Sample records for cber regulated product

  1. CBERS-02 Application Assessment

    GUO Jianning; YU Jin; MIN Xiangjun; LI Xingchao; HOU Minghui


    As the successor of CBERS-01, CBERS-02 was launched successfully on 21October 2003 and transmitted its first downlink data the next day. According to the OBT (On Board Test) outline, CRESDA cooperated with CAST and many remote sensing organizations in China in implementing the test of the satellite payloads, ground processing system and data application. In this paper, the test is briefly illustrated in three parts: Ⅰ. Satellite Parameters Test (especially the test for payloads), Ⅱ. Payload Image Quality Assessment, and Ⅲ. Data Application Assessment. The results of the test show that the image quality of CBERS-02 is much improved over CBERS-01 and will continue to play a more important role in the society and economic development of China.

  2. The Prototype Development for The Second Generation CBERS Initiates



    It's reported that the concept for the second generation CBERS-CBERS-03 & 04 to be jointly developed by China Academy of Space Technology (CAST) and INPE went through the assessment by China Aerospace Science and Technology Corporation (CASC) at the beginning of the year. It means that the prototype development of CBERS-03 & 04 has been initiated.



    CRESDA Application System of CBERS-1 was established in 1999. During the operation of the system for more than two years, about 240 000 scenes of CBERS-1 Level 0 data have been archived and more than 13 000 scenes of Level 2 products have been ordered by end users from different application fields.In this paper, the typical examples of applications in crop yield estimation,calamity alleviation, resources survey and protection, environment monitoring and continuable development, and urban planning are mainly described.

  4. Applications Of CBERS Data In Oceanic Research

    Li Xiaomin; Zhang Jie; Ma Yi; Song Pingjian


    @@ The CBERS series satellite data has been widely used by the First Institute of Oceanography, State Oceanic Administration (SOA) for the studies related to the monitoring of coral islands, land use changes of islands and coastal zone, green tide,implementation of ocean functional zoning, suspended particulate matter,sea ice, rafts cultivation and so on.The data covers the range of islands,coastal zone and inshore sea areas.

  5. The Application Achievements And Perspective Of CBERS Series Satellite Imagery

    Li Xingchao; Qi Xueyong; Lu Yilin


    @@ Since the first China-Brazil Earth Resources Satellite (CBERS-1),launched in 1999,the CBERS data has been applied in many fields extensively.Remarkable social and economic benefits have been achieved.This article presents the application achievements during the past nine years,and gives a perspective for the future.All these applications demonstrate that the CBERS data has been an important data source for resources investigation and monitoring.

  6. Atmospheric correction of CBERS CCD images with MODIS data

    LI Junsheng; ZHANG Bing; CHEN Zhengchao; SHEN Qian


    China Brazil Earth Resource Satellite (CBERS) CCD images have much potential for inland water environmental monitoring. However, their atmospheric accuracy correction can affect their quantitative applications. This paper contains an atmospheric correction algorithm for CBERS CCD images with MODIS data from the same day, the use of which improves the atmospheric correction algorithm of ocean color remote sensing developed by Gordon (1993, 1994) and makes it applicable to inland waters. The improved algorithm retrieves atmospheric parameters from MODIS data and uses them to perform the atmospheric correction of CBERS CCD images. Experimental results show that the atmospheric correction algorithm of CBERS CCD images assisted by MODIS data is reliable. Furthermore, MODIS data can be freely obtained on a daily basis, making the algorithm developed in this paper useful for environmental monitoring of inland waters.

  7. A tasseled cap transformation for CBERS-02B CCD data

    Li SHENG; Jing-feng HUANG; Xiao-lu TANG


    The tasseled cap transformation of remote sensing data has been widely used in agriculture,forest,ecology,and landscape.In this paper,tasseled cap transformation coefficients appropriate for data from a new sensor (China & Brazil Earth Resource Satellite (CBERS-02B)) are presented.The first three components after transformation captured 98% of the four-band variance,and represent the physical characteristics of brightness (coefficients:0.509,0.431,0.330,and 0.668),greenness (coefficients:-0.494,-0.318,-0.324,and 0.741),and blueness (coefficients:0.581,-0.070,-0.811,and 0.003),respectively.We hope these results will enhance the application of CBERS-02B charge-coupled device (CCD) data in the areas of agriculture,forest,ecology,and landscape.

  8. Topographic correction realization based on the CBERS-02B image

    Qin, Hui-ping; Yi, Wei-ning; Fang, Yong-hua


    The special topography of mountain terrain will induce the retrieval distortion in same species and surface spectral lines. In order to improve the research accuracy of topographic surface characteristic, many researchers have focused on topographic correction. Topographic correction methods can be statistical-empirical model or physical model, in which the methods based on the digital elevation model data are most popular. Restricted by spatial resolution, previous model mostly corrected topographic effect based on Landsat TM image, whose spatial resolution is 30 meter that can be easily achieved from internet or calculated from digital map. Some researchers have also done topographic correction based on high spatial resolution images, such as Quickbird and Ikonos, but there is little correlative research on the topographic correction of CBERS-02B image. In this study, liao-ning mountain terrain was taken as the objective. The digital elevation model data was interpolated to 2.36 meter by 15 meter original digital elevation model one meter by one meter. The C correction, SCS+C correction, Minnaert correction and Ekstrand-r were executed to correct the topographic effect. Then the corrected results were achieved and compared. The images corrected with C correction, SCS+C correction, Minnaert correction and Ekstrand-r were compared, and the scatter diagrams between image digital number and cosine of solar incidence angel with respect to surface normal were shown. The mean value, standard variance, slope of scatter diagram, and separation factor were statistically calculated. The analysed result shows that the shadow is weakened in corrected images than the original images, and the three-dimensional affect is removed. The absolute slope of fitting lines in scatter diagram is minished. Minnaert correction method has the most effective result. These demonstrate that the former correction methods can be successfully adapted to CBERS-02B images. The DEM data can be

  9. Whither tobacco product regulation?

    McNeill, Ann; Hammond, David; Gartner, Coral


    Despite decades of industry innovation and regulatory efforts, the harmfulness of conventional cigarettes has not changed. There are several pitfalls in this area, including the long time lag before health impacts of product regulatory changes become apparent, the danger of consumers deriving false reassurance of lesser harm in the interim period, the lack of relevant expertise and the lack of an internationally agreed and evidence-based strategic approach. Articles 9 and 10 of the Framework Convention on Tobacco Control provide the potential for such a global strategy, and knowledge and research has increased significantly over recent years. However, there are huge opportunity costs in implementing product disclosure and regulatory strategies: most national regulators have very limited human and financial resources, which should be focused on other evidence-based tobacco control interventions. We believe therefore that it is now time to abandon the notion of safe or safer cigarettes while moving consumers towards cleaner nicotine products as soon as possible. In parallel to this, we recommend a number of other strategies be implemented including: reducing the appeal of all tobacco products, forbidding new tobacco products or brand variants being marketed without evidence of reduced harm, appeal or addictiveness, and developing a tobacco industry resourced, but industry independent, Framework Convention on Tobacco Control global repository to assist national regulators in understanding and regulating the products on their markets. PMID:22345253

  10. Discriminação de variedades de citros em imagens CCD/CBERS-2 Discrimination of citrus varieties using CCD/CBERS-2 satellite imagery

    Ieda Del'Arco Sanches


    Full Text Available O presente trabalho teve o objetivo de avaliar as imagens CCD/CBERS-2 quanto à possibilidade de discriminarem variedades de citros. A área de estudo localiza-se em Itirapina (SP e, para este estudo, foram utilizadas imagens CCD de três datas (30/05/2004, 16/08/2004 e 11/09/2004. Um modelo que integra os elementos componentes da cena citrícola sensoriada é proposto com o objetivo de explicar a variabilidade das respostas das parcelas de citros em imagens orbitais do tipo CCD/CBERS-2. Foram feitas classificações pelos algoritmos Isoseg e Maxver e, de acordo com o índice kappa, concluiu-se que é possível obterem-se exatidões qualificadas como muito boas, sendo que as melhores classificações foram conseguidas com imagens da estação seca.This paper was aimed at evaluating the possibility of discriminating citrus varieties in CCD imageries from CBERS-2 satellite ("China-Brazil Earth Resouces Satellite". The study area is located in Itirapina, São Paulo State. For this study, three CCD images from 2004 were acquired (May 30, August 16, and September 11. In order to acquire a better understanding and for explaining the variability of the spectral behavior of the citrus areas in orbital images (like as the CCD/CBERS-2 images a model that integrates the elements of the citrus scene is proposed and discussed. The images were classified by Isoseg and MaxVer classifiers. According to kappa index, it was possible to obtain classifications qualified as 'very good'. The best results were obtained with the images from the dry season.

  11. Assessing the Relative Ecological Importance and Deforestation Risks of Unprotected Areas in Western Brazil Using Landsat, CBERS and Quantum GIS

    Smith, A.; Sevilla, C.; Lanclos, A.; Carson, C.; Larson, J.; Sankaran, M.; Saad, M.


    In addition to understanding Brazilian policies and currently utilized methodologies, the measurement of the impacts of deforestation is essential for enhancing techniques to reduce deforestation in the future. Adverse impacts of deforestation include biodiversity loss, increased carbon dioxide emissions, and a reduced rate of evapotranspiration, all of which contribute directly or indirectly to global warming. With the continual growth in population in developing countries such as Brazil, increased demands are placed on infrastructural development and food production. As a result, forested areas are cleared for agricultural production. Recently, exploration for hydrocarbons in Western Brazil has also intensified as a means to stimulate the economy, as abundant oil and gas is believed to be found in these regions. Unfortunately, hydrocarbon-rich regions of Western Brazil are also home to thousands of species. Many of these regions are as of yet untapped but are at risk of ecological disruption as a result of impending human activity. This project utilized Landsat 5 TM to monitor deforestation in a subsection of the Brazilian states of Rondônia and Amazonas. A risk map identifying areas susceptible to future deforestation, based on factors such as proximity to roads, bodies of water, cities, and proposed hydrocarbon activities such as pipeline construction, was created. Areas at higher risk of clearance were recommended to be a target for enhanced monitoring and law enforcement. In addition, an importance map was created based on biodiversity and location of endangered species. This map was used to identify potential areas for future protection. A Chinese-Brazilian satellite, CBERS 2B CCD was also utilized for comparison. The NDVI model was additionally replicated in Quantum GIS, an open source software, so that local communities and policymakers could benefit without having to pay for expensive ArcGIS software. The capabilities of VIIRS were also investigated to

  12. Asbestos products, hazards, and regulation.

    Castleman, Barry


    Asbestos is present in the United States in a multitude of products used in past decades, and in some products that continue to be imported and domestically produced. We have limited information on the hazards posed by some of these individual products and no information at all on most of them. Legal discovery of corporate documents has shed some light on the use of asbestos in some products and exposures from asbestos in others, sometimes adding considerably to what was in the published literature. But liability concerns have motivated corporate efforts to curtail governmental public health guidance on long-recognized hazards to workers. Liability considerations have also evidently led, in the case of asbestos brake linings, to the support of publication in the scientific literature of review articles denying in the 21st century what had been widely accepted and established in health policy in the 20th century. This report is an effort to illustrate the suppression and emergence of scientific knowledge in a climate of regulation and liability. Examples discussed are vinyl-asbestos flooring, feminine hygiene products, automotive friction materials, and asbestos contamination of other minerals such as talc and vermiculite. Global efforts to deal with the hazards of continuing marketing of asbestos products are also discussed. PMID:16878394

  13. Energetic particle radiations measured by particle detector on board CBERS-1 satellite

    HAO YongQiang; XIAO Zuo; ZOU Hong; ZHANG DongHe


    Using the data measured by energetic particle detector on board CBERS-01 and -02 for the past five years, statistics was made to show the general features of MeV electrons and protons along a solar synchronous orbit at an altitude of 780 km. This height is in the bottom region of the Earth's radiation belts. Detectors are inside the satellite cabinet and such continuous monitoring of particle radiation environment inside a satellite has seldom conducted so far. After a proper and careful treatment, it is indicated that the data inside satellite are well correlated with the radiation environment outside. Besides the agreement of the general distribution characteristics of energetic electrons and protons with similar observations from other satellites, attention is particularly paid to the disturbed conditions. Variations of particle fluxes are closely related with solar proton events, in general, electron fluxes of outer belt are well correlated with Dst index after three days' delay while the electron injection occurred almost at the same day during great magnetic storms. It is confirmed that both energetic electrons and protons appear in the Polar Cap region only after the solar proton events.


    E. Amraei


    Full Text Available CCD Camera is a multi-spectral sensor that is carried by CBERS 2 satellite. Imaging technique in this sensor is push broom. In images acquired by the CCD Camera, some vertical striping noise can be seen. This is due to the detectors mismatch, inter detector variability, improper calibration of detectors and low signal-to-noise ratio. These noises are more profound in images acquired from the homogeneous surfaces, which are processed at level 2. However, the existence of these noises render the interpretation of the data and extracting information from these images difficult. In this work, spatial moment matching method is proposed to modify these images. In this method, the statistical moments such as mean and standard deviation of columns in each band are used to balance the statistical specifications of the detector array to those of reference values. After the removal of the noise, some periodic diagonal stripes remain in the image where their removal by using the aforementioned method seems impossible. Therefore, to omit them, frequency domain Butterworth notch filter was applied. Finally to evaluate the results, the image statistical moments such as the mean and standard deviation were deployed. The study proves the effectiveness of the method in noise removal.

  15. FDA 101: Regulating Biological Products

    ... and Human Services FDA U.S. Food and Drug Administration Protecting and Promoting Your Health A to Z ... public health needs enforces regulations to prevent the introduction or spread of communicable diseases within the country ...

  16. Land use mapping from CBERS-2 images with open source tools by applying different classification algorithms

    Sanhouse-García, Antonio J.; Rangel-Peraza, Jesús Gabriel; Bustos-Terrones, Yaneth; García-Ferrer, Alfonso; Mesas-Carrascosa, Francisco J.


    Land cover classification is often based on different characteristics between their classes, but with great homogeneity within each one of them. This cover is obtained through field work or by mean of processing satellite images. Field work involves high costs; therefore, digital image processing techniques have become an important alternative to perform this task. However, in some developing countries and particularly in Casacoima municipality in Venezuela, there is a lack of geographic information systems due to the lack of updated information and high costs in software license acquisition. This research proposes a low cost methodology to develop thematic mapping of local land use and types of coverage in areas with scarce resources. Thematic mapping was developed from CBERS-2 images and spatial information available on the network using open source tools. The supervised classification method per pixel and per region was applied using different classification algorithms and comparing them among themselves. Classification method per pixel was based on Maxver algorithms (maximum likelihood) and Euclidean distance (minimum distance), while per region classification was based on the Bhattacharya algorithm. Satisfactory results were obtained from per region classification, where overall reliability of 83.93% and kappa index of 0.81% were observed. Maxver algorithm showed a reliability value of 73.36% and kappa index 0.69%, while Euclidean distance obtained values of 67.17% and 0.61% for reliability and kappa index, respectively. It was demonstrated that the proposed methodology was very useful in cartographic processing and updating, which in turn serve as a support to develop management plans and land management. Hence, open source tools showed to be an economically viable alternative not only for forestry organizations, but for the general public, allowing them to develop projects in economically depressed and/or environmentally threatened areas.

  17. The Organization of Regulated Production

    Jansen, Jos; Jeon, Doh-Shin; Menicucci, Domenico


    weak positive (respectively, strong positive) correlation. Second, if the firms can collude under VS and know all costs, then VS is equivalent to VI. However, if firms collude under asymmetric information, then collusion does not affect the choice between VS and VI, since the regulator takes advantage...

  18. Product market regulation, firm selection and unemployment

    Felbermayr, Gabriel; Prat, J.


    This paper analyzes the effect of product market regulation (PMR) on unemployment in a search model with heterogeneous multiple-worker firms. In our setup, PMR modifies the distribution of firm productivities, thereby affecting the equilibrium rate of unemployment. We distinguish between PMR related to entry costs and PMR that generates recurrent fixed costs. We find that: (i) higher entry costs raise the rate of unemployment mainly through our novel selection effect, (ii) higher fixed costs ...

  19. Italian air pollution normative regulating energy production

    This paper presents the Italian Normative DPR 203/88 regulating the quality of fossil fuels used by energy production plants and the quality of flue gas in terms of released concentrations of nitrogen and sulfur oxides, carbon monoxide, and total suspended particulates. In addition to large utility power plants, the types of production equipment covered by the guidelines include industrial-plant scaled cogeneration plants. The paper also outlines the administrative procedures related to plant start-up and operation authorization

  20. Identifying Spatial Units of Human Occupation in the Brazilian Amazon Using Landsat and CBERS Multi-Resolution Imagery

    Maria Isabel Sobral Escada


    Full Text Available Every spatial unit of human occupation is part of a network structuring an extensive process of urbanization in the Amazon territory. Multi-resolution remote sensing data were used to identify and map human presence and activities in the Sustainable Forest District of Cuiabá-Santarém highway (BR-163, west of Pará, Brazil. The limits of spatial units of human occupation were mapped based on digital classification of Landsat-TM5 (Thematic Mapper 5 image (30m spatial resolution. High-spatial-resolution CBERS-HRC (China-Brazil Earth Resources Satellite-High-Resolution Camera images (5 m merged with CBERS-CCD (Charge Coupled Device images (20 m were used to map spatial arrangements inside each populated unit, describing intra-urban characteristics. Fieldwork data validated and refined the classification maps that supported the categorization of the units. A total of 133 spatial units were individualized, comprising population centers as municipal seats, villages and communities, and units of human activities, such as sawmills, farmhouses, landing strips, etc. From the high-resolution analysis, 32 population centers were grouped in four categories, described according to their level of urbanization and spatial organization as: structured, recent, established and dependent on connectivity. This multi-resolution approach provided spatial information about the urbanization process and organization of the territory. It may be extended into other areas or be further used to devise a monitoring system, contributing to the discussion of public policy priorities for sustainable development in the Amazon.

  1. Regulation of intraluteal production of prostaglandins

    Ottobre Joseph S


    Full Text Available Abstract There is clear evidence for intraluteal production of prostaglandins (PGs in numerous species and under a variety of experimental conditions. In general, secretion of PGs appears to be elevated in the early corpus luteum (CL and during the period of luteolysis. Regulation of intraluteal PG production is regulated by a variety of factors. An autoamplification pathway in which PGF-2alpha stimulates intraluteal production of PGF-2alpha has been identified in a number of species. The mechanisms underlying this autoamplification pathway appear to differ by species with expression of Cyclooxygenase-2 (Cox-2 and activity of phospholipase A2 acting as important physiological control points. In addition, a number of other responses that are induced by PGF-2alpha (decreased luteal progesterone, increased endothelin-1, increased cytokines also have been found to increase intraluteal PGF-2alpha production. Thus, regulation of intraluteal PG production may serve to initiate or amplify physiological signals to the CL and may be important in specific aspects of luteal physiology particularly during luteal regression.

  2. The ethical aspects of regulating production.

    Swanson, J C


    Polls and surveys conducted within the United States show general agreement that there is public support for the protection of farm livestock and poultry. Concurrent with the growing public sentiment is the recent adoption of socially responsible corporate policies by major food retailers relative to animal welfare. The animal welfare assurance and audit programs developed by the private sector are an attempt to assure consumers that best practice measures and independent oversight result in a reasonable quality of life for food-producing animals. These programs represent voluntary self-regulation and arguably a market-based approach to secure the welfare of food-producing animals. Animal advocacy organizations historically seek regulatory oversight of animal care practice. Legislative routes that require government promulgation and enforcement of animal care regulations represent an involuntary form of animal welfare assurance. There are ethical considerations concerning the employment of voluntary or involuntary regulation of the welfare of food-producing animals. For example, degree of public endangerment, economic impact, viability of small to medium producers, food price, food quality, and food security are prominent among the ethical considerations in deliberating whether to impose regulatory mandates on production. In either regulatory approach, the public must be convinced that the welfare of food-producing animals can be secured in a transparent and convincing manner. PMID:18212384

  3. Remote Sensing of the EnviSat and Cbers-2B satellites rotation around the centre of mass by photometry

    Koshkin, N.; Korobeynikova, E.; Shakun, L.; Strakhova, S.; Tang, Z. H.


    During 2013-2015 the photometric observations of the EnviSat satellite, which became space debris after the failure in April 2012 in low Earth orbit, were performed. The rotation pole position and slow change in sidereal rotation period were updated on the basis of analysis of specular glints observed in 222 light curves using reduction of synodic periods. Apparently, there are minor oscillations of the rotation pole near the normal to the orbital plane. The sense of the EnviSat's spinning is opposite to the sense of its orbital rotation. The sidereal period is best approximated by the second-order polynomial: Psid (sec) = 0.000021534 ·T2 + 0.04936003 · T + 121.18195 where T is measured in days from the beginning of 2013. This method being applied to another representative of space debris, namely the Cbers-2B satellite, has shown a similar result: there is not precise solution for the rotation pole either as it undergoes oscillations with various time scale from several hours to several months. In 2014, the spin axis made the 10 ° angle with the normal to the orbital plane while the sense of spinning is direct in this case, i.e. coincides with the sense of orbital rotation. The sidereal period is best approximated by the following expression: Psid (sec) = 0.000029543 ·T2 + 0.08094931 · T + 81.31775 where T is measured in days starting from March 10, 2014. This method allows of controlling slow changes in the spatial orientation of the rotation axis of the satellites in which specular reflection of light from flat faces of the surface is inherent.

  4. Análise de mapas de represas publicados na web usando imagens orbitais CCD/CBERS no estado de Minas Gerais Analysis of dams maps published on the web by using orbital CCD/CBERS images in Minas Gerais State, Brazil

    Elizabeth Ferreira


    Full Text Available Neste trabalho, bancos de dados públicos e gratuitos disponíveis na World Wide Web (WEB foram utilizados para avaliar as áreas das superfícies dos espelhos d'água das represas de Furnas e do Funil, no Estado de Minas Gerais. O objetivo foi comparar as informações obtidas nos bancos da WEB com os valores das áreas calculadas a partir de imagens do sensor CCD a bordo dos satélites CBERS2 e CBERS2B. A área da represa de Furnas obtida a partir das imagens CCD/CBERS2B, ano 2008, foi de 1.138 km², mas nos bancos de dados consultados esta área estava entre 1.182 e 1.503 km². A represa do Funil, construída em 2003, com superfície de espelho d'água de 29,37 km² e uma ilha com área de 1,93 km² não aparecem nos bancos Atlas, Geominas, IGAM e IBGE. Os resultados mostraram algumas discrepâncias nos bancos de dados publicados na WEB, tais como diferenças em áreas e supressão ou extrapolação de limites do espelho d'água. Concluiu-se que, até o momento, os responsáveis por algumas publicações de bancos de dados no Estado de Minas Gerais não tiveram rigor suficiente com as atualizações. As imagens CCD/CBERS, que também são dados públicos disponíveis na WEB, mostraram ser produtos adequados para verificar, atualizar e melhorar as informações publicadas.In this work some public databases from the World Wide Web (WEB were used to find the area of the Furnas and Funil Dams in Minas Gerais State. The purpose of this work was to compare the WEB public databases values and the real values obtained from the CCD camera images on board CBERS2 and CBERS2B satellites. The Furnas Dam area obtained from CCD/ CBERS2B images, in 2008, was 1.138 km², but in the consulted databases this area ranged from 1.182 to 1.503 km². The dam of the Funil, built in 2003, with a water surface of 29.37 km² and an island with 1.93 km² area, did not appear in Atlas, Geominas, IGAM and IBGE databases. The results revealed some problems in the WEB public

  5. Regulating Homeopathic Products - A Century of Dilute Interest.

    Podolsky, Scott H; Kesselheim, Aaron S


    In 2015, U.S. government agencies began considering greater regulation of both homeopathic drugs and the advertising of such products. These actions came after more than a century of missed opportunities to regulate homeopathic medicines. PMID:26789866

  6. Hungry granulocyte: its fate and regulation of production

    The granulocyte, a phagocytic anti-1 bacterial defense cell, is discussed. Its production, the kinetics of its proliferation, the regulation of its production, and its loss from the blood are reviewed

  7. Concentration of chlorhophyll-a and the limit of the photic zone in the Third River reservoir (Córdoba-Argentina, using images from CBERS-2B satellite

    Claudia Maria Rodriguez


    Full Text Available The satellite images provided by remote sensors represent an important tool for monitoring, controlling and administering water resources. The aim of this work was to model the spatial distribution of the concentration of chlorhophyll-a and the limit of the photic zone in the Rio Tercero reservoir (Córdoba-Argentina, using images from CBERS-2B satellite and a geographical information system (SIG. We selected 15 samples places wherefrom we measured physical, chemical and biological parameters during the fall of 2008. By using a georeferenced image from sensor CBERS-2B and performing an analysis of the principal components (ACP, we were able to identify associations between variables and reflectance values of the satellite bands. Based on these associations and with simple regression models, we were able to know the spatial distribution of the variables: concentration of chlorophyll-a (R2 = 0, 73 and the limit of the photic zone (R2 = 0, 78 in the reservoir as a whole. We may conclude thata there exists a negative correlation between the concentration of chlorophyll-a and the water transparency in reservoir Rio Tercero, as well as that the sensor used allows us to evaluate the quality of the water in a relative short time.

  8. Developing products and services for a deregulated market while regulated

    Products and services developed for a deregulated electric power industry were discussed. The wide-ranging discussion covered products created by unbundling existing services, new products and services related to energy use, products created by expansion into communications services, and the pricing of products and services. In addition to products and services, the discussion also covered strategies for a deregulated market and the challenges of raising equity capital in a regulated environment

  9. Federal Regulation of Unapproved Chelation Products

    Lee, Charles E.


    Chelation products can be helpful in the treatment of metal poisoning. However, many unapproved products with unproven effectiveness and safety are marketed to consumers, frequently via the internet. This paper describes the primary responsibility of the Health Fraud and Consumer Outreach Branch of the United States Food and Drug Administration to identify and address health fraud products. Efforts to prevent direct and indirect hazards to the population’s health through regulatory actions ar...

  10. The discursive production of homosexual regulation

    Baxendale, Graham


    This thesis explores the pivotal place of the 1885 Labouchère Amendment and the 1967 Sexual Offences Act in the discourse of homosexual regulation presented by 20th century homophile histories. These twin events of ‘criminalisation’ and ‘decriminalisation’ are revisited to explore how and why they occurred and how they came to assume such a central position in both academic and popular understanding. The thesis draws on two streams of evidence. The literature on homosexual regulation is exami...

  11. Regulating Advertisements: The Case of Smoking Cessation Products

    Rosemary J. Avery; Donald S. Kenkel; Lillard, Dean R.; Alan D. Mathios


    In this paper we investigate how direct-to-consumer (DTC) advertising of pharmaceutical products in affected by regulations of the Food and Drug Administration and by market conditions. We focus on a relatively under-studied segment of the pharmaceutical market -- the market for smoking cessation products. Because of their proven effectiveness, these products could be the key to meeting public health goals to reduce smoking. However, in many ways, smoking cessation products have been more hea...

  12. Hormonal Regulation Of Hepatic Glucose Production In Health And Disease

    Lin, Hua V.; Accili, Domenico


    We review mechanisms that regulate production of glucose by the liver, focusing on areas of budding consensus, and endeavoring to provide a candid assessment of lingering controversies. We also attempt to reconcile data from tracer studies in humans and large animals with the growing compilation of mouse knockouts that display changes in glucose production. A clinical hallmark of diabetes, excessive glucose production remains key to its treatment. Hence, we attempt to integrate emerging pathw...

  13. Current development in regulation of similar biotherapeutic products in Brazil.

    Castanheira, Laura Gomes; Barbano, Dirceu Brás Aparecido; Rech, Norberto


    Because of the recent expiry of a large number of patents on the originator biological products, interest in the production and marketing of similar biotherapeutic products in Brazil has been increasing. The national producers have significant interest in this market and have been making a large amount of investments in these kinds of products. Since biotherapeutic products consume a large amount of the government health budget, the Brazilian government also has a big interest in the possibility that more affordable biotherapeutic products could be introduced into the market to improve access, but always is concerned with the quality, safety and efficacy of these products Accordingly, it was necessary to review the biological product regulations in Brazil and to establish specific pathways to license similar biotherapeutic products. The new Brazilian regulations, Resolution no. 55/2010, are based on different regulations and guidelines from around the world, including the WHO SBP Guidelines. They follow the same scientific principles as the WHO Guidelines but also have some differences which are due to specific country needs. PMID:21868247

  14. Federal Environmental Regulations Impacting Hydrocarbon Exploration, Drilling, and Production Operations

    Carroll, Herbert B.; Johnson, William I.


    Waste handling and disposal from hydrocarbon exploration, drilling, and production are regulated by the US Environmental Protection Agency (EPA) through federal and state regulations and/or through implementation of federal regulations. Some wastes generated in these operations are exempt under the Resource Conservation and Recovery Act (RCRA) but are not exempt under the Comprehensive Environmental Response, Compensation, and Liability Act (CERCLA), Superfund Amendments and Reauthorization Act (SARA), and other federal environmental laws. Exempt wastes remain exempt only if they are not mixed with hazardous wastes or hazardous substances. Once mixture occurs, the waste must be disposed as a hazardous material in an approved hazardous waste disposal facility. Before the Clean Air Act as amended in 1990, air emissions from production, storage, steam generation, and compression facilities associated with hydrocarbon exploration, drilling, and production industry were not regulated. A critical proposed regulatory change which will significantly effect Class II injection wells for disposal of produced brine and injection for enhanced oil recovery is imminent. Federal regulations affecting hydrocarbon exploration, drilling and production, proposed EPA regulatory changes, and a recent significant US Court of Appeals decision are covered in this report. It appears that this industry will, in the future, fall under more stringent environmental regulations leading to increased costs for operators.

  15. An innovative model for regulating supplement products: Natural health products in Canada

    On 1 January 2004, Health Canada officially added a new term to the global list of synonyms for dietary supplements: natural health products (NHP). Developed with the intent of providing Canadian consumers with ready access to NHP that are safe, effective, and of high quality, the Natural Health Products Regulations (the NHP regulations) are applicable to the sale, manufacture, packaging, labelling, importation, distribution, and storage of NHP, and are administered by the recently formed Natural Health Products Directorate (NHPD) within Health Canada. This paper provides an overview of the process for regulating supplement products in Canada

  16. Regulations for the peat production water pollution control; Turvetuotannon vesiensuojeluohjeisto

    Savolainen, M.; Heikkinen, K.; Ihme, R. [ed.] [VTT Communities and Infrastructure, Espoo (Finland)


    The regulations for peat production water pollution control include the latest information on anti-pollution constructions applicable to peat production including field ditches, sedimentation basins, overland flow areas, forest soil saturation, evaporation basins, chemicalization, detention of runoff and artificial flood plains. Information on subsurface drainage in peat mining is also given. The regulations deal with environmental viewpoints, planning of water protection and information on how to build, use and maintain anti-pollution constructions. Special attention is given to the soil conditions, because they play an important role in the building of different constructions. (orig.) (48 refs.)


    L. Kovalev; I. Kovalev


    The paper presents a brief analysis of the procedures and requirements for the quality and the production of milk in Belarus from the Soviet Union, and to this day, consider some areas of the dairy industry in the Republic of Belarus for 2011-2015, to look at issues and characteristics of milk production in the country. The article raised some important task of unification of Russian and Belarusian industry regulations and standards.

  18. Regulation of ROS Production and Vascular Function by Carbon Monoxide

    Yoon Kyung Choi; Por, Elaine D.; Young-Guen Kwon; Young-Myeong Kim


    Carbon monoxide (CO) is a gaseous molecule produced from heme by heme oxygenase (HO). CO interacts with reduced iron of heme-containing proteins, leading to its involvement in various cellular events via its production of mitochondrial reactive oxygen species (ROS). CO-mediated ROS production initiates intracellular signal events, which regulate the expression of adaptive genes implicated in oxidative stress and functions as signaling molecule for promoting vascular functions, including angio...

  19. Proton production, regulation and pathophysiological roles in the mammalian brain

    Wei-Zheng Zeng; Tian-Le Xu


    The recent demonstration of proton signaling in C elegans muscle contraction suggests a novel mechanism for proton-based intercellular communication and has stimulated enthusiasm for exploring proton signaling in higher organisms.Emerging evidence indicates that protons are produced and regulated in localized space and time.Furthermore,identification of proton regulators and sensors in the brain leads to the speculation that proton production and regulation may be of major importance for both physiological and pathological functions ranging from nociception to learning and memory.Extracellular protons may play a role in signal transmission by not only acting on adjacent cells but also affecting the cell from which they were released.In this review,we summarize the upstream and downstream pathways of proton production and regulation in the mammalian brain,with special emphasis on the proton extruders and sensors that are critical in the homeostatic regulation of pH,and discuss their potential roles in proton signaling under normal and pathophysiological conditions.

  20. PPARalpha regulates the production of serum Vanin-1 by liver.

    Rommelaere, Samuel; Millet, Virginie; Gensollen, Thomas; Bourges, Christophe; Eeckhoute, Jérôme; Hennuyer, Nathalie; Baugé, Eric; Chasson, Lionel; Cacciatore, Ivana; Staels, Bart; Pitari, Giuseppina; Galland, Franck; Naquet, Philippe


    The membrane-bound Vanin-1 pantetheinase regulates tissue adaptation to stress. We investigated Vnn1 expression and its regulation in liver. Vnn1 is expressed by centrolobular hepatocytes. Using novel tools, we identify a soluble form of Vnn1 in mouse and human serum and show the contribution of a cysteine to its catalytic activity. We show that liver contributes to Vanin-1 secretion in serum and that PPARalpha is a limiting factor in serum Vnn1 production. Functional PPRE sites are identified in the Vnn1 promoter. These results indicate that serum Vnn1 might be a reliable reporter of PPARalpha activity in liver. PMID:24140347

  1. Impacts of alternative Great Lakes regulation plans on hydropower production

    Hydropower production is evaluated for two alternative regulation measures developed under the recent International Joint Commission Great Lakes Water Levels Reference. Measure 1.18 included a new control structure to regulate outflows from Lake Erie, while measure 1.21 was a revision of the current regulation plans for lakes Superior and Ontario. A negative impact to the entire hydropower system was calculated to range between US$11.9 and US$20.9 million/year under measure 1.18, while measure 1.21 had a positive impact in the range of US$1 to US$3 million/year. Considering the impacts to all interests, the Reference Study Board recommended no further consideration be given to measure 1.18, but that a measure similar to 1.21 should be implemented. (author). 34 refs., 9 tabs., 2 figs


    Labuza, Theodore P.; Szybist, Lynn M.


    A federally regulated open dating system on food products, instead of the current somewhat random and non-uniform state mandated system, would most likely benefit today's consumers, retailers, and government agencies. Consumers have indicated a strong desire for open dates; it would enhance their ability to make educated choices about the freshness of the foods they consume. A mandatory/uniform system would also assist retail grocers with stock rotation, so that customers can be provided with...

  3. Unregulated Entities, Products, and Markets: Challenges for Monitoring and Regulation

    Morgan, Peter


    The implications for financial stability of lightly regulated and highly leveraged financial institutions such as hedge funds and private equity funds, together with innovative financial products such as derivatives and asset-backed securities, remain a subject of controversy, especially in the current global financial crisis, where issues of systemic risk have not only national, but regional and global implications. This policy brief examines hedge funds, private equity funds, and innovative...

  4. Regulations and guidelines governing stem cell based products: Clinical considerations

    Bobby George


    Full Text Available The use of stem cells as medicines is a promising and upcoming area of research as they may be able to help the body to regenerate damaged or lost tissue in a host of diseases like Parkinson′s, multiple sclerosis, heart disease, liver disease, spinal cord damage, cancer and many more. Translating basic stem cell research into routine therapies is a complex multi-step process which entails the challenge related to managing the expected therapeutic benefits with the potential risks while complying with the existing regulations and guidelines. While in the United States (US and European Union (EU regulations are in place, in India, we do not have a well-defined regulatory framework for "stem cell based products (SCBP". There are several areas that need to be addressed as it is quite different from that of pharmaceuticals. These range from establishing batch consistency, product stability to product safety and efficacy through pre-clinical, clinical studies and marketing authorization. This review summarizes the existing regulations/guidelines in US, EU, India, and the associated challenges in developing SCBP with emphasis on clinical aspects.

  5. The economic value of short-term regulated hydropower production

    The economic value of short-term regulation of hydropower depends on the marginal price of electricity. A systematic method to estimate the revenue from short-term regulated hydropower production has been developed. It can thus be used to compare the cost of different restrictions and constraints imposed on the regulation practice. Constraints on water level or discharge variations in the river can be imposed e.g because of environmental reasons. In this method the total hydropower production of the river is optimized. Input to the model consists of the amount of available water, the marginal price of production, price elasticity and the given constraints. The following constraints can be applied: maximum and minimum discharge at each power plant, maximum and minimum reservoir levels at each power plant, maximum variation of tailwaters at each power plant during the period of interest, maximum change of discharge per time unit and the minimum spinning reserves of the system. Output data comprises power output, discharge and water levels (head) at each power plant, and the calculated revenue based on produced power and the given marginal price of production. The method has two basic components: an optimization algorithm and a river simulation algorithm. The optimization algorithm is based on a quadratic cost function and a linear model. The model has been applied to Oulujoki River in Northern Finland. There are seven hydropower plants along the river, it is over 100 km long and it is extensively used for peak power production. Two typical weeks were simulated with different restrictions set on water level variation and available amount of water

  6. Regulation of Inflammatory Cytokine Production by MKP-5 in Macrophages.

    Hömmö, Tuija; Pesu, Marko; Moilanen, Eeva; Korhonen, Riku


    Mitogen-activated protein kinases (MAPKs) include p38 MAPKs, c-Jun N-terminal kinases (JNKs) and Extracellular signal-regulated kinases (ERKs), and they regulate many cell processes, such as cell division, differentiation and release of inflammatory mediators. MAPK activity is controlled by mitogen-activated protein kinase phosphatases (MKPs), a phosphatase family with 11 members. MKP-1 is the most studied member of MKP family, and it is one of the anti-inflammatory factors induced by glucocorticoids. Less is known about the other MAPK phosphatases although they hold a promise as anti-inflammatory drug targets. In this study, we investigated the effect of MKP-5 on MAPK phosphorylation and cytokine production in J774 mouse macrophages. We used MKP-5 siRNA and an MKP-5 inhibitor (AS077234-4) to modulate MKP-5 function. We found that MKP-5 controlled p38 MAPK phosphorylation, but not that of JNK or ERK. In addition, the production of IL-6 and TNF was suppressed by MKP-5 in macrophages. Our results introduce a novel concept that compounds able to enhance MKP-5 expression and/or activity hold anti-inflammatory potential, because MKP-5 down-regulates the release of inflammatory mediators by controlling p38 MAPK activity. PMID:25615285

  7. Natural regulation of Delia radicum in organic cabbage production

    Meyling, N.; Navntoft, S.; H. Philipsen; Thorup-Kristensen, K


    In a field experiment, we evaluated effects of three different organic white cabbage-cropping systems (O1, O2, O3) on the cabbage root fly, Delia radicum, and its egg predators and pupal parasitoids over 3 years. The three systems all complied with regulations for organic production, but varied in external nutrient input and N-recycling, and were compared to a conventionally farmed control. One organic system (O3) included an intercropped strip of green manure between crop rows. Oviposition b...

  8. Regulation of traditional and complementary medicinal products in Malaysia

    Jayaraj P


    Full Text Available In Malaysia, mainly there are three complimentary systems of medicine practiced they are the traditional Malay, Chinese and Indian systems. The traditional herbal medicines and their preparations have been widely used in Malaysia for thousands of years. The pervasive use of complementary medicines raises several concerns. Many of these arise because most complementary medicines are not licensed as medicines, and therefore evidence of quality, efficacy and safety is not required before marketing. In this paper, I would like to present an overview of the characteristics of regulation, quality and registration of traditional and complementary medicinal (TCM products in Malaysia.

  9. Exploiting the commons: cyclic diguanylate regulation of bacterial exopolysaccharide production.

    Pérez-Mendoza, Daniel; Sanjuán, Juan


    Nowadays, there is increasing interest for bacterial polysaccharides in a wide variety of industrial sectors. This is due to their chemical and reological properties, and also the possibility to be obtained by fermentation processes. Biosynthesis of a growing number of exopolysaccharides (EPS) has been reported to be regulated by the ubiquitous second messenger c-di-GMP in a limited number of bacterial species. Since most bacteria are yet unexplored, it is likely that an unsuspected number and variety of EPS structures activated by c-di-GMP await to be uncovered. In the search of new EPS, manipulation of bacterial c-di-GMP metabolism can be combined with high throughput approaches for screening of large collections of bacteria. In addition, c-di-GMP activation of EPS production and promotion of cell aggregation may have direct applications in environmental industries related with biofuel production or wastewater treatments. PMID:26773798

  10. Productivity growth and price regulation of Slovenian water distribution utilities

    Jelena Zorić


    Full Text Available This paper aims to analyse the price regulation method and performance of thewater industry in Slovenia. A stochastic cost frontier model is employed to estimate and decompose the total factor productivity (TFP growth of water distribution utilities in the 1997-2003 period. The main goal is to find out whether the lack of proper incentives to improve performance has resulted in the low TFP growth of Slovenian water distribution utilities. The evidence suggests that cost inefficiencies are present in water utilities, which indicates considerable cost saving potential in the analysed industry. Technical change is found to have positively affected the TFP growth over time, while cost inefficiency levels remained essentially unchanged. Overall, the average annual TFP growth in the analysed period is estimated to be only slightly above zero, which is a relatively poor result. This can largely be contributed to the present institutional and regulatory setting that does not stimulate utilities to improve productivity. Therefore, the introduction of an independent regulatory agency and an incentive-based price regulation scheme should be seriously considered in order to enhance the performance of Slovenian water distribution utilities.

  11. Adrenergic and noradrenergic regulation of poultry behavior and production.

    Dennis, R L


    Norepinephrine and epinephrine (noradrenaline and adrenaline) are integral in maintaining behavioral and physiological homeostasis during both aversive and rewarding events. They regulate the response to stressful stimuli through direct activation of adrenergic receptors in the central and sympathetic nervous systems, hormonal activity and through the interaction of the brain, gut, and microbiome. The multiple functions of these catecholamines work synergistically to prepare an individual for a "fight or flight" response. However, hyper-reactivity of this system can lead to increased fearfulness and aggression, decreased health and productivity, and a reduction in overall well-being. Behaviors, such as aggression and certain fear-related behaviors, are a serious problem in the poultry industry that can lead to injury and cannibalism. For decades, catecholamines have been used as a measure of stress in animals. However, few studies have specifically targeted the adrenergic systems as means to reduce behaviors that are damaging or maladapted to their rearing environments and improve animal well-being. This article attempts to address our current understanding of specific, adrenergic-regulated behaviors that impact chicken well-being and production. PMID:27345328

  12. EU Regulation of Nanobiocides: Challenges in Implementing the Biocidal Product Regulation (BPR

    Anna Brinch


    Full Text Available The Biocidal Products Regulation (BPR contains several provisions for nanomaterials (NMs and is the first regulation in the European Union to require specific testing and risk assessment for the NM form of a biocidal substance as a part of the information requirements. Ecotoxicological data are one of the pillars of the information requirements in the BPR, but there are currently no standard test guidelines for the ecotoxicity testing of NMs. The overall objective of this work was to investigate the implications of the introduction of nano-specific testing requirements in the BPR and to explore how these might be fulfilled in the case of copper oxide nanoparticles. While there is information and data available in the open literature that could be used to fulfill the BPR information requirements, most of the studies do not take the Organisation for Economic Co-operation and Development’s nanospecific test guidelines into consideration. This makes it difficult for companies as well as regulators to fulfill the BPR information requirements for nanomaterials. In order to enable a nanospecific risk assessment, best practices need to be developed regarding stock suspension preparation and characterization, exposure suspensions preparation, and for conducting ecotoxicological test.


    Bahlool, Qusay Zuhair Mohammad; Buchmann, Kurt; Kania, Per Walter;

    work elucidates the effect of ES substances on the fish immune system by measuring immune gene expression in spleen and liver of rainbow trout (Oncorhynchus mykiss) injected intraperitoneally with ES products isolated from A. simplex third stage larvae. The overall gene expression profile of exposed...... fish showed a generalized down-regulation of the immune genes tested, suggesting a role of ES proteins in minimizing the immune reaction of rainbow trout against invading nematodes. We also tested the enzymatic activity of the ES proteins and found that lipase, esterase lipase, valine and cysteine...... arylamidases, naphthol-AS-BI-phosphohydrolase and a-galactosidase activities were present in the ES solution. This type of hydrolytic enzyme activity may play a role in nematode penetration of host tissue. Based on the notion that A. simplex ES-proteins may have an immune-depressive effect, it could also be...

  14. Natural regulation of Delia radicum in organic cabbage production

    Meyling, N.V.; Navntoft, S.; Philipsen, H.;


    observed in the conventional compared to all organic systems, indicating that immature survival from oviposition to pupation was reduced under all the three organic farming practices. In organic system O2 most small coleopteran predators were recorded, but predation on fly eggs was not significantly higher......In a field experiment, we evaluated effects of three different organic white cabbage-cropping systems (O1, O2, O3) on the cabbage root fly, Delia radicum, and its egg predators and pupal parasitoids over 3 years. The three systems all complied with regulations for organic production, but varied in...... external nutrient input and N-recycling, and were compared to a conventionally farmed control. One organic system (O3) included an intercropped strip of green manure between crop rows. Oviposition by D. radicum was generally not reduced in organic cropping systems. However, higher pupae/egg ratios were...

  15. Environmental Policies, Product Market Regulation and Innovation in Renewable Energy

    We investigate the effectiveness of policies in favor of innovation in renew- able energy under different levels of competition. Using information regarding renewable energy policies, product market regulation and high-quality green patents for OECD countries since the late 1970's, we develop a pre-sample mean count-data econometric specification that also accounts for the endogeneity of policies. We find that renewable energy policies are significantly more effective in fostering green innovation in countries with deregulated energy markets. We also find that public support for renewable energy is crucial only in the generation of high-quality green patents, whereas competition enhances the generation of green patents irrespective of their quality. (authors)

  16. TIM-1 signaling in B cells regulates antibody production

    Highlights: → TIM-1 is highly expressed on anti-IgM + anti-CD40-stimulated B cells. → Anti-TIM-1 mAb enhanced proliferation and Ig production on activated B cell in vitro. → TIM-1 signaling regulates Ab production by response to TI-2 and TD antigens in vivo. -- Abstract: Members of the T cell Ig and mucin (TIM) family have recently been implicated in the control of T cell-mediated immune responses. In this study, we found TIM-1 expression on anti-IgM- or anti-CD40-stimulated splenic B cells, which was further up-regulated by the combination of anti-IgM and anti-CD40 Abs. On the other hand, TIM-1 ligand was constitutively expressed on B cells and inducible on anti-CD3+ anti-CD28-stimulated CD4+ T cells. In vitro stimulation of activated B cells by anti-TIM-1 mAb enhanced proliferation and expression of a plasma cell marker syndecan-1 (CD138). We further examined the effect of TIM-1 signaling on antibody production in vitro and in vivo. Higher levels of IgG2b and IgG3 secretion were detected in the culture supernatants of the anti-TIM-1-stimulated B cells as compared with the control IgG-stimulated B cells. When immunized with T-independent antigen TNP-Ficoll, TNP-specific IgG1, IgG2b, and IgG3 Abs were slightly increased in the anti-TIM-1-treated mice. When immunized with T-dependent antigen OVA, serum levels of OVA-specific IgG2b, IgG3, and IgE Abs were significantly increased in the anti-TIM-1-treated mice as compared with the control IgG-treated mice. These results suggest that TIM-1 signaling in B cells augments antibody production by enhancing B cell proliferation and differentiation.

  17. European and Italian regulation on orphan medicinal products

    Roberta Joppi


    Full Text Available The paper presents an overview of the European and Italian Regulation on Orphan Medicinal Products (OMPs, along with some data on the OMPs licensed in the EU from 2000 to 2012. The EU legislation encourages pharmaceutical companies to develop drugs for rare diseases, so-called “orphan drugs”. The European Medicine Agency recognizes orphan drug status mainly on the basis of the prevalence of the disease (≤ 5/10,000, and potential benefit. Orphan status implies incentives for pharmaceutical companies. From 2000 up to 2012 890 candidate orphan drug designations received a positive opinion and the marketing authorization was granted to 72 OMPs corresponding to 80 different indications. Currently, 59 OMPs are available to Italian patients either because licensed to the market by the AIFA or included in the list of the L. 648/96. Despite of an encouraging regulation nearly all the currently estimated rare diseases still await treatments.

  18. Carboxylesterase1/Esterase-x regulates chylomicron production in mice.

    Ariel D Quiroga

    Full Text Available Elevated postprandial plasma triacylglycerol (TG concentrations are commonly associated with obesity and the risk of cardiovascular disease. Dietary fat contributes to this condition through the production of chylomicrons. Carboxylesterases have been mainly studied for their role in drug metabolism, but recently they have been shown to participate in lipid metabolism; however, their role in intestinal lipid metabolism is unknown. Carboxylesterase1/esterase-x (Ces1/Es-x deficient mice become obese, hyperlipidemic and develop hepatic steatosis even on standard chow diet. Here, we aimed to explore the role of Ces1/Es-x in intestinal lipid metabolism. Six-month old wild-type and Ces1/Es-x deficient mice were maintained on chow diet and intestinal lipid metabolism and plasma chylomicron clearance were analyzed. Along the intestine Ces1/Es-x protein is expressed only in proximal jejunum. Ablation of Ces1/Es-x expression results in postprandial hyperlipidemia due to increased secretion of chylomicrons. The secreted chylomicrons have aberrant protein composition, which results in their reduced clearance. In conclusion, Ces1/Es-x participates in the regulation of chylomicron assembly and secretion. Ces1/Es-x might act as a lipid sensor in enterocytes regulating chylomicron secretion rate. Ces1/Es-x might represent an attractive pharmacological target for the treatment of lipid abnormalities associated with obesity, insulin resistance and fatty liver disease.

  19. The Rate-of-Return Regulated Firm: Cost and Production Duality

    Rolf Fare; James Logan


    A duality between cost and production is established for a firm subject to rate-of-return regulation. To this end, a rate-of-return regulated production function is defined and shown to exist. It is then shown how information regarding the unregulated technology can be obtained from the rate-of-return regulated cost function. With knowledge of the rate-of-return constraint, the rate-of-return regulated production function can be reconstructed.

  20. Oxygen-­dependent regulation of bacterial lipid production

    Lemmer, Kimberly C.; Dohnalkova, Alice; Noguera, Daniel R.; Donohue, Timothy J.


    Understanding the mechanisms of lipid accumulation in microorganisms is important for several reasons. In addition to providing insight into assembly of biological membranes, lipid accumulation has important applications in the production of renewable fuels and chemicals. The photosynthetic bacterium Rhodobacter sphaeroides is an attractive organism to study lipid accumulation, as it has the somewhat unique ability to increase membrane production at low O₂ tensions. Under these conditions, R. sphaeroides develops invaginations of the cytoplasmic membrane to increase its membrane surface area for housing of the membrane-bound components of its photosynthetic apparatus. Here we use fatty acid levels as a reporter of membrane lipid content. We show that, under low-O₂ and anaerobic conditions, the total fatty acid content per cell increases 3-fold. We also find that the increases in the amount of fatty acid and photosynthetic pigment per cell are correlated as O₂ tensions or light intensity are changed. To ask if lipid and pigment accumulation were genetically separable, we analyzed strains with mutations in known photosynthetic regulatory pathways. While a strain lacking AppA failed to induce photosynthetic pigment-protein complex accumulation, it increased fatty acid content under low O2 conditions. We also found that an intact PrrBA pathway is required for low O2-induced fatty acid accumulation. Our findings suggest a previously unknown role of R. sphaeroides transcriptional regulators in increasing fatty acid and phospholipid accumulation in response to decreased O₂ tension.


    Tubalets A. A.


    Full Text Available Theoretical, transformational and practical provisions for the development and regulation of small businesses and farms in the country's economy and agriculture are being cleared up. In the process of studying the problem we used logical reasoning, methods of comparing, and monographic, economic and statistical methods also. It is shown that small farming forms (SFF in agriculture are essential for progressive development of agriculture, which is now recognized as a growth point of import substitution in all national economy. Given the author's interpretation of the category definition "small farming form" in agriculture differs from other definitions, in a more complete evaluation and statistics, provisions regarding private cottages and households as the SFF, their locality of functioning, independence in taking risks, increased adaptation, economic and legal binding, spectrum of production. The article shows the history of definitions of small business and small farming forms, stages of small business development, the scope of its practice abroad and in our country. It is said that a leading role in the formation of small farms belonged to households, which are still playing a leading role in production of agricultural products for their own consumption (without selling on the market. It is noted that at the present stage of industrial transformation of small businesses and small farms they often have a low mechanization level, high cost structure of manual labor. They have problems in adapting to the sector of services, in embedding into a complex system of relationships with medium and large business on the basis of technological specialization and also promoting innovation. It is emphasized that today the growing role of small businesses, small farms makes it more pragmatic to assess the prospects of development of this sector in our country

  2. Occurrence of regulated and non-regulated disinfection by-products in small drinking water systems.

    Guilherme, Stéphanie; Rodriguez, Manuel J


    The occurrence of regulated and non-regulated disinfection by-products (DBPs) was investigated in the drinking water of small systems in two provinces in Canada, Newfoundland and Labrador (NL) and Quebec (QC), through an intensive sampling program. Sixteen DBPs were studied: four trihalomethanes (THMs), five haloacetic acids (HAAs), four haloacetonitriles (HANs), one halonitromethane, chloropikrin (CPK) and two haloketones (HKs). Average measured concentrations of these compounds were much higher than those reported in the literature for medium and large systems. The measured average value for THMs was 75 μg L(-1) (Stdv=69μgL(-1)); HAAs, 77 μg L(-1) (Stdv=75 μg L(-1)); HANs, 2.5 μg L(-1) (Stdv=1.8 μg L(-1)); CPK, 0.4 μg L(-1) (Stdv=0.3 μg L(-1)) and HKs, 6.0 μg L(-1) (Stdv=4.5 μg L(-1)). The gap (some 10 times difference) between the average levels of regulated DBPs (THMs, HAAs) and non-regulated DBPs (HANs, CPK and HKs) is comparable to that observed in large systems where the occurrence of the same compounds has been reported. Generally, investigated DBPs followed a comparable seasonal evolution during the year: they decreased between the fall and winter and then increased to eventually reach a maximum in late summer. This trend was less observable in NL than in QC. However, observed seasonal fluctuations of DBPs were less considerable than those observed in medium and large systems located in similar temperate environments reported in the literature. Spatial variations from the plant to the extremities were high and comparable to those observed in large systems, which is surprising, considering the smaller size of distribution networks supplying small communities. Generally speaking, the results support the premise that problems associated with implementing treatment that removes DBP precursors in water submitted to chlorination can increase population exposure to these contaminants in small systems. PMID:25194329

  3. Regulation of Interleukin—6 Production by Cultured Human Thyrocytes

    段宇; 刘超; 等


    Objective To study the modulation of interleukin-6(IL-6) generation from human thyroid cells.Methods Thryoid tissues were obtained at surgery from patients with Graves disease.IL-6 in the supernatant of cultured thyrocytes was detected with ultra-sensitive ELISA.mRNA was extracted respectively from primany human cultured thyroidal cells under stimulated and unstimulated conditions,and semiquantitative reverse transcriptase-polymerase chain reaction(RTPCR) technique was used for IL-6 mRNA detection.Results:(1) In the basic conditions,thyroid cells can produce high concentration IL-6.Thyrotropin(TSH,103mU/L),tumor necrosis factorα(TNF-α,10-1U/ml),interleukin-1(IL-1,10 U/ml) and adrenaline(10-5 mol/L) significantly increased Il-6 levels in the supernatant of cultured thyroid cells,whereas dexamethasone(10 mmol/L) markedly suppressed IL-6 release from thryocytes.Nal of 10-4 mol/L exerted no effect on the production of Il-6.(2)Compared with the basal results,at a concentration of 10-103 mmol/L,dexamethasone could gradually suppress IL-6 gene expression on human thryocytes,while TNF-α could obviously stimulate the production of IL-6 mRNA in the range of 10-1-102 U/ml.On the level of 102 U/ml,IL-1 increased the expression of IL-6,but the same effect could not be shown when IL-1 was 10-1 U/ml.Sodium iodine(NaI) could not affect Il-6 gene from the level of 10-8 to 10-4 mol/L.Conclusion IL-6 produced by thyrocytes might be regulated by many factors that modulate thyroid functions in vitro as well as in vivo.

  4. Means of regulating combustible materials and products in external walls

    Mikkola Esko


    Full Text Available This report presents proposals for defining means of regulating the use of combustible materials and products in external walls. Required protections are based on the quantities of fire loads and their contribution to fire development. The study is based on life safety and protection of property priorities taking into account reaction to fire classes related to different types of fire loads and fire compartmentation requirements of the adjacent spaces of concern. The proposals include the following main principles in relation to fire-separation requirements: In case of internal fire exposure the protective structure for combustible building parts needs to meet at least half of the fire-separating requirement for the compartment of concern. In case of external fire exposure the protection time requirement can be 15 minutes less than for the internal protection. The proposals are applicable for residential buildings and offices. In case of buildings with longer evacuation times more stringent requirement levels may be considered. For verification of protection performance of fire loads it is proposed to use existing standardized test methods (fire protection ability (K classes and fire-separating function (EI classes validated methods of calculation and/or large scale fire testing.

  5. Regulated Production of Mature Insulin in Rat Hepatoma Cells:Insulin Production is Up-regulated by Dexamethasone and Down-regulated by Insulin

    Xin-Yu QIN; Kun-Tang SHEN; Lu-Jun SONG; Xin ZHANG; Ze-Guang HAN


    We engineered an artificial β cell line that produces an up-regulation of insulin in response to dexamethasone, and a down-regulation in response to insulin. A regulatory secretion system was devised by placing proinsulin cDNA containing genetically engineered furin endoprotease cleavage sites and a regulatory promoter for phosphoenolpyruvate carboxykinase (PEPCK), and an insulin expressing retrovirus vector (pN-PEPCK-mINS) was constructed and transfected into Hepa1-6 cells. The levels of insulin in culture medium and expression of insulin gene was estimated by radioimmunoassay and reverse transcriptionpolymerase chain reaction (RT-PCR), respectively. The clone (Hepa1-6/INS21), which secreted the highest level of insulin (10.79 μIU/106 cells per day), was selected for the regulation experiment. Compared with the non-treated Hepa1-6/INS21 cells, insulin production was augmented 3.6-fold by the addition of 10-7 M of dexamethasone. Addition of exogenous insulin to the culture medium decreased insulin mRNA expression remarkably on RT-PCR results, while dexamethasone increased insulin gene expression at the transcriptional level. The data indicated that genetically engineered Hepa1-6 cells could synthesize process and secrete insulin in a physiological manner.

  6. Regulation of Interleukin-6 Production by Cultured Human Thyrocytes

    段宇; 刘超; 武晓泓; 刘翠萍; 覃又文; 蒋须勤


    Objective To study the modulation of interleukin-6 (IL-6) generation from human thyroid cells.MethodsThyroid tissues were obtained at surgery from patients with Graves disease.IL-6 in the supernatant of cultured thyrocytes was detected with ultra-sensitive ELISA.mRNA was extracted respectively from primary human cultured thyroidal cells under stimulated and unstimulated conditions,and semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR) technique was used for produce high concentration IL-6.Thyrotropin (TSH,103mU/L),tumor necrosis factor-α(TNF-α,10-1 U/ml),interleukin-1(IL-1,10 U/ml) and adrenaline(10-5mol/L) significantly increased IL-6 levels in the supernatant of cultured thyroid cells,whereas dexamethasone (10 mmol/L) markedly suppressed IL-6 release from thyrocytes.NaI of 10-4 mol/L results,at a concentration of 10-103 mmol/L,dexamethasone could gradually suppress IL-6 gene expression on human thyrocytes,while TNF-α could obviously stimulate the production of IL-6 mRNA in the range of 10-1-102 U/ml.On the level of 102 U/ml,IL-1 increased the expression of IL-6,but the same effect could not be shown when IL-1 was 10-1 or 10 U/ml.Sodium iodine (NaI) could not affect IL-6 gene from the level of 10-8 to 10-4 mol/L.ConclusionIL-6 produced by thyrocytes might be regulated by many factors that modulate thyroid functions in vitro as well as in vivo.``

  7. 78 FR 38055 - Building Research Capacity in Global Tobacco Product Regulation Program (U18)


    ... Tobacco Control Act and related regulations, guidance, and other educational information. To implement the... research and produce technical papers on various issues of relevance to tobacco product regulation, e.g... Control Act and related regulations, guidance, and other educational information. C....

  8. 78 FR 29263 - Rules andRegulations Under the Textile Fiber Products Identification Act


    ... Under the Textile Fiber Products Identification Act, 76 FR 68690 (Nov. 7, 2011). This Notice of Proposed...--Rules and Regulations Under the Textile Fiber Products Identification Act, 24 FR 4480, 4485 (June 2... Rulemaking, 50 FR 15100 at 15101 (Apr. 15, 1985). This Notice compared the Customs regulations in 19 CFR...

  9. Proactive compliance? Repercussions of national product regulation in standards of transnational business networks

    Dilling, Olaf


    This paper ('Sfb-Arbeitspapier') illustrates the links between the self-regulation of transnational business networks and the law by analysing the management of chemical substance risks in the electric and electronic equipment industry. National product regulation (and to some extent regulation of production processes) can influence standards employed globally by leading corporations within their network of suppliers and contract manufacturers. However, it is also shown that the diffusion of ...

  10. The new electric regulations. Volume 1: monopoly and competition; Volume 2: Productions, grids and demand

    This bibliographical note presents the content of a book in which the author discusses and comments all the regulations which affect the various aspects of electricity production and distribution: those addressing competition and public services, European regulations, national regulations, the role of the Commission for energy regulation, local regulations for electricity distribution and supply, electricity prices, organized markets of electricity. The author also addresses the regulated access to nuclear electricity, the role of reactive purchasers on the retail market, the competition for local concessions of electricity distribution or supply

  11. A Dirofilaria immitis Polyprotein Up-Regulates Nitric Oxide Production

    Tezuka, Hiroyuki; Imai, Shinjiro; Tsukidate, Setsuko; Fujita, Koichiro


    We investigated the effect of recombinant Dirofilaria immitis polyprotein (rDiAg) on nitric oxide (NO) production by peritoneal macrophages. rDiAg induced NO production by macrophages from wild-type and lipopolysaccharide-hyporesponsive C3H/HeJ, but not CD40−/−, mice. These results suggest that CD40 is involved in rDiAg-driven NO production by murine macrophages. PMID:12183583

  12. 3-Methylindole production is regulated in Clostridium scatologenes ATCC 25775

    Aims: 3-Methylindole (3-MI) is a degradation product of L-tryptophan and is both an animal waste malodorant and threat to ruminant health. Culture conditions which influence 3-MI production in Clostridium scatologenes ATCC 25775 were investigated. Methods and Results: Cells cultured in anaerobic ...

  13. 77 FR 57043 - Regulations Under the Fur Products Labeling Act


    ... false advertising of fur products, and requires labeling of most fur products.\\2\\ Pursuant to this Act... Labeling Act (``TFLA''), and, on its own initiative, deleting unnecessary requirements. \\1\\ 76 FR 13550..., most recently in 1967.\\17\\ \\16\\ 15 U.S.C. 69e(b). \\17\\ 32 FR 6023 (Apr. 15, 1967). C. TFLA In...

  14. Biogas Production on Demand Regulated by Butyric Acid Addition

    Kasper, K.; Schiffels, J.; Krafft, S.; Kuperjans, I.; Elbers, G.; Selmer, T.


    Investigating effects of volatile fatty acids on the biogas process it was observed that butyric acid can be used for transient stimulation of the methane production in biogas plants operating with low energy substrates like cattle manure. Upon addition of butyrate the methane output of the reactors doubled within 24 h and reached almost 3-times higher methane yields within 3-4 days. Butyrate was quantitatively eliminated and the reactors returned to the original productivity state within 3 days when application of butyrate was stopped. The opportunity to use butyrate feeding for increased biogas production on demand is discussed.

  15. State regulation and power plant productivity: background and recommendations

    This report was prepared by representatives of several state regulatory agencies. It is a guide to some of the activities currently under way in state agencies to promote increased availability of electrical generating power plants. Standard measures of plant performance are defined and the nature of data bases that report such measures is discussed. It includes reviews of current state, federal, and industry programs to enhance power plant productivity and provides detailed outlines of programs in effect in California, Illinois, Michigan, New York, North Carolina, Ohio, and Texas. A number of actions are presented that could be adopted by state regulatory agencies, depending on local conditions. They include: develop a commission position or policy statement to encourage productivity improvements by utilities; coordinate state efforts with ongoing industry and government programs to improve the acquisition of power plant performance data and the maintenance of quality information systems; acquire the capability to perform independent analyses of power plant productivity; direct the establishment of productivity improvement programs, including explicit performance objectives for both existing and planned power plants, and a performance program; establish a program of incentives to motivate productivity improvement activities; and participate in ongoing efforts at all levels and initiate new actions to promote productivity improvements

  16. Examples of NRC research products used in regulation

    The key to effective research is a close relationship between information needs and research results. This can only be achieved by close cooperation between the researchers and the regulators. At the NRC, this relationship has matured over the years until now the researchers participate in definition of the information needs and the regulators help define the research programs. The more formal means of ensuring a close match between needs and results include joint research groups, oversight working groups, and a system of Research Information Letters (RILs). On an informal basis there are many day to day discussions and meetings on the various programs which ensure effective program guidance and early identification of significant findings. This paper describes both the formal and informal researcher/regulation interface and discusses some examples of how specific research programs are utilized in the regulatory process. Specific programs described are the pressurized thermal shock program, the seismic margins program and the Category 1 structures program. Other examples cited are the aging and life extension programs

  17. Regulations on the Management of Re- call of Defective Auto Products to be Implemented Next Year


    On October 10, Regulations on the Manage- ment of Recall of Defective Auto Products was ap- proved to implement on January l, 2013 by No. 219 Executive Meeting of the State Council. The product quality supervision departments of the State Council are responsible for supervising and managing the recall of the national defective auto products.

  18. Zinc Regulation of Aminopeptidase B Involved in Neuropeptide Production

    Hwang, Shin-Rong; Hook, Vivian


    Aminopeptidase B (AP-B) is a metallopeptidase that removes basic residues from the N-termini of neuropeptide substrates in secretory vesicles. This study assessed zinc regulation of AP-B activity, since secretory vesicles contain endogenous zinc. AP-B was inhibited by zinc at concentrations typically present in secretory vesicles. Zinc effects were dependent on concentration, incubation time, and the molar ratio of zinc to enzyme. AP-B activity was recovered upon removal of zinc. AP-B with zi...

  19. γ-Butyrolactones : Streptomyces signalling molecules regulating antibiotic production and differentiation

    Takano, Eriko


    Small signalling molecules called γ-butyrolactones are mainly produced by Streptomyces species in which they regulate antibiotic production and morphological differentiation. Their molecular mechanism of action has recently been unravelled in several streptomycetes, revealing a diverse and complex s

  20. 76 FR 34715 - Draft Guidance for Industry; Considering Whether an FDA-Regulated Product Involves the...


    ... the Application of Nanotechnology''. This guidance is intended to provide industry with FDA's current... HUMAN SERVICES Food and Drug Administration Draft Guidance for Industry; Considering Whether an FDA-Regulated Product Involves the Application of Nanotechnology; Availability AGENCY: Food and...

  1. Regulation of slime production in Staphylococcus epidermidis by iron limitation.

    Deighton, M.; Borland, R


    Slime production by most strains of Staphylococcus epidermidis was enhanced by conditions of iron limitation produced by the addition of ethylenediamine-di-o-hydroxyphenol acetic acid to the growth medium. The density of the biofilm which formed on the base of microtiter plates was dependent on the degree of iron limitation, the stage of the growth cycle, and the nutritional state of the initial inoculum. One repeatedly slime-negative S. epidermidis strain, passaged in tryptic soya broth cont...


    King, Carlotta D.


    Since the Food and Drug Administration (“FDAâ€) has control over the regulation of dietary supplements, this paper discusses whether the current regulation is sufficient to guard the safety of the individuals using “sports products.†Recently, the sudden deaths of a number of professional and collegiate athletes have been linked to the use of performance enhancing sports products, and despite other possible causes, many families and...

  3. Collagen I-induced dendritic cells activation is regulated by TNF- production through down-regulation of IRF4

    Barun Poudel; Hyeon-Hui Ki; Young-Mi Lee; Dae-Ki Kim


    Previously we have shown that collagen I enhances the maturation and function of dendritic cells (DCs). Inflammatory mediators such as tumour necrosis factor (TNF)-, interleukin (IL)-1 and lipopolysaccharide (LPS) are also known to activate DCs. Here we investigated the involvement of TNF- on the collagen I-induced DCs activation. TNF-a neutralization inhibited collagen I-induced IL-12 secretions by DCs. Additionally, we observed suppression of collagen I-induced costimulatory molecules expression along with down-regulation of genes involved in DCs activation pathway. Furthermore, TNF- inhibition upon collagen Istimulation up-regulated the expression of interferon regulatory transcription factor IRF4, when compared to collagen I only treated cells. Collectively, our data demonstrate that collagen I induce TNF- production, which is crucial for the activation and function of DCs, through down-regulation of IRF4, and implicates the importance in development of anti- TNF- therapeutics for several inflammatory diseases.

  4. Regulation of Adrenal Aldosterone Production by Serine Protease Prostasin

    Takehiro Ko


    Full Text Available A serine protease prostasin has been demonstrated to have a pivotal role in the activation of the epithelial sodium channel. Systemic administration of adenovirus carrying human prostasin gene in rats resulted in an increase in plasma prostasin and aldosterone levels. However, the mechanism by which the elevation of prostasin levels in the systemic circulation stimulated the plasma aldosterone levels remains unknown. Therefore, we examined if prostasin increases the aldosterone synthesis in a human adrenocortical cell line (H295R cells. Luciferase assay using CYP11B2 promoter revealed that prostasin significantly increased the transcriptional activity of CYP11B2. Prostasin significantly increased both CYP11B2 mRNA expression and aldosterone production in a dose-dependent manner. Surprisingly, treatment with camostat mesilate, a potent prostasin inhibitor, had no effect on the aldosterone synthesis by prostasin and also a protease-dead mutant of prostasin significantly stimulated the aldosterone production. A T-type/L-type calcium channel blocker and a protein kinase C (PKC inhibitor significantly reduced the aldosterone synthesis by prostasin. Our findings suggest a stimulatory effect of prostasin on the aldosterone synthesis by adrenal gland through the nonproteolytic action and indicate a new role of prostasin in the systemic circulation.

  5. DMPD: The atrial natriuretic peptide regulates the production of inflammatorymediators in macrophages. [Dynamic Macrophage Pathway CSML Database

    Full Text Available 11890659 The atrial natriuretic peptide regulates the production of inflammatorymed...tml) (.csml) Show The atrial natriuretic peptide regulates the production of inflammatorymediators in macrop...hages. PubmedID 11890659 Title The atrial natriuretic peptide regulates the production

  6. Children's Development of Self-Regulation in Speech Production

    MacDonald, Ewen; Johnson, Elizabeth K.; Forsythe, Jaime;


    Species-specific vocalizations fall into two broad categories: those that emerge during maturation, independent of experience, and those that depend on early life interactions with conspecifics. Human language and the communication systems of a small number of other species, including songbirds......, fall into this latter class of vocal learning. Self-monitoring has been assumed to play an important role in the vocal learning of speech [1–3] and studies demonstrate that perception of your own voice is crucial for both the development and lifelong maintenance of vocalizations in humans and songbirds...... [4–8]. Experimental modifications of auditory feedback can also change vocalizations in both humans and songbirds [9–13]. However, with the exception of large manipulations of timing [14, 15], no study to date has ever directly examined the use of auditory feedback in speech production under the age...

  7. Encountering Challenges with the EU Regulation on Advance Therapy Medical Products.

    Mansnérus, Juli


    This article aims at analysing how well the Advanced Therapy Medical Product Regulation (EC) No. 1394/2007 (ATMP Regulation) meets the needs of small and medium-sized enterprises (SMES), academia and public tissue establishments developing advanced therapy medical products (ATMPS). Benefits and shortcomings of the ATMP Regulation are identified, and possible amendments are proposed to accelerate the translation of research into advanced therapies and to facilitate the commercialisation of ATMPS whilst ensuring safety. It was set up as a lex specialis to ensure the free movement of ATMPS within the EU in order to facilitate their access to the internal market and to foster the competitiveness of European pharmaceutical companies, while guaranteeing the highest level protection of public health. Since the adoption of the ATMP Regulation in late 2008, only 5 ATMPS have been granted marketing authorisations thus far. Hence, there is a need to analyse whether the ATMP Regulation meets its objectives. PMID:26665690

  8. 77 FR 31026 - Requirements for Importing Food and Drug Administration Regulated Products Into the United States


    ... to be discussed are FDA regulations with respect to importing pharmaceutical products, medical devices, food products, as well as technology which applies to brokers and forwarders. Date and Time: The... HUMAN SERVICES Food and Drug Administration Requirements for Importing Food and Drug...

  9. CdtR Regulates TcdA and TcdB Production in Clostridium difficile.

    Lyon, Shelley A; Hutton, Melanie L; Rood, Julian I; Cheung, Jackie K; Lyras, Dena


    Clostridium difficile is a global health burden and the leading cause of antibiotic-associated diarrhoea worldwide, causing severe gastrointestinal disease and death. Three well characterised toxins are encoded by this bacterium in two genetic loci, specifically, TcdB (toxin B) and TcdA (toxin A) in the Pathogenicity Locus (PaLoc) and binary toxin (CDT) in the genomically distinct CDT locus (CdtLoc). Toxin production is controlled by regulators specific to each locus. The orphan response regulator, CdtR, encoded within the CdtLoc, up-regulates CDT production. Until now there has been no suggestion that CdtR influences TcdA and TcdB production since it is not carried by all PaLoc-containing strains and CdtLoc is not linked genetically to PaLoc. Here we show that, in addition to CDT, CdtR regulates TcdA and TcdB production but that this effect is strain dependent. Of clinical relevance, CdtR increased the production of TcdA, TcdB and CDT in two epidemic ribotype 027 human strains, modulating their virulence in a mouse infection model. Strains traditionally from animal lineages, notably ribotype 078 strains, are increasingly being isolated from humans and their genetic and phenotypic analysis is critical for future studies on this important pathogen. Here we show that CdtR-mediated toxin regulation did not occur in other strain backgrounds, including a ribotype 078 animal strain. The finding that toxin gene regulation is strain dependent highlights the regulatory diversity between C. difficile isolates and the importance of studying virulence regulation in diverse lineages and clinically relevant strains. Our work provides the first evidence that TcdA, TcdB and CDT production is linked by a common regulatory mechanism and that CdtR may act as a global regulator of virulence in epidemic 027 strains. PMID:27414650

  10. CdtR Regulates TcdA and TcdB Production in Clostridium difficile.

    Shelley A Lyon


    Full Text Available Clostridium difficile is a global health burden and the leading cause of antibiotic-associated diarrhoea worldwide, causing severe gastrointestinal disease and death. Three well characterised toxins are encoded by this bacterium in two genetic loci, specifically, TcdB (toxin B and TcdA (toxin A in the Pathogenicity Locus (PaLoc and binary toxin (CDT in the genomically distinct CDT locus (CdtLoc. Toxin production is controlled by regulators specific to each locus. The orphan response regulator, CdtR, encoded within the CdtLoc, up-regulates CDT production. Until now there has been no suggestion that CdtR influences TcdA and TcdB production since it is not carried by all PaLoc-containing strains and CdtLoc is not linked genetically to PaLoc. Here we show that, in addition to CDT, CdtR regulates TcdA and TcdB production but that this effect is strain dependent. Of clinical relevance, CdtR increased the production of TcdA, TcdB and CDT in two epidemic ribotype 027 human strains, modulating their virulence in a mouse infection model. Strains traditionally from animal lineages, notably ribotype 078 strains, are increasingly being isolated from humans and their genetic and phenotypic analysis is critical for future studies on this important pathogen. Here we show that CdtR-mediated toxin regulation did not occur in other strain backgrounds, including a ribotype 078 animal strain. The finding that toxin gene regulation is strain dependent highlights the regulatory diversity between C. difficile isolates and the importance of studying virulence regulation in diverse lineages and clinically relevant strains. Our work provides the first evidence that TcdA, TcdB and CDT production is linked by a common regulatory mechanism and that CdtR may act as a global regulator of virulence in epidemic 027 strains.

  11. Influence of pH Regulation Mode in Glucose Fermentation on Product Selection and Process Stability

    Zuhaida Mohd-Zaki; Juan R. Bastidas-Oyanedel; Yang Lu; Robert Hoelzle; Steven Pratt; Fran R. Slater; Batstone, Damien J


    Mixed culture anaerobic fermentation generates a wide range of products from simple sugars, and is potentially an effective process for producing renewable commodity chemicals. However it is difficult to predict product spectrum, and to control the process. One of the key control handles is pH, but the response is commonly dependent on culture history. In this work, we assess the impact of pH regulation mode on the product spectrum. Two regulation modes were applied: in the first, pH was adju...

  12. Product Market Competition, Regulation and Dividend Payout Policy of Malaysian Banks

    Ameer, Rashid


    This paper investigates the impact of the product market competition, regulations on the dividend policies of We find significant differences in the payout of the banks categorized as selling a non-interest based banking products and mix of both interest and non-interest based banking products. We find that the decision to increase dividends is significantly related to earnings, and the decision to cut dividend is significantly related to the changes in the non-performing loans, corporate...

  13. The feed-back regulation of erythropoietin production in healthy humans

    The proposed oxygen-dependent feed-back loop regulation of EPO (erythropoietin) production is mainly supported by data from studies in animals and cell cultures. The feed-back loop and its dependence on oxygen was therefore challenged by studies in healthy humans: Exposure of humans to different levels of acute and continued altitude hypobaria provided evidence for an oxygen dependence of the EPO response. This response is consistent with the proposed feed-back loop regulation of EPO production; Exposure to continued altitude hypobaria demonstrated that the decline in human EPO production is initiated before an EPO-induced erythopoiesis is detectable, and that this decline is related to a concomitant decrease in the haemoglobin-oxygen affinity. Contrary to the feed-back loop, this time-relation indicate that the feed-back regulation of EPO production during continued hypobaric hypoxia is exerted primarily through a decrease in the haemoglobin-oxygen affinity, rather than by the effects of an EPO-stimulated erythropoiesis; Increased circulating levels of the proinflammatory cytokine IL-6 was found in healthy humans during four days of altitude exposure as compared with sea level. The other proinflammatory cytokines IL-1 beta, and TNF alpha remained unchanged, and the increased serum IL-6 did not induce production of c-reactive protein; Comparable circadian variations in human EPO production were shown in sedentary subjects, athletes, and healthy but hypoxaemic subjects. Human EPO production could not be triggered by one hour of high-intensity exercise, whereas longitudinal changes in exercise showed a trend of relation between human EPO production, serum concentration of free testosterone, and indices of body composition. These results have demonstrated and endogenous, probably hormonal, and oxygen-independent regulation of human EPO production, which is at variance with the oxygen dependent feed-back loop regulation of EPO production. Conclusively, the present

  14. The feed-back regulation of erythropoietin production in healthy humans

    Klausen, T


    The proposed oxygen-dependent feed-back loop regulation of EPO (erythropoietin) production is mainly supported by data from studies in animals and cell cultures. The feed-back loop and its dependence on oxygen was therefore challenged by studies in healthy humans: Exposure of humans to different levels of acute and continued altitude hypobaria provided evidence for an oxygen dependence of the EPO response. This response is consistent with the proposed feed-back loop regulation of EPO production; Exposure to continued altitude hypobaria demonstrated that the decline in human EPO production is initiated before an EPO-induced erythopoiesis is detectable, and that this decline is related to a concomitant decrease in the haemoglobin-oxygen affinity. Contrary to the feed-back loop, this time-relation indicate that the feed-back regulation of EPO production during continued hypobaric hypoxia is exerted primarily through a decrease in the haemoglobin-oxygen affinity, rather than by the effects of an EPO-stimulated erythropoiesis; Increased circulating levels of the proinflammatory cytokine IL-6 was found in healthy humans during four days of altitude exposure as compared with sea level. The other proinflammatory cytokines IL-1 beta, and TNF alpha remained unchanged, and the increased serum IL-6 did not induce production of c-reactive protein; Comparable circadian variations in human EPO production were shown in sedentary subjects, athletes, and healthy but hypoxaemic subjects. Human EPO production could not be triggered by one hour of high-intensity exercise, whereas longitudinal changes in exercise showed a trend of relation between human EPO production, serum concentration of free testosterone, and indices of body composition. These results have demonstrated and endogenous, probably hormonal, and oxygen-independent regulation of human EPO production, which is at variance with the oxygen dependent feed-back loop regulation of EPO production. Conclusively, the present

  15. Multihormonal regulation of thyroglobulin production by the OVNIS 6H thyroid cell line.

    Aouani, A; Hovsépian, S; Fayet, G


    The hormonal regulation of thyroglobulin production has been studied using a clone of the ovine thyroid cell line: OVNIS 6H. 3 among the 6 hormones proposed for serum replacement are required for an optimal thyroglobulin production; insulin, hydrocortisone and thyrotropin. Insulin alone stimulates thyroglobulin production. The presence of insulin is also required to observe hydrocortisone and TSH stimulations. Newborn calf serum inhibits thyroglobulin production. The best conditions for optimal thyroglobulin expression and TSH responsiveness are obtained in serum-free medium supplemented with 5 micrograms/ml insulin, 100 nM hydrocortisone and 1 mU/ml TSH. PMID:3286455

  16. FoxO1 mediates insulin-dependent regulation of hepatic VLDL production in mice

    Kamagate, Adama; Qu, Shen; Perdomo, German; Su, Dongming; Kim, Dae Hyun; Slusher, Sandra; Meseck, Marcia; Dong, H. Henry


    Excessive production of triglyceride-rich VLDL is attributable to hypertriglyceridemia. VLDL production is facilitated by microsomal triglyceride transfer protein (MTP) in a rate-limiting step that is regulated by insulin. To characterize the underlying mechanism, we studied hepatic MTP regulation by forkhead box O1 (FoxO1), a transcription factor that plays a key role in hepatic insulin signaling. In HepG2 cells, MTP expression was induced by FoxO1 and inhibited by exposure to insulin. This ...

  17. Role of Vfr in the regulation of antifungal compound production by Pseudomonas fluorescens FD6.

    Zhang, Qingxia; Ji, Yanyan; Xiao, Qi; Chng, Soonie; Tong, Yunhui; Chen, Xijun; Liu, Fengquan


    Pseudomonas fluorescens FD6 has been shown to possess many beneficial traits involved in the biocontrol of fungal plant pathogens, such as Botrytis cinerea and Monilinia fructicola. Vfr (virulence factor regulator) a highly conserved global regulator of gram-negative bacteria, such as the human pathogen Pseudomonas aeruginosa, is required for the expression of many important virulence traits. The role of Vfr in the regulation of biocontrol traits, such as the production of antibiotics to control fungal pathogens by antagonistic bacteria, has not been elucidated. This study investigated the effect of a vfr mutant derived from P. fluorescens FD6 to better understand the regulation of some important biocontrol traits associated with the bacterium. Biochemical studies indicated that the production of the antibiotics 2,4-diacetylphloroglucinol, pyrrolnitrin and pyoluteorin, was markedly enhanced in the vfr mutant. The vfr mutation also increased biofilm production, swimming motility and the expression of exopolysaccharide-associated gene (pelA, pslA and pslB) transcripts, but reduced protease production. Wheat rhizosphere and root tip colonization by the vfr mutant was higher than that by the wild type at 7 and 21days after inoculation. These findings demonstrate that Vfr modulates the expression of several key traits and the production of important antibiotics involved in the biocontrol potential of P. fluorescens FD6. PMID:27296968

  18. The Canadian Natural Health Products (NHP regulations: industry perceptions and compliance factors

    Boon Heather


    Full Text Available Abstract Background The use of natural health products, such as vitamins, minerals, and herbs, by Canadians has been increasing with time. As a result of consumer concern about the quality of these products, the Canadian Department of Health created the Natural Health Products (NHP Regulations. The new Canadian regulations raise questions about whether and how the NHP industry will be able to comply and what impact they will have on market structure. The objectives of this study were to explore who in the interview sample is complying with Canada's new NHP Regulations (i.e., submitted product licensing applications on time; and explore the factors that affect regulatory compliance. Methods Twenty key informant interviews were conducted with employees of the NHP industry. The structured interviews focused on the level of satisfaction with the Regulations and perceptions of compliance and non-compliance. Interviews were tape recorded and then transcribed verbatim. Data were independently coded, using qualitative content analysis. Team meetings were held after every three to four interviews to discuss emerging themes. Results The major finding of this study is that most (17 out of 20 companies interviewed were beginning to comply with the new regulatory regime. The factors that contribute to likelihood of regulatory compliance were: perceptions and knowledge of the regulations and business size. Conclusion The Canadian case can be instructive for other countries seeking to implement regulatory standards for natural health products. An unintended consequence of the Canadian NHP regulations may be the exit of smaller firms, leading to industry consolidation.




    In this study were evaluated both the growth and yield potentials of three chicory (Cichorium intybus var. sativum) varieties ('Fredonia Nova', 'Oesia' a 'Maurane') growing in natural agro-ecological conditions from 2006 to 2008. Regulation of the crop productivity by foliar application of biologically active substances (Atonik, Polybor 150, and Biafit Gold) was also studied. Evaluation of growth-production performance of chicory was realized as: leaf area index (LAI), photosynthetic potentia...

  20. Regulating workflow speed through product architecture: experiences from the Swedish magazine industry

    Rosenqvist, Christopher; Lindgren, Mats


    Coordination of content providers, producers and distributors has become increasingly important in the magazine industry when working with short life-cycle products. It is therefore interesting to study the product development and manufacturing process of magazines because of its short lead times. Production difficulties in the workflow process are often consequences of the product architecture. The aim of this research was to establish a concept for magazine architecture which could lead to substantial lead time reduction and improved product quality. In this research we studied magazine productions from Sweden's major magazine producer on both the customer site and from the manufacturing site. Monthly magazines, which had long time records about workload and production workflow were selected. The analysis was based on production data from the graphic arts service providers and from the editorial staff combined with open-ended interviews. The analysis shows that a re-arranged product architecture can increase both productivity and quality. It is clear that the product architecture of magazines regulates the workflow speed. The possibility of changing the product architecture might be difficult due to old traditions and different cultures within the editorial and manufacturing units. A solution to these problems should be sought through common efforts of both sides.




    Regulation of acidity and reduction of turbidity in the clarified pomegranate juice production. From sour varieties of pomegranates may obtain normal natural pomegranate juice by anion-exchange resin. There are determined problems quantity of precipitate and unstable color in the pomegranate juice and concentrate by experimentally.

  2. 75 FR 391 - Medical Device Quality System Regulation Educational Forum on Risk Management Through the Product...


    ...The Food and Drug Administration (FDA), Office of Regulatory Affairs (ORA), Southwest Region (SWR), Dallas District Office (DALDO), in collaboration with the FDA Medical Device Industry Coalition (FMDIC), is announcing a public workshop entitled ``Medical Device Quality System Regulation Educational Forum on Risk Management through the Product Life Cycle.'' This public workshop is intended to......

  3. 77 FR 234 - Rules and Regulations Under the Textile Fiber Products Identification Act


    .... SUPPLEMENTARY INFORMATION: On November 7, 2011, the Commission published its ANPR (76 FR 68690) seeking comment...; ] FEDERAL TRADE COMMISSION 16 CFR Part 303 Rules and Regulations Under the Textile Fiber Products... section below. Write ``Textile Rules, 16 CFR Part 303, Project No. P948404'' on your comment, and...

  4. Regulation of Polyphosphate Kinase Production by Antisense RNA in Pseudomonas fluorescens Pf0-1

    Silby, Mark W.; Julie S Nicoll; Levy, Stuart B.


    Pseudomonas spp. adapt rapidly to environmental fluctuations. Loss or overproduction of polyphosphate reduces the fitness of Pseudomonas fluorescens Pf0-1, indicating the importance of the fine-tuning of polyphosphate production. An antisense RNA was investigated and shown to regulate the polyphosphate kinase gene (ppk) by a posttranscriptional mechanism reducing ppk transcript abundance.

  5. Tools Related to the Federal Tobacco Products Regulations: What Retailers Need to Know PSA (:30)


    PSA to announce a new mobile text message program that will help raise retailers' awareness of the new federal tobacco regulations.  Created: 9/16/2010 by The CDC Division of News and Electronic Media and the FDA Center for Tobacco Products.   Date Released: 9/16/2010.

  6. Soybean Production &Trade in China-Implicated Impacts of GMO Regulation on Soybean Market

    ShiRong; ZhangTao; YanXiaoqing


    This paper provides an overview of the economic analysis, policy debate, and methodological issues on soybean production, import and export, and impacts of GMO regulation on soybean foreign trade of China, Thepaper analyzes China's soybean production capability, and discovers that the present yield of China's soybean plant system cannot satisfy the domestic demand. The paper also provides the method to solve such matters by using the result of a modftTed Cobb.Douglas model, in the third section of this paper, the impacts of GMOregulation on soybean trade and market in China are analyzed, fn this section, we provide a methodological issue to analyze the impacts of such regulation on trade. The paper then explains the implicated result induced by such regulations.

  7. SET protein up-regulated testosterone production in the cultured preantral follicles

    Xu Boqun


    Full Text Available Abstract Background We found previously that the expression of SET gene was up-regulated in polycystic ovaries. Evidences suggested that SET protein was essential for regulating both the promoter activity of CYP17A1 and the biological activity of P450c17. In this study, we explored whether SET regulated androgen production in preantral follicles. Methods The mouse preantral follicles were cultured in vitro. Testosterone secretion and expression of steroidogenic enzymes were observed in the preantral follicles treated in vitro by SET overexpression and knockdown. Results Testosterone levels in the media of the AdCMV-SET infected follicles significantly increased, and the CYP17A1 and HSD3B2 expression also significantly increased (P P  Conclusions SET played a positive role in regulating ovarian androgen biosynthesis by enhancing the transcription of steroidogenic enzymes CYP17A1 and HSD3B2, which maybe contribute to the hyperandrogenism in PCOS.

  8. Insights into the global regulation of anaerobic metabolism for improved biohydrogen production.

    Lu, Yuan; Zhao, Hongxin; Zhang, Chong; Xing, Xin-Hui


    To improve the biohydrogen yield in bacterial dark fermentation, a new approach of global anaerobic regulation was introduced. Two cellular global regulators FNR and NarP were overexpressed in two model organisms: facultatively anaerobic Enterobacter aerogenes (Ea) and strictly anaerobic Clostridium paraputrificum (Cp). The overexpression of FNR and NarP greatly altered anaerobic metabolism and increased the hydrogen yield by 40%. Metabolic analysis showed that the global regulation caused more reducing environment inside the cell. To get a thorough understanding of the global metabolic regulation, more genes (fdhF, fhlA, ppk, Cb-fdh1, and Sc-fdh1) were overexpressed in different Ea and Cp mutants. For the first time, it demonstrated that there were approximately linear relationships between the relative change of hydrogen yield and the relative change of NADH yield or ATP yield. It implied that cellular reducing power and energy level played vital roles in the biohydrogen production. PMID:26476162

  9. Advanced Therapy Medicinal Products (ATMPand exemptions to the Regulation 1394/2007: how confident can we be? An exploratory analysis.

    PhilippeVan Wilder


    Two exemptions are foreseen to the ATMP-Regulation: a. Products, which were legally on the Community market when the Regulation became applicable, should comply to the Regulation by 30 December 2012. b.the hospital exemption rule for non routine products for an individual patient. In this work we explored whether the actual application of the Regulation on ATMPs is in line with the aim of the Regulation in terms of guaranteeing the highest level of health protection for patients. Based on the analysis of the relative efficacy of the only EC authorized ATMP and its exempted alternatives, there is evidence against this Regulation 1394/2007 assumption.

  10. Complex marine natural products as potential epigenetic and production regulators of antibiotics from a marine Pseudomonas aeruginosa

    Wang, Bin; Waters, Amanda L.; Sims, James W.; Fullmer, Alexis; Ellison, Serena; Hamann, Mark T.


    Marine microbes are capable of producing secondary metabolites for defense and competition. Factors exerting an impact on secondary metabolite production of microbial communities included bioactive natural products and co-culturing. These external influences may have practical applications such as increased yields or the generation of new metabolites from otherwise silent genes in addition to reducing or limiting the production of undesirable metabolites. In this paper, we discuss the metabolic profiles of a marine Pseudomonas aeruginosa in the presence of a number of potential chemical epigenetic regulators, adjusting carbon sources and co-culturing with other microbes to induce a competitive response. As a result of these stressors certain groups of antibiotics or antimalarial agents were increased most notably when treating P. aeruginosa with sceptrin and co-culturing with another Pseudomonas sp. An interesting cross-talking event between these two Pseudomonas species when cultured together and exposed to sceptrin was observed. PMID:23563743

  11. Temperature regulates methane production through the function centralization of microbial community in anaerobic digestion.

    Lin, Qiang; De Vrieze, Jo; He, Guihua; Li, Xiangzhen; Li, Jiabao


    Temperature is crucial for the performance of anaerobic digestion process. In this study of anaerobic digestion of swine manure, the relationship between the microbial gene expression and methane production at different temperatures (25-55°C) was revealed through metatranscriptomic analysis. Daily methane production and total biogas production increased with temperature up to 50°C, but decreased at 55°C. The functional gene expression showed great variation at different temperatures. The function centralization (opposite to alpha-diversity), assessed by the least proportions of functional pathways contributing for at least 50% of total reads positively correlated to methane production. Temperature regulated methane production probably through reducing the diversity of functional pathways, but enhancing central functional pathways, so that most of cellular activities and resource were invested in methanogenesis and related pathways, enhancing the efficiency of conversion of substrates to methane. This research demonstrated the importance of function centralization for efficient system functioning. PMID:27236402

  12. Regulation Policy on Cell- and Tissue-Based Therapy Products in Korea.

    Lim, Jeong Ok


    Extensive investment on research and development of cell therapy products (CTPs) and tissue-engineered products (TEPs) has been made in Korea, and various commercial products are born in market. The Ministry of Food and Drug Safety (MFDS) in Korea regulates CTPs and TEPs as biological products under the authority of the Pharmaceutical Affairs Act. The Korean MFDS approved 16 CTPs and 4 stem CTPs and authorized 135 clinical trials, including 60 sponsor-investigator trials. Currently, the advent of stem cell technology and new biomaterials gives an impetus to develop more innovative CTPs and TEPs to treat intractable and serious diseases. This article deals about the regulatory process for approving CTPs and TEPs in Korea. Regulatory policies of the MFDS for supporting the development of novel products and ensuring the safety of the CTPs and TEPs are reviewed. PMID:25759938

  13. Performance-based regulation: enterprise responsibility for reducing death, injury, and disease caused by consumer products.

    Sugarman, Stephen D


    This article offers a bold new idea for confronting the staggering level of death, injury, and disease caused by five consumer products: cigarettes, alcohol, guns, junk food, and motor vehicles. Business leaders try to frame these negative outcomes as "collateral damage" that is someone else's problem. That framing not only is morally objectionable but also overlooks the possibility that, with proper prodding, industry could substantially lessen these public health disasters. I seek to reframe the public perception of who is responsible and propose to deploy a promising approach called "performance-based regulation" to combat the problem. Performance-based regulation would impose on manufacturers a legal obligation to reduce the negative social costs of their products. Rather than involving them in litigation or forcing them to operate differently (as "command-and-control" regimes do), performance-based regulation allows the firms to determine how best to decrease bad public health consequences. Like other public health strategies, performance-based regulation focuses on those who are far more likely than individual consumers to achieve real gains. Analogous to a tax on causing harm that exceeds a threshold level, performance-based regulation seeks to harness private initiative in pursuit of the public good. PMID:20018990

  14. Regulation and production of Tcf, a cable-like fimbriae from Salmonella enterica serovar Typhi.

    Leclerc, Jean-Mathieu; Quevillon, Eve-Lyne; Houde, Yoan; Paranjape, Kiran; Dozois, Charles M; Daigle, France


    tcf (Typhi colonization factor) is one of the 12 putative chaperone/usher fimbrial clusters present in the Salmonella enterica serovar Typhi genome. We investigated the production, expression and regulation of tcf as well as its role during interaction with human cells. The tcf gene cluster was cloned and induced in Escherichia coli and S. Typhi, and the production of intertwined fibres similar to the Cbl (cable) pili of Burkholderia cepacia was observed on the bacterial surface by electron microscopy. In S. Typhi, tcf was expressed more after growth in M63 minimal medium than in standard Luria-Bertani medium. Analysis of the promoter region identified putative binding sites for the global regulators RcsB, ArgR and Fur. The expression of tcf was measured in isogenic strains lacking these global regulators. Under the conditions tested, the results showed that tcf expression was higher in the fur mutant and was regulated by iron concentration. Fur may regulate these fimbriae indirectly via the small RNAs RyhB1 and RyhB2. An isogenic mutant harbouring a deletion of the tcf cluster did not demonstrate any defect in adhesion or invasion of human epithelial cells, or in phagocytosis or survival in macrophages, when compared to the WT serovar Typhi strain. However, the tcf cluster contributed to adherence to human epithelial cells when introduced into E. coli. Thus, tcf genes encode functional fimbriae that can act as an adhesin and may contribute to colonization during typhoid fever. PMID:26944792

  15. ATP-Based Ratio Regulation of Glucose and Xylose Improved Succinate Production

    Zhang, Fengyu; Li, Jiaojiao; Liu, Huaiwei; Liang, Quanfeng; Qi, Qingsheng


    We previously engineered E. coli YL104H to efficiently produce succinate from glucose. Furthermore, the present study proved that YL104H could also co-utilize xylose and glucose for succinate production. However, anaerobic succinate accumulation using xylose as the sole carbon source failed, probably because of an insufficient supply of energy. By analyzing the ATP generation under anaerobic conditions in the presence of glucose or xylose, we indicated that succinate production was affected by the intracellular ATP level, which can be simply regulated by the substrate ratio of xylose to glucose. This finding was confirmed by succinate production using an artificial mixture containing different xylose to glucose ratios. Using xylose mother liquor, a waste containing both glucose and xylose derived from xylitol production, a final succinate titer of 61.66 g/L with an overall productivity of 0.95 g/L/h was achieved, indicating that the regulation of the intracellular ATP level may be a useful and efficient strategy for succinate production and can be extended to other anaerobic processes. PMID:27315279

  16. ATP-Based Ratio Regulation of Glucose and Xylose Improved Succinate Production.

    Zhang, Fengyu; Li, Jiaojiao; Liu, Huaiwei; Liang, Quanfeng; Qi, Qingsheng


    We previously engineered E. coli YL104H to efficiently produce succinate from glucose. Furthermore, the present study proved that YL104H could also co-utilize xylose and glucose for succinate production. However, anaerobic succinate accumulation using xylose as the sole carbon source failed, probably because of an insufficient supply of energy. By analyzing the ATP generation under anaerobic conditions in the presence of glucose or xylose, we indicated that succinate production was affected by the intracellular ATP level, which can be simply regulated by the substrate ratio of xylose to glucose. This finding was confirmed by succinate production using an artificial mixture containing different xylose to glucose ratios. Using xylose mother liquor, a waste containing both glucose and xylose derived from xylitol production, a final succinate titer of 61.66 g/L with an overall productivity of 0.95 g/L/h was achieved, indicating that the regulation of the intracellular ATP level may be a useful and efficient strategy for succinate production and can be extended to other anaerobic processes. PMID:27315279

  17. Investigating the role of government trade policies and regulations on smuggling cosmetic products

    Sahar Seifpoor


    Full Text Available This paper investigates the effects of government trade policies as well as the rules and regulations on smuggling cosmetic products in Iran. The study considers the effects of five important factors including high tariffs and bureaucratic procedures, registration process, size and expire date, lack of accurate monitoring of distribution channels and government recent regulation failure on growth of smuggling cosmetic products in Iran. The proposed study uses structural equation modeling to examine the effects of these five components. The results indicate a positive and meaningful relationships between four variables including registration process (β = 0.84, P-value = 0.000, size and expire date (β = 0.86, P-value = 0.000, high rate of tariff (β = 0.88, P-value = 0.000 and government recent regulation failure (β = 0.97, P-value = 0.000 on growth of smuggling cosmetic products in Iran. In addition, the study has detected a negative and meaningful relationship between lack of accurate monitoring of distribution channels and growth of smuggling cosmetic products in Iran (β = -0.18, P-value = 0.000.

  18. AmrZ regulates cellulose production in Pseudomonas syringae pv. tomato DC3000.

    Prada-Ramírez, Harold A; Pérez-Mendoza, Daniel; Felipe, Antonia; Martínez-Granero, Francisco; Rivilla, Rafael; Sanjuán, Juan; Gallegos, María-Trinidad


    In Pseudomonas syringae pv. tomato DC3000, the second messenger c-di-GMP has been previously shown to stimulate pellicle formation and cellulose biosynthesis. A screen for genes involved in cellulose production under high c-di-GMP intracellular levels led to the identification of insertions in two genes, wssB and wssE, belonging to the Pto DC3000 cellulose biosynthesis operon wssABCDEFGHI. Interestingly, beside cellulose-deficient mutants, colonies with a rougher appearance than the wild type also arouse among the transposants. Those mutants carry insertions in amrZ, a gene encoding a transcriptional regulator in different Pseudomonas. Here, we provide evidence that AmrZ is involved in the regulation of bacterial cellulose production at transcriptional level by binding to the promoter region of the wssABCDEFGHI operon and repressing cellulose biosynthesis genes. Mutation of amrZ promotes wrinkly colony morphology, increased cellulose production and loss of motility in Pto DC3000. AmrZ regulon includes putative c-di-GMP metabolising proteins, like AdcA and MorA, which may also impact those phenotypes. Furthermore, an amrZ but not a cellulose-deficient mutant turned out to be impaired in pathogenesis, indicating that AmrZ is a key regulator of Pto DC3000 virulence probably by controlling bacterial processes other than cellulose production. PMID:26564578

  19. Similar biotherapeutic products in Latin America. Regulation and opportunities for patients with autoimmune diseases

    Desanvicente-Celis Z


    Full Text Available Zayrho Desanvicente-Celis, Julian Caro-Moreno, Mateo Enciso-Zuluaga, Juan-Manuel AnayaCenter for Autoimmune Diseases Research (CREA, Universidad del Rosario, Bogotá, ColombiaAbstract: Biotherapeutic products have revolutionized medicine, changing the way we can treat some chronic diseases, such as autoimmune diseases. The patent expiry and the high costs of reference biotherapeutic products, among other factors, have promoted interest in similar biotherapeutic products (SBPs, also known as biosimilars. The objective of developing an SBP is to manufacture a “highly similar” molecule to a reference biotherapeutic product, by conducting a comparability exercise that can demonstrate similar quality, safety, and efficacy. Regulations like those of the World Health Organization, the European Medicines Agency, and the Food and Drug Administration are international reference standards. Herein, we aim to point out the current status in Latin America on SBPs, focusing on regulatory issues within the context of autoimmune diseases. The regulations of Argentina, Peru, Chile, Guatemala, Panama and Costa Rica follow the World Health Organization guidelines. Other countries, such as Cuba, Mexico, Venezuela, and Brazil have regulations that take into account international standards combined with local features. In Colombia, a draft decree is under revision and the debate is ongoing. Some countries have already approved SBPs. Mexico, Chile, Ecuador, Bolivia, and Peru market SBPs of rituximab, and Colombia markets an SBP of etanercept. The advent of SBPs is definitely beneficial. Safety and efficacy must be ensured following clear and comprehensive regulations.Keywords: biological therapy, biotechnology, similar biotherapeutic product, autoimmune disease, Latin America

  20. A Drosophila Genome-Wide Screen Identifies Regulators of Steroid Hormone Production and Developmental Timing.

    Danielsen, E Thomas; Moeller, Morten E; Yamanaka, Naoki; Ou, Qiuxiang; Laursen, Janne M; Soenderholm, Caecilie; Zhuo, Ran; Phelps, Brian; Tang, Kevin; Zeng, Jie; Kondo, Shu; Nielsen, Christian H; Harvald, Eva B; Faergeman, Nils J; Haley, Macy J; O'Connor, Kyle A; King-Jones, Kirst; O'Connor, Michael B; Rewitz, Kim F


    Steroid hormones control important developmental processes and are linked to many diseases. To systematically identify genes and pathways required for steroid production, we performed a Drosophila genome-wide in vivo RNAi screen and identified 1,906 genes with potential roles in steroidogenesis and developmental timing. Here, we use our screen as a resource to identify mechanisms regulating intracellular levels of cholesterol, a substrate for steroidogenesis. We identify a conserved fatty acid elongase that underlies a mechanism that adjusts cholesterol trafficking and steroidogenesis with nutrition and developmental programs. In addition, we demonstrate the existence of an autophagosomal cholesterol mobilization mechanism and show that activation of this system rescues Niemann-Pick type C1 deficiency that causes a disorder characterized by cholesterol accumulation. These cholesterol-trafficking mechanisms are regulated by TOR and feedback signaling that couples steroidogenesis with growth and ensures proper maturation timing. These results reveal genes regulating steroidogenesis during development that likely modulate disease mechanisms. PMID:27326933

  1. AmyR is a novel negative regulator of amylovoran production in Erwinia amylovora.

    Dongping Wang

    Full Text Available In this study, we attempted to understand the role of an orphan gene amyR in Erwinia amylovora, a functionally conserved ortholog of ybjN in Escherichia coli, which has recently been characterized. Amylovoran, a high molecular weight acidic heteropolymer exopolysaccharide, is a virulent factor of E. amylovora. As reported earlier, amylovoran production in an amyR knockout mutant was about eight-fold higher than that in the wild type (WT strain of E. amylovora. When a multicopy plasmid containing the amyR gene was introduced into the amyR mutant or WT strains, amylovoran production was strongly inhibited. Furthermore, amylovoran production was also suppressed in various amylovoran-over-producing mutants, such as grrSA containing multicopies of the amyR gene. Consistent with amylovoran production, an inverse correlation was observed between in vitro expression of amyR and that of amylovoran biosynthetic genes. However, both the amyR knockout mutant and over-expression strains showed reduced levan production, another exopolysaccharide produced by E. amylovora. Virulence assays demonstrated that while the amyR mutant was capable of inducing slightly greater disease severity than that of the WT strain, strains over-expressing the amyR gene did not incite disease on apple shoots or leaves, and only caused reduced disease on immature pear fruits. Microarray studies revealed that amylovoran biosynthesis and related membrane protein-encoding genes were highly expressed in the amyR mutant, but down-regulated in the amyR over-expression strains in vitro. Down-regulation of amylovoran biosynthesis genes in the amyR over-expression strain partially explained why over-expression of amyR led to non-pathogenic or reduced virulence in vivo. These results suggest that AmyR plays an important role in regulating exopolysaccharide production, and thus virulence in E. amylovora.

  2. ApoE Production in Human Monocytes and Its Regulation by Inflammatory Cytokines

    Braesch-Andersen, Sten; Paulie, Staffan; Smedman, Christian; Mia, Sohel; Kumagai-Braesch, Makiko


    The apoE production by tissue macrophages is crucial for the prevention of atherosclerosis and the aim of this study was to further elucidate how this apolipoprotein is regulated by cytokines present during inflammation. Here we studied apoE production in peripheral blood mononuclear cells (PBMC) and analysis was made with a newly developed apoE ELISpot assay. In PBMC, apoE secretion was restricted to monocytes with classical (CD14++CD16−) and intermediate (CD14+CD16+) monocytes being the mai...

  3. Blimp-1-Dependent IL-10 Production by Tr1 Cells Regulates TNF-Mediated Tissue Pathology

    Montes de Oca, Marcela; Kumar, Rajiv; de Labastida Rivera, Fabian; Amante, Fiona H; Sheel, Meru; Faleiro, Rebecca J.; Bunn, Patrick T.; Best, Shannon E.; Beattie, Lynette; Ng, Susanna S.; Edwards, Chelsea L.; Muller, Werner; Cretney, Erika; Nutt, Stephen L.; Smyth, Mark J.; Haque, Ashraful; Hill, Geoffrey R.; Sundar, Shyam; Kallies, Axel; Engwerda, Christian R.


    Tumor necrosis factor (TNF) is critical for controlling many intracellular infections, but can also contribute to inflammation. It can promote the destruction of important cell populations and trigger dramatic tissue remodeling following establishment of chronic disease. Therefore, a better understanding of TNF regulation is needed to allow pathogen control without causing or exacerbating disease. IL-10 is an important regulatory cytokine with broad activities, including the suppression of inflammation. IL-10 is produced by different immune cells; however, its regulation and function appears to be cell-specific and context-dependent. Recently, IL-10 produced by Th1 (Tr1) cells was shown to protect host tissues from inflammation induced following infection. Here, we identify a novel pathway of TNF regulation by IL-10 from Tr1 cells during parasitic infection. We report elevated Blimp-1 mRNA levels in CD4+ T cells from visceral leishmaniasis (VL) patients, and demonstrate IL-12 was essential for Blimp-1 expression and Tr1 cell development in experimental VL. Critically, we show Blimp-1-dependent IL-10 production by Tr1 cells prevents tissue damage caused by IFNγ-dependent TNF production. Therefore, we identify Blimp-1-dependent IL-10 produced by Tr1 cells as a key regulator of TNF-mediated pathology and identify Tr1 cells as potential therapeutic tools to control inflammation. PMID:26765224

  4. A SWI/SNF Chromatin Remodelling Protein Controls Cytokinin Production through the Regulation of Chromatin Architecture

    Jégu, Teddy


    Chromatin architecture determines transcriptional accessibility to DNA and consequently gene expression levels in response to developmental and environmental stimuli. Recently, chromatin remodelers such as SWI/SNF complexes have been recognized as key regulators of chromatin architecture. To gain insight into the function of these complexes during root development, we have analyzed Arabidopsis knock-down lines for one sub-unit of SWI/SNF complexes: BAF60. Here, we show that BAF60 is a positive regulator of root development and cell cycle progression in the root meristem via its ability to down-regulate cytokinin production. By opposing both the deposition of active histone marks and the formation of a chromatin regulatory loop, BAF60 negatively regulates two crucial target genes for cytokinin biosynthesis (IPT3 and IPT7) and one cell cycle inhibitor (KRP7). Our results demonstrate that SWI/SNF complexes containing BAF60 are key factors governing the equilibrium between formation and dissociation of a chromatin loop controlling phytohormone production and cell cycle progression.

  5. Receptor for Advanced Glycation End Products Regulates Adipocyte Hypertrophy and Insulin Sensitivity in Mice

    Monden, Masayo; Koyama, Hidenori; Otsuka, Yoshiko; Morioka, Tomoaki; Mori, Katsuhito; Shoji, Takuhito; Mima, Yohei; Motoyama, Koka; Fukumoto, Shinya; Shioi, Atsushi; Emoto, Masanori; Yamamoto, Yasuhiko; Yamamoto, Hiroshi; Nishizawa, Yoshiki; Kurajoh, Masafumi


    Receptor for advanced glycation end products (RAGE) has been shown to be involved in adiposity as well as atherosclerosis even in nondiabetic conditions. In this study, we examined mechanisms underlying how RAGE regulates adiposity and insulin sensitivity. RAGE overexpression in 3T3-L1 preadipocytes using adenoviral gene transfer accelerated adipocyte hypertrophy, whereas inhibitions of RAGE by small interfering RNA significantly decrease adipocyte hypertrophy. Furthermore, double knockdown o...

  6. Regulation and genetic enhancement of beta-amylase production in Clostridium thermosulfurogenes.

    Hyun, H H; Zeikus, J G


    We studied the general mechanism for regulation of beta-amylase synthesis in Clostridium thermosulfurogenes. beta-Amylase was expressed at high levels only when the organism was grown on maltose or other carbohydrates containing maltose units. Three kinds of mutants altered in beta-amylase production were isolated by using nitrosoguanidine treatment, enrichment on 2-deoxyglucose, and selection of colonies with large clear zones on iodine-stained starch-glucose agar plates. beta-Amylase was pr...

  7. A negative regulator mediates quorum-sensing control of exopolysaccharide production in Pantoea stewartii subsp. stewartii

    von Bodman, Susanne Beck; Majerczak, Doris R.; Coplin, David L.


    Classical quorum-sensing (autoinduction) regulation, as exemplified by the lux system of Vibrio fischeri, requires N-acyl homoserine lactone (AHL) signals to stimulate cognate transcriptional activators for the cell density-dependent expression of specific target gene systems. For Pantoea stewartii subsp. stewartii, a bacterial pathogen of sweet corn and maize, the extracellular polysaccharide (EPS) stewartan is a major virulence factor, and its production is controlled by quorum sensing in a...

  8. Regulation of adiponectin production by insulin: interactions with tumor necrosis factor-α and interleukin-6

    Hajri, Tahar; Tao, Huan; Wattacheril, Julia; Marks-Shulman, Pamela; Abumrad, Naji N.


    Obesity is often associated with insulin resistance, low-grade systemic inflammation, and reduced plasma adiponectin. Inflammation is also increased in adipose tissue, but it is not clear whether the reductions of adiponectin levels are related to dysregulation of insulin activity and/or increased proinflammatory mediators. In this study, we investigated the interactions of insulin, tumor necrosis factor-α (TNF-α) and interleukin 6 (IL-6) in the regulation of adiponectin production using in v...

  9. The Effects of Regulations and Business Cycles on Temporary Contracts, the Organization of Firms and Productivity

    Eslava, Marcela; Haltiwanger, John; Kugler, Adriana; Kugler, Maurice


    In this study, we assess the impact, on workforce contract composition, employment adjustment dynamics and productivity, of a combination of changes in the Colombian labor legislation which increased firm’s ability of using contracts of a temporary nature, and posterior changes that increased the costs associated with longer term contracts. Until 1990, labor regulations in Colombia practically banned the possibility of using fixed-term contracts for horizons of less than one year (see, e.g. K...

  10. Mucosal Immune Regulation in Intestinal Disease. The role of bacterial products, food components and drugs

    Bol-Schoenmakers, M


    The challenge of the mucosal gut associated immune system is to remain unresponsive to food products and commensal microbiota, while mounting an appropriate immune response towards pathogens. This implicates the necessity of tight immune regulation within the gut associated lymphoid tissue (GALT). Imbalance between tolerance and immunity (e.g. intestinal homeostasis) contributes to the pathogenesis of intestinal diseases like inflammatory bowel disease (IBD) and food allergies. The first part...

  11. Emissions Control and the Regulation of Product Markets: The Case of Automobiles

    Rasha Ahmed; Kathleen Segerson


    The paper investigates alternative policies to regulate emissions from polluting product markets, specifically considering the case of the automobiles market. The two policies we consider are: a quota that limits the quantity produced of the polluting model and a more flexible average efficiency standard that requires a minimum energy efficiency across all models produced by a firm, similar to the US Corporate Average Fuel Economy (CAFE) standards. We use a duopoly model of vertical different...

  12. Hsp90 Regulates NADPH Oxidase Activity and Is Necessary for Superoxide but Not Hydrogen Peroxide Production

    Chen, Feng; Pandey, Deepesh; Chadli, Ahmed; Catravas, John D.; Chen, Teng; Fulton, David J. R.


    The goal of this study was to identify whether heat-shock protein 90 (Hsp90) regulates the production of superoxide and other reactive oxygen species from the NADPH oxidases (Nox). We found that pharmacological and genetic inhibition of Hsp90 directly reduced Nox5-derived superoxide without secondarily modifying signaling events. Coimmunoprecipitation and bioluminescence resonance energy transfer studies suggest that the C-terminus of Nox5 binds to Hsp90. Long-term Hsp90 inhibition reduced No...

  13. Growth, yield and seed production of okra as influenced by different growth regulators

    Plant growth regulators (PGRs) affect various aspects of plant physiology, mainly vegetative and reproductive traits including yield and seed production. Therefore, different concentrations (0, 50, 100 and 200 ppm) of gibberellic acid (GA3) and naphthalene acetic acid (NAA), alone or in different combinations were sprayed on okra plants at 2-true leaf stage, to ascertain their impact on plant growth, pod production, seed yield and seed quality. All variables regarding vegetative and reproductive growth were significantly influenced by different concentrations of the growth regulators except number of days taken to flowering. Growth regulators were less effective when applied individually as compared to their combined use; however, performance of plants treated with individual PGR was better than the untreated plants. The number of leaves plant/sup -1/ and plant height was higher in plants when sprayed with GA/sub 3/ and NAA at the rate 200+100 ppm as well as with GA/sub 3/ and NAA at the rate 200+200 ppm. The number of pods plant/sup -1/, pod length, pod fresh and dry weight, seed yield and seed quality (in terms of germination percentage and 1000-seed weight) was maximum in plants receiving foliar spray of both GA3 and NAA at the rate 200+200 ppm. These results signify the role of GA/sub 3/ and NAA in okra pod production for fresh consumption as well as for seed yield. (author)

  14. An R2R3-MYB Transcription Factor Regulates Eugenol Production in Ripe Strawberry Fruit Receptacles.

    Medina-Puche, Laura; Molina-Hidalgo, Francisco Javier; Boersma, Maaike; Schuurink, Robert C; López-Vidriero, Irene; Solano, Roberto; Franco-Zorrilla, José-Manuel; Caballero, José Luis; Blanco-Portales, Rosario; Muñoz-Blanco, Juan


    Eugenol is a volatile phenylpropanoid that contributes to flower and ripe fruit scent. In ripe strawberry (Fragaria × ananassa) fruit receptacles, eugenol is biosynthesized by eugenol synthase (FaEGS2). However, the transcriptional regulation of this process is still unknown. We have identified and functionally characterized an R2R3 MYB transcription factor (emission of benzenoid II [FaEOBII]) that seems to be the orthologous gene of PhEOBII from Petunia hybrida, which contributes to the regulation of eugenol biosynthesis in petals. The expression of FaEOBII was ripening related and fruit receptacle specific, although high expression values were also found in petals. This expression pattern of FaEOBII correlated with eugenol content in both fruit receptacle and petals. The expression of FaEOBII was repressed by auxins and activated by abscisic acid, in parallel to the ripening process. In ripe strawberry receptacles, where the expression of FaEOBII was silenced, the expression of cinnamyl alcohol dehydrogenase1 and FaEGS2, two structural genes involved in eugenol production, was down-regulated. A subsequent decrease in eugenol content in ripe receptacles was also observed, confirming the involvement of FaEOBII in eugenol metabolism. Additionally, the expression of FaEOBII was under the control of FaMYB10, another R2R3 MYB transcription factor that regulates the early and late biosynthetic genes from the flavonoid/phenylpropanoid pathway. In parallel, the amount of eugenol in FaMYB10-silenced receptacles was also diminished. Taken together, these data indicate that FaEOBII plays a regulating role in the volatile phenylpropanoid pathway gene expression that gives rise to eugenol production in ripe strawberry receptacles. PMID:25931522

  15. Chromatin landscaping in algae reveals novel regulation pathway for biofuels production

    Ngan, Chew Yee; Wong, Chee-Hong; Choi, Cindy; Pratap, Abhishek; Han, James; Wei, Chia-Lin


    The diminishing reserve of fossil fuels calls for the development of biofuels. Biofuels are produced from renewable resources, including photosynthetic organisms, generating clean energy. Microalgae is one of the potential feedstock for biofuels production. It grows easily even in waste water, and poses no competition to agricultural crops for arable land. However, little is known about the algae lipid biosynthetic regulatory mechanisms. Most studies relied on the homology to other plant model organisms, in particular Arabidopsis or through low coverage expression analysis to identify key enzymes. This limits the discovery of new components in the biosynthetic pathways, particularly the genetic regulators and effort to maximize the production efficiency of algal biofuels. Here we report an unprecedented and de novo approach to dissect the algal lipid pathways through disclosing the temporal regulations of chromatin states during lipid biosynthesis. We have generated genome wide chromatin maps in chlamydomonas genome using ChIP-seq targeting 7 histone modifications and RNA polymerase II in a time-series manner throughout conditions activating lipid biosynthesis. To our surprise, the combinatory profiles of histone codes uncovered new regulatory mechanism in gene expression in algae. Coupled with matched RNA-seq data, chromatin changes revealed potential novel regulators and candidate genes involved in the activation of lipid accumulations. Genetic perturbation on these candidate regulators further demonstrated the potential to manipulate the regulatory cascade for lipid synthesis efficiency. Exploring epigenetic landscape in microalgae shown here provides powerful tools needed in improving biofuel production and new technology platform for renewable energy generation, global carbon management, and environmental survey.

  16. Product unconformable in the light of legal regulations and the ISO 9001:2000 standards

    Justyna Górna


    Full Text Available The supervision of unconformable product is a key problem in the era of globalization. In Poland the supervision of safety product has been entrusted to the President of the Office of Competition and Consumer Protection. The agency supporting its activities is the Trade Inspection. Growing popularity of the quality systems conformable with the ISO 9000 standard caused that they have been included in the EU regulations as criteria of assessment of conformability with requirements. The certificate of the quality management system is indispensable for companies for functioning in many market areas. One should remember that quality management system will help the company to supervise unconformable products only when it really functions and is not just on paper. Only then it will function efficiently.

  17. Can green consumerism replace environmental regulation? A differentiated-products example

    Eriksson, Clas [Department of Economics, Swedish University of Agricultural Sciences, P.O. Box 7013, S-750 07 Uppsala (Sweden)


    This paper assumes that consumers are willing to pay an extra premium for a good if it has a low impact on the environment. We examine if a little dose of such idealistic behavior has a large impact on the market equilibrium, and to what extent it can replace the environmental regulation. The analysis is carried out in a model with product differentiation, where consumers differ in their preferences for product quality. Consumers' willingness to pay the environmental premium may be uniformly or non-uniformly distributed. Green consumerism will only be modestly influential in both cases, despite the fact that product differentiation leads to relaxed competition and increased profits, and thereby creates leverage.

  18. Can green consumerism replace environmental regulation? A differentiated-products example

    This paper assumes that consumers are willing to pay an extra premium for a good if it has a low impact on the environment. We examine if a little dose of such idealistic behavior has a large impact on the market equilibrium, and to what extent it can replace the environmental regulation. The analysis is carried out in a model with product differentiation, where consumers differ in their preferences for product quality. Consumers' willingness to pay the environmental premium may be uniformly or non-uniformly distributed. Green consumerism will only be modestly influential in both cases, despite the fact that product differentiation leads to relaxed competition and increased profits, and thereby creates leverage

  19. Improving monoterpene geraniol production through geranyl diphosphate synthesis regulation in Saccharomyces cerevisiae.

    Zhao, Jianzhi; Bao, Xiaoming; Li, Chen; Shen, Yu; Hou, Jin


    Monoterpenes have wide applications in the food, cosmetics, and medicine industries and have recently received increased attention as advanced biofuels. However, compared with sesquiterpenes, monoterpene production is still lagging in Saccharomyces cerevisiae. In this study, geraniol, a valuable acyclic monoterpene alcohol, was synthesized in S. cerevisiae. We evaluated three geraniol synthases in S. cerevisiae, and the geraniol synthase Valeriana officinalis (tVoGES), which lacked a plastid-targeting peptide, yielded the highest geraniol production. To improve geraniol production, synthesis of the precursor geranyl diphosphate (GPP) was regulated by comparing three specific GPP synthase genes derived from different plants and the endogenous farnesyl diphosphate synthase gene variants ERG20 (G) (ERG20 (K197G) ) and ERG20 (WW) (ERG20 (F96W-N127W) ), and controlling endogenous ERG20 expression, coupled with increasing the expression of the mevalonate pathway by co-overexpressing IDI1, tHMG1, and UPC2-1. The results showed that overexpressing ERG20 (WW) and strengthening the mevalonate pathway significantly improved geraniol production, while expressing heterologous GPP synthase genes or down-regulating endogenous ERG20 expression did not show positive effect. In addition, we constructed an Erg20p(F96W-N127W)-tVoGES fusion protein, and geraniol production reached 66.2 mg/L after optimizing the amino acid linker and the order of the proteins. The best strain yielded 293 mg/L geraniol in a fed-batch cultivation, a sevenfold improvement over the highest titer previously reported in an engineered S. cerevisiae strain. Finally, we showed that the toxicity of geraniol limited its production. The platform developed here can be readily used to synthesize other monoterpenes. PMID:26883346

  20. Uranium mining and production: A legal perspective on regulating an important resource

    The importance of uranium can be examined from several perspectives. First, natural uranium is a strategic energy resource because it is a key ingredient for the generation of nuclear power and, therefore, it can affect the energy security of a state. Second, natural uranium is also a raw material in relative abundance throughout the world, which can, through certain steps, be transformed into nuclear explosive devices. Thus, there is both an interest in the trade of uranium resources and a need for their regulatory control. The importance of uranium to the worldwide civilian nuclear industry means that its extraction and processing - the so-called 'front end' of the nuclear fuel cycle - is of regulatory interest. Like 'ordinary' metal mining, which is generally regulated within a country, uranium mining must also be considered from the more particular perspective of regulation and control, as part of the international nuclear law regime that is applied to the entire nuclear fuel cycle. The present overview of the regulatory role in overseeing and controlling uranium mining and production will outline the regulation of this resource from an international level, both from early days to the present day. Uranium mining is not regulated internationally; rather, it is a state responsibility. However, developments at the international level have, over time, led to better national regulation. One can note several changes in the approach to the uranium industry since the time that uranium was first mined on a significant scale, so that today the mining and trade of uranium is a well-established and regulated industry much less marked by secrecy and Cold War sentiment. At the same time, it is informed by international standards and conventions, proliferation concerns and a modern regard for environmental protection and the health and safety of workers and the public. (author)

  1. Cross-talk between light and glucose regulation controls toxin production and morphogenesis in Aspergillus nidulans

    Light is a major environmental stimulus that has a broad effect on organisms, triggering a cellular response that results in an optimal adaptation enhancing fitness and survival. In fungi, light affects growth, and causes diverse morphological changes such as those leading to reproduction. Light can also affect fungal metabolism, including the biosynthesis of natural products. In this study we show that in Aspergillus nidulans the effect of light on the production of the sterigmatocystin (ST) toxin depends on the glucose concentration. In cultures grown with 1% glucose and exposed to light, ST production was lower than when grown in the dark. This lower ST production coincided with an elevated rate of cellular damage with partial loss of nuclear integrity and vacuolated cytoplasm. However, in cultures grown with 2% glucose these effects were reversed and light enhanced ST production. Glucose abundance also affected the light-dependent subcellular localization of the VeA (velvet) protein, a key regulator necessary for normal light-dependent morphogenesis and secondary metabolism in Aspergilli and other fungal gen- era. The role of other VeA-associated proteins, particularly the blue-light-sensing proteins LreA and LreB (WC-1 and WC-2 orthologs), on conidiation could also be modified by the abundance of glucose. We also show that LreA and LreB, as well as the phytochrome FphA, modulate not only the synthesis of sterigmat- ocystin, but also the production of the antibiotic penicillin. (author)

  2. Regulator of a plant for joint production of electrical energy and steam

    Granelli, G.P. (Pavia Univ. (IT). Ist. di Elettrotecnica); Montagna, M.; Salomone, R.; Sarti, E.; Silvestri, A.


    The paper shows the new design of a regulation system for joint production of electrical power and steam for technological use. The regulation concerns both with steam pressure and electrical frequency, as the plant (although connectable with the Italian network) runs normally stand-alone. The design was developed on a linearized model for small variations around a normal operating state and, as for the nonlinear characteristics of turbine valves, around a maximum gain condition. The controller now in use carries out the decoupling between pressure and frequency regulation unsatisfactorily: in particular, the latter one causes unacceptable frequency steady state error both for electrical and thermal load changes. The new design aims to avoid such effects: this is done by adding an integrating term to the frequency regulator, and resetting the propotional gain of the actual amplifiers, as to decouple the pressure and frequency feedbach loops. Parameters are set up, too, for pole assignment of the decoupled subsystems. The improvement of control response has been tested by computer simulation, even in conditions different from the design's.

  3. [A contribution to the development of advertising in pharmacy II. Historical development of regulation of advertising of medicinal products].

    Vranová, Vilma


    The article deals with the development of regulation of advertising of medicinal products in the Czech Lands of the Habsburg Monarchy and Czechoslovakia in the years 1775-1938. Advertising medicines had and has its specifics and its regulation had been addressed by specific standards and linked to other health laws and regulations. Regulation of advertising of medicinal products has undergone a long process from the initial total ban on advertising to the establishment of clear rules, some of which, such as restrictions on advertising prescription-only medicines only to the professional healthcare press, are still valid. PMID:23256658

  4. CANDU 9 - the CANDU product to meet customer and regulator requirements now and in the future

    CANDU reactors developed under Canadian licensing regulations that placed the primary responsibility for safety on the licensee. The Atomic Energy Control Board (AECB), Canada's nuclear regulatory agency, state in their regulations what is expected in terms of safety performance so that designers are free to propose the best means of meeting this performance. This goal-oriented approach, besides encouraging innovation, allowed CANDU to be licensed in other jurisdictions. The latest design - the large, single unit, CANDU 9 - explicitly incorporates licensability in Canada through a formal AECB review of the design; lessons learned from licensing CANDU 6 in Asian countries, particularly with Wolsong 2, 3 and 4 in Korea, and more recently with Qinshan in China; utility requirements for modem evolutionary plants; and emerging international standards for safety, sponsored or issued by the IAEA. By combining the assurance of acceptability in Canada with compliance with foreign and international requirements, CANDU 9 becomes an internationally licensable product. (author)

  5. The safety and regulation of natural products used as foods and food ingredients.

    Abdel-Rahman, Ali; Anyangwe, Njwen; Carlacci, Louis; Casper, Steve; Danam, Rebecca P; Enongene, Evaristus; Erives, Gladys; Fabricant, Daniel; Gudi, Ramadevi; Hilmas, Corey J; Hines, Fred; Howard, Paul; Levy, Dan; Lin, Ying; Moore, Robert J; Pfeiler, Erika; Thurmond, T Scott; Turujman, Saleh; Walker, Nigel J


    The use of botanicals and dietary supplements derived from natural substances as an adjunct to an improved quality of life or for their purported medical benefits has become increasingly common in the United States. This review addresses the safety assessment and regulation of food products containing these substances by the U.S. Food and Drug Administration (FDA). The issue of safety is particularly critical given how little information is available on the toxicity of some of these products. The first section uses case studies for stevia and green tea extracts as examples of how FDA evaluates the safety of botanical and herbal products submitted for consideration as Generally Recognized as Safe under the Federal Food, Drug, and Cosmetics Act. The 1994 Dietary Supplement Health Education Act (DSHEA) created a regulatory framework for dietary supplements. The article also discusses the regulation of this class of dietary supplements under DSHEA and addresses the FDA experience in analyzing the safety of natural ingredients described in pre-market safety submissions. Lastly, we discuss an ongoing interagency collaboration to conduct safety testing of nominated dietary supplements. PMID:21821733

  6. The Central Nervous System Regulates Embryonic HSPC Production via Stress-Responsive Glucocorticoid Receptor Signaling.

    Kwan, Wanda; Cortes, Mauricio; Frost, Isaura; Esain, Virginie; Theodore, Lindsay N; Liu, Sarah Y; Budrow, Nadine; Goessling, Wolfram; North, Trista E


    Hematopoietic stem and progenitor cell (HSPC) specification is regulated by numerous defined factors acting locally within the hemogenic niche; however, it is unclear whether production can adapt to fluctuating systemic needs. Here we show that the CNS controls embryonic HSPC numbers via the hypothalamic-pituitary-adrenal/interrenal (HPA/I) stress response axis. Exposure to serotonin or the reuptake inhibitor fluoxetine increased runx1 expression and Flk1(+)/cMyb(+) HSPCs independent of peripheral innervation. Inhibition of neuronal, but not peripheral, tryptophan hydroxlyase (Tph) persistently reduced HSPC number. Consistent with central HPA/I axis induction and glucocorticoid receptor (GR) activation, GR agonists enhanced, whereas GR loss diminished, HSPC formation. Significantly, developmental hypoxia, as indicated by Hif1α function, induced the HPA/I axis and cortisol production. Furthermore, Hif1α-stimulated HSPC enhancement was attenuated by neuronal tph or GR loss. Our data establish that embryonic HSC production responds to physiologic stress via CNS-derived serotonin synthesis and central feedback regulation to control HSC numbers. PMID:27424782

  7. Inhibitory effect of carnosine on interleukin-8 production in intestinal epithelial cells through translational regulation.

    Son, Dong Ok; Satsu, Hideo; Kiso, Yoshinobu; Totsuka, Mamoru; Shimizu, Makoto


    The enhanced intestinal production of pro-inflammatory cytokines leads to inflammation and carcinogenesis, and therefore its down-regulation by nutrients could represent a promising therapeutic approach. We found for the first time that the secretion of interleukin-8 (IL-8) in intestinal epithelial cells stimulated by hydrogen peroxide or TNF-alpha was suppressed in the presence of carnosine (beta-Ala-His), a dietary dipeptide. Interestingly, carnosine had no influence on the stimulus-induced IL-8 mRNA expression, although the intracellular production and secretion of IL-8 were significantly inhibited by carnosine. The inhibitory effect of carnosine on the IL-8 secretion differed from that of other histidine-containing dipeptides like Gly-His, Ala-His, and anserine (beta-Ala-1-methyl-His), which inhibited both the hydrogen peroxide-induced secretion and mRNA expression of IL-8. These observations indicate that carnosine inhibited IL-8 secretion along a unique pathway, in which IL-8 production was suppressed at a post-transcriptional level, for instance, translation. The hypothesis that carnosine inhibited the translation of IL-8 mRNA is supported by the finding that the phosphorylation of eIF4E, an initiation factor, in stimulated Caco-2 cells was inhibited by carnosine. These results suggest that carnosine is a novel type of anti-inflammatory agent that down-regulates the inflammatory response in intestinal epithelial cells by a unique mechanism. PMID:18397832

  8. Life cycle and production of Baetis rhodani in a regulated river in Western Norway: comparison of pre- and post-regulation conditions

    The benthic invertebrate fauna of the lowland part of the Aurland River was investigated in 1966-7 over a full year cycle. The watershed was built out for hydropower production during 1979-83. In this study the life cycle and production of Baetis rhodani from pre-regulated conditions (1966-7) was compared with two types of post-regulation streams(1988-9). Before regulation the water flow was high during May-June and in autumn, combined with heavy rainfall. The lowest flow was in winter and early spring. The pre-regulated temperature was low in winter, increasing from April to a maximum in August (10-14oC). After regulation one part of the river received reduced flow and increased summer temperatures (upper part) and one received hypolimnion release and reduced summer temperatures (lower part). In the upper part the density of B.rhodani increased between 10 and 20 times. The reason for this seems to be increased temperature, reduced accidental drift of larvae and increased amount of stored organic material on the bottom. In the lower part the density increase was two to five times and the production two times higher after regulation. The lower increase in production than density was due to a much higher proportion of small larvae. B.rhodani had mainly an univoltine life cycle before regulation, but a small part of the population was bivoltine. After regulation the species was univoltine in the lower part. In the upper part the life cycle was about one month faster, but no clear indication of bivoltinism was seen. The absence of the second generation is due to low temperatures and probably a lack of signals connected with temperature. (Author)

  9. Regulation of P450 oxidoreductase by gonadotropins in rat ovary and its effect on estrogen production

    Uesaka Miki


    Full Text Available Abstract Background P450 oxidoreductase (POR catalyzes electron transfer to microsomal P450 enzymes. Its deficiency causes Antley-Bixler syndrome (ABS, and about half the patients with ABS have ambiguous genitalia and/or impaired steroidogenesis. POR mRNA expression is up-regulated when mesenchymal stem cells (MSCs differentiate into steroidogenic cells, suggesting that the regulation of POR gene expression is important for steroidogenesis. In this context we examined the regulation of POR expression in ovarian granulosa cells by gonadotropins, and its possible role in steroidogenesis. Methods Changes in gene expression in MSCs during differentiation into steroidogenic cells were examined by DNA microarray analysis. Changes in mRNA and protein expression of POR in the rat ovary or in granulosa cells induced by gonadotropin treatment were examined by reverse transcription-polymerase chain reaction and western blotting. Effects of transient expression of wild-type or mutant (R457H or V492E POR proteins on the production of estrone in COS-7 cells were examined in vitro. Effects of POR knockdown were also examined in estrogen producing cell-line, KGN cells. Results POR mRNA was induced in MSCs following transduction with the SF-1 retrovirus, and was further increased by cAMP treatment. Expression of POR mRNA, as well as Cyp19 mRNA, in the rat ovary were induced by equine chorionic gonadotropin and human chorionic gonadotropin. POR mRNA and protein were also induced by follicle stimulating hormone in primary cultured rat granulosa cells, and the induction pattern was similar to that for aromatase. Transient expression of POR in COS-7 cells, which expressed a constant amount of aromatase protein, greatly increased the rate of conversion of androstenedione to estrone, in a dose-dependent manner. The expression of mutant POR proteins (R457H or V492E, such as those found in ABS patients, had much less effect on aromatase activity than expression of wild

  10. Enhanced pinocembrin production in Escherichia coli by regulating cinnamic acid metabolism

    Cao, Weijia; Ma, Weichao; Wang, Xin; Zhang, Bowen; Cao, Xun; Chen, Kequan; Li, Yan; Ouyang, Pingkai


    Microbial biosynthesis of pinocembrin is of great interest in the area of drug research and human healthcare. Here we found that the accumulation of the pathway intermediate cinnamic acid adversely affected pinocembrin production. Hence, a stepwise metabolic engineering strategy was carried out aimed at eliminating this pathway bottleneck and increasing pinocembrin production. The screening of gene source and the optimization of gene expression was first employed to regulate the synthetic pathway of cinnamic acid, which showed a 3.53-fold increase in pinocembrin production (7.76 mg/L) occurred with the alleviation of cinnamic acid accumulation in the engineered E. coli. Then, the downstream pathway that consuming cinnamic acid was optimized by the site-directed mutagenesis of chalcone synthase and cofactor engineering. S165M mutant of chalcone synthase could efficiently improve the pinocembrin production, and allowed the product titer of pinocembrin increased to 40.05 mg/L coupled with the malonyl-CoA engineering. With a two-phase pH fermentation strategy, the cultivation of the optimized strain resulted in a final pinocembrin titer of 67.81 mg/L. The results and engineering strategies demonstrated here would hold promise for the titer improvement of other flavonoids. PMID:27586788

  11. Early aldosterone-induced gene product regulates the epithelial sodium channel by deubiquitylation.

    Fakitsas, Panagiotis; Adam, Gabriele; Daidié, Dorothée; van Bemmelen, Miguel X; Fouladkou, Fatemeh; Patrignani, Andrea; Wagner, Ulrich; Warth, Richard; Camargo, Simone M R; Staub, Olivier; Verrey, François


    The mineralocorticoid hormone aldosterone controls sodium reabsorption and BP largely by regulating the cell-surface expression and function of the epithelial sodium channel (ENaC) in target kidney tubules. Part of the stimulatory effect of aldosterone on ENaC is mediated by the induction of serum- and glucocorticoid-regulated kinase 1 (Sgk1), a kinase that interferes with the ubiquitylation of ENaC by ubiquitin-protein ligase Nedd4-2. In vivo early aldosterone-regulated mRNA now has been identified in microselected mouse distal nephron by microarray. From 22 mRNA that displayed a two-fold or more change, 13 were downregulated and nine were upregulated. Besides Sgk1, the induced mRNA include Grem2 (protein related to DAN and cerebrus [PRDC]), activating transcription factor 3, cAMP responsive element modulator, and the ubiquitin-specific protease Usp2-45. The induction of this last enzyme isoform was verified in mouse distal nephron tubule at the protein level. With the use of Hek293 cells, Xenopus oocytes, and mpkCCD(c14) cells as expression systems, it was shown that Usp2-45 deubiquitylates ENaC and stimulates ENaC-mediated sodium transport, an effect that is not additive to that of Sgk1. A deubiquitylating enzyme that targets ENaC in vitro and thus may play a role in sodium transport regulation was identified within a series of new in vivo early aldosterone-regulated gene products. PMID:17344426

  12. TGF-β1 regulation of estrogen production in mature rat Leydig cells.

    Man-Li Liu

    Full Text Available BACKGROUND: Besides androgens, estrogens produced in Leydig cells are also crucial for mammalian germ cell differentiation. Transforming growth factor-β1 (TGF-β1 is now known to have multiple effects on regulation of Leydig cell function. The objective of the present study is to determine whether TGF-β1 regulates estradiol (E2 synthesis in adult rat Leydig cells and then to assess the impact of TGF-β1 on Cx43-based gap junctional intercellular communication (GJIC between Leydig cells. METHODOLOGY/PRINCIPAL FINDINGS: Primary cultured Leydig cells were incubated in the presence of recombinant TGF-β1 and the production of E2 as well as testosterone (T were measured by RIA. The activity of P450arom was addressed by the tritiated water release assay and the expression of Cyp19 gene was evaluated by Western blotting and real time RT-PCR. The expression of Cx43 and GJIC were investigated with immunofluorescence and fluorescence recovery after photo-bleaching (FRAP, respectively. Results from this study show that TGF-β1 down-regulates the level of E2 secretion and the activity of P450arom in a dose-dependent manner in adult Leydig cells. In addition, the expression of Cx43 and GJIC was closely related to the regulation of E2 and TGF-β1, and E2 treatment in turn restored the inhibition of TGF-β1 on GJIC. CONCLUSIONS: Our results indicate, for the first time in adult rat Leydig cells, that TGF-β1 suppresses P450arom activity, as well as the expression of the Cyp19 gene, and that depression of E2 secretion leads to down-regulation of Cx43-based GJIC between Leydig cells.

  13. Regulation of toxin production by Bacillus cereus and its food safety implications.

    Ceuppens, Siele; Rajkovic, Andreja; Heyndrickx, Marc; Tsilia, Varvara; Van De Wiele, Tom; Boon, Nico; Uyttendaele, Mieke


    Toxin expression is of utmost importance for the food-borne pathogen B. cereus, both in food poisoning and non-gastrointestinal host infections as well as in interbacterial competition. Therefore it is no surprise that the toxin gene expression is tightly regulated by various internal and environmental signals. An overview of the current knowledge regarding emetic and diarrheal toxin transcription and expression is presented in this review. The food safety aspects and management tools such as temperature control, food preservatives and modified atmosphere packaging are discussed specifically for B. cereus emetic and diarrheal toxin production. PMID:21417966

  14. Variation of muscle efficiency and regulation of heat production in an organism

    Ivanov, K.P.


    The results of over twenty years of studies on the mechanism of heat production during muscle contraction in homiothermic organisms are presented. The mechanisms regulating energy exchange during contractile (or shivering) thermogenesis and noncontractile muscle thermogenesis are examined, with special consideration given to the efficiency coefficients (ECs) of muscle work related to the processes of muscle contraction and ATP synthesis, and to relative changes in these ECs. Special attention is given to the effect of acclimatization to cold on muscle energetics, when the EC of the muscle contraction falls, while the heat production increases; the mechanism of this phenomenon is considered to be related to the increasing degree of uncoupling between the oxidation and phosphorylation processes. The role of hormones and of the sympathetic nervous system in thermoregulation is discussed. 71 references.

  15. Ca(2+)-Calmodulin regulation of testicular androgen production in Mozambique tilapia (Oreochromis mossambicus).

    Martins, Rute S T; Fuentes, Juan; Almeida, Olinda; Power, Deborah M; Canario, Adelino V M


    The Ca(2+)-Calmodulin (CaM) signaling pathway has previously been shown to be involved in the regulation of teleost fish ovarian steroidogenesis. However, a putative role of CaM in testicular steroidogenesis and potential targets has not been examined. To examine whether basal steroidogenesis is modulated by Ca(2+) and CaM levels in the testis of Mozambique tilapia (Oreochromis mossambicus) we have incubated testicular fragments in vitro under different conditions and analyzed steroid output. Calcium-free medium with or without EGTA did not affect testicular basal 11-ketotestosterone (11-KT) and testosterone (T) secretion. However, addition of 80microM the CaM inhibitor W7 significantly reduced basal 11-KT, T and androstenedione secretion. Interestingly, the decreased androgen production by 80microM of W7 was accompanied by increased 11-desoxicortisol output and by the activation of cortisol synthesis in the testis, the latter undetected in untreated tissues. However, production of 17,20alpha-dihydroxy-4-pregnen-3-one was unaltered by W7. This suggests that C17,20 desmolase, 21-hydroxylase and possibly 11beta-hydroxysteroid dehydrogenase are targets for CaM. In addition, androgen production was also found to be regulated by the level of cAMP since incubations with forskolin (FK) significantly increased 11-KT and T output. A cross-talk between the cAMP and Ca(2+)-CaM signaling pathways was detected since W7 administration also decreased FK stimulated androgen production. Altogether, these data show that both basal and cAMP stimulated androgen levels were modulated by intracellular Ca(2+)-dependent CaM and that possibly Ca(2+)-CaM determines the shift in steroidogenesis from C21 steroids to androgens. PMID:19341736

  16. Cloning and characterization of a pair of novel genes that regulate production of extracellular enzymes in Bacillus subtilis.

    Pang, A S; Nathoo, S; Wong, S L


    Two novel Bacillus subtilis genes that regulate the production of several extracellular enzymes were clones and characterized. These two genes are organized as part of an operon. When cloned in a multicopy plasmid, the first gene (tenA, transcription enhancement) stimulates alkaline protease production at the transcriptional level. The second gene (tenI) exerts an opposite effect to reduce alkaline protease production. The production of neutral protease, levansucrase, and alkaline protease ca...

  17. Environmental Regulations on Waste Electrical Equipment Industry: The Production Chain to the Final Consumer

    Marilia Tunes Mazon


    Full Text Available The relevance of the electronics industry requires its transition to sustainable production patterns, as defined by the European directives WEEE, RoHS, and the National Policy on Solid Waste. In 2010, the group began a national project whose purpose is to support sustainability with a focus on the triple bottom line Brazilian electronics industry. The implementation of these proposals began with the implementation of a pilot project with nine companies of electromedical equipment, chosen because they are technology intensive, and require exporters suit environmental regulations. This paper aims to present the main results obtained in the studies with these nine companies in the period Apr/2011 Mar/2012 regarding the suitability of its products, processes, management systems and supply chains. The study was divided into three stages: an assessment to identify general aspects of each organization, a thorough assessment to understand the characteristics of each organization ahead of the general characteristics of the group analyzed and a detailed diagnosis, performed individually during visits in companies. The main findings were that the waste management and reverse logistics associated are still incipient, the products still have dangerous substances and supply chain is still very poorly prepared for the challenges. The level of employment of employees and costs associated with the adequacy of its products and processes, constitute the two biggest problems for companies fit the relevant environmental legislation.

  18. Insulin Regulates Glucose Consumption and Lactate Production through Reactive Oxygen Species and Pyruvate Kinase M2

    Qi Li


    Full Text Available Although insulin is known to regulate glucose metabolism and closely associate with liver cancer, the molecular mechanisms still remain to be elucidated. In this study, we attempt to understand the mechanism of insulin in promotion of liver cancer metabolism. We found that insulin increased pyruvate kinase M2 (PKM2 expression through reactive oxygen species (ROS for regulating glucose consumption and lactate production, key process of glycolysis in hepatocellular carcinoma HepG2 and Bel7402 cells. Interestingly, insulin-induced ROS was found responsible for the suppression of miR-145 and miR-128, and forced expression of either miR-145 or miR-128 was sufficient to abolish insulin-induced PKM2 expression. Furthermore, the knockdown of PKM2 expression also inhibited cancer cell growth and insulin-induced glucose consumption and lactate production, suggesting that PKM2 is a functional downstream effecter of insulin. Taken together, this study would provide a new insight into the mechanism of insulin-induced glycolysis.

  19. Typical investigational medicinal products follow relatively uniform regulations in 10 European Clinical Research Infrastructures Network (ECRIN) countries

    Gluud, Christian; Kubiak, Christine; Whitfield, Kate;


    In order to facilitate multinational clinical research, regulatory requirements need to become international and harmonised. The EU introduced the Directive 2001/20/EC in 2004, regulating investigational medicinal products in Europe.......In order to facilitate multinational clinical research, regulatory requirements need to become international and harmonised. The EU introduced the Directive 2001/20/EC in 2004, regulating investigational medicinal products in Europe....

  20. Multiple-level regulation of 2,4-diacetylphloroglucinol production by the sigma regulator PsrA in Pseudomonas fluorescens 2P24.

    Xiaogang Wu

    Full Text Available BACKGROUND: Pseudomonas fluorescens 2P24 is a rhizospheric bacterium that aggressively colonizes the plant roots. It produces the antibiotic 2,4-diacetylphoroglucinol (2,4-DAPG, which contributes to the protection of various crop plants against soil borne diseases caused by bacterial and fungal pathogens. The biosynthesis of 2,4-DAPG is regulated at the transcriptional level in the expression of the phlACBD operon as well as at the posttranscriptional level by the Gac/Rsm signal transduction pathway. However, the detailed mechanism of such regulation is not clear. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we identified a binding site for the sigma regulator PsrA in the promoter region of the phlA gene. Electrophoretic mobility shift experiments revealed direct and specific binding of PsrA to the phlA promoter region. Consistent with the fact that its binding site locates within the promoter region of phlA, PsrA negatively regulates phlA expression, and its inactivation led to significant increase in 2,4-DAPG production. Interestingly, PsrA also activates the expression of the sigma factor RpoS, which negatively regulates 2,4-DAPG production by inducing the expression of the RNA-binding protein RsmA. CONCLUSIONS/SIGNIFICANCE: These results suggest that PsrA is an important regulator that modulates 2,4-DAPG biosynthesis at both transcriptional and posttranscriptional levels.

  1. TRIM11 negatively regulates IFNβ production and antiviral activity by targeting TBK1.

    Younglang Lee

    Full Text Available The innate immune response is a host defense mechanism against infection by viruses and bacteria. Type I interferons (IFNα/β play a crucial role in innate immunity. If not tightly regulated under normal conditions and during immune responses, IFN production can become aberrant, leading to inflammatory and autoimmune diseases. In this study, we identified TRIM11 (tripartite motif containing 11 as a novel negative regulator of IFNβ production. Ectopic expression of TRIM11 decreased IFNβ promoter activity induced by poly (I:C stimulation or overexpression of RIG-I (retinoic acid-inducible gene-I signaling cascade components RIG-IN (constitutively active form of RIG-I, MAVS (mitochondrial antiviral signaling protein, or TBK1 (TANK-binding kinase-1. Conversely, TRIM11 knockdown enhanced IFNβ promoter activity induced by these stimuli. Moreover, TRIM11 overexpression inhibited the phosphorylation and dimerization of IRF3 and expression of IFNβ mRNA. By contrast, TRIM11 knockdown increased the IRF3 phosphorylation and IFNβ mRNA expression. We also found that TRIM11 and TBK1, a key kinase that phosphorylates IRF3 in the RIG-I pathway, interacted with each other through CC and CC2 domain, respectively. This interaction was enhanced in the presence of the TBK1 adaptor proteins, NAP1 (NF-κB activating kinase-associated protein-1, SINTBAD (similar to NAP1 TBK1 adaptor or TANK (TRAF family member-associated NF-κB activator. Consistent with its inhibitory role in RIG-I-mediated IFNβ signaling, TRIM11 overexpression enhanced viral infectivity, whereas TRIM11 knockdown produced the opposite effect. Collectively, our results suggest that TRIM11 inhibits RIG-I-mediated IFNβ production by targeting the TBK1 signaling complex.

  2. Influence of pH Regulation Mode in Glucose Fermentation on Product Selection and Process Stability

    Zuhaida Mohd-Zaki


    Full Text Available Mixed culture anaerobic fermentation generates a wide range of products from simple sugars, and is potentially an effective process for producing renewable commodity chemicals. However it is difficult to predict product spectrum, and to control the process. One of the key control handles is pH, but the response is commonly dependent on culture history. In this work, we assess the impact of pH regulation mode on the product spectrum. Two regulation modes were applied: in the first, pH was adjusted from 4.5 to 8.5 in progressive steps of 0.5 and in the second, covered the same pH range, but the pH was reset to 5.5 before each change. Acetate, butyrate, and ethanol were produced throughout all pH ranges, but there was a shift from butyrate at pH < 6.5 to ethanol at pH > 6.5, as well as a strong and consistent shift from hydrogen to formate as pH increased. Microbial analysis indicated that progressive pH resulted in dominance by Klebsiella, while reset pH resulted in a bias towards Clostridium spp., particularly at low pH, with higher variance in community between different pH levels. Reset pH was more responsive to changes in pH, and analysis of Gibbs free energy indicated that the reset pH experiments operated closer to thermodynamic equilibrium, particularly with respect to the formate/hydrogen balance. This may indicate that periodically resetting pH conforms better to thermodynamic expectations.

  3. [Characterization of cases contravening of regulations regarding primary aromatic amines originating from azo dyes in commercial textile products and leather products in European Union].

    Kawakami, Tsuyoshi; Isama, Kazuo; Ikarashi, Yoshiaki


    Contraventions of regulations regarding primary aromatic amines (PAAs) originating from azo dyes in commercial textile products and leather products in European Union (EU), notified in the period between 2006 and 2012 were collected from the Rapid Alert System for non-food consumer products (RAPEX), were characterized. Various types of products (clothes, footwear, bedding, etc.) and their raw materials (cotton, silk, viscose, leather, etc.) were reported to have contravened the regulations. The contravention frequencies for products made in China and India were higher than those for other countries. Ten percentage of the country in which the reported products were produced was unknown. The notification frequencies for benzidine and 4-aminoazobenzene were higher than those for other PAAs. Contravention of regulations regarding benzidine, 4-aminoazobenzene, and 3,3'-dimethoxybenzidine were notified every year. Contraventions of regulations regarding five PAAs--classified as IARC group 1--were notified one or several times. Since the scale of the survey conducted in Japan were small compared with RAPEX, it is necessary that many kinds and number of products should be surveyed in Japan. In addition, it is also necessary to pay attention to 4-aminoazobenzene, while it has not been detected in the previous studies conducted in Japan. PMID:24340672

  4. Further European initiatives and regulations concerning radiation protection: drinking water guideline, maximum permissible contamination in food products and feeding stuff

    The radiation protection community has observed intensively the development of basic safety standards concerning protection against hazards of ionizing radiation. The new core part of the European radiation protection legislation is complemented by several specialized regulations relevant for radiation protection. Besides the existing regulations in the field of emergency protection the European Commission initiated a drinking water guideline that will be published in the near future. Furthermore the European commission approved a revised regulation concerning the maximum permissible contamination limits for food products and feeding stuff in case of a future nuclear accident. Together with the new radiation protection basic standards a new complete, coherent and modernized European regulation package will be accomplished.

  5. STMN1 Promotes Progesterone Production Via StAR Up-regulation in Mouse Granulosa Cells

    Dou, Yun-De; Zhao, Han; Huang, Tao; Zhao, Shi-Gang; Liu, Xiao-Man; Yu, Xiao-Chen; Ma, Zeng-Xiang; Zhang, Yu-Chao; Liu, Tao; Gao, Xuan; Li, Lei; Lu, Gang; Chan, Wai-Yee; Gao, Fei; Liu, Hong-Bin; Chen, Zi-Jiang


    Stathmin 1 (STMN1) is a biomarker in several types of neoplasms. It plays an important role in cell cycle progression, mitosis, signal transduction and cell migration. In ovaries, STMN1 is predominantly expressed in granulosa cells (GCs). However, little is known about the role of STMN1 in ovary. In this study, we demonstrated that STMN1 is overexpressed in GCs in patients with polycystic ovary syndrome (PCOS). In mouse primary GCs, the overexpression of STMN1 stimulated progesterone production, whereas knockdown of STMN1 decreased progesterone production. We also found that STMN1 positively regulates the expression of Star (steroidogenic acute regulatory protein) and Cyp11a1 (cytochrome P450 family 11 subfamily A member 1). Promoter and ChIP assays indicated that STMN1 increased the transcriptional activity of Star and Cyp11a1 by binding to their promoter regions. The data suggest that STMN1 mediates the progesterone production by modulating the promoter activity of Star and Cyp11a1. Together, our findings provide novel insights into the molecular mechanisms of STMN1 in ovary GC steroidogenesis. A better understanding of this potential interaction between STMN1 and Star in progesterone biosynthesis in GCs will facilitate the discovery of new therapeutic targets in PCOS. PMID:27270953

  6. Regulations governing veterinary medicinal products containing genetically modified organisms in the European community.

    Moulin, G


    This paper describes particular aspects of the marketing of veterinary medicinal products (VMPs) that contain or consist of genetically modified micro-organisms (GMMs) or genetically modified organisms (GMOs). The regulatory requirements and the procedures applied in the European Union for each phase (pre-marketing, authorisation process, and post-authorisation labelling and monitoring) are explained. In most cases VMPs are subject to both pharmaceutical and GMO regulations. In the early stages of the process, before applications for marketing authorisation are submitted, the assessment of clinical trials and experiments in contained areas is principally the responsibility of national authorities. However, the marketing of all VMPs containing or consisting of GMOs must be authorised at European level, although the national authorities are informed and involved in the assessment process. PMID:16110880

  7. Regulating and Controlling the Rising Prices of Geographical Indication Products in Inflation-taking Geographical Indication Products from Chongqing as an Example



      Since July 2010, the prices of geographical indication products have risen with the occurrence of inflation. In contrast with other products, geographical indication products are distinct. The increasing prices of geographical indication goods have their own necessities. From the perspective of the products, they are equipped with appreciation potential due to the cultural peculiarities. From the historical standpoint, their prices have not been high as well as other agricultural products. Realistically, the increase in their prices results from the costs of labors and raw materials . Therefore, the prices of geographical indication products rise to catch up. Not only are their prices at a reasonable level, but also they are beneficial to increase peasants’income. In conclusion, it is necessary that the strategies which are different from those of other products be adopted to regulate and control the prices of geographical indication products.

  8. Estrogen regulates progesterone production by human placental trophoblast cells in culture

    We have suggested that estrogen regulates placental low-density lipoprotein (LDL) uptake and thus progesterone (P4) production during primate pregnancy based on results obtained in antiestrogen-treated baboons. The objectives of the present study, were to determine whether estrogen is also important to regulation of P4 formation by the human placenta, and whether effects of estrogen were mediated by availability of cholesterol substrate via the LDL, de novo, or deesterification pathways. Term human placenta were dispersed in 0.125% trypsin, cytotrophoblasts were purified via a 70-5% Percoll gradient, incubated 72 h in DMEM with 10% FBS to stimulate formation of syncytia, then incubated an additional 48 h with estradiol (E2). In Experiment 1, 1 μg/ml E2 and 500 μg/MI LDL-protein, stimulated P4 (P 2 increased LDL uptake. Scatchard analysis indicated that trophoblast uptake of [125I]LDL (ng/mg cell protein) was 50% greater (P 2 (mean ± SE, 638 +/- 23; n = 6) than DMEM in the presence of antiestrogen MER-25. Moreover, uptake and degradation of LDL, and cellular content of free and esterified cholesterol, increased in a dose-dependent manner with 0.1 to 1000 ng/ml E2. These results suggest that estrogen regulates placental cell uptake of LDL and thus availability of cholesterol for P4 biosynthesis during human pregnancy. In Experiment 2, E2 Stimulated P4 formation (ng/mg cell protein/48 h) from a control level of 194 ± 25 to 357 ± 62, in the absence of LDL. Under these conditions, cholesterol for P4 biosynthesis must have been derived from de novo synthesis and/or deesterification of cholesteryl ester stores

  9. A negative regulator mediates quorum-sensing control of exopolysaccharide production in Pantoea stewartii subsp. stewartii.

    von Bodman, S B; Majerczak, D R; Coplin, D L


    Classical quorum-sensing (autoinduction) regulation, as exemplified by the lux system of Vibrio fischeri, requires N-acyl homoserine lactone (AHL) signals to stimulate cognate transcriptional activators for the cell density-dependent expression of specific target gene systems. For Pantoea stewartii subsp. stewartii, a bacterial pathogen of sweet corn and maize, the extracellular polysaccharide (EPS) stewartan is a major virulence factor, and its production is controlled by quorum sensing in a population density-dependent manner. Two genes, esaI and esaR, encode essential regulatory proteins for quorum sensing. EsaI is the AHL signal synthase, and EsaR is the cognate gene regulator. esaI, DeltaesaR, and DeltaesaI-esaR mutations were constructed to establish the regulatory role of EsaR. We report here that strains containing an esaR mutation produce high levels of EPS independently of cell density and in the absence of the AHL signal. Our data indicate that quorum-sensing regulation in P. s. subsp. stewartii, in contrast to most other described systems, uses EsaR to repress EPS synthesis at low cell density, and that derepression requires micromolar amounts of AHL. In addition, derepressed esaR strains, which synthesize EPS constitutively at low cell densities, were significantly less virulent than the wild-type parent. This finding suggests that quorum sensing in P. s. subsp. stewartii may be a mechanism to delay the expression of EPS during the early stages of infection so that it does not interfere with other mechanisms of pathogenesis. PMID:9636211

  10. Current products and future plan of regulatory research for risk-informed regulation in Korea

    The first phase of a regulatory research project for risk-informed regulation (RIR) and applications (RIA) was finished in March of 2002. Various results that could be useful for preparing Korean RIR system have been developed. One of the remarkable outputs is development of reactor safety goals and acceptance criteria for RIR and RIA in Korea. The Safety Goal has a 4-tier hierarchical structure and each tier has specified goals classified for their usage. Regulatory review guides for probabilistic safety assessment (PSA) including level-1, level-2 and low power and shutdown PSA have been updated by reflecting new information obtained from not only the overseas documents but also experience and insights from regulatory review in Korea. In addition, draft regulatory guides for risk-informed in-service inspection, in-service testing, importance ranking of motor-operated valves, and AOT/STI change of Technical Specifications have been developed for preparing ongoing and future licensing work. Risk-based inspection guides with inspection items selected from a viewpoint of risk importance have been suggested for Korean standard NPPs as well. In the second phase of a research project (April of 2002 to March of 2005), two regulatory research projects on RIR were initiated. One is a study on institutionalization of risk-informed and performance-based regulation. Main topics of this project are evaluation of benefit and characteristics of RIR, development of optimized Korean RIR model, impact analysis for the change of current regulation framework, and suggestion of RIR-related laws and rules. The other is focusing on the development in the areas of a regulatory audit PSA model and regulatory guides for risk monitoring, and application techniques of risk information to the significance determination of plant performance indicators and inspection findings. It is expected that a concrete scheme and detailed regulatory techniques for embodiment of RIR system in Korea will be

  11. Advanced Glycation End-Products affect transcription factors regulating insulin gene expression

    Advanced Glycation End-Products (AGEs) are generated by the covalent interaction of reducing sugars with proteins, lipids or nucleic acids. AGEs are implicated in diabetic complications and pancreatic β-cell dysfunction. We previously demonstrated that exposure of the pancreatic islet cell line HIT-T15 to high concentrations of AGEs leads to a significant decrease of insulin secretion and content. Insulin gene transcription is positively regulated by the beta cell specific transcription factor PDX-1 (Pancreatic and Duodenal Homeobox-1). On the contrary, the forkhead transcription factor FoxO1 inhibits PDX-1 gene transcription. Activity of FoxO1 is regulated by post-translational modifications: phosphorylation deactivates FoxO1, and acetylation prevents FoxO1 ubiquitination. In this work we investigated whether AGEs affect expression and subcellular localization of PDX-1 and FoxO1. HIT-T15 cells were cultured for 5 days in presence of AGEs. Cells were then lysed and processed for subcellular fractionation. We determined intracellular insulin content, then we assessed the expression and subcellular localization of PDX-1, FoxO1, phosphoFoxO1 and acetylFoxO1. As expected intracellular insulin content was lower in HIT-T15 cells cultured with AGEs. The results showed that AGEs decreased expression and nuclear localization of PDX-1, reduced phosphorylation of FoxO1, and increased expression and acetylation of FoxO1. These results suggest that AGEs decrease insulin content unbalancing transcription factors regulating insulin gene expression.

  12. PPAR-γ activation by Tityus serrulatus venom regulates lipid body formation and lipid mediator production.

    Zoccal, Karina Furlani; Paula-Silva, Francisco Wanderley Garcia; Bitencourt, Claudia da Silva; Sorgi, Carlos Artério; Bordon, Karla de Castro Figueiredo; Arantes, Eliane Candiani; Faccioli, Lúcia Helena


    Tityus serrulatus venom (TsV) consists of numerous peptides with different physiological and pharmacological activities. Studies have shown that scorpion venom increases pro-inflammatory cytokine production, contributing to immunological imbalance, multiple organ dysfunction, and patient death. We have previously demonstrated that TsV is a venom-associated molecular pattern (VAMP) recognized by TLRs inducing intense inflammatory reaction through the production of pro-inflammatory cytokines and arachidonic acid-derived lipid mediators prostaglandin (PG)E2 and leukotriene (LT)B4. Lipid bodies (LBs) are potential sites for eicosanoid production by inflammatory cells. Moreover, recent studies have shown that the peroxisome proliferator-activated receptor gamma (PPAR-γ) is implicated in LB formation and acts as an important modulator of lipid metabolism during inflammation. In this study, we used murine macrophages to evaluate whether the LB formation induced by TsV after TLR recognition correlates with lipid mediator generation by macrophages and if it occurs through PPAR-γ activation. We demonstrate that TsV acts through TLR2 and TLR4 stimulation and PPAR-γ activation to induce LB formation and generation of PGE2 and LTB4. Our data also show that PPAR-γ negatively regulates the pro-inflammatory NF-κB transcription factor. Based on these results, we suggest that during envenomation, LBs constitute functional organelles for lipid mediator production through signaling pathways that depend on cell surface and nuclear receptors. These findings point to the inflammatory mechanisms that might also be triggered during human envenomation by TsV. PMID:25450800

  13. State Regulation Of Licensing In The Sphere Of Production Of Peat In Russian Federation

    Pavel A. Byshkov


    Full Text Available In the article features of legal regulation of production and state licensing of peat in the modern legislation and laws of the Russian Federation are analyzed. Particular attention is paid to the understanding of peat as a mineral that is important for the country's energy. The process of securing right of the peat use in the modern Russian law is analyzed. The question of the relationship of legislation on the subsoil and water legislation is researched, as well as issues of the Law of the Russian Federation "On Subsoil" and the Water Code of the Russian Federation are correlated. In addition the term "swamp", as the object of peat occurrence is considered. In the broader concept of the "wetland" exists in the Ramsar Convention of the 1971. The order of occurrence, termination, as well as the content of a license for the peat use is analyzed. The license is considered as a special governmental approval, including the prescribed form of the document with the State Emblem of the Russian Federation, as well as text, graphics and other supplements that are an integral part of the license and the fundamental conditions for the subsoil use. Rights and obligations of peat users in Russia are analyzed. Importance of the legal regulation of peat extraction as a common mineral in the Russian law understanding is highlighted.

  14. Hfq regulates antibacterial antibiotic biosynthesis and extracellular lytic-enzyme production in Lysobacter enzymogenes OH11.

    Xu, Gaoge; Zhao, Yuxin; Du, Liangcheng; Qian, Guoliang; Liu, Fengquan


    Lysobacter enzymogenes is an important biocontrol agent with the ability to produce a variety of lytic enzymes and novel antibiotics. Little is known about their regulatory mechanisms. Understanding these will be helpful for improving biocontrol of crop diseases and potential medical application. In the present study, we generated an hfq (encoding a putative ribonucleic acid chaperone) deletion mutant, and then utilized a new genomic marker-free method to construct an hfq-complemented strain. We showed for the first time that Hfq played a pleiotropic role in regulating the antibacterial antibiotic biosynthesis and extracellular lytic enzyme activity in L. enzymogenes. Mutation of hfq significantly increased the yield of WAP-8294A2 (an antibacterial antibiotic) as well as the transcription of its key biosynthetic gene, waps1. However, inactivation of hfq almost abolished the extracellular chitinase activity and remarkably decreased the activity of both extracellular protease and cellulase in L. enzymogenes. We further showed that the regulation of hfq in extracellular chitinase production was in part through the impairment of the secretion of chitinase A. Collectively, our results reveal the regulatory roles of hfq in antibiotic metabolite and extracellular lytic enzymes in the underexplored genus of Lysobacter. PMID:25683974

  15. Phosphorylated CpxR restricts production of the RovA global regulator in Yersinia pseudotuberculosis.

    Junfa Liu

    Full Text Available BACKGROUND: RovA is a global transcriptional regulator of gene expression in pathogenic Yersinia. RovA levels are kept in check by a sophisticated layering of distinct transcriptional and post-transcriptional regulatory mechanisms. In the enteropathogen Y. pseudotuberculosis, we have previously reported that the extracytoplasmic stress sensing CpxA-CpxR two-component regulatory system modulates rovA expression. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we characterized CpxR phosphorylation (CpxR∼P in vitro, and determined that phosphorylation was necessary for CpxR to efficiently bind to the PCR-amplified upstream regulatory region of rovA. The precise CpxR∼P binding site was mapped by a nuclease protection assay and directed mutagenesis confirmed that in vivo binding to the rovA promoter inhibits transcription. Reduced RovA production was most pronounced following CpxR∼P accumulation in the Yersinia cytoplasm during chronic Cpx pathway activation and by the indiscriminate phosphodonor action of acetyl phosphate. CONCLUSIONS/SIGNIFICANCE: Cpx pathway activation restricts levels of the RovA global regulator. The regulatory influence of CpxR∼P must therefore extend well beyond periplasmic quality control in the Yersinia envelope, to include genes involved in environmental survival and pathogenicity.

  16. EU regulation concerning genetically modified products: an issue of food security or a measure of disguised protectionism?

    Ana Santos; Jose Caetano


    The biggest producers and exporters of agricultural products have been adopting the genetic engineering in order to improve the factors productivity and the firms profits In the last decade, the United States of America (US) and the European Union (EU) have established a high divergent regulation on production, distribution and consumption of genetically modified organisms (GMOs). Apparently, the EU's complex legislative framework related to GMOs was intend to satisfy the European consumers w...

  17. Trends in the Regulation of Genetically Modified Products in the European Union from 1990 to the Present

    Ricci, Michael


    The EU took its first steps towards regulation of genetically modified organisms and products in 1990. Over the next twenty years, the EU’s regulatory approach evolved to impose greater regulatory burdens on genetically modified products and to mandate ever greater disclosure to member states, EU institutions and to the ultimate consumers of these genetically modified products. As experience under the earlier regulatory initiatives accumulated, it became apparent that member state discretio...

  18. Strain-Level Differences in Porphyrin Production and Regulation in Propionibacterium acnes Elucidate Disease Associations

    Johnson, Tremylla; Kang, Dezhi; Barnard, Emma


    ABSTRACT Propionibacterium acnes is an important skin commensal, but it is also considered a pathogenic factor in several diseases including acne vulgaris, the most common skin disease. While previous studies have revealed P. acnes strain-level differences in health and disease associations, the underlying molecular mechanisms remain unknown. Recently, we demonstrated that vitamin B12 supplementation increases P. acnes production of porphyrins, a group of proinflammatory metabolites important in acne development (D. Kang, B. Shi, M. C. Erfe, N. Craft, and H. Li, Sci. Transl. Med. 7:293ra103, 2015, doi:10.1126/scitranslmed.aab2009). In this study, we compared the porphyrin production and regulation of multiple P. acnes strains. We revealed that acne-associated type IA-2 strains inherently produced significantly higher levels of porphyrins, which were further enhanced by vitamin B12 supplementation. On the other hand, health-associated type II strains produced low levels of porphyrins and did not respond to vitamin B12. Using a small-molecule substrate and inhibitor, we demonstrated that porphyrin biosynthesis was modulated at the metabolic level. We identified a repressor gene (deoR) of porphyrin biosynthesis that was carried in all health-associated type II strains, but not in acne-associated type IA-2 strains. The expression of deoR suggests additional regulation of porphyrin production at the transcriptional level in health-associated strains. Our findings provide one potential molecular mechanism for the different contributions of P. acnes strains to skin health and disease and support the role of vitamin B12 in acne pathogenesis. Our study emphasizes the importance of understanding the role of the commensal microbial community in health and disease at the strain level and suggests potential utility of health-associated P. acnes strains in acne treatment. IMPORTANCE Propionibacterium acnes is a dominant bacterium residing on skin, and it has been thought

  19. Developmentally regulated sesquiterpene production confers resistance to Colletotrichum gloeosporioides in ripe pepper fruits.

    Park, Sangkyu; Park, Ae Ran; Im, Soonduk; Han, Yun-Jeong; Lee, Sungbeom; Back, Kyoungwhan; Kim, Jeong-Il; Kim, Young Soon


    Sesquiterpenoid capsidiol, exhibiting antifungal activity against pathogenic fungus, is accumulated in infected ripe pepper fruits. In this study, we found a negative relation between the capsidiol level and lesion size in fruits infected with Colletotrichum gloeosporioides, depending on the stage of ripening. To understand the developmental regulation of capsidiol biosynthesis, fungal-induced gene expressions in the isoprenoid biosynthetic pathways were examined in unripe and ripe pepper fruits. The sterol biosynthetic pathway was almost shut down in healthy ripe fruits, showing very low expression of hydroxymethyl glutaryl CoA reductase (HMGR) and squalene synthase (SS) genes. In contrast, genes in the carotenoid pathway were highly expressed in ripe fruits. In the sesquiterpene pathway, 5-epi-aristolochene synthase (EAS), belonging to a sesquiterpene cyclase (STC) family, was significantly induced in the ripe fruits upon fungal infection. Immunoblot and enzyme activity analyses showed that the STCs were induced both in the infected unripe and ripe fruits, while capsidiol was synthesized discriminatively in the ripe fruits, implying diverse enzymatic specificity of multiple STCs. Thereby, to divert sterol biosynthesis into sesquiterpene production, infected fruits were pretreated with an SS inhibitor, zaragozic acid (ZA), resulting in increased levels of capsidiol by more than 2-fold in the ripe fruits, with concurrent reduction of phytosterols. Taken together, the present results suggest that the enhanced expression and activity of EAS in the ripe fruits play an important role in capsidiol production, contributing to the incompatibility between the anthracnose fungus and the ripe pepper fruits. PMID:25286411

  20. A family of indoles regulate virulence and Shiga toxin production in pathogenic E. coli.

    Bettina Bommarius

    Full Text Available Enteropathogenic Escherichia coli (EPEC, enterohemorrhagic E. coli (EHEC and enteroaggregative E. coli (EAEC are intestinal pathogens that cause food and water-borne disease in humans. Using biochemical methods and NMR-based comparative metabolomics in conjunction with the nematode Caenorhabditis elegans, we developed a bioassay to identify secreted small molecules produced by these pathogens. We identified indole, indole-3-carboxaldehyde (ICA, and indole-3-acetic acid (IAA, as factors that only in combination are sufficient to kill C. elegans. Importantly, although lethal to C. elegans, these molecules downregulate several bacterial processes important for pathogenesis in mammals. These include motility, biofilm formation and production of Shiga toxins. Some pathogenic E. coli strains are known to contain a Locus of Enterocyte Effacement (LEE, which encodes virulence factors that cause "attaching and effacing" (A/E lesions in mammals, including formation of actin pedestals. We found that these indole derivatives also downregulate production of LEE virulence factors and inhibit pedestal formation on mammalian cells. Finally, upon oral administration, ICA inhibited virulence and promoted survival in a lethal mouse infection model. In summary, the C. elegans model in conjunction with metabolomics has facilitated identification of a family of indole derivatives that broadly regulate physiology in E. coli, and virulence in pathogenic strains. These molecules may enable development of new therapeutics that interfere with bacterial small-molecule signaling.

  1. A Human Variant of Glucose-Regulated Protein 94 That Inefficiently Supports IGF Production.

    Marzec, Michal; Hawkes, Colin P; Eletto, Davide; Boyle, Sarah; Rosenfeld, Ron; Hwa, Vivian; Wit, Jan M; van Duyvenvoorde, Hermine A; Oostdijk, Wilma; Losekoot, Monique; Pedersen, Oluf; Yeap, Bu Beng; Flicker, Leon; Barzilai, Nir; Atzmon, Gil; Grimberg, Adda; Argon, Yair


    IGFs are critical for normal intrauterine and childhood growth and sustaining health throughout life. We showed previously that the production of IGF-1 and IGF-2 requires interaction with the chaperone glucose-regulated protein 94 (GRP94) and that the amount of secreted IGFs is proportional to the GRP94 activity. Therefore, we tested the hypothesis that functional polymorphisms of human GRP94 affect IGF production and thereby human health. We describe a hypomorphic variant of human GRP94, P300L, whose heterozygous carriers have 9% lower circulating IGF-1 concentration. P300L was found first in a child with primary IGF deficiency and was later shown to be a noncommon single-nucleotide polymorphism with frequencies of 1%-4% in various populations. When tested in the grp94(-/-) cell-based complementation assay, P300L supported only approximately 58% of IGF secretion relative to wild-type GRP94. Furthermore, recombinant P300L showed impaired nucleotide binding activity. These in vitro data strongly support a causal relationship between the GRP94 variant and the decreased concentration of circulating IGF-1, as observed in human carriers of P300L. Thus, mutations in GRP94 that affect its IGF chaperone activity represent a novel causal genetic mechanism that limits IGF biosynthesis, quite a distinct mechanism from the known genes in the GH/IGF signaling network. PMID:26982636

  2. Insulin-like growth factor binding protein production and regulation in fetal rat lung cells.

    Price, W A; Moats-Staats, B M; D'Ercole, A J; Stiles, A D


    Insulin-like growth factor binding proteins (IGFBPs) are expressed in lung from early in gestation and may modulate IGF-stimulated fetal lung cell proliferation and/or differentiation. To begin to define IGFBP production and regulation in lung cells during development, we prepared primary cultures of 19 day gestation fetal rat lung fibroblasts and epithelial cells and identified IGFBPs secreted into medium. Ligand blot analysis of conditioned media (CM) from both cell types demonstrated IGFBP bands of approximately 39,000-45,000, 32,000, 24,000, and 22,000 M(r). These migration characteristics allowed the identification of the 39,000-45,000 M(r) bands as IGFBP-3 and the 24,000 M(r) band as IGFBP-4, while Western immunoblot analyses localized IGFBP-2 to the 32,000 M(r) band and IGFBP-5 to the 22,000 M(r) band. Polymerase chain reaction amplification of cDNAs generated by reverse transcription of fibroblast and epithelial cell RNA using specific oligodeoxynucleotide primers for IGFBPs 1 through 6, demonstrated the presence of amplified products for IGFBP-2, -3, -4, -5, and -6. In both cell types, IGFBP-2 and -3 production was sustained during 48 h of incubation in serum-free medium, whereas IGFBP-4 abundance increased only during the first 6 to 12 h of incubation. CM from fibroblasts and epithelial cells plated at low densities contained a high abundance of IGFBP-2 per microgram cellular DNA compared with cells at higher densities. In contrast, IGFBP-3 and -4 abundance normalized to cell DNA did not change with differing cell densities.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7682822

  3. Accuracy of drug advertisements in medical journals under new law regulating the marketing of pharmaceutical products in Switzerland

    Nordmann Alain J; Bucher Heiner C; Santiago Macarena


    Abstract Background New legal regulations for the marketing of pharmaceutical products were introduced in 2002 in Switzerland. We investigated whether claims in drug advertisements citing published scientific studies were justified by these studies after the introduction of these new regulations. Methods In this cross-sectional study, two independent reviewers screened all issues of six major Swiss medical journals published in the year 2005 to identify all drug advertisements for analgesic, ...

  4. Successful new product development by optimizing development process effectiveness in highly regulated sectors: the case of the Spanish medical devices sector

    Pullen, Annemien J.J.; Cabello-Medina, Carmen; Weerd-Nederhof, de, Petra C.; Visscher, Klaasjan; AARD J. GROEN


    Rapid development and commercialization of new products is of vital importance for small and medium sized enterprises (SME) in regulated sectors. Due to strict regulations, competitive advantage can hardly be achieved through the effectiveness of product concepts only. If an SME in a highly regulated sector wants to excell in new product development (NPD) performance, the company should focus on the flexibility, speed, and productivity of its NPD function: i.e. the development process effecti...

  5. A Nitric Oxide-Responsive Quorum Sensing Circuit in Vibrio harveyi Regulates Flagella Production and Biofilm Formation

    Yueming Xu


    Full Text Available Cell signaling plays an important role in the survival of bacterial colonies. They use small molecules to coordinate gene expression in a cell density dependent manner. This process, known as quorum sensing, helps bacteria regulate diverse functions such as bioluminescence, biofilm formation and virulence. In Vibrio harveyi, a bioluminescent marine bacterium, four parallel quorum-sensing systems have been identified to regulate light production. We have previously reported that nitric oxide (NO, through the H-NOX/HqsK quorum sensing pathway contributes to light production in V. harveyi through the LuxU/LuxO/LuxR quorum sensing pathway. In this study, we show that nitric oxide (NO also regulates flagellar production and enhances biofilm formation. Our data suggest that V. harveyi is capable of switching between lifestyles to be able to adapt to changes in the environment.

  6. A nitric oxide-responsive quorum sensing circuit in Vibrio harveyi regulates flagella production and biofilm formation.

    Henares, Bernadette M; Xu, Yueming; Boon, Elizabeth M


    Cell signaling plays an important role in the survival of bacterial colonies. They use small molecules to coordinate gene expression in a cell density dependent manner. This process, known as quorum sensing, helps bacteria regulate diverse functions such as bioluminescence, biofilm formation and virulence. In Vibrio harveyi, a bioluminescent marine bacterium, four parallel quorum-sensing systems have been identified to regulate light production. We have previously reported that nitric oxide (NO), through the H-NOX/HqsK quorum sensing pathway contributes to light production in V. harveyi through the LuxU/LuxO/LuxR quorum sensing pathway. In this study, we show that nitric oxide (NO) also regulates flagellar production and enhances biofilm formation. Our data suggest that V. harveyi is capable of switching between lifestyles to be able to adapt to changes in the environment. PMID:23965964

  7. Sirtuin-3 (Sirt3) regulates skeletal muscle metabolism and insulin signaling via altered mitochondrial oxidation and reactive oxygen species production

    Jing, Enxuan; Emanuelli, Brice; Hirschey, Matthew D;


    Sirt3 is a member of the sirtuin family of protein deacetylases that is localized in mitochondria and regulates mitochondrial function. Sirt3 expression in skeletal muscle is decreased in models of type 1 and type 2 diabetes and regulated by feeding, fasting, and caloric restriction. Sirt3 knockout......, activation of JNK, increased serine and decreased tyrosine phosphorylation of IRS-1, and decreased insulin signaling. Thus, Sirt3 plays an important role in diabetes through regulation of mitochondrial oxidation, reactive oxygen species production, and insulin resistance in skeletal muscle....

  8. Successful new product development by optimizing development process effectiveness in highly regulated sectors: the case of the Spanish medical devices sector

    Pullen, Annemien J.J.; Cabello-Medina, Carmen; Weerd-Nederhof, de Petra C.; Visscher, Klaasjan; Groen, Aard J.


    Rapid development and commercialization of new products is of vital importance for small and medium sized enterprises (SME) in regulated sectors. Due to strict regulations, competitive advantage can hardly be achieved through the effectiveness of product concepts only. If an SME in a highly regulate

  9. Lessons from the 'Humanitarian Golden Rice' project: regulation prevents development of public good genetically engineered crop products.

    Potrykus, Ingo


    Compared to a non-Genetically Engineered (GE) variety, the deployment of Golden Rice has suffered from a delay of at least ten years. The cause of this delay is exclusively GE-regulation. Considering the potential impact of Golden Rice on the reduction in vitamin A-malnutrition, this delay is responsible for an unjustifiable loss of millions of lives, mostly children and women. GE-regulation is also responsible for the fact that no public institution can deliver a public good GE-product and that thus we have a de facto monopoly in favour of a few potent industries. Considering the forgone benefits from prevented public good GE-products, GE-regulation is responsible for hundreds of millions of lives, all of them, of course, in developing countries. As there is no scientific justification for present GE-regulation, and as it has, so far, not prevented any harm, our society has the urgent responsibility to reconsider present regulation, which is based on an extreme interpretation of the precautionary principle, and change it to science-based regulation on the basis of traits instead of technology. GE-technology has an unprecedented safety record and is far more precise and predictable than any other 'traditional' and unregulated breeding technology. Not to change GE-regulation to a scientific basis is considered by the author 'a crime against humanity'. PMID:20650337

  10. Regulations of evapotranspiration and ecosystem productivity from biophysical and human drivers in drylands Northern Eurasia

    Chen, J.; Ouyang, Z.; John, R.; Henebry, G. M.; Xie, Y.; de Beurs, K.; Fan, Y.; Shao, C.; Qi, J.; Wu, J.; Liu, Y.


    The concept of coupled human and environmental systems (CHES) has been a dominant framework in the past decade for understanding the cohesive connections between natural and human systems. Here we focus on how socio-ecological services may be regulated by the regional and local water cycles and by ecosystem production in the drylands of Northern Asia (>40 degree N), which includes Inner Mongolia of China, Kazakhstan, Kyrgyzstan, Mongolia, Tajikistan, Turkmenistan, and Uzbekistan. Total precipitation and evapotranspiration are used as the primary drivers to explain ecosystem production (e.g., GPP) and indicators of social function and structure (e.g., GDP, population) using the data collected from 1980 through 2010 of these seven areas. We hypothesize that the changes in the regional and local water cycles in these contrasting regions and socioeconomic settings significantly affect CHES functioning. Institutional changes, including shifts in policy, can play a much stronger role than those caused by the physical changes in determining the relationships between water cycle and CHES functioning. The complex connections among the biophysical and socioeconomic variables are analyzed through structural equation modeling (SEM) at country and regional scales. The highest water use efficiency (GPP:PET=0.57) was found for Uzbekistan, which also had the highest GDP:GPP (0.66) among the seven areas. In contrast, Mongolia exhibited the lowest values during the study period despite its very high GPP:Population value (45.8). The low population in Mongolia appeared responsible for its rank within the dryland region. Regional institutional changes with global ramifications, such as the collapse of Soviet Union and China joining the World Trade Organization, appears to have affected the CHES of the study areas.

  11. The Impact of Water Regulation on the Availability of Shale Gas Resources for Production

    Victor, D. G.


    Visions for a large increase in North American production of natural gas from shale are based heavily on the sharp rise in the estimated available resource. Those estimates are prepared by looking at the underlying geology as well as the cost and availability of technologies for extracting gas. We add to that equation the potential current and future regulation of water injection (subsurface) and runoff (surface). Using the political science theory of "veto points" we show that US water legislation is organized in ways that allow for large numbers of political forces to block (or make costly) access to gas resources. By our estimate, 26% of the shale gas resource will be unavailable-a fraction that could rise if there are strong contagion effects as jurisdictions that have traditionally had industry-friendly regulatory systems apply much stricter rules. This work has potentially large implications for visions of the new natural gas revolution and the price of North American (and potentially world) natural gas.

  12. Npk mediated improvement in biomass production, photosynthesis and na+ regulation in panicum antidotale under saline conditions

    Panicum antidotale is a promising grass species for use as fodder and forage using non-conventional agricultural practices. It was therefore grown using brackish water irrigation to determine the optimal spacing and fertilizer treatment required for sustainable growth, ion relations and photosynthesis. Planting distance of 1.5 ft2 resulted in higher biomass yield. Composite NPK fertilizer (NPK120) at the rate 120 kg ha-1 supported better plant growth rather than N, P, K individually or their various combinations (NP, NK, PK, NPK). Addition of fermented farmyard manure (NPK120+FM) improved ion regulation (lower Na+ uptake, higher K+/Na+ ratio), photosynthetic rates and water use efficiency but did not improve biomass production compared to NPK120. However, higher Na+ uptake with NPK120 would result in lower ion accumulation in the root zone and delayed soil degradation. We conclude that NPK120 could support sustainable growth of Panicum antidotale in our cropping system by keeping leaf Na+ within safe limits for CO/sub 2/ assimilation and reducing the need for frequent re-planting of salinized root stock. (author)

  13. Dairy product intake in relation to glucose regulation indices and risk of type 2 diabetes

    Struijk, E A; Heraclides, A; Witte, Daniel Rinse;


    and milk products, cheese and fermented dairy. Fasting plasma glucose (FPG), 2-h plasma glucose (2hPG), HbA(1c), insulin resistance (HOMA2-IR) and beta-cell function (HOMA2-B) were considered at 5-year follow-up. In the maximally-adjusted model (demographics, lifestyle factors, dietary factors and...... waist), cheese intake was inversely associated with 2hPG (β = -0.048, 95% CI -0.095; -0.001). Fermented dairy intake was inversely associated with FPG (β = -0.028, 95% CI -0.048; -0.008) and HbA(1c) (β = -0.016, 95% CI -0.030; -0.001). Total dairy intake and the dairy subgroups were not related to HOMA......-IR and HOMA-B in the maximally-adjusted model. Furthermore, there was no significant association between intake of total dairy or any of the dairy subgroups and incidence of T2D. CONCLUSION: Our data suggest a modest beneficial effect of cheese and fermented dairy on glucose regulation measures; however...

  14. Radiological Impacts and Regulation of Rare Earth Elements in Non-Nuclear Energy Production

    Timothy Ault


    Full Text Available Energy industries account for a significant portion of total rare earth usage, both in the US and worldwide. Rare earth minerals are frequently collocated with naturally occurring radioactive material, imparting an occupational radiological dose during recovery. This paper explores the extent to which rare earths are used by various non-nuclear energy industries and estimates the radiological dose which can be attributed to these industries on absolute and normalized scales. It was determined that typical rare earth mining results in an occupational collective dose of approximately 0.0061 person-mSv/t rare earth elements, amounting to a total of 330 person-mSv/year across all non-nuclear energy industries (about 60% of the annual collective dose from one pressurized water reactor operated in the US, although for rare earth mining the impact is spread out over many more workers. About half of the collective dose from non-nuclear energy production results from use of fuel cracking catalysts for oil refining, although given the extent of the oil industry, it is a small dose when normalized to the energy equivalent of the oil that is used annually. Another factor in energy industries’ reliance on rare earths is the complicated state of the regulation of naturally occurring radiological materials; correspondingly, this paper also explores regulatory and management implications.

  15. Comparative studies of environmental regulations in connection with combustive energy production

    The study of environmental regulations for energy production, specifically related to stack gas emission from combustion plants, was undertaken in order to investigate to what degree existing provisions were fuel neutral. 'Fuel' is here taken to mean a material whose combustion is used to supply heat for any purpose. The report consists of three parts, viz., 1. Environmental regulations for energy production in combustion plants. Presented data refer mainly to Sweden, Germany, France, Switzerland, and The European Union, but some data from Belgium, Denmark, Italy, The Netherlands, and Spain are also given. A dividing line between conventional fuels (coal, wood, oil, etc) and waste fuel (that is municipal solid waste, MSW) becomes apparent. As a rule, requirements for the former comprise particulates, sulphur oxides, nitrogen oxides, and carbon monoxide only, while requirements for dioxins, mercury and other heavy metals befall MSW only. In Germany, substances common to both fuel categories are subjected to stricter regulations if they occur in MSW, while no pronounced discrimination - except for particulates - is discernible in Sweden. France has emission limits for MSW as far as carbon monoxide and hydrogen halides are concerned, but none for conventional fuels. The EU directive for large combustion plants sets requirements for particulates and sulphur oxides for MSW combustion, but not for plants of comparative size (2, i.e., unit air factor (λ = 1). 2. Heat and power plant data and their treatment. This section contains case studies of three fluidized-bed plants, one with a stationary bed burning MSW, and two circulating beds fired with conventional solid fuels, and chipped wood waste in combination with packaging manufacturing loss consisting of polyethylene coated cardboard, respectively. Current reporting of this kind of data was found to be rather inconsistent and its proper treatment requires an unreasonable amount of time and effort. It is therefore

  16. NADPH-dependent glutamate dehydrogenase in Penicillium chrysogenum is involved in regulation of beta-lactam production

    Thykær, Jette; Kildegaard, Kanchana Rueksomtawin; Noorman, H.; Nielsen, Jens


    The interactions between the ammonium assimilatory pathways and beta-lactam production were investigated by disruption of the NADPH-dependent glutamate dehydrogenase gene (gdhA) in two industrial beta-lactam-producing strains of Penicillium chrysogenum. The strains used were an adipoyl-7-ADCA- an...... results indicate that the NADPH-dependent glutamate dehydrogenase may be directly or indirectly involved in the regulation of beta-lactann production in industrial strains of P. chrysogenum....

  17. The effects of rate of return and environmental regulations on the productivity performance in the US electric utility industry

    Productivity growth in the US electric power industry has been declining since the late 1960's. Rate of return regulation and environmental regulations are hypothesized to adversely affect the productivity performance. Employing a Divisa index of the total factor productivity (TEP) an electric utility's performance is measured based on a profit maximization framework subject to both regulatory constraints. The empirical analysis attempts to analyze the effects of these regulations on the productivity growth employing data from privately-owned, fossil-fueled electric utilities. Results show a consistent decline in productivity growth over time averaging at 2% annually during 1977 and 1982, as well as the existence of regional differences in TFP growth among utilities. It shows positive and significant relationships between TFP growth and the rate of return, regulatory lag, the use of future test year, and deferred tax credit in the rate-making process. In the environmental case, results show that a stringent emission standard, using scrubbers for sulfur reduction and the utilization of aging power plants all contribute to the decline in productivity growth

  18. Nitric oxide production by Biomphalaria glabrata haemocytes: effects of Schistosoma mansoni ESPs and regulation through the extracellular signal-regulated kinase pathway

    Kirk Ruth S


    Full Text Available Abstract Background Schistosoma mansoni uses Biomphalaria glabrata as an intermediate host during its complex life cycle. In the snail, the parasite initially transforms from a miracidium into a mother sporocyst and during this process excretory-secretory products (ESPs are released. Nitric oxide (NO and its reactive intermediates play an important role in host defence responses against pathogens. This study therefore aimed to determine the effects of S. mansoni ESPs on NO production in defence cells (haemocytes from schistosome-susceptible and schistosome-resistant B. glabrata strains. As S. mansoni ESPs have previously been shown to inhibit extracellular signal-regulated kinase (ERK phosphorylation (activation in haemocytes from susceptible, but not resistant, B. glabrata the regulation of NO output by ERK in these cells was also investigated. Results Haemocytes from resistant snails challenged with S. mansoni ESPs (20 μg/ml over 5 h displayed an increase in NO production that was 3.3 times greater than that observed for unchallenged haemocytes; lower concentrations of ESPs (0.1–10 μg/ml did not significantly increase NO output. In contrast, haemocytes from susceptible snails showed no significant change in NO output following challenge with ESPs at any concentration used (0.1–20 μg/ml. Western blotting revealed that U0126 (1 μM or 10 μM blocked the phosphorylation (activation status of ERK in haemocytes from both snail strains. Inhibition of ERK signalling by U0126 attenuated considerably intracellular NO production in haemocytes from both susceptible and resistant B. glabrata strains, identifying ERK as a key regulator of NO output in these cells. Conclusion S. mansoni ESPs differentially influence intracellular NO levels in susceptible and resistant B. glabrata haemocytes, possibly through modulation of the ERK signalling pathway. Such effects might facilitate survival of S. mansoni in its intermediate host.

  19. Evaluation of petroleum products pricing regulation in Nova Scotia : a 2 year review

    Gasoline price regulation was introduced in Nova Scotia on July 1st, 2006. This report presented the findings and recommendations of a review of the first two years of the gasoline price regulation in Nova Scotia. The regulations had three main objectives. This review examined whether, and to what extent, they were achieved. The objectives were to stabilize price, maintain industry infrastructure, and minimize cost to consumers. The report described the rationale for the regulation, study objectives, and approach taken to gasoline regulation in Nova Scotia, including the objectives and technical aspects of how regulation works. The gasoline market in Nova Scotia was examined, including the market structure and competitive behaviour in an unregulated market. The report also provided some theoretical perspectives on how regulation was likely to affect industry structure and competitive behaviour. The extent to which the regulation was meeting its objectives was then assessed and perspectives on the regulation from consumers, retailers and wholesalers were offered. Last, the report provided a review of the findings in terms of the key elements of regulatory design and set out recommendations for improving the system. It was recommended that in order to improve certainty, particularly given the regulated price differences amongst grades, the regulations should be amended to include grade specifications referencing octane ratings. tabs., figs

  20. Petroleum products price regulation in Nov Scotia : a six-month review

    Gasoline pricing regulation was introduced in July 2006 in order to achieve the following 3 main objectives: (1) stabilize prices by reducing the frequency of price changes and creating more uniform pricing across the province, (2) maintain industry infrastructure by slowing or halting the decline in the dealer network, particularly in rural areas, by improving viability through regulated margins, and (3) minimize the cost to consumers since higher prices are expected to result from the actions needed to maintain price stability and the higher margins needed to maintain industry infrastructure. This report examined the extent to which these objectives were achieved and contained the findings and recommendations of a review of the first six months of gasoline price regulation in Nova Scotia. The report discussed the rationale for regulation, study objectives, approach, and warning signs. It also discussed gasoline regulation in Nova Scotia including how regulation works and implementing regulation. The Nova Scotia gasoline market was presented with reference to industry structure; pre-regulation competition and pricing; and how regulation may affect structure and competition. Last, the report discussed whether regulation was meeting the objectives and perspectives on regulation. Several recommendations were presented, such as reducing the benchmark price adjustment period from two weeks to one week; removing the price cap on full-serve gasoline; adopting a fixed and transparent formula for forward averaging and applying it at each adjustment; and considering a framework for regulatory review. 12 refs., 15 figs

  1. Regulation of P450 oxidoreductase by gonadotropins in rat ovary and its effect on estrogen production

    Uesaka Miki; Kangawa Kenji; Kokame Koichi; Mizutani Tetsuya; Yazawa Takashi; Inaoka Yoshihiko; Umezawa Akihiro; Miyamoto Kaoru


    Abstract Background P450 oxidoreductase (POR) catalyzes electron transfer to microsomal P450 enzymes. Its deficiency causes Antley-Bixler syndrome (ABS), and about half the patients with ABS have ambiguous genitalia and/or impaired steroidogenesis. POR mRNA expression is up-regulated when mesenchymal stem cells (MSCs) differentiate into steroidogenic cells, suggesting that the regulation of POR gene expression is important for steroidogenesis. In this context we examined the regulation of POR...

  2. Thermal regulation of methane hydrate dissociation: Implications for gas production models

    Circone, S.; Kirby, S.H.; Stern, L.A.


    Thermal self-regulation of methane hydrate dissociation at pressure, temperature conditions along phase boundaries, illustrated by experiment in this report, is a significant effect with potential relevance to gas production from gas hydrate. In surroundings maintained at temperatures above the ice melting point, the temperature in the vicinity of dissociating methane hydrate will decrease because heat flow is insufficient to balance the heat absorbed by the endothermic reaction: CH4??nH2O (s) = CH4 (g) + nH2O (l). Temperature decreases until either all of the hydrate dissociates or a phase boundary is reached. At pressures above the quadruple point, the temperature-limiting phase boundary is that of the dissociation reaction itself. At lower pressures, the minimum temperature is limited by the H2O solid/liquid boundary. This change in the temperature-limiting phase boundary constrains the pressure, temperature conditions of the quadruple point for the CH4-H2O system to 2.55 ?? 0.02 MPa and 272.85 ?? 0.03 K. At pressures below the quadruple point, hydrate dissociation proceeds as the liquid H2O produced by dissociation freezes. In the laboratory experiments, dissociation is not impeded by the formation of ice byproduct per se; instead rates are proportional to the heat flow from the surroundings. This is in contrast to the extremely slow dissociation rates observed when surrounding temperatures are below the H2O solid/liquid boundary, where no liquid water is present. This "anomalous" or "self" preservation behavior, most pronounced near 268 K, cannot be accessed when surrounding temperatures are above the H2O solid/liquid boundary. ?? 2005 American Chemical Society.

  3. Early aldosterone-induced gene product regulates the epithelial sodium channel by deubiquitylation

    Fakitsas, P; Adam, G.; Daidié, D; van Bemmelen, M X; Fouladkou, F; Patrignani, A; U. Wagner; Warth, R.; Camargo, S M R; Staub, O.; Verrey, F


    The mineralocorticoid hormone aldosterone controls sodium reabsorption and BP largely by regulating the cell-surface expression and function of the epithelial sodium channel (ENaC) in target kidney tubules. Part of the stimulatory effect of aldosterone on ENaC is mediated by the induction of serum- and glucocorticoid-regulated kinase 1 (Sgk1), a kinase that interferes with the ubiquitylation of ENaC by ubiquitin-protein ligase Nedd4-2. In vivo early aldosterone-regulated mRNA now has been ide...

  4. 76 FR 68690 - Rules and Regulations Under the Textile Fiber Products Identification Act


    ... Under the Textile Fiber Products Identification Act: Final Rule, 63 FR 36171 (Jul. 2, 1998) (new generic... the Textile Fiber Products Identification Act: Final Rule, 67 FR 4901 (Feb. 1, 2002) (new generic... Textile Fiber Products Identification Act: Final Rule, 68 FR 3813 (Jan. 27, 2003) (new generic fiber...

  5. Challenges and problems of organic seed production in the EU – the EU Organic Seed Regulation

    Wilbois , Klaus-Peter


    Content: - Organic Seed regime in the EU - Overview EU Organic Seed data base - Data Base Exeample: OrganicXseeds - Problems of the Organic Seed Regulation - Problems with MS's Data Base - How to overcome these problems - Recommendations for new MS

  6. Positive allosteric feedback regulation of the stringent response enzyme RelA by its product

    Shyp, Viktoriya; Tankov, Stoyan; Ermakov, Andrey; Kudrin, Pavel; English, Brian P.; Ehrenberg, Måns; Tenson, Tanel; Elf, Johan; Hauryliuk, Vasili


    This report identifies a new mechanism of enzyme activation—positive allosteric regulation by the product—in the context of the bacterial stringent response, which is essential for bacterial adaptation to environmental conditions.

  7. Vibrio cholerae VpsT Regulates Matrix Production and Motility by Directly Sensing Cyclic di-GMP

    Krasteva, P.; Fong, J; Shikuma, N; Beyhan, S; Navarro, M; Yildiz, F; Sondermann, H


    Microorganisms can switch from a planktonic, free-swimming life-style to a sessile, colonial state, called a biofilm, which confers resistance to environmental stress. Conversion between the motile and biofilm life-styles has been attributed to increased levels of the prokaryotic second messenger cyclic di-guanosine monophosphate (c-di-GMP), yet the signaling mechanisms mediating such a global switch are poorly understood. Here we show that the transcriptional regulator VpsT from Vibrio cholerae directly senses c-di-GMP to inversely control extracellular matrix production and motility, which identifies VpsT as a master regulator for biofilm formation. Rather than being regulated by phosphorylation, VpsT undergoes a change in oligomerization on c-di-GMP binding.


    I. P. Stamat


    Full Text Available In the recent years, products that are produced using natural minerals with a high content of natural radionuclides have become widely used by households. The natural background radiation level can vary by tens and hundred times even for similar products, while areas of their application can differ from jewelry to medicine. However, normative documents (guidelines on the content of natural radionuclides in such products have not been yet created. To ensure radiation safety in the use of these products, the dose limit is set: the effective annual dose due to direct use of these products must not exceed 0.1 mSv. This article discusses issues related to the application of the dedicated sections of the documents OSPORB-99/2010 and SanPiN during sanitary-epidemiological assessment of the products, for which regulations on the content of natural radionuclide’s are not created. Possible scenarios of humanexposure when using these products with the primary purpose are considered. Based on the limit of 0.1 mSv annual effective dose, the criteria for a rapid compliance assessment of the radiological characteristics of the individual groups of these products are proposed.

  9. Deciphering the regulon of the Streptomyces coelicolor AbrC3, a positive response regulator of antibiotic production.

    Rico, Sergio; Santamaría, Ramón I; Yepes, Ana; Rodríguez, Héctor; Laing, Emma; Bucca, Giselda; Smith, Colin P; Díaz, Margarita


    The atypical two-component system (TCS) AbrC1/C2/C3 (encoded by SCO4598, SCO4597, and SCO4596), comprising two histidine kinases (HKs) and a response regulator (RR), is crucial for antibiotic production in Streptomyces coelicolor and for morphological differentiation under certain nutritional conditions. In this study, we demonstrate that deletion of the RR-encoding gene, abrC3 (SCO4596), results in a dramatic decrease in actinorhodin (ACT) and undecylprodiginine (RED) production and delays m...

  10. Tropodithietic Acid Production in Phaeobacter gallaeciensis Is Regulated by N-Acyl Homoserine Lactone-Mediated Quorum Sensing▿

    Berger, Martine; Neumann, Alexander; Schulz, Stefan; Simon, Meinhard; Brinkhoff, Thorsten


    The production of N-acyl homoserine lactones (AHLs) is widely distributed within the marine Roseobacter clade, and it was proposed that AHL-mediated quorum sensing (QS) is one of the most common cell-to-cell communication mechanisms in roseobacters. The traits regulated by AHL-mediated QS are yet not known for members of the Roseobacter clade, but production of the antibiotic tropodithietic acid (TDA) was supposed to be controlled by AHL-mediated QS in Phaeobacter spp. We describe here for th...

  11. Lipid phosphate phosphatases regulate lysophosphatidic acid production and signaling in platelets: studies using chemical inhibitors of lipid phosphate phosphatase activity.

    Smyth, Susan S; Sciorra, Vicki A; Sigal, Yury J; Pamuklar, Zehra; Wang, Zuncai; Xu, Yong; Prestwich, Glenn D; Morris, Andrew J


    Blood platelets play an essential role in ischemic heart disease and stroke contributing to acute thrombotic events by release of potent inflammatory agents within the vasculature. Lysophosphatidic acid (LPA) is a bioactive lipid mediator produced by platelets and found in the blood and atherosclerotic plaques. LPA receptors on platelets, leukocytes, endothelial cells, and smooth muscle cells regulate growth, differentiation, survival, motility, and contractile activity. Definition of the opposing pathways of synthesis and degradation that control extracellular LPA levels is critical to understanding how LPA bioactivity is regulated. We show that intact platelets and platelet membranes actively dephosphorylate LPA and identify the major enzyme responsible as lipid phosphate phosphatase 1 (LPP1). Localization of LPP1 to the platelet surface is increased by exposure to LPA. A novel receptor-inactive sn-3-substituted difluoromethylenephosphonate analog of phosphatidic acid that is a potent competitive inhibitor of LPP1 activity potentiates platelet aggregation and shape change responses to LPA and amplifies LPA production by agonist-stimulated platelets. Our results identify LPP1 as a pivotal regulator of LPA signaling in the cardiovascular system. These findings are consistent with genetic and cell biological evidence implicating LPPs as negative regulators of lysophospholipid signaling and suggest that the mechanisms involve both attenuation of lysophospholipid actions at cell surface receptors and opposition of lysophospholipid production. PMID:12909631

  12. Characterization of a two-component system in Streptococcus pyogenes which is involved in regulation of hyaluronic acid production.

    Bernish, B; van de Rijn, I


    Hyaluronic acid production by group A streptococci is regulated by transcriptional control. In this study, transposon mutagenesis of an unencapsulated strain yielded an encapsulated mutant. Two genes homologous to sensors and response regulators of bacterial two-component systems were identified downstream of the transposon insertion. Inactivation of the putative sensor gene, csrS, in three different unencapsulated strains yielded encapsulated mutant strains. Electrophoretic mobility shift assays determined factor(s) in a cytoplasmic extract of an unencapsulated group A streptococcal strain was binding to a double-stranded DNA fragment derived from the has operon promoter. In contrast, similarly prepared cytoplasmic extracts from a csrS deletion mutant did not shift the fragment. The putative response regulator, CsrR, was partially purified and was shown to bind the has operon promoter fragment. The affinity and specificity of CsrR for the fragment were increased significantly after incubation with acetyl phosphate. DNase I footprinting determined that the acetyl phosphate-treated CsrR was binding to key sequences in the promoter and the coding region of hasA. Therefore, a two-component system is repressing the production of hyaluronic acid in group A streptococci using a phosphorylation-dependent binding interaction between the response regulator CsrR and the promoter region of the has operon. PMID:9988717

  13. Adoption of ISO9001 through supply chain in Vietnam : impacts of FDI and product-related environmental regulation

    Iguchi, Hakaru; Arimura, Toshi H.; Michida, Etsuyo


    The objective of the present study is to examine the determinants of ISO 9001 certification, focusing on the effect of Product-related Environmental Regulations on Chemicals (PRERCs) and FDI using the answers to several questions in our Vietnam survey conducted from December 2011 to January 2012. Our findings suggest that PRERCs may help with the improvement in quality control of Vietnamese firms. If Vietnamese manufacturing firms with ISO 9001 certification are more likely to adopt ISO 14001...

  14. Aspergillus nidulans Natural Product Biosynthesis Is Regulated by MpkB, a Putative Pheromone Response Mitogen-Activated Protein Kinase

    The Aspergillus nidulans putative mitogen-activated protein kinase encoded by mpkB has a role in natural product biosynthesis. An mpkB mutant exhibited a decrease in sterigmatocystin gene expression and low mycotoxin levels. The mutation also affected the expression of genes involved in penicillin and terrequinone A synthesis. mpkB was necessary for normal expression of laeA, which has been found to regulate secondary metabolism gene clusters. (author)

  15. Impact on Asian firms of product-related environmental regulations through global supply chains : a study of firms in Malaysia

    Michida, Etsuyo; Ueki, Yasushi; Nabeshima, Kaoru


    This paper sheds light on the important role played by global supply chains in the adaptation to product-related environmental regulations imposed by importing countries, with a focus on chemicals management. By utilizing a unique data collected in Penang, Malaysia, we depict the supply chain structures and how differences among firms in participation to global supply chain link to differences in chemical management. We found that firms belonging to a supply chain are in a better position to ...

  16. Robust production of purified H-2 in a stable, self-regulating, and continuously operating solar fuel generator

    Modestino, Miguel A.; Walczak, Kart A.; Berger, Alan; Evans, Christopher M.; Haussener, Sophia; Koval, Carl; Newman, John S.; Ager, Joel W.; Segalman, Rachel A.


    The development of practical solar-driven electrochemical fuel generators requires the integration of light absorbing and electrochemical components into an architecture that must also provide easy separation of the product fuels. Unfortunately, many of these components are not stable under the extreme pH conditions necessary to facilitate ionic transport between redox reaction sites. By using a controlled recirculating stream across reaction sites, this work demonstrates a stable, self-regul...

  17. A γ-butyrolactone autoregulator-receptor system involved in the regulation of auricin production in Streptomyces aureofaciens CCM 3239.

    Mingyar, Erik; Feckova, Lubomira; Novakova, Renata; Bekeova, Carmen; Kormanec, Jan


    The γ-butyrolactone (GBL) autoregulator-receptor systems play a role in controlling secondary metabolism and/or morphological differentiation in many Streptomyces species. We previously identified the aur1 gene cluster, located on the Streptomyces aureofaciens CCM 3239 large linear plasmid pSA3239, which is responsible for the production of the angucycline antibiotic auricin. Here, we describe the characterisation of two genes, sagA and sagR, encoding GBL autoregulatory signalling homologues, which lie in the upstream part of the aur1 cluster. SagA was similar to GBL synthases and SagR to GBL receptors. The expression of each gene is directed by its own promoter, sagAp for sagA and sagRp for sagR. Both genes were active mainly during the exponential phase, and their transcription was interdependent. The disruption of sagA abolished auricin production, while the disruption of sagR resulted in precocious but dramatically reduced auricin production. Transcription from the aur1Pp and aur1Rp promoters, which direct the expression of auricin-specific cluster-situated regulators (CSRs), was also precocious and increased in the sagR mutant strain. In addition, SagR was also shown to specifically bind both promoters in vitro. These results indicated that the SagA-SagR GBL system regulates auricin production. Unlike many other GBL receptors, SagR does not bind its own promoter, but Aur1R, an auricin-specific repressor from the family of pseudo GBL receptors, does bind both sagAp and sagRp promoters. Moreover, the expression of both promoters was deregulated in an aur1R mutant, indicating that the SagA-SagR GBL system is regulated by a feedback mechanism involving the auricin-specific CSR Aur1R, which regulates downstream. PMID:25219533

  18. Research on the Legal Regulation of Market Access for Agricultural Products in China


    On the basis of defining the concept of market access for agricultural products,this paper analyzes the necessity of establishing market access system of agricultural products,proposes the conception of establishing market access system of agricultural products in China;sets up the frame of market access system of agricultural products;analyzes the rationality of the frame of market access system of agricultural products;poses the consideration of economic law regarding setup of market access system of agricultural products.This paper also puts forward the legislative suggestions for establishing market access system of agricultural products as follows:establish the frame of market access system of agricultural products taking quality access as core;establish and perfect the compensation and relief system of guaranteeing benefit of manager and producers;establish the market access system of agricultural products with hierarchical structure;sort out existing laws and form the sound the legal frame of market access system of agricultural products.

  19. Bile-acid-activated farnesoid X receptor regulates hydrogen sulfide production and hepatic microcirculation

    Barbara Renga; Andrea Mencarelli; Marco Migliorati; Eleonora Distrutti; Stefano Fiorucci


    AIM: To investigate whether the farnesoid X receptor (FXR) regulates expression of liver cystathionase (CSE), a gene involved in hydrogen sulfide (H2S) generation. METHODS: The regulation of CSE expression in response to FXR ligands was evaluated in HepG2 cells and in wild-type and FXR null mice treated with 6-ethyl chenodeoxycholic acid (6E-CDCA), a synthetic FXR ligand. The analysis demonstrated an FXR responsive element in the 5'-flanking region of the human CSE gene. The function of this site was investigated by luciferase reporter assays, chromatin immunoprecipitation and electrophoretic mobility shift assays. Livers obtained from rats treated with carbon tetrachloride alone, or in combination with 6-ethyl chenodeoxycholic acid, were studied for hydrogen sulphide generation and portal pressure measurement. RESULTS: Liver expression of CSE is regulated by bile acids by means of an FXR-mediated mechanism. Western blotting, qualitative and quantitative polymerase chain reaction, as well as immunohistochemical analysis, showed that expression of CSE in HepG2 cells and in mice is induced by treatment with an FXR ligand. Administration of 6E-CDCA to carbon tetrachloride treated rats protected against the down-regulation of CSE expression, increased H2S generation, reduced portal pressure and attenuated the endothelial dysfunction of isolated and perfused cirrhotic rat livers. CONCLUSION: These results demonstrate that CSE is an FXR-regulated gene and provide a new molecular explanation for the pathophysiology of portal hypertension.

  20. Similar biotherapeutic products in Latin America. Regulation and opportunities for patients with autoimmune diseases

    Desanvicente-Celis Z; Caro-Moreno J; Enciso-Zuluaga M; Anaya JM


    Zayrho Desanvicente-Celis, Julian Caro-Moreno, Mateo Enciso-Zuluaga, Juan-Manuel AnayaCenter for Autoimmune Diseases Research (CREA), Universidad del Rosario, Bogotá, ColombiaAbstract: Biotherapeutic products have revolutionized medicine, changing the way we can treat some chronic diseases, such as autoimmune diseases. The patent expiry and the high costs of reference biotherapeutic products, among other factors, have promoted interest in similar biotherapeutic products (SBPs), also kn...

  1. Similar biotherapeutic products in Latin America. Regulation and opportunities for patients with autoimmune diseases

    Anaya, Juan-Manuel


    Zayrho Desanvicente-Celis, Julian Caro-Moreno, Mateo Enciso-Zuluaga, Juan-Manuel AnayaCenter for Autoimmune Diseases Research (CREA), Universidad del Rosario, Bogotá, ColombiaAbstract: Biotherapeutic products have revolutionized medicine, changing the way we can treat some chronic diseases, such as autoimmune diseases. The patent expiry and the high costs of reference biotherapeutic products, among other factors, have promoted interest in similar biotherapeutic products (SBPs), als...

  2. Bioequivalence of Oral Products and the Biopharmaceutics Classification System: Science, Regulation, and Public Policy

    Amidon, KS; Langguth, P; Lennernäs, H; Yu, L; Amidon, GL


    The demonstration of bioequivalence (BE) is an essential requirement for ensuring that patients receive a product that performs as indicated by the label. The BE standard for a particular product is set by its innovator, and this standard must subsequently be matched by generic drug products. The Biopharmaceutics Classification System (BCS) sets a scientific basis for an improved BE standard for immediate-release solid oral dosage forms. In this paper, we discuss BE and the BCS, as well as th...

  3. Methods of regulation of sulfur contents at intermediate stages and in products of oil stock. Processing

    Safin Rashit Rafailovich


    Mathematical models of distribution of charge flows at oil-processing plants, allowing to optimize sulfur contents at intermediate stages and end pro-ducts, are offered in the paper. The possibility of sulfur contents redistribution in various products by modifying technological parameters of oil products pro-cessing and by changing the directions and (or) the volume of the flows, is shown. This allows to cut down the cost of sulfur refinement and reduce the pollution made by sulfur-containin...

  4. Global harmonization of food safety regulation from the perspective of Korea and a novel fast automatic product recall system.

    Sohn, Mun-Gi; Oh, Sangsuk


    Efforts have been made for global harmonization of food safety regulations among countries through international organizations such as WTO and WHO/FAO. Global harmonization of food safety regulations is becoming increasingly important for Korean consumers because more than half of food and agricultural products are imported and consumed. Through recent reorganization of the Korean government, a consolidated national food safety authority-the Ministry of Food and Drug Safety (MFDS)-has been established for more efficient food safety control and better communication with consumers. The Automatic Sales Blocking System (ASBS), which blocks the sales of the recalled food products at the point of sale, has been implemented at over 40,000 retail food stores around the nation using state-of-the art information and communication technology (ICT) for faster recall of adulterated food products, and the e-Food Safety Control System has been developed for more efficient monitoring of national food safety surveillance situations. The National Food Safety Information Service was also established for monitoring and collecting food safety information and incidents worldwide, and shares relevant information with all stakeholders. The new approaches adopted by the Korean Food Safety Authority are expected to enhance public trust with regard to food safety issues and expedite the recall process of adulterated products from the market. PMID:23794245

  5. Photoperiodic regulation of the sucrose transporter StSUT4 affects the expression of circadian-regulated genes and ethylene production

    Izabela eChincinska


    Full Text Available Several recent publications report different subcellular localisation of members of the SUT4 subfamily of sucrose transporters. The physiological function of SUT4 sucrose transporters is still not entirely clarified as down-regulation of members of the SUT4 clade had very different effects in rice, poplar and potato. Here, we provide new data on the localization and function of the Solanaceous StSUT4 protein, further elucidating involvement in the onset of flowering, tuberization and in the shade avoidance syndrome of potato plants.Induction of early flowering and tuberization in SUT4-inhibited potato plants correlates with increased sucrose export from leaves and increased sucrose and starch accumulation in terminal sink organs such as developing tubers. SUT4 does not only affect the expression of gibberellin and ethylene biosynthetic enzymes, but also the rate of ethylene synthesis in potato. In SUT4-inhibited plants, the ethylene production no longer follows a diurnal rhythm, leading to the assumption that StSUT4 controls circadian gene expression, potentially by regulating sucrose export from leaves. Furthermore, SUT4 expression affects clock-regulated genes such as StFT, StSOC1 and StCO, which might also be involved in a photoperiod-dependently controlled tuberization. A model is proposed in which StSUT4 controls a phloem-mobile signalling molecule generated in leaves which together with enhanced sucrose export affects developmental switches in apical meristems. SUT4 seems to link photoreceptor-perceived information about the light quality and day length, with phytohormone biosynthesis and the expression of circadian genes.

  6. 9 CFR 327.3 - No product to be imported without compliance with applicable regulations.


    ... larger forms, shall be permitted entry except under the following conditions: (1) A complete procedure... microbiological testing of the finished product shall be installed by the processor, the product is subjected to such testing, and the results thereof are furnished to the Administrator and are acceptable to him...

  7. Characteristic features of ghrelin cells in the gastrointestinal tract and the regulation of stomach ghrelin expression and production

    Zheng Zhao; Takafumi Sakai


    Ghrelin was isolated as an endogenous ligand for the GH secretagogue receptor from the rat stomach. Although physiological effects of ghrelin have been revealed by numerous studies, the regulation of stomach ghrelin remains obscure, and the factor that directly regulates ghrelin expression and production has not been identified. Here, we show some data regarding the characteristic features of ghrelin cells and the regulation of stomach ghrelin. In the gastrointestinal tract, ghrelin cells were identified as opened- and closed-type cells, and it was found that the number of ghrelin cells decreased from the stomach to the colon. The postnatal change in number of ghrelin cells in the stomach showed a sexually dimorphic pattern, indicating a role of estrogen in the regulation of stomach ghrelin. In vitro studies revealed that estrogen stimulated both ghrelin expression and production and that treatment with formestane, an aromatase (estrogen synthetase) inhibitor, decreased ghrelin expression level. On the other hand, leptin was found to inhibit both basal and estrogen-stimulated ghrelin expression. Moreover, both aromatase mRNA-expressing cells and leptin cells were found to be located close to ghrelin cells in the gastric mucosa. Furthermore, we found an inverse relationship between gastric ghrelin and leptin levels in a fasting state, and we revealed relative changes in expression of gastric ghrelin, estrogen and leptin in the postnatal rats. We propose that gastric estrogen and leptin directly regulate stomach ghrelin and that the balance control through gastric estrogen and leptin contributes to the altered ghrelin expression level in some physiological states.

  8. The CpAL Quorum Sensing System Regulates Production of Hemolysins CPA and PFO To Build Clostridium perfringens Biofilms

    Shak, Joshua R.; Canizalez-Roman, Adrian


    Clostridium perfringens strains produce severe diseases, including myonecrosis and enteritis necroticans, in humans and animals. Diseases are mediated by the production of potent toxins that often damage the site of infection, e.g., skin epithelium during myonecrosis. In planktonic cultures, the regulation of important toxins, such as CPA, CPB, and PFO, is controlled by the C. perfringens Agr-like (CpAL) quorum sensing (QS) system. Strains also encode a functional LuxS/AI-2 system. Although C. perfringens strains form biofilm-like structures, the regulation of biofilm formation is poorly understood. Therefore, our studies investigated the role of CpAL and LuxS/AI-2 QS systems and of QS-regulated factors in controlling the formation of biofilms. We first demonstrate that biofilm production by reference strains differs depending on the culture medium. Increased biomass correlated with the presence of extracellular DNA in the supernatant, which was released by lysis of a fraction of the biofilm population and planktonic cells. Whereas ΔagrB mutant strains were not able to produce biofilms, a ΔluxS mutant produced wild-type levels. The transcript levels of CpAL-regulated cpa and pfoA genes, but not cpb, were upregulated in biofilms compared to planktonic cultures. Accordingly, Δcpa and ΔpfoA mutants, in type A (S13) or type C (CN3685) backgrounds, were unable to produce biofilms, whereas CN3685Δcpb made wild-type levels. Biofilm formation was restored in complemented Δcpa/cpa and ΔpfoA/pfoA strains. Confocal microscopy studies further detected CPA partially colocalizing with eDNA on the biofilm structure. Thus, CpAL regulates biofilm formation in C. perfringens by increasing levels of certain toxins required to build biofilms. PMID:25824838

  9. Macrophage migration inhibitory factor regulates interleukin-6 production by facilitating nuclear factor-kappa B activation during Vibrio vulnificus infection

    Choi Pui-Ching


    Full Text Available Abstract Background Patients infected with Vibrio vulnificus (V. vulnificus show severe inflammatory responses characterised by the upregulation of proinflammatory cytokines. Macrophage migration inhibitory factor (MIF, an upstream proinflammatory regulator, increases the inflammation caused by sepsis. Whether MIF regulates responses to V. vulnificus infection and the actual mechanism by which V. vulnificus initiates these MIF-modulated proinflammatory cytokines remain unclear. Results MIF increased inflammation during V. vulnificus infection in vivo. In V. vulnificus-infected mice, MIF was produced earlier than tumour necrosis factor (TNF-α and interleukin (IL-6 and was expressed in a time-dependent manner. ISO-1 ((S, R-3-(4-hydroxyphenyl-4,5-dihydro-5-isoxazole acetic acid methyl ester, a small-molecule inhibitor of MIF, significantly decreased IL-6, IL-8, and TNF-α production in a time- and dose-dependent manner in human peripheral blood cells infected with V. vulnificus. The induction of IL-6, IL-8, and TNF-α production by V. vulnificus infection was mediated via the NF-κB- and p38 MAPK-regulated pathways but not via the Akt pathway. ISO-1-treated human peripheral blood cells showed lower V. vulnificus-induced NF-κB activation, IL-6 mRNA expression, and IκB phosphorylation, but they did not show lower p38 MAPK activation. Conclusions We conclude that MIF regulates V. vulnificus-induced IL-6 production via NF-κB activation and that p38 MAPK activation in V. vulnificus infection is not MIF dependent.

  10. Entropy Production Rate Changes in Lysogeny/Lysis Switch Regulation of Bacteriophage Lambda

    According to the chemical kinetic model of lysogeny/lysis switch in Escherichia coli (E. coli) infected by bacteriophage λ, the entropy production rates of steady states are calculated. The results show that the lysogenic state has lower entropy production rate than lytic state, which provides an explanation on why the lysogenic state of λ phage is so stable. We also notice that the entropy production rates of both lysogenic state and lytic state are lower than that of saddle-point and bifurcation state, which is consistent with the principle of minimum entropy production for living organism in nonequilibrium stationary state. Subsequently, the relations between CI and Cro degradation rates at two bifurcations and the changes of entropy production rate with CI and Cro degradation are deduced. The theory and method can be used to calculate entropy change in other molecular network. (interdisciplinary physics and related areas of science and technology)

  11. An R2R3-MYB Transcription Factor Regulates Eugenol Production in Ripe Strawberry Fruit Receptacles

    L. Medina-Puche; F.J. Molina-Hidalgo; M. Boersma; R.C. Schuurink; I. López-Vidriero; R. Solano; J.M. Franco-Zorrilla; J.L. Caballero; R. Blanco-Portales; J. Muñoz-Blanco


    Eugenol is a volatile phenylpropanoid that contributes to flower and ripe fruit scent. In ripe strawberry (Fragaria x ananassa) fruit receptacles, eugenol is biosynthesized by eugenol synthase (FaEGS2). However, the transcriptional regulation of this process is still unknown. We have identified and

  12. Mapping of a gene that regulates hemolysin production in Vibrio cholerae.

    von Mechow, S; Vaidya, A B; Bramucci, M G


    A gene that regulates the hemolysin structural gene (hly) was found to be tightly linked to the tox-1000 locus of Vibrio cholerae RJ1 and separated from hly by a large section of the V. cholerae genetic map. This hemolysin regulatory gene was designated hlyR.

  13. Cyclin Y Is Involved in the Regulation of Adipogenesis and Lipid Production.

    Weiwei An

    Full Text Available A new member of the cyclin family cyclin Y (CCNY is involved in the regulation of various physiological processes. In this study, the role of CCNY in energy metabolism was characterized. We found that compared with wild-type (WT mice, Ccny knockout (KO mice had both lower body weight and lower fat content. The Ccny KO mice also had a higher metabolic rate, resisted the stress of a high-fat diet, and were sensitive to calorie restriction. The expression levels of UCP1 and PGC1α were significantly higher in the brown adipose tissue (BAT of the Ccny KO mice than that of the WT littermate controls, whereas there was no significant difference in BAT weight between the WT and the Ccny KO mice. In addition, the down-regulation of Ccny resulted in suppression of white adipocyte differentiation both in vivo and in vitro, while the expression of Ccny was up-regulated by C/EBPα. Furthermore, both hepatocytes and HepG2 cells that were depleted of Ccny were insensitive to insulin stimulation, consistent with the significant inhibition of insulin sensitivity in the liver of the Ccny KO mice, but no significant changes in WAT and muscle, indicating that CCNY is involved in regulating the hepatic insulin signaling pathway. The hepatic insulin resistance generated by Ccny depletion resulted in down-regulation of the sterol-regulatory element-binding protein (SREBP1 and fatty acid synthase (FASN. Together, these results provide a new link between CCNY and lipid metabolism in mice, and suggest that inhibition of CCNY may offer a therapeutic approach to obesity and diabetes.

  14. Typical investigational medicinal products follow relatively uniform regulations in 10 European Clinical Research Infrastructures Network (ECRIN countries

    Gluud Christian


    Full Text Available Abstract Background In order to facilitate multinational clinical research, regulatory requirements need to become international and harmonised. The EU introduced the Directive 2001/20/EC in 2004, regulating investigational medicinal products in Europe. Methods We conducted a survey in order to identify the national regulatory requirements for major categories of clinical research in ten European Clinical Research Infrastructures Network (ECRIN countries-Austria, Denmark, France, Germany, Hungary, Ireland, Italy, Spain, Sweden, and United Kingdom-covering approximately 70% of the EU population. Here we describe the results for regulatory requirements for typical investigational medicinal products, in the ten countries. Results Our results show that the ten countries have fairly harmonised definitions of typical investigational medicinal products. Clinical trials assessing typical investigational medicinal products require authorisation from a national competent authority in each of the countries surveyed. The opinion of the competent authorities is communicated to the trial sponsor within the same timelines, i.e., no more than 60 days, in all ten countries. The authority to which the application has to be sent to in the different countries is not fully harmonised. Conclusion The Directive 2001/20/EC defined the term 'investigational medicinal product' and all regulatory requirements described therein are applicable to investigational medicinal products. Our survey showed, however, that those requirements had been adopted in ten European countries, not for investigational medicinal products overall, but rather a narrower category which we term 'typical' investigational medicinal products. The result is partial EU harmonisation of requirements and a relatively navigable landscape for the sponsor regarding typical investigational medicinal products.

  15. Divergent signaling pathways regulate IL-12 production induced by different species of Lactobacilli in human dendritic cells.

    Amar, Yacine; Rizzello, Valeria; Cavaliere, Riccardo; Campana, Stefania; De Pasquale, Claudia; Barberi, Chiara; Oliveri, Daniela; Pezzino, Gaetana; Costa, Gregorio; Meddah, Aicha Tirtouil; Ferlazzo, Guido; Bonaccorsi, Irene


    Recent studies have indicated that different strains of Lactobacilli differ in their ability to regulate IL-12 production by dendritic cells (DCs), as some strains are stronger inducer of IL-12 while other are not and can even inhibit IL-12 production stimulated by IL-12-inducer Lactobacilli. In this report we demonstrate that Lactobacillus reuteri 5289, as previously described for other strains of L. reuteri, can inhibit DC production of IL-12 induced by Lactobacilllus acidophilus NCFM. Remarkably, L. reuteri 5289 was able to inhibit IL-12 production induced not only by Lactobacilli, as so far reported, but also by bacteria of different genera, including pathogens. We investigated in human DCs the signal transduction pathways involved in the inhibition of IL-12 production induced by L. reuteri 5289, showing that this potential anti-inflammatory activity, which is also accompanied by an elevated IL-10 production, is associated to a prolonged phosphorilation of ERK1/2 MAP kinase pathway. Improved understanding of the immune regulatory mechanisms exerted by Lactobacilli is crucial for a more precise employment of these commensal bacteria as probiotics in human immune-mediated pathologies, such as allergies or inflammatory bowel diseases. PMID:25977118

  16. A Paired RNAi and RabGAP Overexpression Screen Identifies Rab11 as a Regulator of β-Amyloid Production

    Vinod Udayar


    Full Text Available Alzheimer’s disease (AD is characterized by cerebral deposition of β-amyloid (Aβ peptides, which are generated from amyloid precursor protein (APP by β- and γ-secretases. APP and the secretases are membrane associated, but whether membrane trafficking controls Aβ levels is unclear. Here, we performed an RNAi screen of all human Rab-GTPases, which regulate membrane trafficking, complemented with a Rab-GTPase-activating protein screen, and present a road map of the membrane-trafficking events regulatingproduction. We identify Rab11 and Rab3 as key players. Although retromers and retromer-associated proteins control APP recycling, we show that Rab11 controlled β-secretase endosomal recycling to the plasma membrane and thus affected Aβ production. Exome sequencing revealed a significant genetic association of Rab11A with late-onset AD, and network analysis identified Rab11A and Rab11B as components of the late-onset AD risk network, suggesting a causal link between Rab11 and AD. Our results reveal trafficking pathways that regulate Aβ levels and show how systems biology approaches can unravel the molecular complexity underlying AD.

  17. The fermentation stress response protein Aaf1p/Yml081Wp regulates acetate production in Saccharomyces cerevisiae.

    Christopher J Walkey

    Full Text Available The production of acetic acid during wine fermentation is a critical issue for wineries since the sensory quality of a wine can be affected by the amount of acetic acid it contains. We found that the C2H2-type zinc-finger transcription factor YML081Wp regulated the mRNA levels of ALD4 and ALD6, which encode a cytosolic acetaldehyde dehydrogenase (ACDH and a mitochondrial ACDH, respectively. These enzymes produce acetate from acetaldehyde as part of the pyruvate dehydrogenase bypass. This regulation was also reflected in the protein levels of Ald4p and Ald6p, as well as total ACDH activity. In the absence of ALD6, YML081W had no effect on acetic acid levels, suggesting that this transcription factor's effects are mediated primarily through this gene. lacZ reporter assays revealed that Yml081wp stimulates ALD6 transcription, in large part from a GAGGGG element 590 base pairs upstream of the translation start site. The non-annotated ORF YML081W therefore encodes a transcription factor that regulates acetate production in Saccharomyces cerevisiae. We propose AAF1 as a gene name for the YML081W ORF.

  18. Regulating ehrlich and demethiolation pathways for alcohols production by the expression of ubiquitin-protein ligase gene HUWE1.

    Zhang, Quan; Jia, Kai-Zhi; Xia, Shi-Tao; Xu, Yang-Hua; Liu, Rui-Sang; Li, Hong-Mei; Tang, Ya-Jie


    Ehrlich and demethiolation pathways as two competing branches converted amino acid into alcohols. Controlling both pathways offers considerable potential for industrial applications including alcohols overproduction, flavor-quality control and developing new flavors. While how to regulate ehrlich and demethiolation pathways is still not applicable. Taking the conversion of methionine into methionol and methanethiol for example, we constructed two suppression subtractive cDNA libraries of Clonostachys rosea by using suppression subtractive hybridization (SSH) technology for screening regulators controlling the conversion. E3 ubiquitin-protein ligase gene HUWE1 screened from forward SSH library was validated to be related with the biosynthesis of end products. Overexpressing HUWE1 in C. rosea and S. cerevisiae significantly increased the biosynthesis of methanethiol and its derivatives in demethiolation pathway, while suppressed the biosynthesis of methional and methionol in ehrlich pathway. These results attained the directional regulation of both pathways by overexpressing HUWE1. Thus, HUWE1 has potential to be a key target for controlling and enhancing alcohols production by metabolic engineering. PMID:26860895

  19. 76 FR 32843 - Defense Federal Acquisition Regulation Supplement; Fire-Resistant Fiber for Production of...


    ... Nomex) or The Lenzing Group, Austria (product called Fire-Resistant Rayon). In order to manufacture a... Twaron by Teijin (the Netherlands)); and Either Nomex (DuPont) or Fire-Resistant Rayon (Lenzing)....

  20. Is the European Medical Products Authorisation Regulation Equipped to Cope with the Challenges of Nanomedicines?

    Dorbeck-Jung, Bärbel; Chowdhury, Nupur


    This article analyses the emerging European regulatory activities in relation to nanopharmaceuticals. The central question is whether the regulatory responses are appropriate to cope with the regulatory problems nanomedicinal development is posing. The article explores whether the medical product re

  1. Differential Regulation of Eicosanoid and Endocannabinoid Production by Inflammatory Mediators in Human Choriodecidua.

    M D Mitchell

    Full Text Available An increase in intrauterine prostaglandin production is critical for the onset and progression of labor in women and indeed all mammalian species studied. Endocannabinoids can act as substrates for enzymes of the prostaglandin biosynthetic pathways and can be utilized to generate other related compounds such as prostamides. The end products are indistinguishable by radioimmunoassay. We have separated such compounds by mass spectrometry. We now show that inflammatory stimuli such as LPS and proinflammatory cytokines act differentially on these pathways in human choriodecidua and preferentially create drive through to prostaglandin end products. These findings create doubt about the interpretation of data on prostaglandin biosynthesis in intrauterine tissues from pregnant women especially in the presence of an infection. The possibility is raised that separation of these products might reduce variability in results and lead to potential uses for their measurement in the diagnosis of preterm labor.

  2. [Special considerations for the regulation of biological medicinal products in individualised medicine. More than stratified medicine].

    Müller-Berghaus, J; Volkers, P; Scherer, J; Cichutek, K


    The term individualised medicine, also called personalised medicine, is commonly used as an equivalent to stratified medicine. However, this is erroneous since quite often it is forgotten that especially biological medicinal products have other aspects of individualization that go beyond mere stratification. The principles of stratified medicine have been applied for biological medicinal products for many years. A historical example is diphtheria antitoxin made from horse serum, while current examples are transfusion of red blood cells and the administration of factor VIII in haemophilia A. The stratifying aspects of these medicinal products are given by the following considerations: diphtheria antitoxin is only administered after a diagnosis of diphtheria and not in other forms of tonsillitis, red blood cells should only be transfused once blood group compatibility as been established and factor VIII replacement is only administered in haemophilia A as opposed to other acquired or hereditary disease of the coagulation system. The peculiarities of biological medicinal products, in particular the inherent variability of the drug, are especially important for autologous cellular medicinal products. In addition to the expected variability of the biological source material there is interindividual variability of patients as cell donors, which make definition of specifications and determination of criteria for pharmaceutical quality and potency tests difficult. Therapy with modified autologous cells, a common and important application of advanced therapy medicinal products, is exemplary for the special considerations that must be made when evaluating pharmaceutical quality, mode of action and toxicological properties of the biological medicine. The clinical investigation of advanced therapy medicinal products with the intent of demonstrating safety and efficacy is particularly challenging because of the complexity of therapy, which often involves invasive interventions

  3. Functional Foods Examined: The Health Claims Being Made for Food Products and the Need for Regulation

    Bradbury, Jane; Lobstein, Tim; Lund, Vivien


    This report examines food products which claim, or imply, that they possess a health or nutritional benefit to the consumer. These include the recently-promoted ‘functional’ foods — such as those with added bacterial cultures, fish oils or soluble polysaccharides supposedly of benefit to the eater — as well as foods which have for some time been promoting themselves as having the benefit of added nutrients or being a rich source of certain nutrients. That a food product should ...

  4. Regulation of Genetically Engineered Food Products: A Market-Oriented Perspective

    Badros, Mark J.


    Only twenty years after the landmark Asilomar meeting where scientists discussed the opportunities and possible risks presented by the ability to transfer DNA from one organism to another,' bioengineered products have moved outside the confines of the laboratory into commercial uses in the pharmaceutical and food-processing industries. Recent advances in molecular biology and the application of new technologies to the production of food have opened the door to a new world of bioengineered foo...

  5. METABOLIC PROPERTIES OF RYE PRODUCTS Focusing on insulinaemia, glycaemic profile and appetite regulation in healthy subjects

    Rosén, Liza


    The prevalence of metabolic disorders, such as type 2 diabetes, cardiovascular diseases and the insulin resistance syndrome (IRS) are increasing worldwide. However, disturbances in the metabolic status can be prevented by changing the daily diet towards more whole grains, vegetables, legumes and dairy products. Also the dietary glycaemic- and insulinaemic indices of foods may play a role. Rye products are interesting in this context as they are usually consumed in wholegrain form and have bee...

  6. Effect of Food Regulation on the Spanish Food Processing Industry: A Dynamic Productivity Analysis

    Magdalena Kapelko; Alfons Oude Lansink; Stefanou, Spiro E.


    This article develops the decomposition of the dynamic Luenberger productivity growth indicator into dynamic technical change, dynamic technical inefficiency change and dynamic scale inefficiency change in the dynamic directional distance function context using Data Envelopment Analysis. These results are used to investigate for the Spanish food processing industry the extent to which dynamic productivity growth and its components are affected by the introduction of the General Food Law in 20...

  7. Regulation of the human stress response gene GADD153 expression: role of ETS1 and FLI-1 gene products.

    Seth, A; Giunta, S; Franceschil, C; Kola, I; Venanzoni, M C


    We have previously shown that ETS transcription factors, regulate cell growth and differentiation, and ETS1 and ETS2 are able to transcriptionally regulate wt p53 gene expression. In the present study we show that the ETS transcription factors also play a role in regulating expression of GADD153, a wt p53 inducible gene, which induces growth arrest and apoptosis in response to stress signals or DNA damage. We report the presence of a single EBS in the human GADD153 promoter, and that the GADD45 gene promoter lacks EBSs. The GADD153 promoter EBS shows a very high affinity for ETS1 and FLI-1 gene products. In addition, our data show that both ETS1 and FLI-1 strongly activate transcription of the GADD153 EBS linked to the CAT reporter gene. Our results also demonstrate how ETS1 and FLI-1 specifically regulate GADD153 expression. In addition, ectopic ETS2 protein expression resulted in only a weak induction of the same CAT reporter construct. The ETS1 and FLI-1 proteins provide a novel mechanism of activation for GADD153, allowing these two ETS genes to control its expression during cell growth and differentiation, rather than in response to oxidative stress. PMID:10510472

  8. Safety regulations for the nuclear uranium-graphite production reactors decommissioning in the Russian Federation

    There are different types of nuclear installations in the Russian Federation. Among them there are: nuclear power plants (NPPs), research reactors and critical facilities, fuel cycle facilities including uranium mining, conversion, enrichment, nuclear fuel fabrication, spent nuclear fuel (SNF) reprocessing, SNF and radioactive waste (RAW) storage facilities, radiochemistry, production reactors, etc. The first experience in the nuclear fuel cycle facilities decommissioning in Russia was gained from the uranium graphite production reactors shutdown at 'Mayak' site (Ozersk, Chelyabinsk region). The first uranium-graphite reactor was shutdown in 1987 at 'Mayak' site (it was the research uranium-graphite reactor AI). Sometime later in that year the next production reactor (A) was shutdown at the same site. This decommissioning project was used as the prototype for the decommissioning projects of the next two production reactors (AV-2 and AV-3) at the 'Mayak' site (both were shutdown in 1990). In the same year two uranium-graphite production reactors (I1 and EI-2) were shutdown at the 'SChC' site (Seversk, Tomsk region). In 1992 three uranium-graphite production reactors were shutdown - one (ADE-3) at the 'SChC' site and two (AD and ADE-1) at 'MChC' site (Zeleznogorsk, Krasnoyarsk region). (author)

  9. Down-regulation of stathmin expression is required for megakaryocyte maturation and platelet production

    Iancu-Rubin, Camelia; Gajzer, David; Tripodi, Joseph; Najfeld, Vesna; Gordon, Ronald E; Hoffman, Ronald; Atweh, George F.


    The final stages of of megakaryocyte (MK) maturation involve a series of steps, including polyploidization and proplatelet formation. Although these processes are highly dependent on dynamic changes in the microtubule (MT) cytoskeleton, the mechanisms responsible for regulation of MTs in MKs remain poorly defined. Stathmin is a highly conserved MT-regulatory protein that has been suggested to play a role in MK differentiation of human leukemic cell lines. However, previous studies defining th...

  10. A Genetic Strategy to Measure Circulating Drosophila Insulin Reveals Genes Regulating Insulin Production and Secretion

    Sangbin Park; Alfa, Ronald W.; Topper, Sydni M.; Grace E S Kim; Lutz Kockel; Kim, Seung K.


    Insulin is a major regulator of metabolism in metazoans, including the fruit fly Drosophila melanogaster. Genome-wide association studies (GWAS) suggest a genetic basis for reductions of both insulin sensitivity and insulin secretion, phenotypes commonly observed in humans with type 2 diabetes mellitus (T2DM). To identify molecular functions of genes linked to T2DM risk, we developed a genetic tool to measure insulin-like peptide 2 (Ilp2) levels in Drosophila, a model organism with superb exp...