a specific inhibitor of GSK-3 activity. Results: Overactivatingthe Wnt/β-catenin pathway at tooth initiation upregulated and ectopically expressed the epithelial markers Sonic Hedgehog (Shh, Epiprofin (Epfn and Fibroblast growth factor8 (Fgf8, which are involved in the delimitation of odontogenic fields in the oral ectoderm. This result indicated an ectopic extension of the odontogenic potential. During tooth morphogenesis, Fibroblast growth factor4 (Fgf4, Fibroblast growth factor10 (Fgf10, Muscle segment homeobox 1 (Msx-1, Bone Morphogenetic protein 4 (Bmp4 and Dickkopf WNT signaling pathway inhibitor 1 (Dkk-1 were overexpressed in first molars cultured with BIO. Conversely, the expression levels of Wingless integration site 10b (Wnt-10b and Shh were reduced. Additionally, the odontoblast differentiation markers Nestin and Epfn showed ectopic overexpression in the dental mesenchyme of BIO-treated molars. Moreover, alkaline phosphatase activity increased in the dental mesenchyme, again suggesting aberrant, ectopic mesenchymal cell differentiation. Finally, Bmp4 downregulated Epfn expression during dental morphogenesis. Conclusions: We suggest the presence of a positive feedback loop wherein Epfn and β-catenin activate each other. The balance of the expression of these two molecules is essential for proper tooth development. We propose a possible link between Wnt, Bmp and Epfn that would critically determine the correct patterning of dental cusps and the differentiation of odontoblasts and ameloblasts.

  6. Microalgal Biomethane Production Integrated with an Existing Biogas Plant: A Case Study in Sweden

    OpenAIRE

    Wang, Xiaoqiang; Nordlander, Eva; Thorin, Eva; Yan, Jinyue

    2012-01-01

    Microalgae are considered as potential sources for biodiesel production due to the higher growth rate than terrestrial plants. However, the large-scale application of algal biodiesel would be limited by the downstream cost of lipid extraction and the availability of water, CO2 and nutrients. A possible solution is to integrate algae cultivation with existing biogas plant, where algae can be cultivated using the discharges of CO2 and digestate as nutrient input, and then the attained biomass c...

  7. Bio-methane & Bio-hydrogen. Status and perspectives of biological methane and hydrogen production

    OpenAIRE

    Wijffels, R. H.; Janssen, M.G.J.

    2003-01-01

    Eerst wordt het kader geschetst voor de potentiële rol van bio-methaan en bio-waterstof in de energiehuishouding en de invloeden daarop van de ontwikkeling van eindgebruikstechnologie en infrastructuur, en het energiebeleid. Daarna wordt uitvoerig ingegaan op de technieken voor bio-methaan en bio-waterstof productie. Achtereenvolgens worden belicht: methaanproductie via anaërobe vergisting, biologische waterstofproductie via (donker) fermentatie, en fotobiologische waterstofproductie.

  8. Efficient retina formation requires suppression of both Activin and BMP signaling pathways in pluripotent cells

    Directory of Open Access Journals (Sweden)

    Kimberly A. Wong

    2015-03-01

    Full Text Available Retina formation requires the correct spatiotemporal patterning of key regulatory factors. While it is known that repression of several signaling pathways lead to specification of retinal fates, addition of only Noggin, a known BMP antagonist, can convert pluripotent Xenopus laevis animal cap cells to functional retinal cells. The aim of this study is to determine the intracellular molecular events that occur during this conversion. Surprisingly, blocking BMP signaling alone failed to mimic Noggin treatment. Overexpressing Noggin in pluripotent cells resulted in a concentration-dependent suppression of both Smad1 and Smad2 phosphorylation, which act downstream of BMP and Activin signaling, respectively. This caused a decrease in downstream targets: endothelial marker, xk81, and mesodermal marker, xbra. We treated pluripotent cells with dominant-negative receptors or the chemical inhibitors, dorsomorphin and SB431542, which each target either the BMP or Activin signaling pathway. We determined the effect of these treatments on retina formation using the Animal Cap Transplant (ACT assay; in which treated pluripotent cells were transplanted into the eye field of host embryos. We found that inhibition of Activin signaling, in the presence of BMP signaling inhibition, promotes efficient retinal specification in Xenopus tissue, mimicking the affect of adding Noggin alone. In whole embryos, we found that the eye field marker, rax, expanded when adding both dominant-negative Smad1 and Smad2, as did treating the cells with both dorsomorphin and SB431542. Future studies could translate these findings to a mammalian culture assay, in order to more efficiently produce retinal cells in culture.

  9. Haplotypes in BMP4 and FGF Genes Increase the Risk of Peri-Implantitis.

    Science.gov (United States)

    Coelho, Renata Barboza; Gonçalves, Roberto; Villas-Boas, Ricardo de Mello; Bonato, Leticia Ladeira; Quinelato, Valquiria; Pinheiro, Aristides da Rosa; Machado, Aldir; Nunes, Carlos Henrique Ramirez; Gonçalves, Rackel; Vieira, Alexandre Resende; Granjeiro, José Mauro; Casado, Priscila Ladeira

    2016-01-01

    Despite the success of osseointegrated implants, failures have increased significantly, associated with development of peri-implantitis. Multiple factors influence the peri-implant bone loss, including environmental and genetic causes. BMPs (Bone morphogenetic proteins) are growth factors that induce bone formation. FGF (fibroblast growth factors) and their receptors (FGFRs) play important roles by controlling the levels of cell proliferation, differentiation and migration. BMP/FGF relationship is responsible for promoting bone regeneration and bone loss. The aim of this study was to analyze the correlation between BMP4, FGF3, FGF10 and FGFR1 genes and peri-implant bone loss. Two hundred and fifteen volunteers, with 754 dental implants, were submitted to oral examination and divided in healthy group (n=129) and peri-implantitis group (n=86). Thirteen polymorphisms in BMP4, FGF3, FGF10 and FGFR1 genes were analyzed individually and in haplotype. The chi-square test correlated genotypes, allelic and haplotype frequencies. Values of pimplantitis demonstrated high incidence of total edentulism (pimplant phenotype (pimplant mobility was observed in peri-implantitis group (pimplant (p=0.01). FGF3 rs4631909 (TT+CT genotype) also showed association with the control group (p=0.04). The frequency of C allele for FGF3 rs4631909 showed a tendency for association with peri-implantitis (p=0.08). FGF10 CCTG (p=0.03), BMP4 GAAA (p=0.05) and GGGA (p=0.02) haplotypes were associated with peri-implantitis (p=0.03). Therefore, it may be concluded that BMP4 and FGF10 haplotypes are associated with peri-implantitis. PMID:27652695

  10. BMP4 and LGL1 are Down Regulated in an Ovine Model of Congenital Diaphragmatic Hernia

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    Heather eEmmerton-Coughlin

    2014-11-01

    Full Text Available Background/Purpose: The molecular pathophysiology of lung hypoplasia in congenital diaphragmatic hernia (CDH remains poorly understood. The Wnt signaling pathway and downstream targets, such as bone morphogenetic proteins (BMP 4 and other factors such as late gestation lung protein 1 (LGL1, are essential to normal lung development. Nitrofen-induced hypoplastic CDH rodent lungs demonstrate down regulation of the Wnt pathway including BMP4 and reduced LGL1 expression. The aim of the current study was to examine the molecular pathophysiology associated with a surgically induced CDH in an ovine model. Methods: Left thoracotomy was performed at 80 days in 14 fetal sheep; CDH was created in 7 experimental animals. Lungs were harvested at 136 days (term=145d. Lung weight and mean terminal bronchiole density (MTBD were measured to determine the degree of pulmonary hypoplasia. Quantitative real time PCR was undertaken to analyze Wnt2, Wnt7b, BMP4 and LGL1 mRNA expression. Results: Total lung weight was decreased while MTBD was increased in the CDH group (p<0.05, confirming pulmonary hypoplasia. BMP4 and LGL1 mRNA was significantly reduced in CDH lungs (p<0.05. Wnt2 mRNA was decreased, although not significantly (p<0.06. Conclusions: For the first time, down regulation of BMP4 and Lgl1 are reported in an ovine CDH model. In contrast to other animal models, these changes are persistent to near term. These findings suggest that mechanical compression from herniated viscera may play a more important role in causing pulmonary hypoplasia in CDH, rather than a primary defect in lung organogenesis.

  11. PARM-1 promotes cardiomyogenic differentiation through regulating the BMP/Smad signaling pathway

    Energy Technology Data Exchange (ETDEWEB)

    Nakanishi, Naohiko [Department of Cardiovascular Medicine, Kyoto Prefectural University of Medicine, Kyoto 602-8566 (Japan); Takahashi, Tomosaburo, E-mail: ttaka@koto.kpu-m.ac.jp [Department of Cardiovascular Medicine, Kyoto Prefectural University of Medicine, Kyoto 602-8566 (Japan); Ogata, Takehiro; Adachi, Atsuo; Imoto-Tsubakimoto, Hiroko [Department of Cardiovascular Medicine, Kyoto Prefectural University of Medicine, Kyoto 602-8566 (Japan); Ueyama, Tomomi, E-mail: toueyama-circ@umin.ac.jp [Department of Cardiovascular Medicine, Kyoto Prefectural University of Medicine, Kyoto 602-8566 (Japan); Matsubara, Hiroaki [Department of Cardiovascular Medicine, Kyoto Prefectural University of Medicine, Kyoto 602-8566 (Japan)

    2012-11-30

    Highlights: Black-Right-Pointing-Pointer PARM-1 expression is induced during cardiomyogenesis. Black-Right-Pointing-Pointer PARM-1 expression precedes Nkx2.5 and Tbx5 during cardiomyogenesis. Black-Right-Pointing-Pointer PARM-1 activates BMP/Smad signaling. Black-Right-Pointing-Pointer PARM-1 enhances cardiac specification, resulting in promoted cardiomyogenesis. -- Abstract: PARM-1, prostatic androgen repressed message-1, is an endoplasmic reticulum (ER) molecule that is involved in ER stress-induced apoptosis in cardiomyocytes. In this study, we assessed whether PARM-1 plays a role in the differentiation of stem cells into cardiomyocytes. While PARM-1 was not expressed in undifferentiated P19CL6 embryonic carcinoma cells, PARM-1 expression was induced during cardiomyogenic differentiation. This expression followed expression of mesodermal markers, and preceded expression of cardiac transcription factors. PARM-1 overexpression did not alter the expression of undifferentiated markers and the proliferative property in undifferentiated P19CL6 cells. Expression of cardiac transcription factors during cardiomyogenesis was markedly enhanced by overexpression of PARM-1, while expression of mesodermal markers was not altered, suggesting that PARM-1 is involved in the differentiation from the mesodermal lineage to cardiomyocytes. Furthermore, overexpression of PARM-1 induced BMP2 mRNA expression in undifferentiated P19CL6 cells and enhanced both BMP2 and BMP4 mRNA expression in the early phase of cardiomyogenesis. PARM-1 overexpression also enhanced phosphorylation of Smads1/5/8. Thus, PARM-1 plays an important role in the cardiomyogenic differentiation of P19CL6 cells through regulating BMP/Smad signaling pathways, demonstrating a novel role of PARM-1 in the cardiomyogenic differentiation of stem cells.

  12. Histone deacetylases control neurogenesis in embryonic brain by inhibition of BMP2/4 signaling.

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    Maya Shakèd

    Full Text Available BACKGROUND: Histone-modifying enzymes are essential for a wide variety of cellular processes dependent upon changes in gene expression. Histone deacetylases (HDACs lead to the compaction of chromatin and subsequent silencing of gene transcription, and they have recently been implicated in a diversity of functions and dysfunctions in the postnatal and adult brain including ocular dominance plasticity, memory consolidation, drug addiction, and depression. Here we investigate the role of HDACs in the generation of neurons and astrocytes in the embryonic brain. PRINCIPAL FINDINGS: As a variety of HDACs are expressed in differentiating neural progenitor cells, we have taken a pharmacological approach to inhibit multiple family members. Inhibition of class I and II HDACs in developing mouse embryos with trichostatin A resulted in a dramatic reduction in neurogenesis in the ganglionic eminences and a modest increase in neurogenesis in the cortex. An identical effect was observed upon pharmacological inhibition of HDACs in in vitro-differentiating neural precursors derived from the same brain regions. A reduction in neurogenesis in ganglionic eminence-derived neural precursors was accompanied by an increase in the production of immature astrocytes. We show that HDACs control neurogenesis by inhibition of the bone morphogenetic protein BMP2/4 signaling pathway in radial glial cells. HDACs function at the transcriptional level by inhibiting and promoting, respectively, the expression of Bmp2 and Smad7, an intracellular inhibitor of BMP signaling. Inhibition of the BMP2/4 signaling pathway restored normal levels of neurogenesis and astrogliogenesis to both ganglionic eminence- and cortex-derived cultures in which HDACs were inhibited. CONCLUSIONS: Our results demonstrate a transcriptionally-based regulation of BMP2/4 signaling by HDACs both in vivo and in vitro that is critical for neurogenesis in the ganglionic eminences and that modulates cortical

  13. Induction of chronic pancreatitis by pancreatic duct ligation activates BMP2, apelin, and PTHrP expression in mice.

    Science.gov (United States)

    Rastellini, Cristiana; Han, Song; Bhatia, Vandanajay; Cao, Yanna; Liu, Ka; Gao, Xuxia; Ko, Tien C; Greeley, George H; Falzon, Miriam

    2015-10-01

    Chronic pancreatitis (CP) is a devastating disease with no treatments. Experimental models have been developed to reproduce the parenchyma and inflammatory responses typical of human CP. For the present study, one objective was to assess and compare the effects of pancreatic duct ligation (PDL) to those of repetitive cerulein (Cer)-induced CP in mice on pancreatic production of bone morphogenetic protein-2 (BMP2), apelin, and parathyroid hormone-related protein (PTHrP). A second objective was to determine the extent of cross talk among pancreatic BMP2, apelin, and PTHrP signaling systems. We focused on BMP2, apelin, and PTHrP since these factors regulate the inflammation-fibrosis cascade during pancreatitis. Findings showed that PDL- and Cer-induced CP resulted in significant elevations in expression and peptide/protein levels of pancreatic BMP2, apelin, and PTHrP. In vivo mouse and in vitro pancreatic cell culture experiments demonstrated that BMP2 stimulated pancreatic apelin expression whereas apelin expression was inhibited by PTHrP exposure. Apelin or BMP2 exposure inhibited PTHrP expression, and PTHrP stimulated upregulation of gremlin, an endogenous inhibitor of BMP2 activity. Transforming growth factor-β (TGF-β) stimulated PTHrP expression. Together, findings demonstrated that PDL- and Cer-induced CP resulted in increased production of the pancreatic BMP2, apelin, and PTHrP signaling systems and that significant cross talk occurred among pancreatic BMP2, apelin, and PTHrP. These results together with previous findings imply that these factors interact via a pancreatic network to regulate the inflammation-fibrosis cascade during CP. More importantly, this network communicated with TGF-β, a key effector of pancreatic pathophysiology. This novel network may be amenable to pharmacologic manipulations during CP in humans. PMID:26229008

  14. Effect of growth factors (BMP-4/7 & bFGF on proliferation & osteogenic differentiation of bone marrow stromal cells

    Directory of Open Access Journals (Sweden)

    Shaohui Yuan

    2013-01-01

    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.

  15. 开发产业沼气实现生物天然气对天然气的替代——有机废弃物厌氧处理从"环保主导"向"能源-环保双赢"的转型%Tapping biogas industry,substituting biomethane to natural gas——transition of organic wastes disposal from"environment-center" model to"win-win"one of producing bioenergy and degrading pollutants

    Institute of Scientific and Technical Information of China (English)

    程序; 郑恒受; 梁近光; 朱万斌; 崔宗均

    2011-01-01

    论述了我国沼气技术和工程升级换代的必要性和可行路线,沼气资源在中国的多样性,分析了若干探索性的案例.研究发现全国生物天然气生产潜力超过1 000亿m3/a,将成为我国部分地替代供应日趋紧缺的天然气的重要途径.%This paper discussed the necessity of upgrading biogas technology and relevant technical framework. Diversified feedstock of biogas in China was evaluated, and a few cases were analyzed. It is concluded that biomethane has potentials of annual production of above 100 billion cubic meters, and it will become very important origin for partly substituting natural gas that its resource is badly inadequate in China.

  16. Establishment of Immortalized Mouse Bmp2 Knock-Out Dental Papilla Mesenchymal Cells Necessary for Study of Odontoblastic Differentiation and Odontogenesis.

    Science.gov (United States)

    Wu, Lian; Wang, Feng; Donly, Kevin J; Wan, Chunyan; Luo, Daoshu; Harris, Stephen E; MacDougall, Mary; Chen, Shuo

    2015-11-01

    Bmp2 is essential for dentin formation. Bmp2 cKO mice exhibited similar phenotype to dentinogenesis imperfecta, showing dental pulp exposure, hypomineralized dentin, and delayed odontoblast differentiation. As it is relatively difficult to obtain lot of primary Bmp2 cKO dental papilla mesenchymal cells and to maintain a long-term culture of these primary cells, availability of immortalized deleted Bmp2 dental papilla mesenchymal cells is critical for studying the underlying mechanism of Bmp2 signal in odontogenesis. In this study, our goal was to generate an immortalized deleted Bmp2 dental papilla mesenchymal (iBmp2(ko/ko)dp) cell line by introducing Cre recombinase and green fluorescent protein (GFP) into the immortalized mouse floxed Bmp2 dental papilla mesenchymal (iBmp2(fx/fx)dp) cells. iBmp2(ko/ko)dp cells were confirmed by GFP and PCR. The deleted Bmp2 cells exhibited slow cell proliferation rate and cell growth was arrested in G2 phase. Expression of tooth-related marker genes and cell differentiation were decreased in the deleted cells. Importantly, extracellular matrix remodeling was impaired in the iBmp2(ko/ko)dp cells as reflected by the decreased Mmp-9 expression. In addition, with exogenous Bmp2 induction, these cell differentiation and mineralization were rescued as well as extracellular matrix remodeling was enhanced. Therefore, we for the first time described establishment of iBmp(ko/ko) cells that are useful for study of mechanisms in regulating dental papilla mesenchymal cell lineages. PMID:26037045

  17. Gene gun transferring-bone morphogenetic protein 2 (BMP-2) gene enhanced bone fracture healing in rabbits

    OpenAIRE

    Li, Wenju; Wei, Haifeng; Xia, Chunmei; Zhu, Xiaomeng; Hou, Guozhu; Xu, Feng; Xinghua SONG; Zhan, Yulin

    2015-01-01

    Purpose: Transferring the bone morphogenetic protein 2 (BMP-2) genes into the tissues or cells can improve the bone healing of the fracture has been widely accepted. We evaluated the efficiency of using gene gun to transfer the BMP-2 gene thereby affected the healing of a fractured bone. Methods: The vector coding for BMP-2 was constructed by a non-replicating encephalo-myocarditis virus (ECMV)-based vector. The segmental bone defect (1.5 cm) model was created by a wire-saw at the middle part...

  18. A Novel Human TGF-β1 Fusion Protein in Combination with rhBMP-2 Increases Chondro-Osteogenic Differentiation of Bone Marrow Mesenchymal Stem Cells

    Science.gov (United States)

    Claros, Silvia; Rico-Llanos, Gustavo A.; Becerra, José; Andrades, José A.

    2014-01-01

    Transforming growth factor-beta (TGF-β) is involved in processes related to the differentiation and maturation of osteoprogenitor cells into osteoblasts. Rat bone marrow (BM) cells were cultured in a collagen-gel containing 0.5% fetal bovine serum (FBS) for 10 days in the presence of rhTGF (recombinant human TGF)-β1-F2, a fusion protein engineered to include a high-affinity collagen-binding decapeptide derived from von Willebrand factor. Subsequently, cells were moderately expanded in medium with 10% FBS for 4 days and treated with a short pulse of rhBMP (recombinant human bone morphogenetic protein)-2 for 4 h. During the last 2 days, dexamethasone and β-glycerophosphate were added to potentiate osteoinduction. Concomitant with an up-regulation of cell proliferation, DNA synthesis levels were determined. Polymerase chain reaction was performed to reveal the possible stemness of these cells. Osteogenic differentiation was evaluated in terms of alkaline phosphatase activity and mineralized matrix formation as well as by mRNA expression of osteogenic marker genes. Moreover, cells were placed inside diffusion chambers and implanted subcutaneously into the backs of adult rats for 4 weeks. Histological study provided evidence of cartilage and bone-like tissue formation. This experimental procedure is capable of selecting cell populations from BM that, in the presence of rhTGF-β1-F2 and rhBMP-2, achieve skeletogenic potential in vitro and in vivo. PMID:24968268

  19. A Novel Human TGF-β1 Fusion Protein in Combination with rhBMP-2 Increases Chondro-Osteogenic Differentiation of Bone Marrow Mesenchymal Stem Cells

    Directory of Open Access Journals (Sweden)

    Silvia Claros

    2014-06-01

    Full Text Available Transforming growth factor-beta (TGF-β is involved in processes related to the differentiation and maturation of osteoprogenitor cells into osteoblasts. Rat bone marrow (BM cells were cultured in a collagen-gel containing 0.5% fetal bovine serum (FBS for 10 days in the presence of rhTGF (recombinant human TGF-β1-F2, a fusion protein engineered to include a high-affinity collagen-binding decapeptide derived from von Willebrand factor. Subsequently, cells were moderately expanded in medium with 10% FBS for 4 days and treated with a short pulse of rhBMP (recombinant human bone morphogenetic protein-2 for 4 h. During the last 2 days, dexamethasone and β-glycerophosphate were added to potentiate osteoinduction. Concomitant with an up-regulation of cell proliferation, DNA synthesis levels were determined. Polymerase chain reaction was performed to reveal the possible stemness of these cells. Osteogenic differentiation was evaluated in terms of alkaline phosphatase activity and mineralized matrix formation as well as by mRNA expression of osteogenic marker genes. Moreover, cells were placed inside diffusion chambers and implanted subcutaneously into the backs of adult rats for 4 weeks. Histological study provided evidence of cartilage and bone-like tissue formation. This experimental procedure is capable of selecting cell populations from BM that, in the presence of rhTGF-β1-F2 and rhBMP-2, achieve skeletogenic potential in vitro and in vivo.

  20. Recent Advances in Factors and Methods for Stimulation of Biomethane Production.

    Science.gov (United States)

    Thakur, Neha; Khardenavis, Anshuman; Purohit, Hemant J

    2015-01-01

    The role of methanogenesis in the global carbon cycle is very important for recycle of renewable biomass which, has the potential for contribution to independence from fossil fuels. Anaerobic microbes comprised of fermentative and acetogenic species decompose the complex biomass to hydrogen, formate and, acetate that are further metabolized to methane by methanogens. A general review of biogenic production of methane and methanogenic diversity involved is presented. This review gives an overview of recent patents on methane production and focuses mainly on different methods, systems and, microbial methanogenic community involved in anaerobic digestion that can be used for improved understanding of the microbial community function and relationships in methanogenesis. PMID:26825255

  1. Bioenergy Consumption and Biogas Potential in Cambodian Households

    Directory of Open Access Journals (Sweden)

    Jyrki Luukkanen

    2013-04-01

    Full Text Available Residential bioenergy consumption and bioenergy resources based on by-products of residential agricultural production and animal husbandry have been analyzed statistically, based on a nationwide residential livelihood and energy survey conducted in Cambodia in 2009. Furthermore, the potential for biomethanation, residential biogas consumption and small-scale power generation for non-electrified rural areas has been assessed. Household potential of biogas substrates in Cambodia, based on nationally representative data has not been presented earlier. This paper proposes mixtures of substrates for biogas production for various livelihood zones of Cambodia. The occurrence of biomass suitable for biomethanation is most favorable in unelectrified rural areas, except for fishing villages. The theoretical daily biogas potential from animal dung and rice husk appears to be promising for households in unelectrified rural villages, both for household digesters and units designed for small-scale electricity generation. Theoretical CH4 content of biogas was 63.9% and specific biogas yield 0.41 Nm3/kg for households in unelectrified villages. Based on the survey, the energy content of biogas potential is 25.5 PJ per year. This study shows that biogas has nationally significant technical potential in Cambodia.

  2. Seasonal variation of chemical composition and biomethane production from the brown seaweed Ascophyllum nodosum.

    Science.gov (United States)

    Tabassum, Muhammad Rizwan; Xia, Ao; Murphy, Jerry D

    2016-09-01

    Ascophyllum nodosum, an abundant Irish brown seaweed, shows significant seasonal variation in chemical composition and biogas production. The polyphenol content is shown to be a more important factor in biogas production than ash content. High polyphenol content in summer months adversely affected biogas production; suggesting two potential harvest dates, March and October. A. nodosum harvested in October showed a relatively low level of polyphenols (2% of TS) and ash (23% of volatile solids), and exhibited a specific methane yield of 215LCH4kgVS(-1), which was 44% of theoretical yield. The highest yield per wet weight of 47m(3)CH4t(-1) was achieved in October, which is 2.9 times higher than the lowest value (16m(3)CH4t(-1)), obtained in December. The gross energy yield of A. nodosum based on the optimal biogas production can achieve 116GJha(-1)yr(-1) in October. PMID:27240238

  3. Potential Biogas Production from Artichoke Byproducts in Sardinia, Italy

    Directory of Open Access Journals (Sweden)

    Fabio De Menna

    2016-02-01

    Full Text Available The paper aims at evaluating the potential biogas production, both in terms of CH4 and theoretical energy potential, from globe artichoke agricultural byproducts in Sardinia. Field data about the productivity of byproducts were collected on five artichoke varieties cultivated in Sardinia, to assess the biomethane production of their aboveground non-food parts (excluding the head. Moreover, secondary data from previous studies and surveys at regional scale were collected to evaluate the potential biogas production of the different districts. Fresh globe artichoke residues yielded, on average, 292.2 Nm3·tDOM−1, with dissimilarities among cultivars. Fresh samples were analyzed in two series: (a wet basis; and (b wet basis with catalytic enzymes application. Enzymes proved to have some beneficial effects in terms of anticipated biomethane availability. At the regional level, ab. 20 × 106 Nm3 CH4 could be produced, corresponding to the 60% of current installed capacity. However, districts potentials show some differences, depending on the specific biomass partitioning and on the productivity of cultivated varieties. Regional assessments should encompass the sensitiveness of results to agro-economic variables and the economic impacts of globe artichoke residue use in the current regional biogas sector.

  4. Sphingosine 1-phosphate receptor activation enhances BMP-2-induced osteoblast differentiation

    Energy Technology Data Exchange (ETDEWEB)

    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: tsuyo-i@huhs.ac.jp [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)

    2012-06-22

    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

  5. Endothelial follistatin-like 1 regulates the maturation of the pulmonary vasculature by modulating BMP/SMAD signaling

    NARCIS (Netherlands)

    Tania, Navessa Padma; Maarsingh, Harm; Bos, Sophie T.; Mattiotti, Andrea; Prakash, Stuti; Timens, Wim; Schmidt, Martina; Van Den Hoff, Maurice; Gosens, Reinoud

    2016-01-01

    Pulmonary arterial hypertension (PAH) is a progressive disease that is characterized by vascular remodeling and sustained vasoconstriction which consequently lead to high blood pressure in the pulmonary vasculature and right ventricle remodeling. Altered bone morphogenetic protein (BMP) signaling ha

  6. BMP-15 m-RNA expression of mouse oocytes in vitro maturation in different droplet medium volume

    Institute of Scientific and Technical Information of China (English)

    Sri Rahayu; Nashi Widodo; Yumi Hoshino; Eimei Sato

    2015-01-01

    Objective:To investigate droplet medium volume effect on the BMP-15 mRNA expression. Methods:Oocytes are collected from mice ovaries by puncturing with a sterile 26-G needle. The droplet medium volumes are using 50 µL, 100 µL and 200 µL. The BMP-15 mRNA expression is determined in each group.Results:The results indicated that BMP-15 mRNA expression did not significantly differ when oocyte were cultured in 50 and 100 µL/droplet medium volume, but significant difference (P < 0.05) was found when oocytes were cultured in 200 µL/droplet medium volume.Conclusions:The highest BMP-15 m-RNA expression occur when oocytes are cultured in 200 µL/droplet medium volume.

  7. Spatially Resolved Genome-wide Transcriptional Profiling Identifies BMP Signaling as Essential Regulator of Zebrafish Cardiomyocyte Regeneration.

    Science.gov (United States)

    Wu, Chi-Chung; Kruse, Fabian; Vasudevarao, Mohankrishna Dalvoy; Junker, Jan Philipp; Zebrowski, David C; Fischer, Kristin; Noël, Emily S; Grün, Dominic; Berezikov, Eugene; Engel, Felix B; van Oudenaarden, Alexander; Weidinger, Gilbert; Bakkers, Jeroen

    2016-01-11

    In contrast to mammals, zebrafish regenerate heart injuries via proliferation of cardiomyocytes located near the wound border. To identify regulators of cardiomyocyte proliferation, we used spatially resolved RNA sequencing (tomo-seq) and generated a high-resolution genome-wide atlas of gene expression in the regenerating zebrafish heart. Interestingly, we identified two wound border zones with distinct expression profiles, including the re-expression of embryonic cardiac genes and targets of bone morphogenetic protein (BMP) signaling. Endogenous BMP signaling has been reported to be detrimental to mammalian cardiac repair. In contrast, we find that genetic or chemical inhibition of BMP signaling in zebrafish reduces cardiomyocyte dedifferentiation and proliferation, ultimately compromising myocardial regeneration, while bmp2b overexpression is sufficient to enhance it. Our results provide a resource for further studies on the molecular regulation of cardiac regeneration and reveal intriguing differential cellular responses of cardiomyocytes to a conserved signaling pathway in regenerative versus non-regenerative hearts.

  8. BMP-2 functions independently of SHH signaling and triggers cell condensation and apoptosis in regenerating axolotl limbs

    Directory of Open Access Journals (Sweden)

    Finnson Kenneth

    2010-02-01

    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

  9. Establishment of Immortalized Mouse Bmp2 Knock-Out Dental Papilla Mesenchymal Cells Necessary for Study of Odontoblastic Differentiation and Odontogenesis

    Science.gov (United States)

    Wu, Lian; Wang, Feng; Donly, Kevin J.; Wan, Chunyan; Luo, Daoshu; Harris, Stephen E.; Macdougall, Mary; Chen, Shuo

    2016-01-01

    Bmp2 is essential for dentin formation. Bmp2 cKO mice exhibited similar phenotype to dentinogenesis imperfecta, showing dental pulp exposure, hypomineralized dentin, and delayed odontoblast differentiation. As it is relatively difficult to obtain lot of primary Bmp2 cKO dental papilla mesenchymal cells and to maintain a long-term culture of these primary cells, availability of immortalized deleted Bmp2 dental papilla mesenchymal cells is critical for studying the underlying mechanism of Bmp2 signal in odontogenesis. In this study, our goal was to generate an immortalized deleted Bmp2 dental papilla mesenchymal (iBmp2ko/ko dp) cell line by introducing Cre fluorescent protein (GFP) into the immortalized mouse floxed Bmp2 dental papilla mesenchymal (iBmp2fx/fx dp) cells. iBmp2ko/ko dp cells were confirmed by GFP and PCR. The deleted Bmp2 cells exhibited slow cell proliferation rate and cell growth was arrested in G2 phase. Expression of tooth-related marker genes and cell differentiation were decreased in the deleted cells. Importantly, extracellular matrix remodeling was impaired in the iBmp2ko/ko dp cells as reflected by the decreased Mmp-9 expression. In addition, with exogenous Bmp2 induction, these cell differentiation and mineralization were rescued as well as extracellular matrix remodeling was enhanced. Therefore, we for the first time described establishment of iBmpko/ko cells that are useful for study of mechanisms in regulating dental papilla mesenchymal cell lineages. PMID:26037045

  10. Heterozygous Mutations in BMP6 Pro-peptide Lead to Inappropriate Hepcidin Synthesis and Moderate Iron Overload in Humans

    OpenAIRE

    Daher, Raed; Kannengiesser, Caroline; Houamel, Dounia; Lefebvre, Thibaud; Bardou-Jacquet, Edouard; Ducrot, Nicolas; Kerguenec, Caroline,; Jouanolle, Anne-Marie; Robreau, Anne-Marie; Oudin, Claire; Le Gac, Gerald; Moulouel, Boualem; Loustaud-Ratti, Véronique; Bedossa, Pierre; Valla, Dominique

    2015-01-01

    Background & Aims Hereditary hemochromatosis is a heterogeneous group of genetic disorders characterized by parenchymal iron overload. It is caused by defective expression of liver hepcidin, the main regulator of iron homeostasis. Iron stimulates the gene encoding (HAMP) hepcidin via the BMP6 signaling to SMAD. Although several genetic factors have been found to cause late-onset hemochromatosis, many patients have unexplained signs of iron overload. We investigated BMP6 function in these indi...

  11. A secreted BMP antagonist, Cer1, fine tunes the spatial organization of the ureteric bud tree during mouse kidney development.

    Directory of Open Access Journals (Sweden)

    Lijun Chi

    Full Text Available The epithelial ureteric bud is critical for mammalian kidney development as it generates the ureter and the collecting duct system that induces nephrogenesis in dicrete locations in the kidney mesenchyme during its emergence. We show that a secreted Bmp antagonist Cerberus homologue (Cer1 fine tunes the organization of the ureteric tree during organogenesis in the mouse embryo. Both enhanced ureteric expression of Cer1 and Cer1 knock out enlarge kidney size, and these changes are associated with an altered three-dimensional structure of the ureteric tree as revealed by optical projection tomography. Enhanced Cer1 expression changes the ureteric bud branching programme so that more trifid and lateral branches rather than bifid ones develop, as seen in time-lapse organ culture. These changes may be the reasons for the modified spatial arrangement of the ureteric tree in the kidneys of Cer1+ embryos. Cer1 gain of function is associated with moderately elevated expression of Gdnf and Wnt11, which is also induced in the case of Cer1 deficiency, where Bmp4 expression is reduced, indicating the dependence of Bmp expression on Cer1. Cer1 binds at least Bmp2/4 and antagonizes Bmp signalling in cell culture. In line with this, supplementation of Bmp4 restored the ureteric bud tip number, which was reduced by Cer1+ to bring it closer to the normal, consistent with models suggesting that Bmp signalling inhibits ureteric bud development. Genetic reduction of Wnt11 inhibited the Cer1-stimulated kidney development, but Cer1 did not influence Wnt11 signalling in cell culture, although it did inhibit the Wnt3a-induced canonical Top Flash reporter to some extent. We conclude that Cer1 fine tunes the spatial organization of the ureteric tree by coordinating the activities of the growth-promoting ureteric bud signals Gndf and Wnt11 via Bmp-mediated antagonism and to some degree via the canonical Wnt signalling involved in branching.

  12. Potential and limitations of tissue analysis as a BMP in vegetable production

    OpenAIRE

    Hartz, Tim

    2009-01-01

    The use of tissue testing of crop nitrogen status is widespread in vegetable production; given the high value of vegetable crops the interest in nutrient testing has historically been to ensure maximum production and cosmetic quality rather than to achieve high fertilizer use efficiency. In drip-irrigated culture, growers have the ability to inject N throughout the season, and the use of tissue testing to ‘fine tune’ the N fertility program is common. However, increased awareness of the env...

  13. 生物甲烷系统技术评价与集成的研究进展%Progress of evaluation and integration of biomethane system

    Institute of Scientific and Technical Information of China (English)

    武斌; 张香平; 许亚晶; 黄莺

    2014-01-01

    Biomethane route/system is one of the most important ways of reasonablely utilizing biomass,reducing emissions of carbon dioxide and other pollutants. There is not an insight analysis focusing on the material and energy conversion,economic and environment issues of the system. In order to have an insight understanding of biomethane system,this paper reviews the related units and sub-systems which affect the system from the viewpoint of process system engineering,including feedstock fermentation , biogas upgrading and product transportation , and makes analysis and evaluation. Research progress of evaluation of the effects of biomethane process on technology, economy and environment and multi-objective optimization in China and the rest of the world is presented,and technical bottlenecks and challenges of research on biomethane system are discussed. Aimed at the specialties of resources,a system integration method comprehensively considering process simulation,energy efficiency analysis,whole life cycle,and economic evaluation is required to evaluate and analyze material conversion,energy efficiency,and environmental impact in digestion of biomethane,product separation,storage,and transportation to find out the bottleneck of sustainable performance,and further to make multi-objective optimization of technology,economy and environment to achieve optimized utilization of biomethane and optimized allocation of energy resources.%生物甲烷系统是实现生物质资源化高效转化利用和二氧化碳减排的重要途径之一,符合我国国家战略的重大需求,但目前对该系统中的能量物质转化效率、经济环境性等问题的分析不够深入。为了深入认识生物甲烷系统的物质能量转化和利用情况,实现生烷甲烷体系结构的最优,本文从系统工程的思路出发,对影响整个生物甲烷系统的关键单元和子系统中的关键技术进行了分析对比,包括原料收集、发酵、甲烷提

  14. Study of orotidine 5'-monophosphate decarboxylase in complex with the top three OMP, BMP, and PMP ligands by molecular dynamics simulation.

    Science.gov (United States)

    Jamshidi, Shirin; Jalili, Seifollah; Rafii-Tabar, Hashem

    2015-01-01

    Catalytic mechanism of orotidine 5'-monophosphate decarboxylase (OMPDC), one of the nature most proficient enzymes which provides large rate enhancement, has not been fully understood yet. A series of 30 ns molecular dynamics (MD) simulations were run on X-ray structure of the OMPDC from Saccharomyces cerevisiae in its free form as well as in complex with different ligands, namely 1-(5'-phospho-D-ribofuranosyl) barbituric acid (BMP), orotidine 5'-monophosphate (OMP), and 6-phosphonouridine 5'-monophosphate (PMP). The importance of this biological system is justified both by its high rate enhancement and its potential use as a target in chemotherapy. This work focuses on comparing two physicochemical states of the enzyme (protonated and deprotonated Asp91) and three ligands (substrate OMP, inhibitor, and transition state analog BMP and substrate analog PMP). Detailed analysis of the active site geometry and its interactions is properly put in context by extensive comparison with relevant experimental works. Our overall results show that in terms of hydrogen bond occupancy, electrostatic interactions, dihedral angles, active site configuration, and movement of loops, notable differences among different complexes are observed. Comparison of the results obtained from these simulations provides some detailed structural data for the complexes, the enzyme, and the ligands, as well as useful insights into the inhibition mechanism of the OMPDC enzyme. Furthermore, these simulations are applied to clarify the ambiguous mechanism of the OMPDC enzyme, and imply that the substrate destabilization and transition state stabilization contribute to the mechanism of action of the most proficient enzyme, OMPDC.

  15. Low-power GaAlAs laser irradiation promotes the proliferation and osteogenic differentiation of stem cells via IGF1 and BMP2.

    Directory of Open Access Journals (Sweden)

    Jyun-Yi Wu

    Full Text Available Low-power laser irradiation (LPLI has been found to induce various biological effects and cellular processes. Also, LPLI has been shown to promote fracture repair. Until now, it has been unclear how LPLI promotes bone formation and fracture healing. The aim of this study was to investigate the potential mechanism of LPLI-mediated enhancement of bone formation using mouse bone marrow mesenchymal stem cells (D1 cells. D1 cells were irradiated daily with a gallium-aluminum-arsenide (GaAlAs laser at dose of 0, 1, 2, or 4 J/cm(2. The lactate dehydrogenase (LDH assay showed no cytotoxic effects of LPLI on D1 cells, and instead, LPLI at 4 J/cm(2 significantly promoted D1 cell proliferation. LPLI also enhanced osteogenic differentiation in a dose-dependent manner and moderately increased expression of osteogenic markers. The neutralization experiments indicated that LPLI regulated insulin-like growth factor 1 (IGF1 and bone morphogenetic protein 2 (BMP2 signaling to promote cell proliferation and/or osteogenic differentiation. In conclusion, our study suggests that LPLI may induce IGF1 expression to promote both the proliferation and osteogenic differentiation of D1 cells, whereas it may induce BMP2 expression primarily to enhance osteogenic differentiation.

  16. Overexpression of constitutively active BMP-receptor-IB in mouse skin causes an ichthyosis-vulgaris-like disease.

    Science.gov (United States)

    Yu, Xueyan; Espinoza-Lewis, Ramón A; Sun, Cheng; Lin, Lisong; He, Fenglei; Xiong, Wei; Yang, Jing; Wang, Alun; Chen, Yiping

    2010-12-01

    The skin is the outer layer of protection against the environment. The development and formation of the skin is regulated by several genetic cascades including the bone morphogenetic protein (BMP) signaling pathway, which has been suggested to play an important role during embryonic organ development. Several skin defects and diseases are caused by genetic mutations or disorders. Ichthyosis is a common genetic skin disorder characterized by dry scaly skin. Loss-of-function mutations in the filaggrin (FLG) gene have been identified as the cause of the ichthyosis vulgaris (IV) phenotype; however, the direct regulation of filaggrin expression in vivo is unknown. We present evidence that BMP signaling regulates filaggrin expression in the epidermis. Mice expressing a constitutively active form of BMP-receptor-IB in the developing epidermis exhibit a phenotype resembling IV in humans, including dry flaky skin, compact hyperkeratosis, and an attenuated granular layer associated with a significantly downregulated expression of filaggrin. Regulation of filaggrin expression by BMP signaling has been further confirmed by the application of exogenous BMP2 in skin explants and by a transgenic model overexpressing Noggin in the epidermis. Our results demonstrate that aberrant BMP signaling in the epidermis causes overproliferation and hyperkeratinization, leading to an IV-like skin disease.

  17. RhBMP-2 microspheres-loaded chitosan/collagen scaffold enhanced osseointegration: an experiment in dog.

    Science.gov (United States)

    Shi, Shanshan; Cheng, Xiangrong; Wang, Jiawei; Zhang, Wei; Peng, Lin; Zhang, Yufeng

    2009-01-01

    The purpose of this study is to develop a novel recombinant human bone morphogenetic protein-2 (rhBMP-2) sustained release scaffold for dental implant osseointegration, and to evaluate the effect of this scaffold on promoting bone formation. RhBMP-2 was encapsulated in the poly-D,L-lactide-co-glycolide (PLGA) biodegradable microspheres, which were subsequently dispersed in a chitosan/collagen composite scaffold. This rhBMP-2 microspheres-loaded scaffold (S-MB) was compared with a chitosan/collagen scaffold without microspheres that directly encapsulated rhBMP-2 (S-B) in vitro and in vivo. The microstructure of the new scaffold was examined with scanning electron microscopy. The release profile of rhBMP-2 in vitro was measured at interval periods. The effect of rhBMP-2 encapsulated scaffolds on enhancing bone formation through implantation in dogs' mandibles was identified by histological examination of the regenerated bone after 4 weeks of implantation. Due to PLGA microspheres being loaded, the S-MB exhibited lower values at porosity and swelling rate, as well as a higher effective release dose than that of the S-B. Bone density, bone-implant contact, and bone-fill values measured from dog experiments demonstrated that the S-MB induced bone regeneration more quickly and was timely substituted by new bone. It was concluded that this sustained carrier scaffold based on microspheres was more effective to induce implant osseointegration. PMID:18667455

  18. Bone marrow stromal cells with a combined expression of BMP-2 and VEGF-165 enhanced bone regeneration

    Energy Technology Data Exchange (ETDEWEB)

    Xiao Caiwen; Zhou Huifang; Fu Yao; Gu Ping; Fan Xianqun [Department of Ophthalmology, Shanghai Ninth People' s Hospital, Shanghai JiaoTong University School of Medicine, Shanghai 200011 (China); Liu Guangpeng [Key Laboratory of Tissue Engineering, Shanghai Ninth People' s Hospital, Shanghai JiaoTong University School of Medicine, Shanghai 200011 (China); Zhang Peng [Center for Translational Medicine Research and Development, Shenzhen Institute of Advanced Technology, Chinese Academy of Science (China); Hou Hongliang; Tang Tingting, E-mail: drfanxianqun@126.com [Department of Orthopedics, Shanghai Ninth People' s Hospital, Shanghai JiaoTong University School of Medicine, Shanghai 200011 (China)

    2011-02-15

    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.

  19. Canonical Wnt activity regulates trunk neural crest delamination linking BMP/noggin signaling with G1/S transition.

    Science.gov (United States)

    Burstyn-Cohen, Tal; Stanleigh, Jonathan; Sela-Donenfeld, Dalit; Kalcheim, Chaya

    2004-11-01

    Delamination of premigratory neural crest cells depends on a balance between BMP/noggin and on successful G1/S transition. Here, we report that BMP regulates G1/S transition and consequent crest delamination through canonical Wnt signaling. Noggin overexpression inhibits G1/S transition and blocking G1/S abrogates BMP-induced delamination; moreover, transcription of Wnt1 is stimulated by BMP and by the developing somites, which concomitantly inhibit noggin production. Interfering with beta-catenin and LEF/TCF inhibits G1/S transition, neural crest delamination and transcription of various BMP-dependent genes, which include Cad6B, Pax3 and Msx1, but not that of Slug, Sox9 or FoxD3. Hence, we propose that developing somites inhibit noggin transcription in the dorsal tube, resulting in activation of BMP and consequent Wnt1 production. Canonical Wnt signaling in turn stimulates G1/S transition and generation of neural crest cell motility independently of its proposed role in earlier neural crest specification. PMID:15456730

  20. The BMP pathway is essential for re-specification and maintenance of the dorsoventral axis in regenerating and intact planarians.

    Science.gov (United States)

    Molina, M Dolores; Saló, Emili; Cebrià, Francesc

    2007-11-01

    The bone morphogenetic protein (BMP) pathway has been shown to play an important role in the establishment of the dorsoventral axis during development in both vertebrate and invertebrate species. In an attempt to unravel the role of BMPs in pattern formation during planarian regeneration, we studied this signaling pathway in Schmidtea mediterranea. Here, we functionally characterize planarian homologues of two key elements of the pathway: Smed-BMP and Smed-Smad1. Whole-mount in situ hybridization showed that Smed-BMP is expressed at the planarian dorsal midline, suggesting a role in dorsoventral patterning, while Smed-Smad1 is widely expressed throughout the mesenchyme and in the central nervous system. RNA interference (RNAi) knockdowns of Smed-BMP or Smed-Smad1 led to the disappearance of dorsal markers along with the ectopic expression of ventral markers on the dorsal side of the treated animals. In almost all cases, a duplicated central nervous system differentiated dorsally after Smed-BMP or Smed-Smad1 RNAi. These defects were observed not only during regeneration but also in intact non-regenerating animals. Our results suggest that the BMP signaling pathway is conserved in planarians and that it plays a key role in the regeneration and maintenance of the dorsoventral axis. PMID:17905225

  1. 慢性肾脏病患者血清PTH与BMP-2的变化及意义

    Institute of Scientific and Technical Information of China (English)

    范旗; 赵燕凌; 甘西伦

    2008-01-01

    选择慢性肾脏病(CKD)患者65例和健康查体者20例(对照组),根据肾小球滤过率(GFR)将CKD患者分为五组,分别采用化学发光法和酶联免疫吸附法测定血清血清甲状旁腺激素(PTH)及骨形态发生蛋白-2(BMP-2)浓度,分析血清PTH及BMP-2浓度变化的规律.结果 CKD患者血清PTH、BMP-2浓度均明显高于对照组(P<0.01);CKD患者血清BMP-2浓度与PTH呈正相关(r=0.678,P=0.006).认为CKD患者血清PTH及BMP-2浓度随肾功能损害程度加重逐渐升高,提示PTH、BMP-2与CKD患者病情进展有一定关系.

  2. Experimental Comparison of Cranial Particulate Bone Graft, rhBMP-2, and Split Cranial Bone Graft for Inlay Cranioplasty.

    Science.gov (United States)

    Hassanein, Aladdin H; Couto, Rafael A; Kurek, Kyle C; Rogers, Gary F; Mulliken, John B; Greene, Arin K

    2013-05-01

    Background :  Particulate bone graft and recombinant human bone morphogenetic protein-2 (rhBMP-2) are options for inlay cranioplasty in children who have not developed a diploic space. The purpose of this study was to determine whether particulate bone graft or rhBMP-2 has superior efficacy for inlay cranioplasty and to compare these substances to split cranial bone. Methods :  A 17 mm × 17 mm critical-sized defect was made in the parietal bones of 22 rabbits and managed in four ways: Group I (no implant; n=5), Group II (particulate bone graft; n=5), Group III (rhBMP-2; n=7), and Group IV (split cranial bone graft; n=5). Animals underwent microcomputed tomography and histologic analysis 16 weeks after cranioplasty. Results :  Defects without an implant (Group I) demonstrated inferior ossification (41.4%; interquartile range [IQR], 28.9% to 42.5%) compared to those treated with particulate bone graft (Group II: 99.5%; IQR, 97.8% to 100%), rhBMP-2 (Group III: 99.6%; IQR, 99.5% to 100%), or split cranial bone (Group IV: 100%) (P inlay calvarial defect areas equally, although the thickness of bone healed with rhBMP-2 is inferior. Clinically, particulate bone graft or split cranial bone graft may be superior to rhBMP-2 for inlay cranioplasty.

  3. Bone marrow stromal cells with a combined expression of BMP-2 and VEGF-165 enhanced bone regeneration

    International Nuclear Information System (INIS)

    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.

  4. EMBRYO DEVELOPMENT. BMP gradients: A paradigm for morphogen-mediated developmental patterning.

    Science.gov (United States)

    Bier, Ethan; De Robertis, Edward M

    2015-06-26

    Bone morphogenetic proteins (BMPs) act in dose-dependent fashion to regulate cell fate choices in a myriad of developmental contexts. In early vertebrate and invertebrate embryos, BMPs and their antagonists establish epidermal versus central nervous system domains. In this highly conserved system, BMP antagonists mediate the neural-inductive activities proposed by Hans Spemann and Hilde Mangold nearly a century ago. BMPs distributed in gradients subsequently function as morphogens to subdivide the three germ layers into distinct territories and act to organize body axes, regulate growth, maintain stem cell niches, or signal inductively across germ layers. In this Review, we summarize the variety of mechanisms that contribute to generating reliable developmental responses to BMP gradients and other morphogen systems. PMID:26113727

  5. The Wnt and BMP Families of Signaling Morphogens at the Vertebrate Neuromuscular Junction

    Directory of Open Access Journals (Sweden)

    Juan P. Henríquez

    2011-12-01

    Full Text Available The neuromuscular junction has been extensively employed in order to identify crucial determinants of synaptogenesis. At the vertebrate neuromuscular synapse, extracellular matrix and signaling proteins play stimulatory and inhibitory roles on the assembly of functional synapses. Studies in invertebrate species have revealed crucial functions of early morphogens during the assembly and maturation of the neuromuscular junction. Here, we discuss growing evidence addressing the function of Wnt and Bone morphogenetic protein (BMP signaling pathways at the vertebrate neuromuscular synapse. We focus on the emerging role of Wnt proteins as positive and negative regulators of postsynaptic differentiation. We also address the possible involvement of BMP pathways on motor neuron behavior for the assembly and/or regeneration of the neuromuscular junction.

  6. The BMP signaling pathway at the Drosophila neuromuscular junction and its links to neurodegenerative diseases

    OpenAIRE

    Bayat, Vafa; Jaiswal, Manish; Bellen, Hugo J

    2010-01-01

    The Drosophila neuromuscular junction (NMJ) has recently provided new insights into the roles of various proteins in neurodegenerative diseases including Amyotrophic Lateral Sclerosis (ALS), Spinal Muscular Atrophy (SMA), Multiple Sclerosis (MS) Hereditary Spastic Paraplegia (HSP), and Huntington’s Disease (HD). Several developmental signaling pathways including WNT, MAPK and BMP/TGF-β signaling play important roles in the formation and growth of the Drosophila NMJ. Studies of the fly homolog...

  7. BMP-2 in der Therapie der Pseudarthrose langer Röhrenknochen

    OpenAIRE

    Hellriegel, Tom

    2010-01-01

    Effective therapy for long bone non-unions is still a challenge in trauma and orthopedic surgery and treatment is time and cost-intensive. Complications can lead to ensuing health-related problems for the patient and their ability to work can be restricted. An innovative approach to stimulate bone regeneration is the application of growth factors. Bone morphogenetic protein-2 (BMP-2) has a high osteoinductive capacity and might stimulate human non-union healing. The purpose of this stud...

  8. Efficient differentiation of embryonic stem cells into mesodermal precursors by BMP, retinoic acid and Notch signalling.

    Directory of Open Access Journals (Sweden)

    Josema Torres

    Full Text Available The ability to direct differentiation of mouse embryonic stem (ES cells into specific lineages not only provides new insights into the pathways that regulate lineage selection but also has translational applications, for example in drug discovery. We set out to develop a method of differentiating ES cells into mesodermal cells at high efficiency without first having to induce embryoid body formation. ES cells were plated on a feeder layer of PA6 cells, which have membrane-associated stromal-derived inducing activity (SDIA, the molecular basis of which is currently unknown. Stimulation of ES/PA6 co-cultures with Bone Morphogenetic Protein 4 (BMP4 both favoured self-renewal of ES cells and induced differentiation into a Desmin and Nestin double positive cell population. Combined stimulation with BMP4 and all-trans Retinoic Acid (RA inhibited self-renewal and resulted in 90% of cells expressing Desmin and Nestin. Quantitative reverse transcription-polymerase chain reaction (qPCR analysis confirmed that the cells were of mesodermal origin and expressed markers of mesenchymal and smooth muscle cells. BMP4 activation of a MAD-homolog (Smad-dependent reporter in undifferentiated ES cells was attenuated by co-stimulation with RA and co-culture with PA6 cells. The Notch ligand Jag1 was expressed in PA6 cells and inhibition of Notch signalling blocked the differentiation inducing activity of PA6 cells. Our data suggest that mesodermal differentiation is regulated by the level of Smad activity as a result of inputs from BMP4, RA and the Notch pathway.

  9. A Novel, Noncanonical BMP Pathway Modulates Synapse Maturation at the Drosophila Neuromuscular Junction

    OpenAIRE

    Sulkowski, Mikolaj J.; Tae Hee Han; Carolyn Ott; Qi Wang; Verheyen, Esther M.; Jennifer Lippincott-Schwartz; Mihaela Serpe

    2016-01-01

    Author Summary Synaptic activity and synapse development are intimately linked, but our understanding of the coupling mechanisms remains limited. Anterograde and retrograde signals together with trans-synaptic complexes enable intercellular communications. How synapse activity status is monitored and relayed across the synaptic cleft remains poorly understood. The Drosophila NMJ is a very powerful genetic system to study synapse development. BMP signaling modulates NMJ growth via a canonical,...

  10. Smurf1 plays a role in EGF inhibition of BMP2-induced osteogenic differentiation

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Hye-Lim; Park, Hyun-Jung; Kwon, Arang [Department of Molecular Genetics, School of Dentistry and Dental Research Institute, Seoul National University, Seoul 110-749 (Korea, Republic of); Baek, Kyunghwa [Department of Pharmacology, College of Dentistry and Research Institute of Oral Science, Gangneung-Wonju National University, Gangneung 210-702, Gangwondo (Korea, Republic of); Woo, Kyung Mi; Ryoo, Hyun-Mo; Kim, Gwan-Shik [Department of Molecular Genetics, School of Dentistry and Dental Research Institute, Seoul National University, Seoul 110-749 (Korea, Republic of); Baek, Jeong-Hwa, E-mail: baekjh@snu.ac.kr [Department of Molecular Genetics, School of Dentistry and Dental Research Institute, Seoul National University, Seoul 110-749 (Korea, Republic of)

    2014-05-01

    It has been demonstrated that epidermal growth factor (EGF) plays a role in supporting the proliferation of bone marrow stromal cells in bone but inhibits their osteogenic differentiation. However, the mechanism underlying EGF inhibition of osteoblast differentiation remains unclear. Smurf1 is an E3 ubiquitin ligase that targets Smad1/5 and Runx2, which are critical transcription factors for bone morphogenetic protein 2 (BMP2)-induced osteoblast differentiation. In this study, we investigated the effect of EGF on the expression of Smurf1, and the role of Smurf1 in EGF inhibition of osteogenic differentiation using C2C12 cells, a murine myoblast cell line. EGF increased Smurf1 expression, which was blocked by inhibiting the activity of either JNK or ERK. Chromatin immunoprecipitation and Smurf1 promoter assays demonstrated that c-Jun and Runx2 play roles in the EGF induction of Smurf1 transcription. EGF suppressed BMP2-induced expression of osteogenic marker genes, which were rescued by Smurf1 knockdown. EGF downregulated the protein levels of Runx2 and Smad1 in a proteasome-dependent manner. EGF decreased the transcriptional activity of Runx2 and Smurf1, which was partially rescued by Smurf1 silencing. Taken together, these results suggest that EGF increases Smurf1 expression via the activation of JNK and ERK and the subsequent binding of c-Jun and Runx2 to the Smurf1 promoter and that Smurf1 mediates the inhibitory effect of EGF on BMP2-induced osteoblast differentiation. - Highlights: • EGF increases the expression level of Smurf1 in mesenchymal precursor cells. • EGF reduces the protein levels and transcriptional activity of Runx2 and Smad1. • EGF suppresses BMP2-induced osteogenic differentiation, which is rescued by Smurf1 knockdown.

  11. 伯氏疏螺旋体膜蛋白BmpA研究进展%Progresses on Borrelia burgdorferi Membrance Protein A (BmpA)

    Institute of Scientific and Technical Information of China (English)

    宝福凯; 赖名耀; 张云波; 董坚; 赵桂萍; 陈明清; 柳爱华

    2012-01-01

    Lyme disease, a global health concern, is a zoonosis, which has been a serious threat to human. The spiroehete Borrelia burgdorferi that is transmitted by the bite of hard tick (Ixodidae) is the pathogen of Lyme disease. Borrelia burgdorferi contains many membrane proteins with immungenicity and pathogenicity. Recent researches show that BmpA is an dominant immune protein of Borrelia burgdorferi, a laminin-binding protein, and an arthritogennic factor. Research progresses of BmpA protein in biological function, Lyme arthritis pathogenesis and diagnosis of lyme disease are reviewed.%莱姆病是一种人兽共患病,已严重威胁人类健康,成全球公共卫生问题,引起全球关注.伯氏疏螺旋体是莱姆病病原体,通过蜱叮咬传播而引起莱姆病,其表面存在的膜蛋白具有免疫性和致病性.BmpA (Borreli burgdorferi membrance protein A)是伯氏疏螺旋体的主要抗原之一,为层粘连蛋白结合蛋白,是莱姆关节炎的重要致病因子,对蛋白功能、诊断应用和莱姆关节炎致病机理三方面的研究进展进行概述.

  12. Lineage tracking of mesenchymal and endothelial progenitors in BMP-induced bone formation.

    Science.gov (United States)

    Kolind, Mille; Bobyn, Justin D; Matthews, Brya G; Mikulec, Kathy; Aiken, Alastair; Little, David G; Kalajzic, Ivo; Schindeler, Aaron

    2015-12-01

    To better understand the relative contributions of mesenchymal and endothelial progenitor cells to rhBMP-2 induced bone formation, we examined the distribution of lineage-labeled cells in Tie2-Cre:Ai9 and αSMA-creERT2:Col2.3-GFP:Ai9 reporter mice. Established orthopedic models of ectopic bone formation in the hind limb and spine fusion were employed. Tie2-lineage cells were found extensively in the ectopic bone and spine fusion masses, but co-staining was only seen with tartrate-resistant acid phosphatase (TRAP) activity (osteoclasts) and CD31 immunohistochemistry (vascular endothelial cells), and not alkaline phosphatase (AP) activity (osteoblasts). To further confirm the lack of a functional contribution of Tie2-lineage cells to BMP-induced bone, we developed conditional knockout mice where Tie2-lineage cells are rendered null for key bone transcription factor osterix (Tie2-cre:Osx(fx/fx) mice). Conditional knockout mice showed no difference in BMP-induced bone formation compared to littermate controls. Pulse labeling of mesenchymal cells with Tamoxifen in mice undergoing spine fusion revealed that αSMA-lineage cells contributed to the osteoblastic lineage (Col2.3-GFP), but not to endothelial cells or osteoclast populations. These data indicate that the αSMA+ and Tie2+ progenitor lineages make distinct cellular contributions to bone formation, angiogenesis, and resorption/remodeling. PMID:26141839

  13. Dominant negative Bmp5 mutation reveals key role of BMPs in skeletal response to mechanical stimulation

    Directory of Open Access Journals (Sweden)

    Kingsley David M

    2008-04-01

    Full Text Available Abstract Background Over a hundred years ago, Wolff originally observed that bone growth and remodeling are exquisitely sensitive to mechanical forces acting on the skeleton. Clinical studies have noted that the size and the strength of bone increase with weight bearing and muscular activity and decrease with bed rest and disuse. Although the processes of mechanotransduction and functional response of bone to mechanical strain have been extensively studied, the molecular signaling mechanisms that mediate the response of bone cells to mechanical stimulation remain unclear. Results Here, we identify a novel germline mutation at the mouse Bone morphogenetic protein 5 (Bmp5 locus. Genetic analysis shows that the mutation occurs at a site encoding the proteolytic processing sequence of the BMP5 protein and blocks proper processing of BMP5. Anatomic studies reveal that this mutation affects the formation of multiple skeletal features including several muscle-induced skeletal sites in vivo. Biomechanical studies of osteoblasts from these anatomic sites show that the mutation inhibits the proper response of bone cells to mechanical stimulation. Conclusion The results from these genetic, biochemical, and biomechanical studies suggest that BMPs are required not only for skeletal patterning during embryonic development, but also for bone response and remodeling to mechanical stimulation at specific anatomic sites in the skeleton.

  14. Shaping skeletal growth by modular regulatory elements in the Bmp5 gene.

    Directory of Open Access Journals (Sweden)

    Catherine Guenther

    2008-12-01

    Full Text Available Cartilage and bone are formed into a remarkable range of shapes and sizes that underlie many anatomical adaptations to different lifestyles in vertebrates. Although the morphological blueprints for individual cartilage and bony structures must somehow be encoded in the genome, we currently know little about the detailed genomic mechanisms that direct precise growth patterns for particular bones. We have carried out large-scale enhancer surveys to identify the regulatory architecture controlling developmental expression of the mouse Bmp5 gene, which encodes a secreted signaling molecule required for normal morphology of specific skeletal features. Although Bmp5 is expressed in many skeletal precursors, different enhancers control expression in individual bones. Remarkably, we show here that different enhancers also exist for highly restricted spatial subdomains along the surface of individual skeletal structures, including ribs and nasal cartilages. Transgenic, null, and regulatory mutations confirm that these anatomy-specific sequences are sufficient to trigger local changes in skeletal morphology and are required for establishing normal growth rates on separate bone surfaces. Our findings suggest that individual bones are composite structures whose detailed growth patterns are built from many smaller lineage and gene expression domains. Individual enhancers in BMP genes provide a genomic mechanism for controlling precise growth domains in particular cartilages and bones, making it possible to separately regulate skeletal anatomy at highly specific locations in the body.

  15. BMP Signaling Modulates Hepcidin Expression in Zebrafish Embryos Independent of Hemojuvelin

    Science.gov (United States)

    Gibert, Yann; Lattanzi, Victoria J.; Zhen, Aileen W.; Vedder, Lea; Brunet, Frédéric; Faasse, Sarah A.; Babitt, Jodie L.; Lin, Herbert Y.; Hammerschmidt, Matthias; Fraenkel, Paula G.

    2011-01-01

    Hemojuvelin (Hjv), a member of the repulsive-guidance molecule (RGM) family, upregulates transcription of the iron regulatory hormone hepcidin by activating the bone morphogenetic protein (BMP) signaling pathway in mammalian cells. Mammalian models have identified furin, neogenin, and matriptase-2 as modifiers of Hjv's function. Using the zebrafish model, we evaluated the effects of hjv and its interacting proteins on hepcidin expression during embryonic development. We found that hjv is strongly expressed in the notochord and somites of the zebrafish embryo and that morpholino knockdown of hjv impaired the development of these structures. Knockdown of hjv or other hjv-related genes, including zebrafish orthologs of furin or neogenin, however, failed to decrease hepcidin expression relative to liver size. In contrast, overexpression of bmp2b or knockdown of matriptase-2 enhanced the intensity and extent of hepcidin expression in zebrafish embryos, but this occurred in an hjv-independent manner. Furthermore, we demonstrated that zebrafish hjv can activate the human hepcidin promoter and enhance BMP responsive gene expression in vitro, but is expressed at low levels in the zebrafish embryonic liver. Taken together, these data support an alternative mechanism for hepcidin regulation during zebrafish embryonic development, which is independent of hjv. PMID:21283739

  16. Delta-like 1/fetal antigen 1(DLK1/FA1) inhibits BMP2 induced osteoblast differentiation through modulation of NFκB signaling pathway

    DEFF Research Database (Denmark)

    Qiu, Weimin; Abdallah, Basem; Kassem, Moustapha

    as assessed by reduced Alp activity and osteogenic gene expression including Alp, Col1a1, Runx2 and Bglap. In addition, DLK1/FA1 inhibited BMP signaling as demonstrated by reduced gene expression of BMP-responsive genes: Junb and Id1, reduced BMP2 induced luciferase activity in C2C12 BMP luciferase reporter....... Besides, we observed that DLK1/FA1 induced strong NFκB activity evidenced by NFκB responsive luciferase reporter assay and real-time RT-PCR analysis of NFκB target genes. The inhibitory effect of NFκB signaling on BMP signaling was confirmed by luciferase assay in C2C12 BMP luciferase reporter cells...

  17. BMP-2 regulates the formation of oral sulcus in mouse tongue by altering the balance between TIMP-1 and MMP-13.

    Science.gov (United States)

    Fukui, Tadayoshi; Suga, Takeo; Iida, Ryo-Hei; Morito, Mitsuhiko; Luan, Xianghong; Diekwisch, Thomas G H; Nakamura, Yoshiki; Yamane, Akira

    2010-08-01

    The aim of this study is to investigate whether BMP-2 regulates the oral sulcus formation of mouse embryonic tongue by modifying the expression of TIMP and MMP. The BMP-2 siRNA induced a 180% increase in the depth of oral sulcus cavity (P sulcus into the mesenchymal tissues consisting of tongue floor, whereas the recombinant BMP-2 suppressed the process in the organ culture system of mouse embryonic tongue. The BMP-2 siRNA induced a 60% decrease in the expression of TIMP-1 mRNA (P sulcus in the BMP-2 siRNA treated mandibles. The recombinant BMP-2 induced a 220% increases in the expression of TIMP-1 mRNA and the area of the immunostaining for TIMP-1 around the oral sulcus was larger in the mandibles treated with the recombinant BMP-2 than the vehicle. The BMP-2 siRNA induced a 60% increase in the expression of MMP-13 protein and a marked increase in the staining intensity for MMP-13 was observed in the epithelial region of the BMP-2 siRNA treated mandibles. The recombinant BMP-2 induced a 70% decrease in the expression of MMP-13 mRNA and the decrease was mainly observed in the tissues around oral sulcus. The expressions of BMP-2, TIMP-1, and MMP-13 were verified in the tissues around in vivo developing oral sulcus at E11, 12, and 13 by immunohistochemistry. These results suggest that BMP-2 regulates the formation of oral sulcus by altering the balance between TIMP-1 and MMP-13.

  18. Safety and efficacy of rhBMP2 in posterior cervical spinal fusion for subaxial degenerative spine disease: Analysis of outcomes in 204 patients

    OpenAIRE

    Xu, Risheng; Bydon, Mohamad; Sciubba, Daniel M.; Witham, Timothy F.; Wolinsky, Jean-Paul; Gokaslan, Ziya L; Bydon, Ali

    2011-01-01

    Background: Many studies offer excellent demonstration of the ability of bone morphogenic protein (BMP) to enhance fusion rates in anterior as well as posterior lumbar surgery. Recently, BMP has also been shown to increase arthrodesis rates in anterior cervical surgery, albeit with concomitant increases in complication rates. To date, however, few studies have investigated the safety and efficacy of BMP in cervical surgeries approached posteriorly. Methods: We retrospectively reviewed 204 con...

  19. BIOMETHANE FOR TRANSPORTATION

    Science.gov (United States)

    During phase I of this project we designed and built two different small-scale biogas refineries. The first design used a caustic absorption system. Our initial results showed an increase in CH4 (methane) content from 60.50 Mol% in the raw biogas to 93.62 Mol% in th...

  20. Induction of Dental Pulp Stem Cell Odontogenic Differentiation by Overexpression of Msx1, Pax9 and Bmp4%过表达Msx1、Pax9和Bmp4对牙髓干细胞牙向分化的影响

    Institute of Scientific and Technical Information of China (English)

    黄义德; 王放放; 胡雪峰

    2011-01-01

    Tooth regeneration based on stem cells is a promising biological strategy in tissue engineering. Studies showed that odontogenesis involves in epithelial-mesenchymal interaction in developing embryo, tooth regeneration using stem cells also requires both epithelium-derived stem cells and mesenchyme-derived stem cells. In recent studies, dental pulp stem cell (DPSC), which were isolated from dental pulp tissues, showed excellent pluri-potency potential, and might be used as suitable mesenchyme-derived stem cells for tooth regeneration. In order to induce DPSCs into odontogenic lineage, we over-expressed Msxl, Pax9 and Bmp4 by lentivirus-mediated method in DPSCs, respectively. Our results showed that over-expression of Msxl, Pax9 and Bmp4 induced expression of dentin sialoprotein, osteocalcin and osteopontin, differentiation markers for odontoblasts, formed mineralized tissues, and all leaded to an elevated alkaline phosphatase in DPSCs in vitro. The ability to induce differentiation of DPSCs into odontoblasts has some difference for Msxl, Pax9 and Bmp4. Over-expression of Msxl bad the most effective induction on odontogenic differentiation in DPSCs in vitro, the second was over-expression of Bmp4, Pax9-expressing DPSCs didn't obviously express osteopontin and form calcified tissues.%在组织工程研究领域中,利用干细胞进行牙齿再生是一种途径.目前,研究认为牙齿的发育过程是上皮与间充质相互诱导的结果,利用干细胞进行再生牙齿时也需要有上皮源性和间充质源性干细胞的参与.牙髓干细胞是牙齿自体的干细胞,具有多向分化潜能,在牙齿再生中是一种理想的间充质源性千细胞.该研究通过慢病毒介导在牙髓干细胞中分别过表达人Msx1、Pax9和Bmp4基因,研究其对牙向分化的诱导潜能.过表达这三个基因均能显著提高牙髓干细胞碱性磷酸酶的水平,并且促使牙髓干细胞表达成牙本质细胞标志蛋白——牙本质涎磷蛋白

  1. Characteristics and Stimulation Potential with BMP-2 and BMP-7 of Tenocyte-Like Cells Isolated from the Rotator Cuff of Female Donors

    OpenAIRE

    Franka Klatte-Schulz; Stephan Pauly; Markus Scheibel; Stefan Greiner; Christian Gerhardt; Jelka Hartwig; Gerhard Schmidmaier; Britt Wildemann

    2013-01-01

    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...

  2. Patterning of the dorsal-ventral axis in echinoderms: insights into the evolution of the BMP-chordin signaling network.

    Directory of Open Access Journals (Sweden)

    François Lapraz

    2009-11-01

    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

  3. Compositional analysis of excavated landfill samples and the determination of residual biogas potential of the organic fraction.

    Science.gov (United States)

    García, J; Davies, S; Villa, R; Gomes, D M; Coulon, F; Wagland, S T

    2016-09-01

    The objectives of this study were to assess the biogas potential of landfilled materials and to further validate the suitability of the enzymatic hydrolysis test EHT as a valuable alternative to substitute the standardised test currently in use (BMP). Both tests were applied to a range of landfill waste samples. The waste composition and volatile solids content (VS) profile together with the BMP test results showed that the biogas potential of the waste samples was directly related to their VS content, as expected. The positive correlation between the VS and the BMP test (r=0.67) suggests that the first could be used as a primary indicator of biogas potential of waste samples. Nevertheless, it should be validated against the BMP test because, occasionally, the VS content does not equate to the biogas production. This was mainly due to the paper content of the samples which also correlates positively (r=0.77) with the BMP biogas production. The EHT results showed a higher correlation with the BMP test (r=0.91) than in previous studies which used a wider mixture of enzymes containing cellulase, hemicellulase and carbohydrase. This finding positions the EHT as a quick assessing method for the biodegradability of waste samples in future sample regimes. PMID:27290632

  4. SMAD-PI3K-Akt-mTOR pathway mediates BMP-7 polarization of monocytes into M2 macrophages.

    Directory of Open Access Journals (Sweden)

    Crystal Rocher

    Full Text Available Previously we demonstrated that bone morphogenetic protein-7 (BMP-7 treatment polarizes monocytes into M2 macrophages and increases the expression of anti-inflammatory cytokines. Despite these findings, the mechanisms for the observed BMP-7 induced monocyte polarization into M2 macrophages are completely unknown. In this study, we demonstrate the mechanisms involved in the polarization of monocytes into M2 macrophages. Apoptotic conditioned media (ACM was generated to mimic the stressed conditions, inducing monocyte polarization. Monocytes were treated with ACM along with BMP-7 and/or its inhibitor, follistatin, for 48 hours. Furthermore, an inhibitor of the PI3K pathway, LY-294002, was also studied. Our data show that BMP-7 induces polarization of monocytes into M2 macrophages while significantly increasing the expression of anti-inflammatory markers, arginase-1 and IL-10, and significantly (p<0.05 decreasing the expression of pro-inflammatory markers iNOS, IL-6, TNF-α and MCP-1; (p<0.05. Moreover, addition of the PI3K inhibitor, LY-294002, significantly (p<0.05 decreases upregulation of IL-10 and arginase-1, suggesting involvement of the PI3K pathway in M2 macrophage polarization. Next, following BMP-7 treatment, a significant (p<0.05 increase in p-SMAD1/5/8 and p-PI3K expression resulting in downstream activation of p-Akt and p-mTOR was observed. Furthermore, expression of p-PTEN, an inhibitor of the PI3K pathway, was significantly (p<0.05 increased in the ACM group. However, BMP-7 treatment inhibited its expression, suggesting involvement of the PI3K-Akt-mTOR pathway. In conclusion, we demonstrate that BMP-7 polarizes monocytes into M2 macrophages and enhances anti-inflammatory cytokine expression which is mediated by the activated SMAD-PI3K-Akt-mTOR pathway.

  5. Limiting hepatic Bmp-Smad signaling by matriptase-2 is required for erythropoietin-mediated hepcidin suppression in mice.

    Science.gov (United States)

    Nai, Antonella; Rubio, Aude; Campanella, Alessandro; Gourbeyre, Ophélie; Artuso, Irene; Bordini, Jessica; Gineste, Aurélie; Latour, Chloé; Besson-Fournier, Céline; Lin, Herbert Y; Coppin, Hélène; Roth, Marie-Paule; Camaschella, Clara; Silvestri, Laura; Meynard, Delphine

    2016-05-12

    Hepcidin, the main regulator of iron homeostasis, is repressed when erythropoiesis is acutely stimulated by erythropoietin (EPO) to favor iron supply to maturing erythroblasts. Erythroferrone (ERFE) has been identified as the erythroid regulator that inhibits hepcidin in stress erythropoiesis. A powerful hepcidin inhibitor is the serine protease matriptase-2, encoded by TMPRSS6, whose mutations cause iron refractory iron deficiency anemia. Because this condition has inappropriately elevated hepcidin in the presence of high EPO levels, a role is suggested for matriptase-2 in EPO-mediated hepcidin repression. To investigate the relationship between EPO/ERFE and matriptase-2, we show that EPO injection induces Erfe messenger RNA expression but does not suppress hepcidin in Tmprss6 knockout (KO) mice. Similarly, wild-type (WT) animals, in which the bone morphogenetic protein-mothers against decapentaplegic homolog (Bmp-Smad) pathway is upregulated by iron treatment, fail to suppress hepcidin in response to EPO. To further investigate whether the high level of Bmp-Smad signaling of Tmprss6 KO mice counteracts hepcidin suppression by EPO, we generated double KO Bmp6-Tmprss6 KO mice. Despite having Bmp-Smad signaling and hepcidin levels that are similar to WT mice under basal conditions, double KO mice do not suppress hepcidin in response to EPO. However, pharmacologic downstream inhibition of the Bmp-Smad pathway by dorsomorphin, which targets the BMP receptors, improves the hepcidin responsiveness to EPO in Tmprss6 KO mice. We concluded that the function of matriptase-2 is dominant over that of ERFE and is essential in facilitating hepcidin suppression by attenuating the BMP-SMAD signaling. PMID:26755707

  6. Distinct and overlapping gene regulatory networks in BMP- and HDAC-controlled cell fate determination in the embryonic forebrain

    Directory of Open Access Journals (Sweden)

    Scholl Catharina

    2012-07-01

    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.

  7. Wnt1 and BMP2: two factors recruiting multipotent neural crest progenitors isolated from adult bone marrow.

    Science.gov (United States)

    Glejzer, A; Laudet, E; Leprince, P; Hennuy, B; Poulet, C; Shakhova, O; Sommer, L; Rogister, B; Wislet-Gendebien, S

    2011-06-01

    Recent studies have shown that neural crest-derived progenitor cells can be found in diverse mammalian tissues including tissues that were not previously shown to contain neural crest derivatives, such as bone marrow. The identification of those "new" neural crest-derived progenitor cells opens new strategies for developing autologous cell replacement therapies in regenerative medicine. However, their potential use is still a challenge as only few neural crest-derived progenitor cells were found in those new accessible locations. In this study, we developed a protocol, based on wnt1 and BMP2 effects, to enrich neural crest-derived cells from adult bone marrow. Those two factors are known to maintain and stimulate the proliferation of embryonic neural crest stem cells, however, their effects have never been characterized on neural crest cells isolated from adult tissues. Using multiple strategies from microarray to 2D-DIGE proteomic analyses, we characterized those recruited neural crest-derived cells, defining their identity and their differentiating abilities. PMID:20976520

  8. 沼气提纯生物天然气技术研究进展%Review on biogas upgrading technologies for producing biomethane

    Institute of Scientific and Technical Information of China (English)

    郑戈; 张全国

    2013-01-01

    Biogas can be upgraded to biomethane, giving more utilization possibilities, such as utilization as autogas, or distant utilization by using the existing natural gas grid. Upgrading of biogas has gained increased attention due to rising oil and natural gas prices and increasing targets for renewable fuel quotes in many countries. This paper analyzes the possibility of the substitution of natural gas by biogas according to the characteristics and components of biogas and natural gas, and reviewed the biogas upgrading technologies including water scrubbing, organic physical scrubbing, chemical scrubbing, pressure swing adsorption (PSA), membrane separation, cryogenic upgrading, and the in situ methane enrichment processes. Among these upgrading technologies, water scrubbing and PSA are the main two processes from the point of view of commercialization, because of their comprehensive advantages in technical and economic aspects. Water scrubbing is a very simple process. In a scrubber, CO2 and H2S dissolve into the water, while CH4 does not because of their difference in solubility. PSA is the second most employed technique. In PSA processes, biogas is compressed to a vessel where it is put in contact with an adsorbent that will selectively retain CO2. In a similar manner to water scrubbing, it is possible to use chemicals to absorb CO2. However, chemical scrubbing may have higher energetic penalties since the CO2 removal in biogas is a bulk removal process. Membrane separation technology is an excellent technology with good prospects for separating CO2 and CH4. Owing to its superiority in upgrading cost and simplifying upgrading equipment, in situ methane enrichment technology is relatively simple, and there is no need for much auxiliary equipment. Therefore, it has a potential for a lower upgrading cost compared to other techniques, especially when it is used in a biogas plant with high concentration solids as materials. Furthermore, research and application of new

  9. Traf2 interacts with Smad4 and regulates BMP signaling pathway in MC3T3-E1 osteoblasts

    Energy Technology Data Exchange (ETDEWEB)

    Shimada, Koichi, E-mail: shimada-ki@dent.nihon-u.ac.jp [Department of Periodontology, Nihon University School of Dentistry, Tokyo (Japan); Division of Advanced Dental Treatment, Dental Research Center, Nihon University School of Dentistry, Tokyo (Japan); Ikeda, Kyoko [Department of Periodontology, Nihon University School of Dentistry, Tokyo (Japan); Ito, Koichi [Department of Periodontology, Nihon University School of Dentistry, Tokyo (Japan); Division of Advanced Dental Treatment, Dental Research Center, Nihon University School of Dentistry, Tokyo (Japan)

    2009-12-18

    Bone morphogenetic proteins (BMPs) play important roles in osteoblast differentiation and maturation. In mammals, the BMP-induced receptor-regulated Smads form complexes with Smad4. These complexes translocate and accumulate in the nucleus, where they regulate the transcription of various target genes. However, the function of Smad4 remains unclear. We performed a yeast two-hybrid screen using Smad4 as bait and a cDNA library derived from bone marrow, to indentify the proteins interacting with Smad4. cDNA clones for Tumor necrosis factor (TNF) receptor-associated factor 2 (Traf2) were identified, and the interaction between the endogenous proteins was confirmed in the mouse osteoblast cell line MC3T3-E1. To investigate the function of Traf2, we silenced it with siRNA. The level of BMP-2 protein in the medium, the expression levels of the Bmp2 gene and BMP-induced transcription factor genes, including Runx2, Dlx5, Msx2, and Sp7, and the phosphorylated-Smad1 protein level were increased in cells transfected with Traf2 siRNA. The nuclear accumulation of Smad1 increased with TNF-{alpha} stimulation for 30 min at Traf2 silencing. These results suggest that the TNF-{alpha}-stimulated nuclear accumulation of Smad1 may be dependent on Traf2. Thus, the interaction between Traf2 and Smad4 may play a role in the cross-talk between TNF-{alpha} and BMP signaling pathways.

  10. FGF and BMP derived from dorsal root ganglia regulate blastema induction in limb regeneration in Ambystoma mexicanum.

    Science.gov (United States)

    Satoh, Akira; Makanae, Aki; Nishimoto, Yurie; Mitogawa, Kazumasa

    2016-09-01

    Urodele amphibians have a remarkable organ regeneration ability that is regulated by neural inputs. The identification of these neural inputs has been a challenge. Recently, Fibroblast growth factor (Fgf) and Bone morphogenic protein (Bmp) were shown to substitute for nerve functions in limb and tail regeneration in urodele amphibians. However, direct evidence of Fgf and Bmp being secreted from nerve endings and regulating regeneration has not yet been shown. Thus, it remained uncertain whether they were the nerve factors responsible for successful limb regeneration. To gather experimental evidence, the technical difficulties involved in the usage of axolotls had to be overcome. We achieved this by modifying the electroporation method. When Fgf8-AcGFP or Bmp7-AcGFP was electroporated into the axolotl dorsal root ganglia (DRG), GFP signals were detectable in the regenerating limb region. This suggested that Fgf8 and Bmp7 synthesized in neural cells in the DRG were delivered to the limbs through the long axons. Further knockdown experiments with double-stranded RNA interference resulted in impaired limb regeneration ability. These results strongly suggest that Fgf and Bmp are the major neural inputs that control the organ regeneration ability. PMID:27432514

  11. mTOR signaling promotes stem cell activation via counterbalancing BMP-mediated suppression during hair regeneration.

    Science.gov (United States)

    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

    2015-02-01

    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.

  12. mTOR signaling promotes stem cell activation via counterbalancing BMP-mediated suppression during hair regeneration.

    Science.gov (United States)

    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

    2015-02-01

    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. PMID:25609845

  13. Zirconium ions up-regulate the BMP/SMAD signaling pathway and promote the proliferation and differentiation of human osteoblasts.

    Directory of Open Access Journals (Sweden)

    Yongjuan Chen

    Full Text Available Zirconium (Zr is an element commonly used in dental and orthopedic implants either as zirconia (ZrO2 or in metal alloys. It can also be incorporated into calcium silicate-based ceramics. However, the effects of in vitro culture of human osteoblasts (HOBs with soluble ionic forms of Zr have not been determined. In this study, primary culture of human osteoblasts was conducted in the presence of medium containing either ZrCl4 or Zirconium (IV oxynitrate (ZrO(NO32 at concentrations of 0, 5, 50 and 500 µM, and osteoblast proliferation, differentiation and calcium deposition were assessed. Incubation of human osteoblast cultures with Zr ions increased the proliferation of human osteoblasts and also gene expression of genetic markers of osteoblast differentiation. In 21 and 28 day cultures, Zr ions at concentrations of 50 and 500 µM increased the deposition of calcium phosphate. In addition, the gene expression of BMP2 and BMP receptors was increased in response to culture with Zr ions and this was associated with increased phosphorylation of SMAD1/5. Moreover, Noggin suppressed osteogenic gene expression in HOBs co-treated with Zr ions. In conclusion, Zr ions appear able to induce both the proliferation and the differentiation of primary human osteoblasts. This is associated with up-regulation of BMP2 expression and activation of BMP signaling suggesting this action is, at least in part, mediated by BMP signaling.

  14. BMP-2-enhanced chondrogenesis involves p38 MAPK-mediated down-regulation of Wnt-7a pathway.

    Science.gov (United States)

    Jin, Eun-Jung; Lee, Sun-Young; Choi, Young-Ae; Jung, Jae-Chang; Bang, Ok-Sun; Kang, Shin-Sung

    2006-12-31

    The bone morphogenetic protein (BMP) family has been implicated in control of cartilage development. Here, we demonstrate that BMP-2 promotes chondrogenesis by activating p38 mitogen-activated protein kinase (MAPK), which in turn downregulates Wnt-7a/b-catenin signaling responsible for proteasomal degradation of Sox9. Exposure of mesenchymal cells to BMP-2 resulted in upregulation of Sox9 protein and a concomitant decrease in the level of b-catenin protein and Wnt-7a signaling. In agreement with this, the interaction of Sox9 with b-catenin was inhibited in the presence of BMP-2. Inhibition of the p38 MAPK pathway using a dominant negative mutant led to sustained Wnt-7a signaling and decreased Sox9 expression, with consequent inhibition of precartilage condensation and chondrogenic differentiation. Moreover, overexpression of b-catenin caused degradation of Sox9 via the ubiquitin/26S proteasome pathway. Our results collectively indicate that the increase in Sox9 protein resulting from downregulation of b-catenin/Wnt-7a signaling is mediated by p38 MAPK during BMP-2 induced chondrogenesis in chick wing bud mesenchymal cells. PMID:17202865

  15. AP2γ regulates neural and epidermal development downstream of the BMP pathway at early stages of ectodermal patterning

    Institute of Scientific and Technical Information of China (English)

    Yunbo Qiao; Yue Zhu; Nengyin Sheng; Jun Chen; Ran Tao; Qingqing Zhu; Ting Zhang; Cheng Qian; Naihe Jing

    2012-01-01

    Bone morphogenetic protein (BMP) inhibits neural specification and induces epidermal differentiation during ectodermal patterning.However,the mechanism of this process is not well understood.Here we show that AP2γ,a transcription factor activator protein (AP)-2 family member,is upregulated by BMP4 during neural differentiation of pluripotent stem cells.Knockdown of AP2γ facilitates mouse embryonic stem cell (ESC) neural fate determination and impairs epidermal differentiation,whereas AP2γ overexpression inhibits neural conversion and promotes epidermal commitment.In the early chick embryo,AP2γ is expressed in the entire epiblast before HH stage 3 and gradually shifts to the putative epidermal ectoderm during HH stage 4.In the future neural plate AP2γ inhibits excessive neural expansion and it also promotes epidermal development in the surface ectoderm.Moreover,AP2γ knockdown in ESCs and chick embryos partially rescued the neural inhibition and epidermal induction effects of BMP4.Mechanistic studies showed that BMP4 directly regulates AP2γ expression through Smad1 binding to the AP2γ promoter.Taken together,we propose that during the early stages of ectodermal patterning in the chick embryo,AP2γ acts downstream of the BMP pathway to restrict precocious neural expansion in the prospective neural plate and initiates epidermal differentiation in the future epidermal ectoderm.

  16. Osteogenic differentiation as a result of BMP-2 plasmid DNA based gene therapy in vitro and in vivo.

    Science.gov (United States)

    Wegman, F; Bijenhof, A; Schuijff, L; Oner, F C; Dhert, W J A; Alblas, J

    2011-03-15

    Bone regeneration is one of the major focus points in the field of regenerative medicine. A well-known stimulus of bone formation is bone morphogenetic protein-2 (BMP-2), which has already been extensively used in clinical applications. We investigated the possibility of achieving osteogenic differentiation both in vitro and in vivo as a result of prolonged presence of BMP-2 using plasmid DNA-based gene therapy. By delivering BMP-2 cDNA in an alginate hydrogel, a versatile formulation is developed. High transfection efficiencies of up to 95% were obtained in both human multipotent stromal cells (MSCs) and MG-63 cells using naked DNA in vitro. Over a period of 5 weeks, an increasing amount of biologically active BMP-2 was released from the cells and remained present in the gel. In vivo, transfected cells were found after both two and six weeks implantation in naked mice, even in groups without seeded cells, thus indicating in vivo transfection of endogenous cells. The protein levels were effective in inducing osteogenic differentiation in vitro, as seen by elevated alkaline phosphatase (ALP) production and in vivo, as demonstrated by the production of collagen I and osteocalcin in a mineralised alginate matrix. We conclude that BMP-2 cDNA incorporated in alginate hydrogel appears to be a promising new strategy for minimal-invasive delivery of growth factors in bone regeneration.

  17. FGF and BMP derived from dorsal root ganglia regulate blastema induction in limb regeneration in Ambystoma mexicanum.

    Science.gov (United States)

    Satoh, Akira; Makanae, Aki; Nishimoto, Yurie; Mitogawa, Kazumasa

    2016-09-01

    Urodele amphibians have a remarkable organ regeneration ability that is regulated by neural inputs. The identification of these neural inputs has been a challenge. Recently, Fibroblast growth factor (Fgf) and Bone morphogenic protein (Bmp) were shown to substitute for nerve functions in limb and tail regeneration in urodele amphibians. However, direct evidence of Fgf and Bmp being secreted from nerve endings and regulating regeneration has not yet been shown. Thus, it remained uncertain whether they were the nerve factors responsible for successful limb regeneration. To gather experimental evidence, the technical difficulties involved in the usage of axolotls had to be overcome. We achieved this by modifying the electroporation method. When Fgf8-AcGFP or Bmp7-AcGFP was electroporated into the axolotl dorsal root ganglia (DRG), GFP signals were detectable in the regenerating limb region. This suggested that Fgf8 and Bmp7 synthesized in neural cells in the DRG were delivered to the limbs through the long axons. Further knockdown experiments with double-stranded RNA interference resulted in impaired limb regeneration ability. These results strongly suggest that Fgf and Bmp are the major neural inputs that control the organ regeneration ability.

  18. Traf2 interacts with Smad4 and regulates BMP signaling pathway in MC3T3-E1 osteoblasts

    International Nuclear Information System (INIS)

    Bone morphogenetic proteins (BMPs) play important roles in osteoblast differentiation and maturation. In mammals, the BMP-induced receptor-regulated Smads form complexes with Smad4. These complexes translocate and accumulate in the nucleus, where they regulate the transcription of various target genes. However, the function of Smad4 remains unclear. We performed a yeast two-hybrid screen using Smad4 as bait and a cDNA library derived from bone marrow, to indentify the proteins interacting with Smad4. cDNA clones for Tumor necrosis factor (TNF) receptor-associated factor 2 (Traf2) were identified, and the interaction between the endogenous proteins was confirmed in the mouse osteoblast cell line MC3T3-E1. To investigate the function of Traf2, we silenced it with siRNA. The level of BMP-2 protein in the medium, the expression levels of the Bmp2 gene and BMP-induced transcription factor genes, including Runx2, Dlx5, Msx2, and Sp7, and the phosphorylated-Smad1 protein level were increased in cells transfected with Traf2 siRNA. The nuclear accumulation of Smad1 increased with TNF-α stimulation for 30 min at Traf2 silencing. These results suggest that the TNF-α-stimulated nuclear accumulation of Smad1 may be dependent on Traf2. Thus, the interaction between Traf2 and Smad4 may play a role in the cross-talk between TNF-α and BMP signaling pathways.

  19. Influence of BMP-2 on early follicular development and mRNA expression of oocyte specific genes in bovine preantral follicles cultured in vitro.

    Science.gov (United States)

    Rossi, Rodrigo O D S; da Cunha, Ellen V; Portela, Antonia M L R; Passos, José R S; Costa, José J N; Silva, Anderson W B; Saraiva, Márcia V A; Peixoto, Christina A; Donato, Mariana A M; van den Hurk, Robert; Silva, José R V

    2016-03-01

    This study evaluates the effect of different concentrations (0, 10, 50 and 100ng/mL) of bone morphogenetic protein-2 (BMP-2) on primordial and secondary follicle development. It also investigates the effects of FSH and BMP-2 on the growth, morphology, ultrastructure and expression of mRNA for GDF9, NLRP5 and NPM2 genes in secondary follicles cultured for 18 days. The presence of BMP-2 at all tested concentrations increased the development of primordial follicles in vitro, but the highest concentration of BMP-2 (100 ng/mL) reduced the percentage of normal follicles when compared with tissues cultured with 10 ng/mL BMP-2. During culture of secondary follicles, in contrast to higher concentrations (50 or 100 ng/mL), 10 ng/mL BMP-2 kept the morphology of follicles during initial stages of in vitro culture. This concentration of BMP-2 also benefits maintenance of the ultrastructure of 18-day cultured follicles. The presence of both BMP-2 and FSH in culture medium resulted in a significant (PFSH and BMP-2 reduced follicular mRNA expression of GDF9 and NLRP5 when compared to follicles cultured in media containing only FSH. In combination with FSH, BMP-2 reduced the mRNA levels of NPM2, when compared to follicles cultured in control medium. It is concluded from these data that 10 ng/mL BMP-2 promotes the growth of primordial in vitro and it helps to maintain the ultrastructure of secondary follicles, while FSH is more important for better expression of follicular markers like GDF9 and NLRP5. PMID:26435174

  20. The Balance of Cell Surface and Soluble Type III TGF-β Receptor Regulates BMP Signaling in Normal and Cancerous Mammary Epithelial Cells

    Directory of Open Access Journals (Sweden)

    Catherine E. Gatza

    2014-06-01

    Full Text Available Bone morphogenetic proteins (BMPs are members of the TGF-β superfamily that are over-expressed in breast cancer, with context dependent effects on breast cancer pathogenesis. The type III TGF-β receptor (TβRIII mediates BMP signaling. While TβRIII expression is lost during breast cancer progression, the role of TβRIII in regulating BMP signaling in normal mammary epithelium and breast cancer cells has not been examined. Restoring TβRIII expression in a 4T1 murine syngeneic model of breast cancer suppressed Smad1/5/8 phosphorylation and inhibited the expression of the BMP transcriptional targets, Id1 and Smad6, in vivo. Similarly, restoring TβRIII expression in human breast cancer cell lines or treatment with sTβRIII inhibited BMP-induced Smad1/5/8 phosphorylation and BMP-stimulated migration and invasion. In normal mammary epithelial cells, shRNA-mediated silencing of TβRIII, TβRIII over-expression, or treatment with sTβRIII inhibited BMP-mediated phosphorylation of Smad1/5/8 and BMP induced migration. Inhibition of TβRIII shedding through treatment with TAPI-2 or expression of a non-shedding TβRIII mutant rescued TβRIII mediated inhibition of BMP induced Smad1/5/8 phosphorylation and BMP induced migration and/or invasion in both in normal mammary epithelial cells and breast cancer cells. Conversely, expression of a TβRIII mutant, which exhibited increased shedding, significantly reduced BMP-mediated Smad1/5/8 phosphorylation, migration, and invasion. These data demonstrate that TβRIII regulates BMP-mediated signaling and biological effects, primarily through the ligand sequestration effects of sTβRIII in normal and cancerous mammary epithelial cells and suggest that the ratio of membrane bound versus sTβRIII plays an important role in mediating these effects.

  1. Effects of rhBMP-2 on Mandibular Distraction Osteogenesis and its OPG Expression in Rabbits%rhBMP-2对兔下颌骨牵引成骨区骨保护素表达的影响

    Institute of Scientific and Technical Information of China (English)

    周蕊; 付颖; 李新

    2011-01-01

    目的:通过动物实验,研究应用外源性rhBMP-2对兔下颌骨牵引成骨区骨保护素( osteoprotegerin,OPG)的影响.方法:在48只成年大耳白兔的一侧下颌骨前部行骨切开术,分别将空白胶原、rhBMP-2 1.5 mg胶原复合物植入下颌骨切开处,用牵引器延长一侧下颌骨4 mm,稳定期第1、3、7、14天,分别处死各组动物,取牵引区新生骨痂行组织学及OPG免疫组化染色.结果:下颌牵引延长后牵引间隙均有新骨形成,应用rhBMP-2 1.5mg效果好.免疫组化染色OPG主要定位于成骨细胞的胞浆中.在同一时间内,应用rhBMP-2组较对照组有显著性差异(P<0.05).结论:动物实验表明,rhBMP-2能促进兔下颌骨牵引成骨区新骨的生成.%Objective: To investigate the effects of rhBMP- 2 on mandibular distraction osteogenesis and the expression of OPG in the period of distraction osteogenesis. Methods: Unilateral mandibular osteotomies were performed in 48 mature rabbit. rhBMP - 2 1. 5mg with the collagen carrier was implanted in the osteotomy side of mandibles. Only collagen sponge was implanted in the control group. The mandibles of 48 rabbits were lengthened by 4 mm using a distractor , The animals were killed on 1,3,7,14 days of consolidation period. The distracted calluses were harvested and processed for histological and immunohistochemistry study of OPG. Results: The regenerated bone was found in the distraction gap after mandibular lengthening. But the rhBMP-2 was better. Staining for OPG was localized in osteoblasts of the periosteal region after completion of distraction. The mandibular side treated with rhBMP-2 had greater amount of new bone formation than that treated with collagen sponge. OPG was found in the cytoplasm of osteoblasts and stained brown or dark brown by immunohistochemistry. At the same time, OPG expression indicated that there was siganificant difference between rhBMP-2 group and control group(P<0. 05). Conclusion: rhBMP -2 could accelerate

  2. Investigation of Serum BMP-7 and Insulin Resistance Levels in Pregnant Women%肥胖孕妇血清BMP-7及胰岛素抵抗水平的研究

    Institute of Scientific and Technical Information of China (English)

    汪小娟; 郝艳华; 李建梅; 刘莉莉; 刘香萍; 李小永

    2012-01-01

    Objective To investigate the changes and significances of serum BMP-7 and insulin resistance levels in obese pregnant women. Methods A number of 22 obese pregnant women were presented as case group, and 122 normal pregnant women were presented as control group. Fasting serum BMP-7,fasting glucose and fasting insulin (FINS) were examined to evaluate the insulin resistance index (HOMA-IR). Results The serum level of BMP-7 was significantly higher in obese pregnant women than that in normal pregnant women (P<0. 05) ,with an average of 1 619. 61i633. 23 ng/L and 1 472. 05 + 1 196. 18 ng/L,respectively. The HOMA-IR in obese pregnant women and normal pregnant women was 2. 30±l. 21 and 1. 80± 1. 41, respectively. Significant difference was obtained between these two groups (P<0. 05). Statistical Results showed that fasting serum BMP-7 level had a positive correlation with FINS (P<0. 05). Conclusion The rising level of serum BMP-7 in obese pregnant women may be involved in pathological insulin resistance during pregnancy.%目的 探讨肥胖孕妇血清BMP-7(人骨成形蛋白7)和胰岛素抵抗水平的变化及意义.方法 选取妊娠期肥胖孕妇22例,正常妊娠孕妇122例,测定空腹血清BMP-7、空腹血糖、空腹胰岛素(FINS),计算胰岛素抵抗指数(HOMA-IR).结果 妊娠期肥胖组血清BMP-7含量平均值1 619.61±633.23 ng/L,正常妊娠组血清BMP-7含量平均值1 472.05±1196.18 ng/L;妊娠期肥胖组血清BMP-7水平明显高于正常妊娠组(P<0.05);妊娠期肥胖组胰岛素抵抗指数平均值2.30±1.21,正常妊娠组胰岛素抵抗指数平均值1.80±1.41,两组之间的差异有统计学意义(P<0.05);分析结果显示,空腹血清BMP-7水平与FINS呈正相关(P<0.05).结论 妊娠期肥胖组孕妇血清BMP-7水平的升高,可能参与了妊娠期糖尿病病理性胰岛素抵抗的发生.

  3. Hydrogen Sulfide Improves Endothelial Dysfunction via Downregulating BMP4/COX-2 Pathway in Rats with Hypertension

    Science.gov (United States)

    2016-01-01

    Aims. We object to elucidate that protective effect of H2S on endothelium is mediated by downregulating BMP4 (bone morphogenetic protein 4)/cyclooxygenase- (COX-) 2 pathway in rats with hypertension. Methods and Results. The hypertensive rat model induced by two-kidney one-clip (2K1C) model was used. Exogenous NaHS administration (56 μmol/kg/day, intraperitoneally once a day) reduced mean arterial pressure (MAP) of 2K1C rats from 199.9 ± 3.312 mmHg to 159.4 ± 5.434 mmHg, while NaHS did not affect the blood pressure in the Sham rats and ameliorated endothelium-dependent contractions (EDCs) of renal artery in 2K1C rats. 2K1C reduced CSE level twofold, decreased plasma levels of H2S about 6-fold, increased BMP4, Nox2, and Nox4 levels 2-fold and increased markers of oxidative stress MDA and nitrotyrosine 1.5-fold, upregulated the expression of phosphorylation-p38 MAPK 2-fold, and increased protein levels of COX-2 1.5-fold, which were abolished by NaHS treatment. Conclusions. Our results demonstrate that H2S prevents activation of BMP4/COX-2 pathway in hypertension, which may be involved in the ameliorative effect of H2S on endothelial impairment. These results throw light on endothelial protective effect of H2S and provide new target for prevention and therapy of hypertension.

  4. Inhibitory Smads and bone morphogenetic protein (BMP) modulate anterior photoreceptor cell number during planarian eye regeneration.

    Science.gov (United States)

    González-Sastre, Alejandro; Molina, Ma Dolores; Saló, Emili

    2012-01-01

    Planarians represent an excellent model to study the processes of body axis and organ re-specification during regeneration. Previous studies have revealed a conserved role for the bone morphogenetic protein (BMP) pathway and its intracellular mediators Smad1/5/8 and Smad4 in planarian dorsoventral (DV) axis re-establishment. In an attempt to gain further insight into the role of this signalling pathway in planarians, we have isolated and functionally characte-rized the inhibitory Smads (I-Smads) in Schmidtea mediterranea. Two I-Smad homologues have been identified: Smed-smad6/7-1 and Smed-smad6/7-2. Expression of smad6/7-1 was detected in the parenchyma, while smad6/7-2 was found to be ex-pressed in the central nervous system and the eyes. Neither single smad6/7-1 and smad6/7-2 nor double smad6/7-1,-2 silencing gave rise to any apparent disruption of the DV axis. However, both regenerating and intact smad6/7-2 (RNAi) planarians showed defects in eye morphogenesis and displayed small, rounded eyes that lacked the anterior subpopulation of photoreceptor cells. The number of pigment cells was also reduced in these animals at later stages of regeneration. In contrast, after low doses of Smed-bmp(RNAi), planarians regenerated larger eyes in which the anterior subpopulation of photoreceptor cells was expanded. Our results suggest that Smed-smad6/7-2 and Smed-bmp control the re-specification and maintenance of anterior photoreceptor cell number in S. mediterranea. PMID:22451003

  5. Hydrogen Sulfide Improves Endothelial Dysfunction via Downregulating BMP4/COX-2 Pathway in Rats with Hypertension.

    Science.gov (United States)

    Xiao, Lin; Dong, Jing-Hui; Jin, Sheng; Xue, Hong-Mei; Guo, Qi; Teng, Xu; Wu, Yu-Ming

    2016-01-01

    Aims. We object to elucidate that protective effect of H2S on endothelium is mediated by downregulating BMP4 (bone morphogenetic protein 4)/cyclooxygenase- (COX-) 2 pathway in rats with hypertension. Methods and Results. The hypertensive rat model induced by two-kidney one-clip (2K1C) model was used. Exogenous NaHS administration (56 μmol/kg/day, intraperitoneally once a day) reduced mean arterial pressure (MAP) of 2K1C rats from 199.9 ± 3.312 mmHg to 159.4 ± 5.434 mmHg, while NaHS did not affect the blood pressure in the Sham rats and ameliorated endothelium-dependent contractions (EDCs) of renal artery in 2K1C rats. 2K1C reduced CSE level twofold, decreased plasma levels of H2S about 6-fold, increased BMP4, Nox2, and Nox4 levels 2-fold and increased markers of oxidative stress MDA and nitrotyrosine 1.5-fold, upregulated the expression of phosphorylation-p38 MAPK 2-fold, and increased protein levels of COX-2 1.5-fold, which were abolished by NaHS treatment. Conclusions. Our results demonstrate that H2S prevents activation of BMP4/COX-2 pathway in hypertension, which may be involved in the ameliorative effect of H2S on endothelial impairment. These results throw light on endothelial protective effect of H2S and provide new target for prevention and therapy of hypertension. PMID:27642495

  6. Anti-Müllerian hormone (AMH), inhibin-α, growth differentiation factor 9 (GDF9), and bone morphogenic protein-15 (BMP15) mRNA and protein are influenced by photoperiod-induced ovarian regression and recrudescence in Siberian hamster ovaries.

    Science.gov (United States)

    Shahed, Asha; Young, Kelly A

    2013-11-01

    Exposure of Siberian hamsters to short photoperiod (SD) inhibits ovarian function, including folliculogenesis, whereas function is restored with their transfer to long photoperiods (LD). To investigate the mechanism of photo-stimulated recrudescence, we assessed key folliculogenic factors-anti-Müllerian hormone (AMH), inhibin-α, growth differentiation factor-9 (GDF9), and bone morphogenic protein-15 (BMP15)-across the estrus cycle and in photo-regressed and recrudescing ovaries. Adult hamsters were exposed to either LD or SD for 14 weeks, which respectively represent functional and regressed ovaries. Select regressed hamsters were transferred back to LD for 2 (post-transfer week 2; PTw2) or 8 weeks (PTw8). Ovaries were collected and fixed in formalin for immunohistochemistry or frozen in liquid nitrogen for real-time PCR. AMH, inhibin-α, GDF9, and BMP15 mRNA and protein were detected in all stages of the estrus cycle. Fourteen weeks of SD exposure increased (P hamsters to stimulatory long photoperiod for 8 weeks returned AMH and GDF9 mRNA levels to LD-treated levels, and further increased mRNA levels for inhibin-α and BMP15. Immunostaining for AMH, inhibin-α, GDF9, and BMP15 proteins was most intense in preantral/antral follicles and oocytes. The overall immunostaining extent for AMH and inhibin-α generally mirrored the mRNA data, though no changes were observed for GDF9 or BMP15 immunostaining. Shifts in mRNA and protein levels across photoperiod conditions suggest possible syncretic roles for these folliculogenic factors in photo-stimulated recrudescence via potential regulation of follicle recruitment, preservation, and development.

  7. BMP2基因修饰犬脂肪源性基质细胞修复自体大段骨缺损%Repairing canine segmental bone defects using BMP2 gene modified adipose-derived stromal cells

    Institute of Scientific and Technical Information of China (English)

    李慧武; 戴尅戎; 汤亭亭; 张晓玲; 唐坚; 孙晓江; 张双燕; 楼觉人

    2008-01-01

    Objective To evaluate osteogenetic effectiveness of porous β-tricalcium phosphate(β-TCP) ceramic mixed with human bone morphogenetic protein2 gene(Adv-hBMP2)modified adipose derived stromal cells (ADSCs) in the repair of critical-sized bone defects..Methods The ADSCs taken from the back of beagle dogs were modified by the BMP2 gene.The expression and bone-induction ability of BMP2 was identified by ELISA and ectopic bone formation in nude mice.The cells were applied to a β-tricalcium phosphate (TGP)carrier and implanted into ulnar bone defects in the canine model.18 ulnar bone defects were divided into three groups randomly and filled with granular TCP alone,granular TCP and ADSCs,or TCP and ADSCs transduced with Adv-hBMP2 respectively.All dogs were followed clinically and roentgenographically for 16 weeks and then sacrificed.Results ELISA and ectopic bone formation in nude mice showed the recombinant ADSCs could express BMP2 highly and stably.No bone defects healed after implanting granular TCP alone or granular TCP and ADSCs.In the TCP and ADSCs transduced with AdvhBMP2 group,two defects healed,four partly healed.Histological examination showed woven bone at the both end of the cortices but entirelv fibrous tissue in the middle in which defects filled with TCP alone or TCP and ADSCs.Defects filled with TCP and transduced ADSCs showed substatial new bone formation.Histomorphometry showed TCP combined with ADSCs did not significantly increase new bone area compared with TCP alone.TCP and recombinant ADSCs produced a significant increase in newly formed bone area.Conclusion ADSCs tansduced with BMP2 gene in a TCP carrier can enhance bone regeneratmn to repair the critically-sized bone defect.%目的 评价BMP2基因修饰的犬脂肪源性基质细胞(ADSCs)与β-磷酸三钙(β-TCP)复合修复自体大段骨缺损的疗效.方法 从比格犬背部脂肪组织中提取基质细胞,转染腺病毒介导的人BMP2基因(Adv-hBMP2),通过ELISA和裸鼠体内异位成骨实验鉴定BMP

  8. Disequilibrium of BMP2 Levels in the Breast Stem Cell Niche Launches Epithelial Transformation by Overamplifying BMPR1B Cell Response

    Directory of Open Access Journals (Sweden)

    Marion Chapellier

    2015-02-01

    Full Text Available Understanding the mechanisms of cancer initiation will help to prevent and manage the disease. At present, the role of the breast microenvironment in transformation remains unknown. As BMP2 and BMP4 are important regulators of stem cells and their niches in many tissues, we investigated their function in early phases of breast cancer. BMP2 production by tumor microenvironment appeared to be specifically upregulated in luminal tumors. Chronic exposure of immature human mammary epithelial cells to high BMP2 levels initiated transformation toward a luminal tumor-like phenotype, mediated by the receptor BMPR1B. Under physiological conditions, BMP2 controlled the maintenance and differentiation of early luminal progenitors, while BMP4 acted on stem cells/myoepithelial progenitors. Our data also suggest that microenvironment-induced overexpression of BMP2 may result from carcinogenic exposure. We reveal a role for BMP2 and the breast microenvironment in the initiation of stem cell transformation, thus providing insight into the etiology of luminal breast cancer.

  9. Disequilibrium of BMP2 Levels in the Breast Stem Cell Niche Launches Epithelial Transformation by Overamplifying BMPR1B Cell Response

    Science.gov (United States)

    Chapellier, Marion; Bachelard-Cascales, Elodie; Schmidt, Xenia; Clément, Flora; Treilleux, Isabelle; Delay, Emmanuel; Jammot, Alexandre; Ménétrier-Caux, Christine; Pochon, Gaëtan; Besançon, Roger; Voeltzel, Thibault; Caron de Fromentel, Claude; Caux, Christophe; Blay, Jean-Yves; Iggo, Richard; Maguer-Satta, Véronique

    2015-01-01

    Summary Understanding the mechanisms of cancer initiation will help to prevent and manage the disease. At present, the role of the breast microenvironment in transformation remains unknown. As BMP2 and BMP4 are important regulators of stem cells and their niches in many tissues, we investigated their function in early phases of breast cancer. BMP2 production by tumor microenvironment appeared to be specifically upregulated in luminal tumors. Chronic exposure of immature human mammary epithelial cells to high BMP2 levels initiated transformation toward a luminal tumor-like phenotype, mediated by the receptor BMPR1B. Under physiological conditions, BMP2 controlled the maintenance and differentiation of early luminal progenitors, while BMP4 acted on stem cells/myoepithelial progenitors. Our data also suggest that microenvironment-induced overexpression of BMP2 may result from carcinogenic exposure. We reveal a role for BMP2 and the breast microenvironment in the initiation of stem cell transformation, thus providing insight into the etiology of luminal breast cancer. PMID:25601208

  10. Surface delivery of tunable doses of BMP-2 from an adaptable polymeric scaffold induces volumetric bone regeneration.

    Science.gov (United States)

    Bouyer, Michael; Guillot, Raphael; Lavaud, Jonathan; Plettinx, Cedric; Olivier, Cécile; Curry, Véronique; Boutonnat, Jean; Coll, Jean-Luc; Peyrin, Françoise; Josserand, Véronique; Bettega, Georges; Picart, Catherine

    2016-10-01

    The rapid and effective bone regeneration of large non-healing defects remains challenging. Bioactive proteins, such as bone morphogenetic protein (BMP)-2, are proved their osteoinductivity, but their clinical use is currently limited to collagen as biomaterial. Being able to deliver BMP-2 from any other biomaterial would broaden its clinical use. This work presents a novel means for repairing a critical size volumetric bone femoral defect in the rat by combining a osteoinductive surface coating (2D) to a polymeric scaffold (3D hollow tube) made of commercially-available PLGA. Using a polyelectrolyte film as BMP-2 carrier, we tune the amount of BMP-2 loaded in and released from the polyelectrolyte film coating over a large extent by controlling the film crosslinking level and initial concentration of BMP-2 in solution. Using microcomputed tomography and quantitative analysis of the regenerated bone growth kinetics, we show that the amount of newly formed bone and kinetics can be modulated: an effective and fast repair was obtained in 1-2 weeks in the best conditions, including complete defect bridging, formation of vascularized and mineralized bone tissue. Histological staining and high-resolution computed tomography revealed the presence of bone regeneration inside and around the tube with spatially distinct organization for trabecular-like and cortical bones. The amount of cortical bone and its thickness increased with the BMP-2 dose. In view of the recent developments in additive manufacturing techniques, this surface-coating technology may be applied in combination with various types of polymeric or metallic scaffolds to offer new perspectives of bone regeneration in personalized medicine. PMID:27454063

  11. Co-generation of biohydrogen and biomethane through two-stage batch co-fermentation of macro- and micro-algal biomass.

    Science.gov (United States)

    Ding, Lingkan; Cheng, Jun; Xia, Ao; Jacob, Amita; Voelklein, Markus; Murphy, Jerry D

    2016-10-01

    Aquatic micro-algae can be used as feedstocks for gaseous biofuel production via biological fermentation. However, micro-algae usually have low C/N ratios, which are not advantageous for fermentation. In this study, carbon-rich macro-algae (Laminaria digitata) mixed with nitrogen-rich micro-algae (Chlorella pyrenoidosa and Nannochloropsis oceanica) were used to maintain a suitable C/N ratio of 20 for a two-stage process combining hydrogen and methane fermentation. Co-fermentation of L. digitata and micro-algae facilitated hydrolysis and acidogenesis, resulting in hydrogen yields of 94.5-97.0mL/gVS; these values were 15.5-18.5% higher than mono-fermentation using L. digitata. Through the second stage of methane co-fermentation, a large portion of energy remaining in the hydrogenogenic effluents was recovered in the form of biomethane. The two-stage batch co-fermentation markedly increased the energy conversion efficiencies (ECEs) from 4.6-6.6% during the hydrogen fermentation to 57.0-70.9% in the combined hydrogen and methane production.

  12. Co-generation of biohydrogen and biomethane through two-stage batch co-fermentation of macro- and micro-algal biomass.

    Science.gov (United States)

    Ding, Lingkan; Cheng, Jun; Xia, Ao; Jacob, Amita; Voelklein, Markus; Murphy, Jerry D

    2016-10-01

    Aquatic micro-algae can be used as feedstocks for gaseous biofuel production via biological fermentation.