78 FR 66941 - Design Considerations for Pivotal Clinical Investigations for Medical Devices; Guidance for...

Science.gov (United States)

2013-11-07

.... 66, rm. 2110, Silver Spring, MD 20993-0002, 301- 796-5750. For devices regulated by CBER: Stephen... the best clinical and statistical practices for investigational medical device studies. A medical...

[Legislative regulation of production and turnover of products for people with different diseases].

Science.gov (United States)

Pritul'skaia, N V; Motuzka, Iu N; Antiushko, D L

2013-01-01

This article presents results of analysis of existing regulatory documents and approaches to the legislative regulation of production and turnover of special dietary products for people with specific diseases in EU, Ukraine and Russian Federation. According to the EU legislation, production and turnover of food products for nutritional support of people during specific diseases and the rehabilitation period are regulated by the Commission Directive 1999/21/EC, 2009/39/ES, by Regulation Commission (EU) No 953/2009 and documents of Codex Committee. Special food products for people with specific diseases in Ukrainian legislation are classified as nutrition products for special dietary use and are regulated by the following Laws of Ukraine "On the safety and quality of food", "On ensuring of sanitary and epidemiological welfare of the population", "On Consumer Rights Protection", "On advertising" and by other non-legislative acts. According to the current legislation of the Russian Federation, the products for people with specific diseases are classified as healthy dietary food products. The basis of the legal framework are federal laws "On the quality and safety of food", "On the sanitary-epidemiological welfare of the populations", "On technical regulations and technical regulations of the Customs Union "On Food Safety" and "On the safety of certain types of specialized food products, including healthy dietary food products and therapeutic dietary food products". There is no common approach to the legal regulation of production and turnover of products for people with specific diseases in the world. The proposals for further harmonization of regulatory control in this area have been developed.

Regulation of intraluteal production of prostaglandins

Directory of Open Access Journals (Sweden)

Ottobre Joseph S

2003-11-01

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.

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

International Nuclear Information System (INIS)

Nestmann, Earle R.; Harwood, Melody; Martyres, Stephanie

2006-01-01

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

Federal approaches to the regulation of noncigarette tobacco products.

Science.gov (United States)

Freiberg, Michael J A

2012-11-01

Under a grant funded by ClearWay Minnesota(SM) and in partnership with nationally recognized experts in tobacco product regulation, the Public Health Law Center investigated how laws at every level apply, or fail to apply, to noncigarette tobacco products--also called "other tobacco products." During the years 2010-2011, standard legal research techniques were used to identify and compile relevant statutes, regulations, decisions, pleadings, proposals, and related materials. Sources included standard commercial legal databases such as LexisNexis and Westlaw, online sources for pending rules and legislation, and direct contact with courts for legal pleadings and unpublished decisions. These legal authorities related to many aspects of the regulation, including price, flavorants, youth access, marketing restrictions, and product design of other tobacco products. Five of these products were used as case studies: dissolvable tobacco products, electronic cigarettes, little cigars, snus, and water pipes. Research during the years 2010-2011 revealed that the federal regulation of other tobacco products lags behind the regulation of more "traditional" tobacco products, such as cigarettes and moist snuff. Federal regulatory options to expand regulation of these products were identified. The article highlights several federal policy interventions that would address gaps in the regulation of other tobacco products. The FDA must determine whether these interventions will benefit public health and, if so, to what extent--the legal criteria for intervention under the federal Family Smoking Prevention and Tobacco Control Act. Copyright © 2012 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.

75 FR 4081 - Agency Information Collection Activities; Proposed Collection; Comment Request; General Licensing...

Science.gov (United States)

2010-01-26

... any changes, in the product, production process, quality controls, equipment, facilities, or... from studies in animals). Section 601.93 provides that biological products approved under subpart H are... an Antibiotic Drug for Human Use'' to harmonize application procedures between CBER and CDER. The...

Verification of product design using regulation knowledge base and Web services

Energy Technology Data Exchange (ETDEWEB)

Kim, Ik June [KAERI, Daejeon (Korea, Republic of); Lee, Jae Chul; Mun Du Hwan [Kyungpook National University, Daegu (Korea, Republic of); Kim, Byung Chul [Dong-A University, Busan (Korea, Republic of); Hwang, Jin Sang [PartDB Co., Ltd., Daejeom (Korea, Republic of); Lim, Chae Ho [Korea Institute of Industrial Technology, Incheon (Korea, Republic of)

2015-11-15

Since product regulations contain important rules or codes that manufacturers must follow, automatic verification of product design with the regulations related to a product is necessary. For this, this study presents a new method for the verification of product design using regulation knowledge base and Web services. Regulation knowledge base consisting of product ontology and rules was built with a hybrid technique combining ontology and programming languages. Web service for design verification was developed ensuring the flexible extension of knowledge base. By virtue of two technical features, design verification is served to various products while the change of system architecture is minimized.

Verification of product design using regulation knowledge base and Web services

International Nuclear Information System (INIS)

Kim, Ik June; Lee, Jae Chul; Mun Du Hwan; Kim, Byung Chul; Hwang, Jin Sang; Lim, Chae Ho

2015-01-01

Since product regulations contain important rules or codes that manufacturers must follow, automatic verification of product design with the regulations related to a product is necessary. For this, this study presents a new method for the verification of product design using regulation knowledge base and Web services. Regulation knowledge base consisting of product ontology and rules was built with a hybrid technique combining ontology and programming languages. Web service for design verification was developed ensuring the flexible extension of knowledge base. By virtue of two technical features, design verification is served to various products while the change of system architecture is minimized.

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

DEFF Research Database (Denmark)

Brinch, Anna; Hansen, Steffen Foss; Hartmann, Nanna B.

2016-01-01

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...

Regulating interface science healthcare products: myths and uncertainties.

Science.gov (United States)

Bravery, Christopher A

2010-12-06

Whenever new technology emerges it brings with it concerns and uncertainties about whether or how it will need to be regulated, particularly when it is applied to human healthcare. Drawing on the recent history in the European Union (EU) of the regulation of cell-based medicinal products, and in particular tissue-engineered products, this paper explores the myths that persist around their regulation and speculates on whether the existing regulatory landscape in the EU is flexible enough to incorporate nanotechnology and other new technologies into healthcare products. By untangling these myths a number of clear conclusions are revealed that, when considered in the context of risk-benefit, make it clear that what hinders the uptake of new technology is not regulatory process but basic science.

77 FR 71194 - Draft Guidance for Industry: Preclinical Assessment of Investigational Cellular and Gene Therapy...

Science.gov (United States)

2012-11-29

...] Draft Guidance for Industry: Preclinical Assessment of Investigational Cellular and Gene Therapy... Industry: Preclinical Assessment of Investigational Cellular and Gene Therapy Products,'' dated November... Evaluation (CBER), Office of Cellular, Tissue, and Gene Therapies (OCTGT). The product areas covered by this...

21 CFR 610.53 - Dating periods for licensed biological products.

Science.gov (United States)

2010-04-01

... hours from date of collection, provided labeling recommends storage between 1 and 6 °C. Yellow Fever... Research (CBER). Pneumococcal Vaccine Polyvalent: 1. Final bulk powder ......do 24 months after potency... Evaluation and Research or the Director of the Center for Drug Evaluation and Research. [50 FR 4134, Jan. 29...

The feed-back regulation of erythropoietin production in healthy humans

International Nuclear Information System (INIS)

Klausen, T.

1998-01-01

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

Regulation of natural health products in Canada.

Science.gov (United States)

Smith, Alysyn; Jogalekar, Sumedha; Gibson, Adam

2014-12-02

In Canada, all natural health products (NHPs) are regulated by Health Canada (HC) under the Food and Drugs Act and the Natural Health Product Regulations. All authorized products undergo pre-market assessment for safety, efficacy and quality and the degree of pre-market oversight varies depending on the risk of the product. In Canada, over 70,000 products have been authorized for sale and over 2000 sites have been licensed to produce NHPs. In the management of NHPs on the Canadian market, HC employs a number of active and collaborative methods to address the most common issues such as contamination, adulteration and deceptive or misleading advertising practices. HC is currently evolving its approaches to NHPs to recognize them as part of the larger group of health products available without a prescription. As such, the regulatory responsibility for all over-the-counter (OTC) drugs, including non-prescription drugs and NHPs, has been transferred to a single federal division. As a result of this transition a number of benefits are being realized with respect to government efficiency, clarity for industry, support for new innovations and consolidated government interactions with the Canadian market. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Hungry granulocyte: its fate and regulation of production

International Nuclear Information System (INIS)

Cronkite, E.P.

1978-01-01

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

Implications of environmental regulations on refinery product specification, operation and investment

International Nuclear Information System (INIS)

Amin, M.M.

1992-01-01

During the 1980s, refiners mainly in OECD countries were occupied with improving their refinery configurations for producing high-value light products which would not only satisfy the product demand slate but also meet the increasingly restrictive environmental regulations. In the 1990s refiners will continue to be challenged to improve the world's air quality not only by producing products that minimize emissions of toxic and hazardous hydrocarbons, but also through the refinery operation itself by investment in upgrading the industry and products to cope with the constant flow of new regulations. These investments will not only be limited to consuming centres but will also be extended to cover exporting refineries as well due to competition of acquiring market shares for product exports. The additional cost will be directly related to product quality and site regulations and will vary from one country to the other. This paper deals mainly with the air pollution and the impact of related environmental issues on the refining industry. Environmental regulations for refinery products in the USA and Europe are examined and international regulations for the tanker industry are noted. (author)

75 FR 32786 - Agency Information Collection Activities; Submission for Office of Management and Budget Review...

Science.gov (United States)

2010-06-09

... follow specific procedures to submit information to FDA of any changes, in the product, production... feasible (or based on evidence of effectiveness from studies in animals). Section 601.93 provides that... an Antibiotic Drug for Human Use'' to harmonize application procedures between CBER and CDER. The...

Regulation of primary productivity rate in the equatorial Pacific

International Nuclear Information System (INIS)

Barber, R.T.; Chavez, F.P.

1991-01-01

Analysis of the Chl-specific rate of primary productivity (P B ) as a function of subsurface nutrient concentration at >300 equatorial stations provides an answer to the question: What processes regulate primary productivity rate in the high-nutrient, low-chlorophyll waters of the equatorial Pacific? In the western Pacific where there is a gradient in 60-m [NO 3 ] from 0 to ∼12 μM, the productivity rate is a linear function of nutrient concentration; in the eastern Pacific where the gradient is from 12 to 28 μM, the productivity rate is independent of nutrient concentration and limited to ∼36 mg C(mg Chl) -1 d -1 , or a mean euphotic zone C-specific growth rate (μ) of 0.47 d -1 . However, rates downstream of the Galapagos Islands are not limited; they are 46.4 mg C(mg Chl) -1 d -1 and μ = 0.57 d -1 , very close to the predicted nutrient-regulated rates in the absence of other limitation. This pattern of rate regulation can be accounted for by a combination of eolian Fe, subsurface nutrients, and sedimentary Fe derived from the Galapagos platform. In the low-nutrient western Pacific the eolian supply of Fe is adequate to allow productivity rate to be set by subsurface nutrient concentration. In the nutrient-rich easter equatorial region eolian Fe is inadequate to support productivity rates proportional to the higher nutrient concentrations, so in this region eolian Fe is rate limiting. Around the Galapagos Islands productivity rates reach levels consistent with nutrient concentrations; sedimentary Fe from the Galapagos platform seems adequate to support increased nutrient-regulated productivity rates in this region

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

Energy Technology Data Exchange (ETDEWEB)

Carroll, Herbert B.; Johnson, William I.

1999-04-27

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.

Climate change and regulation of hepatotoxin production in Cyanobacteria.

Science.gov (United States)

Gehringer, Michelle M; Wannicke, Nicola

2014-04-01

Harmful, bloom-forming cyanobacteria (CyanoHABs) are occurring with increasing regularity in freshwater and marine ecosystems. The most commonly occurring cyanobacterial toxins are the hepatotoxic microcystin and nodularin. These cyclic hepta- and pentapeptides are synthesised nonribosomally by the gene products of the toxin gene clusters mcy and nda, respectively. Understanding of the regulation of hepatotoxin production is incomplete, although there is strong evidence supporting the roles of iron, light, higher nitrate availability and inorganic carbon in modulating microcystin levels. The majority of these studies have focused on the unicellular freshwater, microcystin-producing strain of Microcystis aeruginosa, with little attention being paid to terrestrial or marine toxin producers. This review intends to investigate the regulation of microcystin and nodularin production in unicellular and filamentous diazotrophic cyanobacteria against the background of changing climate conditions. Special focus is given to diazotrophic filamentous cyanobacteria, for example Nodularia spumigena, capable of regulating their nitrogen levels by actively fixing dinitrogen. By combining data from significant studies, an overall scheme of the regulation of toxin production is presented, focussing specifically on nodularin production in diazotrophs against the background of increasing carbon dioxide concentrations and temperatures envisaged under current climate change models. Furthermore, the risk of sustaining and spreading CyanoHABs in the future ocean is evaluated. © 2014 Federation of European Microbiological Societies. Published by John Wiley & Sons Ltd. All rights reserved.

75 FR 35493 - Guidance for Industry on Systemic Lupus Erythematosus-Developing Medical Products for Treatment...

Science.gov (United States)

2010-06-22

...: The Food and Drug Administration (FDA) is announcing the availability of a guidance for industry... and Research (CBER), Food and Drug Administration, 1401 Rockville Pike, suite 200N, Rockville, MD...-0002, 301- 796-2280; or Stephen Ripley, Center for Biologics Evaluation and Research (HFM- 17), Food...

Medicinal Product Regulation: Portugal׳s Framework.

Science.gov (United States)

Herdeiro, Maria Teresa; Bastos, Paulo D; Teixeira-Rodrigues, António; Roque, Fátima

2016-09-01

The pharmaceutical industry is one of the most tightly regulated sectors, and it is essential to know each country׳s legal framework to understand the regulation, approval, and marketing of medicinal products for human use. This article describes the main statutes and procedures governing medicinal products for human use in Portugal and the role of the country׳s National Medicines and Health Products Authority (Autoridade Nacional do Medicamento e Produtos de Saúde, I.P.; INFARMED). From the most recently available data, an update of requests and approvals concerning marketing authorizations, variations, pricing, and reimbursements is provided. Data were sourced from the INFARMED website, Infomed (database of medicinal products for human use), and periodic reports issued by national authorities. Organic laws, acts, and law decrees published in the government gazette (Diário da República) are cited and reproduced as required. In 2015 Portugal ranked fifth in the European System of Medicines Evaluation in terms of the number of completed procedures as a reference member state. Approximately 80% of all approved drug applications in Portugal in 2015 were for generic drugs, mostly pertaining to the nervous system. In Portugal, INFARMED monitors drug quality, safety profile, and efficacy in all stages of the drug life cycle, ensuring patients' safety. The Portuguese market for medicinal products for human use has been appreciably changed by the advent of generic drugs. There is an increased trend for new request applications for biological and biotechnological substances. Copyright © 2016 Elsevier HS Journals, Inc. All rights reserved.

Regulations for the peat production water pollution control

International Nuclear Information System (INIS)

Savolainen, M.; Heikkinen, K.; Ihme, R.

1996-01-01

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.)

Impact of Environmental Regulation on Productivity: Case Studies of Three Industries in Japan

OpenAIRE

Chalermthanakom, Adisak; Ueta, Kazuhiro

2011-01-01

Although fi rms bear the cost of compliance, strict but fl exible environmental regulation may benefi t them by spurring the innovation process. However, the relationship between environmental regulation and productivity is unclear. We calculate productivity growth by using data envelopment analysis; we then conduct regression analysis, using panel data on productivity growth by environmental regulation stringency. A one-year lag of environmental regulation stringency is included in the model...

78 FR 70306 - Distribution of In Vitro Diagnostic Products Labeled for Research Use Only or Investigational Use...

Science.gov (United States)

2013-11-25

... Development (HFM-40), Center for Biologics Evaluation and Research (CBER), Food and Drug Administration, 1401...: Guidance for Industry and Food and Drug Administration Staff; Availability AGENCY: Food and Drug... Research (HFM-17), Food and Drug Administration, 1401 Rockville Pike, Suite 200N, Rockville, MD 20852-1448...

Future development of global regulations of Chinese herbal products.

Science.gov (United States)

Fan, Tai-Ping; Deal, Greer; Koo, Hoi-Lun; Rees, Daryl; Sun, He; Chen, Shaw; Dou, Jin-Hui; Makarov, Valery G; Pozharitskaya, Olga N; Shikov, Alexander N; Kim, Yeong Shik; Huang, Yi-Tsau; Chang, Yuan Shiun; Jia, William; Dias, Alberto; Wong, Vivian Chi-Woon; Chan, Kelvin

2012-04-10

GP-TCM is the first EU-funded Coordination Action consortium dedicated to traditional Chinese medicine (TCM) research. One of the key deliverables of the Work Package 7 in GP-TCM was to investigate information of the existing requirements for registration of TCM products listed by global regulatory bodies. The paper aims to collate data and draw comparison of these regulations. Case studies are also presented to illustrate the problems involved in registering TCM products in different regions worldwide. A collaborative network task force was established during the early stage of the GP-TCM project and operated through exchanges, teleconferences and focused discussions at annual meetings. The task force involved coordinators, academics who are actively involved with R&D of Chinese herbal medicines, experts on monographic standards of Chinese materia medica, representatives from regulatory agencies, experts from industries in marketing Chinese medicines/herbal medicines and natural products. The co-ordinators took turns to chair teleconferences, led discussions on specific issues at AGM discussion sessions, at joint workshops with other work-packages such as WP1 (quality issues), WP3 (toxicology issues) and WP6 (clinical trial issues). Collectively the authors were responsible for collating discussion outcomes and updating written information. A global overview of regulations on herbal registration has been compiled during the three years of the consortium. The regulatory requirements for registration of herbal products in the EU and China were compared, and this is extended to other regions/countries: Africa, Australia, Brazil, Canada, Japan, Russia, South Korea, Taiwan, and the United States. A wide variation of the regulations for the categories of herbal products exists: food (functional food, novel foods, dietary food for special medical purpose, foods for particular nutritional use, food supplement); cosmetic, traditional herbal medicine products; herbal

Duodenal mucosal protein kinase C-δ regulates glucose production in rats.

Science.gov (United States)

Kokorovic, Andrea; Cheung, Grace W C; Breen, Danna M; Chari, Madhu; Lam, Carol K L; Lam, Tony K T

2011-11-01

Activation of protein kinase C (PKC) enzymes in liver and brain alters hepatic glucose metabolism, but little is known about their role in glucose regulation in the gastrointestinal tract. We investigated whether activation of PKC-δ in the duodenum is sufficient and necessary for duodenal nutrient sensing and regulates hepatic glucose production through a neuronal network in rats. In rats, we inhibited duodenal PKC and evaluated whether nutrient-sensing mechanisms, activated by refeeding, have disruptions in glucose regulation. We then performed gain- and loss-of-function pharmacologic and molecular experiments to target duodenal PKC-δ; we evaluated the impact on glucose production regulation during the pancreatic clamping, while basal levels of insulin were maintained. PKC-δ was detected in the mucosal layer of the duodenum; intraduodenal infusion of PKC inhibitors disrupted glucose homeostasis during refeeding, indicating that duodenal activation of PKC-δ is necessary and sufficient to regulate glucose homeostasis. Intraduodenal infusion of the PKC activator 1-oleoyl-2-acetyl-sn-glycerol (OAG) specifically activated duodenal mucosal PKC-δ and a gut-brain-liver neuronal pathway to reduce glucose production. Molecular and pharmacologic inhibition of duodenal mucosal PKC-δ negated the ability of duodenal OAG and lipids to reduce glucose production. In the duodenal mucosa, PKC-δ regulates glucose homeostasis. Copyright © 2011 AGA Institute. Published by Elsevier Inc. All rights reserved.

CdtR Regulates TcdA and TcdB Production in Clostridium difficile.

Directory of Open Access Journals (Sweden)

Shelley A Lyon

2016-07-01

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.

Productivity and environmental regulations. A long run analysis of the Swedish industry

Energy Technology Data Exchange (ETDEWEB)

Braennlund, Runar

2008-01-15

The aim with this study is to evaluate the potential effects on productivity development in the Swedish manufacturing industry due to changes in environmental regulations over a long time period. The issue is closely related to the so called Porter hypothesis, i.e. whether environmental regulations (of the right kind) that usually is associated with costs triggers mechanisms that enhances efficiency and productivity that finally outweighs the initial cost increase. To test our hypothesis we use historical data spanning over the period 1913-1999 for the Swedish manufacturing sector. The model used is a two stage model were the total factor productivity is calculated in the first stage, and is then used in a second stage as the dependent variable in a regression analysis where one of the independent variables is a measure of regulatory intensity. The results show that the productivity growth has varied considerably over time. The least productive period was the second world war period, whereas the period with the highest productivity growth was the period after the second world war until 1970. Development of emissions follows essentially the same path as productivity growth until 1970. After 1970, however, there is a decoupling in the sense that emissions are decreasing, both in absolute level and as emissions per unit of value added. A rather robust conclusion is that there is no evident relationship between environmental regulations and productivity growth. One explanation is that regulations and productivity actually is unrelated. Another potential explanation is that the regulatory measure used does not capture perceived regulations in a correct way

Pupils' Readiness for Self-Regulated Learning in the Forethought Phase of Exploratory Production

Science.gov (United States)

Metsärinne, Mika; Kallio, Manne; Virta, Kalle

2015-01-01

This article discusses pupils' readiness for self-regulation in Exploratory Production in Technology Education. In the forethought phase of Exploratory Production, pupils envision and regulate their technological production activities. Next, in the performance phase, the envisioned goals are tried and implemented through ideating, planning and…

Developing products and services for a deregulated market while regulated

International Nuclear Information System (INIS)

Haites, E.F.

1997-01-01

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

The importance of product definitions in US e-cigarette laws and regulations.

Science.gov (United States)

Lempert, Lauren K; Grana, Rachel; Glantz, Stanton A

2016-04-01

How electronic cigarettes and similar products (e-cigarettes) are defined affects how they are regulated, particularly whether existing laws for cigarettes apply, including sales and marketing, youth access, smoke-free and taxation laws. We examined the text of 46 bills that define e-cigarettes enacted in 40 states and characterised how e-cigarettes and similar products were defined. States enact laws creating new product categories for e-cigarettes separate from the 'tobacco product' category (eg, 'alternative nicotine product,' 'vapour product,' 'electronic nicotine device'), with four states explicitly excluding e-cigarettes from 'tobacco products.' Twenty-eight states do not include e-cigarettes in their definitions of 'tobacco products' or 'smoking,' eight include e-cigarettes as 'tobacco products,' three include e-cigarettes in 'smoking.' Sixteen states' definitions of e-cigarettes require nicotine, and five states pre-empt more stringent local laws. Tobacco and e-cigarette industry representatives tried to shape laws that benefit their interests. Definitions separating e-cigarettes from other tobacco products are common. Similar to past 'Trojan horse' policies, e-cigarette policies that initially appear to restrict sales (eg, limit youth access) may actually undermine regulation if they establish local pre-emption or create definitions that divide e-cigarettes from other tobacco products. Comparable issues are raised by the European Union Tobacco Products Directive and e-cigarette regulations in other countries. Policymakers should carefully draft legislation with definitions of e-cigarettes that broadly define the products, do not require nicotine or tobacco, do not pre-empt stronger regulations and explicitly include e-cigarettes in smoke-free and taxation laws. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

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

Directory of Open Access Journals (Sweden)

Boon Heather

2006-05-01

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.

Monitoring of transcriptional regulation in Pichia pastoris under protein production conditions

Directory of Open Access Journals (Sweden)

Bhattacharyya Anamitra

2007-06-01

Full Text Available Abstract Background It has become evident that host cells react to recombinant protein production with a variety of metabolic and intrinsic stresses such as the unfolded protein response (UPR pathway. Additionally, environmental conditions such as growth temperature may have a strong impact on cell physiology and specific productivity. However, there is little information about the molecular reactions of the host cells on a genomic level, especially in context to recombinant protein secretion. For the first time, we monitored transcriptional regulation of a subset of marker genes in the common production host Pichia pastoris to gain insights into the general physiological status of the cells under protein production conditions, with the main focus on secretion stress related genes. Results Overexpression of the UPR activating transcription factor Hac1p was employed to identify UPR target genes in P. pastoris and the responses were compared to those known for Saccharomyces cerevisiae. Most of the folding/secretion related genes showed similar regulation patterns in both yeasts, whereas genes associated with the general stress response were differentially regulated. Secretion of an antibody Fab fragment led to induction of UPR target genes in P. pastoris, however not to the same magnitude as Hac1p overproduction. Overexpression of S. cerevisiae protein disulfide isomerase (PDI1 enhances Fab secretion rates 1.9 fold, but did not relief UPR stress. Reduction of cultivation temperature from 25°C to 20°C led to a 1.4-fold increase of specific product secretion rate in chemostat cultivations, although the transcriptional levels of the product genes (Fab light and heavy chain were significantly reduced at the lower temperature. A subset of folding related genes appeared to be down-regulated at the reduced temperature, whereas transcription of components of the ER associated degradation and the secretory transport was enhanced. Conclusion Monitoring of

Regulation of Cell and Gene Therapy Medicinal Products in Taiwan.

Science.gov (United States)

Lin, Yi-Chu; Wang, Po-Yu; Tsai, Shih-Chih; Lin, Chien-Liang; Tai, Hsuen-Yung; Lo, Chi-Fang; Wu, Shiow-Ing; Chiang, Yu-Mei; Liu, Li-Ling

2015-01-01

Owing to the rapid and mature development of emerging biotechnology in the fields of cell culture, cell preservation, and recombinant DNA technology, more and more cell or gene medicinal therapy products have been approved for marketing, to treat serious diseases which have been challenging to treat with current medical practice or medicine. This chapter will briefly introduce the Taiwan Food and Drug Administration (TFDA) and elaborate regulation of cell and gene therapy medicinal products in Taiwan, including regulatory history evolution, current regulatory framework, application and review procedures, and relevant jurisdictional issues. Under the promise of quality, safety, and efficacy of medicinal products, it is expected the regulation and environment will be more flexible, streamlining the process of the marketing approval of new emerging cell or gene therapy medicinal products and providing diverse treatment options for physicians and patients.

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

Science.gov (United States)

Mansnérus, Juli

2015-12-01

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.

Biotin deficiency up-regulates TNF-alpha production in murine macrophages.

Science.gov (United States)

Kuroishi, Toshinobu; Endo, Yasuo; Muramoto, Koji; Sugawara, Shunji

2008-04-01

Biotin, a water-soluble vitamin of the B complex, functions as a cofactor of carboxylases that catalyze an indispensable cellular metabolism. Although significant decreases in serum biotin levels have been reported in patients with chronic inflammatory diseases, the biological roles of biotin in inflammatory responses are unclear. In this study, we investigated the effects of biotin deficiency on TNF-alpha production. Mice were fed a basal diet or a biotin-deficient diet for 8 weeks. Serum biotin levels were significantly lower in biotin-deficient mice than biotin-sufficient mice. After i.v. administration of LPS, serum TNF-alpha levels were significantly higher in biotin-deficient mice than biotin-sufficient mice. A murine macrophage-like cell line, J774.1, was cultured in a biotin-sufficient or -deficient medium for 4 weeks. Cell proliferation and biotinylation of intracellular proteins were decreased significantly in biotin-deficient cells compared with biotin-sufficient cells. Significantly higher production and mRNA expression of TNF-alpha were detected in biotin-deficient J774.1 cells than biotin-sufficient cells in response to LPS and even without LPS stimulation. Intracellular TNF-alpha expression was inhibited by actinomycin D, indicating that biotin deficiency up-regulates TNF-alpha production at the transcriptional level. However, the expression levels of TNF receptors, CD14, and TLR4/myeloid differentiation protein 2 complex were similar between biotin-sufficient and -deficient cells. No differences were detected in the activities of the NF-kappaB family or AP-1. The TNF-alpha induction by biotin deficiency was down-regulated by biotin supplementation in vitro and in vivo. These results indicate that biotin deficiency may up-regulate TNF-alpha production or that biotin excess down-regulates TNF-alpha production, suggesting that biotin status may influence inflammatory diseases.

Regulation of adrenomedullin and nitric oxide production by periodontal bacteria.

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Hussain, Q A; McKay, I J; Gonzales-Marin, C; Allaker, R P

2015-10-01

In periodontitis the host response to bacterial challenge includes activity of the multifunctional molecules adrenomedullin (AM) and nitric oxide (NO). The aim of this study was to investigate the role of periodontal bacteria in regulating the production of these molecules from cultured cells. Regulation of AM and NO production from oral keratinocytes when challenged with culture supernatants from Aggregatibacter actinomycetemcomitans, Campylobacter rectus, Fusobacterium nucleatum, Porphyromonas gingivalis, Prevotella intermedia, Veillonella atypica, Streptococcus salivarius and Candida albicans was examined. AM and NO were measured in cell culture supernatants using an enzyme-linked immunosorbent assay and the nitrate/nitrite (NO metabolites) Griess assay respectively. Cellular production of AM and inducible NO synthase was also analysed in target cells by immunofluorescence and Western blot analysis. The inter-relationship of AM and NO production were further investigated with macrophages. A. actinomycetemcomitans and C. rectus induced maximal levels of both AM and NO after 6 and 48 h respectively from oral keratinocytes. AM production in macrophages was upregulated in response to the NO donor S-nitrosoglutathione and partially blocked by the inducible NO synthase inhibitor, N(ω) -Nitro-l-arginine methyl ester hydrochloride. Likewise, NO production was increased upon exposure to AM, while the AM receptor antagonist AM 22-52 reduced the release of NO. Pathogens associated with aggressive periodontitis, A. actinomycetemcomitans and C. rectus, were more effective than those associated with chronic periodontitis, P. gingivalis and Prev. intermedia, and commensals, S. salivarius and V. atypica, as regards the upregulation of AM and NO production from oral keratinocytes. Interaction between these molecules was also demonstrated with macrophages. Understanding the coordinated regulation of AM and NO production in response to periodontal bacteria may identify

Regulations for the peat production water pollution control; Turvetuotannon vesiensuojeluohjeisto

Energy Technology Data Exchange (ETDEWEB)

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

1996-12-31

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.)

China’s Relations with Portuguese-speaking Countries: A Growing but Unnoticed Relation

Science.gov (United States)

2012-09-01

Brazil and China Expand Satellite Program and African Countries Receive data from CBERS) Ministerio da Ciencia e Tecnologia do Brasil (Brazilian Ministry...Washington D.C. Ministerio da Ciencia e Tecnologia do Brasil (Brazilian Ministry of Science and Technology). “Brasil e China Ampliao Base do Programa CBERS

Food Safety Regulation and Firm Productivity: Evidence from the French Food Industry

OpenAIRE

Requillart, Vincent; Nauges, Celine; Simioni, Michel; Bontemps, Christophe

2012-01-01

The purpose of this article is to assess whether food safety regulations imposed by the European Union in the 2000s may have induced a slow-down in the productivity of firms in the food processing sector. The impact of regulations on costs and productivity has seldom been studied. This article contributes to the literature by measuring productivity change using a panel of French food processing firms for the years 1996 to 2006. To do so, we develop an original iterative testing procedure b...

Regulations applicable to plant food supplements and related products in the European Union.

Science.gov (United States)

Silano, Vittorio; Coppens, Patrick; Larrañaga-Guetaria, Ainhoa; Minghetti, Paola; Roth-Ehrang, René

2011-12-01

This paper deals with the current regulatory and legal settings of traditional plant food supplements and herbal medicinal products in the European Union (EU). Marketing of botanicals in foods and food supplements in the EU is subject to several provisions of food law, which cover aspects of safety, production, labelling and product composition, including the use of additives and maximum levels of contaminants and residues. However, due to limited harmonization at the EU level, specific national regulations adopted at a Member State level also apply and mutual recognition is the mechanism through which such products can be marketed in EU countries other than those of origin. Unlike food supplements, marketing of traditional herbal medicinal products is regulated by an ad hoc Directive (i.e. Directive 2004/24/EC) covering in detail all the relevant aspects of these products, including a facilitated registration procedure at national level. However, by distinguishing traditional herbal medicinal products from plant food supplements and establishing selective marketing modalities for these two product categories, the EU has been confronted with implementation difficulties for traditional herbal medicinal products and a lack of homogeneity in the regulatory approaches adopted in different EU Member States. In fact, currently the nature of the commercial botanical products made available to consumers as traditional medicinal products or food supplements, depends largely on the EU Member State under consideration as a consequence of how competent National Authorities and manufacturing companies interpret and apply current regulations rather than on the intrinsic properties of the botanical products and their constituents. When the EU approach is compared with approaches adopted in some non-European countries to regulate these product categories, major differences become evident.

Use and declaration of additives in meat products: New legal regulations

Directory of Open Access Journals (Sweden)

Vuković Ilija

2005-01-01

Full Text Available The paper presents the more important additives used in meat products, their functional characteristics, the permitted quantities and declaration in keeping with the new legal regulations. Additives important for meat products, according to their functional characteristics, can be preservatives, antioxidants, stabilizers, emulsifiers, emulsifying salts, acidity regulators, sequestrants, thickeners, gelling agents, modified starches, acids, colours, aroma enhancers, packaging gases and coating powders, and it must be pointed out that many additives have several functional characteristics at the same time. In stating additives in the list of contents of a product, the elementary functional characteristic of the additive is given with the E number or name of the additive in brackets; modified starches are declared as „starch" without giving the E number. The declaration does not state the quantity of the additive added to the product, or the biggest permitted quantity of the additive in the given product.

LnqR, a TetR-family transcriptional regulator, positively regulates lacticin Q production in Lactococcus lactis QU 5.

Science.gov (United States)

Iwatani, Shun; Ishibashi, Naoki; Flores, Floirendo P; Zendo, Takeshi; Nakayama, Jiro; Sonomoto, Kenji

2016-09-01

Lacticin Q is an unmodified leaderless bacteriocin produced by Lactococcus lactis QU 5. It has been revealed that the production and self-immunity of lacticin Q are facilitated by a gene cluster lnqQBCDEF The gene for a putative TetR-family transcriptional regulator, termed lnqR, was found nearby the lnqQBCDEF cluster, but its involvement in lacticin Q biosynthesis remained unknown. In this study, we created an LnqR-overexpressing QU 5 recombinant by using lactococcal constitutive promoter P32 The recombinant QU 5 showed enhanced production of and self-immunity to lacticin Q. RT-PCR analysis has revealed that an overexpression of LnqR increases the amounts of lnqQBCDEF transcripts, and these six genes are transcribed as an operon in a single transcriptional unit. Interestingly, LnqR expression and thus lacticin Q production by L. lactis QU 5 was found temperature dependent, while LnzR, an LnqR-homologue, in L. lactis QU 14 was expressed in a similar but not identical manner to LnqR, resulting in dissimilar bacteriocin productivities by these strains. This report demonstrates LnqR as the first TetR-family transcriptional regulator involved in LAB bacteriocin biosynthesis and that, as an exceptional case of TetR-family regulators, LnqR positively regulates the transcription of these biosynthetic genes. © FEMS 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

10 CFR 431.402 - Preemption of State regulations for commercial HVAC & WH products.

Science.gov (United States)

2010-01-01

... 10 Energy 3 2010-01-01 2010-01-01 false Preemption of State regulations for commercial HVAC & WH... regulations for commercial HVAC & WH products. Beginning on the effective date of such standard, an energy conservation standard set forth in this Part for a commercial HVAC & WH product supersedes any State or local...

Evaluation of the California Safer Consumer Products Regulation and the impact on consumers and product manufacturers.

Science.gov (United States)

Cowan, Dallas M; Kingsbury, Tony; Perez, Angela L; Woods, Tyler A; Kovochich, Michael; Hill, Denise S; Madl, Amy K; Paustenbach, Dennis J

2014-02-01

Chemistry enables more than 95% of products in the marketplace. Over the past 20 years, various entities began to generate inventories of chemicals ("chemical watch lists") potentially associated with human or environmental health risks. Some lists included thousands of chemicals, while others listed only a few chemistries with limited properties or toxicological endpoints (e.g., neurotoxicants). Enacted on October 1, 2013, the California Safer Consumer Products Regulation (SCP) utilized data from chemical inventory lists to create one master list. This paper aims to discuss the background and requirements of this regulation. Additionally, we wanted to understand the universe of Candidate Chemicals identified by the Regulation. Data from all 23 chemical lists identified in the SCP Regulation were entered into a database. The most prevalent chemicals among the ∼2900 chemicals are identified, including the most prevalent chemical, lead, appearing on 65% of lists, followed by DEHP (52%), perchloroethylene (48%), and benzene (48%). Our results indicated that the most prevalent Candidate Chemicals were either persistent, bioaccumulative, carcinogenic, or reprotoxic. This regulation will have wide-ranging impact in California and throughout the global supply chain, which is highlighted through selected examples and case studies. Copyright © 2013 Elsevier Inc. All rights reserved.

Uso de imagens orbitais como base de dados para projetos de reforma agrária The use of orbital images as subsidies to agrarian reform projects

Directory of Open Access Journals (Sweden)

Marina de Fátima Vilela

2005-08-01

Full Text Available Análises técnica e econômica foram realizadas em imagens dos sensores IKONOS, TM/Landsat 5, ETM+/Landsat 7 e CCD/CBERS, objetivando a verificação da viabilidade destas como base de dados em projetos de reforma agrária. Essas análises efetuadas e a situação de mercado indicaram que a imagem IKONOS apresenta excelente desempenho técnico, mas o custo de aquisição inviabiliza sua utilização como base de dados para a reforma agrária. A imagem do Landsat 7, com baixo custo de aquisição, apresentou grande viabilidade técnica para fins de reforma agrária. No entanto, a perda do contato com a plataforma Landsat 7 inviabilizou a compra de novas imagens do sensor ETM+. A imagem CCD/CBERS apresentou a segunda maior similaridade com a verdade de campo e o menor índice Kappa para a classificação. Apesar do baixo índice de exatidão para a classificação, as análises de custo, o lançamento do CBERS-2 e a possibilidade de correção dos problemas de radiometria podem tornar as imagens da plataforma CBERS-2 concorrentes de peso no mercado e, ainda, preencher a lacuna deixada pela perda do Landsat 7. A imagem do Landsat 5 apresentou o mais baixo desempenho técnico nas análises efetuadas. Entretanto, seu potencial como base de dados é amplamente reconhecido pelo INCRA, que ainda utiliza tais imagens. O declínio da vida útil do Landsat-5 atribui mais importância ao lançamento do CBERS-2.Technical and economical analyses were performed on IKONOS, Landsat TM 5 and Landsat ETM+ 7 and CCD/CBERS data in order to verify their feasibilities to subsidy agrarian reform projects. Results showed that IKONOS data presented excellent technical viability but its high cost prevents its use. Landsat ETM+ 7 data, with low cost, presented good technical viability, however due to the problems occurring in the satellite operation, its use was also prevented . CCD/CBERS data presented the second best similarity with the ground truth data, although it

Management practices in Australasian ethical investment products: a role for regulation?

DEFF Research Database (Denmark)

Haigh, Matthew; Guthrie, James

2010-01-01

This paper adds to the literatures on socially responsible investment (SRI), investment management, regulation of financial services and social accounting by providing a comprehensive survey of investment methods used in SRI products and regulated social reporting in financial services. Australian...... a four-year period: 2004-2007. These aspects were further examined in 18 case studies. Over the period, diversity and intensity of construction methods had increased both within and between investment managers. The non-standard nature of management consultation used in SRI products, marketing needs...... debates and other public reports. Portfolio construction styles of 86 SRI products managed by 63 financial institutions in Australia and New Zealand were chosen for analysis. Statistical analysis was conducted to identify associations between styles, construction methods and assessment techniques over...

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

International Nuclear Information System (INIS)

Raddum, G.G.; Fjellheim, A.

1993-01-01

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 (10-14 o C). 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)

Transcriptional regulation of genes related to progesterone production.

Science.gov (United States)

Mizutani, Tetsuya; Ishikane, Shin; Kawabe, Shinya; Umezawa, Akihiro; Miyamoto, Kaoru

2015-01-01

Steroid hormones are synthesized from cholesterol in various tissues, mainly in the adrenal glands and gonads. Because these lipid-soluble steroid hormones immediately diffuse through the cells in which they are produced, their secretion directly reflects the activity of the genes related to their production. Progesterone is important not only for luteinization and maintenance of pregnancy, but also as a substrate for most other steroids. Steroidogenic acute regulatory protein (STAR), cytochrome P450 cholesterol side-chain cleavage enzyme (P450scc), and 3β-hydroxysteroid dehydrogenase/Δ(5)-Δ(4) isomerase (3β-HSD) are well-known proteins essential for progesterone production. In addition to them, glutathione S-transferase A1-1 and A3-3 are shown to exert Δ(5)-Δ(4) isomerization activity to produce progesterone in a cooperative fashion with 3β-HSD. 5-Aminolevulinic acid synthase 1, ferredoxin 1, and ferredoxin reductase also play a role in steroidogenesis as accessory factors. Members of the nuclear receptor 5A (NR5A) family (steroidogenic factor 1 and liver receptor homolog 1) play a crucial role in the transcriptional regulation of these genes. The NR5A family activates these genes by binding to NR5A responsive elements present within their promoter regions, as well as to the elements far from their promoters. In addition, various NR5A-interacting proteins including peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α), nuclear receptor subfamily 0, group B, member 1 (DAX-1), and CCAAT/enhancer-binding proteins (C/EBP) are involved in the transcription of NR5A target genes and regulate the transcription either positively or negatively under both basal and tropic hormone-stimulated conditions. In this review, we describe the transcriptional regulation of genes related to progesterone production.

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

Directory of Open Access Journals (Sweden)

Anna Brinch

2016-02-01

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.

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

Science.gov (United States)

Brinch, Anna; Hansen, Steffen Foss; Hartmann, Nanna B; Baun, Anders

2016-02-16

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.

Effects of growth regulator herbicide on downy brome (Bromus tectorum) seed production

Science.gov (United States)

Previous research showed growth regulator herbicides, such as picloram and aminopyralid, have a sterilizing effect on Japanese brome (Bromus japonicus Thunb.) that can reduce this invasive annual grass’s seed production nearly 100%. This suggests growth regulators might be used to control invasive ...

Basic Substances under EU Pesticide Regulation: An Opportunity for Organic Production?

Directory of Open Access Journals (Sweden)

Patrice A. Marchand

2017-02-01

Full Text Available Some of the active substances allowed in organic production are now approved as basic sub- stances under the EU plant protection products regulation. Previously, all organic farming permitted active substances were approved as conventional plant protection products. In accordance with the criteria of Article 23 of the EU regulation (EC No 1107/2009, basic substances are granted without maximum residue limits and have a good prospect for being included in Annex II of organic farming Regulation (EC 889/2008. In fact, most of them are already permitted in organic farming. At this stage, it seems desirable to organize applications in order to avoid duplications and to clarify strategy across Europe. This organization should be planned in order to identify corresponding knowledge and data from field experiments, and to further constitute the most crucial issues related to organic production. A work of this nature was initially supported by IFOAM-EU for lecithin, calcium hydroxide and Quassia extract. The Institut Technique de l’Agriculture Biologique (ITAB was previously engaged in a large-scale approval plan motivated by the continuous demand for the regularization of compounds/substances already in use and has a mandate for testing and approving new compatible substances. Thus, the horsetail extract (Equisetum arvense was the first approved basic substance and ITAB has obtained 11 of the 15 basic substances approved at the EU level.

Normalization of NDVI from Different Sensor System using MODIS Products as Reference

International Nuclear Information System (INIS)

Wenxia, Gan; Liangpei, Zhang; Wei, Gong; Huanfeng, Shen

2014-01-01

Medium Resolution NDVI(Normalized Difference Vegetation Index) from different sensor systems such as Landsat, SPOT, ASTER, CBERS and HJ-1A/1B satellites provide detailed spatial information for studies of ecosystems, vegetation biophysics, and land cover. Limitation of sensor designs, cloud contamination, and sensor failure highlighted the need to normalize and integrate NDVI from multiple sensor system in order to create a consistent, long-term NDVI data set. In this paper, we used a reference-based method for NDVI normalization. And present an application of this approach which covert Landsat ETM+ NDVI calculated by digital number (NDVI DN ) to NDVI calculated by surface reflectance (NDVI SR ) using MODIS products as reference, and different cluster was treated differently. Result shows that this approach can produce NDVI with highly agreement to NDVI calculated by surface reflectance from physical approaches based on 6S (Second Simulation of the satellite Signal in the Solar Spectrum). Although some variability exists, the cluster specified reference based approach shows considerable potential for NDVI normalization. Therefore, NDVI products in MODIS era from different sources can be combined for time-series analysis, biophysical parameter retrievals, and other downstream analysis

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

Lifescience Database Archive (English)

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 produ

Engineering of an Lrp family regulator SACE_Lrp improves erythromycin production in Saccharopolyspora erythraea.

Science.gov (United States)

Liu, Jing; Chen, Yunfu; Wang, Weiwei; Ren, Min; Wu, Panpan; Wang, Yansheng; Li, Changrun; Zhang, Lixin; Wu, Hang; Weaver, David T; Zhang, Buchang

2017-01-01

Leucine-responsive regulatory proteins (Lrps) are a group of transcriptional regulators that regulate diverse cellular processes in bacteria and archaea. However, the regulatory role of Lrps in antibiotic biosynthesis remains poorly understood. In this study, we show that SACE_5388, an Lrp family regulator named as SACE_Lrp, is an efficient regulator for transporting and catabolizing branched-chain amino acids (BCAAs), playing an important role in regulating erythromycin production in Saccharopolyspora erythraea. SACE_Lrp directly controlled the expression of the divergently transcribed SACE_5387-5386 operon putatively encoding a BCAA ABC transporter by interacting with the intergenic region between SACE_Lrp and SACE_5387 (SACE_Lrp-5387-int), and indirectly controlled the expression of ilvE putatively encoding an aminotransferase catabolizing BCAAs. BCAA catabolism is one source of the precursors for erythromycin biosynthesis. Lysine and arginine promoted the dissociation of SACE_Lrp from SACE_Lrp -5387-int, whereas histidine increased their binding. Gene disruption of SACE_Lrp (ΔSACE_Lrp) in S. erythraea A226 resulted in a 25% increase in erythromycin production, while overexpression of SACE_5387-5386 in A226 enhanced erythromycin production by 36%. Deletion of SACE_Lrp (WBΔSACE_Lrp) in the industrial strain S. erythraea WB enhanced erythromycin production by 19%, and overexpression of SACE_5387-5386 in WBΔSACE_Lrp (WBΔSACE_Lrp/5387-5386) increased erythromycin production by 41% compared to WB. Additionally, supplement of 10mM valine to WBΔSACE_Lrp/5387-5386 culture further increased total erythromycin production up to 48%. In a 5-L fermenter, the erythromycin accumulation in the engineered strain WBΔSACE_Lrp/5387-5386 with 10mM extra valine in the industrial culture media reached 5001mg/L, a 41% increase over 3503mg/L of WB. These insights into the molecular regulation of antibiotic biosynthesis by SACE_Lrp in S. erythraea are instrumental in increasing

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

Directory of Open Access Journals (Sweden)

Philippe eVan Wilder

2012-02-01

Full Text Available The market authorisation procedure for medicinal products for human use is relying on their demonstrated efficacy, safety and pharmaceutical quality. This applies to all medicinal products whether of chemical or biological origin. Since October 2009, the first advanced therapy medicinal product (ATMP has been authorised through the centralized procedure. ATMPs are gene therapy medicinal products, somatic cell therapy medicinal products or tissue-engineered products.An appropriate ATMP- Regulation is dealing with ATMP requirements.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.

Advanced Therapy Medicinal Products and Exemptions to the Regulation 1394/2007: How Confident Can We be? An Exploratory Analysis.

Science.gov (United States)

Van Wilder, Philippe

2012-01-01

The market authorization procedure for medicinal products for human use is relying on their demonstrated efficacy, safety, and pharmaceutical quality. This applies to all medicinal products whether of chemical or biological origin. Since October 2009, the first advanced therapy medicinal product (ATMP) has been authorized through the centralized procedure. ATMPs are gene therapy medicinal products, somatic cell therapy medicinal products or tissue-engineered products. An appropriate ATMP - Regulation is dealing with ATMP requirements. 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 December 30, 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.

Biosphere science news roundup. The Center for Biospheric Education and Research

Science.gov (United States)

Cotten, J H

1994-01-01

The Center for Biospheric Education and Research (CBER) is an exciting and truly unique addition to The Huntsville-Madison County Botanical Garden. The mission of CBER is to increase the knowledge and understanding of closed ecological life support systems, including both natural and man-made biospheres. Its primary emphasis will be on the Earth biosphere with particular attention to the role of plants in maintaining a balanced environment. Secondary emphasis will be on the space station and lunar habitation biospheres, both of which employ plants for environmental control, food, and aesthetics. CBER will serve as a catalyst providing both a forum and a facility for research, education, and display of methodologies and technologies relevant to the creation and maintenance of such biospheric systems.

Bringing smart pills to market: FDA regulation of ingestible drug/device combination products.

Science.gov (United States)

Avery, Matthew; Liu, Dan

2011-01-01

Imagine a pill that, after you swallow it, can track its position in your body. Or imagine a pill that can transmit a message to a doctor to tell him that you have taken your bitter medicine. Pills like this already exist. These so-called smart pills are an emerging type of medical therapy. However, this nascent technology has yet to reach the market and developers of these novel therapies face significant regulatory challenges. This article predicts how the Food and Drug Administration will regulate smart pills and shows how the current regulatory regime is inadequate. The article then proposes modifying the current regulatory regime to encourage development of smart pills and other innovative combination products by: (1) regulating combination products based on their "novel mode of action" rather than their "primary mode of action," (2) creating a marketing approval pathway specifically for combination products, and (3) eliminating regulations that require sponsors to get marketing approval from multiple centers within FDA and providing regulatory guidance specifically for ingestible drug/device combination products.

Chromatin landscaping in algae reveals novel regulation pathway for biofuels production

Energy Technology Data Exchange (ETDEWEB)

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

2013-02-19

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.

Regulated production of free radicals by the mitochondrial electron transport chain: Cardiac ischemic preconditioning.

Science.gov (United States)

Matsuzaki, Satoshi; Szweda, Pamela A; Szweda, Luke I; Humphries, Kenneth M

2009-11-30

Excessive production of free radicals by mitochondria is associated with, and likely contributes to, the progression of numerous pathological conditions. Nevertheless, the production of free radicals by the mitochondria may have important biological functions under normal or stressed conditions by activating or modulating redox-sensitive cellular signaling pathways. This raises the intriguing possibility that regulated mitochondrial free radical production occurs via mechanisms that are distinct from pathologies associated with oxidative damage. Indeed, the capacity of mitochondria to produce free radicals in a limited manner may play a role in ischemic preconditioning, the phenomenon whereby short bouts of ischemia protect from subsequent prolonged ischemia and reperfusion. Ischemic preconditioning can thus serve as an important model system for defining regulatory mechanisms that allow for transient, signal-inducing, production of free radicals by mitochondria. Defining how these mechanism(s) occur will provide insight into therapeutic approaches that minimize oxidative damage without altering normal cellular redox biology. The aim of this review is to present and discuss evidence for the regulated production of superoxide by the electron transport chain within the ischemic preconditioning paradigm of redox regulation.

The Canadian Natural Health Products (NHP) regulations: industry compliance motivations.

Science.gov (United States)

Laeeque, Hina; Boon, Heather; Kachan, Natasha; Cohen, Jillian Clare; D'Cruz, Joseph

2007-06-01

This qualitative study explores corporations' motivations to comply with new natural health products (NHP) Regulations in Canada. Interviews were conducted with representatives from 20 Canadian NHP companies. Findings show that the rationale for compliance differs for large compared to small and medium-sized enterprises (SMEs). Large firms are motivated to comply with the regulations because of the deterrent fear of negative media coverage, social motivations, ability to comply and maintaining a competitive market advantage. In contrast, SMEs are motivated to comply due to the deterrent fear of legal prosecution and a sense of duty.

Mangotoxin production of Pseudomonas syringae pv. syringae is regulated by MgoA.

Science.gov (United States)

Carrión, Víctor J; van der Voort, Menno; Arrebola, Eva; Gutiérrez-Barranquero, José A; de Vicente, Antonio; Raaijmakers, Jos M; Cazorla, Francisco M

2014-02-21

The antimetabolite mangotoxin is a key factor in virulence of Pseudomonas syringae pv. syringae strains which cause apical necrosis of mango trees. Previous studies showed that mangotoxin biosynthesis is governed by the mbo operon. Random mutagenesis led to the identification of two other gene clusters that affect mangotoxin biosynthesis. These are the gacS/gacA genes and mgo operon which harbors the four genes mgoBCAD. The current study shows that disruption of the nonribosomal peptide synthetase (NRPS) gene mgoA resulted in loss of mangotoxin production and reduced virulence on tomato leaves. Transcriptional analyses by qPCR and promoter reporter fusions revealed that mbo expression is regulated by both gacS/gacA and mgo genes. Also, expression of the mgo operon was shown to be regulated by gacS/gacA. Heterologous expression under the native promoter of the mbo operon resulted in mangotoxin production in non-producing P. syringae strains, but not in other Pseudomonas species. Also introduction of the mbo and mgo operons in nonproducing P. protegens Pf-5 did not confer mangotoxin production but did enhance transcription of the mbo promoter. From the data obtained in this study, we conclude that both mbo and mgo operons are under the control of the gacS/gacA two-component system and that the MgoA product acts as a positive regulator of mangotoxin biosynthesis.

Stakeholders' perspectives on the regulation and integration of complementary and alternative medicine products in Lebanon: a qualitative study

Science.gov (United States)

2011-01-01

Background The regulation of the markets for Complementary and Alternative Medicine (CAM) products presents a global challenge. There is a dearth of studies that have examined or evaluated the regulatory policies of CAM products in the Eastern Mediterranean Region (EMR). We investigate the regulatory frameworks and the barriers for the proper regulation and integration of CAM products in Lebanon, as an example of an EMR country with a weak public infrastructure. Methods We utilized a qualitative study design involving a series of semi-structured interviews with stakeholders of the CAM market in Lebanon. Snowball sampling was used to identify interviewees; interviews continued until the "saturation" point was reached. A total of 16 interviews were carried out with decision makers, representatives of professional associations, academic researchers, CAM product importers, policy makers and a media representative. Interviews were transcribed and thematic analysis of scripts was carried out. Results There was a consensus among all stakeholders that the regulation of the market for CAM products in Lebanon needs to be strengthened. Thematic analysis identified a number of impediments jeopardizing the safety of public consumption and hindering the integration of CAM therapies into mainstream medicine; including: weak infrastructure, poor regulation, ineffective policies and politics, weak CAM awareness and sub-optimal coordination and cooperation among stakeholders. With respect to policy instruments, voluntary instruments (self regulation) were deemed ineffective by stakeholders due to poor awareness of both users and providers on safe use of CAM products. Stakeholders' rather recommended the adoption of a combination of mixed (enhancing public awareness and integration of CAM into medical and nursing curricula) and compulsory (stricter governmental regulation) policy instruments for the regulation of the market for CAM products. Conclusions The current status quo with

'No, the government doesn't need to, it's already self-regulated': a qualitative study among vape shop operators on perceptions of electronic vapor product regulation.

Science.gov (United States)

Nayak, Pratibha; Barker, Dianne C; Huang, Jidong; Kemp, Catherine B; Wagener, Theodore L; Chaloupka, Frank

2018-03-26

While the market share of electronic vapor products (EVPs), sold primarily through vape shops and other outlets, has increased rapidly, these products remained largely unregulated until 2016. This study, conducted prior to announcement of the deeming regulations, provides insights into vape shop operator attitudes toward potential government regulations of EVPs. In 2015, we conducted 37 in-person interviews of vape shop operators across nine US cities. Shops were identified through extensive web-searches. We used QSR International's NVivo 11 qualitative data analysis software to analyze the transcripts. Many vape shop operators viewed regulations requiring safe production of e-liquids, child-resistant bottles and listing e-juice ingredients as acceptable. They disagreed with the elimination of free samples and bans on flavored e-liquid sales, which generate significant revenue for their stores. Many held negative perceptions of pre-market review of new product lines and EVP-specific taxes. All agreed that EVPs should not be sold to minors, but most felt that owners should not be fined if minors visited vape shops. Findings from this study offer insights into the acceptability of proposed regulations, as well as barriers to effective regulation implementation.

Regulation of advanced therapy medicinal products in Europe and the role of academia.

Science.gov (United States)

Pearce, Kim F; Hildebrandt, Martin; Greinix, Hildegard; Scheding, Stefan; Koehl, Ulrike; Worel, Nina; Apperley, Jane; Edinger, Matthius; Hauser, Andrea; Mischak-Weissinger, Eva; Dickinson, Anne M; Lowdell, Mark W

2014-03-01

Advanced therapy medicinal products (ATMP) are gene therapy, somatic cell therapy or tissue-engineered products regulated under (EC) No. 1394/2007 to ensure their free movement within the European Union while guaranteeing the highest level of health protection for patients. Academic good manufacturing practice (GMP) centers are major contributors in the development of ATMPs and this study assessed the impact of regulations on them. European academic and non-industrial facilities (n = 747) were contacted, and a representative sample of 50 replied to a detailed questionnaire. Experienced centres were further selected in every Member State (MS) for semi-structured interviews. Indicators of ATMP production and development success were statistically assessed, and opinions about directive implementation were documented. Facilities experienced in manufacturing cell therapy transplant products are the most successful in developing ATMPs. New centres lacking this background struggle to enter the field, and there remains a shortage of facilities in academia participating in translational research. This is compounded by heterogeneous implementation of the regulations across MS. GMP facilities successfully developing ATMPs are present in all MS. However, the implementation of regulations is heterogeneous between MS, with substantial differences in the definition of ATMPs and in the approved manufacturing environment. The cost of GMP compliance is underestimated by research funding bodies. This is detrimental to development of new ATMPs and commercialization of any that are successful in early clinical trials. Academic GMP practitioners should strengthen their political visibility and contribute to the development of functional and effective European Union legislation in this field. Copyright © 2014 International Society for Cellular Therapy. All rights reserved.

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

Energy Technology Data Exchange (ETDEWEB)

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

2004-09-01

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.

Impact of Environmental Factors on the Regulation of Cyanotoxin Production

Science.gov (United States)

Boopathi, Thangavelu; Ki, Jang-Seu

2014-01-01

Cyanobacteria are capable of thriving in almost all environments. Recent changes in climatic conditions due to increased human activities favor the occurrence and severity of harmful cyanobacterial bloom all over the world. Knowledge of the regulation of cyanotoxins by the various environmental factors is essential for effective management of toxic cyanobacterial bloom. In recent years, progress in the field of molecular mechanisms involved in cyanotoxin production has paved the way for assessing the role of various factors on the cyanotoxin production. In this review, we present an overview of the influence of various environmental factors on the production of major group of cyanotoxins, including microcystins, nodularin, cylindrospermopsin, anatoxins and saxitoxins. PMID:24967641

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

International Nuclear Information System (INIS)

Eriksson, Clas

2004-01-01

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

Efficient L-Alanine Production by a Thermo-Regulated Switch in Escherichia coli.

Science.gov (United States)

Zhou, Li; Deng, Can; Cui, Wen-Jing; Liu, Zhong-Mei; Zhou, Zhe-Min

2016-01-01

L-Alanine has important applications in food, pharmaceutical and veterinary and is used as a substrate for production of engineered thermoplastics. Microbial fermentation could reduce the production cost and promote the application of L-alanine. However, the presence of L-alanine significantly inhibit cell growth rate and cause a decrease in the ultimate L-alanine productivity. For efficient L-alanine production, a thermo-regulated genetic switch was designed to dynamically control the expression of L-alanine dehydrogenase (alaD) from Geobacillus stearothermophilus on the Escherichia coli B0016-060BC chromosome. The optimal cultivation conditions for the genetically switched alanine production using B0016-060BC were the following: an aerobic growth phase at 33 °C with a 1-h thermo-induction at 42 °C followed by an oxygen-limited phase at 42 °C. In a bioreactor experiment using the scaled-up conditions optimized in a shake flask, B0016-060BC accumulated 50.3 g biomass/100 g glucose during the aerobic growth phase and 96 g alanine/100 g glucose during the oxygen-limited phase, respectively. The L-alanine titer reached 120.8 g/l with higher overall and oxygen-limited volumetric productivities of 3.09 and 4.18 g/l h, respectively, using glucose as the sole carbon source. Efficient cell growth and L-alanine production were reached separately, by switching cultivation temperature. The results revealed the application of a thermo-regulated strategy for heterologous metabolic production and pointed to strategies for improving L-alanine production.

The lipid accumulation product as a useful index for identifying abnormal glucose regulation in young Korean women.

Science.gov (United States)

Oh, J-Y; Sung, Y-A; Lee, H J

2013-04-01

The lipid accumulation product, a combination of waist circumference and triglycerides concentration, has been suggested as a better marker for abnormal glucose regulation than BMI. We aimed to compare the lipid accumulation product and BMI as useful markers for abnormal glucose regulation in young Korean women. The lipid accumulation product was calculated using the formula [waist circumference (cm) - 58] × triglycerides (mmol/l). Glucose tolerance status was determined using a 75-g oral glucose tolerance test in 2810 Korean women aged 18-39 years from the general population. The prevalence of abnormal glucose regulation was 6.8% (isolated impaired fasting glucose 1.8%, isolated impaired glucose tolerance 4.0%; impaired fasting glucose + impaired glucose tolerance 0.4% and diabetes mellitus 0.6%). According to the quintile distributions of the lipid accumulation product and BMI, women with a lipid accumulation product quintile greater than their BMI quintile exhibited significantly greater areas under the curve and higher levels of 2-h post-load glucose, insulin, homeostasis model analysis of insulin resistance and lipid profiles than did women with a BMI quintile greater than their lipid accumulation product quintile. Multiple logistic regression revealed that the lipid accumulation product exhibited a higher odds ratio for abnormal glucose regulation than did BMI after adjusting for age, systolic blood pressure, HDL cholesterol, previous history of gestational diabetes and family history of diabetes (odds ratios 3.5 and 2.6 of the highest vs. the lowest quintiles of lipid accumulation product and BMI, respectively). The lipid accumulation product could be useful for identifying the young Korean women with abnormal glucose regulation. © 2012 The Authors. Diabetic Medicine © 2012 Diabetes UK.

The global regulator LaeA controls production of citric acid and endoglucanases in Aspergillus carbonarius

DEFF Research Database (Denmark)

Linde, Tore; Zoglowek, Marta; Lübeck, Mette

2016-01-01

The global regulatory protein LaeA is known for regulating the production of many kinds of secondary metabolites in Aspergillus species, as well as sexual and asexual reproduction, and morphology. In Aspergillus carbonarius, it has been shown that LaeA regulates production of ochratoxin. We have ...

Increasing Malonyl-CoA Derived Product through Controlling the Transcription Regulators of Phospholipid Synthesis in Saccharomyces cerevisiae.

Science.gov (United States)

Chen, Xiaoxu; Yang, Xiaoyu; Shen, Yu; Hou, Jin; Bao, Xiaoming

2017-05-19

Malonyl-CoA is a precursor of a variety of compounds such as polyketides and flavonoids. In Saccharomyces cerevisiae, malonyl-CoA concentration is tightly regulated and therefore maintained at a very low level, limiting the production of malonyl-CoA-derived chemicals. Here we manipulated the phospholipid synthesis transcriptional regulators to control the malonyl-CoA levels and increase the downstream product. Through manipulating different regulators including Ino2p, Ino4p, Opi1p, and a series of synthetic Ino2p variants, combining with studying the inositol and choline effect, the engineered strain achieved a 9-fold increase of the titer of malonyl-CoA-derived product 3-hydroxypropionic acid, which is among the highest improvement relative to previously reported strategies. Our study provides a new strategy to regulate malonyl-CoA availability and will contribute to the production of other highly valued malonyl-CoA-derived chemicals.

Smokers' reactions to FDA regulation of tobacco products: Findings from the 2009 ITC United States survey

Directory of Open Access Journals (Sweden)

Fix Brian V

2011-12-01

Full Text Available Abstract Background On June 22, 2009, the US FDA was granted the authority to regulate tobacco products through the Family Smoking Prevention and Tobacco Control Act (FSPTCA. The intent is to improve public health through regulations on tobacco product marketing and tobacco products themselves. This manuscript reports baseline data on smokers' attitudes and beliefs on specific issues relevant to the FSPTCA. Method Between November 2009 and January 2010, a telephone survey among a nationally representative sample of n = 678 smokers in the US was performed as part of the International Tobacco Control (ITC United States Survey. Participants answered a battery of questions on their attitudes and beliefs about aspects of the FSPTCA. Results Most smokers were unaware of the new FDA tobacco regulations. Smokers indicated support for banning cigarette promotion and nearly a quarter supported requiring tobacco companies to sell cigarettes in plain packaging. Seventy two percent of smokers supported reducing nicotine levels to make cigarettes less addictive if nicotine was made easily available in non-cigarette form. Conclusion Most smokers were limited in their understanding of efforts to regulate tobacco products in general. Smokers were supportive of efforts to better inform the public about health risks, restrict advertising, and make tobacco products less addictive.

Carboxymethyl-cellulase from Erwina chrysanthemi. I. Production and regulation of extracellular carboxymethyl-cellulase

Energy Technology Data Exchange (ETDEWEB)

Boyer, M.H.; Chambost, J.P.; Magnan, M.; Cattaneo, J.

1984-01-01

Erwinia chrysanthemi strain 3665 growing aerobically in a mineral salts medium containing various carbon sources constitutively secreted low levels of carboxymethyl-cellulase activity. Increased production of this activity was triggered by conditions which reduced the growth rate. The results obtained with continuous culture suggested that this production was controlled by a mechanism similar to catabolite repression. However, other factors might be implicated in the regulation of cellulase production.

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

Directory of Open Access Journals (Sweden)

Xu Boqun

2013-02-01

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.

State regulation of the biotechnology (GM agricultural products: analysis of different approaches in the world

Directory of Open Access Journals (Sweden)

Irina Vladimirovna Yakovleva

2015-06-01

Full Text Available Although GM crops are cultivated on 175 million hectares in 27 countries, the regulation of agricultural biotechnology is in its becoming. In the future, many countries, of course, will lead to market biotech products, and the main focus will be biosafety issues for humans and the environment. Some countries have special regulatory mechanisms, others do not have the original national regulatory system, but their actions are under the provisions of international treaties for the production and handling of GM products. What are the main components of a strict but not stifling regulatory system? What are the disadvantages of existing systems? The article presents an overview of the state regulation systems of biotech agricultural products in the US, the EU, Argentina, South Africa and Brazil.

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

Science.gov (United States)

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

2015-01-01

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 2002 (Regulation (EC) No 178/2002). The empirical application uses panel data of Spanish meat, dairy, and oils and fats industries over the period 1996-2011. The results suggest that in the oils and fats industry the impact of food regulation on dynamic productivity growth is negative initially and then positive over the long run. In contrast, the opposite pattern is observed for the meat and dairy processing industries. The results further imply that firms in the meat processing and oils and fats industries face similar impacts of food safety regulation on dynamic technical change, dynamic inefficiency change and dynamic scale inefficiency change.

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

Science.gov (United States)

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

2015-01-01

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 2002 (Regulation (EC) No 178/2002). The empirical application uses panel data of Spanish meat, dairy, and oils and fats industries over the period 1996-2011. The results suggest that in the oils and fats industry the impact of food regulation on dynamic productivity growth is negative initially and then positive over the long run. In contrast, the opposite pattern is observed for the meat and dairy processing industries. The results further imply that firms in the meat processing and oils and fats industries face similar impacts of food safety regulation on dynamic technical change, dynamic inefficiency change and dynamic scale inefficiency change. PMID:26057878

Thyrotropin (TSH) regulates triiodothyronine (T3) production in the unicellular Tetrahymena.

Science.gov (United States)

Csaba, G; Pállinger, Eva

2011-09-01

The aim of the experiments was to study the regulation of triiodothyronine (T3) production in the unicellular Tetrahymena. Untreated and troph-hormone treated specimen were prepared and in different timepoints T3 content was measured and compared by immunocytochemical flow cytometry. 0.1 or 0.001 IU TSH in tryptone-yeast medium stimulated T3 synthesis at 10, 20, 30 min, but does not stimulate after 1 h. The overlapping gonadotropic hormone (GTH) also did it, however only at 10 min. In Losina salt solution (physiological for Tetrahymena) the effect was weaker, however outer amino acid source was not absolutely needed for the production of the hormone. The results show that the TSH regulation of thyroid hormone synthesis (storage, secretion) and troph-hormone overlap can be deduced to a unicellular level. This may allow the hypothesis that the endocrine mechanisms proved at a low level of phylogeny are preserved for the higher ranked organisms.

Regulation (EC No 1901/2006 on medicinal products for paediatric use & clinical research in vulnerable populations

Directory of Open Access Journals (Sweden)

Lehmann Birka

2008-12-01

Full Text Available Abstract Before any medicinal product is authorised for use in adults, it must undergo extensive pharmaceutical consistency and stability tests, toxicological tests and clinical trials to ensure that it is of high quality, safe and effective. The same approach may not always be applied to medicinal products used to treat children. Studies showed that over 50% of the medicinal products used in children may not have been tested for use in this age group. The absence of suitable authorised medicinal products to treat conditions in children results from the fact that pharmaceutical companies do not adapt medicinal products to the needs of the paediatric population. This leaves health care professionals with no alternative other than to use medicinal products "off-label" and to use unauthorised products with the associated risks of inefficacy and/or adverse reactions. The Regulation (EC No 1901/2006 sets up a system of requirements, rewards and incentives, together with horizontal measures, to ensure that medicinal products are researched, developed and authorised to meet the therapeutic needs of children. The Regulation is addressed to: 1. The pharmaceutical industry by setting out the legal framework for receiving rewards and incentives by conducting clinical trials in the paediatric population. 2. The Member States to set out to support research into, and the development and availability of, medicinal products for paediatric use. 3. The Community as funds for research into medicinal products for the paediatric population shall be provided for in the Community budget in order to support studies relating to medicinal products or active substances not covered by a patent or a supplementary protection certificate. The legal framework for conducting clinical trials, including children/minors, is set up in Directive 2001/20/EC, the Clinical Trials Directive (CTD, for the European Union (EU. The CTD establishes specific provisions regarding conduct of

Regulation of cerebrospinal fluid production by caffeine consumption

Directory of Open Access Journals (Sweden)

Yoon Sik

2009-09-01

Full Text Available Abstract Background Caffeine is the most commonly consumed psycho-stimulant in the world. The effects of caffeine on the body have been extensively studied; however, its effect on the structure of the brain has not been investigated to date. Results In the present study we found that the long-term consumption of caffeine can induce ventriculomegaly; this was observed in 40% of the study rats. In the caffeine-treated rats with ventriculomegaly, there was increased production of CSF, associated with the increased expression of Na+, K+-ATPase and increased cerebral blood flow (CBF. In contrast to the chronic effects, acute treatment with caffeine decreased the production of CSF, suggesting 'effect inversion' associated with caffeine, which was mediated by increased expression of the A1 adenosine receptor, in the choroid plexus of rats chronically treated with caffeine. The involvement of the A1 adenosine receptor in the effect inversion of caffeine was further supported by the induction of ventriculomegaly and Na+, K+-ATPase, in A1 agonist-treated rats. Conclusion The results of this study show that long-term consumption of caffeine can induce ventriculomegaly, which is mediated in part by increased production of CSF. Moreover, we also showed that adenosine receptor signaling can regulate the production of CSF by controlling the expression of Na+, K+-ATPase and CBF.

Productivity growth and price regulation of Slovenian water distribution utilities

Directory of Open Access Journals (Sweden)

Jelena Zorić

2010-06-01

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.

TIM-1 signaling in B cells regulates antibody production

International Nuclear Information System (INIS)

Ma, Juan; Usui, Yoshihiko; Takeda, Kazuyoshi; Harada, Norihiro; Yagita, Hideo; Okumura, Ko; Akiba, Hisaya

2011-01-01

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.

TIM-1 signaling in B cells regulates antibody production

Energy Technology Data Exchange (ETDEWEB)

Ma, Juan [Department of Immunology, Juntendo University, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421 (Japan); Usui, Yoshihiko [Department of Immunology, Juntendo University, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421 (Japan); Department of Ophthalmology, Tokyo Medical University, 6-7-1 Nishi-shinjuku-ku, Tokyo 160-0023 (Japan); Takeda, Kazuyoshi [Department of Immunology, Juntendo University, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421 (Japan); Harada, Norihiro [Department of Immunology, Juntendo University, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421 (Japan); Department of Respiratory Medicine, Juntendo University, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421 (Japan); Research Institute for Diseases of Old Ages, Juntendo University, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421 (Japan); Yagita, Hideo; Okumura, Ko [Department of Immunology, Juntendo University, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421 (Japan); Akiba, Hisaya, E-mail: hisaya@juntendo.ac.jp [Department of Immunology, Juntendo University, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421 (Japan)

2011-03-11

Highlights: {yields} TIM-1 is highly expressed on anti-IgM + anti-CD40-stimulated B cells. {yields} Anti-TIM-1 mAb enhanced proliferation and Ig production on activated B cell in vitro. {yields} 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{sup +} anti-CD28-stimulated CD4{sup +} 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.

Impact of Environmental Regulation and Technical Progress on Industrial Carbon Productivity: An Approach Based on Proxy Measure

Directory of Open Access Journals (Sweden)

Huan Zhang

2016-08-01

Full Text Available This research aims to study the main influencing factors of China’s industrial carbon productivity by incorporating environmental regulation and technical progress into an econometric model. The paper focuses on data from 35 of China’s industrial sectors and covers the period from 2006 to 2014, in order to examine the impact of environmental regulation and technical progress on carbon productivity. Methods applied include panel fixed effect model, panel random effect model and two stage least squares with instrumental variables (IV-2SLS. The effect of environmental regulation and technical progress has industrial heterogeneity. The paper subdivides industrial sectors into capital and technology intensive, resource intensive and labor intensive sectors according to factor intensiveness. The estimation results of the subgroups have uncovered that for capital and technology intensive and resource intensive sectors, environmental regulation has a more significant impact than technical progress; while for labor intensive sectors, innovation more significantly influences carbon productivity. In addition, foreign direct investment (FDI and industrialization level facilitate improving carbon productivity for the full sample. By contrast, industrial structure inhibits the overall industrial carbon productivity. The industry-specific results indicate that for capital and technology intensive sectors, optimizing of the industrial structure can improve carbon productivity; for resource intensive sectors, FDI and energy consumption structure should be emphasized more; for labor intensive sectors, industrialization levels help enhance carbon productivity. Finally the industrial sector-specific policy suggestions are proposed.

Reproductive toxicity of a mixture of regulated drinking-water disinfection by-products in a multigenerational rat bioassay

Science.gov (United States)

BACKGROUND:Trihalomethanes (THMs) and haloaretic acids (HAAs) are regulated disinfection by-products (DBPs); their joint reproductive toxicity in drinking water is unknown.OBJECTIVE: We aimed to evaluate a drinking water mixture of the four regulated THMs and five regulated HAAs ...

Regulation of hydrogen production by Enterobacter aerogenes by external NADH and NAD{sup +}

Energy Technology Data Exchange (ETDEWEB)

Zhang, Chong; Ma, Kun; Xing, Xin-Hui [Department of Chemical Engineering, Tsinghua University, Beijing 100084 (China)

2009-02-15

Experiments involving the addition of external nicotinamide adenine dinucleotide, reduced form (NADH) or nicotinamide adenine dinucleotide (NAD{sup +}) have been designed to examine how the hydrogen in Enterobacter aerogenes is liberated by NADH or NAD{sup +}. The addition of external NADH or NAD{sup +} was found to regulate hydrogen production by E. aerogenes in resting cells, batch cultures, and chemostat cultures. Particularly in chemostat cultivation, with the external addition of NADH, hydrogen production via the NADH pathway was decreased, while that via the formate pathway was increased; in the end, the overall hydrogen p was decreased. The addition of NAD{sup +}, on the other hand, gave the opposite results. The membrane-bound hydrogenase was found to play a central role in regulating hydrogen production. The occurrence of NADH oxidation (NAD{sup +} reduction) on the cell membrane resulted in an electron flow across the membrane; this changed the oxidation state and metabolic pattern of the cells, which eventually affected the hydrogen evolution. (author)

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

DEFF Research Database (Denmark)

Gluud, Christian; Kubiak, Christine; Whitfield, Kate

2012-01-01

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....

DasR is a pleiotropic regulator required for antibiotic production, pigment biosynthesis, and morphological development in Saccharopolyspora erythraea.

Science.gov (United States)

Liao, Cheng-Heng; Xu, Ya; Rigali, Sébastien; Ye, Bang-Ce

2015-12-01

The GntR-family transcription regulator, DasR, was previously identified as pleiotropic, controlling the primary amino sugar N-acetylglucosamine (GlcNAc) and chitin metabolism in Saccharopolyspora erythraea and Streptomyces coelicolor. Due to the remarkable regulatory impact of DasR on antibiotic production and development in the model strain of S. coelicolor, we here identified and characterized the role of DasR to secondary metabolite production and morphological development in industrial erythromycin-producing S. erythraea. The physiological studies have shown that a constructed deletion of dasR in S. erythraea resulted in antibiotic, pigment, and aerial hyphae production deficit in a nutrient-rich condition. DNA microarray assay, combined with quantitative real-time reverse transcription PCR (qRT-PCR), confirmed these results by showing the downregulation of the genes relating to secondary metabolite production in the dasR null mutant. Notably, electrophoretic mobility shift assays (EMSA) showed DasR as being the first identified regulator that directly regulates the pigment biosynthesis rpp gene cluster. In addition, further studies indicated that GlcNAc, the major nutrient signal of DasR-responsed regulation, blocked secondary metabolite production and morphological development. The effects of GlcNAc were shown to be caused by DasR mediation. These findings demonstrated that DasR is an important pleiotropic regulator for both secondary metabolism and morphological development in S. erythraea, providing new insights for the genetic engineering of S. erythraea with increased erythromycin production.

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

KAUST Repository

Jégu, Teddy

2015-10-12

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.

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

KAUST Repository

Jé gu, Teddy; Domenichini, Sé verine; Blein, Thomas; Ariel, Federico; Christ, Auré lie; Kim, SoonKap; Crespi, Martin; Boutet-Mercey, Sté phanie; Mouille, Gré gory; Bourge, Mickaë l; Hirt, Heribert; Bergounioux, Catherine; Raynaud, Cé cile; Benhamed, Moussa

2015-01-01

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.

FEATURES OF THE STATE REGULATION OF THE PRODUCTION OF GENETICALLY MODIFIED PRODUCTS IN THE WORLD AND IN UKRAINE

Directory of Open Access Journals (Sweden)

Viktoriya Bashuk

2017-11-01

Full Text Available The purpose of this article is to investigate the regulation of the use, consumption, and trade of genetically modified organisms in different countries of the world, as well as in Ukraine. The definition of international approaches to risk assessment of genetically modified products is of particular importance for international trade. Methodology. The study is based on data from different sources, beginning with the first mention of genetically modified organisms, ending with the latest received data from different countries. Purpose. Show how different countries refer differently to the production of genetically modified products, differently perceive it and are guided by different principles. Find ways to solve the problems associated with the introduction of GMOs in Ukraine and compare them with other countries. Results. The study showed that developed countries have developed clear rules for the production, labelling, consumption, and trade of products containing GMOs. Also, the bodies and structures responsible for compliance with all these rules are defined and a large number of legislative acts has been adopted, which cannot be said of Ukraine. In Ukraine, this is a large gap because “on paper” also seems that there are some rules according to GMOs but they are not clear, consistent, and they are not followed due to their observance, as these powers are entrusted to a large number of structures. Due to imperfect legislation and lack of funds, products that are imported are not tested for GMOs content, there are no studies on the safety of their consumption and cultivation, the reliability of information on labels is not followed. Practical implications. In Ukraine, in order to ensure the proper level of state regulation, protection, and use of genetically modified products obtained with the help of modern biotechnologies, it is necessary to adhere strictly to the fulfilment of the main criteria: 1 adoption and further improvement of

[Effects of menthol as an additive in tobacco products and the need for regulation].

Science.gov (United States)

Kahnert, S; Nair, U; Mons, U; Pötschke-Langer, M

2012-03-01

Menthol is the most widely used and the most prominent tobacco additive in tobacco products advertised and marketed by the tobacco industry. Besides its characteristic flavor, it possesses a variety of pharmacological properties facilitating tobacco smoke inhalation and potentiating dependence. These properties of menthol not only favor tobacco initiation and consumption but can also prevent smoking cessation. This article summarizes the effect of menthol as an additive in tobacco products and its effect on tobacco consumption that causes a number of chronic diseases and premature death and, therefore, counteracts tobacco control measures. Currently, there is no legislative regulation in Germany that considers the health hazard, addiction-enhancing and attractiveness-increasing properties of additives permitted in tobacco products. Effective regulation or even a ban could contribute to a reduction of tobacco consumption and, hence, save many people from a long-lasting tobacco dependence.

The Organization of Regulated Production

DEFF Research Database (Denmark)

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

2008-01-01

We analyze the choice between vertical separation (VS) and vertical integration (VI) when two regulated firms produce complementary inputs with correlated costs and are protected by ex post break-even constraints. First, in the absence of collusion the regulator prefers VI (VS) for negative...

Differential effect of glucocorticoids on tumour necrosis factor production in mice: up-regulation by early pretreatment with dexamethasone.

Science.gov (United States)

Fantuzzi, G; Demitri, M T; Ghezzi, P

1994-04-01

Glucocorticoids (GC) are well known inhibitors of tumour necrosis factor (TNF) production. We investigated the role of endogenous GC in the regulation of TNF production in mice treated with lipopolysaccharide (LPS) using a pretreatment with dexamethasone (DEX) to down-regulate the hypothalamus-pituitary-adrenal axis (HPA). Short-term DEX pretreatment (up to 12 h before LPS) inhibited TNF production, but earlier (24-48 h) pretreatments potentiated it. This up-regulating effect was not observed in adrenalectomized mice or when GC synthesis was inhibited with cyanoketone (CK). This effect could not be explained only by the suppression of LPS-induced corticosterone (CS) levels induced by DEX, since a 48-h pretreatment potentiated TNF production without affecting LPS-induced CS levels. On the other hand, mice chronically pretreated with DEX were still responsive to its inhibitory effect on TNF production, thus ruling out the possibility of a decreased responsiveness to GC.

Bombyx mori nucleopolyhedrovirus BM5 protein regulates progeny virus production and viral gene expression

International Nuclear Information System (INIS)

Kokusho, Ryuhei; Koh, Yoshikazu; Fujimoto, Masaru; Shimada, Toru; Katsuma, Susumu

2016-01-01

Bombyx mori nucleopolyhedrovirus (BmNPV) orf5 (Bm5) is a core gene of lepidopteran baculoviruses and encodes the protein with the conserved amino acid residues (DUF3627) in its C-terminus. Here, we found that Bm5 disruption resulted in lower titers of budded viruses and fewer numbers of occlusion bodies (OBs) in B. mori cultured cells and larvae, although viral genome replication was not affected. Bm5 disruption also caused aberrant expression of various viral genes at the very late stage of infection. Immunocytochemical analysis revealed that BM5 localized to the nuclear membrane. We also found that DUF3627 is important for OB production, transcriptional regulation of viral genes, and subcellular localization of BM5. Compared with wild-type BmNPV infection, larval death was delayed when B. mori larvae were infected with Bm5 mutants. These results suggest that BM5 is involved in progeny virus production and regulation of viral gene expression at the very late stage of infection. -- Highlights: •The role of BmNPV BM5 protein was examined in B. mori cultured cells and larvae. •BM5 contributes to efficient production of budded viruses and occlusion bodies. •BM5 regulates viral gene expression at the very late stage of infection. •BM5 dominantly localizes to the nuclear membrane. •Bm5 mutant showed v-cath down-regulation and resulting delay of larval death.

Bombyx mori nucleopolyhedrovirus BM5 protein regulates progeny virus production and viral gene expression

Energy Technology Data Exchange (ETDEWEB)

Kokusho, Ryuhei, E-mail: kokusho@ss.ab.a.u-tokyo.ac.jp; Koh, Yoshikazu; Fujimoto, Masaru; Shimada, Toru; Katsuma, Susumu, E-mail: katsuma@ss.ab.a.u-tokyo.ac.jp

2016-11-15

Bombyx mori nucleopolyhedrovirus (BmNPV) orf5 (Bm5) is a core gene of lepidopteran baculoviruses and encodes the protein with the conserved amino acid residues (DUF3627) in its C-terminus. Here, we found that Bm5 disruption resulted in lower titers of budded viruses and fewer numbers of occlusion bodies (OBs) in B. mori cultured cells and larvae, although viral genome replication was not affected. Bm5 disruption also caused aberrant expression of various viral genes at the very late stage of infection. Immunocytochemical analysis revealed that BM5 localized to the nuclear membrane. We also found that DUF3627 is important for OB production, transcriptional regulation of viral genes, and subcellular localization of BM5. Compared with wild-type BmNPV infection, larval death was delayed when B. mori larvae were infected with Bm5 mutants. These results suggest that BM5 is involved in progeny virus production and regulation of viral gene expression at the very late stage of infection. -- Highlights: •The role of BmNPV BM5 protein was examined in B. mori cultured cells and larvae. •BM5 contributes to efficient production of budded viruses and occlusion bodies. •BM5 regulates viral gene expression at the very late stage of infection. •BM5 dominantly localizes to the nuclear membrane. •Bm5 mutant showed v-cath down-regulation and resulting delay of larval death.

Consumer and Commercial Products, Group IV: Control Techniques Guidelines in Lieu of Regulations

Science.gov (United States)

EPA has determined that control techniques guidelines (CTGs) will be substantially as effective as regulations in reducing volatile organic compound (VOC) emissions in ozone nonattainment areas for certain consumer and commercial product categories.

Unfinished business in the regulation of shale gas production in the United States.

Science.gov (United States)

Centner, Terence J; O'Connell, Laura Kathryn

2014-04-01

With increased drilling for natural gas, toxic chemicals used to fracture wells have been introduced into the environment accompanied by allegations of injuries. This article evaluates laws and regulations governing shale gas production to disclose ideas for offering further protection to people and the environment. The aim of the study is to offer state governments ideas for addressing contractual obligations of drilling operators, discerning health risks, disclosing toxic chemicals, and reporting sufficient information to detect problems and enforce regulations. The discussion suggests opportunities for state regulators to become more supportive of public health through greater oversight of shale gas extraction. Copyright © 2014 Elsevier B.V. All rights reserved.

Recent advances in microbial production of mannitol: utilization of low-cost substrates, strain development and regulation strategies.

Science.gov (United States)

Zhang, Min; Gu, Lei; Cheng, Chao; Ma, Jiangfeng; Xin, Fengxue; Liu, Junli; Wu, Hao; Jiang, Min

2018-02-26

Mannitol has been widely used in fine chemicals, pharmaceutical industries, as well as functional foods due to its excellent characteristics, such as antioxidant protecting, regulation of osmotic pressure and non-metabolizable feature. Mannitol can be naturally produced by microorganisms. Compared with chemical manufacturing, microbial production of mannitol provides high yield and convenience in products separation; however the fermentative process has not been widely adopted yet. A major obstacle to microbial production of mannitol under industrial-scale lies in the low economical efficiency, owing to the high cost of fermentation medium, leakage of fructose, low mannitol productivity. In this review, recent advances in improving the economical efficiency of microbial production of mannitol were reviewed, including utilization of low-cost substrates, strain development for high mannitol yield and process regulation strategies for high productivity.

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

Science.gov (United States)

Sugarman, Stephen D

2009-12-01

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.

Mapping medical marijuana: state laws regulating patients, product safety, supply chains and dispensaries, 2017.

Science.gov (United States)

Klieger, Sarah B; Gutman, Abraham; Allen, Leslie; Pacula, Rosalie Liccardo; Ibrahim, Jennifer K; Burris, Scott

2017-12-01

(1) To describe open source legal data sets, created for research use, that capture the key provisions of US state medical marijuana laws. The data document how state lawmakers have regulated a medicine that remains, under federal law, a Schedule I illegal drug with no legitimate medical use. (2) To demonstrate the variability that exists across states in rules governing patient access, product safety and dispensary practice. Two legal researchers collected and coded state laws governing marijuana patients, product safety and dispensaries in effect on 1 February 2017, creating three empirical legal data sets. We used summary tables to identify the variation in specific statutory provisions specified in each state's medical marijuana law as it existed on 1 February 2017. We compared aspects of these laws to the traditional Federal approach to regulating medicine. Full data sets, codebooks and protocols are available through the Prescription Drug Abuse Policy System (http://www.pdaps.org/; Archived at http://www.webcitation.org/6qv5CZNaZ on 2 June 2017). Twenty-eight states (including the District of Columbia) have authorized medical marijuana. Twenty-seven specify qualifying diseases, which differ across states. All states protect patient privacy; only 14 protect patients against discrimination. Eighteen states have mandatory product safety testing before any sale. While the majority have package/label regulations, states have a wide range of specific requirements. Most regulate dispensaries (25 states), with considerable variation in specific provisions such as permitted product supply sources number of dispensaries per state and restricting proximity to various types of location. The federal ban in the United States on marijuana has resulted in a patchwork of regulatory strategies that are not uniformly consistent with the approach usually taken by the Federal government and whose effectiveness remains unknown. © 2017 Society for the Study of Addiction.

Do Environmental Regulations Influence the Competitiveness of Pollution-Intensive Products?

OpenAIRE

Yang Lu

2010-01-01

According to "Pollution Haven Effect," in order to circumvent stringent environment standards, polluting industries in developed countries will be chosen to locate into developing countries; another way is that developed countries increase imports of pollution-intensive products instead of producing by their own, both of which can contribute to the changes of comparative advantages in the past 30 years. Since 1990s, many scholars have paid special attention on whether environmental regulation...

β-cryptoxanthin regulates bone resorption related-cytokine production in human periodontal ligament cells.

Science.gov (United States)

Nishigaki, Masaru; Yamamoto, Toshiro; Ichioka, Hiroaki; Honjo, Ken-Ichi; Yamamoto, Kenta; Oseko, Fumishige; Kita, Masakazu; Mazda, Osam; Kanamura, Narisato

2013-07-01

β-cryptoxanthin (β-cry) is a type of carotenoid found in certain fruits and vegetables. Although it has been shown that β-cry inhibits alveolar bone resorption, the molecular mechanisms for this have not yet been clarified. In the present study, we investigated the effects of β-cry on bone resorption related-cytokine production in human periodontal ligament (hPDL) cells. hPDL cells were stimulated with β-cry (1×10(-7)mol/l), mechanical stress (1 or 6MPa), and P. gingivalis. The production of interleukin (IL)-1β, IL-6, IL-8, tumour necrosis factor (TNF)-α, osteoprotegerin (OPG), and receptor activator of nuclear factor kappa-B ligand (RANKL) were analyzed by RT-PCR and ELISA. The production of IL-1β, IL-6, IL-8, and TNF-α was not induced in hPDL cells after stimulation with β-cry, although these cytokines were produced after stimulation with P. gingivalis. On the other hand, IL-6 and IL-8 were produced after exposure to 6MPa of mechanical stress. The production of IL-6 and IL-8 was significantly decreased by the addition of β-cry. Furthermore, β-cry up-regulated the production of OPG, but not RANKL. β-cry inhibited the production of IL-6 and IL-8 induced by mechanical stress and periodontopathogenic bacteria in hPDL cells. Moreover, β-cry up-regulated OPG production. These results suggest that β-cry may prevent bone resorption in periodontitis. Copyright © 2013 Elsevier Ltd. All rights reserved.

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

Science.gov (United States)

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

2011-10-01

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.

Towards healthier bakery products, impact of the EU Food-Nutrition-Health regulation and the healthgrain project

NARCIS (Netherlands)

Kamp, J.W. van der

2008-01-01

Consumer interest in healthy cereal products is resulting to a growing number of product launches and an even larger increase in nutrition and health related statements on packaged products. The new EU Regulation on nutrition and health claims made on foods (EC 1924/2006) does not allow having

Basic substances under EC 1107/2009 phytochemical regulation: experience with non-biocide and food products as biorationals

Directory of Open Access Journals (Sweden)

Marchand Patrice A.

2016-07-01

Full Text Available Basic Substances are a newly effective category of Plant Protection Product under EC Regulation No 1107/2009. The first approved application of Equisetum arvense L. opened Part C of Implementing Regulation (EU No 540/2011, which lists the basic substance approved. Although E. arvense was described as a fungicide extract, subsequent applications like chitosan were related to non-biocide molecules. Consequently, plant protection product data were collected from research on alternative or traditional crop protection methods. They are notably issued or derived from foodstuffs (plants, plant by-products, plant derived products, substances and derived substances from animal origin. Applications are currently submitted by our Institute, under evaluation at different stages of the approval process or already approved. Remarkably, this Basic Substance category under pesticide EU Regulation was surprisingly designed for these non-biocidal plant protection products. In fact, components described as the “active substance” of most of the actual applications are food products like sugars and lecithin. Basic Substance applications for these foodstuffs are therefore a straightforward way of easily gaining approval for them. Here we describe the approval context and detail the agricultural uses of theses food products as Biological Control Agents (BCAs or biorationals for crop protection. From all deposited or approved Basic Substance Application (BSA, a proof has been provided that non-biocide and food products via physical barrier or lure effects may be effective plant protection products with an acceptable low profile of concern for public and agricultural safety.

Clonorchis sinensis excretory-secretory products regulate migration and invasion in cholangiocarcinoma cells via extracellular signal-regulated kinase 1/2/nuclear factor-κB-dependent matrix metalloproteinase-9 expression.

Science.gov (United States)

Pak, Jhang Ho; Shin, Jimin; Song, In-Sung; Shim, Sungbo; Jang, Sung-Wuk

2017-01-01

Matrix metalloproteinase-9 plays an important role in the invasion and metastasis of various types of cancer cells. We have previously reported that excretory-secretory products from Clonorchis sinensis increases matrix metalloproteinase-9 expression. However, the regulatory mechanisms through which matrix metalloproteinase-9 expression affects cholangiocarcinoma development remain unclear. In the current study, we examined the potential role of excretory-secretory products in regulating the migration and invasion of various cholangiocarcinoma cell lines. We demonstrated that excretory-secretory products significantly induced matrix metalloproteinase-9 expression and activity in a concentration-dependent manner. Reporter gene and chromatin immunoprecipitation assays showed that excretory-secretory products induced matrix metalloproteinase-9 expression by enhancing the activity of nuclear factor-kappa B. Moreover, excretory-secretory products induced the degradation and phosphorylation of IκBα and stimulated nuclear factor-kappa B p65 nuclear translocation, which was regulated by extracellular signal-regulated kinase 1/2. Taken together, our findings indicated that the excretory-secretory product-dependent enhancement of matrix metalloproteinase-9 activity and subsequent induction of IκBα and nuclear factor-kappa B activities may contribute to the progression of cholangiocarcinoma. Copyright © 2016 Australian Society for Parasitology. Published by Elsevier Ltd. All rights reserved.

IMMUNE REGULATING ES-PRODUCTS IN PARASITIC NEMATODES

DEFF Research Database (Denmark)

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...

Regulation – Do or Die: An Analysis of Factors Critical to New Product Development in a Regulatory Context

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Clare O'Dwyer

2017-04-01

Full Text Available This study explores new product development in a strict regulatory and historically secretive environment. Adopting a systems perspective and a mixed methods approach in our research, we examine medical device development in Ireland. Findings indicate that the possession of a regulatory strategy expedites the rate of commercialization, so too does the generation of clear product definitions and marketing claims in the earliest developmental phases. Moreover, results suggest that if the regulated industry strengthens its culture for regulation by prioritizing regulation over speed to market, by encouraging cross-functional team collaborations, and by taking a more proactive approach in post-marketing surveillance activities, it has the potential to improve customer satisfaction and enhance product innovation. This study provides unique empirical data enriched by the homogeneity of its sample. It also contributes guidance to practitioners of new product development within a regulatory context.

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

Science.gov (United States)

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

2016-05-01

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.

Regulation of Clinical Trials with Advanced Therapy Medicinal Products in Germany.

Science.gov (United States)

Renner, Matthias; Anliker, Brigitte; Sanzenbacher, Ralf; Schuele, Silke

2015-01-01

In the European Union, clinical trials for Advanced Therapy Medicinal Products are regulated at the national level, in contrast to the situation for a Marketing Authorisation Application, in which a centralised procedure is foreseen for these medicinal products. Although based on a common understanding regarding the regulatory requirement to be fulfilled before conduct of a clinical trial with an Advanced Therapy Investigational Medicinal Product, the procedures and partly the scientific requirements for approval of a clinical trial application differ between the European Union Member States. This chapter will thus give an overview about the path to be followed for a clinical trial application and the subsequent approval process for an Advanced Therapy Investigational Medicinal Product in Germany and will describe the role of the stakeholders that are involved. In addition, important aspects of manufacturing, quality control and non-clinical testing of Advanced Therapy Medicinal Products in the clinical development phase are discussed. Finally, current and future approaches for harmonisation of clinical trial authorisation between European Union Member States are summarised.

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

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Kirk Ruth S

2009-04-01

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.

GGA1 regulates signal-dependent sorting of BACE1 to recycling endosomes, which moderates Aβ production

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Toh, Wei Hong; Chia, Pei Zhi Cheryl; Hossain, Mohammed Iqbal; Gleeson, Paul A.

2018-01-01

The diversion of the membrane-bound β-site amyloid precursor protein–(APP) cleaving enzyme (BACE1) from the endolysosomal pathway to recycling endosomes represents an important transport step in the regulation of amyloid beta (Aβ) production. However, the mechanisms that regulate endosome sorting of BACE1 are poorly understood. Here we assessed the transport of BACE1 from early to recycling endosomes and have identified essential roles for the sorting nexin 4 (SNX4)-mediated, signal-independent pathway and for a novel signal-mediated pathway. The signal-mediated pathway is regulated by the phosphorylation of the DXXLL-motif sequence DISLL in the cytoplasmic tail of BACE1. The phosphomimetic S498D BACE1 mutant was trafficked to recycling endosomes at a faster rate compared with wild-type BACE1 or the nonphosphorylatable S498A mutant. The rapid transit of BACE1 S498D from early endosomes was coupled with reduced levels of amyloid precursor protein processing and Aβ production, compared with the S498A mutant. We show that the adaptor, GGA1, and retromer are essential to mediate rapid trafficking of phosphorylated BACE1 to recycling endosomes. In addition, the BACE1 DISLL motif is phosphorylated and regulates endosomal trafficking, in primary neurons. Therefore, post-translational phosphorylation of DISLL enhances the exit of BACE1 from early endosomes, a pathway mediated by GGA1 and retromer, which is important in regulating Aβ production. PMID:29142073

Regulation of tumour necrosis factor production by adrenal hormones in vivo: insights into the antiinflammatory activity of rolipram.

Science.gov (United States)

Pettipher, E R; Labasi, J M; Salter, E D; Stam, E J; Cheng, J B; Griffiths, R J

1996-04-01

1. The role of adrenal hormones in the regulation of the systemic and local production of tumour necrosis factor (TNF alpha) was examined in male Balb/c mice. 2. Intraperitoneal injection of 0.3 mg E. coli lipopolysaccharide (LPS, 0111:B4) led to high levels of circulating TNF alpha without stimulating TNF alpha production in the peritoneal cavity. Systemic production of TNF alpha in response to LPS was increased in adrenalectomized animals and in normal animals treated with the beta-adrenoceptor antagonist, propranolol. The glucocorticoid antagonist, RU 486, did not modify systemic TNF alpha production. These results indicate that systemic TNF alpha production is regulated by adrenaline but not by corticosterone. 3. When mice were primed with thioglycollate, TNF alpha was produced in the peritoneal cavity in response to low dose LPS (1 micrograms). The levels of TNF alpha in the peritoneal cavity were not enhanced by adrenalectomy or by treatment with either propranolol or RU 486, indicating local production of TNF alpha in the peritoneal cavity is not regulated by adrenaline or corticosterone. 4. The phosphodiesterase type IV (PDE-IV) inhibitor, rolipram, inhibited both the systemic production of TNF alpha in response to high dose endotoxin (ED50 = 1.3 mg kg-1) and the local production of TNF alpha in the peritoneal cavity in response to low dose endotoxin (ED50 = 9.1 mg kg-1). In adrenalectomized mice there was a slight reduction in the ability of rolipram to inhibit the systemic production of TNF alpha (ED50 = 3.3 mg kg-1) while the ability of rolipram to inhibit the local production of TNF alpha in the peritoneal cavity was virtually abolished (24% inhibition at 30 mg kg-1). The glucocorticoid antagonist, RU 486, also reduced the ability of rolipram to inhibit local TNF alpha production while propranolol was without effect. 5. Systemic treatment with rolipram increased the plasma concentrations of corticosterone in normal mice but not in adrenalectomized mice

Crosstalk between Rac1-mediated actin regulation and ROS production.

Science.gov (United States)

Acevedo, Alejandro; González-Billault, Christian

2018-02-20

The small RhoGTPase Rac1 is implicated in a variety of events related to actin cytoskeleton rearrangement. Remarkably, another event that is completely different from those related to actin regulation has the same relevance; the Rac1-mediated production of reactive oxygen species (ROS) through NADPH oxidases (NOX). Each outcome involves different Rac1 downstream effectors; on one hand, events related to the actin cytoskeleton require Rac1 to bind to WAVEs proteins and PAKs that ultimately promote actin branching and turnover, on the other, NOX-derived ROS production demands active Rac1 to be bound to a cytosolic activator of NOX. How Rac1-mediated signaling ends up promoting actin-related events, NOX-derived ROS, or both is poorly understood. Rac1 regulators, including scaffold proteins, are known to exert tight control over its functions. Hence, evidence of Rac1 regulatory events leading to both actin remodeling and NOX-mediated ROS generation are discussed. Moreover, cellular functions linked to physiological and pathological conditions that exhibit crosstalk between Rac1 outcomes are analyzed, while plausible roles in neuronal functions (and dysfunctions) are highlighted. Together, discussed evidence shed light on cellular mechanisms which requires Rac1 to direct either actin- and/or ROS-related events, helping to understand crucial roles of Rac1 dual functionality. Copyright © 2018 Elsevier Inc. All rights reserved.

Human Lung Mast Cell Products Regulate Airway Smooth Muscle CXCL10 Levels.

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Alkhouri, H; Cha, V; Tong, K; Moir, L M; Armour, C L; Hughes, J M

2014-01-01

In asthma, the airway smooth muscle (ASM) produces CXCL10 which may attract CXCR3(+) mast/T cells to it. Our aim was to investigate the effects of mast cell products on ASM cell CXCL10 production. ASM cells from people with and without asthma were stimulated with IL-1 β , TNF- α , and/or IFN γ and treated with histamine (1-100  μ M) ± chlorpheniramine (H1R antagonist; 1  μ M) or ranitidine (H2R antagonist; 50  μ M) or tryptase (1 nM) ± leupeptin (serine protease inhibitor; 50  μ M), heat-inactivated tryptase, or vehicle for 4 h or 24 h. Human lung mast cells (MC) were isolated and activated with IgE/anti-IgE and supernatants were collected after 2 h or 24 h. The supernatants were added to ASM cells for 48 h and ASM cell CXCL10 production detected using ELISA (protein) and real-time PCR (mRNA). Histamine reduced IL-1 β /TNF- α -induced CXCL10 protein, but not mRNA, levels independent of H1 and H2 receptor activation, whereas tryptase and MC 2 h supernatants reduced all cytokine-induced CXCL10. Tryptase also reduced CXCL10 levels in a cell-free system. Leupeptin inhibited the effects of tryptase and MC 2 h supernatants. MC 24 h supernatants contained TNF- α and amplified IFN γ -induced ASM cell CXCL10 production. This is the first evidence that MC can regulate ASM cell CXCL10 production and its degradation. Thus MC may regulate airway myositis in asthma.

Nitrogen availability regulates proline and ethylene production and alleviates salinity stress in mustard (Brassica juncea).

Science.gov (United States)

Iqbal, Noushina; Umar, Shahid; Khan, Nafees A

2015-04-15

Proline content and ethylene production have been shown to be involved in salt tolerance mechanisms in plants. To assess the role of nitrogen (N) in the protection of photosynthesis under salt stress, the effect of N (0, 5, 10, 20 mM) on proline and ethylene was studied in mustard (Brassica juncea). Sufficient N (10 mM) optimized proline production under non-saline conditions through an increase in proline-metabolizing enzymes, leading to osmotic balance and protection of photosynthesis through optimal ethylene production. Excess N (20 mM), in the absence of salt stress, inhibited photosynthesis and caused higher ethylene evolution but lower proline production compared to sufficient N. In contrast, under salt stress with an increased demand for N, excess N optimized ethylene production, which regulates the proline content resulting in recovered photosynthesis. The effect of excess N on photosynthesis under salt stress was further substantiated by the application of the ethylene biosynthesis inhibitor, 1-aminoethoxy vinylglycine (AVG), which inhibited proline production and photosynthesis. Without salt stress, AVG promoted photosynthesis in plants receiving excess N by inhibiting stress ethylene production. The results suggest that a regulatory interaction exists between ethylene, proline and N for salt tolerance. Nitrogen differentially regulates proline production and ethylene formation to alleviate the adverse effect of salinity on photosynthesis in mustard. Copyright © 2015 Elsevier GmbH. All rights reserved.

The FlbA-regulated predicted transcription factor Fum21 of Aspergillus niger is involved in fumonisin production.

Science.gov (United States)

Aerts, David; Hauer, Esther E; Ohm, Robin A; Arentshorst, Mark; Teertstra, Wieke R; Phippen, Christopher; Ram, Arthur F J; Frisvad, Jens C; Wösten, Han A B

2018-03-01

Aspergillus niger secretes proteins throughout the colony except for the zone that forms asexual spores called conidia. Inactivation of flbA that encodes a regulator of G-protein signaling results in colonies that are unable to reproduce asexually and that secrete proteins throughout the mycelium. In addition, the ΔflbA strain shows cell lysis and has thinner cell walls. Expression analysis showed that 38 predicted transcription factor genes are differentially expressed in strain ΔflbA. Here, the most down-regulated predicted transcription factor gene, called fum21, was inactivated. Growth, conidiation, and protein secretion were not affected in strain Δfum21. Whole genome expression analysis revealed that 63 and 11 genes were down- and up-regulated in Δfum21, respectively, when compared to the wild-type strain. Notably, 24 genes predicted to be involved in secondary metabolism were down-regulated in Δfum21, including 10 out of 12 genes of the fumonisin cluster. This was accompanied by absence of fumonisin production in the deletion strain and a 25% reduction in production of pyranonigrin A. Together, these results link FlbA-mediated sporulation-inhibited secretion with mycotoxin production.

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

International Nuclear Information System (INIS)

Durongkaveroj, P.

1991-01-01

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

A CRE1- regulated cluster is responsible for light dependent production of dihydrotrichotetronin in Trichoderma reesei.

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Alberto Alonso Monroy

Full Text Available Changing light conditions, caused by the rotation of earth resulting in day and night or growth on the surface or within a substrate, result in considerably altered physiological processes in fungi. For the biotechnological workhorse Trichoderma reesei, regulation of glycoside hydrolase gene expression, especially cellulase expression was shown to be a target of light dependent gene regulation. Analysis of regulatory targets of the carbon catabolite repressor CRE1 under cellulase inducing conditions revealed a secondary metabolite cluster to be differentially regulated in light and darkness and by photoreceptors. We found that this cluster is involved in production of trichodimerol and that the two polyketide synthases of the cluster are essential for biosynthesis of dihydrotrichotetronine (syn. bislongiquinolide or bisorbibutenolide. Additionally, an indirect influence on production of the peptaibol antibiotic paracelsin was observed. The two polyketide synthetase genes as well as the monooxygenase gene of the cluster were found to be connected at the level of transcription in a positive feedback cycle in darkness, but negative feedback in light, indicating a cellular sensing and response mechanism for the products of these enzymes. The transcription factor TR_102497/YPR2 residing within the cluster regulates the cluster genes in a light dependent manner. Additionally, an interrelationship of this cluster with regulation of cellulase gene expression was detected. Hence the regulatory connection between primary and secondary metabolism appears more widespread than previously assumed, indicating a sophisticated distribution of resources either to degradation of substrate (feed or to antagonism of competitors (fight, which is influenced by light.

Structure, control and regulation of the formal market for medicinal plants' products in Nigeria.

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Oguntade, Adegboyega E; Oluwalana, Isaac B

2011-01-01

There are informal and formal markets for medicinal plants' products in Nigeria. The formal market is subject to the national regulatory framework for Food and Drug Administration and Control. It is relatively new and underdeveloped. This study was designed to appraise this market with special emphasis on the market participants, market structure, marketing functions performed, conduct of sellers in the market and; standards and regulations to which the market is subject. Information used for this study was collected through personal interviews and interactions with key participants in the market; especially the officials of regulatory agency. The market structure was analysed in terms of the share of market controlled by participants and product types. Concentration Ratios (CR2 and CR4) were used to assess the market share. Marketing functions being performed were described in terms of the exchange, physical and facilitating functions while the conduct was described in terms of pricing and promotional strategies. The regulatory framework under which the market operates was appraised. The market was highly concentrated with a CR2 and CR4 of 58.5% and 80.8 %; respectively. Imported products accounted for only 12.3% of the market. The predominant modes of presentation of the product were capsule (41.6%) and liquid (36.2%). About 20.77% of the products were classified as multivitamins, 13.85% were antibiotics while 10.77% addressed sexual dysfunctional problems. These products were regulated under the Food and Drug Administration and Control (NAFDAC) decrees, 1993-1999. Only 2.3% of the products have received full registration status while the others were only listed.

Regulation of acidity and reduction of turbidity in the clarified pomegranate juice production

OpenAIRE

ESHMATOV FOZIL KHIDIROVICH; MAKSUMOVA DILRABO KUCHKAROVNA; DODAEVA LAYLO KUCHKAROVNA

2016-01-01

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.

DEVELOPING AN INDEX FOR FOREST PRODUCTIVITY MAPPING - A CASE STUDY FOR MARITIME PINE PRODUCTION REGULATION IN PORTUGAL

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Susana Mestre

2018-02-01

Full Text Available ABSTRACT Productivity is very dependent on the environmental and biotic factors present at the site where the forest species of interest is present. Forest site productivity is usually assessed using empirical models applied to inventory data providing discrete predictions. While the use of GIS-based models enables building a site productivity distribution map. Therefore, the aim of this study was to derive a productivity index using multivariate statistics and coupled GIS-geostatistics to obtain a forest productivity map. To that end, a study area vastly covered by naturally regenerated forests of maritime pine in central Portugal was used. First, a productivity index (PI was built based on Factorial Correspondence Analysis (FCA by incorporating a classical site index for the species and region (Sh25 - height index model and GIS-derived environmental variables (slope and aspect. After, the PI map was obtained by multi-Gaussian kriging and used as a GIS layer to evaluate maritime pine areas by productivity class (e.g., low, intermediate and high. In the end, the area control method was applied to assess the size and the number of compartments to establish by productivity class. The management compartments of equal productivity were digitized as GIS layer and organized in a temporal progression of stands’ age regularly available for cutting each year during a 50-year schedule. The methodological approach developed in this study proved that can be used to build forest productivity maps which are crucial tools to support forest production regulation.

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

Science.gov (United States)

2010-01-05

...] Medical Device Quality System Regulation Educational Forum on Risk Management Through the Product Life... on Risk Management through the Product Life Cycle.'' This public workshop is intended to provide... discussed at the workshop: (1) Standards and guidance, (2) risk management in design, (3) risk management in...

Plant species richness regulates soil respiration through changes in productivity.

Science.gov (United States)

Dias, André Tavares Corrêa; van Ruijven, Jasper; Berendse, Frank

2010-07-01

Soil respiration is an important pathway of the C cycle. However, it is still poorly understood how changes in plant community diversity can affect this ecosystem process. Here we used a long-term experiment consisting of a gradient of grassland plant species richness to test for effects of diversity on soil respiration. We hypothesized that plant diversity could affect soil respiration in two ways. On the one hand, more diverse plant communities have been shown to promote plant productivity, which could increase soil respiration. On the other hand, the nutrient concentration in the biomass produced has been shown to decrease with diversity, which could counteract the production-induced increase in soil respiration. Our results clearly show that soil respiration increased with species richness. Detailed analysis revealed that this effect was not due to differences in species composition. In general, soil respiration in mixtures was higher than would be expected from the monocultures. Path analysis revealed that species richness predominantly regulates soil respiration through changes in productivity. No evidence supporting the hypothesized negative effect of lower N concentration on soil respiration was found. We conclude that shifts in productivity are the main mechanism by which changes in plant diversity may affect soil respiration.

Alleviation of harmful effect in stillage reflux in food waste ethanol fermentation based on metabolic and side-product accumulation regulation.

Science.gov (United States)

Ma, Hongzhi; Yang, Jian; Jia, Yan; Wang, Qunhui; Ma, Xiaoyu; Sonomoto, Kenji

2016-10-01

Stillage reflux fermentation in food waste ethanol fermentation could reduce sewage discharge but exert a harmful effect because of side-product accumulation. In this study, regulation methods based on metabolic regulation and side-product alleviation were conducted. Result demonstrated that controlling the proper oxidation-reduction potential value (-150mV to -250mV) could reduce the harmful effect, improve ethanol yield by 21%, and reduce fermentation time by 20%. The methods of adding calcium carbonate to adjust the accumulated lactic acid showed that ethanol yield increased by 17.3%, and fermentation time decreased by 20%. The accumulated glyceal also shows that these two methods can reduce the harmful effect. Fermentation time lasted for seven times without effect, and metabolic regulation had a better effect than side-product regulation. Copyright © 2016 Elsevier Ltd. All rights reserved.

Successful New Product Development by Optimizing Development Process Effectiveness in Highly Regulated Sectors: The Case of the Spanish Medical Devices Sector

NARCIS (Netherlands)

Pullen, A.J.J.; Cabello-Medina, Carmen; de Weerd-Nederhof, Petronella C.; Visscher, Klaasjan; Groen, Arend J.; Tschirky, H.; Herstatt, C.; Probert, D.; Gemunden, H.G.; Colombo, M.G.; Durand, T.; de Weerd-Nederhof, P.C.; Schweisfurth, T.

2010-01-01

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

Economies of scale in biogas production and the significance of flexible regulation

International Nuclear Information System (INIS)

Skovsgaard, Lise; Jacobsen, Henrik Klinge

2017-01-01

Biogas production is characterised by economies of scale in capital and operational costs of the plant and diseconomies of scale from transport of input materials. We analyse biogas in a Danish setting where most biogas is based on manure, we use a case study with actual distances, and find that the benefits of scale in capital and operational costs dominate the diseconomies of increasing transport distances to collect manure. To boost the yield it is common to use co-substrates in the biogas production. We investigate how costs and income changes, when sugar beet is added in this case study, and demonstrate that transport cost can be critical in relation to co-substrates. Further we compare the new Danish support for upgraded biogas with the traditional support for biogas being used in Combined Heat and Power production in relation to scale economies. We argue that economies of scale is facilitated by the new regulation providing similar support to upgraded biogas fed into the natural gas grid, however in order to keep transport costs low, we suggest that the biogas plants should be allowed to use and combine as many co-substrates as possible, respecting the sustainability criteria regarding energy crops in Danish legislation. - Highlights: • For Denmark we find economies of scale in biogas production based on pure manure. • Adding sugar beet outweigh economy of scale due to increased transport costs. • We investigate the main risks associated with input prices, yield and output prices. • Biogas fed into the gas grid should receive similar support as directly used in CHP. • Regulation should allow large biogas plants with few restrictions on co-substrates.

Asexual sporulation signalling regulates autolysis of Aspergillus nidulans via modulating the chitinase ChiB production.

Science.gov (United States)

Pócsi, I; Leiter, E; Kwon, N-J; Shin, K-S; Kwon, G-S; Pusztahelyi, T; Emri, T; Abuknesha, R A; Price, R G; Yu, J-H

2009-08-01

Elucidation of the regulation of ChiB production in Aspergillus nidulans. Mutational inactivation of the A. nidulans chiB gene resulted in a nonautolytic phenotype. To better understand the mechanisms controlling both developmental progression and fungal autolysis, we examined a range of autolysis-associated parameters in A. nidulans developmental and/or autolytic mutants. Investigation of disorganization of mycelial pellets, loss of biomass, extra-/intracellular chitinase activities, ChiB production and chiB mRNA levels in various cultures revealed that, in submerged cultures, initialization of autolysis and stationary phase-induced ChiB production are intimately coupled, and that both processes are controlled by the FluG-BrlA asexual sporulation regulatory pathway. ChiB production does not affect the progression of apoptotic cell death in the aging A. nidulans cultures. The endochitinase ChiB plays an important role in autolysis of A. nidulans, and its production is initiated by FluG-BrlA signalling. Despite the fact that apoptosis is an inseparable part of fungal autolysis, its regulation is independent to FluG-initiated sporulation signalling. Deletion of chiB and fluG homologues in industrial filamentous fungal strains may stabilize the hyphal structures in the autolytic phase of growth and limit the release of autolytic hydrolases into the culture medium.

The Regulation of Behavioral Plasticity by Performance-Based Feedback and an Experimental Test with Avian Egg Production.

Science.gov (United States)

Sockman, Keith W

2016-05-01

Optimizing plasticity in behavioral performances requires the abilities to regulate physiological effort and to estimate the effects of the environment. To describe how performance-based feedback could play a role in regulating recursive or continuous behavioral performances, I developed two models, one (environmental feedback) that assumes an initial ability to regulate effort but not to predict the effects of the environment and the other (effort feedback) that assumes an initial ability to predict the effects of the environment but not to regulate effort. I tested them by manipulating feedback on egg production, using an egg-substitution experiment in wild, free-ranging Lincoln's sparrows (Melospiza lincolnii). I discovered that females adjusted the size of their clutches' third laid eggs in response to the size of an experimentally substituted first laid egg, such that the size of the third laid egg increased with the size of the substitute. Results were largely consistent with the environmental feedback model, though small portions of the response surface were consistent with the effort feedback model or with neither. Regardless, such feedback-based regulation predicted by either model may help females maximize net benefits of egg production and may be a basis for mechanisms regulating a wide range of other behavioral performances, as well.

Regulation of schistosome egg production by HMG CoA reductase

International Nuclear Information System (INIS)

VandeWaa, E.A.; Bennett, J.L.

1986-01-01

Hydroxymethylglutaryl coenzyme A reductase (HMG CoA reductase) catalyzes the conversion of HMG CoA to mevalonate in the synthesis of steroids, isoprenoids and terpenes. Mevinolin, an inhibitor of this enzyme, decreased egg production in Schistosoma mansoni during in vitro incubations. This was associated with a reduction in the incorporation of 14 C-acetate into polyisoprenoids and a reduction in the formation of a lipid-linked oligosaccharide. In vivo, mevinolin in daily doses of 50 mg/kg (p.o., from days 30-48 post-infection) caused no change in gross liver pathology in S. mansoni infected mice. However, when parasites exposed to mevinolin or its vehicle in vivo were cultured in vitro, worms from mevinolin-treated mice produced six times more eggs than control parasites. When infected mice were dosed with 250 mg/kg mevinolin daily (p.o., from days 35-45 post-infection), liver pathology was reduced in comparison to control mice. Thus, during in vivo exposure to a high dose of the drug egg production is decreased, while at a lower dose it appears unaffected until the parasites are cultured in a drug-free in vitro system wherein egg production is stimulated to extraordinarily high levels. It may be that at low doses mevinolin, by inhibiting the enzyme, is blocking the formation of a product (such as an isoprenoid) which normally acts to down-regulate enzyme synthesis, resulting in enzyme induction. Induction of HMG CoA reductase is then expressed as increased egg production when the worms are removed from the drug. These data suggest that HMG CoA reductase plays a role in schistosome egg production

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

Directory of Open Access Journals (Sweden)

Marcela Montes de Oca

2016-01-01

Full Text Available 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.

Increasing Avermectin Production in Streptomyces avermitilis by Manipulating the Expression of a Novel TetR-Family Regulator and Its Target Gene Product.

Science.gov (United States)

Liu, Wenshuai; Zhang, Qinling; Guo, Jia; Chen, Zhi; Li, Jilun; Wen, Ying

2015-08-01

Avermectins produced by Streptomyces avermitilis are commercially important anthelmintic agents. The detailed regulatory mechanisms of avermectin biosynthesis remain unclear. Here, we identified SAV3619, a TetR-family transcriptional regulator designated AveT, to be an activator for both avermectin production and morphological differentiation in S. avermitilis. AveT was shown to indirectly stimulate avermectin production by affecting transcription of the cluster-situated activator gene aveR. AveT directly repressed transcription of its own gene (aveT), adjacent gene pepD2 (sav_3620), sav_7490 (designated aveM), and sav_7491 by binding to an 18-bp perfect palindromic sequence (CGAAACGKTKYCGTTTCG, where K is T or G and Y is T or C and where the underlining indicates inverted repeats) within their promoter regions. aveM (which encodes a putative transmembrane efflux protein belonging to the major facilitator superfamily [MFS]), the important target gene of AveT, had a striking negative effect on avermectin production and morphological differentiation. Overexpression of aveT and deletion of aveM in wild-type and industrial strains of S. avermitilis led to clear increases in the levels of avermectin production. In vitro gel-shift assays suggested that C-5-O-B1, the late pathway precursor of avermectin B1, acts as an AveT ligand. Taken together, our findings indicate positive-feedback regulation of aveT expression and avermectin production by a late pathway intermediate and provide the basis for an efficient strategy to increase avermectin production in S. avermitilis by manipulation of AveT and its target gene product, AveM. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Inactivation of SACE_3446, a TetR family transcriptional regulator, stimulates erythromycin production in Saccharopolyspora erythraea.

Science.gov (United States)

Wu, Hang; Wang, Yansheng; Yuan, Li; Mao, Yongrong; Wang, Weiwei; Zhu, Lin; Wu, Panpan; Fu, Chengzhang; Müller, Rolf; Weaver, David T; Zhang, Lixin; Zhang, Buchang

2016-03-01

Erythromycin A is a widely used antibiotic produced by Saccharopolyspora erythraea ; however, its biosynthetic cluster lacks a regulatory gene, limiting the yield enhancement via regulation engineering of S. erythraea . Herein, six TetR family transcriptional regulators (TFRs) belonging to three genomic context types were individually inactivated in S. erythraea A226, and one of them, SACE_3446, was proved to play a negative role in regulating erythromycin biosynthesis. EMSA and qRT-PCR analysis revealed that SACE_3446 covering intact N-terminal DNA binding domain specifically bound to the promoter regions of erythromycin biosynthetic gene eryAI , the resistant gene ermE and the adjacent gene SACE_3447 (encoding a long-chain fatty-acid CoA ligase), and repressed their transcription. Furthermore, we explored the interaction relationships of SACE_3446 and previously identified TFRs (SACE_3986 and SACE_7301) associated with erythromycin production. Given demonstrated relatively independent regulation mode of SACE_3446 and SACE_3986 in erythromycin biosynthesis, we individually and concomitantly inactivated them in an industrial S. erythraea WB. Compared with WB, the WBΔ 3446 and WBΔ 3446 Δ 3986 mutants respectively displayed 36% and 65% yield enhancement of erythromycin A, following significantly elevated transcription of eryAI and ermE . When cultured in a 5 L fermentor, erythromycin A of WBΔ 3446 and WBΔ 3446 Δ 3986 successively reached 4095 mg/L and 4670 mg/L with 23% and 41% production improvement relative to WB. The strategy reported here will be useful to improve antibiotics production in other industrial actinomycete.

Improvement of Nutritional and Bioactive Compound Production by Lion's Mane Medicinal Mushroom, Hericium erinaceus (Agaricomycetes), by Spraying Growth Regulators.

Science.gov (United States)

Vi, Minhthuan; Yang, Xueqin; Zeng, Xianlu; Chen, Rui'an; Guo, Liqiong; Lin, Junfang; He, Qianyun; Zheng, Qianwang; Wei, Tao

2018-01-01

Hericium erinaceus is a popular culinary and medicinal mushroom in China because of its broad beneficial effects. In this study we evaluated the effects of stimulation with 7 growth regulators at 5 different concentrations on improving the production of nutritional and bioactive compounds by H. erinaceus. Results showed that among all the tested regulators, gibberellic acid (GA) increased protein content (165%), free amino acids (100%), polysaccharides (108%), and polyphenols (26%). Spraying nephthyl acetic acid increased polysaccharides and triterpenoids to 4.37 and 17.27 g/100 g, respectively. Spraying chitosan significantly increased polyphenols by 42%. The addition of triacontanol, indole acetic acid, and 2,4-dichlorophenoxyacetic acid improved the production of proteins, free amino acids, polysaccharides, and polyphenols, but not to the extent that GA did. These results indicate that adding certain growth regulators can effectively improve the production of nutritional and bioactive compounds in H. erinaceus.

GM-CSF and IL-4 produced by NKT cells inversely regulate IL-1β production by macrophages.

Science.gov (United States)

Ahn, Sehee; Jeong, Dongjin; Oh, Sae Jin; Ahn, Jiye; Lee, Seung Hyo; Chung, Doo Hyun

2017-02-01

Natural Killer T (NKT) cells are distinct T cell subset that link innate and adaptive immune responses. IL-1β, produced by various immune cells, plays a key role in the regulation of innate immunity in vivo. However, it is unclear whether NKT cells regulate IL-1β production by macrophages. To address this, we co-cultured NKT cells and peritoneal macrophages in the presence of TCR stimulation and inflammasome activators. Among cytokines secreted from NKT cells, GM-CSF enhanced IL-1β production by macrophages via regulating LPS-mediated pro-IL-1β expression and NLRP3-dependent inflammasome activation, whereas IL-4 enhanced M2-differentiation of macrophages and decreased IL-1β production. Together, our findings suggest the NKT cells have double-sided effects on IL-1β-mediated innate immune responses by producing IL-4 and GM-CSF. These findings may be helpful for a comprehensive understanding of NKT cell-mediated regulatory mechanisms of the pro-inflammatory effects of IL-1β in inflammatory diseases in vivo. Copyright © 2017 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.

Hypothalamic peroxisome proliferator-activated receptor gamma regulates ghrelin production and food intake.

Science.gov (United States)

Li, Qingjie; Yu, Quan; Lin, Li; Zhang, Heng; Peng, Miao; Jing, Chunxia; Xu, Geyang

2018-04-09

Peroxisome proliferator-activated receptor-γ (PPARγ) regulates fatty acid storage, glucose metabolism, and food intake. Ghrelin, a gastric hormone, provides a hunger signal to the central nervous system to stimulate appetite. However, the effects of PPARγ on ghrelin production are still unclear. In the present study, the effects of PPARγ on ghrelin production were examined in lean- or high-fat diet-induced obese (DIO) C57BL/6J mice and mHypoE-42 cells, a hypothalamic cell line. 3rd intracerebroventricular injection of adenoviral-directed overexpression of PPARγ (Ad-PPARγ) reduced hypothalamic and plasma ghrelin, food intake in both lean C57BL/6J mice and diet-induced obese mice. These changes were associated with a significant increase in mechanistic target of rapamycin complex 1 (mTORC1) activity. Overexpression of PPARγ enhanced mTORC1 signaling and suppressed ghrelin production in cultured mHypoE-42 cells. Our results suggest that hypothalamic PPARγ plays a vital role in ghrelin production and food intake in mice. Copyright © 2018 Elsevier Ltd. All rights reserved.

Natural products, an important resource for discovery of multitarget drugs and functional food for regulation of hepatic glucose metabolism.

Science.gov (United States)

Li, Jian; Yu, Haiyang; Wang, Sijian; Wang, Wei; Chen, Qian; Ma, Yanmin; Zhang, Yi; Wang, Tao

2018-01-01

Imbalanced hepatic glucose homeostasis is one of the critical pathologic events in the development of metabolic syndromes (MSs). Therefore, regulation of imbalanced hepatic glucose homeostasis is important in drug development for MS treatment. In this review, we discuss the major targets that regulate hepatic glucose homeostasis in human physiologic and pathophysiologic processes, involving hepatic glucose uptake, glycolysis and glycogen synthesis, and summarize their changes in MSs. Recent literature suggests the necessity of multitarget drugs in the management of MS disorder for regulation of imbalanced glucose homeostasis in both experimental models and MS patients. Here, we highlight the potential bioactive compounds from natural products with medicinal or health care values, and focus on polypharmacologic and multitarget natural products with effects on various signaling pathways in hepatic glucose metabolism. This review shows the advantage and feasibility of discovering multicompound-multitarget drugs from natural products, and providing a new perspective of ways on drug and functional food development for MSs.

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

International Nuclear Information System (INIS)

Thiele, Lisa

2013-01-01

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)

Studies on the mechanism of endogenous pyrogen production. II. Role of cell products in the regulation of pyrogen release from blood leukocytes.

Science.gov (United States)

Bodel, P

1974-09-01

Some characteristics of the process by which endogenous pyrogen (EP), the mediator of fever, is released from cells were examined by using human blood leukocytes incubated in vitro. Studies were designed to examine a possible role for leukocyte products, including EP, in the induction, augmentation, or suppression of pyrogen release by blood leukocytes. Products of stimulated leukocytes, including a partially purified preparation of EP, did not induce significant activation of nonstimulated cells. Also, no evidence was obtained that stimulated cell products either augment or inhibit pyrogen production by other stimulated cells. A feedback control of EP production was thus not observed. A crude preparation of EP, containing other products of activated cells, maintained its pyrogenicity when incubated at pH 7.4 but not at pH 5.0. These studies thus provide no support for hypothesized control mechanisms regulating production of EP by blood leukocytes. By contrast, local inactivation of EP at inflammatory sites may modify the amount of EP entering the blood, and hence fever.

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

NARCIS (Netherlands)

Bol-Schoenmakers, M.

2009-01-01

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).

Removal of the effect of ammonium on the regulation of nitrogenase enzyme in Rhodobacter capsulatus DSM1710 for improved hydrogen production

Energy Technology Data Exchange (ETDEWEB)

Pekgoez, Guelsah; Guenduez, Ufuk [Middle East Technical Univ. (Turkey). Dept. of Biology; Eroglu, Inci [Middle East Technical Univ. (Turkey). Dept. of Chemical Engineering; Rakhely, Gabor [Szeged Univ. (Hungary). Dept. of Biotechnology

2010-07-01

Photofermentative biohydrogen production by purple non-sulfur (PNS) bacteria is a renewable and clean way of producing hydrogen. Hydrogen production by PNS bacteria, Rhodobacter capsulatus, is mediated mainly by nitrogenases, which primarily fix molecular nitrogen to ammonium and produce hydrogen as byproduct. The reaction catalyzed by nitrogenases requires a lot of energy. Hence, there is a complex regulation on nitrogenase enzyme complex, consequently, on hydrogen production. Whenever ammonium, which is the end product of nitrogen fixation reaction, is found in the environment, hydrogen production stops. GlnB and GlnK proteins are the critical regulatory proteins in ammonium dependent regulation of the nitrogenase gene expression. In this study, the aim is to release the ammonium regulation on nitrogenase enzyme by inactivating glnB and glnK genes. For this purpose, relevant recombinant vectors were constructed; R.capsulatus glnB- strain was obtained. The double R.capsulatus glnB{sup -}glnK{sup -} strain, able to produce hydrogen independent of ammonium concentration of the environment is to be obtained. (orig.)

Transcriptional regulation of genes involved in terpenoid índole alkaloid production in Catharanthus roseus seedlings

Directory of Open Access Journals (Sweden)

Pedro J. Rocha

2002-07-01

Full Text Available Catharanthus roseus (L. G Don is a medicinal plant that produces a variety of terpenoid indole alkaloids (TIAs, some of which display pharmacological activity. C. roseus plants and cell cultures have been used to elucidate the TIAs biosynthetic pathway. A considerable number or enzymes have also been characterised, and their respective genes cloned. TIAs production in C. roseus plant and cell cultures is highly regulated at transcriptional-, develop-mental-, and environmental-level. Studies into TIAs biosynthetic gene regulation have been carried out using cell cultures. However, regulation in plants is almost unknown. Here, biosynthetic genes idc, strl, d4h and dat expres-sion levels are qualitatively examined in a developmental series of C. roseus seedlings. The effect of water- and light-stress and methyl jasmonate (MeJa and acetyl salicylic acid (ASA elicitation is also examined. Comparison between seedlings and cell cultures strongly suggests that TIAs biosynthetic gene transcriptional regulation is different in C.roseus plants and cell cultures.

Bayesian Computational Approaches for Gene Regulation Studies of Bioethanol and Biohydrogen Production. Final Scientific/Technical Report

Energy Technology Data Exchange (ETDEWEB)

Newberg, Lee; McCue, Lee Anne; Van Roey, Patrick

2014-04-17

The project developed mathematical models and first-version software tools for the understanding of gene regulation across multiple related species. The project lays the foundation for understanding how certain alpha-proteobacterial species control their own genes for bioethanol and biohydrogen production, and sets the stage for exploiting bacteria for the production of fuels. Enabling such alternative sources of fuel is a high priority for the Department of Energy and the public.

Environmental Policies, Product Market Regulation and Innovation in Renewable Energy

International Nuclear Information System (INIS)

Nesta, Lionel; Vona, Francesco; Nicolli, Francesco

2012-10-01

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)

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

Directory of Open Access Journals (Sweden)

Justyna Górna

2009-01-01

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.

Characterization of an Lrp/AsnC family regulator SCO3361, controlling actinorhodin production and morphological development in Streptomyces coelicolor.

Science.gov (United States)

Liu, Jing; Li, Jie; Dong, Hong; Chen, Yunfu; Wang, Yansheng; Wu, Hang; Li, Changrun; Weaver, David T; Zhang, Lixin; Zhang, Buchang

2017-07-01

Lrp/AsnC family regulators have been found in many bacteria as crucial regulators controlling diverse cellular processes. By genomic alignment, we found that SCO3361, an Lrp/AsnC family protein from Streptomyces coelicolor, shared the highest similarity to the SACE_Lrp from Saccharopolyspora erythraea. Deletion of SCO3361 led to dramatic reduction in actinorhodin (Act) production and delay in aerial mycelium formation and sporulation on solid media. Dissection of the mechanism underlying the function of SCO3361 in Act production revealed that it altered the transcription of the cluster-situated regulator gene actII-ORF4 by directly binding to its promoter. SCO3361 was an auto-regulator and simultaneously activated the transcription of its adjacent divergently transcribed gene SCO3362. SCO3361 affected aerial hyphae formation and sporulation of S. coelicolor by activating the expression of amfC, whiB, and ssgB. Phenylalanine and cysteine were identified as the effector molecules of SCO3361, with phenylalanine reducing the binding affinity, whereas cysteine increasing it. Moreover, interactional regulation between SCO3361 and SACE_Lrp was discovered for binding to each other's target gene promoter in this work. Our findings indicate that SCO3361 functions as a pleiotropic regulator controlling secondary metabolism and morphological development in S. coelicolor.

Dissecting and engineering of the TetR family regulator SACE_7301 for enhanced erythromycin production in Saccharopolyspora erythraea.

Science.gov (United States)

Wu, Hang; Chen, Meng; Mao, Yongrong; Li, Weiwei; Liu, Jingtao; Huang, Xunduan; Zhou, Ying; Ye, Bang-Ce; Zhang, Lixin; Weaver, David T; Zhang, Buchang

2014-11-13

Saccharopolyspora erythraea was extensively utilized for the industrial-scale production of erythromycin A (Er-A), a macrolide antibiotic commonly used in human medicine. Yet, S. erythraea lacks regulatory genes in the erythromycin biosynthetic gene (ery) cluster, hampering efforts to enhance Er-A production via the engineering of regulatory genes. By the chromosome gene inactivation technique based on homologous recombination with linearized DNA fragments, we have inactivated a number of candidate TetR family transcriptional regulators (TFRs) and identified one TFR (SACE_7301) positively controlling erythromycin biosynthesis in S. erythraea A226. qRT-PCR and EMSA analyses demonstrated that SACE_7301 activated the transcription of erythromycin biosynthetic gene eryAI and the resistance gene ermE by interacting with their promoter regions with low affinities, similar to BldD (SACE_2077) previously identified to regulate erythromycin biosynthesis and morphological differentiation. Therefore, we designed a strategy for overexpressing SACE_7301 with 1 to 3 extra copies under the control of PermE* in A226. Following up-regulated transcriptional expression of SACE_7301, eryAI and ermE, the SACE_7301-overexpressed strains all increased Er-A production over A226 proportional to the number of copies. Likewise, when SACE_7301 was overexpressed in an industrial S. erythraea WB strain, Er-A yields of the mutants WB/7301, WB/2×7301 and WB/3×7301 were respectively increased by 17%, 29% and 42% relative to that of WB. In a 5 L fermentor, Er-A accumulation increased to 4,230 mg/L with the highest-yield strain WB/3×7301, an approximately 27% production improvement over WB (3,322 mg/L). We have identified and characterized a TFR, SACE_7301, in S. erythraea that positively regulated erythromycin biosynthesis, and overexpression of SACE_7301 in wild-type and industrial S. erythraea strains enhanced Er-A yields. This study markedly improves our understanding of the unusual

A novel regulator controls Clostridium difficile sporulation, motility and toxin production.

Science.gov (United States)

Edwards, Adrianne N; Tamayo, Rita; McBride, Shonna M

2016-06-01

Clostridium difficile is an anaerobic pathogen that forms spores which promote survival in the environment and transmission to new hosts. The regulatory pathways by which C. difficile initiates spore formation are poorly understood. We identified two factors with limited similarity to the Rap sporulation proteins of other spore-forming bacteria. In this study, we show that disruption of the gene CD3668 reduces sporulation and increases toxin production and motility. This mutant was more virulent and exhibited increased toxin gene expression in the hamster model of infection. Based on these phenotypes, we have renamed this locus rstA, for regulator of sporulation and toxins. Our data demonstrate that RstA is a bifunctional protein that upregulates sporulation through an unidentified pathway and represses motility and toxin production by influencing sigD transcription. Conserved RstA orthologs are present in other pathogenic and industrial Clostridium species and may represent a key regulatory protein controlling clostridial sporulation. © 2016 John Wiley & Sons Ltd.

Kinetics and Regulation Studies of the Production of β-Galactosidase from Kluyveromyces marxianus Grown on Different Substrates

Directory of Open Access Journals (Sweden)

Samia Khan

2003-01-01

Full Text Available Lactose-intolerance is manifested in 50 % of the world’s population. This can be remediated by removing lactose from the diet or converting it into glucose and galactose with β-galactosidase (EC 3.2.1.23. In this work, batch production of this enzyme in the presence of lactose, galactose, cellobiose, xylose, arabinose, sucrose and glucose was investigated using Kluyveromyces marxianus in shake flask culture studies. Substrate type and temperature were the independent variables that directly regulated the specific growth and β-galactosidase production rates. Lactose (2 % supported the maximum specific product yield (YP/X, followed by galactose, sucrose, cellobiose, xylose, arabinose and glucose. Its synthesis was regulated by an induction and a growth-dependent repression mechanism. The optimum temperature for the production was found to be 35–37 °C. The highest volumetric productivity of enzyme (80.0 IU/L/h occurred on lactose-corn steep liquor medium. This was significantly higher than the calculated values reported in the literature. Thermodynamic studies revealed that the cells provided a defence mechanism against thermal inactivation. The enzyme was stable at 60 °C and pH=5.0–7.0, and it may find application in commercial lactose hydrolysis.

Abnormal regulation for progesterone production in placenta with prenatal cocaine exposure in rats.

Science.gov (United States)

Wu, L; Yan, J; Qu, S C; Feng, Y Q; Jiang, X L

2012-12-01

Cocaine abuse in pregnant women is currently a significant public hygiene problem and is tightly associated with elevated risk for preterm delivery. Placental steroidogenesis especially progesterone production was essential for success and maintenance of pregnancy in humans and rodents. In the present study, we determined the impact of prenatal cocaine exposure on pathways of placental progesterone synthesis in rats. Pregnant rats were treated cocaine twice daily (15 mg/kg/day) during the third trimester, and the maternal and fetal plasma progesterone and pregnenolone concentrations were detected. We also examined both the protein and mRNA expression of some key enzymes and regulators for progesterone production in placenta. Results showed that, after maternal cocaine use during pregnancy, progesterone and pregnenolone concentrations in both maternal and fetal rats were significantly decreased. Although prenatal cocaine exposure had no effects on placental 3β-hydroxysteroid dehydrogenase type 1 (3βHSD1) expression, protein and mRNA expression of the cholesterol side-chain cleavage enzyme (P450scc/CYP11a) in placenta was significantly inhibited. Moreover, protein and mRNA expressions of MLN64 that regulating cholesterol transport and activating protein 2γ (AP2γ/Tfap2c) that controlling P450scc/CYP11a gene expression in placenta were both decreased following maternal cocaine use in pregnancy. Collectively, this study suggested that prenatal cocaine exposure could insult the placental progesterone production in rats possibly associated with the high risk for preterm delivery. Copyright © 2012 Elsevier Ltd. All rights reserved.

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

Directory of Open Access Journals (Sweden)

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.

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

International Nuclear Information System (INIS)

Puddu, A.; Storace, D.; Odetti, P.; Viviani, G.L.

2010-01-01

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.

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

Centers for Disease Control (CDC) Podcasts

2010-09-16

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.

Environmental Regulation and Competitiveness: Evidence from Trade and Production in the Manufacturing Sector

OpenAIRE

Yang, Tsung Yu

2014-01-01

Previous empirical studies of the pollution haven hypothesis (PHH) have not reached a consistent conclusion. The existing literature is primarily based on anecdotes and scattered case studies. This study analyzes the trade flows and composition change of the most polluting industries in manufacturing sectors among countries in order to offer a more general conclusion. This study finds that stricter environmental regulation stringency decreases the net export and production share of the most p...

Activin A, B and AB decrease progesterone production by down-regulating StAR in human granulosa cells.

Science.gov (United States)

Chang, Hsun-Ming; Cheng, Jung-Chien; Huang, He-Feng; Shi, Feng-Tao; Leung, Peter C K

2015-09-05

Activins are homo- or heterodimers of inhibin β subunits that play important roles in the reproductive system. Our previous work has shown that activins A (βAβA), B (βBβB) and AB (βAβB) induce aromatase/estradiol, but suppress StAR/progesterone production in human granulosa-lutein cells. However, the underlying molecular determinants of these effects have not been examined. In this continuing study, we used immortalized human granulosa cells (SVOG) to investigate the effects of activins in regulating StAR/progesterone and the potential mechanisms of action. In SVOG cells, activins A, B and AB produced comparable down-regulation of StAR expression and progesterone production. In addition, all three activin isoforms induced equivalent phosphorylation of both SMAD2 and SMAD3. Importantly, the activin-induced down-regulation of StAR, increase in SMAD2/3 phosphorylation, and decrease in progesterone were abolished by the TGF-β type I receptor inhibitor SB431542. Interestingly, the small interfering RNA-mediated knockdown of ALK4 but not ALK5 reversed the activin-induced suppression of StAR. Furthermore, the knockdown of SMAD4 or SMAD2 but not SMAD3 abolished the inhibitory effects of all three activin isoforms on StAR expression. These results provide evidence that activins A, B and AB down-regulate StAR expression and decrease progesterone production in human granulosa cells, likely via an ALK4-mediated SMAD2/SMAD4-dependent pathway. Our findings provide important insights into the molecular mechanisms underlying the regulatory effects of activins on human granulosa cell steroidogenesis. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

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

Science.gov (United States)

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

2016-02-10

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.

The RNA chaperone, Hfq, controls two luxR-type regulators and plays a key role in pathogenesis and production of antibiotics in Serratia sp. ATCC 39006.

Science.gov (United States)

Wilf, Nabil M; Williamson, Neil R; Ramsay, Joshua P; Poulter, Simon; Bandyra, Kasia J; Salmond, George P C

2011-10-01

Serratia sp. ATCC 39006 (S39006) is a Gram-negative bacterium that is virulent in plant (potato) and animal (Caenorhabditis elegans) models. It produces two secondary metabolite antibiotics, a prodigiosin and a carbapenem, and the exoenzymes, pectate lyase and cellulase. A complex regulatory network that includes quorum sensing (QS) controls production of prodigiosin. While many aspects of the regulation of the metabolites and exoenzymes are well understood, the potential role in this network of the RNA chaperone Hfq and dependent small regulatory RNAs has not been characterized. Hfq is an RNA chaperone involved in post-transcriptional regulation that plays a key role in stress response and virulence in diverse bacterial species. To explore whether Hfq-dependent processes might contribute to the regulation of antibiotic production we constructed an S39006 Δhfq mutant. Production of prodigiosin and carbapenem was abolished in this mutant strain, while production of the QS signalling molecule, butanoyl homoserine lactone (BHL), was unaffected. Using transcriptional fusions, we found that Hfq regulates the QS response regulators, SmaR and CarR. Additionally, exoenzyme production and swimming motility were decreased in a Δhfq mutant, and virulence was attenuated in potato and C. elegans models. These results suggest that an Hfq-dependent pathway is involved in the regulation of virulence and secondary metabolite production in S39006. © 2011 Society for Applied Microbiology and Blackwell Publishing Ltd.

76 FR 76168 - Regulatory Site Visit Training Program

Science.gov (United States)

2011-12-06

... quality of its regulatory efforts and interactions, by providing CBER staff with a better understanding of... may include the following: (1) Packaging facilities, (2) quality control and pathology/toxicology...

76 FR 4919 - Regulatory Site Visit Training Program

Science.gov (United States)

2011-01-27

... quality of its regulatory efforts and interactions, by providing CBER staff with a better understanding of... may include the following: (1) Packaging facilities, (2) quality control and pathology/toxicology...

[Food supplements on the Hungarian market: regulations of marketing and of the composition of the products].

Science.gov (United States)

Lugasi, Andrea; Horacsek, Márta; Martos, Eva

2010-09-26

According to recent legislation, food supplements are foodstuffs with the purpose of supplementing normal diet. Food supplements are concentrated sources of nutrients such as vitamins and minerals and other substances with a physiological or nutritional effect. In Hungary, marketing of food supplements has not been bound to pre-market authorization since joining to the European Union. The food business operator, who is responsible for production or distribution of the product, must notify it at National Institute for Food and Nutrition Science latest at the time when the product has been placed on the market and it can be distributed simultaneously. Distribution, ingredients, and all those information which appear on the label are determined by numerous regulations and prescriptions but at the same time the lack of harmonized legislation at certain places may cause a lot of problems on Community level. The first part of the study shows the laws and regulations influencing the distribution and ingredients of food supplements, while the main target of the second part is to introduce the evaluation process of components from nutritional and physiological point of view, and the role played by the food supplements in nutrition.

Market, Regulation, Market, Regulation

DEFF Research Database (Denmark)

Frankel, Christian; Galland, Jean-Pierre

2015-01-01

barriers to trade in Europe, realized the free movement of products by organizing progressively several orders of markets and regulation. Based on historical and institutional documents, on technical publications, and on interviews, this article relates how the European Commission and the Member States had......This paper focuses on the European Regulatory system which was settled both for opening the Single Market for products and ensuring the consumers' safety. It claims that the New Approach and Standardization, and the Global Approach to conformity assessment, which suppressed the last technical...... alternatively recourse to markets and to regulations, at the three main levels of the New Approach Directives implementation. The article focuses also more specifically on the Medical Devices sector, not only because this New Approach sector has long been controversial in Europe, and has recently been concerned...

Regulation of metabolic products and gene expression in Fusarium asiaticum by agmatine addition.

Science.gov (United States)

Suzuki, Tadahiro; Kim, Young-Kyung; Yoshioka, Hifumi; Iwahashi, Yumiko

2013-05-01

The metabolic products resulting from the cultivation of F. asiaticum in agmatine were identified using capillary electrophoresis-time of flight mass spectrometry. Glyoxylic acid was detected from fungal cultures grown in agmatine, while it was absent in control cells. The abundance of other metabolic products of the glycolytic pathway also increased because of agmatine; however, there was no increase in the amounts of pyruvic acid or metabolites from the tricarboxylic acid cycle. Moreover, gene expression levels within Fusarium asiaticum exposed to agmatine were analyzed by DNA microarray. Changes in gene expression levels directed the changes in metabolic products. Our results suggest that acetyl coenzyme A, which is a starting substrate for the biosynthesis of deoxynivalenol (DON), was simultaneously produced by activated β-oxidation. Furthermore, the content of 4-aminobutyrate (GABA) was increased in the agmatine addition culture medium. GABA can be synthesized from agmatine through putrescine and might influence the regulation of DON-related genes.

Reproduction-Related Sound Production of Grasshoppers Regulated by Internal State and Actual Sensory Environment

Science.gov (United States)

Heinrich, Ralf; Kunst, Michael; Wirmer, Andrea

2012-01-01

The interplay of neural and hormonal mechanisms activated by entero- and extero-receptors biases the selection of actions by decision making neuronal circuits. The reproductive behavior of acoustically communicating grasshoppers, which is regulated by short-term neural and longer-term hormonal mechanisms, has frequently been used to study the cellular and physiological processes that select particular actions from the species-specific repertoire of behaviors. Various grasshoppers communicate with species- and situation-specific songs in order to attract and court mating partners, to signal reproductive readiness, or to fend off competitors. Selection and coordination of type, intensity, and timing of sound signals is mediated by the central complex, a highly structured brain neuropil known to integrate multimodal pre-processed sensory information by a large number of chemical messengers. In addition, reproductive activity including sound production critically depends on maturation, previous mating experience, and oviposition cycles. In this regard, juvenile hormone released from the corpora allata has been identified as a decisive hormonal signal necessary to establish reproductive motivation in grasshopper females. Both regulatory systems, the central complex mediating short-term regulation and the corpora allata mediating longer-term regulation of reproduction-related sound production mutually influence each other’s activity in order to generate a coherent state of excitation that promotes or suppresses reproductive behavior in respective appropriate or inappropriate situations. This review summarizes our current knowledge about extrinsic and intrinsic factors that influence grasshopper reproductive motivation, their representation in the nervous system and their integrative processing that mediates the initiation or suppression of reproductive behaviors. PMID:22737107

Reproduction-related sound production of grasshoppers regulated by internal state and actual sensory environment

Directory of Open Access Journals (Sweden)

Ralf eHeinrich

2012-06-01

Full Text Available The interplay of neural and hormonal mechanisms activated by entero- and exteroreceptors biases the selection of actions by decision making neuronal circuits. The reproductive behaviour of acoustically communicating grasshoppers, which is regulated by short-term neural and longer-term hormonal mechanisms, has frequently been used to study the cellular and physiological processes that select particular actions from the species-specific repertoire of behaviours. Various grasshoppers communicate with species- and situation-specific songs in order to attract and court mating partners, to signal reproductive readiness or to fend off competitors. Selection and coordination of type, intensity and timing of sound signals is mediated by the central complex, a highly structured brain neuropil known to integrate multimodal pre-processed sensory information by a large number of chemical messengers. In addition, reproductive activity including sound production critically depends on maturation, previous mating experience and oviposition cycles. In this regard, juvenile hormone released from the corpora allata has been identified as a decisive hormonal signal necessary to establish reproductive motivation in grasshopper females. Both regulatory systems, the central complex mediating short-term regulation and the corpora allata mediating longer-term regulation of reproduction related sound production mutually influence each other’s activity in order to generate a coherent state of excitation that promotes or suppresses reproductive behaviour in respective appropriate or inappropriate situations.This review summarizes our current knowledge about extrinsic and intrinsic factors that influence grasshopper reproductive motivation, their representation in the nervous system and their integrative processing that mediates the initiation or suppression of reproductive behaviors.

Tradeable emission permits regulations in the presence of imperfectly competitive product markets. Welfare implications

International Nuclear Information System (INIS)

Sartzetakis, E.S.

1997-01-01

In the present paper, we analyse the interaction of a competitive market for emission permits with an oligopolistic product market. It is well known that a competitive permits market achieves the cost minimizing distribution of abatement effort among the polluting firms for a given reduction in emissions. However, when the product market is oligopolistic, it may redistribute production inefficiently among firms. It has been suggested that this inefficiency can outweigh the gains obtained from using emission permits instead of command and control. Although this argument is clearly correct under full information, it is shown in the present paper that it reverses under incomplete information. In particular, it is shown that when tradeable emission permits are specified according to the standard textbook example, they yield higher social welfare than the command and control regulation. 1 fig., 2 appendices, 11 refs

Postgraduate education and research in Brazil: regulation and reconfiguration processes of academic work formation and production

Directory of Open Access Journals (Sweden)

João Ferreira de Oliveira

2015-07-01

Full Text Available This text analyses some of the processes of formation and production regulation and reconfiguration of the scholarly work in Brazil. Initially we examine the context and meaning of knowledge production in times of flexible accumulation, as well as the current landscape of Postgraduate education in the country. We seek to understand how public policies in the area, particularly the actions of evaluation and promotion, and the new modus operandi of the Postgraduate study and research organization have been reconfiguring the work production of teaching and students within the programs, especially in education. Above all, we seek to highlight the role of promotion and evaluation agencies, increasingly committed to a vision of expansion that drives the production of knowledge associated with demands of economic-productivity, rather than a consistent formative project that would result in a significant advancement in the production and dissemination of knowledge in the different areas.

Does regulation stimulate productivity? The effect of air quality policies on the efficiency of US power plants

International Nuclear Information System (INIS)

Fleishman, Rachel; Alexander, Rob; Bretschneider, Stuart; Popp, David

2009-01-01

This research examines the effect of air quality regulations on the productivity of US power plants based on both economic and environmental outputs. Using data envelopment analysis (DEA) to estimate an efficiency measure incorporating both economic and environmental outcomes, we look at changes in efficiency in US power plants over an eleven-year time period (1994-2004) during which several different regulations were implemented for the control of nitrogen oxides (NO x ) and sulfur dioxide (SO 2 ). The paper then models how estimated efficiency behaves over time as a function of regulatory changes. Findings suggest mixed effects of regulations on power plant efficiency when pollution abatement and electricity generation are both included as outputs.

Nitric oxide production from macrophages is regulated by arachidonic acid metabolites.

Science.gov (United States)

Imai, Y; Kolb, H; Burkart, V

1993-11-30

In activated macrophages the inducible form of the enzyme nitric oxide (NO) synthase generates high amounts of the toxic mediator NO. After 20 h of treatment with LPS rat peritoneal macrophages release 12-16 nmol NO2-/10(5) cells which is detectable in the culture supernatant by the Griess reaction as a measure of NO formation. The addition of aminoguanidine (1 mM), a preferential inhibitor of the inducible NO-synthase, completely abolished NO2-accumulation. Incubation with indomethacin or acetyl-salicylic acid, preferential inhibitors of the cyclooxygenase pathway of the arachidonic acid metabolism, did not influence NO2- levels. Nordihydro-guaiaretic acid (50 microM), a preferential inhibitor of the lipoxygenase pathway, caused strong reduction of NO2- accumulation to 1.9 +/- 0.3 nmol/200 microliter. Simultaneous inhibition of cyclo- and lipoxygenase by BW755c resulted in an intermediate effect (7.3 +/- 1.1 nmol/200 microliter NO2-). These results show that the induction of NO production in activated macrophages is regulated by products of the lipoxygenase-pathway of the arachidonic acid metabolism.

Electron acceptor-based regulation of microbial greenhouse gas production from thawing permafrost

DEFF Research Database (Denmark)

Bak, Ebbe Norskov; Jones, Eleanor; Yde, Jacob Clement

layer as well in the permafrost. These investigations are accompanied by characterization of the carbon, iron and sulfate content in the soil and will be followed by characterization of the microbial community structure. The aim of this study is to get a better understanding of how the availability...... of sulfate and iron and the microbial community structure regulate the production of CO2 and CH4 in thawing permafrost, and to elucidate how the rate of the organic carbon degradation changes with depth in permafrost-affected soils. This study improves our understanding of climate feedback mechanisms...

Intestinal intraepithelial lymphocyte-enterocyte crosstalk regulates production of bactericidal angiogenin 4 by Paneth cells upon microbial challenge.

Directory of Open Access Journals (Sweden)

Catherine R Walker

Full Text Available Antimicrobial proteins influence intestinal microbial ecology and limit proliferation of pathogens, yet the regulation of their expression has only been partially elucidated. Here, we have identified a putative pathway involving epithelial cells and intestinal intraepithelial lymphocytes (iIELs that leads to antimicrobial protein (AMP production by Paneth cells. Mice lacking γδ iIELs (TCRδ(-/- express significantly reduced levels of the AMP angiogenin 4 (Ang4. These mice were also unable to up-regulate Ang4 production following oral challenge by Salmonella, leading to higher levels of mucosal invasion compared to their wild type counterparts during the first 2 hours post-challenge. The transfer of γδ iIELs from wild type (WT mice to TCRδ(-/- mice restored Ang4 production and Salmonella invasion levels were reduced to those obtained in WT mice. The ability to restore Ang4 production in TCRδ(-/- mice was shown to be restricted to γδ iIELs expressing Vγ7-encoded TCRs. Using a novel intestinal crypt co-culture system we identified a putative pathway of Ang4 production initiated by exposure to Salmonella, intestinal commensals or microbial antigens that induced intestinal epithelial cells to produce cytokines including IL‑23 in a TLR-mediated manner. Exposure of TCR-Vγ7(+ γδ iIELs to IL-23 promoted IL‑22 production, which triggered Paneth cells to secrete Ang4. These findings identify a novel role for γδ iIELs in mucosal defence through sensing immediate epithelial cell cytokine responses and influencing AMP production. This in turn can contribute to the maintenance of intestinal microbial homeostasis and epithelial barrier function, and limit pathogen invasion.

A genomics resource for investigating regulation of essential oil production in Lavandula angustifolia.

Science.gov (United States)

Lane, Alexander; Boecklemann, Astrid; Woronuk, Grant N; Sarker, Lukman; Mahmoud, Soheil S

2010-03-01

We are developing Lavandula angustifolia (lavender) as a model system for investigating molecular regulation of essential oil (a mixture of mono- and sesquiterpenes) production in plants. As an initial step toward building the necessary 'genomics toolbox' for this species, we constructed two cDNA libraries from lavender leaves and flowers, and obtained sequence information for 14,213 high-quality expressed sequence tags (ESTs). Based on homology to sequences present in GenBank, our EST collection contains orthologs for genes involved in the 1-deoxy-D: -xylulose-5-phosphate (DXP) and the mevalonic acid (MVA) pathways of terpenoid biosynthesis, and for known terpene synthases and prenyl transferases. To gain insight into the regulation of terpene metabolism in lavender flowers, we evaluated the transcriptional activity of the genes encoding for 1-deoxy-D: -xylulose-5-phosphate synthase (DXS) and HMG-CoA reductase (HMGR), which represent regulatory steps of the DXP and MVA pathways, respectively, in glandular trichomes (oil glands) by real-time PCR. While HMGR transcripts were barely detectable, DXS was heavily expressed in this tissue, indicating that essential oil constituents are predominantly produced through the DXP pathway in lavender glandular trichomes. As anticipated, the linalool synthase (LinS)-the gene responsible for the production of linalool, a major constituent of lavender essential oil-was also strongly expressed in glands. Surprisingly, the most abundant transcript in floral glandular trichomes corresponded to a sesquiterpene synthase (cadinene synthase, CadS), although sesquiterpenes are minor constituents of lavender essential oils. This result, coupled to the weak activity of the MVA pathway (the main route for sesquiterpene production) in trichomes, indicates that precursor supply may represent a bottleneck in the biosynthesis of sesquiterpenes in lavender flowers.

Retail sales of scheduled listed chemical products; self-certification of regulated sellers of scheduled listed chemical products. Interim final rule with request for comment.

Science.gov (United States)

2006-09-26

In March 2006, the President signed the Combat Methamphetamine Epidemic Act of 2005, which establishes new requirements for retail sales of over-the-counter (nonprescription) products containing the List I chemicals ephedrine, pseudoephedrine, and phenylpropanolamine. The three chemicals can be used to manufacture methamphetamine illegally. DEA is promulgating this rule to incorporate the statutory provisions and make its regulations consistent with the new requirements. This action establishes daily and 30-day limits on the sales of scheduled listed chemical products to individuals and requires recordkeeping on most sales.

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

Directory of Open Access Journals (Sweden)

Uesaka Miki

2008-12-01

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

SIRT3 deacetylates mitochondrial 3-hydroxy-3-methylglutaryl CoA synthase 2 and regulates ketone body production

DEFF Research Database (Denmark)

Shimazu, Tadahiro; Hirschey, Matthew D; Hua, Lan

2010-01-01

with SIRT3 and in vivo by overexpression of SIRT3. Deacetylation of HMGCS2 lysines 310, 447, and 473 by incubation with wild-type SIRT3 or by mutation to arginine enhances its enzymatic activity. Molecular dynamics simulations show that in silico deacetylation of these three lysines causes conformational...... changes of HMGCS2 near the active site. Mice lacking SIRT3 show decreased β-hydroxybutyrate levels during fasting. Our findings show SIRT3 regulates ketone body production during fasting and provide molecular insight into how protein acetylation can regulate enzymatic activity....

Autonomic regulation of hepatic glucose production.

Science.gov (United States)

Bisschop, Peter H; Fliers, Eric; Kalsbeek, Andries

2015-01-01

Glucose produced by the liver is a major energy source for the brain. Considering its critical dependence on glucose, it seems only natural that the brain is capable of monitoring and controlling glucose homeostasis. In addition to neuroendocrine pathways, the brain uses the autonomic nervous system to communicate with peripheral organs. Within the brain, the hypothalamus is the key region to integrate signals on energy status, including signals from lipid, glucose, and hormone sensing cells, with afferent neural signals from the internal and external milieu. In turn, the hypothalamus regulates metabolism in peripheral organs, including the liver, not only via the anterior pituitary gland but also via multiple neuropeptidergic pathways in the hypothalamus that have been identified as regulators of hepatic glucose metabolism. These pathways comprise preautonomic neurons projecting to nuclei in the brain stem and spinal cord, which relay signals from the hypothalamus to the liver via the autonomic nervous system. The neuroendocrine and neuronal outputs of the hypothalamus are not separate entities. They appear to act as a single integrated regulatory system, far more subtle, and complex than when each is viewed in isolation. Consequently, hypothalamic regulation should be viewed as a summation of both neuroendocrine and neural influences. As a result, our endocrine-based understanding of diseases such as diabetes and obesity should be expanded by integration of neural inputs into our concept of the pathophysiological process. © 2014 American Physiological Society.

A comparison of US and Norwegian regulation of coumarin in tobacco products

Science.gov (United States)

Givel, M

2003-01-01

Objective: This paper examines policy processes regarding why the USA and Norway have not regulated coumarin in tobacco. Design: A qualitative analysis of all tobacco industry documents regarding coumarin since the 1950s from the 1998 US Master Settlement Agreement and subsequent legal settlements. Additional data were collected from newspaper reports, general internet search engines, journal articles, scholarly reports, court cases, statutes, regulations, and informal correspondence with tobacco control experts in Norway. Main outcome measure: An overview, summary, and analysis of all documents related to coumarin. Results: In the USA from 1954 until 1985 when coumarin was reportedly removed from domestic cigarettes, but not from pipe tobacco until 1996, and not at all from imported Indian bidi cigarettes, regulatory efforts were stymied. In Norway, from 1973 to the present, the tobacco industry has never disclosed whether its tobacco products contain coumarin. In both the USA and Norway, the extreme delay and lack of vigorous evidence gathering and significant remedies were caused by tobacco industry assertions that revealing tobacco additives was a violation of trade secrets, and by weak regulatory authority and efforts to regulate coumarin. Conclusion: Vigorous and expeditious regulatory investigations and remedies for harmful additives in tobacco, such as coumarin, can protect the public health. Astute insider and outsider political advocacy by health advocates is required to hold elected officials and civil servants publicly accountable for failing to enact disclosure laws and to engage in effective regulatory efforts. PMID:14660776

Functional Characterization of NAC and MYB Transcription Factors Involved in Regulation of Biomass Production in Switchgrass (Panicum virgatum.

Directory of Open Access Journals (Sweden)

Ruiqin Zhong

Full Text Available Switchgrass is a promising biofuel feedstock due to its high biomass production and low agronomic input requirements. Because the bulk of switchgrass biomass used for biofuel production is lignocellulosic secondary walls, studies on secondary wall biosynthesis and its transcriptional regulation are imperative for designing strategies for genetic improvement of biomass production in switchgrass. Here, we report the identification and functional characterization of a group of switchgrass transcription factors, including several NACs (PvSWNs and a MYB (PvMYB46A, for their involvement in regulating secondary wall biosynthesis. PvSWNs and PvMYB46A were found to be highly expressed in stems and their expression was closely associated with sclerenchyma cells. Overexpression of PvSWNs and PvMYB46A in Arabidopsis was shown to result in activation of the biosynthetic genes for cellulose, xylan and lignin and ectopic deposition of secondary walls in normally parenchymatous cells. Transactivation and complementation studies demonstrated that PvSWNs were able to activate the SNBE-driven GUS reporter gene and effectively rescue the secondary wall defects in the Arabidopsis snd1 nst1 double mutant, indicating that they are functional orthologs of Arabidopsis SWNs. Furthermore, we showed that PvMYB46A could activate the SMRE-driven GUS reporter gene and complement the Arabidopsis myb46 myb83 double mutant, suggesting that it is a functional ortholog of Arabidopsis MYB46/MYB83. Together, these results indicate that PvSWNs and PvMYB46A are transcriptional switches involved in regulating secondary wall biosynthesis, which provides molecular tools for genetic manipulation of biomass production in switchgrass.

DksA-HapR-RpoS axis regulates haemagglutinin protease production in Vibrio cholerae.

Science.gov (United States)

Basu, Pallabi; Pal, Ritesh Ranjan; Dasgupta, Shreya; Bhadra, Rupak K

2017-06-01

DksA acts as a co-factor for the intracellular small signalling molecule ppGpp during the stringent response. We recently reported that the expression of the haemagglutinin protease (HAP), which is needed for shedding of the cholera pathogen Vibrio cholerae during the late phase of infection, is significantly downregulated in V. cholerae ∆dksA mutant (∆dksAVc) cells. So far, it has been shown that HAP production by V. cholerae cells is critically regulated by HapR and also by RpoS. Here, we provide evidence that V. cholerae DksA (DksAVc) positively regulates HapR at both the transcriptional and post-transcriptional levels. We show that in ∆dksAVc cells the CsrB/C/D sRNAs, required for the maintenance of intracellular levels of hapR transcripts during the stationary growth, are distinctly downregulated. Moreover, the expression of exponential phase regulatory protein Fis, a known negative regulator of HapR, was found to continue even during the stationary phase in ∆dksAVc cells compared to that of wild-type strain, suggesting another layer of complex regulation of HapR by DksAVc. Extensive reporter construct-based and quantitative reverse-transcriptase PCR (qRT-PCR) analyses supported that RpoS is distinctly downregulated at the post-transcriptional/translational levels in stationary phase-grown ∆dksAVc cells. Since HAP expression through HapR and RpoS is stationary phase-specific in V. cholerae, it appears that DksAVc is also a critical stationary phase regulator for fine tuning of the expression of HAP. Moreover, experimental evidence provided in this study clearly supports that DksAVc is sitting at the top of the hierarchy of regulation of expression of HAP in V. cholerae.

Insulin-like peptide 5 is a microbially regulated peptide that promotes hepatic glucose production

DEFF Research Database (Denmark)

Lee, Ying Shiuan; De Vadder, Filipe; Tremaroli, Valentina

2016-01-01

expression in the brain was higher in CONV-R versus GF mice. We also observed that colonic Insl5 expression was suppressed by increasing the energy supply in GF mice by colonization or high-fat feeding. We did not observe any differences in food intake, gut transit or oral glucose tolerance between Insl5......-/- and wild-type mice. However, we showed impaired intraperitoneal glucose tolerance in Insl5-/- mice. We also observed improved insulin tolerance and reduced hepatic glucose production in Insl5-/- mice. CONCLUSIONS: We have shown that colonic Insl5 expression is regulated by the gut microbiota and energy...... availability. We propose that INSL5 is a hormone that could play a role in promoting hepatic glucose production during periods of energy deprivation....

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

Directory of Open Access Journals (Sweden)

Izabela eChincinska

2013-02-01

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.

[Analysis of difficult problems on European Union laws and regulations of traditional herbal medicinal products].

Science.gov (United States)

Qu, Li-Ping; Zhang, Xiao-Qun; Xiong, Yan; Wang, Yi-Tao; Zou, Wen-Jun

2017-10-01

Registration of Chinese patent medicine in European Union (EU) is of great significance to the internationalization of traditional Chinese medicine as EU market acts as an important position in the global botanical market. In retrospect, the domestic studies on EU regulations of traditional herbal medicinal products have been conducted for more than 10 years, but there is still some cognitive bias and lack of research. In this paper, a review of the relevant research progress and the main misunderstanding problems about Directive 2004/24/EC, like the centralized and decentralized supervision system of traditional herbal medicinal products in the EU, marketing authorization procedures for traditional herbal medicinal products, Community Herbal Monograph and List Entries, would be systematically analyzed, so as to provide reference for the registration of Chinese patent medicine in EU. Copyright© by the Chinese Pharmaceutical Association.

Regulation of non-relevant metabolites of plant protection products in drinking and groundwater in the EU: Current status and way forward.

Science.gov (United States)

Laabs, V; Leake, C; Botham, P; Melching-Kollmuß, S

2015-10-01

Non-relevant metabolites are defined in the EU regulation for plant protection product authorization and a detailed definition of non-relevant metabolites is given in an EU Commission DG Sanco (now DG SANTE - Health and Food Safety) guidance document. However, in water legislation at EU and member state level non-relevant metabolites of pesticides are either not specifically regulated or diverse threshold values are applied. Based on their inherent properties, non-relevant metabolites should be regulated based on substance-specific and toxicity-based limit values in drinking and groundwater like other anthropogenic chemicals. Yet, if a general limit value for non-relevant metabolites in drinking and groundwater is favored, an application of a Threshold of Toxicological Concern (TTC) concept for Cramer class III compounds leads to a threshold value of 4.5 μg L(-1). This general value is exemplarily shown to be protective for non-relevant metabolites, based on individual drinking water limit values derived for a set of 56 non-relevant metabolites. A consistent definition of non-relevant metabolites of plant protection products, as well as their uniform regulation in drinking and groundwater in the EU, is important to achieve legal clarity for all stakeholders and to establish planning security for development of plant protection products for the European market. Copyright © 2015 Elsevier Inc. All rights reserved.

[Plant protection products and their residues : Aspects of consumer safety in context of the new EU regulations].

Science.gov (United States)

Banasiak, U; Michalski, B; Pfeil, R; Solecki, R

2010-06-01

The law regulating plant protection products (PPP) in the European Union (EU) was fundamentally revised through the introduction of Regulation (EC) No. 1107/2009 which is due to enter into force on 14 June 2011. EU-wide harmonized maximum residue levels (MRLs) for the active substances of PPP in foods are laid down in Regulation (EC) No. 396/2005 and apply since entry into force of the regulation on 1 September 2008. The goal of both regulations is to strengthen the level of consumer protection. PPP are subject to a strict assessment of active substances, which is regulated at the EU level as well as an authorization procedure in the EU Member States. Prior to application for authorization of a PPP, the active substance(s) it contains must be included in a positive list. Tests regarding the toxicity and residue behavior of PPP must be conducted by the applicant, and the respective documents must be submitted to the authorities for evaluation. Following review of the required data, toxicological threshold values are derived, consumer exposure is assessed, and the risk to health is evaluated. The goal of this evaluation is to ensure that the use of PPP according to good plant protection practice does not have any harmful effects on human health.

The AreA transcription factor in Fusarium graminearum regulates the use of some nonpreferred nitrogen sources and secondary metabolite production.

Science.gov (United States)

Giese, Henriette; Sondergaard, Teis Esben; Sørensen, Jens Laurids

2013-01-01

Growth conditions are known to affect the production of secondary metabolites in filamentous fungi. The influence of different nitrogen sources and the transcription factor AreA on the production of mycotoxins in Fusarium graminearum was examined. Growth on glutamine or NH4-sources was poor and asparagine was found to be a preferential nitrogen source for F. graminearum. Deletion of areA led to poor growth on NaNO₃ suggesting its involvement in regulation of the nitrate reduction process. In addition utilization of aspartic acid, histidine, isoleucine, leucine, threonine, tyrosine, and valine as nitrogen sources was shown to depend of a functional AreA. AreA was shown to be required for the production of the mycotoxins deoxynivalenol (DON), zearalenone, and fusarielin H regardless of the nutrient medium. Deletion of nmr, the repressor of AreA under nitrogen sufficient conditions, had little effect on either growth or toxin production. AreA appears to regulate production of some mycotoxins directly or indirectly independent on nitrogen status and plays a role in utilization of certain amino acids. Copyright © 2013 The British Mycological Society. All rights reserved.

Estrogen regulates progesterone production by human placental trophoblast cells in culture

International Nuclear Information System (INIS)

Grimes, R.W.

1990-01-01

We have suggested that estrogen regulates placental low-density lipoprotein (LDL) uptake and thus progesterone (P 4 ) 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 P 4 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 E 2 and 500 μg/MI LDL-protein, stimulated P 4 (P 2 increased LDL uptake. Scatchard analysis indicated that trophoblast uptake of [ 125 I]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 E 2 . These results suggest that estrogen regulates placental cell uptake of LDL and thus availability of cholesterol for P 4 biosynthesis during human pregnancy. In Experiment 2, E 2 Stimulated P 4 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 P 4 biosynthesis must have been derived from de novo synthesis and/or deesterification of cholesteryl ester stores

REGULATION D'UNE PRODUCTION EN SITUATION D'INCERTITUDES ET DE FORTES CONTRAINTES : EXEMPLE DES SYSTEMES RIZICOLES DU LAC ALAOTRA (MADAGASCAR)

OpenAIRE

Ducrot , Raphaele

1996-01-01

With state disengagement from land irrigation management, producers have to manage their production systems in an atmosphere of increasing risk and uncertainty. To achieve this, they implement adaptation processes and technical strategies for regulating production We have studied such behavior in the rice-production systems of Lake Alaotra in Madagascar. Strategies mainly rely on the organisation of land and on crop system management. A dual methodological approach was used to understand thes...

Interactions between calcium and phosphorus in the regulation of the production of fibroblast growth factor 23 in vivo

Science.gov (United States)

Quinn, Stephen J.; Thomsen, Alex R. B.; Pang, Jian L.; Kantham, Lakshmi; Bräuner-Osborne, Hans; Pollak, Martin; Goltzman, David

2013-01-01

Calcium and phosphorus homeostasis are highly interrelated and share common regulatory hormones, including FGF23. However, little is known about calcium's role in the regulation of FGF23. We sought to investigate the regulatory roles of calcium and phosphorus in FGF23 production using genetic mouse models with targeted inactivation of PTH (PTH KO) or both PTH and the calcium-sensing receptor (CaSR; PTH-CaSR DKO). In wild-type, PTH KO, and PTH-CaSR DKO mice, elevation of either serum calcium or phosphorus by intraperitoneal injection increased serum FGF23 levels. In PTH KO and PTH-CaSR DKO mice, however, increases in serum phosphorus by dietary manipulation were accompanied by severe hypocalcemia, which appeared to blunt stimulation of FGF23 release. Increases in dietary phosphorus in PTH-CaSR DKO mice markedly decreased serum 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] despite no change in FGF23, suggesting direct regulation of 1,25(OH)2D3 synthesis by serum phosphorus. Calcium-mediated increases in serum FGF23 required a threshold level of serum phosphorus of about 5 mg/dl. Analogously, phosphorus-elicited increases in FGF23 were markedly blunted if serum calcium was less than 8 mg/dl. The best correlation between calcium and phosphorus and serum FGF23 was found between FGF23 and the calcium × phosphorus product. Since calcium stimulated FGF23 production in the PTH-CaSR DKO mice, this effect cannot be mediated by the full-length CaSR. Thus the regulation of FGF23 by both calcium and phosphorus appears to be fundamentally important in coordinating the serum levels of both mineral ions and ensuring that the calcium × phosphorus product remains within a physiological range. PMID:23233539

The stationary phase sigma factor, RpoS, regulates the production of a carbapenem antibiotic, a bioactive prodigiosin and virulence in the enterobacterial pathogen Serratia sp. ATCC 39006.

Science.gov (United States)

Wilf, Nabil M; Salmond, George P C

2012-03-01

Serratia sp. ATCC 39006 (S39006) is a Gram-negative bacterium that is virulent in plant (potato) and invertebrate animal (Caenorhabditis elegans) models. It produces two secondary metabolite antibiotics, a prodigiosin and a carbapenem, and the exoenzymes pectate lyase and cellulase. We showed previously that deletion of the RNA chaperone Hfq abolished antibiotic production and attenuated virulence in both animal and plant hosts. Hfq and dependent small RNAs (sRNAs) are known to regulate the post-transcriptional expression of rpoS, which encodes σ(S), the stationary phase sigma factor subunit of RNA polymerase. An S39006 hfq deletion mutant showed decreased transcript levels of rpoS. Therefore, in this study we investigated whether the phenotypes regulated by Hfq were mediated through its control of rpoS. Whereas loss of Hfq abolished prodigiosin and carbapenem production and attenuated virulence in both C. elegans and potato, characterization of an S39006 rpoS mutant showed unexpectedly elevated prodigiosin and carbapenem production. Furthermore, the rpoS mutant exhibited attenuated animal pathogenesis, but not plant pathogenesis. Additionally, a homologue of the Hfq-dependent sRNA, RprA, was identified and shown to regulate prodigiosin production in a manner consistent with its role in positively regulating translation of rpoS mRNA. Combined, these results demonstrate that Hfq regulation of secondary metabolism and plant pathogenesis is independent of RpoS and establishes RpoS and RprA as regulators of antibiotic production.

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

International Nuclear Information System (INIS)

Mundigl, Stefan

2013-01-01

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.

Adaptive Regulation of Osteopontin Production by Dendritic Cells Through the Bidirectional Interaction With Mesenchymal Stromal Cells

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Sara Scutera

2018-06-01

Full Text Available Mesenchymal stromal cells (MSCs exert immunosuppressive effects on immune cells including dendritic cells (DCs. However, many details of the bidirectional interaction of MSCs with DCs are still unsolved and information on key molecules by which DCs can modulate MSC functions is limited. Here, we report that osteopontin (OPN, a cytokine involved in homeostatic and pathophysiologic responses, is constitutively expressed by DCs and regulated in the DC/MSC cocultures depending on the activation state of MSCs. Resting MSCs promoted OPN production, whereas the production of OPN was suppressed when MSCs were activated by proinflammatory cytokines (i.e., TNF-α, IL-6, and IL-1β. OPN induction required cell-to-cell contact, mediated at least in part, by β1 integrin (CD29. Conversely, activated MSCs inhibited the release of OPN via the production of soluble factors with a major role played by Prostaglandin E2 (PGE2. Accordingly, pretreatment with indomethacin significantly abrogated the MSC-mediated suppression of OPN while the direct addition of exogenous PGE2 inhibited OPN production by DCs. Furthermore, DC-conditioned medium promoted osteogenic differentiation of MSCs with a concomitant inhibition of adipogenesis. These effects were paralleled by the repression of the adipogenic markers PPARγ, adiponectin, and FABP4, and induction of the osteogenic markers alkaline phosphatase, RUNX2, and of the bone-anabolic chemokine CCL5. Notably, blocking OPN activity with RGD peptides or with an antibody against CD29, one of the OPN receptors, prevented the effects of DC-conditioned medium on MSC differentiation and CCL5 induction. Because MSCs have a key role in maintenance of bone marrow (BM hematopoietic stem cell niche through reciprocal regulation with immune cells, we investigated the possible MSC/DC interaction in human BM by immunohistochemistry. Although DCs (CD1c+ are a small percentage of BM cells, we demonstrated colocalization of CD271+ MSCs with

Klotho expression in long bones regulates FGF23 production during renal failure.

Science.gov (United States)

Kaludjerovic, Jovana; Komaba, Hirotaka; Sato, Tadatoshi; Erben, Reinhold G; Baron, Roland; Olauson, Hannes; Larsson, Tobias E; Lanske, Beate

2017-05-01

Circulating levels of bone-derived fibroblast growth factor 23 (FGF23) increase early during acute and chronic kidney disease and are associated with adverse outcomes. Membrane-bound Klotho acts as a permissive coreceptor for FGF23, and its expression was recently found in osteoblasts/osteocytes. We hypothesized that Klotho in bone cells is part of an autocrine feedback loop that regulates FGF23 expression during renal failure. Thus, we induced renal failure in mice with targeted deletion of Klotho in long bones. Uremic wild-type ( KL fl/fl ) and knockout ( Prx1-Cre;KL fl/fl ) mice both responded with reduced body weight, kidney atrophy, hyperphosphatemia, and increased bone turnover. Importantly, long bones of Prx1-Cre;KL fl/fl mice but not their axial skeleton failed to increase FGF23 expression as observed in uremic KL fl/fl mice. Consequently, Prx1-Cre;KL fl/fl mice had significantly lower serum FGF23 and parathyroid hormone levels, and higher renal 1-α-hydroxylase expression, serum 1,25-dihydroxyvitamin D, and calcium levels than KL fl/fl mice. These results were confirmed in two independent models of renal failure, adenine diet induced and 5/6 nephrectomy. Moreover, FGF23-treated bone cells required Klotho to increase FGF23 mRNA and ERK phosphorylation. In summary, our novel findings show that Klotho in bone is crucial for inducing FGF23 production upon renal failure. We propose the presence of an autocrine feedback loop in which Klotho senses the need for FGF23.-Kaludjerovic, J., Komaba, H., Sato, T., Erben, R. G., Baron, R., Olauson, H., Larsson, T. E., Lanske, B. Klotho expression in long bones regulates FGF23 production during renal failure. © FASEB.

78 FR 72893 - Agency Information Collection Activities; Submission for Office of Management and Budget Review...

Science.gov (United States)

2013-12-04

..., including Source Plasma, unlicensed registered blood establishments, and transfusion services, who had... blood components including Source Plasma; (3) unlicensed registered blood establishments; (4... currently accept electronic filings) further streamlines the report submission process. CBER developed a Web...

75 FR 27347 - Agency Information Collection Activities; Submission for Office of Management and Budget Review...

Science.gov (United States)

2010-05-14

... human blood and blood components, including Source Plasma; an unlicensed registered blood establishment... and blood components including Source Plasma, unlicensed registered blood establishments, transfusion... accept electronic filings) further streamlines the report submission process. CBER has developed an...

Competitiveness regulation of dairy products production in the Crimea

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Domozhilkina Zh. V.

2016-05-01

Full Text Available the article outlines the results of studying the major problems concerning supporting competitiveness and quality of dairy products in the Crimea. The researchers compared the level of competitiveness of the dairy enterprise ltd. «Бег» with other brands of milk and suggested measures to improve the efficiency and effectiveness of competitiveness management of dairy products in this region.

Regulating Tobacco Product Advertising and Promotions in the Retail Environment: A Roadmap for States and Localities.

Science.gov (United States)

Lange, Tamara; Hoefges, Michael; Ribisl, Kurt M

2015-01-01

Recent amendments to federal law and a burgeoning body of research have intensified public health officials' interest in reducing youth initiation of tobacco use, including by regulating the time, place, or manner of tobacco product advertising at the point of sale. This article analyzes legal obstacles to various strategies for reducing youth initiation. © 2015 American Society of Law, Medicine & Ethics, Inc.

Direct regulation of the Akt proto-oncogene product by phosphatidylinositol-3,4-bisphosphate.

Science.gov (United States)

Franke, T F; Kaplan, D R; Cantley, L C; Toker, A

1997-01-31

The regulation of the serine-threonine kinase Akt by lipid products of phosphoinositide 3-kinase (PI 3-kinase) was investigated. Akt activity was found to correlate with the amount of phosphatidylinositol-3,4-bisphosphate (PtdIns-3,4-P2) in vivo, and synthetic PtdIns-3,4-P2 activated Akt both in vitro and in vivo. Binding of PtdIns-3,4-P2 occurred within the Akt pleckstrin homology (PH) domain and facilitated dimerization of Akt. Akt mutated in the PH domain was not activated by PI 3-kinase in vivo or by PtdIns-3, 4-P2 in vitro, and it was impaired in binding to PtdIns-3,4-P2. Examination of the binding to other phosphoinositides revealed that they bound to the Akt PH domain with much lower affinity than did PtdIns-3,4-P2 and failed to increase Akt activity. Thus, Akt is apparently regulated by the direct interaction of PtdIns-3,4-P2 with the Akt PH domain.

TPL-2-ERK1/2 signaling promotes host resistance against intracellular bacterial infection by negative regulation of type I IFN production.

Science.gov (United States)

McNab, Finlay W; Ewbank, John; Rajsbaum, Ricardo; Stavropoulos, Evangelos; Martirosyan, Anna; Redford, Paul S; Wu, Xuemei; Graham, Christine M; Saraiva, Margarida; Tsichlis, Philip; Chaussabel, Damien; Ley, Steven C; O'Garra, Anne

2013-08-15

Tuberculosis, caused by Mycobacterium tuberculosis, remains a leading cause of mortality and morbidity worldwide, causing ≈ 1.4 million deaths per year. Key immune components for host protection during tuberculosis include the cytokines IL-12, IL-1, and TNF-α, as well as IFN-γ and CD4(+) Th1 cells. However, immune factors determining whether individuals control infection or progress to active tuberculosis are incompletely understood. Excess amounts of type I IFN have been linked to exacerbated disease during tuberculosis in mouse models and to active disease in patients, suggesting tight regulation of this family of cytokines is critical to host resistance. In addition, the immunosuppressive cytokine IL-10 is known to inhibit the immune response to M. tuberculosis in murine models through the negative regulation of key proinflammatory cytokines and the subsequent Th1 response. We show in this study, using a combination of transcriptomic analysis, genetics, and pharmacological inhibitors, that the TPL-2-ERK1/2 signaling pathway is important in mediating host resistance to tuberculosis through negative regulation of type I IFN production. The TPL-2-ERK1/2 signaling pathway regulated production by macrophages of several cytokines important in the immune response to M. tuberculosis as well as regulating induction of a large number of additional genes, many in a type I IFN-dependent manner. In the absence of TPL-2 in vivo, excess type I IFN promoted IL-10 production and exacerbated disease. These findings describe an important regulatory mechanism for controlling tuberculosis and reveal mechanisms by which type I IFN may promote susceptibility to this important disease.

Interferon Potentiates Toll-Like Receptor-Induced Prostaglandin D2 Production through Positive Feedback Regulation between Signal Transducer and Activators of Transcription 1 and Reactive Oxygen Species

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Ji-Yun Kim

2017-12-01

Full Text Available Prostaglandin D2 (PGD2 is a potent lipid mediator that controls inflammation, and its dysregulation has been implicated in diverse inflammatory disorders. Despite significant progress made in understanding the role of PGD2 as a key regulator of immune responses, the molecular mechanism underlying PGD2 production remains unclear, particularly upon challenge with different and multiple inflammatory stimuli. Interferons (IFNs potentiate macrophage activation and act in concert with exogenous inflammatory mediators such as toll-like receptor (TLR ligands to amplify inflammatory responses. A recent study found that IFN-γ enhanced lipopolysaccharide-induced PGD2 production, indicating a role of IFNs in PGD2 regulation. Here, we demonstrate that TLR-induced PGD2 production by macrophages was significantly potentiated by signaling common to IFN-β and IFN-γ in a signal transducer and activators of transcription (STAT1-dependent mechanism. Such potentiation by IFNs was also observed for PGE2 production, despite the differential regulation of PGD synthase and PGE synthase isoforms mediating PGD2 and PGE2 production under inflammatory conditions. Mechanistic analysis revealed that the generation of intracellular reactive oxygen species (ROS was remarkably potentiated by IFNs and required for PGD2 production, but was nullified by STAT1 deficiency. Conversely, the regulation of STAT1 level and activity by IFNs was largely dependent on ROS levels. Using a model of zymosan-induced peritonitis, the relevance of this finding in vivo was supported by marked inhibition of PGD2 and ROS produced in peritoneal exudate cells by STAT1 deficiency. Collectively, our findings suggest that IFNs, although not activating on their own, are potent amplifiers of TLR-induced PGD2 production via positive-feedback regulation between STAT1 and ROS.

Expression regulation of design process gene in product design

DEFF Research Database (Denmark)

Li, Bo; Fang, Lusheng; Li, Bo

2011-01-01

To improve the design process efficiency, this paper proposes the principle and methodology that design process gene controls the characteristics of design process under the framework of design process reuse and optimization based on design process gene. First, the concept of design process gene...... is proposed and analyzed, as well as its three categories i.e., the operator gene, the structural gene and the regulator gene. Second, the trigger mechanism that design objectives and constraints trigger the operator gene is constructed. Third, the expression principle of structural gene is analyzed...... with the example of design management gene. Last, the regulation mode that the regulator gene regulates the expression of the structural gene is established and it is illustrated by taking the design process management gene as an example. © (2011) Trans Tech Publications....

The CpAL quorum sensing system regulates production of hemolysins CPA and PFO to build Clostridium perfringens biofilms.

Science.gov (United States)

Vidal, Jorge E; Shak, Joshua R; Canizalez-Roman, Adrian

2015-06-01

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. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

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

Science.gov (United States)

Shak, Joshua R.; Canizalez-Roman, Adrian

2015-01-01

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

A systems biology approach to investigate the effect of pH-induced gene regulation on solvent production by Clostridium acetobutylicum in continuous culture

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Bahl Hubert

2011-01-01

Full Text Available Abstract Background Clostridium acetobutylicum is an anaerobic bacterium which is known for its solvent-producing capabilities, namely regarding the bulk chemicals acetone and butanol, the latter being a highly efficient biofuel. For butanol production by C. acetobutylicum to be optimized and exploited on an industrial scale, the effect of pH-induced gene regulation on solvent production by C. acetobutylicum in continuous culture must be understood as fully as possible. Results We present an ordinary differential equation model combining the metabolic network governing solvent production with regulation at the genetic level of the enzymes required for this process. Parameterizing the model with experimental data from continuous culture, we demonstrate the influence of pH upon fermentation products: at high pH (pH 5.7 acids are the dominant product while at low pH (pH 4.5 this switches to solvents. Through steady-state analyses of the model we focus our investigations on how alteration in gene expression of C. acetobutylicum could be exploited to increase butanol yield in a continuous culture fermentation. Conclusions Incorporating gene regulation into the model of solvent production by C. acetobutylicum enables an accurate representation of the pH-induced switch to solvent production to be obtained and theoretical investigations of possible synthetic-biology approaches to be pursued. Steady-state analyses suggest that, to increase butanol yield, alterations in the expression of single solvent-associated genes are insufficient; a more complex approach targeting two or more genes is required.

ApiAP2 Factors as Candidate Regulators of Stochastic Commitment to Merozoite Production in Theileria annulata.

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Marta Pieszko

Full Text Available Differentiation of one life-cycle stage to the next is critical for survival and transmission of apicomplexan parasites. A number of studies have shown that stage differentiation is a stochastic process and is associated with a point that commits the cell to a change over in the pattern of gene expression. Studies on differentiation to merozoite production (merogony in T. annulata postulated that commitment involves a concentration threshold of DNA binding proteins and an auto-regulatory loop.In this study ApiAP2 DNA binding proteins that show changes in expression level during merogony of T. annulata have been identified. DNA motifs bound by orthologous domains in Plasmodium were found to be enriched in upstream regions of stage-regulated T. annulata genes and validated as targets for the T. annulata AP2 domains by electrophoretic mobility shift assay (EMSA. Two findings were of particular note: the gene in T. annulata encoding the orthologue of the ApiAP2 domain in the AP2-G factor that commits Plasmodium to gametocyte production, has an expression profile indicating involvement in transmission of T. annulata to the tick vector; genes encoding related domains that bind, or are predicted to bind, sequence motifs of the type 5'-(ACACAC(A are implicated in differential regulation of gene expression, with one gene (TA11145 likely to be preferentially up-regulated via auto-regulation as the cell progresses to merogony.We postulate that the Theileria factor possessing the AP2 domain orthologous to that of Plasmodium AP2-G may regulate gametocytogenesis in a similar manner to AP2-G. In addition, paralogous ApiAP2 factors that recognise 5'-(ACACAC(A type motifs could operate in a competitive manner to promote reversible progression towards the point that commits the cell to undergo merogony. Factors possessing AP2 domains that bind (or are predicted to bind this motif are present in the vector-borne genera Theileria, Babesia and Plasmodium, and other

Crystallization and preliminary X-ray analysis of AbsC, a novel regulator of antibiotic production in Streptomyces coelicolor

International Nuclear Information System (INIS)

Stevenson, Clare E. M.; Kock, Holger; Mootien, Saraspadee; Davies, Sîan C.; Bibb, Mervyn J.; Lawson, David M.

2007-01-01

A novel regulator of antibiotic production in S. coelicolor, AbsC, has been crystallized in space group P2 1 2 1 2 1 . X-ray data to 2.25 Å resolution were collected on station PX 14.1 at Daresbury. Crystals of recombinant AbsC (subunit MW = 18 313 Da; 158 amino acids), a novel regulator of antibiotic production from Streptomyces coelicolor, were grown by vapour diffusion. The protein crystallizes in space group P2 1 2 1 2 1 , with unit-cell parameters a = 43.53, b = 121.30, c = 143.75 Å. Native data to a resolution of 2.25 Å were recorded at station PX 14.1 (Daresbury) from a single crystal. Preliminary analysis of these data suggests that the asymmetric unit contains four copies of the AbsC monomer, giving an estimated solvent content of 47.0%. AbsC belongs to the MarR family of proteins that mediate ligand-responsive transcriptional control

PGE2 maintains self-renewal of human adult stem cells via EP2-mediated autocrine signaling and its production is regulated by cell-to-cell contact.

Science.gov (United States)

Lee, Byung-Chul; Kim, Hyung-Sik; Shin, Tae-Hoon; Kang, Insung; Lee, Jin Young; Kim, Jae-Jun; Kang, Hyun Kyoung; Seo, Yoojin; Lee, Seunghee; Yu, Kyung-Rok; Choi, Soon Won; Kang, Kyung-Sun

2016-05-27

Mesenchymal stem cells (MSCs) possess unique immunomodulatory abilities. Many studies have elucidated the clinical efficacy and underlying mechanisms of MSCs in immune disorders. Although immunoregulatory factors, such as Prostaglandin E2 (PGE2), and their mechanisms of action on immune cells have been revealed, their effects on MSCs and regulation of their production by the culture environment are less clear. Therefore, we investigated the autocrine effect of PGE2 on human adult stem cells from cord blood or adipose tissue, and the regulation of its production by cell-to-cell contact, followed by the determination of its immunomodulatory properties. MSCs were treated with specific inhibitors to suppress PGE2 secretion, and proliferation was assessed. PGE2 exerted an autocrine regulatory function in MSCs by triggering E-Prostanoid (EP) 2 receptor. Inhibiting PGE2 production led to growth arrest, whereas addition of MSC-derived PGE2 restored proliferation. The level of PGE2 production from an equivalent number of MSCs was down-regulated via gap junctional intercellular communication. This cell contact-mediated decrease in PGE2 secretion down-regulated the suppressive effect of MSCs on immune cells. In conclusion, PGE2 produced by MSCs contributes to maintenance of self-renewal capacity through EP2 in an autocrine manner, and PGE2 secretion is down-regulated by cell-to-cell contact, attenuating its immunomodulatory potency.

Surface association and the MreB cytoskeleton regulate pilus production, localization and function in Pseudomonas aeruginosa.

Science.gov (United States)

Cowles, Kimberly N; Gitai, Zemer

2010-06-01

Spatial organization of bacterial proteins influences many cellular processes, including division, chromosome segregation and motility. Virulence-associated proteins also localize to specific destinations within bacterial cells. However, the functions and mechanisms of virulence factor localization remain largely unknown. In this work, we demonstrate that polar assembly of the Pseudomonas aeruginosa PAO1 type IV pilus is regulated by surface association in a manner that affects gene transcription, protein levels and protein localization. We also uncover one mechanism for this regulation that acts through the actin homologue MreB. Inactivation of MreB leads to mislocalization of the pilus retraction ATPase PilT, mislocalization of the pili themselves and a reduction in motility. Furthermore, the role of MreB in polar localization of PilT is modulated by surface association, corroborating our results that environmental factors influence the regulation of pilus production. Specifically, MreB mediates both the initiation and maintenance of PilT localization when cells are grown in suspension but only affects the initiation of localization when cells are grown on a surface. Together, these results suggest that the bacterial cytoskeleton provides a mechanism for the polar localization of P. aeruginosa pili and demonstrate that protein localization may represent an important aspect of virulence factor regulation in bacterial pathogens.

One carbon metabolism in anaerobic bacteria: Regulation of carbon and electron flow during organic acid production: Progress report, February 1, 1987-February 1, 1988

International Nuclear Information System (INIS)

Zeikus, J.G.; Shen, Gwo-Jenn.

1988-01-01

These studies concern the fundamental biochemical mechanisms that control carbon and electron flow in anaerobic bacteria that conserve energy when coupling hydrogen consumption to the production of acetic, propionic, or butyric acids. Two acidogens, Propionispira arboris and Butyribacterium methylotrophicum were chosen as model systems to understand the function of oxidoreductases and electron carriers in the regulation of hydrogen metabolism and single carbon metabolism. In P. arboris, H 2 consumption was linked to the inhibition of CO 2 production and an increase in the propionate/acetate rate; whereas, H 2 consumption was linked to a stimulation of CO 2 consumption and an increase in the butyrate/acetate ratio in B. methylotrophicum. We report studies on the enzymes involved in the regulation of singe carbon metabolism, the enzyme activities and pathways responsible for conversion of multicarbon components to acetate and propionate or butyrate, and how low pH inhibits H 2 and acetic acid production in Sarcina ventriculi as a consequence of hydrogenase regulation. 9 refs

Negative Regulation of Interferon-β Production by Alternative Splicing of Tumor Necrosis Factor Receptor-Associated Factor 3 in Ducks

Directory of Open Access Journals (Sweden)

Xiaoqin Wei

2018-03-01

Full Text Available Tumor necrosis factor receptor-associated factor 3 (TRAF3, an intracellular signal transducer, is identified as an important component of Toll-like receptors and RIG-I-like receptors induced type I interferon (IFN signaling pathways. Previous studies have clarified TRAF3 function in mammals, but little is known about the role of TRAF3 in ducks. Here, we cloned and characterized the full-length duck TRAF3 (duTRAF3 gene and an alternatively spliced isoform of duTRAF3 (duTRAF3-S lacking the fragment encoding amino acids 217–319, from duck embryo fibroblasts (DEFs. We found that duTRAF3 and duTRAF3-S played different roles in regulating IFN-β production in DEFs. duTRAF3 through its TRAF domain interacted with duMAVS or duTRIF, leading to the production of IFN-β. However, duTRAF3-S, containing the TRAF domain, was unable to bind duMAVS or duTRIF due to the intramolecular binding between the N- and C-terminal of duTRAF3-S that blocked the function of its TRAF domain. Further analysis identified that duTRAF3-S competed with duTRAF3 itself for binding to duTRAF3, perturbing duTRAF3 self-association, which impaired the assembly of duTRAF3-duMAVS/duTRIF complex, ultimately resulted in a reduced production of IFN-β. These findings suggest that duTRAF3 is an important regulator of duck innate immune signaling and reveal a novel mechanism for the negative regulation of IFN-β production via changing the formation of the homo-oligomerization of wild molecules, implying a novel regulatory role of truncated proteins.

VanT, a homologue of Vibrio harveyi LuxR, regulates serine, metalloprotease, pigment, and biofilm production in Vibrio anguillarum.

Science.gov (United States)

Croxatto, Antony; Chalker, Victoria J; Lauritz, Johan; Jass, Jana; Hardman, Andrea; Williams, Paul; Cámara, Miguel; Milton, Debra L

2002-03-01

Vibrio anguillarum possesses at least two N-acylhomoserine lactone (AHL) quorum-sensing circuits, one of which is related to the luxMN system of Vibrio harveyi. In this study, we have cloned an additional gene of this circuit, vanT, encoding a V. harveyi LuxR-like transcriptional regulator. A V. anguillarum Delta vanT null mutation resulted in a significant decrease in total protease activity due to loss of expression of the metalloprotease EmpA, but no changes in either AHL production or virulence. Additional genes positively regulated by VanT were identified from a plasmid-based gene library fused to a promoterless lacZ. Three lacZ fusions (serA::lacZ, hpdA-hgdA::lacZ, and sat-vps73::lacZ) were identified which exhibited decreased expression in the Delta vanT strain. SerA is similar to 3-phosphoglycerate dehydrogenases and catalyzes the first step in the serine-glycine biosynthesis pathway. HgdA has identity with homogentisate dioxygenases, and HpdA is homologous to 4-hydroxyphenylpyruvate dioxygenases (HPPDs) involved in pigment production. V. anguillarum strains require an active VanT to produce high levels of an L-tyrosine-induced brown color via HPPD, suggesting that VanT controls pigment production. Vps73 and Sat are related to Vibrio cholerae proteins encoded within a DNA locus required for biofilm formation. A V. anguillarum Delta vanT mutant and a mutant carrying a polar mutation in the sat-vps73 DNA locus were shown to produce defective biofilms. Hence, a new member of the V. harveyi LuxR transcriptional activator family has been characterized in V. anguillarum that positively regulates serine, metalloprotease, pigment, and biofilm production.

Global approaches to regulating electronic cigarettes

OpenAIRE

Kennedy, Ryan David; Awopegba, Ayodeji; De Le?n, Elaine; Cohen, Joanna E

2016-01-01

Objectives Classify and describe the policy approaches used by countries to regulate e-cigarettes. Methods National policies regulating e-cigarettes were identified by (1) conducting web searches on Ministry of Health websites, and (2) broad web searches. The mechanisms used to regulate e-cigarettes were classified as new/amended laws, or existing laws. The policy domains identified include restrictions or prohibitions on product: sale, manufacturing, importation, distribution, use, product d...

76 FR 26305 - Agency Information Collection Activities; Proposed Collection; Comment Request; Certification To...

Science.gov (United States)

2011-05-06

... to satisfy the previously mentioned statutory requirement. The importance of obtaining these data.... Marketing Applications/Submissions In 2010, CDER and CBER received 165 new drug applications (NDA... ANDA marketing applications and submissions. It is assumed that the sponsor/applicant/submitter has...

Role of plant growth regulators on oil yield and biodiesel production of linseed (linum usitatissimum l)

International Nuclear Information System (INIS)

Faizanullah, A.; Bano, A.; Nosheen, A.

2010-01-01

A field experiment was conducted to compare the effect of plant growth regulators (PGRs) viz. kinetin (K), chlorocholine chloride (CCC) and salicylic acid (SA) on seed yield, oil content and oil quality of Linseed (Linum usitatissimum L) cv. Chandni with a new perspective to biodiesel production. The growth regulators (10-6M) were applied as seed soaking for 10 h prior to cultivation. Kinetin significantly increased the number of capsules/plant, seed number/capsule, 1000 seed weight and total seed yield (kg/h). The growth regulators increased the seed oil content maximum being in kinetin and CCC treatments. Kinetin and CCC significantly decreased the oil acid value, free fatty acid content (% oleic acid) and increased the pH of oil. Nevertheless, SA significantly decreased the oil specific gravity and did not alter the pH. Only kinetin significantly increased the oil iodine value. The oil extracted from seeds of kinetin and CCC treated plants showed maximum conversion (% w/w) to methyl esters/biodiesel after transesterification. It can be inferred that PGRs can be utilized successfully for improving the biodiesel yield of linseed. (author)

The cross-pathway control system regulates production of the secondary metabolite toxin, sirodesmin PL, in the ascomycete, Leptosphaeria maculans

Directory of Open Access Journals (Sweden)

Fox Ellen M

2011-07-01

Full Text Available Abstract Background Sirodesmin PL is a secondary metabolite toxin made by the ascomycetous plant pathogen, Leptosphaeria maculans. The sirodesmin biosynthetic genes are clustered in the genome. The key genes are a non-ribosomal peptide synthetase, sirP, and a pathway-specific transcription factor, sirZ. Little is known about regulation of sirodesmin production. Results Genes involved in regulation of sirodesmin PL in L. maculans have been identified. Two hundred random insertional T-DNA mutants were screened with an antibacterial assay for ones producing low levels of sirodesmin PL. Three such mutants were isolated and each transcribed sirZ at very low levels. One of the affected genes had high sequence similarity to Aspergillus fumigatus cpcA, which regulates the cross-pathway control system in response to amino acid availability. This gene was silenced in L. maculans and the resultant mutant characterised. When amino acid starvation was artificially-induced by addition of 3-aminotriazole for 5 h, transcript levels of sirP and sirZ did not change in the wild type. In contrast, levels of sirP and sirZ transcripts increased in the silenced cpcA mutant. After prolonged amino acid starvation the silenced cpcA mutant produced much higher amounts of sirodesmin PL than the wild type. Conclusions Production of sirodesmin PL in L. maculans is regulated by the cross pathway control gene, cpcA, either directly or indirectly via the pathway-specific transcription factor, sirZ.

Epigenetic regulation of vascular NADPH oxidase expression and reactive oxygen species production by histone deacetylase-dependent mechanisms in experimental diabetes

Directory of Open Access Journals (Sweden)

Simona-Adriana Manea

2018-06-01

Full Text Available Reactive oxygen species (ROS generated by up-regulated NADPH oxidase (Nox contribute to structural-functional alterations of the vascular wall in diabetes. Epigenetic mechanisms, such as histone acetylation, emerged as important regulators of gene expression in cardiovascular disorders. Since their role in diabetes is still elusive we hypothesized that histone deacetylase (HDAC-dependent mechanisms could mediate vascular Nox overexpression in diabetic conditions. Non-diabetic and streptozotocin-induced diabetic C57BL/6J mice were randomized to receive vehicle or suberoylanilide hydroxamic acid (SAHA, a pan-HDAC inhibitor. In vitro studies were performed on a human aortic smooth muscle cell (SMC line. Aortic SMCs typically express Nox1, Nox4, and Nox5 subtypes. HDAC1 and HDAC2 proteins along with Nox1, Nox2, and Nox4 levels were found significantly elevated in the aortas of diabetic mice compared to non-diabetic animals. Treatment of diabetic mice with SAHA mitigated the aortic expression of Nox1, Nox2, and Nox4 subtypes and NADPH-stimulated ROS production. High concentrations of glucose increased HDAC1 and HDAC2 protein levels in cultured SMCs. SAHA significantly reduced the high glucose-induced Nox1/4/5 expression, ROS production, and the formation malondialdehyde-protein adducts in SMCs. Overexpression of HDAC2 up-regulated the Nox1/4/5 gene promoter activities in SMCs. Physical interactions of HDAC1/2 and p300 proteins with Nox1/4/5 promoters were detected at the sites of active transcription. High glucose induced histone H3K27 acetylation enrichment at the promoters of Nox1/4/5 genes in SMCs. The novel data of this study indicate that HDACs mediate vascular Nox up-regulation in diabetes. HDAC inhibition reduces vascular ROS production in experimental diabetes, possibly by a mechanism involving negative regulation of Nox expression. Keywords: NADPH oxidase, Epigenetics, HDAC, Histone acetylation, Diabetes

7 CFR 301.50-2 - Regulated articles.

Science.gov (United States)

2010-01-01

... 7 Agriculture 5 2010-01-01 2010-01-01 false Regulated articles. 301.50-2 Section 301.50-2... articles. The following are regulated articles: (a) Pine products (Pinus spp.), as follows: Bark products... pine wreaths and garlands; and stumps. (b) Any article, product, or means of conveyance not covered by...

Functional characterization of a three-component regulatory system involved in quorum sensing-based regulation of peptide antibiotic production in Carnobacterium maltaromaticum

Directory of Open Access Journals (Sweden)

Quadri Luis EN

2006-10-01

Full Text Available Abstract Background Quorum sensing is a form of cell-to-cell communication that allows bacteria to control a wide range of physiological processes in a population density-dependent manner. Production of peptide antibiotics is one of the processes regulated by quorum sensing in several species of Gram-positive bacteria, including strains of Carnobacterium maltaromaticum. This bacterium and its peptide antibiotics are of interest due to their potential applications in food preservation. The molecular bases of the quorum sensing phenomenon controlling peptide antibiotic production in C. maltaromaticum remain poorly understood. The present study was aimed at gaining a deeper insight into the molecular mechanism involved in quorum sensing-mediated regulation of peptide antibiotic (bacteriocin production by C. maltaromaticum. We report the functional analyses of the CS (autoinducer-CbnK (histidine protein kinase-CbnR (response regulator three-component regulatory system and the three regulated promoters involved in peptide antibiotic production in C. maltaromaticum LV17B. Results CS-CbnK-CbnR system-dependent activation of carnobacterial promoters was demonstrated in both homologous and heterologous hosts using a two-plasmid system with a β-glucuronidase (GusA reporter read-out. The results of our analyses support a model in which the CbnK-CbnR two-component signal transduction system is necessary and sufficient to transduce the signal of the peptide autoinducer CS into the activation of the promoters that drive the expression of the genes required for production of the carnobacterial peptide antibiotics and the immunity proteins that protect the producer bacterium. Conclusions The CS-CbnK-CbnR triad forms a three-component regulatory system by which production of peptide antibiotics by C. maltaromaticum LV17B is controlled in a population density-dependent (or cell proximity-dependent manner. This regulatory mechanism would permit the bacterial

The AMP-activated protein kinase is involved in the regulation of ketone body production by astrocytes.

Science.gov (United States)

Blázquez, C; Woods, A; de Ceballos, M L; Carling, D; Guzmán, M

1999-10-01

The possible role of the AMP-activated protein kinase (AMPK), a highly conserved stress-activated kinase, in the regulation of ketone body production by astrocytes was studied. AMPK activity in rat cortical astrocytes was three times higher than in rat cortical neurons. AMPK in astrocytes was shown to be functionally active. Thus, incubation of astrocytes with 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR), a cell-permeable activator of AMPK, stimulated both ketogenesis from palmitate and carnitine palmitoyltransferase I. This was concomitant to a decrease of intracellular malonyl-CoA levels and an inhibition of acetyl-CoA carboxylase/fatty acid synthesis and 3-hydroxy-3-methylglutaryl-CoA reductase/cholesterol synthesis. Moreover, in microdialysis experiments AICAR was shown to stimulate brain ketogenesis markedly. The effect of chemical hypoxia on AMPK and the ketogenic pathway was studied subsequently. Incubation of astrocytes with azide led to a remarkable drop of fatty acid beta-oxidation. However, activation of AMPK during hypoxia compensated the depression of beta-oxidation, thereby sustaining ketone body production. This effect seemed to rely on the cascade hypoxia --> increase of the AMP/ATP ratio --> AMPK stimulation --> acetyl-CoA carboxylase inhibition --> decrease of malonyl-CoA concentration --> carnitine palmitoyltransferase I deinhibition --> enhanced ketogenesis. Furthermore, incubation of neurons with azide blunted lactate oxidation, but not 3-hydroxybutyrate oxidation. Results show that (a) AMPK plays an active role in the regulation of ketone body production by astrocytes, and (b) ketone bodies produced by astrocytes during hypoxia might be a substrate for neuronal oxidative metabolism.

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

International Nuclear Information System (INIS)

2007-03-01

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

Monocyte to macrophage differentiation-associated (MMD) positively regulates ERK and Akt activation and TNF-α and NO production in macrophages.

Science.gov (United States)

Liu, Qiang; Zheng, Jin; Yin, Dan-Dan; Xiang, Jie; He, Fei; Wang, Yao-Chun; Liang, Liang; Qin, Hong-Yan; Liu, Li; Liang, Ying-Min; Han, Hua

2012-05-01

Macrophage activation is modulated by both environmental cues and endogenous programs. In the present study, we investigated the role of a PAQR family protein, monocyte to macrophage differentiation-associated (MMD), in macrophage activation and unveiled its underlying molecular mechanism. Our results showed that while MMD expression could be detected in all tissues examined, its expression level is significantly up-regulated upon monocyte differentiation. Within cells, EGFP-MMD fusion protein could be co-localized to endoplasmic reticulum, mitochondria, Golgi apparatus, but not lysosomes and cytoplasm. MMD expression is up-regulated in macrophages after LPS stimulation, and this might be modulated by RBP-J, the critical transcription factor of Notch signaling. Overexpression of MMD in macrophages increased the production of TNF-α and NO upon LPS stimulation. We found that MMD overexpression enhanced ERK1/2 and Akt phosphorylation in macrophages after LPS stimulation. Blocking Erk or Akt by pharmacological agent reduced TNF-α or NO production in MMD-overexpressing macrophages, respectively. These results suggested that MMD modulates TNF-α and NO production in macrophages, and this process might involves Erk or Akt.

Natural regulation of Delia radicum in organic cabbage production

DEFF Research Database (Denmark)

Meyling, Nicolai Vitt; Navntoft, Søren; Philipsen, Holger Frederik

2013-01-01

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...... 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...

Cytological, molecular mechanisms and temperature stress regulating production of diploid male gametes in Dianthus caryophyllus L.

Science.gov (United States)

Zhou, Xuhong; Mo, Xijun; Gui, Min; Wu, Xuewei; Jiang, Yalian; Ma, Lulin; Shi, Ziming; Luo, Ying; Tang, Wenru

2015-12-01

In plant evolution, because of its key role in sexual polyploidization or whole genome duplication events, diploid gamete formation is considered as an important component in diversification and speciation. Environmental stress often triggers unreduced gamete production. However, the molecular, cellular mechanisms and adverse temperature regulating diplogamete production in carnation remain poorly understood. Here, we investigate the cytological basis for 2n male gamete formation and describe the isolation and characterization of the first gene, DcPS1 (Dianthus Caryophyllus Parallel Spindle 1). In addition, we analyze influence of temperature stress on diploid gamete formation and transcript levels of DcPS1. Cytological evidence indicated that 2n male gamete formation is attributable to abnormal spindle orientation at male meiosis II. DcPS1 protein is conserved throughout the plant kingdom and carries domains suggestive of a regulatory function. DcPS1 expression analysis show DcPS1 gene probably have a role in 2n pollen formation. Unreduced pollen formation in various cultivation was sensitive to high or low temperature which was probably regulated by the level of DcPS1 transcripts. In a broader perspective, these findings can have potential applications in fundamental polyploidization research and plant breeding programs. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Models for estimation of the presence of non-regulated disinfection by-products in small drinking water systems.

Science.gov (United States)

Guilherme, Stéphanie; Rodriguez, Manuel J

2017-10-23

Among all the organic disinfection by-products (DBPs), only trihalomethanes (THMs) and haloacetic acids (HAAs) are regulated in drinking water, while most DBPs are not. Very little information exists on the occurrence of non-regulated DBPs, particularly in small water systems (SWS). Paradoxically, SWS are more vulnerable to DBPs because of a low capacity to implement adequate treatment technologies to remove DBP precursors. Since DBP analyses are expensive, usually SWS have difficulties to implement a rigorous characterization of these contaminants. The purpose of this study was to estimate non-regulated DBP levels in SWS from easy measurements of relevant parameters regularly monitored. Since no information on non-regulated DBPs in SWS was available, a sampling program was carried out in 25 SWS in two provinces of Canada. Five DBP families were investigated: THMs, HAAs, haloacetonitriles (HANs), halonitromethanes (HNMs), and haloketones (HKs). Multivariate linear mixed regression models were developed to estimate HAN, HK, and HNM levels from water quality characteristics in the water treatment plant, concentrations of regulated DBPs, and residual disinfectant levels. The models obtained have a good explanatory capacity since R 2 varies from 0.77 to 0.91 according to compounds and conditions for application (season and type of treatment). Model validation with an independent database suggested their ability for generalization in similar SWS in North America.

76 FR 4360 - Guidance for Industry on Process Validation: General Principles and Practices; Availability

Science.gov (United States)

2011-01-25

... and Development (HFM-40), Center for Biologics Evaluation and Research (CBER), Food and Drug...] Guidance for Industry on Process Validation: General Principles and Practices; Availability AGENCY: Food... of Drug Information, Center for Drug Evaluation and Research, Food and Drug Administration, 10903 New...

75 FR 54351 - Cell and Gene Therapy Clinical Trials in Pediatric Populations; Public Workshop

Science.gov (United States)

2010-09-07

...] Cell and Gene Therapy Clinical Trials in Pediatric Populations; Public Workshop AGENCY: Food and Drug... Biologics Evaluation and Research (CBER) is announcing a public workshop entitled ``Cell and Gene Therapy... Institutional Review Boards (IRBs), gene and cellular therapy clinical researchers, and other stakeholders...

The sensitivity and significance analysis of parameters in the model of pH regulation on lactic acid production by Lactobacillus bulgaricus.

Science.gov (United States)

Liu, Ke; Zeng, Xiangmiao; Qiao, Lei; Li, Xisheng; Yang, Yubo; Dai, Cuihong; Hou, Aiju; Xu, Dechang

2014-01-01

The excessive production of lactic acid by L. bulgaricus during yogurt storage is a phenomenon we are always tried to prevent. The methods used in industry either control the post-acidification inefficiently or kill the probiotics in yogurt. Genetic methods of changing the activity of one enzyme related to lactic acid metabolism make the bacteria short of energy to growth, although they are efficient ways in controlling lactic acid production. A model of pH-induced promoter regulation on the production of lactic acid by L. bulgaricus was built. The modelled lactic acid metabolism without pH-induced promoter regulation fitted well with wild type L. bulgaricus (R2LAC = 0.943, R2LA = 0.942). Both the local sensitivity analysis and Sobol sensitivity analysis indicated parameters Tmax, GR, KLR, S, V0, V1 and dLR were sensitive. In order to guide the future biology experiments, three adjustable parameters, KLR, V0 and V1, were chosen for further simulations. V0 had little effect on lactic acid production if the pH-induced promoter could be well induced when pH decreased to its threshold. KLR and V1 both exhibited great influence on the producing of lactic acid. The proposed method of introducing a pH-induced promoter to regulate a repressor gene could restrain the synthesis of lactic acid if an appropriate strength of promoter and/or an appropriate strength of ribosome binding sequence (RBS) in lacR gene has been designed.

Examples of NRC research products used in regulation

International Nuclear Information System (INIS)

Anderson, N.R.

1987-01-01

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

Complement C1q regulates LPS-induced cytokine production in bone marrow-derived dendritic cells.

Science.gov (United States)

Yamada, Masahide; Oritani, Kenji; Kaisho, Tsuneyasu; Ishikawa, Jun; Yoshida, Hitoshi; Takahashi, Isao; Kawamoto, Shinichirou; Ishida, Naoko; Ujiie, Hidetoshi; Masaie, Hiroaki; Botto, Marina; Tomiyama, Yoshiaki; Matsuzawa, Yuji

2004-01-01

We show here that C1q suppresses IL-12p40 production in LPS-stimulated murine bone marrow-derived dendritic cells (BMDC). Serum IL-12p40 concentration of C1q-deficient mice was higher than that of wild-type mice after intraperitoneal LPS-injection. Because neither globular head of C1q (gC1q) nor collagen-like region of C1q (cC1q) failed to suppress LPS-induced IL-12p40 production, both gC1q and cC1q, and/or some specialized conformation of native C1q may be required for the inhibition. While C1q did not affect mRNA expression of Toll-like receptor 4 (TLR4), MD-2, and myeloid differentiation factor 88 (MyD88), BMDC treated with C1q showed the reduced activity of NF-kappaB and the delayed phosphorylation of p38, c-Jun N-terminal kinase, and extracellular signal-regulated kinase after LPS-stimulation. CpG oligodeoxynucleotide-induced IL-12p40 and TNF-alpha production, another MyD88-dependent TLR-mediated signal, was also suppressed by C1q treatment. Therefore, C1q is likely to suppress MyD88-dependent pathway in TLR-mediated signals. In contrast, C1q failed to suppress colony formation of B cells responding to LPS or LPS-induced CD40 and CD86 expression on BMDC in MyD88-deficient mice, indicating that inhibitory effects of C1q on MyD88-independent pathways may be limited. Taken together, C1q may regulate innate and adaptive immune systems via modification of signals mediated by interactions between invading pathogens and TLR.

27 CFR 5.2 - Related regulations.

Science.gov (United States)

2010-04-01

... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Related regulations. 5.2 Section 5.2 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY LIQUORS LABELING AND ADVERTISING OF DISTILLED SPIRITS Scope § 5.2 Related regulations...

27 CFR 4.5 - Related regulations.

Science.gov (United States)

2010-04-01

... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Related regulations. 4.5 Section 4.5 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY LIQUORS LABELING AND ADVERTISING OF WINE Scope § 4.5 Related regulations. The following...

American Ginseng Stimulates Insulin Production and Prevents Apoptosis through Regulation of Uncoupling Protein-2 in Cultured β Cells

Directory of Open Access Journals (Sweden)

John Zeqi Luo

2006-01-01

Full Text Available American ginseng root displays the ability to achieve glucose homeostasis both experimentally and clinically but the unknown mechanism used by ginseng to achieve its therapeutic effects on diabetes limits its application. Disruption in the insulin secretion of pancreatic β cells is considered the major cause of diabetes. A mitochondrial protein, uncoupling protein-2 (UCP-2 has been found to play a critical role in insulin synthesis and β cell survival. Our preliminary studies found that the extracts of American ginseng inhibit UCP-2 expression which may contribute to the ability of ginseng protecting β cell death and improving insulin synthesis. Therefore, we hypothesized that ginseng extracts suppress UCP-2 in the mitochondria of pancreatic β cells, promoting insulin synthesis and anti-apoptosis (a programmed cell-death mechanism. To test the hypothesis, the serum-deprived quiescent β cells were cultured with or without interleukin-1β (IL-1β, (200 pg ml−1, a cytokine to induce β cell apoptosis and water extracts of American ginseng (25 μg per 5 μl administered to wells of 0.5 ml culture for 24 h. We evaluated effects of ginseng on UCP-2 expression, insulin production, anti-/pro-apoptotic factors Bcl-2/caspase-9 expression and cellular ATP levels. We found that ginseng suppresses UCP-2, down-regulates caspase-9 while increasing ATP and insulin production/secretion and up-regulates Bcl-2, reducing apoptosis. These findings suggest that stimulation of insulin production and prevention of β cell loss by American ginseng extracts can occur via the inhibition of mitochondrial UCP-2, resulting in increase in the ATP level and the anti-apoptotic factor Bcl-2, while down-regulation of pro-apoptotic factor caspase-9 occurs, lowering the occurrence of apoptosis, which support the hypothesis.

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

International Nuclear Information System (INIS)

Atoui, A.; Larey, C.; Thokala, R.; Calvo, A.M.; Kastner, C.; Fischer, R.; Etxebeste, O; Espeso, E.A.

2010-01-01

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)

A comprehensive data set of lake surface water temperature over the Tibetan Plateau derived from MODIS LST products 2001-2015.

Science.gov (United States)

Wan, Wei; Li, Huan; Xie, Hongjie; Hong, Yang; Long, Di; Zhao, Limin; Han, Zhongying; Cui, Yaokui; Liu, Baojian; Wang, Cunguang; Yang, Wenting

2017-07-25

Lake surface water temperature (LSWT) is sensitive to long-term changes in thermal structure of lakes and regional air temperature. In the context of global climate change, recent studies showed a significant warming trend of LSWT based on investigating 291 lakes (71% are large lakes, ≥50 km 2 each) globally. However, further efforts are needed to examine variation in LSWT at finer regional spatial and temporal scales. The Tibetan Plateau (TP), known as 'the Roof of the World' and 'Asia's water towers', exerts large influences on and is sensitive to regional and even global climates. Aiming to examine detailed changing patterns and potential driven mechanisms for temperature variations of lakes across the TP region, this paper presents the first comprehensive data set of 15-year (2001-2015) nighttime and daytime LSWT for 374 lakes (≥10 km 2 each), using MODIS (Moderate Resolution Imaging Spectroradiometer) Land Surface Temperature (LST) products as well as four lake boundary shapefiles (i.e., 2002, 2005, 2009, and 2014) derived from Landsat/CBERS/GaoFen-1 satellite images. The data set itself reveals significant information on LSWT and its changes over the TP and is an indispensable variable for numerous applications related to climate change, water budget analysis (particularly lake evaporation), water storage changes, glacier melting and permafrost degradation, etc.

Metabolic regulation of yeast

Science.gov (United States)

Fiechter, A.

1982-12-01

Metabolic regulation which is based on endogeneous and exogeneous process variables which may act constantly or time dependently on the living cell is discussed. The observed phenomena of the regulation are the result of physical, chemical, and biological parameters. These parameters are identified. Ethanol is accumulated as an intermediate product and the synthesis of biomass is reduced. This regulatory effect of glucose is used for the aerobic production of ethanol. Very high production rates are thereby obtained. Understanding of the regulation mechanism of the glucose effect has improved. In addition to catabolite repression, several other mechanisms of enzyme regulation have been described, that are mostly governed by exogeneous factors. Glucose also affects the control of respiration in a third class of yeasts which are unable to make use of ethanol as a substrate for growth. This is due to the lack of any anaplerotic activity. As a consequence, diauxic growth behavior is reduced to a one-stage growth with a drastically reduced cell yield. The pulse chemostat technique, a systematic approach for medium design is developed and medium supplements that are essential for metabolic control are identified.

Substrate specificity changes for human reticulocyte and epithelial 15-lipoxygenases reveal allosteric product regulation.

Science.gov (United States)

Wecksler, Aaron T; Kenyon, Victor; Deschamps, Joshua D; Holman, Theodore R

2008-07-15

Human reticulocyte 15-lipoxygenase (15-hLO-1) and epithelial 15-lipoxygenase (15-hLO-2) have been implicated in a number of human diseases, with differences in their substrate specificity potentially playing a central role. In this paper, we present a novel method for accurately measuring the substrate specificity of the two 15-hLO isozymes and demonstrate that both cholate and specific LO products affect substrate specificity. The linoleic acid (LA) product, 13-hydroperoxyoctadienoic acid (13-HPODE), changes the ( k cat/ K m) (AA)/( k cat/ K m) (LA) ratio more than 5-fold for 15-hLO-1 and 3-fold for 15-hLO-2, while the arachidonic acid (AA) product, 12-( S)-hydroperoxyeicosatetraenoic acid (12-HPETE), affects only the ratio of 15-hLO-1 (more than 5-fold). In addition, the reduced products, 13-( S)-hydroxyoctadecadienoic acid (13-HODE) and 12-( S)-hydroxyeicosatetraenoic acid (12-HETE), also affect substrate specificity, indicating that iron oxidation is not responsible for the change in the ( k cat/ K m) (AA)/( k cat/ K m) (LA) ratio. These results, coupled with the dependence of the 15-hLO-1 k cat/ K m kinetic isotope effect ( (D) k cat/ K m) on the presence of 12-HPETE and 12-HETE, indicate that the allosteric site, previously identified in 15-hLO-1 [Mogul, R., Johansen, E., and Holman, T. R. (1999) Biochemistry 39, 4801-4807], is responsible for the change in substrate specificity. The ability of LO products to regulate substrate specificity may be relevant with respect to cancer progression and warrants further investigation into the role of this product-feedback loop in the cell.

Comparative studies of oil product regulation in polluted soil for several industrialized countries

Science.gov (United States)

Paccassoni, F.; Kalnina, D.; Piga, L.

2017-10-01

Oil contaminated sites are the consequence of a long period of industrialization. Oil is a complex mixture including aliphatic and aromatic hydrocarbons, which are known to have negative effects on human health and the environment. Dividing oil products in groups (fractions) of petroleum hydrocarbons that act alike in soil and water, one can better know what happens to them. Being able to understand the behaviour of oil products in soil, it will allow to implement prevention and remediation actions. Interventions on contaminated sites are bound to comply with regulatory limits that each country has set in their own environmental legislation. The different concentration thresholds of oil products in soil for several EU countries and Canada has led to compare: limit values, analytical method, soil characteristics and/or land use. This will allow to evaluate what could be the best regulation approach, assessing if it is better to consider soil matrix in the site or the specific land use or both of them. It will also assess what is the best analytical methodology to be adopted to achieve the pollutant concentrations in the soil in order to have comparable results among different countries, such as: Baltic countries (Latvia, Estonia, Lithuania), Nordic countries (Finland, Sweden, Norway, Denmark), Western countries (Italy and The Netherlands) and Canada, like gaschromatography in the range from C10 - C50. The study presents an overview of environmental regulatory system of several EU countries and Canada and the correlation between different parameters about oil products indicated in each environmental legislation.

Specific interaction between hnRNP H and HPV16 L1 proteins: Implications for late gene auto-regulation enabling rapid viral capsid protein production

Energy Technology Data Exchange (ETDEWEB)

Zheng, Zi-Zheng; Sun, Yuan-Yuan; Zhao, Min; Huang, Hui [National Institute of Diagnostics and Vaccine Development in Infectious Diseases, Xiamen University, Xiamen, Fujian 361005 (China); School of Life Sciences, Xiamen University, Xiamen, Fujian 361005 (China); Zhang, Jun; Xia, Ning-Shao [National Institute of Diagnostics and Vaccine Development in Infectious Diseases, Xiamen University, Xiamen, Fujian 361005 (China); School of Life Sciences, Xiamen University, Xiamen, Fujian 361005 (China); School of Public Health, Xiamen University, Xiamen, Fujian 361005 (China); Miao, Ji, E-mail: jmiao@xmu.edu.cn [National Institute of Diagnostics and Vaccine Development in Infectious Diseases, Xiamen University, Xiamen, Fujian 361005 (China); School of Life Sciences, Xiamen University, Xiamen, Fujian 361005 (China); Zhao, Qinjian, E-mail: qinjian_zhao@xmu.edu.cn [National Institute of Diagnostics and Vaccine Development in Infectious Diseases, Xiamen University, Xiamen, Fujian 361005 (China); School of Public Health, Xiamen University, Xiamen, Fujian 361005 (China)

2013-01-18

Highlights: ► The RNA-binding hnRNP H regulates late viral gene expression. ► hnRNP H activity was inhibited by a late viral protein. ► Specific interaction between HPV L1 and hnRNP H was demonstrated. ► Co-localization of HPV L1 and hnRNP H inside cells was observed. ► Viral capsid protein production, enabling rapid capsid assembly, was implicated. -- Abstract: Heterogeneous nuclear ribonucleoproteins (hnRNPs), including hnRNP H, are RNA-binding proteins that function as splicing factors and are involved in downstream gene regulation. hnRNP H, which binds to G triplet regions in RNA, has been shown to play an important role in regulating the staged expression of late proteins in viral systems. Here, we report that the specific association between hnRNP H and a late viral capsid protein, human papillomavirus (HPV) L1 protein, leads to the suppressed function of hnRNP H in the presence of the L1 protein. The direct interaction between the L1 protein and hnRNP H was demonstrated by complex formation in solution and intracellularly using a variety of biochemical and immunochemical methods, including peptide mapping, specific co-immunoprecipitation and confocal fluorescence microscopy. These results support a working hypothesis that a late viral protein HPV16 L1, which is down regulated by hnRNP H early in the viral life cycle may provide an auto-regulatory positive feedback loop that allows the rapid production of HPV capsid proteins through suppression of the function of hnRNP H at the late stage of the viral life cycle. In this positive feedback loop, the late viral gene products that were down regulated earlier themselves disable their suppressors, and this feedback mechanism could facilitate the rapid production of capsid proteins, allowing staged and efficient viral capsid assembly.

Cosmetic Regulations: A Comparative Study.

Science.gov (United States)

Suhag, Jyoti; Dureja, Harish

2015-01-01

The regulatory framework, compliance requirement, efficacy, safety, and marketing of cosmetic products are considered the most important factors for growth of the cosmetic industry. There are different regulatory bodies across the globe that have their own insights for regulation; moreover, governments such as the United States, European Union, and Japan follow a stringent regulatory framework, whereas cosmetics are not so much strictly regulated in countries such as India, Brazil, and China. The alignment of a regulatory framework will play a significant role in the removal of barriers to trade, growth of market at an international level, innovation in the development and presentation of new products, and most importantly safety and efficacy of the marketed products. The present contribution gives insight into the important cosmetic regulations in areas of premarket approval, ingredient control, and labeling and warnings, with a special focus on the cosmetic regulatory environments in the United States, European Union, Japan, and India. Most importantly, the authors highlight the dark side of cosmetics associated with allergic reactions and even skin cancer. The importance of cosmetic regulations has been highlighted by dint of which the society can be healthier, accomplished by more stringent and harmonized regulations.

Circulating Glucagon 1-61 Regulates Blood Glucose by Increasing Insulin Secretion and Hepatic Glucose Production

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Nicolai J. Wewer Albrechtsen

2017-11-01

Full Text Available Glucagon is secreted from pancreatic α cells, and hypersecretion (hyperglucagonemia contributes to diabetic hyperglycemia. Molecular heterogeneity in hyperglucagonemia is poorly investigated. By screening human plasma using high-resolution-proteomics, we identified several glucagon variants, among which proglucagon 1-61 (PG 1-61 appears to be the most abundant form. PG 1-61 is secreted in subjects with obesity, both before and after gastric bypass surgery, with protein and fat as the main drivers for secretion before surgery, but glucose after. Studies in hepatocytes and in β cells demonstrated that PG 1-61 dose-dependently increases levels of cAMP, through the glucagon receptor, and increases insulin secretion and protein levels of enzymes regulating glycogenolysis and gluconeogenesis. In rats, PG 1-61 increases blood glucose and plasma insulin and decreases plasma levels of amino acids in vivo. We conclude that glucagon variants, such as PG 1-61, may contribute to glucose regulation by stimulating hepatic glucose production and insulin secretion.

Differential regulation of TNF-α and IL-1β production from endotoxin stimulated human monocytes by phosphodiesterase inhibitors

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K. L. Molnar-Kimber

1992-01-01

Full Text Available The effect of selective PDE-I (vinpocetine, PDE-III (milrinone, CI-930, PDE-IV (rolipram, nitroquazone, and PDE-V (zaprinast isozyme inhibitors on TNF-α and IL-1β production from LPS stimulated human monocytes was investigated. The PDE-IV inhibitors caused a concentration dependent inhibition of TNF-α production, but only partially inhibited IL-1β at high concentrations. High concentrations of the PDE-III inhibitors weakly inhibited TNF-α, but had no effect on IL-1β production. PDE-V inhibition was associated with an augmentation of cytokine secretion. Studies with combinations of PDE isozyme inhibitors indicated that PDE-III and PDE-V inhibitors modulate rolipram's suppression of TNF production in an additive manner. These data confirm that TNF-α and IL-1β production from LPS stimulated human monocytes are differentially regulated, and suggest that PDE-IV inhibitors have the potential to suppress TNF levels in man.

Cellular regulation of basal and FSH-stimulated cyclic AMP production in irradiated rat testes

International Nuclear Information System (INIS)

Kangasniemi, M.; Kaipia, A.; Toppari, J.; Mali, P.; Huhtaniemi, I.; Parvinen, M.

1990-01-01

Basal and follicle-stimulating hormone (FSH)-stimulated cyclic AMP (cAMP) productions by seminiferous tubular segments from irradiated adult rats were investigated at defined stages of the epithelial cycle when specific spermatogenic cells were low in number. Seven days post-irradiation, depletion of spermatogonia did not influence the basal cAMP production, but FSH response increased in stages II-VIII. Seventeen days post-irradiation when spermatocytes were low in number, there was a small increase in basal cAMP level in stages VII-VIII and FSH-stimulated cAMP production increased in stages VII-XII and XIII-I. At 38 days when pachytene spermatocytes and round spermatids (steps 1-6) were low in number, a decreased basal cAMP production was measured in stages II-VI and IX-XII. FSH-stimulated cAMP output increased in stages VII-XII but decreased in stages II-VI. At 52 days when all spermatids were low in number, basal cAMP levels decreased in all stages of the cycle, whereas FSH response was elevated only in stages VII-XII. All spermatogenic cell types seem to have an effect on cAMP production by the seminiferous tubule in a stage-specific fashion. Germ cells appear to regulate Sertoli cell FSH response in a paracrine way, and a part of cAMP may originate from spermatids stimulated by an unknown FSH-dependent Sertoli cell factor. The FSH-dependent functions may control such phenomena as spermatogonial proliferation, final maturation of spermatids, and onset of meiosis

HIV-1 infection induces changes in expression of cellular splicing factors that regulate alternative viral splicing and virus production in macrophages

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Purcell Damian FJ

2008-02-01

Full Text Available Abstract Background Macrophages are important targets and long-lived reservoirs of HIV-1, which are not cleared of infection by currently available treatments. In the primary monocyte-derived macrophage model of infection, replication is initially productive followed by a decline in virion output over ensuing weeks, coincident with a decrease in the levels of the essential viral transactivator protein Tat. We investigated two possible mechanisms in macrophages for regulation of viral replication, which appears to be primarily regulated at the level of tat mRNA: 1 differential mRNA stability, used by cells and some viruses for the rapid regulation of gene expression and 2 control of HIV-1 alternative splicing, which is essential for optimal viral replication. Results Following termination of transcription at increasing times after infection in macrophages, we found that tat mRNA did indeed decay more rapidly than rev or nef mRNA, but with similar kinetics throughout infection. In addition, tat mRNA decayed at least as rapidly in peripheral blood lymphocytes. Expression of cellular splicing factors in uninfected and infected macrophage cultures from the same donor showed an inverse pattern over time between enhancing factors (members of the SR family of RNA binding proteins and inhibitory factors (members of the hnRNP family. While levels of the SR protein SC35 were greatly up-regulated in the first week or two after infection, hnRNPs of the A/B and H groups were down-regulated. Around the peak of virus production in each culture, SC35 expression declined to levels in uninfected cells or lower, while the hnRNPs increased to control levels or above. We also found evidence for increased cytoplasmic expression of SC35 following long-term infection. Conclusion While no evidence of differential regulation of tat mRNA decay was found in macrophages following HIV-1 infection, changes in the balance of cellular splicing factors which regulate alternative

Growth regulators and essential oil production

OpenAIRE

Prins, Cláudia L; Vieira, Ivo J. C; Freitas, Silvério P

2010-01-01

The aroma and fragrance industry is a billion-dollar world market which grows annually. Essential oils comprise the majority of compounds used by these industries. These sets of metabolites are formed mainly by monoterpenes, which are products of the plants' secondary metabolism. Biosynthesized from mevalonate and methylerythitol phosphate, the essential oil production depends not only on genetic factors and the developmental stage of plants, but also on environmental factors which could resu...

Close teamwork between Nrf2 and peroxiredoxins 1 and 6 for the regulation of prostaglandin D2 and E2 production in macrophages in acute inflammation.

Science.gov (United States)

Ishii, Tetsuro

2015-11-01

Inflammation is a complex biological self-defense reaction triggered by tissue damage or infection by pathogens. Acute inflammation is regulated by the time- and cell type-dependent production of cytokines and small signaling molecules including reactive oxygen species and prostaglandins. Recent studies have unveiled the important role of the transcription factor Nrf2 in the regulation of prostaglandin production through transcriptional regulation of peroxiredoxins 1 and 6 (Prx1 and Prx6) and lipocalin-type prostaglandin D synthase (L-PGDS). Prx1 and Prx6 are multifunctional proteins important for cell protection against oxidative stress, but also work together to facilitate production of prostaglandins E2 and D2 (PGE2 and PGD2). Prx1 secreted from cells under mild oxidative stress binds Toll-like receptor 4 and induces NF-κB activation, important for the expression of cyclooxygenase-2 and microsomal PGE synthase-1 (mPGES-1) expression. The activated MAPKs p38 and ERK phosphorylate Prx6, leading to NADPH oxidase-2 activation, which contributes to production of PGD2 by hematopoietic prostaglandin D synthase (H-PGDS). PGD2 and its end product 15-deoxy-∆(12,14)-prostaglandin J2 (15d-PGJ2) activate Nrf2 thereby forming a positive feedback loop for further production of PGD2 by L-PGDS. Maintenance of cellular glutathione levels is an important role of Nrf2 not only for cell protection but also for the synthesis of prostaglandins, as mPGES-1 and H-PGDS require glutathione for their activities. This review is aimed at describing the functions of Prx1 and Prx6 in the regulation of PGD2 and PGE2 production in acute inflammation in macrophages and the importance of 15d-PGJ2 as an intrinsic Nrf2 activator. Copyright © 2015 Elsevier Inc. All rights reserved.

CRP-Mediated Carbon Catabolite Regulation of Yersinia pestis Biofilm Formation Is Enhanced by the Carbon Storage Regulator Protein, CsrA.

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Stephan P Willias

Full Text Available The natural transmission of Yersinia pestis is reliant upon biofilm blockage of the flea vector. However, the environmentally-responsive adaptive regulators which facilitate Y. pestis biofilm production in accordance with the flea midgut milieu are not well understood. We seek to establish the impact of available carbon source metabolism and storage upon Y. pestis biofilm production. Our findings demonstrate that Y. pestis biofilm production is subject to carbon catabolite regulation in which the presence of glucose impairs biofilm production; whereas, the sole metabolism of alternate carbon sources promotes robust biofilm formation. This observation is facilitated by the cAMP receptor protein, CRP. In accordance with a stark growth defect, deletion of crp in both CO92 and KIM6+ Y. pestis strains significantly impaired biofilm production when solely utilizing alternate carbon sources. Media supplementation with cAMP, a small-molecule activator of CRP, did not significantly alter Y. pestis biofilm production. Furthermore, CRP did not alter mRNA abundance of previously-characterized hms biofilm synthesis and regulation factors. Therefore, our findings indicate CRP does not confer a direct stimulatory effect, but may indirectly promote Y. pestis biofilm production by facilitating the alternate carbon source expression profile. Additionally, we assessed the impact of the carbon storage regulator protein, CsrA, upon Y. pestis biofilm production. Contrary to what has been described for E. coli, Y. pestis biofilm formation was found to be enhanced by CsrA. Regardless of media composition and available carbon source, deletion of csrA significantly impaired Y. pestis biofilm production. CsrA was found to promote Y. pestis biofilm production independent of glycogen regulation. Loss of csrA did not significantly alter relative hmsH, hmsP, or hmsT mRNA abundance. However, deletion of hmsP in the csrA-deficient mutant enabled excessive biofilm production

76 FR 18226 - Guidance for Industry on Postmarketing Studies and Clinical Trials-Implementation of Section 505...

Science.gov (United States)

2011-04-01

... and Development (HFM-40), Center for Biologics Evaluation and Research (CBER), Food and Drug... Drug Information, Center for Drug Evaluation and Research, Food and Drug Administration, 10903 New..., Center for Drug Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 51...

75 FR 35492 - Guidance for Industry on Lupus Nephritis Caused By Systemic Lupus Erythematosus-Developing...

Science.gov (United States)

2010-06-22

... Communication, Outreach and Development (HFM-40), Center for Biologics Evaluation and Research (CBER), Food and...: The Food and Drug Administration (FDA) is announcing the availability of a guidance for industry... the Division of Drug Information, Center for Drug Evaluation and Research, Food and Drug...

Radiation Regulation Bodies in South Africa

International Nuclear Information System (INIS)

Mavunda, R.D.

2010-01-01

Tthere are two types Regulatory Bodies in South Africa: department of Health - Radiation Control (DoH) and National Nuclear Regulator (NNR). The function DoH include of Promotion and maintenance of health within the framework of National health plan, Protection against injury or disease caused by technological devises, Protection against injury or disease caused by radiation, Promote safe and legal use of such products. The National Nuclear Regulator authorizes Nuclear Installation License, Nuclear Vessel License, Certificate of Registration and Certificate of Exemption. Some of the Electronic Products include licensing electro-medical products, Import or manufactured License conditions, Radiation workers, Report forms, Use and Radio-nuclides. Nuclear Authorization is the process of granting, by the National Nuclear Regulator, a written approval to applicants or / and operating organizations to perform nuclear related activities as detailed in the scope of the authorization. International Trade Administration Commission of South Africa (ITAC) issue license for import and export of all products including electronic X-Ray products and Radio-nuclides

Rac1 regulates the NLRP3 inflammasome which mediates IL-1beta production in Chlamydophila pneumoniae infected human mononuclear cells.

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Julia Eitel

Full Text Available Chlamydophila pneumoniae causes acute respiratory tract infections and has been associated with development of asthma and atherosclerosis. The production of IL-1β, a key mediator of acute and chronic inflammation, is regulated on a transcriptional level and additionally on a posttranslational level by inflammasomes. In the present study we show that C. pneumoniae-infected human mononuclear cells produce IL-1β protein depending on an inflammasome consisting of NLRP3, the adapter protein ASC and caspase-1. We further found that the small GTPase Rac1 is activated in C. pneumoniae-infected cells. Importantly, studies with specific inhibitors as well as siRNA show that Rac1 regulates inflammasome activation in C. pneumoniae-infected cells. In conclusion, C. pneumoniae infection of mononuclear cells stimulates IL-1β production dependent on a NLRP3 inflammasome-mediated processing of proIL-1β which is controlled by Rac1.

PD-L2 Regulates B-1 Cell Antibody Production against Phosphorylcholine through an IL-5-Dependent Mechanism.

Science.gov (United States)

McKay, Jerome T; Haro, Marcela A; Daly, Christina A; Yammani, Rama D; Pang, Bing; Swords, W Edward; Haas, Karen M

2017-09-15

B-1 cells produce natural Abs which provide an integral first line of defense against pathogens while also performing important homeostatic housekeeping functions. In this study, we demonstrate that programmed cell death 1 ligand 2 (PD-L2) regulates the production of natural Abs against phosphorylcholine (PC). Naive PD-L2-deficient (PD-L2 -/- ) mice produced significantly more PC-reactive IgM and IgA. This afforded PD-L2 -/- mice with selectively enhanced protection against PC-expressing nontypeable Haemophilus influenzae , but not PC-negative nontypeable Haemophilus influenzae , relative to wild-type mice. PD-L2 -/- mice had significantly increased PC-specific CD138 + splenic plasmablasts bearing a B-1a phenotype, and produced PC-reactive Abs largely of the T15 Id. Importantly, PC-reactive B-1 cells expressed PD-L2 and irradiated chimeras demonstrated that B cell-intrinsic PD-L2 expression regulated PC-specific Ab production. In addition to increased PC-specific IgM, naive PD-L2 -/- mice and irradiated chimeras reconstituted with PD-L2 -/- B cells had significantly higher levels of IL-5, a potent stimulator of B-1 cell Ab production. PD-L2 mAb blockade of wild-type B-1 cells in culture significantly increased CD138 and Blimp1 expression and PC-specific IgM, but did not affect proliferation. PD-L2 mAb blockade significantly increased IL-5 + T cells in culture. Both IL-5 neutralization and STAT5 inhibition blunted the effects of PD-L2 mAb blockade on B-1 cells. Thus, B-1 cell-intrinsic PD-L2 expression inhibits IL-5 production by T cells and thereby limits natural Ab production by B-1 cells. These findings have broad implications for the development of therapeutic strategies aimed at altering natural Ab levels critical for protection against infectious disease, autoimmunity, allergy, cancer, and atherosclerosis. Copyright © 2017 by The American Association of Immunologists, Inc.

Contributions of citrate in redox potential maintenance and ATP production: metabolic pathways and their regulation in Lactobacillus panis PM1.

Science.gov (United States)

Kang, Tae Sun; Korber, Darren R; Tanaka, Takuji

2013-10-01

Lactobacillus panis PM1 belongs to the group III heterofermentative lactobacilli and can utilize various NADH-reoxidizing routes (e.g., citrate, glycerol, and oxygen) according to environmental conditions. In this study, we investigated the ability of L. panis PM1 to produce succinate, acetate, and lactate via citrate utilization. Possible pathways, as well as regulation, for citrate metabolism were examined on the basis of the genome sequence data and metabolic profiles of L. panis PM1. The presence of citrate led to the up-regulation, at the transcriptional level, of the genes encoding for citrate lyase, malate dehydrogenase, and malic enzyme of the citrate pathways by 10- to 120-fold. The transcriptional regulator of the dha operon coding for glycerol dehydratase of L. panis PM1 repressed the expression of the citrate lyase gene (10-fold). Metabolite analyses indicated that the transcriptional enhancement by citrate stimulated succinate yield. Citrate metabolism contributed to energy production by providing a major alternate pathway for NAD(+) regeneration and allowed acetyl phosphate to yield acetate/ATP instead of ethanol/NAD(+). Additionally, a branching pathway from oxaloacetate to pyruvate increased the pool of lactate, which was then used to produce ATP during stationary phase. However, the redirection of NADH-to-citrate utilization resulted in stress caused by end-products (i.e., succinate and acetate). This stress reduced succinate production by up to 50 % but did not cause significant changes at transcriptional level. Overall, citrate utilization was beneficial for the growth of L. panis PM1 by providing a NAD(+) regeneration route and producing extra ATP.

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

Science.gov (United States)

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

2016-06-08

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.

Production of Cellulases by Rhizopus stolonifer from Glucose-Containing Media Based on the Regulation of Transcriptional Regulator CRE.

Science.gov (United States)

Zhang, Yingyiing; Tang, Bin; Du, Guocheng

2017-03-28

Carbon catabolite repression is a crucial regulation mechanism in microorganisms, but its characteristic in Rhizopus is still unclear. We extracted a carbon regulation gene, cre , that encoded a carbon catabolite repressor protein (CRE) from Rhizopus stolonifer TP-02, and studied the regulation of CRE by real-time qPCR. CRE responded to glucose in a certain range, where it could significantly regulate part of the cellulase genes ( eg, bg, and cbh2 ) without cbh1 . In the comparison of the response of cre and four cellulase genes to carboxymethylcellulose sodium and a simple carbon source (lactose), the effect of CRE was only related to the concentration of reducing sugars. By regulating the reducing sugars to range from 0.4% to 0.6%, a glucose-containing medium with lactose as the inducer could effectively induce cellulases without the repression of CRE. This regulation method could potentially reduce the cost of enzymes produced in industries and provide a possible solution to achieve the large-scale synthesis of cellulases.

Issues with monitoring the safety of psychoactive products under a legal regulated market for new psychoactive substances ('legal highs') in New Zealand.

Science.gov (United States)

Rychert, Marta; Wilkins, Chris; Witten, Karen

2017-09-01

New Zealand's Psychoactive Substances Act (2013) established the world's first regulated market for 'low risk' psychoactive products ('legal highs'). Under an interim PSA regime, 47 existing products were permitted to be continued to be sold. To explore issues with the implementation of regulatory systems to monitor the safety of products on the legal market under the interim Psychoactive Substances Act regime. Semi-structured interviews with 30 key stakeholders, including industry, government agency, health and drug service professionals were conducted, transcribed and analysed thematically. In retrospect stakeholders questioned the decision to approve strong synthetic cannabinoid smoking products, noting their health risks because of product formulation, inconsistent manufacturing practices and smoking as the means of administration. Industry actors claimed the decision to approve synthetic cannabinoid smokeable products prevented potentially safer products from gaining market share. The system for withdrawing approved products which were subsequently found to be harmful was criticised for the poor quality of data available, limited engagement with health professionals and the slowness of product withdrawal. Many of the problems with the regime were attributed to the urgency under which the legal market under the interim Psychoactive Substances Act was established and implemented. The selection of 'safer' products, implementation of the product monitoring system, and engagement with health professionals may have benefited from more time and resources. An incremental approach to establishing the new market may have made the regulatory management of the new regime more workable. [Rychert M, Wilkins C, Witten K. Issues with monitoring the safety of psychoactive products under a legal regulated market for new psychoactive substances ('legal highs') in New Zealand. Drug Alcohol Rev 2017;00:000-000]. © 2017 Australasian Professional Society on Alcohol and other Drugs.

Global approaches to regulating electronic cigarettes

Science.gov (United States)

Kennedy, Ryan David; Awopegba, Ayodeji; De León, Elaine; Cohen, Joanna E

2017-01-01

Objectives Classify and describe the policy approaches used by countries to regulate e-cigarettes. Methods National policies regulating e-cigarettes were identified by (1) conducting web searches on Ministry of Health websites, and (2) broad web searches. The mechanisms used to regulate e-cigarettes were classified as new/amended laws, or existing laws. The policy domains identified include restrictions or prohibitions on product: sale, manufacturing, importation, distribution, use, product design including e-liquid ingredients, advertising/promotion/sponsorship, trademarks, and regulation requiring: taxation, health warning labels and child-safety standards. The classification of the policy was reviewed by a country expert. Results The search identified 68 countries that regulate e-cigarettes: 22 countries regulate e-cigarettes using existing regulations; 25 countries enacted new policies to regulate e-cigarettes; 7 countries made amendments to existing legislation; 14 countries use a combination of new/amended and existing regulation. Common policies include a minimum-age-of-purchase, indoor-use (vape-free public places) bans and marketing restrictions. Few countries are applying a tax to e-cigarettes. Conclusions A range of regulatory approaches are being applied to e-cigarettes globally; many countries regulate e-cigarettes using legislation not written for e-cigarettes. PMID:27903958

Means of regulating combustible materials and products in external walls

Directory of Open Access Journals (Sweden)

Mikkola Esko

2016-01-01

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.

Environmental compatible design of power operated products. Contribution of the ecological design regulation to the energy efficiency targets of the EU; Umweltgerechte Gestaltung energiebetriebener Produkte. Der Beitrag der Oekodesign-Richtlinie zu den Energieeffizienzzielen der EU

Energy Technology Data Exchange (ETDEWEB)

Oehme, Ines; Halatsch, Andreas; Schuberth, Jens; Mordziol, Christoph

2009-07-15

The ecological design regulation and its further arrangement are a central component of the climatic protection politics and the policy of the European Union according to the sustainability in production and consumption. This regulation is to contribute to reduce the environmental impacts caused by power operated products. In the contribution under consideration, the Federal Office for Environment Protection (Dessau-Rosslau, Federal Republic of Germany) reports on the ecological design regulation and answers the following questions: (a) Which goals pursues the ecological design regulation and which processes lead to their arrangement?; (b) Which contribution does the regulation perform to the energy saving?; (c) Which challenges and chances exist for the manufacturers?; (d) What are the effects of the ecological design regulation for the consumers?; (e) What mean the ecological design requirements concretely for the individual products? The ecological design requirements not only reduce the environmental impacts but also contribute to the climate protection and reduce the energy costs in the phase of utilization. The consumers receive comprehensive information on the technical characteristics of the products as well as their quality and environmental fairness. Parallel to the conversion of the ecological design regulation, the European Union updates the marking of the energy consumption for numerous products. The ecological design requirements refer to technical characteristics. They do not forbid products or techniques as such.

Entry Regulations, Product Differentiation and Determinants of Market Structure

OpenAIRE

Maican, Florin; Orth, ´Matilda

2013-01-01

We use a dynamic oligopoly model of entry and exit to evaluate how entry regulations affect profitability and market structure in retail. The model incorporates demand and store-level heterogeneity. Based on unique data for all retail food stores in Sweden, we find that the average entry costs for small and large stores are 10 and 18 percent lower, respectively, in markets with liberal compared with restrictive regulations. Counterfactual simulations show that lower entry costs in restrictive...

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

DEFF Research Database (Denmark)

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

2011-01-01

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...... mice exhibit decreased oxygen consumption and develop oxidative stress in skeletal muscle, leading to JNK activation and impaired insulin signaling. This effect is mimicked by knockdown of Sirt3 in cultured myoblasts, which exhibit reduced mitochondrial oxidation, increased reactive oxygen species......, 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....

Interactions between calcium and phosphorus in the regulation of the production of fibroblast growth factor 23 in vivo

DEFF Research Database (Denmark)

Quinn, S.J.; Thomsen, A.R.B.; Pang, J.L.

2013-01-01

, however, increases in serum phosphorus by dietary manipulation were accompanied by severe hypocalcemia, which appeared to blunt stimulation of FGF23 release. Increases in dietary phosphorus in PTH-CaSR DKO mice markedly decreased serum 1,25-dihydroxyvitamin D [1,25(OH)D] despite no change in FGF23...... correlation between calcium and phosphorus and serum FGF23 was found between FGF23 and the calcium × phosphorus product. Since calcium stimulated FGF23 production in the PTH-CaSR DKO mice, this effect cannot be mediated by the full-length CaSR. Thus the regulation of FGF23 by both calcium and phosphorus...

fundTPL-2 – ERK1/2 Signaling Promotes Host Resistance against Intracellular Bacterial Infection by Negative Regulation of Type I Interferon Production3

Science.gov (United States)

McNab, Finlay W.; Ewbank, John; Rajsbaum, Ricardo; Stavropoulos, Evangelos; Martirosyan, Anna; Redford, Paul S.; Wu, Xuemei; Graham, Christine M.; Saraiva, Margarida; Tsichlis, Philip; Chaussabel, Damien; Ley, Steven C.; O’Garra, Anne

2013-01-01

Tuberculosis, caused by Mycobacterium tuberculosis (Mtb), remains a leading cause of mortality and morbidity worldwide, causing approximately 1.4 million deaths per year. Key immune components for host protection during tuberculosis include the cytokines IL-12, IL-1 and TNF-α, as well as IFN-γ and CD4+ Th1 cells. However, immune factors determining whether individuals control infection or progress to active tuberculosis are incompletely understood. Excess amounts of type I interferon have been linked to exacerbated disease during tuberculosis in mouse models and to active disease in patients, suggesting tight regulation of this family of cytokines is critical to host resistance. In addition, the immunosuppressive cytokine IL-10 is known to inhibit the immune response to Mtb in murine models through the negative regulation of key pro-inflammatory cytokines and the subsequent Th1 response. We show here, using a combination of transcriptomic analysis, genetics and pharmacological inhibitors that the TPL-2-ERK1/2 signaling pathway is important in mediating host resistance to tuberculosis through negative regulation of type I interferon production. The TPL-2-ERK1/2 signalling pathway regulated production by macrophages of several cytokines important in the immune response to Mtb as well as regulating induction of a large number of additional genes, many in a type I IFN dependent manner. In the absence of TPL-2 in vivo, excess type I interferon promoted IL-10 production and exacerbated disease. These findings describe an important regulatory mechanism for controlling tuberculosis and reveal mechanisms by which type I interferon may promote susceptibility to this important disease. PMID:23842752

The effects of customer benefit and regulation on environmental product innovation. Empirical evidence from appliance manufacturers in Germany

International Nuclear Information System (INIS)

Kammerer, Daniel

2009-01-01

Environmental product (EP) innovations and their determinants have received increasing attention from researchers during the past years. So far, empirical studies have shown inconsistent results, especially regarding the impact of regulation. In this paper, I seek to advance the understanding of EP-innovation by introducing and testing a novel research framework. First, a novel unit of analysis, the environmental issue level, is applied. EP-innovation is not studied in broad terms but specifically for four environmental issues that are relevant to the electrical and electronic appliances industry: energy efficiency, toxic substances, material efficiency, and electromagnetic fields. Second, the customer benefit, a concept from the green marketing literature, is included as an explanatory variable for EP-innovation for the first time. The argument is that green products which besides their public benefits have private environmental benefits for the customer (e.g., energy savings) will generate stronger consumer demand and can thus constitute the firm's motivation to implement those innovations in the first place. Third, EP-innovation is observed more comprehensively, measuring its extent and level of novelty. I apply this research framework to study EP-innovations of German manufacturers of electrical and electronic appliances. My results support the issue level as unit of analysis. The impact of customer benefit and regulation on EP-innovation is analyzed with logit regression and the results clearly show that both customer benefit and regulation play a key role for EP-innovation. They not only foster the implementation of EP-innovations but also their broad application and their level of novelty. (author)

Grandfather regulations, new source bias, and state air toxics regulations

International Nuclear Information System (INIS)

Levinson, Arik

1999-01-01

This paper uses plant-level data from the Census of Manufactures and the variation in toxic air pollution regulations across states to measure the effects of laws that are more stringent for new sources of pollution than for existing sources (so-called 'grandfather' regulations). Of particular interest is the resulting 'new source bias' and its effects on capital vintage and investment. Two industries are examined: commercial printing, which has a local product market; and paint manufacturing, which has a more national market. In general, there seem to be no statistically significant differences in capital vintage or investment between plants in states that grandfather new sources of pollution, plants in states that have no air toxics regulations, and plants in states that regulate both new and existing sources

Study of the effect of plant growth regulators, size, and cultivar of the grape inflorescence explant on production of phenolic compounds in an in vitro condition

Directory of Open Access Journals (Sweden)

Sedighi Azam

2014-01-01

Full Text Available Introduction: Phenolic compounds are a large number of secondary metabolites that have useful and desirable effects in the field of agriculture, medicine, and food. This research was aimed to achieve methods of in vitro propagation of grapevine in order to apply biotechnologies for correction, growth, and optimization of products and compounds of the cultivated plant in relation to phenol ratio. Methods: In this interventional study, the effects of cultivar and size of the inflorescence explant and the gibberellin hormone in two levels, benzylaminopurine, and auxin hormones in three levels with three replicates per treatment were evaluated in relation to phenol ratio, in order to evaluate the effect of plant growth regulators, the type and size of the grape inflorescence explant on the phenol production. Results: The type of plant growth regulators affected phenolic substances production. The production of phenolic substances decreased in a medium with the highest concentration of growth regulators, 4 and 2.5 μM concentration of benzylaminopurine, and 4.9 μM of auxin. Production of phenolic substances increased in the free-plant hormone medium. In smaller samples tendency to turn brown was more regarding high amount of the sugar. Conclusion: The plant sample and the cultivar as important factors in producing phenol environment are induced by environmental stimuli like sugar, light, temperature, stress, ozone, and wound and can be actually applied to increase phenol production.

Role of plnB gene in the regulation of bacteriocin production in Lactobacillus paraplantarum L-XM1.

Science.gov (United States)

Zhang, Xiangmei; Shang, Nan; Zhang, Xu; Gui, Meng; Li, Pinglan

2013-06-12

Homologues of plnB gene have been shown to participate in regulation of bacteriocin production through quorum sensing system in other organisms, to investigate the possible role of plnB gene in Lactobacillus paraplantarum L-XM1, we cloned and insertionally inactivated the plnB gene. The plnB knockout mutant ΔplnB21 showed loss of bacteriocin production, its Bac⁺ phenotype could not be restored even after the addition of PlnA. Furthermore, reverse transcription-PCR analysis from total RNA preparations showed that the bacteriocin structural genes of the plnEF and plnJK were not transcribed in the plnB knockout mutant compared with the wild-type strain. It was therefore concluded that plnB is invovled in a quorum sensing based bacteriocin production. This is the first demonstration of a role for plnB by gene knockout in L. paraplantarum. Copyright © 2012 Elsevier GmbH. All rights reserved.

Autonomous control of metabolic state by a quorum sensing (QS)-mediated regulator for bisabolene production in engineered E. coli

DEFF Research Database (Denmark)

Kim, Eun-Mi; Min Woo, Han; Tian, Tian

2017-01-01

as it is self-regulated and does not require the addition of inducer compounds, which reduce operational costs for inducer. In this study, a QS system was developed for inducer-free production of the biofuel compound bisabolene from engineered E. coli. Seven variants of the Sensor plasmid, which carry the lux......I-luxR genes, and four variants of the Response plasmid, which carry bisabolene producing pathway genes under the control of the PluxI promoter, were designed for optimization of bisabolene production. Furthermore, a chromosome-integrated QS strain was engineered with the best combination of Sensor...

77 FR 12312 - Electronic Submission of Nonclinical Study Data; Notice of Pilot Project

Science.gov (United States)

2012-02-29

...] Electronic Submission of Nonclinical Study Data; Notice of Pilot Project AGENCY: Food and Drug Administration... and Research (CBER) is announcing an invitation to participate in a pilot evaluation program to test.... Participation in the pilot program is open to all sponsors. The pilot program is intended to provide industry...

75 FR 15639 - Revision of the Requirements for Constituent Materials

Science.gov (United States)

2010-03-30

... preservative, except that a preservative need not be added to Yellow Fever Vaccine; Poliovirus Vaccine Live... and Research (CBER) or the Director of the Center for Drug Evaluation and Research (CDER), as... and Research (HFM-17), Food and Drug Administration, 1401 Rockville Pike, suite 200N, Rockville, MD...

78 FR 20924 - Center for Biologics Evaluation and Research eSubmitter Pilot Evaluation Program for...

Science.gov (United States)

2013-04-08

..., Office of Blood Research and Review, Center for Biologics Evaluation and Research (HFM-375), Food and... assist CBER in the final development and release of this electronic program for use by industry. III... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2013-N-0248...

Latinamerican, Mercosur and imported countries regulations

Directory of Open Access Journals (Sweden)

Jacqueline Cea

2011-04-01

Full Text Available Mycotoxins attract worldwide attention because of the significant economic losses associated with their impact on human health, animal production and both domestic and international trade. Those mycotoxins that are currently considered to be worldwide  importance are aflatoxins, trichothecenes, zearalenone, fumonisins, ochratoxin A, patulin (Coker, 2000. The knowledge that mycotoxins can have serious effects on humans and animals has led many countries to establish regulations on mycotoxins in food and feed in the last decades to safeguard the health of humans, as well as the economical interests of producers and traders. Setting mycotoxin regulations is a complex activity which involves many factors and interested parties. In 1995, 23 percent of the world's inhabitants were living in a region where no known mycotoxin regulations were in force. This percentage had decreased to 13 percent in 2003, due to a slight increase in coverage in Latin America and Europe, and more significant increases in Africa and Asia/Oceania.The major Latin American agricultural crops (maize, wheat, coffee, cotton, soybeans, barley, sunflower, groundnuts and tree nuts, cocoa and dairy products are highly susceptible to fungal contamination and mycotoxin production (Pineiro, 2004. Nineteen countries, accounting for 91 percent of the population of the region, were known to have specific mycotoxin regulations. Uruguay has the most detailed regulations, including limits for ergot alkaloids in feeds, which is rather unique in the mycotoxin regulatory world. The same for deoxynivalenol in wheat products and barley products.MERCOSUR consists of Argentina, Brazil, Paraguay and Uruguay. These countries apply common limits for total aflatoxins in peanuts, maize and products thereof, and for aflatoxin M1 in fluid and powdered milk. The MERCOSUR regulations for mycotoxins also include official methods of sampling and analysis. In Europe, approximately 99 percent of the continent

Should Anthroposophic Medicinal Products Be Regulated in Europe?

Science.gov (United States)

Michaux, Geneviève

2017-03-01

European Commission’s reports suggest that the European Union should address the status of anthroposophic products, i.e. products that are developed, manufactured and prescribed in accordance with the holistic approach on which anthroposophic medicine is based. Anthroposophic products cannot be placed as such on the European market because they cannot meet the marketing authorisation or even registration requirements set out by European or national pharmaceutical law. Yet, the 95-year European tradition and good safety profile of anthroposophic products justify giving them an easier access to market. Such access can result from specific rules on anthroposophic products, but can be more efficiently achieved by encouraging the Member States to better apply the existing rules on marketing authorisation procedures or on registration of homeopathic and traditional herbal medicinal products, or by including anthroposophic substances, manufacturing methods or uses in monographs.

l-Arginine-Dependent Epigenetic Regulation of Interleukin-10, but Not Transforming Growth Factor-β, Production by Neonatal Regulatory T Lymphocytes

Science.gov (United States)

Yu, Hong-Ren; Tsai, Ching-Chang; Chang, Ling-Sai; Huang, Hsin-Chun; Cheng, Hsin-Hsin; Wang, Jiu-Yao; Sheen, Jiunn-Ming; Kuo, Ho-Chang; Hsieh, Kai-Sheng; Huang, Ying-Hsien; Yang, Kuender D.; Hsu, Te-Yao

2017-01-01

A growing number of diseases in humans, including trauma, certain cancers, and infection, are known to be associated with l-arginine deficiency. In addition, l-arginine must be supplemented by diet during pregnancy to aid fetal development. In conditions of l-arginine depletion, T cell proliferation is impaired. We have previously shown that neonatal blood has lower l-arginine levels than adult blood, which is associated with poor neonatal lymphocyte proliferation, and that l-arginine enhances neonatal lymphocyte proliferation through an interleukin (IL)-2-independent pathway. In this study, we have further investigated how exogenous l-arginine enhances neonatal regulatory T-cells (Tregs) function in relation to IL-10 production under epigenetic regulation. Results showed that cord blood mononuclear cells (CBMCs) produced higher levels of IL-10 than adult peripheral blood mononuclear cells (PBMCs) by phytohemagglutinin stimulation but not by anti-CD3/anti-CD28 stimulation. Addition of exogenous l-arginine had no effect on transforming growth factor-β production by PBMCs or CBMCs, but enhanced IL-10 production by neonatal CD4+CD25+FoxP3+ Tregs. Further studies showed that IL-10 promoter DNA hypomethylation, rather than histone modification, corresponded to the l-arginine-induced increase in IL-10 production by neonatal CD4+ T cells. These results suggest that l-arginine modulates neonatal Tregs through the regulation of IL-10 promoter DNA methylation. l-arginine supplementation may correct the Treg function in newborns with l-arginine deficiency. PMID:28487700

l-Arginine-Dependent Epigenetic Regulation of Interleukin-10, but Not Transforming Growth Factor-β, Production by Neonatal Regulatory T Lymphocytes

Directory of Open Access Journals (Sweden)

Kuender D. Yang

2017-04-01

Full Text Available A growing number of diseases in humans, including trauma, certain cancers, and infection, are known to be associated with l-arginine deficiency. In addition, l-arginine must be supplemented by diet during pregnancy to aid fetal development. In conditions of l-arginine depletion, T cell proliferation is impaired. We have previously shown that neonatal blood has lower l-arginine levels than adult blood, which is associated with poor neonatal lymphocyte proliferation, and that l-arginine enhances neonatal lymphocyte proliferation through an interleukin (IL-2-independent pathway. In this study, we have further investigated how exogenous l-arginine enhances neonatal regulatory T-cells (Tregs function in relation to IL-10 production under epigenetic regulation. Results showed that cord blood mononuclear cells (CBMCs produced higher levels of IL-10 than adult peripheral blood mononuclear cells (PBMCs by phytohemagglutinin stimulation but not by anti-CD3/anti-CD28 stimulation. Addition of exogenous l-arginine had no effect on transforming growth factor-β production by PBMCs or CBMCs, but enhanced IL-10 production by neonatal CD4+CD25+FoxP3+ Tregs. Further studies showed that IL-10 promoter DNA hypomethylation, rather than histone modification, corresponded to the l-arginine-induced increase in IL-10 production by neonatal CD4+ T cells. These results suggest that l-arginine modulates neonatal Tregs through the regulation of IL-10 promoter DNA methylation. l-arginine supplementation may correct the Treg function in newborns with l-arginine deficiency.

Hydrogen sulfide potentiates interleukin-1β-induced nitric oxide production via enhancement of extracellular signal-regulated kinase activation in rat vascular smooth muscle cells

International Nuclear Information System (INIS)

Jeong, Sun-Oh; Pae, Hyun-Ock; Oh, Gi-Su; Jeong, Gil-Saeng; Lee, Bok-Soo; Lee, Seoul; Kim, Du Yong; Rhew, Hyun Yul; Lee, Kang-Min; Chung, Hun-Taeg

2006-01-01

Hydrogen sulfide (H 2 S) and nitric oxide (NO) are endogenously synthesized from L-cysteine and L-arginine, respectively. They might constitute a cooperative network to regulate their effects. In this study, we investigated whether H 2 S could affect NO production in rat vascular smooth muscle cells (VSMCs) stimulated with interleukin-1β (IL-1β). Although H 2 S by itself showed no effect on NO production, it augmented IL-β-induced NO production and this effect was associated with increased expression of inducible NO synthase (iNOS) and activation of nuclear factor (NF)-κB. IL-1β activated the extracellular signal-regulated kinase 1/2 (ERK1/2), and this activation was also enhanced by H 2 S. Inhibition of ERK1/2 activation by the selective inhibitor U0126 inhibited IL-1β-induced NF-κB activation, iNOS expression, and NO production either in the absence or presence of H 2 S. Our findings suggest that H 2 S enhances NO production and iNOS expression by potentiating IL-1β-induced NF-κB activation through a mechanism involving ERK1/2 signaling cascade in rat VSMCs

7 CFR 301.91-2 - Regulated articles.

Science.gov (United States)

2010-01-01

... 7 Agriculture 5 2010-01-01 2010-01-01 false Regulated articles. 301.91-2 Section 301.91-2... Regulations § 301.91-2 Regulated articles. The following are regulated articles: (a) Logs, pulpwood, branches...) Any other product, article, or means of conveyance, of any character whatsoever, not covered by...

Role of glycolytic intermediate in regulation: Improving lycopene production in Escherichia coli by engineering metabolic control

Energy Technology Data Exchange (ETDEWEB)

Farmer, W.R.; Liao, J.C.

2001-06-01

Metabolic engineering in the postgenomic era is expected to benefit from a full understanding of the biosynthetic capability of microorganisms as a result of the progress being made in bioinformatics and functional genomics. The immediate advantage of such information is to allow the rational design of novel pathways and the elimination of native reactions that are detrimental or unnecessary for the desired purpose. However, with the ability to manipulate metabolic pathways becoming more effective, metabolic engineering will need to face a new challenge: the reengineering of the regulatory hierarchy that controls gene expression in those pathways. In addition to constructing the genetic composition of a metabolic pathway, they propose that it will become just as important to consider the dynamics of pathways gene expression. It has been widely observed that high-level induction of a recombinant protein or pathway leads to growth retardation and reduced metabolic activity. These phenotypic characteristics result from the fact that the constant demands of production placed upon the cell interfere with its changing requirements for growth. They believe that this common situation in metabolic engineering can be alleviated by designing a dynamic controller that is able to sense the metabolic state of the cell and regulate the expression of the recombinant pathway accordingly. This approach, which is termed metabolic control engineering, involves redesigning the native regulatory circuits and applying them to the recombinant pathway. The general goal of such an effort will be to control the flux to the recombinant pathway adaptively according to the cell's metabolic state. The dynamically controlled recombinant pathway can potentially lead to enhanced production, minimized growth retardation, and reduced toxic by-product formation. The regulation of gene expression in response to the physiological state is also essential to the success of gene therapy. Here they

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

International Nuclear Information System (INIS)

Atoui, A.; Bao, D.; Kaur, N.; Grayburn, W.S.; Calvo, A.M.

2008-01-01

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)

Analysis co-regulation model of safety of fishery products in Morocco through the example of “histamine”, “parasites” and “sulphites” dangers

Directory of Open Access Journals (Sweden)

S. Dahani

2018-01-01

Full Text Available Co-regulation in food safety represents the shared responsibility between food business operators and the competent authority (CA to ensure food safety and to comply with the health requirements of importing countries. The evolution of food regulation on one hand and the quality assurance of the veterinary services of the ONSSA according to the ISO 17020 standard on the other hand, need studying the regulation model adopted at national level. The objective of this work is to analyze the main health risks associated with fishery products from a co-regulatory perspective. The hazards targeted by this study are histamine, parasites and sulfites. The approach is based on structured interviews with fishery products professionals and veterinary inspectors responsible for control and certification. The main hazards are controlled by adopting health control plans (PMS by the professionals within the establishments as well as the official control carried out by the inspecting veterinarians. The PMS implementation can produce conflicting injunctions for the veterinary inspectors of the competent authority.

The Optimal Regulation of Product Quality under Monopoly

OpenAIRE

Hans Zenger

2006-01-01

This paper characterizes the optimal quality regulation of a monopolist when quality is observable. In contrast to Sheshinski (1976) it is shown that a minimum quality standard may be desirable even if it induces the firm to reduce output.

Hydrogen peroxide production regulates the mitochondrial function in insulin resistant muscle cells: effect of catalase overexpression.

Science.gov (United States)

Barbosa, Marina R; Sampaio, Igor H; Teodoro, Bruno G; Sousa, Thais A; Zoppi, Claudio C; Queiroz, André L; Passos, Madla A; Alberici, Luciane C; Teixeira, Felipe R; Manfiolli, Adriana O; Batista, Thiago M; Cappelli, Ana Paula Gameiro; Reis, Rosana I; Frasson, Danúbia; Kettelhut, Isis C; Parreiras-e-Silva, Lucas T; Costa-Neto, Claudio M; Carneiro, Everardo M; Curi, Rui; Silveira, Leonardo R

2013-10-01

The mitochondrial redox state plays a central role in the link between mitochondrial overloading and insulin resistance. However, the mechanism by which the ROS induce insulin resistance in skeletal muscle cells is not completely understood. We examined the association between mitochondrial function and H2O2 production in insulin resistant cells. Our hypothesis is that the low mitochondrial oxygen consumption leads to elevated ROS production by a mechanism associated with reduced PGC1α transcription and low content of phosphorylated CREB. The cells were transfected with either the encoded sequence for catalase overexpression or the specific siRNA for catalase inhibition. After transfection, myotubes were incubated with palmitic acid (500μM) and the insulin response, as well as mitochondrial function and fatty acid metabolism, was determined. The low mitochondrial oxygen consumption led to elevated ROS production by a mechanism associated with β-oxidation of fatty acids. Rotenone was observed to reduce the ratio of ROS production. The elevated H2O2 production markedly decreased the PGC1α transcription, an effect that was accompanied by a reduced phosphorylation of Akt and CREB. The catalase transfection prevented the reduction in the phosphorylated level of Akt and upregulated the levels of phosphorylated CREB. The mitochondrial function was elevated and H2O2 production reduced, thus increasing the insulin sensitivity. The catalase overexpression improved mitochondrial respiration protecting the cells from fatty acid-induced, insulin resistance. This effect indicates that control of hydrogen peroxide production regulates the mitochondrial respiration preventing the insulin resistance in skeletal muscle cells by a mechanism associated with CREB phosphorylation and β-oxidation of fatty acids. Copyright © 2013 Elsevier B.V. All rights reserved.

Panel presentation: Should some type of incentive regulation replace traditional methods for regulating LDC's?

International Nuclear Information System (INIS)

Farman, R.D.

1992-01-01

This paper discusses the wants and fears of gas utility companies with regards to incentive regulation. The idea of replacing the traditional rate-of-return regulation with incentive regulation sound very desirous in that it should provide greater management flexibility, quicker and more streamlined regulatory processes, and utility financial rewards based on how well customer needs are met. However, the main fear is that this could result in arbitrary, inappropriate productivity or efficiency targets, or would embody a risk/reward ratio skewed more heavily toward financial penalties than opportunities to increase earnings. The paper presents some of the obstacles of traditional regulation which include a lack of incentive to minimize operational costs; a lack of incentive to introduce new technology, products, or services; prevent the need for flexibility to compete in contestable markets; and the diversion caused by utility managers having to manage the regulatory process rather than delivering value to customers. The paper concludes by comparing the incentive regulation program used in the telecommunications industry to the natural gas industry to demonstrate why the success of the telecommunications model doesn't apply to the gas utilities incentive model

Effects of irradiation on the production of factors regulating humoral hematopoiesis

International Nuclear Information System (INIS)

Seki, Masatoshi; Yoshida, Kazuko

1974-01-01

Changes in factors regulating humoral hematopoiesis after irradiation were studied by intraperitoneal insertion of cellulose acetate membrane (CA membrane). There is little possibility that regulation factors is produced by macrophage itself. The growth of the colony depends mainly on increase or decrease of regulation factors in the host. However, there is a possibility that the macrophage interferes the action of these regulation factors. From the fact that there is no action of EPO (erythropoiesis) in Sl/slsup(d) mice having abnormal function of microenvironment, it is suggested that the action of EPO is brought about through the function of the microenvironment. In the analysis of the colony formation by intraperitoneal insertion of CA membrane, it is considered that the erythroblastic colony can be formed by the macrophage through the action of EPO. In short, it is concluded that factors regulating humoral hematopoiesis increased in the body of the mouse which have been irradiated to the whole body, and the increase in these factors is not constant, but remarkably changes with time. (Namekawa, K.)

7 CFR 981.15 - Almond product.

Science.gov (United States)

2010-01-01

... 7 Agriculture 8 2010-01-01 2010-01-01 false Almond product. 981.15 Section 981.15 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements... Regulating Handling Definitions § 981.15 Almond product. Almond product means any edible preparation other...

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

DEFF Research Database (Denmark)

Thomas Danielsen, E.; E. Møller, Morten; Yamanaka, Naoki

2016-01-01

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...

Regulation of estradiol and progesterone production by CRH-R1 and -R2 is through divergent signaling pathways in cultured human placental trophoblasts.

Science.gov (United States)

Gao, Lu; Tao, Yi; Hu, Tianxiao; Liu, Weina; Xu, Chen; Liu, Jie; You, Xingji; Gu, Hang; Ni, Xin

2012-10-01

CRH and its related peptides urocortins (UCN) have been identified in placenta and implicated to play pivotal roles in the regulation of pregnancy and parturition in humans. The objectives of present study were to investigate the effects of endogenous CRH and its related peptides in the regulation of steroid production in placenta. Placental trophoblasts were isolated from term placenta tissues and cultured for 72 h. Estradiol (E(2)) and progesterone (P(4)) contents in culture media were determined by radioimmunoassay. Treatment of cultured trophoblasts with CRH or UCNI antibody showed decreased E(2), whereas increased P(4) production. Treatment of cells with CRH receptor type 1 antagonist antalarmin or CRH receptor type 2 (CRH-R2) antagonist astressin-2b also decreased E(2) but increased P(4) production. Knockdown of CRH receptor type 1 or CRH-R2 cells showed a decrease in E(2) production and an increase in P(4) production. In CRH-R2 knockdown cells, CRH stimulated GTP-bound Gαs protein and phosphorylated phospholipase C-β3. Adenylyl cyclase and protein kinase A inhibitors blocked CRH-induced increased E(2) production but not decreased P(4) production. PLC inhibitor U73122 and protein kinase C inhibitor chelerythrine blocked the effects of CRH on E(2) and P(4) production in CRH-R2 knockdown cells. UCNIII, the specific CRH-R2 agonist, stimulated GTP-bound Gαi protein and phosphorylated phospholipase C-β3 expression. Both U73122 and chelerythrine blocked UCNIII-induced increased E(2) production and decreased P(4) production. We suggest that CRH and its related peptides might be involved in changes in the progesterone to estrogen ratio during human pregnancy.

Proposed federal petroleum products and allied petroleum products storage tank systems regulations under CEPA 1999 : report of consultation sessions February 2003 to September 2003 : summary of input from participants and response from Environment Canada

International Nuclear Information System (INIS)

2004-04-01

Between February and September of 2003, Environment Canada held a series of consultation sessions on a set of proposed regulations in order to eliminate the contamination of groundwater and soil caused by petroleum products and allied petroleum products stored by the federal house in storage tank systems. This document presents a summary of comments, issues, ideas and perspectives raised throughout consultation sessions. It also outlines Environment Canada's responses to generated input. Sessions took place in each of Environment Canada's five regions. A full description of the consultation procedures and methodology was provided. The document provides a rationale for cases where Environment Canada has rejected or only partially accepted stakeholder recommendations. A list of general prohibitions and obligations was provided along with details of registration and tagging; provincially-approved installers and installation procedures; monitoring and leak detection; operation and maintenance; upgrading; withdrawal, re-use and removal of storage tank systems; report of releases; and an environmental emergency plan and record keeping. First Nation issues were also discussed. Several changes to proposed regulations have been made during the course of the consultations, including an extension of timelines for compliance with proposed regulations; the definition of a storage tank system is now defined as the delivery point first connection to the discharge of the pump; and records are now required for only 7 years as opposed to the life of the tank. It was also stated that a draft regulation will be published in the Canadian Gazette, followed by a 60 day comment period. The final regulation will be published a few months later

Health products inspection

International Nuclear Information System (INIS)

Stoltz, M.

2009-01-01

To protect public health, the Health Products Inspection is a public service mission where the application of regulations concerning activities on human health products and cosmetic products is verified. This mission permits a global approach to assess the health products risk-based benefit and, in monitoring by laboratory testing and by on site inspections, to verify their compliance with appropriate regulations. The seventy five inspectors perform about eight hundred inspections per year, in France and abroad. These inspections are related to data provided in the health products assessment and also to manufacturing and delivery practices. The French inspection body is also involved in the training of foreign inspectors and in the harmonization of national, European and international practices either for operators than for the competent authorities. (author)

A quantitative model of regulator's preference factor (RPF) in electricity-environment coordinated regulation system

Energy Technology Data Exchange (ETDEWEB)

Ren, Yulong; Fu, Shijun [Economy and Business Administration School of Chongqing University, Chongqing 400030 (China)

2010-12-15

This paper explores quantification of regulator's preference factor (RPF) in electricity-environment coordinated regulation system. Based on social welfare economics, we articulately depict RPF's qualitative concept and its economic meaning. Then, applying abstract functions (i.e., abstract social welfare function, abstract utility function, and abstract production function), we deduce the partial-social-welfare elasticity, and build the mathematics model of maximizing social welfare. We nest this elasticity into the model's Kuhn-Tucker conditions, and obtain RPF's definition formula. By solving the Kuhn-Tucker conditions, we get RPF's quantitative formula, which solves the problem of hard to quantify regulator's preference in electricity-environment coordinated regulation system. The result shows that RPF only has relationship to subsystems' production function, and is independent of social welfare function and subsystems' utility function. Finally, we provide an empirical research based on the western region of China from year 1995 to 2004. It reveals that regulator has relative stability preference to mitigating pollutants. And validity test confirms that the empirical result is fit well to the practice. The RPF is truly a more general and valid instrument to measure regulator's preference in its regulated field. (author)

Retinoic Acid Modulates Interferon-γ Production by Hepatic Natural Killer T Cells via Phosphatase 2A and the Extracellular Signal-Regulated Kinase Pathway

Science.gov (United States)

Chang, Heng-Kwei

2015-01-01

Retinoic acid (RA), an active metabolite converted from vitamin A, plays an active role in immune function, such as defending against infections and immune regulation. Although RA affects various types of immune cells, including antigen-presenting cells, B lymphocytes, and T lymphocytes, whether it affects natural killer T (NKT) cells remain unknown. In this study, we found that RA decreased interferon (IFN)-γ production by activated NKT cells through T-cell receptor (TCR) and CD28. We also found that RA reduced extracellular signal-regulated kinase (ERK) phosphorylation, but increased phosphatase 2A (PP2A) activity in TCR/CD28-stimulated NKT cells. The increased PP2A activity, at least partly, contributed to the reduction of ERK phosphorylation. Since inhibition of ERK activation decreases IFN-γ production by TCR/CD28-stimulated NKT cells, RA may downregulate IFN-γ production by TCR/CD28-stimulated NKT cells through the PP2A-ERK pathway. Our results demonstrated a novel function of RA in modulating the IFN-γ expression by activated NKT cells. PMID:25343668

41 CFR 101-29.213 - Commercial product.

Science.gov (United States)

2010-07-01

... 41 Public Contracts and Property Management 2 2010-07-01 2010-07-01 true Commercial product. 101... Regulations System FEDERAL PROPERTY MANAGEMENT REGULATIONS SUPPLY AND PROCUREMENT 29-FEDERAL PRODUCT DESCRIPTIONS 29.2-Definitions § 101-29.213 Commercial product. A commercial product is any item, component, or...

pH regulation of recombinant glucoamylase production in Fusarium venenatum JeRS 325, a transformant with a Fusarium oxysporum alkaline (trypsin-like) protease promoter.

Science.gov (United States)

Wiebe, M G; Robson, G D; Shuster, J R; Trinci, A P

1999-08-05

Fusarium venenatum (formerly Fusarium graminearum) JeRS 325 produces heterologous glucoamylase (GAM) under the regulation of a Fusarium oxysporum alkaline (trypsin-like) protease promoter. The glucoamylase gene was used as a reporter gene to study the effects of ammonium and pH on GAM production under the control of the alkaline protease promoter. Between pH 4.0 and 5.8, GAM production in glucose-limited chemostat cultures of JeRS 325 grown at a dilution rate of 0.10 h-1 (doubling time, 6.9 h) on (NH4)2SO4 medium increased in a linear manner with increase in pH. However, at pH 4.0 and below GAM production was almost completely repressed in glucose-limited chemostat cultures grown on (NH4)2SO4 or NaNO3 medium. Thus GAM production in JeRS 325 is regulated by culture pH, not by the nature of the nitrogen source in the medium. The difficulty of using unbuffered medium when investigating putative ammonium repression is also shown. The study demonstrates the potential for use of the alkaline protease promoter in F. graminearum for the production of recombinant proteins in a pH dependent man ner. Copyright 1999 John Wiley & Sons, Inc.

Demand Forecasting for Heavy-Duty Diesel Engines Considering Emission Regulations

Directory of Open Access Journals (Sweden)

Yoon Seong Kim

2017-01-01

Full Text Available Makers of heavy-duty diesel engines (HDDEs need to reduce their inventory of old-generation products in preparation for the demand for next-generation products that satisfy new emission regulations. In this paper, a new demand forecasting model is proposed to reflect special conditions raised by the technological generational shift owing to new emission regulation enforcement. In addition, sensitivity analyses are conducted to better accommodate uncertainty involved at the time of prediction. Our proposed model can help support manufacturers’ production and sales management for a series of products in response to new emission regulations.

Up-regulation of avian uncoupling protein in cold-acclimated and hyperthyroid ducklings prevents reactive oxygen species production by skeletal muscle mitochondria

Directory of Open Access Journals (Sweden)

Servais Stéphane

2010-04-01

Full Text Available Abstract Background Although identified in several bird species, the biological role of the avian homolog of mammalian uncoupling proteins (avUCP remains extensively debated. In the present study, the functional properties of isolated mitochondria were examined in physiological or pharmacological situations that induce large changes in avUCP expression in duckling skeletal muscle. Results The abundance of avUCP mRNA, as detected by RT-PCR in gastrocnemius muscle but not in the liver, was markedly increased by cold acclimation (CA or pharmacological hyperthyroidism but was down-regulated by hypothyroidism. Activators of UCPs, such as superoxide with low doses of fatty acids, stimulated a GDP-sensitive proton conductance across the inner membrane of muscle mitochondria from CA or hyperthyroid ducklings. The stimulation was much weaker in controls and not observed in hypothyroid ducklings or in any liver mitochondrial preparations. The production of endogenous mitochondrial reactive oxygen species (ROS was much lower in muscle mitochondria from CA and hyperthyroid ducklings than in the control or hypothyroid groups. The addition of GDP markedly increased the mitochondrial ROS production of CA or hyperthyroid birds up to, or above, the level of control or hypothyroid ducklings. Differences in ROS production among groups could not be attributed to changes in antioxidant enzyme activities (superoxide dismutase or glutathione peroxidase. Conclusion This work provides the first functional in vitro evidence that avian UCP regulates mitochondrial ROS production in situations of enhanced metabolic activity.

Up-regulation of avian uncoupling protein in cold-acclimated and hyperthyroid ducklings prevents reactive oxygen species production by skeletal muscle mitochondria.

Science.gov (United States)

Rey, Benjamin; Roussel, Damien; Romestaing, Caroline; Belouze, Maud; Rouanet, Jean-Louis; Desplanches, Dominique; Sibille, Brigitte; Servais, Stéphane; Duchamp, Claude

2010-04-28

Although identified in several bird species, the biological role of the avian homolog of mammalian uncoupling proteins (avUCP) remains extensively debated. In the present study, the functional properties of isolated mitochondria were examined in physiological or pharmacological situations that induce large changes in avUCP expression in duckling skeletal muscle. The abundance of avUCP mRNA, as detected by RT-PCR in gastrocnemius muscle but not in the liver, was markedly increased by cold acclimation (CA) or pharmacological hyperthyroidism but was down-regulated by hypothyroidism. Activators of UCPs, such as superoxide with low doses of fatty acids, stimulated a GDP-sensitive proton conductance across the inner membrane of muscle mitochondria from CA or hyperthyroid ducklings. The stimulation was much weaker in controls and not observed in hypothyroid ducklings or in any liver mitochondrial preparations. The production of endogenous mitochondrial reactive oxygen species (ROS) was much lower in muscle mitochondria from CA and hyperthyroid ducklings than in the control or hypothyroid groups. The addition of GDP markedly increased the mitochondrial ROS production of CA or hyperthyroid birds up to, or above, the level of control or hypothyroid ducklings. Differences in ROS production among groups could not be attributed to changes in antioxidant enzyme activities (superoxide dismutase or glutathione peroxidase). This work provides the first functional in vitro evidence that avian UCP regulates mitochondrial ROS production in situations of enhanced metabolic activity.

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

International Nuclear Information System (INIS)

2008-11-01

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

The science and regulations of probiotic food and supplement product labeling.

Science.gov (United States)

Sanders, Mary Ellen; Levy, Dan D

2011-02-01

Presented by the New York Academy of Sciences, the U.S. Food and Drug Administration (FDA), and the U.S. Office of Dietary Supplements of the National Institutes of Health, the symposium "Probiotic Foods and Supplements: The Science and Regulations of Labeling," was held on June 12, 2010 at the New York Academy of Sciences, New York, NY, the goals of which were to facilitate the exchange of ideas regarding labeling and substantiation of claims for probiotics among academic, industry, and regulatory professionals, and to discuss ways to translate and communicate research results in a truthful way to the consumer and to such health professionals as physicians, pharmacists, and dieticians. The target audience for this symposium included academicians interested in conducting research on the health benefits of probiotics; scientists; communications personnel, and regulatory specialists from companies involved in, or interested in, the marketing of probiotics; U.S. government regulatory experts tasked with oversight of probiotic foods and dietary supplement products; and other experts in the field interested in the development of probiotics for the U.S. market. © 2011 New York Academy of Sciences.

The AINTEGUMENTA genes, MdANT1 and MdANT2, are associated with the regulation of cell production during fruit growth in apple (Malus × domestica Borkh.).

Science.gov (United States)

Dash, Madhumita; Malladi, Anish

2012-06-25

Fruit growth in apple (Malus × domestica Borkh.) is mediated by cell production and expansion. Genes involved in regulating these processes and thereby fruit growth, are not well characterized. We hypothesized that the apple homolog(s) of AINTEGUMENTA (ANT), an APETALA2-repeat containing transcription factor, regulates cell production during fruit growth in apple. Two ANT genes, MdANT1 and MdANT2, were isolated from apple and their expression was studied during multiple stages of fruit development. MdANT1 and MdANT2 expression was high during early fruit growth coincident with the period of cell production, rapidly declined during exit from cell production, and remained low during the rest of fruit development. The effects of increase in carbohydrate availability during fruit growth were characterized. Increase in carbohydrate availability enhanced fruit growth largely through an increase in cell production. Expression of MdANT1 and MdANT2 increased sharply by up to around 5-fold in response to an increase in carbohydrate availability. Expression of the ANT genes was compared across two apple genotypes, 'Gala' and 'Golden Delicious Smoothee' (GS), which differ in the extent of fruit growth, largely due to differences in cell production. In comparison to 'Gala', the larger fruit-size genotype, GS, displayed higher levels and a longer duration of MdANT1 and MdANT2 expression. Expression of the ANTs and cell cycle genes in the fruit core and cortex tissues isolated using laser capture microdissection was studied. During early fruit growth, expression of the MdANTs was higher within the cortex, the tissue that constitutes the majority of the fruit. Additionally, MdANT1 and MdANT2 expression was positively correlated with that of A- and B-type CYCLINS, B-type CYCLIN-DEPENDENT-KINASES (CDKBs) and MdDEL1. Multiple lines of evidence from this study suggest that MdANT1 and MdANT2 regulate cell production during fruit growth in apple. ANTs may coordinate the expression of

Screening of French groundwater for regulated and emerging contaminants.

Science.gov (United States)

Lopez, Benjamin; Ollivier, Patrick; Togola, Anne; Baran, Nicole; Ghestem, Jean-Philippe

2015-06-15

Nationwide screening of 411 emerging contaminants and other regulated compounds, including parent molecules and transformation products (TPs) having various uses and origins, was done at 494 groundwater sites throughout France during two sampling campaigns in the Spring and the Fall of 2011. One hundred and eighty substances (44% of the targeted compounds) were quantified in at least one sampling point. These included pharmaceuticals, industrial products, pesticides, their transformation products and other emerging compounds. Fifty-five compounds were quantified in more than 1% of the samples. Both regulated and emerging compounds were found. Among the unregulated compounds, acetaminophen, carbamazepine, perfluorinated compounds, dioxins/furans, tolyltriazole, bisphenol A, triazine transformation products, and caffeine were quantified in more than 10% of the samples analyzed. Concentrations exceeding the threshold of toxicological concern of 0.1 μg/L were found for tolyltriazole, bisphenol A and some of the triazine transformation products (DEDIA). These new results should help the water resource managers and environmental regulators develop sound policies regarding the occurrence and distribution of regulated and emerging contaminants in groundwater. Copyright © 2015 Elsevier B.V. All rights reserved.

Production, regulation and transportation of bacillibactin in bacillus subtilis

International Nuclear Information System (INIS)

Raza, W.; Hussain, Q.; Shen, Q.

2012-01-01

Bacillus subtilis produces a catecholate type siderophore 'Bacillibactin'. This review focuses on the non-ribosomal synthesis, transport and regulation of bacillibactin. Bacillibactin biosynthetic operon contains five genes (dhbACEBF). The uptake of bacillibactin requires the FeuABC transporter, inner-membrane permease, FepDG and YusV ATPase and an esterase encoding gene, besA and while export required YmfE major facilitator super-family (MFS)-type transporter. Fur is the major iron-controlled transcriptional regulator in B. subtilis, which acts as an iron-dependent repressor of the dhb operon in vivo while an iron-independent repressor in vitro. Knowledge of the Fur regulon will be useful in interpreting other global analysis of transcriptional responses. (author)

The Crc protein participates in down-regulation of the Lon gene to promote rhamnolipid production and rhl quorum sensing in Pseudomonas aeruginosa.

Science.gov (United States)

Yang, Nana; Ding, Shuting; Chen, Feifei; Zhang, Xue; Xia, Yongjie; Di, Hongxia; Cao, Qiao; Deng, Xin; Wu, Min; Wong, Catherine C L; Tian, Xiao-Xu; Yang, Cai-Guang; Zhao, Jing; Lan, Lefu

2015-05-01

Rhamnolipid acts as a virulence factor during Pseudomonas aeruginosa infection. Here, we show that deletion of the catabolite repression control (crc) gene in P. aeruginosa leads to a rhamnolipid-negative phenotype. This effect is mediated by the down-regulation of rhl quorum sensing (QS). We discover that a disruption of the gene encoding the Lon protease entirely offsets the effect of crc deletion on the production of both rhamnolipid and rhl QS signal C4-HSL. Crc is unable to bind lon mRNA in vitro in the absence of the RNA chaperon Hfq, while Crc contributes to Hfq-mediated repression of the lon gene expression at a posttranscriptional level. Deletion of crc, which results in up-regulation of lon, significantly reduces the in vivo stability and abundance of the RhlI protein that synthesizes C4-HSL, causing the attenuation of rhl QS. Lon is also capable of degrading the RhlI protein in vitro. In addition, constitutive expression of rhlI suppresses the defects of the crc deletion mutant in rhamnolipid, C4-HSL and virulence on lettuce leaves. This study therefore uncovers a novel posttranscriptional regulatory cascade, Crc-Hfq/Lon/RhlI, for the regulation of rhamnolipid production and rhl QS in P. aeruginosa. © 2015 John Wiley & Sons Ltd.

NLRP12 negatively regulates proinflammatory cytokine production and host defense against Brucella abortus.

Science.gov (United States)

Silveira, Tatiana N; Gomes, Marco Túlio R; Oliveira, Luciana S; Campos, Priscila C; Machado, Gabriela G; Oliveira, Sergio C

2017-01-01

Brucella abortus is the causative agent of brucellosis, which causes abortion in domestic animals and undulant fever in humans. This bacterium infects and proliferates mainly in macrophages and dendritic cells, where it is recognized by pattern recognition receptors (PRRs) including Nod-like receptors (NLRs). Our group recently demonstrated the role of AIM2 and NLRP3 in Brucella recognition. Here, we investigated the participation of NLRP12 in innate immune response to B. abortus. We show that NLRP12 inhibits the early production of IL-12 by bone marrow-derived macrophages upon B. abortus infection. We also observed that NLRP12 suppresses in vitro NF-κB and MAPK signaling in response to Brucella. Moreover, we show that NLRP12 modulates caspase-1 activation and IL-1β secretion in B. abortus infected-macrophages. Furthermore, we show that mice lacking NLRP12 are more resistant in the early stages of B. abortus infection: NLRP12 -/- infected-mice have reduced bacterial burdens in the spleens and increased production of IFN-γ and IL-1β compared with wild-type controls. In addition, NLRP12 deficiency leads to reduction in granuloma number and size in mouse livers. Altogether, our findings suggest that NLRP12 plays an important role in negatively regulating the early inflammatory responses against B. abortus. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Genetic manipulation of longevity-related genes as a tool to regulate yeast life span and metabolite production during winemaking.

Science.gov (United States)

Orozco, Helena; Matallana, Emilia; Aranda, Agustín

2013-01-02

Yeast viability and vitality are essential for different industrial processes where the yeast Saccharomyces cerevisiae is used as a biotechnological tool. Therefore, the decline of yeast biological functions during aging may compromise their successful biotechnological use. Life span is controlled by a variety of molecular mechanisms, many of which are connected to stress tolerance and genomic stability, although the metabolic status of a cell has proven a main factor affecting its longevity. Acetic acid and ethanol accumulation shorten chronological life span (CLS), while glycerol extends it. Different age-related gene classes have been modified by deletion or overexpression to test their role in longevity and metabolism. Overexpression of histone deacetylase SIR2 extends CLS and reduces acetate production, while overexpression of SIR2 homolog HST3 shortens CLS, increases the ethanol level, and reduces acetic acid production. HST3 overexpression also enhances ethanol tolerance. Increasing tolerance to oxidative stress by superoxide dismutase SOD2 overexpression has only a moderate positive effect on CLS. CLS during grape juice fermentation has also been studied for mutants on several mRNA binding proteins that are regulators of gene expression at the posttranscriptional level; we found that NGR1 and UTH4 deletions decrease CLS, while PUF3 and PUB1 deletions increase it. Besides, the pub1Δ mutation increases glycerol production and blocks stress granule formation during grape juice fermentation. Surprisingly, factors relating to apoptosis, such as caspase Yca1 or apoptosis-inducing factor Aif1, play a positive role in yeast longevity during winemaking as their deletions shorten CLS. Manipulation of regulators of gene expression at both transcriptional (i.e., sirtuins) and posttranscriptional (i.e., mRNA binding protein Pub1) levels allows to modulate yeast life span during its biotechnological use. Due to links between aging and metabolism, it also influences the

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

DEFF Research Database (Denmark)

Marzec, Michal; Hawkes, Colin P; Eletto, Davide

2016-01-01

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...... 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...

Enhancing cellulase production by overexpression of xylanase regulator protein gene, xlnR, in Talaromyces cellulolyticus cellulase hyperproducing mutant strain.

Science.gov (United States)

Okuda, Naoyuki; Fujii, Tatsuya; Inoue, Hiroyuki; Ishikawa, Kazuhiko; Hoshino, Tamotsu

2016-10-01

We obtained strains with the xylanase regulator gene, xlnR, overexpressed (HXlnR) and disrupted (DXlnR) derived from Talaromyces cellulolyticus strain C-1, which is a cellulase hyperproducing mutant. Filter paper degrading enzyme activity and cellobiohydrolase I gene expression was the highest in HXlnR, followed by C-1 and DXlnR. These results indicate that the enhancement of cellulase productivity was succeeded by xlnR overexpression.

Endothelial surface glycocalyx can regulate flow-induced nitric oxide production in microvessels in vivo.

Directory of Open Access Journals (Sweden)

Wanyi Yen

Full Text Available Due to its unique location, the endothelial surface glycocalyx (ESG at the luminal side of the microvessel wall may serve as a mechano-sensor and transducer of blood flow and thus regulate endothelial functions. To examine this role of the ESG, we used fluorescence microscopy to measure nitric oxide (NO production in post-capillary venules and arterioles of rat mesentery under reduced (low and normal (high flow conditions, with and without enzyme pretreatment to remove heparan sulfate (HS of the ESG and in the presence of an endothelial nitric oxide synthase (eNOS inhibitor, NG-monomethyl-L-arginine (L-NMMA. Rats (SD, 250-300 g were anesthetized. The mesentery was gently taken out from the abdominal cavity and arranged on the surface of a glass coverslip for the measurement. An individual post-capillary venule or arteriole was cannulated and loaded for 45 min with 5 μM 4, 5-Diaminofluorescein diacetate, a membrane permeable fluorescent indictor for NO, then the NO production was measured for ~10 min under a low flow (~300 μm/s and for ~60 min under a high flow (~1000 μm/s. In the 15 min after switching to the high flow, DAF-2-NO fluorescence intensity increased to 1.27-fold of its baseline, DAF-2-NO continuously increased under the high flow, to 1.53-fold of its baseline in 60 min. Inhibition of eNOS by 1 mM L-NMMA attenuated the flow-induced NO production to 1.13-fold in 15 min and 1.30-fold of its baseline in 60 min, respectively. In contrast, no significant increase in NO production was observed after switching to the high flow for 60 min when 1 h pretreatment with 50 mU/mL heparanase III to degrade the ESG was applied. Similar NO production was observed in arterioles under low and high flows and under eNOS inhibition. Our results suggest that ESG participates in endothelial cell mechanosensing and transduction through its heparan sulfate to activate eNOS.

Four hundred and sixty brands of e-cigarettes and counting: implications for product regulation.

Science.gov (United States)

Zhu, Shu-Hong; Sun, Jessica Y; Bonnevie, Erika; Cummins, Sharon E; Gamst, Anthony; Yin, Lu; Lee, Madeleine

2014-07-01

E-cigarettes are largely unregulated and internet sales are substantial. This study examines how the online market for e-cigarettes has changed over time: in product design and in marketing messages appearing on websites. Comprehensive internet searches of English-language websites from May-August 2012 and December 2013-January 2014 identified brands, models, flavours, nicotine strengths, ingredients and product claims. Brands were divided into older and newer groups (by the two searches) for comparison. By January 2014 there were 466 brands (each with its own website) and 7764 unique flavours. In the 17 months between the searches, there was a net increase of 10.5 brands and 242 new flavours per month. Older brands were more likely than newer brands to offer cigalikes (86.9% vs. 52.1%, p<0.01), and newer brands more likely to offer the more versatile eGos and mods (75.3% vs. 57.8%, p<0.01). Older brands were significantly more likely to claim that they were healthier and cheaper than cigarettes, were good substitutes where smoking was banned and were effective smoking cessation aids. Newer brands offered more flavours per brand (49 vs. 32, p<0.01) and were less likely to compare themselves with conventional cigarettes. The number of e-cigarette brands is large and has been increasing. Older brands tend to highlight their advantages over conventional cigarettes while newer brands emphasise consumer choice in multiple flavours and product versatility. These results can serve as a benchmark for future research on the impact of upcoming regulations on product design and advertising messages of e-cigarettes. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

The adaptor protein SAP regulates type II NKT-cell development, cytokine production, and cytotoxicity against lymphoma.

Science.gov (United States)

Weng, Xiufang; Liao, Chia-Min; Bagchi, Sreya; Cardell, Susanna L; Stein, Paul L; Wang, Chyung-Ru

2014-12-01

CD1d-restricted NKT cells represent a unique lineage of immunoregulatory T cells that are divided into two groups, type I and type II, based on their TCR usage. Because there are no specific tools to identify type II NKT cells, little is known about their developmental requirements and functional regulation. In our previous study, we showed that signaling lymphocytic activation molecule associated protein (SAP) is essential for the development of type II NKT cells. Here, using a type II NKT-cell TCR transgenic mouse model, we demonstrated that CD1d-expressing hematopoietic cells, but not thymic epithelial cells, meditate efficient selection of type II NKT cells. Furthermore, we showed that SAP regulates type II NKT-cell development by controlling early growth response 2 protein and promyelocytic leukemia zinc finger expression. SAP-deficient 24αβ transgenic T cells (24αβ T cells) exhibited an immature phenotype with reduced Th2 cytokine-producing capacity and diminished cytotoxicity to CD1d-expressing lymphoma cells. The impaired IL-4 production by SAP-deficient 24αβ T cells was associated with reduced IFN regulatory factor 4 and GATA-3 induction following TCR stimulation. Collectively, these data suggest that SAP is critical for regulating type II NKT cell responses. Aberrant responses of these T cells may contribute to the immune dysregulation observed in X-linked lymphoproliferative disease caused by mutations in SAP. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

15-Lipoxygenases regulate the production of chemokines in human lung macrophages.

Science.gov (United States)

Abrial, C; Grassin-Delyle, S; Salvator, H; Brollo, M; Naline, E; Devillier, P

2015-09-01

15-Lipoxygenase (15-LOX) activity is associated with inflammation and immune regulation. The objectives of the present study were to investigate the expression of 15-LOX-1 and 15-LOX-2 and evaluate the enzymes' roles in the polarization of human lung macrophages (LMs) in response to LPS and Th2 cytokines (IL-4/-13). LMs were isolated from patients undergoing surgery for carcinoma. The cells were cultured with a 15-LOX inhibitor (PD146176 or ML351), a COX inhibitor (indomethacin), a 5-LOX inhibitor (MK886) or vehicle and then stimulated with LPS (10 ng · mL(-1)), IL-4 (10 ng · mL(-1)) or IL-13 (50 ng · mL(-1)) for 24 h. Levels of ALOX15 (15-LOX-1) and ALOX15B (15-LOX-2) transcripts were determined by real-time quantitative PCR. Immunoassays were used to measure levels of LPS-induced cytokines (TNF-α, CCL2, CCL3, CCL4, CXCL1, CXCL8 and CXCL10) and Th2 cytokine-induced chemokines (CCL13, CCL18 and CCL22) in the culture supernatant. Stimulation of LMs with LPS was associated with increased expression of ALOX15B, whereas stimulation with IL-4/IL-13 induced the expression of ALOX15. PD146176 and ML351 (10 μM) reduced the release of the chemokines induced by LPS and Th2 cytokines. The effects of these 15-LOX inhibitors were maintained in the presence of indomethacin and MK886. Furthermore, indomethacin revealed the inhibitory effect of PD146176 on TNF-α release. Inhibition of the 15-LOX pathways is involved in the down-regulation of the in vitro production of chemokines in LMs. Our results suggest that the 15-LOX pathways have a role in the pathogenesis of inflammatory lung disorders and may thus constitute a potential drug target. © 2015 The British Pharmacological Society.

Regulation of sporicides under the European Biocidal Products Directive.

Science.gov (United States)

Low, A

2011-03-01

Disinfectants (including sporicides) used in the healthcare setting fall within the scope of the European Biocidal Products Directive (98/8/EC). The active substances used in these products will be evaluated as part of an EU wide review programme, to determine whether they can be used in biocidal products without undue risks to humans, animals and the environment, and that these products will be effective. Following the review of an active substance, biocidal products containing the active substance will become subject to regulatory controls in all EU Member States. This paper discusses how the Directive operates, both through the review programme and the authorisation of biocidal products at the Member State level, together with the requirements to provide data on the efficacy of both the active substances and end-use biocidal products. Crown Copyright © 2010. Published by Elsevier Ltd. All rights reserved.

UK medicines regulation: responding to current challenges.

Science.gov (United States)

Richards, Natalie; Hudson, Ian

2016-12-01

The medicines regulatory environment is evolving rapidly in response to the changing environment. Advances in science and technology have led to a vast field of increasingly complicated pharmaceutical and medical device products; increasing globalization of the pharmaceutical industry, advances in digital technology and the internet, changing patient populations, and shifts in society also affect the regulatory environment. In the UK, the Medicines and Healthcare products Regulatory Agency (MHRA) regulates medicines, medical devices and blood products to protect and improve public health, and supports innovation through scientific research and development. It works closely with other bodies in a single medicines network across Europe and takes forward UK health priorities. This paper discusses the range of initiatives in the UK and across Europe to support innovation in medicines regulation. The MHRA leads a number of initiatives, such as the Innovation Office, which helps innovators to navigate the regulatory processes to progress their products or technologies; and simplification of the Clinical Trials Regulations and the Early Access to Medicines Scheme, to bring innovative medicines to patients faster. The Accelerated Access Review will identify reforms to accelerate access for National Health Service patients to innovative medicines and medical technologies. PRIME and Adaptive Pathways initiatives are joint endeavours within the European regulatory community. The MHRA runs spontaneous reporting schemes and works with INTERPOL to tackle counterfeiting and substandard products sold via the internet. The role of the regulator is changing rapidly, with new risk-proportionate, flexible approaches being introduced. International collaboration is a key element of the work of regulators, and is set to expand. © 2016 The British Pharmacological Society.

Development of waste management regulations

International Nuclear Information System (INIS)

Elnour, E.G.

2012-04-01

Radioactive wastes are generated during nuclear fuel cycle operation, production and application of radioisotope in medicine, industry, research, and agriculture, and as a by product of natural resource exploitation, which includes mining and processing of ores. To ensure the protection of human health and the environment from the hazard of these wastes, a planned integrated radioactive waste management practice should be applied. The purpose of this study is to develop regulations for radioactive waste management for low and intermediate radioactive level waste (LILW), and other purpose of regulations is to establish requirements with which all organizations must comply in Sudan from LILW in particular disused/spent sources, not including radioactive waste for milling and mining practices. The national regulations regarding the radioactive waste management, should prescribe the allocation of responsibilities and roles of the Country, the regulatory body, user/owner, waste management organization, including regulations on transport packaging of waste and applied a quality assurance programme, to ensure that radioactive waste management is done safely and securely. (author)

7 CFR 301.55-2 - Regulated articles.

Science.gov (United States)

2010-01-01

... 7 Agriculture 5 2010-01-01 2010-01-01 false Regulated articles. 301.55-2 Section 301.55-2... Regulated articles. The following are regulated articles: (a) The South American cactus moth, in any living..., Nopalea, and Opuntia. (c) Any other product, article, or means of conveyance not listed in paragraphs (a...

7 CFR 301.87-2 - Regulated articles.

Science.gov (United States)

2010-01-01

... 7 Agriculture 5 2010-01-01 2010-01-01 false Regulated articles. 301.87-2 Section 301.87-2... Regulations § 301.87-2 Regulated articles. (a) Sugarcane plants, whole or in part, including true seed and...) Any other product, article, or means of conveyance, of any character whatsoever, not covered by...

Membrane-anchored MucR mediates nitrate-dependent regulation of alginate production in Pseudomonas aeruginosa

KAUST Repository

Wang, Yajie

2015-04-29

Alginates exhibit unique material properties suitable for medical and industrial applications. However, if produced by Pseudomonas aeruginosa, it is an important virulence factor in infection of cystic fibrosis patients. The alginate biosynthesis machinery is activated by c-di-GMP imparted by the inner membrane protein, MucR. Here, it was shown that MucR impairs alginate production in response to nitrate in P. aeruginosa. Subsequent site-specific mutagenesis of MucR revealed that the second MHYT sensor motif (MHYT II, amino acids 121–124) of MucR sensor domain was involved in nitrate sensing. We also showed that both c-di-GMP synthesizing and degrading active sites of MucR were important for alginate production. Although nitrate and deletion of MucR impaired alginate promoter activity and global c-di-GMP levels, alginate yields were not directly correlated with alginate promoter activity or c-di-GMP levels, suggesting that nitrate and MucR modulate alginate production at a post-translational level through a localized pool of c-di-GMP. Nitrate increased pel promoter activity in the mucR mutant while in the same mutant the psl promoter activity was independent of nitrate. Nitrate and deletion of mucR did not impact on swarming motility but impaired attachment to solid surfaces. Nitrate and deletion of mucR promoted the formation of biofilms with increased thickness, cell density, and survival. Overall, this study provided insight into the functional role of MucR with respect to nitrate-mediated regulation of alginate biosynthesis. © 2015 Springer-Verlag Berlin Heidelberg

Assessment of safety regulation using an artificial society

International Nuclear Information System (INIS)

Furuta, Kazuo; Nagase, Masaya

2005-01-01

This study proposes using an artificial society to assess impacts of safety regulation on the society. The artificial society used in this study is a multi-agent system, which consists of many agents representing companies. The agents cannot survive unless they get profits by producing some products. Safety regulation functions as the business environment, which the agents will evolve to fit to. We modeled this process of survival and adaptation by the genetic algorithm. Using the proposed model, case simulations were performed to compare various regulation styles, and some interesting insights were obtained how regulation style influences behavior of the agents and then productivity and safety level of the industry. In conclusion, an effective method for assessment of safety regulation has been developed, and then several insights were shown in this study

Seed regulations and local seed systems

NARCIS (Netherlands)

Louwaars, N.

2000-01-01

Seed regulations have been introduced in most countries based on the development of formal seed production. Concerns about seed quality and about the varietal identity of the seeds have commonly led to seed laws. However, formal regulations are often inappropriate for informal seed systems, which

Transcription factor VdCmr1 is required for pigment production, protection from UV irradiation, and regulates expression of melanin biosynthetic genes in Verticillium dahliae.

Science.gov (United States)

Wang, Yonglin; Hu, Xiaoping; Fang, Yulin; Anchieta, Amy; Goldman, Polly H; Hernandez, Gustavo; Klosterman, Steven J

2018-04-01

Verticillium dahliae is a soilborne fungus that causes vascular wilt diseases on numerous plant species worldwide. The production of darkly melanized microsclerotia is crucial in the disease cycle of V. dahliae, as these structures allow for long-term survival in soil. Previously, transcriptomic and genomic analysis identified a cluster of genes in V. dahliae that encodes some dihydroxynaphthalene (DHN) melanin biosynthetic pathway homologues found in related fungi. In this study, we explored the roles of cluster-specific transcription factor VdCmr1, as well as two other genes within the cluster encoding a polyketide synthase (VdPKS1) and a laccase (VdLac1), enzymes at initial and endpoint steps in DHN melanin production. The results revealed that VdCmr1 and VdPKS1 are required for melanin production, but neither is required for microsclerotia production. None of the three genes were required for pathogenesis on tobacco and lettuce. Exposure of ΔVdCmr1 and wild-type strains to UV irradiation, or to high temperature (40 °C), revealed an approx. 50 % reduction of survival in the ΔVdCmr1 strain, relative to the wild-type strain, in response to either condition. Expression profiles revealed that expression of some melanin biosynthetic genes are in part dependent on VdCmr1. Combined data indicate VdCmr1 is a key regulator of melanin biosynthesis, and that via regulation of melanogenesis, VdCmr1 affects survival of V. dahliae in response to abiotic threats. We conclude with a model showing regulation of VdCmr1 by a high osmolarity glycerol response (Hog)-type MAP kinase pathway.

Engineering of the glycerol decomposition pathway and cofactor regulation in an industrial yeast improves ethanol production.

Science.gov (United States)

Zhang, Liang; Tang, Yan; Guo, Zhongpeng; Shi, Guiyang

2013-10-01

Glycerol is a major by-product of industrial ethanol production and its formation consumes up to 4 % of the sugar substrate. This study modified the glycerol decomposition pathway of an industrial strain of Saccharomyces cerevisiae to optimize the consumption of substrate and yield of ethanol. This study is the first to couple glycerol degradation with ethanol formation, to the best of our knowledge. The recombinant strain overexpressing GCY1 and DAK1, encoding glycerol dehydrogenase and dihydroxyacetone kinase, respectively, in glycerol degradation pathway, exhibited a moderate increase in ethanol yield (2.9 %) and decrease in glycerol yield (24.9 %) compared to the wild type with the initial glucose concentration of 15 % under anaerobic conditions. However, when the mhpF gene, encoding acetylating NAD⁺-dependent acetaldehyde dehydrogenase from Escherichia coli, was co-expressed in the aforementioned recombinant strain, a further increase in ethanol yield by 5.5 % and decrease in glycerol yield by 48 % were observed for the resultant recombinant strain GDMS1 when acetic acid was added into the medium prior to inoculation compared to the wild type. The process outlined in this study which enhances glycerol consumption and cofactor regulation in an industrial yeast is a promising metabolic engineering strategy to increase ethanol production by reducing the formation of glycerol.

Evidence of a local negative role for cocaine and amphetamine regulated transcript (CART, inhibins and low molecular weight insulin like growth factor binding proteins in regulation of granulosa cell estradiol production during follicular waves in cattle

Directory of Open Access Journals (Sweden)

Ireland James J

2006-04-01

Full Text Available Abstract The ability of ovarian follicles to produce large amounts of estradiol is a hallmark of follicle health status. Estradiol producing capacity is lost in ovarian follicles before morphological signs of atresia. A prominent wave like pattern of growth of antral follicles is characteristic of monotocous species such as cattle, horses and humans. While our knowledge of the role of pituitary gonadotropins in support of antral follicle growth and development is well established, the intrinsic factors that suppress estradiol production and may help promote atresia during follicular waves are not well understood. Numerous growth factors and cytokines have been reported to suppress granulosa cell estradiol production in vitro, but the association of expression of many such factors in vivo with follicle health status and their physiological significance are not clear. The purpose of this review is to discuss the in vivo and in vitro evidence supporting a local physiological role for cocaine and amphetamine regulated transcript, inhibins and low molecular weight insulin like growth factor binding proteins in negative regulation of granulosa cell estradiol production, with emphasis on evidence from the bovine model system.

The Neurofibromatosis 2 Tumor Suppressor Gene Product, Merlin, Regulates Human Meningioma Cell Growth by Signaling through YAP

Directory of Open Access Journals (Sweden)

Katherine Striedinger

2008-11-01

Full Text Available Neurofibromatosis type 2 (NF2 is an autosomal dominant disorder characterized by the occurrence of schwannomas and meningiomas. Several studies have examined the ability of the NF2 gene product, merlin, to function as a tumor suppressor in diverse cell types; however, little is known about merlin growth regulation in meningiomas. In Drosophila, merlin controls cell proliferation and apoptosis by signaling through the Hippo pathway to inhibit the function of the transcriptional coactivator Yorkie. The Hippo pathway is conserved in mammals. On the basis of these observations, we developed human meningioma cell lines matched for merlin expression to evaluate merlin growth regulation and investigate the relationship between NF2 status and Yes-associated protein (YAP, the mammalian homolog of Yorkie. NF2 loss in meningioma cells was associated with loss of contact-dependent growth inhibition, enhanced anchorage-independent growth and increased cell proliferation due to increased S-phase entry. In addition, merlin loss in both meningioma cell lines and primary tumors resulted in increased YAP expression and nuclear localization. Finally, siRNA-mediated reduction of YAP in NF2-deficient meningioma cells rescued the effects of merlin loss on cell proliferation and S-phase entry. Collectively, these results represent the first demonstration that merlin regulates cell growth in human cancer cells by suppressing YAP.

The Adaptor Protein SAP Regulates Type II NKT Cell Development, Cytokine Production and Cytotoxicity Against Lymphoma1

Science.gov (United States)

Weng, Xiufang; Liao, Chia-Min; Bagchi, Sreya; Cardell, Susanna L.; Stein, Paul L.; Wang, Chyung-Ru

2014-01-01

CD1d-restricted NKT cells represent a unique lineage of immunoregulatory T cells that are divided into two groups, type I and type II, based on their TCR usage. Because there are no specific tools to identify type II NKT cells, little is known about their developmental requirements and functional regulation. In our previous study, we showed that signaling lymphocytic activation molecule-associated protein (SAP) is essential for the development of type II NKT cells. Here, using a type II NKT cell TCR transgenic mouse model (24αβTg), we demonstrated that CD1d-expressing hematopoietic cells but not thymic epithelial cells meditate efficient selection of type II NKT cells. Further, we showed that SAP regulates type II NKT cell development by controlling Egr2 and PLZF expression. SAP-deficient 24αβ transgenic T cells (24αβ T cells) exhibited an immature phenotype with reduced Th2 cytokine-producing capacity and diminished cytotoxicity to CD1d-expressing lymphoma cells. The impaired IL-4 production by SAP-deficient 24αβ T cells was associated with reduced IRF4 and GATA-3 induction following TCR stimulation. Collectively, these data suggest that SAP is critical for regulating type II NKT cell responses. Aberrant responses of these T cells may contribute to the immune dysregulation observed in X-linked lymphoproliferative disease caused by mutations in SAP. PMID:25236978

Optimum regulation of grid monopoly in the power trade; Optimal regulering av nettmonopoler i kraftomsetningen

Energy Technology Data Exchange (ETDEWEB)

Hope, E.

1994-06-01

The report discusses the organization and behaviour of grid monopolies in the Norwegian power trade and relations to the socio-economic effectiveness. The main attention is laid on analyzing regulation mechanisms and measures leading to an efficient short-term operation and to the investment of optimum production capacity in a long run. Regarding the management, measures are discussed for increasing the efficiency of total power trade by evaluating the existing marketing function of Statnett. Some basic conditions are accounted concerning the regulation problem of grid monopolies with a particular attention to asymmetric information between the authority and the monopoly. In addition, forms of regulation and regulation mechanisms together with the incentive characteristics of these, are discussed. The existing profit regulation principles in relation to an alternative system design such as maximum price regulation combined with standard regulation, are evaluated. 16 refs., 7 figs.

Peculiarities of toxic effects exerted by hexyl ether of 5-aminolevulinic acid and grounds for working our regulations of its safe production and application

Directory of Open Access Journals (Sweden)

Е.К. Vlasenko

2017-09-01

Full Text Available Our research object was hexyl ether of 5-aminolevulinic acid applied as plants growth regulator which was synthe-sized with an original technology by Bioorganic Chemistry Institute of Belarus National Academy of science. Our research goal was to determine peculiarities of toxic effects exerted by this new plants protector on experimental models in vivo/in vitro and to give grounds for hygienic standards of its contents in various media which were to provide its safe production and application. We conducted our research with the use of toxicological, physiological, hematological, biochemical, immu-nologic, cytogenetic, cytological, and statistical methods. We were the first to perform toxicological assessment of this new plants growth regulator under different regimes, doses and ways of introduction into laboratory animals' bodies and it helped us to detect its toxicometric parameters and peculiarities of its biological effects which became apparent through skin-resorptive and cumulative properties, irritating impacts on mucous tunics, moderate reproductive toxicity without sub-stantial signs of gonadotropic, mutagenic, and allergenic impacts on a body. We detected that toxic impacts exerted by the examined substance on a body was combined with membrane-tropic and cytotoxic effects. We determined criteria and limit-ing parameters of hazardous effects exerted by hexyl ether of 5-aminolevulinic acid in the course of a chronic experiment, and it gave us grounds for fixing allowable daily dose for a man and for working out a number of regulations on the sub-stance contents in environmental objects (working area air, water, and soil, in food raw materials, and in food products (grain, rape, rape and linen oil. The obtained results were used as a basis for fixing 9 hygienic standards and were used for the state registration of this plant growth regulator; it will provide its safe production and application in agriculture.

Plain packaging and indirect expropriation of trademark rights under BITs: does FCTC help to establish a right to regulate tobacco products?

Science.gov (United States)

Lo, Chang-Fa

2012-12-01

Recently the giant tobacco company Philip Morris served its notice to launch an investor-to-state dispute settlement proceeding against the Australian Government for its introduction of plain packaging requirements on tobacco products. It is an important event in the field of intellectual property, investment and international health law. The fundamental questions involved are whether the restriction of trademark rights as a result of the plain packaging requirement is a compensable indirect expropriation under BITs or whether it falls within the scope of government's right to regulate and thus become not compensable. This paper is of the view that the requirement of plain packaging will deprive the essential value or core function of trademark rights and thus constitutes an indirect expropriation under BITs. However, such indirect expropriation meets the public interest requirement and the necessity requirement. The paper further argues that sovereign States have an inherent right to regulate domestic economic activities. Since the pain packaging requirements provided in the FCTC Guidelines are expected to protect the value of human lives and health, the protected values clearly outweigh the affected commercial interests of tobacco companies. Also the justification for host States to adopt a plain packaging policy is strong. Thus, the interpreters of BITs need to pay higher respect to the host State's sovereign power concerning its right to regulate tobacco products for a legitimate purpose. The conclusion of the paper is that the host States should enjoy a defense of the right to regulate to refuse compensation. The author believes that this is the only reasonable conclusion to avoid possible conflicts between different treaty systems (BITs and the FCTC) and between different legal systems and fields (trademark law, investment law and international health law).

Federal Gasoline Regulations

Science.gov (United States)

The Clean Air Act requires EPA to regulate fuels and fuel additives for use in mobile sources if such fuel, fuel additive or any emission products causes or contributes to air or water pollution that may endanger the public health or welfare.

Long-chain bases and their phosphorylated derivatives differentially regulate cryptogein-induced production of reactive oxygen species in tobacco (Nicotiana tabacum) BY-2 cells.

Science.gov (United States)

Coursol, Sylvie; Fromentin, Jérôme; Noirot, Elodie; Brière, Christian; Robert, Franck; Morel, Johanne; Liang, Yun-Kuan; Lherminier, Jeannine; Simon-Plas, Françoise

2015-02-01

The proteinaceous elicitor cryptogein triggers defence reactions in Nicotiana tabacum (tobacco) through a signalling cascade, including the early production of reactive oxygen species (ROS) by the plasma membrane (PM)-located tobacco respiratory burst oxidase homologue D (NtRbohD). Sphingolipid long-chain bases (LCBs) are emerging as potent positive regulators of plant defence-related mechanisms. This led us to question whether both LCBs and their phosphorylated derivatives (LCB-Ps) are involved in the early signalling process triggered by cryptogein in tobacco BY-2 cells. Here, we showed that cryptogein-induced ROS production was inhibited by LCB kinase (LCBK) inhibitors. Additionally, Arabidopsis thaliana sphingosine kinase 1 and exogenously supplied LCB-Ps increased cryptogein-induced ROS production, whereas exogenously supplied LCBs had a strong opposite effect, which was not driven by a reduction in cellular viability. Immunogold-electron microscopy assay also revealed that LCB-Ps are present in the PM, which fits well with the presence of a high LCBK activity associated with this fraction. Our data demonstrate that LCBs and LCB-Ps differentially regulate cryptogein-induced ROS production in tobacco BY-2 cells, and support a model in which a cooperative synergism between LCBK/LCB-Ps and NtRbohD/ROS in the cryptogein signalling pathway is likely at the PM in tobacco BY-2 cells. © 2014 INRA New Phytologist © 2014 New Phytologist Trust.

41 CFR 101-29.214 - Commercial-type product.

Science.gov (United States)

2010-07-01

... 41 Public Contracts and Property Management 2 2010-07-01 2010-07-01 true Commercial-type product... Regulations System FEDERAL PROPERTY MANAGEMENT REGULATIONS SUPPLY AND PROCUREMENT 29-FEDERAL PRODUCT DESCRIPTIONS 29.2-Definitions § 101-29.214 Commercial-type product. A commercial-type product is defined as: (a...

The role of nitrogen and phosphorus in regulating Phormidium sp. (cyanobacteria) growth and anatoxin production.

Science.gov (United States)

Heath, Mark; Wood, Susie A; Young, Roger G; Ryan, Ken G

2016-03-01

Benthic proliferations of the cyanobacteria Phormidium can cover many kilometres of riverbed. Phormidium can produce neurotoxic anatoxins and ingestion of benthic mats has resulted in numerous animal poisonings in the last decade. Despite this, there is a poor understanding of the environmental factors regulating growth and anatoxin production. In this study, the effects of nitrogen and phosphorus on the growth of two Phormidium strains (anatoxin-producing and non-anatoxin-producing) were examined in batch monocultures. Cell concentrations were significantly reduced under reduced nitrogen (ca. production. Cellular anatoxin concentrations were lowest (169 fg cell(-1)) under the high-nitrogen and high-phosphorus treatment. This supports the growth-differentiation balance hypothesis that suggests actively dividing and expanding cells are less likely to produce secondary-metabolites. Anatoxin quota was highest (>407 fg cell(-1)) in the reduced phosphorus treatments, possibly suggesting that it is produced as a stress response to growth limiting conditions. In all treatments there was a 4-5-fold increase in anatoxin quota in the lag growth phase, possibly indicating it may provide a physiological benefit during initial substrate colonization. © FEMS 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Trib1 Is Overexpressed in Systemic Lupus Erythematosus, While It Regulates Immunoglobulin Production in Murine B Cells

Directory of Open Access Journals (Sweden)

Léa Simoni

2018-03-01

Full Text Available Systemic lupus erythematosus (SLE is a severe and heterogeneous autoimmune disease with a complex genetic etiology, characterized by the production of various pathogenic autoantibodies, which participate in end-organ damages. The majority of human SLE occurs in adults as a polygenic disease, and clinical flares interspersed with silent phases of various lengths characterize the usual evolution of the disease in time. Trying to understand the mechanism of the different phenotypic traits of the disease, and considering the central role of B cells in SLE, we previously performed a detailed wide analysis of gene expression variation in B cells from quiescent SLE patients. This analysis pointed out an overexpression of TRIB1. TRIB1 is a pseudokinase that has been implicated in the development of leukemia and also metabolic disorders. It is hypothesized that Trib1 plays an adapter or scaffold function in signaling pathways, notably in MAPK pathways. Therefore, we planned to understand the functional significance of TRIB1 overexpression in B cells in SLE. We produced a new knock-in model with B-cell-specific overexpression of Trib1. We showed that overexpression of Trib1 specifically in B cells does not impact B cell development nor induce any development of SLE symptoms in the mice. By contrast, Trib1 has a negative regulatory function on the production of immunoglobulins, notably IgG1, but also on the production of autoantibodies in an induced model. We observed a decrease of Erk activation in BCR-stimulated Trib1 overexpressing B cells. Finally, we searched for Trib1 partners in B cells by proteomic analysis in order to explore the regulatory function of Trib1 in B cells. Interestingly, we find an interaction between Trib1 and CD72, a negative regulator of B cells whose deficiency in mice leads to the development of autoimmunity. In conclusion, the overexpression of Trib1 could be one of the molecular pathways implicated in the negative regulation

Regulatory network controlling extracellular proteins in Erwinia carotovora subsp. carotovora: FlhDC, the master regulator of flagellar genes, activates rsmB regulatory RNA production by affecting gacA and hexA (lrhA) expression.

Science.gov (United States)

Cui, Yaya; Chatterjee, Asita; Yang, Hailian; Chatterjee, Arun K

2008-07-01

Erwinia carotovora subsp. carotovora produces an array of extracellular proteins (i.e., exoproteins), including plant cell wall-degrading enzymes and Harpin, an effector responsible for eliciting hypersensitive reaction. Exoprotein genes are coregulated by the quorum-sensing signal, N-acyl homoserine lactone, plant signals, an assortment of transcriptional factors/regulators (GacS/A, ExpR1, ExpR2, KdgR, RpoS, HexA, and RsmC) and posttranscriptional regulators (RsmA, rsmB RNA). rsmB RNA production is positively regulated by GacS/A, a two-component system, and negatively regulated by HexA (PecT in Erwinia chrysanthemi; LrhA [LysR homolog A] in Escherichia coli) and RsmC, a putative transcriptional adaptor. While free RsmA, an RNA-binding protein, promotes decay of mRNAs of exoprotein genes, binding of RsmA with rsmB RNA neutralizes the RsmA effect. In the course of studies of GacA regulation, we discovered that a locus bearing strong homology to the flhDC operon of E. coli also controls extracellular enzyme production. A transposon insertion FlhDC(-) mutant produces very low levels of pectate lyase, polygalacturonase, cellulase, protease, and E. carotovora subsp. carotovora Harpin (Harpin(Ecc)) and is severely attenuated in its plant virulence. The production of these exoproteins is restored in the mutant carrying an FlhDC(+) plasmid. Sequence analysis and transcript assays disclosed that the flhD operon of E. carotovora subsp. carotovora, like those of other enterobacteria, consists of flhD and flhC. Complementation analysis revealed that the regulatory effect requires functions of both flhD and flhC products. The data presented here show that FlhDC positively regulates gacA, rsmC, and fliA and negatively regulates hexA (lrhA). Evidence shows that FlhDC controls extracellular protein production through cumulative effects on hexA and gacA. Reduced levels of GacA and elevated levels of HexA in the FlhDC(-) mutant are responsible for the inhibition of rsmB RNA

Regulatory Network Controlling Extracellular Proteins in Erwinia carotovora subsp. carotovora: FlhDC, the Master Regulator of Flagellar Genes, Activates rsmB Regulatory RNA Production by Affecting gacA and hexA (lrhA) Expression▿

Science.gov (United States)

Cui, Yaya; Chatterjee, Asita; Yang, Hailian; Chatterjee, Arun K.

2008-01-01

Erwinia carotovora subsp. carotovora produces an array of extracellular proteins (i.e., exoproteins), including plant cell wall-degrading enzymes and Harpin, an effector responsible for eliciting hypersensitive reaction. Exoprotein genes are coregulated by the quorum-sensing signal, N-acyl homoserine lactone, plant signals, an assortment of transcriptional factors/regulators (GacS/A, ExpR1, ExpR2, KdgR, RpoS, HexA, and RsmC) and posttranscriptional regulators (RsmA, rsmB RNA). rsmB RNA production is positively regulated by GacS/A, a two-component system, and negatively regulated by HexA (PecT in Erwinia chrysanthemi; LrhA [LysR homolog A] in Escherichia coli) and RsmC, a putative transcriptional adaptor. While free RsmA, an RNA-binding protein, promotes decay of mRNAs of exoprotein genes, binding of RsmA with rsmB RNA neutralizes the RsmA effect. In the course of studies of GacA regulation, we discovered that a locus bearing strong homology to the flhDC operon of E. coli also controls extracellular enzyme production. A transposon insertion FlhDC− mutant produces very low levels of pectate lyase, polygalacturonase, cellulase, protease, and E. carotovora subsp. carotovora Harpin (HarpinEcc) and is severely attenuated in its plant virulence. The production of these exoproteins is restored in the mutant carrying an FlhDC+ plasmid. Sequence analysis and transcript assays disclosed that the flhD operon of E. carotovora subsp. carotovora, like those of other enterobacteria, consists of flhD and flhC. Complementation analysis revealed that the regulatory effect requires functions of both flhD and flhC products. The data presented here show that FlhDC positively regulates gacA, rsmC, and fliA and negatively regulates hexA (lrhA). Evidence shows that FlhDC controls extracellular protein production through cumulative effects on hexA and gacA. Reduced levels of GacA and elevated levels of HexA in the FlhDC− mutant are responsible for the inhibition of rsmB RNA production

Eosinophils Regulate Interferon Alpha Production in Plasmacytoid Dendritic Cells Stimulated with Components of Neutrophil Extracellular Traps.

Science.gov (United States)

Skrzeczynska-Moncznik, Joanna; Zabieglo, Katarzyna; Bossowski, Jozef P; Osiecka, Oktawia; Wlodarczyk, Agnieszka; Kapinska-Mrowiecka, Monika; Kwitniewski, Mateusz; Majewski, Pawel; Dubin, Adam; Cichy, Joanna

2017-03-01

Eosinophils constitute an important component of helminth immunity and are not only associated with various allergies but are also linked to autoinflammatory disorders, including the skin disease psoriasis. Here we demonstrate the functional relationship between eosinophils and plasmacytoid dendritic cells (pDCs) as related to skin diseases. We previously showed that pDCs colocalize with neutrophil extracellular traps (NETs) in psoriatic skin. Here we demonstrate that eosinophils are found in psoriatic skin near neutrophils and NETs, suggesting that pDC responses can be regulated by eosinophils. Eosinophils inhibited pDC function in vitro through a mechanism that did not involve cell contact but depended on soluble factors. In pDCs stimulated by specific NET components, eosinophil-conditioned media attenuated the production of interferon α (IFNα) but did not affect the maturation of pDCs as evidenced by the unaltered expression of the costimulatory molecules CD80 and CD86. As pDCs and IFNα play a key role in autoimmune skin inflammation, these data suggest that eosinophils may influence autoinflammatory responses through their impact on the production of IFNα by pDCs.

Flammability tests for regulation of building and construction materials

Science.gov (United States)

K. Sumathipala

2006-01-01

The regulation of building materials and products for flammability is critical to ensure the safety of occupants in buildings and other structures. The involvement of exposed building materials and products in fires resulting in the loss of human life often spurs an increase in regulation and new test methods to address the problem. Flammability tests range from those...

OXYGEN PRESSURE REGULATOR DESIGN AND ANALYSIS THROUGH FINITE ELEMENT MODELING

Directory of Open Access Journals (Sweden)

Asterios KOSMARAS

2017-05-01

Full Text Available Oxygen production centers produce oxygen in high pressure that needs to be defused. A regulator is designed and analyzed in the current paper for medical use in oxygen production centers. This study aims to design a new oxygen pressure regulator and perform an analysis using Finite Element Modeling in order to evaluate its working principle. In the design procedure,the main elements and the operating principles of a pressure regulator are taking into account. The regulator is designed and simulations take place in order to assessthe proposed design. Stress analysis results are presented for the main body of the regulator, as well as, flow analysis to determine some important flow characteristics in the inlet and outlet of the regulator.

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

International Nuclear Information System (INIS)

Sung, Key Yong; Lee, Chang Ju; Kim, Woong Sik; Kim, Hho Jung

2003-01-01

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

ABC transporter content diversity in Streptococcus pneumoniae impacts competence regulation and bacteriocin production.

Science.gov (United States)

Wang, Charles Y; Patel, Nisha; Wholey, Wei-Yun; Dawid, Suzanne

2018-06-19

The opportunistic pathogen Streptococcus pneumoniae (pneumococcus) uses natural genetic competence to increase its adaptability through horizontal gene transfer. One method of acquiring DNA is through predation of neighboring strains with antimicrobial peptides called "bacteriocins." Competence and production of the major family of pneumococcal bacteriocins, pneumocins, are regulated by the quorum-sensing systems com and blp , respectively. In the classical paradigm, the ABC transporters ComAB and BlpAB each secretes its own system's signaling pheromone and in the case of BlpAB also secretes the pneumocins. While ComAB is found in all pneumococci, only 25% of strains encode an intact version of BlpAB [BlpAB(+)] while the rest do not [BlpAB(-)]. Contrary to the classical paradigm, it was previously shown that BlpAB(-) strains can activate blp through ComAB-mediated secretion of the blp pheromone during brief periods of competence. To better understand the full extent of com - blp crosstalk, we examined the contribution of each transporter to competence development and pneumocin secretion. We found that BlpAB(+) strains have a greater capacity for competence activation through BlpAB-mediated secretion of the com pheromone. Similarly, we show that ComAB and BlpAB are promiscuous and both can secrete pneumocins. Consequently, differences in pneumocin secretion between BlpAB(+) and BlpAB(-) strains derive from the regulation and kinetics of transporter expression rather than substrate specificity. We speculate that BlpAB(-) strains (opportunists) use pneumocins mainly in a narrowly tailored role for DNA acquisition and defense during competence while BlpAB(+) strains (aggressors) expand their use for the general inhibition of rival strains. Copyright © 2018 the Author(s). Published by PNAS.

Becoming a refinery leader by changing operations to match new product quality regulations

Energy Technology Data Exchange (ETDEWEB)

Mendez, Maryro P. [KBC Advanced Technologies, Surrey (United Kingdom)

2012-07-01

Global environmental concerns have forced the automotive and oil industries to increase efficiency and reduce emissions, which has led to the tightening of fuels specifications around the world. The implementation of ultra-low sulphur transport fuels has become a worldwide trend with growing momentum. Compliance with these standards requires the refiner to make decisions in advance of the implementation date. Therefore, in order to make changes on time, refiners are currently assessing options and changes required to comply with regulations by 2016. Similar regulations have been implemented in Europe already and KBC has the methodology and experience to assess the existing refinery configuration, unit capability and facility infrastructure to provide the basis for decision making. This paper focus on KBC's methodology which looks at the molecular management needed to produce the low levels of sulfur and toxic required in today's refined products. A key element to the study is the use of Petro-SIM for development of a representative detailed non-linear model, of the refinery which has been used to test ideas and configurations and help confirm the Refinery LP development activities. Using a Petro-SIM representation, KBC is able to make an assessment of the impact of imposing Tier 3 gasoline (sulphur to < 10 ppm) on the refinery, examining critical blending constraints, unused stream qualities and quantities and likely type and scale of capital investment that would be required while optimising unit operations and maximising margins. This paper illustrates KBC's current thinking based on studies done to date to review clean fuels and Tier 3 specifications options for specific refinery configurations. (author)

Nanometrology - challenges for health regulation

Directory of Open Access Journals (Sweden)

Jailton Carreteiro Damasceno

2013-11-01

Full Text Available The relationship between metrology, nanotechnology and nanoscience and sanitary regulation is discussed from the point of view of its importance and the interrelationship between the themes for the development of products and services involving nanotech-nology. The discussion involves the main techniques for measuring dimensional, chemical and biological properties of materials, and presents some of the challenges for the future. Issues such as processes of standardization and regulation in Europe, U.S. and Brazil are also addressed, providing an overview of how these processes are related to sanitary regulation.

A sensitive fluorescence reporter for monitoring quorum sensing regulated protease production in Vibrio harveyi.

Science.gov (United States)

Rajamani, Sathish; Sayre, Richard T

2011-02-01

Many bacteria produce and secrete proteases during host invasion and pathogenesis. Vibrio harveyi, an opportunistic pathogen of shrimp, is known to use a two-component quorum sensing (QS) mechanism for coordination of gene expression including protease secretion at high population densities. We examined the role of V. harveyi's QS signaling molecules, N-(3-hydroxybutanoyl)-L-homoserine lactone (AI-1) and the boron derivative of autoinducer-2 (BAI-2) in extracellular protease production. A fusion protein, M3CLPY (Rajamani et al., 2007), consisting of a large protease sensitive BAI-2 mutant receptor LuxP (~38kDa) flanked by two protease insensitive cyan and yellow variants of GFP (~28kDa each) was utilized as a substrate to detect secreted protease activity. The M3CLPY fusion, with the addition of wild-type V. harveyi (BB120) cell-free culture filtrate showed a time-dependent loss in fluorescence resonance energy transfer (FRET) associated with the cleavage of the LuxP linker protein and hence separation of the two fluorophores. This cleavage of LuxP linker protein leading to decreased FRET efficiency was further confirmed by immunoblotting using anti-GFP antibody. The addition of cell-free filtrates from strains defective in one or both of the two-component QS pathways: luxN(-) (defective in AI-1), luxS(-) (defective in BAI-2), and luxN(-)/luxS(-) (defective in both AI-1/BAI-2) showed differential levels of protease production. The observed protease activities were most pronounced in wild-type, followed by the AI-1 defective mutant (BB170) and the least for luxS(-) mutant (MM30) and luxN(-)/luxS(-) double mutant (MM32) strains. Incidentally, the lowest protease producing strains MM30 and MM32 were both defective in BAI-2 production. This observation was validated by addition of synthetic BAI-2 to MM30 and MM32 strains to restore protease production. Our results indicate that BAI-2 signaling in the two-component QS pathway plays the key role in regulating

"Their Packaging Has Always Been Like a Power": A Qualitative Study of U.S. Smokers' Perceptions of Cigarette Pack Visual Design Features to Inform Product Regulation.

Science.gov (United States)

Lee, Joseph G L; Averett, Paige E; Blanchflower, Tiffany; Landi, Nunzio; Gregory, Kyle R

2017-10-17

Cigarette packaging matters to consumer behavior. However, it is less clear which changes to packaging design would be salient for adult smokers. Such information is critically important to regulators in the United States who are charged with reviewing new tobacco products for their impact on population health. In this qualitative study, U.S. adult smokers ( n = 33) participated in six telephone-based focus groups in March 2017. Separate groups were comprised of lesbian, gay, and bisexual (LGB) participants; participants with less than four years of post-secondary education; a mix of LGB and straight participants; and, the general population. All groups were purposely selected for diversity. Open thematic coding identified salient design elements used on cigarette packaging. Smokers articulated design elements' use, meaning, and links with consumer behaviors. Three themes were identified: (1) the power of color, (2) supporting color with other design elements (e.g., logos/images, typography, the pack itself), and (3) the combined product brand experience of multiple design elements. Participants linked design elements to product characteristics and to consumer behavior (e.g., purchase). As the Food and Drug Administration is charged with regulating tobacco products, these findings suggest the importance of considering the cigarette pack part of the characteristics of a product.

Identification of a response regulator involved in surface attachment, cell-cell aggregation, exopolysaccharide production and virulence in the plant pathogen Xylella fastidiosa.

Science.gov (United States)

Voegel, Tanja M; Doddapaneni, Harshavardhan; Cheng, Davis W; Lin, Hong; Stenger, Drake C; Kirkpatrick, Bruce C; Roper, M Caroline

2013-04-01

Xylella fastidiosa, the causal agent of Pierce's disease of grapevine, possesses several two-component signal transduction systems that allow the bacterium to sense and respond to changes in its environment. Signals are perceived by sensor kinases that autophosphorylate and transfer the phosphate to response regulators (RRs), which direct an output response, usually by acting as transcriptional regulators. In the X. fastidiosa genome, 19 RRs were found. A site-directed knockout mutant in one unusual RR, designated XhpT, composed of a receiver domain and a histidine phosphotransferase output domain, was constructed. The resulting mutant strain was analysed for changes in phenotypic traits related to biofilm formation and gene expression using microarray analysis. We found that the xhpT mutant was altered in surface attachment, cell-cell aggregation, exopolysaccharide (EPS) production and virulence in grapevine. In addition, this mutant had an altered transcriptional profile when compared with wild-type X. fastidiosa in genes for several biofilm-related traits, such as EPS production and haemagglutinin adhesins. © 2012 BSPP AND BLACKWELL PUBLISHING LTD.

Regulations And Control Of Food And Drugs

International Nuclear Information System (INIS)

Osuide, G.E.; Director General, National Agency For Food And Drugs Administration And Control, Federal Secretariat, Ikoyi, Lagos, Nigeria.

1996-01-01

Effective control of processed food and medicines is crucial for the maintenance of public health. Issues of wholesomeness, quality, efficacy and safety are of paramount concern to both consumers and regulatory agencies alike. Laws and regulatory are put in in place to ensure minimum standards of practice by the various operators in the food and pharmaceutical sub-sectors, such as will guarantee that the regulated products (food, drugs, cosmetics, medical devices, chemicals and bottled water) they deal in satisfy all the parameters of quality, wholesomeness, efficacy and safety. National Agency for Food and Drug Administration and Control (NAFDAC) was established to enforce all relevant laws and regulations on food and drugs among other-regulated products. NAFDAC has put in place appropriate administrative structures and procedures in its efforts to fulfill its mandate. Finally, the agency is in the process of extending its regulatory and control activities to cover irradiated food products in order to safeguard public health

Genetic manipulation of longevity-related genes as a tool to regulate yeast life span and metabolite production during winemaking

Directory of Open Access Journals (Sweden)

Orozco Helena

2013-01-01

Full Text Available Abstract Background Yeast viability and vitality are essential for different industrial processes where the yeast Saccharomyces cerevisiae is used as a biotechnological tool. Therefore, the decline of yeast biological functions during aging may compromise their successful biotechnological use. Life span is controlled by a variety of molecular mechanisms, many of which are connected to stress tolerance and genomic stability, although the metabolic status of a cell has proven a main factor affecting its longevity. Acetic acid and ethanol accumulation shorten chronological life span (CLS, while glycerol extends it. Results Different age-related gene classes have been modified by deletion or overexpression to test their role in longevity and metabolism. Overexpression of histone deacetylase SIR2 extends CLS and reduces acetate production, while overexpression of SIR2 homolog HST3 shortens CLS, increases the ethanol level, and reduces acetic acid production. HST3 overexpression also enhances ethanol tolerance. Increasing tolerance to oxidative stress by superoxide dismutase SOD2 overexpression has only a moderate positive effect on CLS. CLS during grape juice fermentation has also been studied for mutants on several mRNA binding proteins that are regulators of gene expression at the posttranscriptional level; we found that NGR1 and UTH4 deletions decrease CLS, while PUF3 and PUB1 deletions increase it. Besides, the pub1Δ mutation increases glycerol production and blocks stress granule formation during grape juice fermentation. Surprisingly, factors relating to apoptosis, such as caspase Yca1 or apoptosis-inducing factor Aif1, play a positive role in yeast longevity during winemaking as their deletions shorten CLS. Conclusions Manipulation of regulators of gene expression at both transcriptional (i.e., sirtuins and posttranscriptional (i.e., mRNA binding protein Pub1 levels allows to modulate yeast life span during its biotechnological use. Due to

9 CFR 381.27 - Inauguration of service; notification concerning regulations; status of uninspected poultry...

Science.gov (United States)

2010-01-01

... concerning regulations; status of uninspected poultry products. 381.27 Section 381.27 Animals and Animal...; MANDATORY MEAT AND POULTRY PRODUCTS INSPECTION AND VOLUNTARY INSPECTION AND CERTIFICATION POULTRY PRODUCTS... concerning regulations; status of uninspected poultry products. The inspector in charge or his supervisor...

Pseudomonas aeruginosa AlgR Phosphorylation Status Differentially Regulates Pyocyanin and Pyoverdine Production

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Alexander S. Little

2018-01-01

Full Text Available Pseudomonas aeruginosa employs numerous, complex regulatory elements to control expression of its many virulence systems. The P. aeruginosa AlgZR two-component regulatory system controls the expression of several crucial virulence phenotypes. We recently determined, through transcriptomic profiling of a PAO1 ΔalgR mutant strain compared to wild-type PAO1, that algZR and hemCD are cotranscribed and show differential iron-dependent gene expression. Previous expression profiling was performed in strains without algR and revealed that AlgR acts as either an activator or repressor, depending on the gene. Thus, examination of P. aeruginosa gene expression from cells locked into different AlgR phosphorylation states reveals greater physiological relevance. Therefore, gene expression from strains carrying algR alleles encoding a phosphomimetic (AlgR D54E or a phosphoablative (AlgR D54N form were compared by microarray to PAO1. Transcriptome analyses of these strains revealed 25 differentially expressed genes associated with iron siderophore biosynthesis or heme acquisition or production. The PAO1 algR D54N mutant produced lower levels of pyoverdine but increased expression of the small RNAs prrf1 and prrf2 compared to PAO1. In contrast, the algR D54N mutant produced more pyocyanin than wild-type PAO1. On the other hand, the PAO1 algR D54E mutant produced higher levels of pyoverdine, likely due to increased expression of an iron-regulated gene encoding the sigma factor pvdS, but it had decreased pyocyanin production. AlgR specifically bound to the prrf2 and pvdS promoters in vitro. AlgR-dependent pyoverdine production was additionally influenced by carbon source rather than the extracellular iron concentration per se. AlgR phosphorylation effects were also examined in a Drosophila melanogaster feeding, murine acute pneumonia, and punch wound infection models. Abrogation of AlgR phosphorylation attenuated P. aeruginosa virulence in these infection

BMP15 suppresses progesterone production by down-regulating StAR via ALK3 in human granulosa cells.

Science.gov (United States)

Chang, Hsun-Ming; Cheng, Jung-Chien; Klausen, Christian; Leung, Peter C K

2013-12-01

In addition to somatic cell-derived growth factors, oocyte-derived growth differentiation factor (GDF)9 and bone morphogenetic protein (BMP)15 play essential roles in female fertility. However, few studies have investigated their effects on human ovarian steroidogenesis, and fewer still have examined their differential effects or underlying molecular determinants. In the present study, we used immortalized human granulosa cells (SVOG) and human granulosa cell tumor cells (KGN) to compare the effects of GDF9 and BMP15 on steroidogenic enzyme expression and investigate potential mechanisms of action. In SVOG cells, neither GDF9 nor BMP15 affects the mRNA levels of P450 side-chain cleavage enzyme or 3β-hydroxysteroid dehydrogenase. However, treatment with BMP15, but not GDF9, significantly decreases steroidogenic acute regulatory protein (StAR) mRNA and protein levels as well as progesterone production. These suppressive effects, along with the induction of Sma and Mad-related protein (SMAD)1/5/8 phosphorylation, are attenuated by cotreatment with 2 different BMP type I receptor inhibitors (dorsomorphin and DMH-1). Furthermore, depletion of activin receptor-like kinase (ALK)3 using small interfering RNA reverses the effects of BMP15 on SMAD1/5/8 phosphorylation and StAR expression. Similarly, knockdown of ALK3 abolishes BMP15-induced SMAD1/5/8 phosphorylation in KGN cells. These results provide evidence that oocyte-derived BMP15 down-regulates StAR expression and decreases progesterone production in human granulosa cells, likely via ALK3-mediated SMAD1/5/8 signaling. Our findings suggest that oocyte may play a critical role in the regulation of progesterone to prevent premature luteinization during the late stage of follicle development.

7 CFR 54.1027 - Application of other regulations to appeal service.

Science.gov (United States)

2010-01-01

... MARKETING SERVICE (Standards, Inspections, Marketing Practices), DEPARTMENT OF AGRICULTURE (CONTINUED) REGULATIONS AND STANDARDS UNDER THE AGRICULTURAL MARKETING ACT OF 1946 AND THE EGG PRODUCTS INSPECTION ACT..., Processing, and Packaging of Livestock and Poultry Products § 54.1027 Application of other regulations to...

Innovation in regulation of rapidly changing health markets.

Science.gov (United States)

Bloom, Gerald; Henson, Spencer; Peters, David H

2014-06-24

The rapid evolution and spread of health markets across low and middle-income countries (LMICs) has contributed to a significant increase in the availability of health-related goods and services around the world. The support institutions needed to regulate these markets have lagged behind, with regulatory systems that are weak and under-resourced. This paper explores the key issues associated with regulation of health markets in LMICs, and the different goals of regulation, namely quality and safety of care, value for money, social agreement over fair access and financing, and accountability. Licensing, price controls, and other traditional approaches to the regulation of markets for health products and services have played an important role, but they have been of questionable effectiveness in ensuring safety and efficacy at the point of the user in LMICs. The paper proposes a health market systems conceptual framework, using the value chain for the production, distribution and retail of health goods and services, to examine regulation of health markets in the LMIC context. We conclude by exploring the changing context going forwards, laying out implications for future heath market regulation. We argue that the case for new approaches to the regulation of markets for health products and services in LMICs is compelling. Although traditional "command and control" approaches will have a place in the toolkit of regulators, a broader bundle of approaches is needed that is adapted to the national and market-level context of particular LMICs. The implication is that it is not possible to apply standard or single interventions across countries, as approaches proven to work well in one context will not necessarily work well elsewhere.

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

Directory of Open Access Journals (Sweden)

Sangkyu Park

Full Text Available 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.

The regulation mechanisms of soluble starch and glycerol for production of azaphilone pigments in Monascus purpureus FAFU618 as revealed by comparative proteomic and transcriptional analyses.

Science.gov (United States)

Huang, Zi-Rui; Zhou, Wen-Bin; Yang, Xue-Ling; Tong, Ai-Jun; Hong, Jia-Li; Guo, Wei-Ling; Li, Tian-Tian; Jia, Rui-Bo; Pan, Yu-Yang; Lin, Jun; Lv, Xu-Cong; Liu, Bin

2018-04-01

Monascus spp. have been used for thousands of years as a traditional food additive in China. This mold can produce many different types of commercially valuable secondary metabolites of biological activity. Soluble starch and glycerol are the two principal carbon sources universally utilized by Monascus for the production of beneficial metabolites. In this study, the effects and regulation mechanisms of soluble starch and glycerol for M. purpureus FAFU618 on Monascus azaphilone pigments (MonAzPs) were investigated through ultra-performance liquid chromatography quadrupole time of flight mass spectrometry (UPLC-QTOF-MS/MS), comparative proteomics and quantitative real-time reverse transcription polymerase chain reaction (RT-qPCR). The production of intracellular and extracellular pigments was significantly different between the soluble starch group (SSG) and glycerol group (GCG). Additionally, the components of intracellular pigments revealed by UPLC-QTOF-MS/MS showed that Monascin and Ankaflavin increased significantly in the GCG, while Rubropunctatin and Monascorubrin increased in the SSG. Differentially expressed proteins of mycelia between SSG and GCG were analyzed by two-dimensional gel electrophoresis (2-DE) and MALDI-TOF/TOF MS. We identified 27 proteins with statistically altered expression, of which 18 proteins associated with the EMP (glycolytic pathway), translation, energy generation, proteolysis, etc. were up-regulated, and 9 proteins, including ribosomal proteins, heat shock proteins (HSPs) and others, were down-regulated in GCG. Meanwhile, the expression levels of MonAzP biosynthetic genes were also analyzed by RT-qPCR, and the results showed that mppA, mppC, mppR1 and mppR2 were down-regulated, whereas genes MpPKS5, MpFasA2, MpFasB2, mppB, mppD and mppE were up-regulated. Collectively, these findings illustrate that the regulation of MonAzPs is not only closely related to the expression levels of certain proteins in the polyketide synthesis pathway

Nuclear power for energy production and hazardous waste regulations in India

International Nuclear Information System (INIS)

Sharma, Prabhakar; Goel, Gaurav

2010-01-01

Before installing any nuclear power- generation plants in India, it is important to implement stringent regulations for the health and safety of the people and for protection of the environment, soil and water from the nuclear and hazardous waste produced in the power plants. Although some initiatives have been taken for radioactive waste disposal in India, the current hazardous and nuclear waste storage/disposal regulations are still too soft and are not being implemented properly in the country

The Canonical Immediate Early 3 Gene Product pIE611 of Mouse Cytomegalovirus Is Dispensable for Viral Replication but Mediates Transcriptional and Posttranscriptional Regulation of Viral Gene Products.

Science.gov (United States)

Rattay, Stephanie; Trilling, Mirko; Megger, Dominik A; Sitek, Barbara; Meyer, Helmut E; Hengel, Hartmut; Le-Trilling, Vu Thuy Khanh

2015-08-01

Transcription of mouse cytomegalovirus (MCMV) immediate early ie1 and ie3 is controlled by the major immediate early promoter/enhancer (MIEP) and requires differential splicing. Based on complete loss of genome replication of an MCMV mutant carrying a deletion of the ie3-specific exon 5, the multifunctional IE3 protein (611 amino acids; pIE611) is considered essential for viral replication. Our analysis of ie3 transcription resulted in the identification of novel ie3 isoforms derived from alternatively spliced ie3 transcripts. Construction of an IE3-hemagglutinin (IE3-HA) virus by insertion of an in-frame HA epitope sequence allowed detection of the IE3 isoforms in infected cells, verifying that the newly identified transcripts code for proteins. This prompted the construction of an MCMV mutant lacking ie611 but retaining the coding capacity for the newly identified isoforms ie453 and ie310. Using Δie611 MCMV, we demonstrated the dispensability of the canonical ie3 gene product pIE611 for viral replication. To determine the role of pIE611 for viral gene expression during MCMV infection in an unbiased global approach, we used label-free quantitative mass spectrometry to delineate pIE611-dependent changes of the MCMV proteome. Interestingly, further analysis revealed transcriptional as well as posttranscriptional regulation of MCMV gene products by pIE611. Cytomegaloviruses are pathogenic betaherpesviruses persisting in a lifelong latency from which reactivation can occur under conditions of immunosuppression, immunoimmaturity, or inflammation. The switch from latency to reactivation requires expression of immediate early genes. Therefore, understanding of immediate early gene regulation might add insights into viral pathogenesis. The mouse cytomegalovirus (MCMV) immediate early 3 protein (611 amino acids; pIE611) is considered essential for viral replication. The identification of novel protein isoforms derived from alternatively spliced ie3 transcripts prompted

State regulation and power plant productivity: background and recommendations

International Nuclear Information System (INIS)

1980-09-01

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

Knowledge Management for Safety Regulators: Cooperation to Achieve a Much Needed Product

International Nuclear Information System (INIS)

Mallick, S.

2016-01-01

Full text: Knowledge management (KM) has been identified by a number of IAEA documents as one of the key factors that can contribute to the safe and efficient operation of nuclear facilities in Member States. The IAEA Strategic Approaches to Education and Training in Nuclear and Radiation, Transport and Waste Safety identify and underline KM as an important line of action for effective national and organizational strategies in education and training. The capacity building “umbrella concept”, developed within the Action Plan in Nuclear Safety, also recognizes KM as one of the main four pillars (Education and Training, Human Resource Development, Knowledge Management and Knowledge Networks) of capacity building. Within existing IAEA publications, there is currently no specific practical guidance on how to develop and implement KM programmes for regulators. As such, in 2014, the IAEA Steering Committee on Regulatory Capacity Building and Knowledge Management requested the IAEA to develop a publication providing such practical guidance. The objective of the publication is to provide practical guidance to Member States on how to plan, establish and maintain an effective safety KM programme for regulators of facilities and activities. The report will identify benefits and uses of KM by regulators and will describe how a regulator could use KM in support of its functions. This presentation will provide an overview of the Knowledge Management for Safety Regulators document while highlighting the cross-departmental cooperation (i.e., NS and NE) used in its development. Furthermore, this presentation will provide insight into the challenges currently being faced by safety regulators vis-à-vis KM programmes and present potential paths forward with respect to the definition of efficient and effective KM indicators. (author

Taxation and regulation of uranium mining in Canada

International Nuclear Information System (INIS)

Anon.

1990-01-01

Government taxation and regulation have a profound influence on mineral operations. In Canada, taxation occurs both on the federal and provincial levels. In addition, both federal and provincial regulations also affect mine operations, sometimes with overlapping, or conflicting, legislation and jurisdiction. Three broad areas of regulation affect the mine production of uranium in Canada: (1) mining law or mineral rights; (2) the licensing procedures; and (3) regulation of occupational health and safety

Moderate extracellular acidification inhibits capsaicin-induced cell death through regulating calcium mobilization, NF-κB translocation and ROS production in synoviocytes

International Nuclear Information System (INIS)

Hu, Fen; Yang, Shuang; Zhao, Dan; Zhu, Shuyan; Wang, Yuxiang; Li, Junying

2012-01-01

Highlights: ► Moderate extracellular acidification regulates intracellular Ca 2+ mobilization. ► Moderate acidification activates NF-κB nuclear translocation in synoviocytes. ► Moderate acidification depresses the ROS production induced by capsaicin. ► Moderate acidification inhibits capsaicin-caused synoviocyte death. -- Abstract: We previously show the expression of transient receptor potential vanilloid 1 (TRPV1) in primary synoviocytes from collagen-induced arthritis (CIA) rats. Capsaicin and lowered extracellular pH from 7.4 to 5.5 induce cell death through TRPV1-mediated Ca 2+ entry and reactive oxygen species (ROS) production. However, under the pathological condition in rheumatoid arthritis, the synovial fluid is acidified to a moderate level (about pH 6.8). In the present study, we examined the effects of pH 6.8 on the TRPV1-mediated cell death. Our finding is different or even opposite from what was observed at pH 5.5. We found that the moderate extracellular acidification (from pH 7.4 to 6.8) inhibited the capsaicin-induced Ca 2+ entry through attenuating the activity of TRPV1. In the mean time, it triggered a phospholipse C (PLC)-related Ca 2+ release from intracellular stores. The nuclear translocation of NF-κB was found at pH 6.8, and this also depends on PLC activation. Moreover, the capsaicin-evoked massive ROS production and cell death were depressed at pH 6.8, both of which are dependent on the activation of PLC and NF-κB. Taken together, these results suggested that the moderate extracellular acidification inhibited the capsaicin-induced synoviocyte death through regulating Ca 2+ mobilization, activating NF-κB nuclear translocation and depressing ROS production.

Moderate extracellular acidification inhibits capsaicin-induced cell death through regulating calcium mobilization, NF-{kappa}B translocation and ROS production in synoviocytes

Energy Technology Data Exchange (ETDEWEB)

Hu, Fen; Yang, Shuang; Zhao, Dan; Zhu, Shuyan; Wang, Yuxiang [Department of Biophysics, School of Physics and Key Laboratory of Bioactive Materials of Education Ministry, Nankai University, Tianjin 300071 (China); Li, Junying, E-mail: jyli04@nankai.edu.cn [Department of Biophysics, School of Physics and Key Laboratory of Bioactive Materials of Education Ministry, Nankai University, Tianjin 300071 (China)

2012-07-20

Highlights: Black-Right-Pointing-Pointer Moderate extracellular acidification regulates intracellular Ca{sup 2+} mobilization. Black-Right-Pointing-Pointer Moderate acidification activates NF-{kappa}B nuclear translocation in synoviocytes. Black-Right-Pointing-Pointer Moderate acidification depresses the ROS production induced by capsaicin. Black-Right-Pointing-Pointer Moderate acidification inhibits capsaicin-caused synoviocyte death. -- Abstract: We previously show the expression of transient receptor potential vanilloid 1 (TRPV1) in primary synoviocytes from collagen-induced arthritis (CIA) rats. Capsaicin and lowered extracellular pH from 7.4 to 5.5 induce cell death through TRPV1-mediated Ca{sup 2+} entry and reactive oxygen species (ROS) production. However, under the pathological condition in rheumatoid arthritis, the synovial fluid is acidified to a moderate level (about pH 6.8). In the present study, we examined the effects of pH 6.8 on the TRPV1-mediated cell death. Our finding is different or even opposite from what was observed at pH 5.5. We found that the moderate extracellular acidification (from pH 7.4 to 6.8) inhibited the capsaicin-induced Ca{sup 2+} entry through attenuating the activity of TRPV1. In the mean time, it triggered a phospholipse C (PLC)-related Ca{sup 2+} release from intracellular stores. The nuclear translocation of NF-{kappa}B was found at pH 6.8, and this also depends on PLC activation. Moreover, the capsaicin-evoked massive ROS production and cell death were depressed at pH 6.8, both of which are dependent on the activation of PLC and NF-{kappa}B. Taken together, these results suggested that the moderate extracellular acidification inhibited the capsaicin-induced synoviocyte death through regulating Ca{sup 2+} mobilization, activating NF-{kappa}B nuclear translocation and depressing ROS production.

“Their Packaging Has Always Been Like a Power”: A Qualitative Study of U.S. Smokers’ Perceptions of Cigarette Pack Visual Design Features to Inform Product Regulation

Science.gov (United States)

Blanchflower, Tiffany; Landi, Nunzio; Gregory, Kyle R.

2017-01-01

Cigarette packaging matters to consumer behavior. However, it is less clear which changes to packaging design would be salient for adult smokers. Such information is critically important to regulators in the United States who are charged with reviewing new tobacco products for their impact on population health. In this qualitative study, U.S. adult smokers (n = 33) participated in six telephone-based focus groups in March 2017. Separate groups were comprised of lesbian, gay, and bisexual (LGB) participants; participants with less than four years of post-secondary education; a mix of LGB and straight participants; and, the general population. All groups were purposely selected for diversity. Open thematic coding identified salient design elements used on cigarette packaging. Smokers articulated design elements’ use, meaning, and links with consumer behaviors. Three themes were identified: (1) the power of color, (2) supporting color with other design elements (e.g., logos/images, typography, the pack itself), and (3) the combined product brand experience of multiple design elements. Participants linked design elements to product characteristics and to consumer behavior (e.g., purchase). As the Food and Drug Administration is charged with regulating tobacco products, these findings suggest the importance of considering the cigarette pack part of the characteristics of a product. PMID:29039769

“Their Packaging Has Always Been Like a Power”: A Qualitative Study of U.S. Smokers’ Perceptions of Cigarette Pack Visual Design Features to Inform Product Regulation

Directory of Open Access Journals (Sweden)

Joseph G. L. Lee

2017-10-01

Full Text Available Cigarette packaging matters to consumer behavior. However, it is less clear which changes to packaging design would be salient for adult smokers. Such information is critically important to regulators in the United States who are charged with reviewing new tobacco products for their impact on population health. In this qualitative study, U.S. adult smokers (n = 33 participated in six telephone-based focus groups in March 2017. Separate groups were comprised of lesbian, gay, and bisexual (LGB participants; participants with less than four years of post-secondary education; a mix of LGB and straight participants; and, the general population. All groups were purposely selected for diversity. Open thematic coding identified salient design elements used on cigarette packaging. Smokers articulated design elements’ use, meaning, and links with consumer behaviors. Three themes were identified: (1 the power of color, (2 supporting color with other design elements (e.g., logos/images, typography, the pack itself, and (3 the combined product brand experience of multiple design elements. Participants linked design elements to product characteristics and to consumer behavior (e.g., purchase. As the Food and Drug Administration is charged with regulating tobacco products, these findings suggest the importance of considering the cigarette pack part of the characteristics of a product.

Measurement of the heat production of bacteria in the bioreactor. Calorimetric regulation of bio-processes for the production of recombinant proteins; Messung der Waermeproduktion von Bakterien im Bioreaktor. Kalorimetrische Regelung von Bioprozessen zur Herstellung von rekombinanten Proteinen

Energy Technology Data Exchange (ETDEWEB)

Biener, Richard [Hochschule Esslingen (Germany); Steinkaempfer, Anne; Horn, Thomas; Hofmann, Johannes

2012-09-15

Recombinant proteins such as insulin or interferons are the most important products of the modern biotechnology. Recombinant proteins are produced with genetically engineered organisms. Here, besides microorganisms (E. coli or yeast cells) also animal cell cultures are used. In order to increase the productivity and the reproducibility of the cultivation process, an automated process control is required. The authors of the contribution under consideration report on the regulation of the specific rate of growth of microorganisms during cultivation in a bioreactor using standard calorimetric methods. This automation strategy results in a significant increase in productivity and reproducibility of the process.

Repletion of zinc in zinc-deficient cells strongly up-regulates IL-1β-induced IL-2 production in T-cells.

Science.gov (United States)

Daaboul, Doha; Rosenkranz, Eva; Uciechowski, Peter; Rink, Lothar

2012-10-01

Mild zinc deficiency in humans negatively affects IL-2 production resulting in declined percentages of cytolytic T cells and decreased NK cell lytic activity, which enhances the susceptibility to infections and malignancies. T-cell activation is critically regulated by zinc and the normal physiological zinc level in T-cells slightly lies below the optimal concentration for T-cell functions. A further reduction in zinc level leads to T-cell dysfunction and autoreactivity, whereas high zinc concentrations (100 μM) were shown to inhibit interleukin-1 (IL-1)-induced IL-1 receptor kinase (IRAK) activation. In this study, we investigated the molecular mechanism by which zinc regulates the IL-1β-induced IL-2 expression in T-cells. Zinc supplementation to zinc-deficient T-cells increased intracellular zinc levels by altering the expression of zinc transporters, particularly Zip10 and Zip12. A zinc signal was observed in the murine T-cell line EL-4 6.1 after 1 h of stimulation with IL-1β, measured by specific zinc sensors FluoZin-3 and ZinPyr-1. This signal is required for the phosphorylation of MAPK p38 and NF-κB subunit p65, which triggers the transcription of IL-2 and strongly increases its production. These results indicate that short-term zinc supplementation to zinc-deficient T-cells leads to a fast rise in zinc levels which subsequently enhance cytokine production. In conclusion, low and excessive zinc levels might be equally problematic for zinc-deficient subjects, and stabilized zinc levels seem to be essential to avoid negative concentration-dependent zinc effects on T-cell activation.

Down-regulation of mTOR leads to up-regulation of osteoprotegerin in bone marrow cells

International Nuclear Information System (INIS)

Mogi, Makio; Kondo, Ayami

2009-01-01

Osteoprotegerin (OPG)/osteoclastogenesis inhibitory factor regulates bone mass by inhibiting osteoclastic bone resorption. mTOR, which is the mammalian target of rapamycin, is a kinase and central regulator of cell growth, proliferation, and survival. By using Rapamycin, we studied whether mTOR pathway is associated with OPG protein production in the mouse bone marrow-derived stromal cell line ST2. Rapamycin markedly increased the level of soluble OPG in ST2 cells. This antibiotic treatment resulted in the suppression of phosphorylation of mTOR. Rapamycin had no effects on the proliferation, differentiation, or apoptosis of the cells. Treatment with bone morphogenetic protein-4, which can induce OPG protein in ST2 cells, also resulted in a decrease in the density of the phospho-mTOR-band, suggesting that the suppression of the phospho-mTOR pathway is necessary for OPG production in ST2 cells. Thus, suitable suppression of mTOR phosphorylation is a necessary requirement for OPG production in bone marrow stromal cells.

MicroRNA-451 Negatively Regulates Hepatic Glucose Production and Glucose Homeostasis by Targeting Glycerol Kinase-Mediated Gluconeogenesis.

Science.gov (United States)

Zhuo, Shu; Yang, Mengmei; Zhao, Yanan; Chen, Xiaofang; Zhang, Feifei; Li, Na; Yao, Pengle; Zhu, Tengfei; Mei, Hong; Wang, Shanshan; Li, Yu; Chen, Shiting; Le, Yingying

2016-11-01

MicroRNAs (miRNAs) are a new class of regulatory molecules implicated in type 2 diabetes, which is characterized by insulin resistance and hepatic glucose overproduction. We show that miRNA-451 (miR-451) is elevated in the liver tissues of dietary and genetic mouse models of diabetes. Through an adenovirus-mediated gain- and loss-of-function study, we found that miR-451 negatively regulates hepatic gluconeogenesis and blood glucose levels in normal mice and identified glycerol kinase (Gyk) as a direct target of miR-451. We demonstrate that miR-451 and Gyk regulate hepatic glucose production, the glycerol gluconeogenesis axis, and the AKT-FOXO1-PEPCK/G6Pase pathway in an opposite manner; Gyk could reverse the effect of miR-451 on hepatic gluconeogenesis and AKT-FOXO1-PEPCK/G6Pase pathway. Moreover, overexpression of miR-451 or knockdown of Gyk in diabetic mice significantly inhibited hepatic gluconeogenesis, alleviated hyperglycemia, and improved glucose tolerance. Further studies showed that miR-451 is upregulated by glucose and insulin in hepatocytes; the elevation of hepatic miR-451 in diabetic mice may contribute to inhibiting Gyk expression. This study provides the first evidence that miR-451 and Gyk regulate the AKT-FOXO1-PEPCK/G6Pase pathway and play critical roles in hepatic gluconeogenesis and glucose homeostasis and identifies miR-451 and Gyk as potential therapeutic targets against hyperglycemia in diabetes. © 2016 by the American Diabetes Association.

Transcription and translation products of the cytolysin gene psm-mec on the mobile genetic element SCCmec regulate Staphylococcus aureus virulence.

Directory of Open Access Journals (Sweden)

Chikara Kaito

Full Text Available The F region downstream of the mecI gene in the SCCmec element in hospital-associated methicillin-resistant Staphylococcus aureus (HA-MRSA contains two bidirectionally overlapping open reading frames (ORFs, the fudoh ORF and the psm-mec ORF. The psm-mec ORF encodes a cytolysin, phenol-soluble modulin (PSM-mec. Transformation of the F region into the Newman strain, which is a methicillin-sensitive S. aureus (MSSA strain, or into the MW2 (USA400 and FRP3757 (USA300 strains, which are community-acquired MRSA (CA-MRSA strains that lack the F region, attenuated their virulence in a mouse systemic infection model. Introducing the F region to these strains suppressed colony-spreading activity and PSMα production, and promoted biofilm formation. By producing mutations into the psm-mec ORF, we revealed that (i both the transcription and translation products of the psm-mec ORF suppressed colony-spreading activity and promoted biofilm formation; and (ii the transcription product of the psm-mec ORF, but not its translation product, decreased PSMα production. These findings suggest that both the psm-mec transcript, acting as a regulatory RNA, and the PSM-mec protein encoded by the gene on the mobile genetic element SCCmec regulate the virulence of Staphylococcus aureus.

Identification and regulation of fusA, the polyketide synthase gene responsible for fusarin production in Fusarium fujikuroi.

Science.gov (United States)

Díaz-Sánchez, Violeta; Avalos, Javier; Limón, M Carmen

2012-10-01

Fusarins are a class of mycotoxins of the polyketide family produced by different Fusarium species, including the gibberellin-producing fungus Fusarium fujikuroi. Based on sequence comparisons between polyketide synthase (PKS) enzymes for fusarin production in other Fusarium strains, we have identified the F. fujikuroi orthologue, called fusA. The participation of fusA in fusarin biosynthesis was demonstrated by targeted mutagenesis. Fusarin production is transiently stimulated by nitrogen availability in this fungus, a regulation paralleled by the fusA mRNA levels in the cell. Illumination of the cultures results in a reduction of the fusarin content, an effect partially explained by a high sensitivity of these compounds to light. Mutants of the fusA gene exhibit no external phenotypic alterations, including morphology and conidiation, except for a lack of the characteristic yellow and/or orange pigmentation of fusarins. Moreover, the fusA mutants are less efficient than the wild type at degrading cellophane on agar cultures, a trait associated with pathogenesis functions in Fusarium oxysporum. The fusA mutants, however, are not affected in their capacities to grow on plant tissues.

Pakistan nuclear safety and radiation protection regulation 1990

International Nuclear Information System (INIS)

1990-01-01

In this act regulations of nuclear safety and radiation protection in Pakistan has been explained. A legal and licensing procedure to handle protection of nuclear materials, processing storage of radioactive products has been described under this regulation. In these regulations full explanation of accidental exposure, delegation of powers and record keeping/waste disposal of radioactive has been given. (A.B.)

Regulating Cannabis Manufacturing: Applying Public Health Best Practices from Tobacco Control.

Science.gov (United States)

Orenstein, Daniel G; Glantz, Stanton A

2018-01-01

State legalization and regulation of cannabis, despite continued federal illegality, is a massive shift in regulatory approach. Manufactured cannabis, including concentrates, extracts, edibles, tinctures, topicals and other products, has received less attention than more commonly used dried flower, but represents emerging regulatory challenges due to additives, potency, consumption methods, and abuse and misuse potential. In November 2017, the California Department of Public Health (CDPH) released initial cannabis manufacturing regulations as part of a new state regulatory structure. As the largest U.S. medical cannabis market (and largest legal adult use market in the world beginning in 2018), California's regulatory approach will potentially influence national and global policy. Comparing CDPH's initial regulations to tobacco control best practices reveals that, while the regulations recognize the need to protect public health, prioritizing public health over business interests requires stronger approaches to labeling, packaging, and product formulations. Based on tobacco best practices, we recommend that cannabis regulations incorporate large and proportionately sized informational labels, a prominent universal cannabis symbol, rotating and pictorial health warnings, mandatory plain packaging, a comprehensive ban on characterizing flavors and addictive additives, and strict limits on the potency of inhalable products and those easily confused with non-cannabis products.

Developmentally Regulated Production of meso-Zeaxanthin in Chicken Retinal Pigment Epithelium/Choroid and Retina.

Science.gov (United States)

Gorusupudi, Aruna; Shyam, Rajalekshmy; Li, Binxing; Vachali, Preejith; Subhani, Yumna K; Nelson, Kelly; Bernstein, Paul S

2016-04-01

meso-Zeaxanthin is a carotenoid that is rarely encountered in nature outside of the vertebrate eye. It is not a constituent of a normal human diet, yet this carotenoid comprises one-third of the primate macular pigment. In the current study, we undertook a systematic approach to biochemically characterize the production of meso-zeaxanthin in the vertebrate eye. Fertilized White Leghorn chicken eggs were analyzed for the presence of carotenoids during development. Yolk, liver, brain, serum, retina, and RPE/choroid were isolated, and carotenoids were extracted. The samples were analyzed on C-30 or chiral HPLC columns to determine the carotenoid composition. Lutein and zeaxanthin were found in all studied nonocular tissues, but no meso-zeaxanthin was ever detected. Among the ocular tissues, the presence of meso-zeaxanthin was consistently observed starting at embryonic day 17 (E17) in the RPE/choroid, several days before its consistent detection in the retina. If RPE/choroid of an embryo was devoid of meso-zeaxanthin, the corresponding retina was always negative as well. This is the first report of developmentally regulated synthesis of meso-zeaxanthin in a vertebrate system. Our observations suggest that the RPE/choroid is the primary site of meso-zeaxanthin synthesis. Identification of meso-zeaxanthin isomerase enzyme in the developing chicken embryo will facilitate our ability to determine the biochemical mechanisms responsible for production of this unique carotenoid in other higher vertebrates, such as humans.

48 CFR 908.7109 - Fuels and packaged petroleum products.

Science.gov (United States)

2010-10-01

... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Fuels and packaged petroleum products. 908.7109 Section 908.7109 Federal Acquisition Regulations System DEPARTMENT OF ENERGY....7109 Fuels and packaged petroleum products. Acquisitions of fuel and packaged petroleum products by DOE...

Card9-dependent IL-1β regulates IL-22 production from group 3 innate lymphoid cells and promotes colitis-associated cancer.

Science.gov (United States)

Bergmann, Hanna; Roth, Susanne; Pechloff, Konstanze; Kiss, Elina A; Kuhn, Sabine; Heikenwälder, Mathias; Diefenbach, Andreas; Greten, Florian R; Ruland, Jürgen

2017-08-01

Inflammatory bowel diseases (IBD) are key risk factors for the development of colorectal cancer, but the mechanisms that link intestinal inflammation with carcinogenesis are insufficiently understood. Card9 is a myeloid cell-specific signaling protein that regulates inflammatory responses downstream of various pattern recognition receptors and which cooperates with the inflammasomes for IL-1β production. Because polymorphisms in Card9 were recurrently associated with human IBD, we investigated the function of Card9 in a colitis-associated cancer (CAC) model. Card9 -/- mice develop smaller, less proliferative and less dysplastic tumors compared to their littermates and in the regenerating mucosa we detected dramatically impaired IL-1β generation and defective IL-1β controlled IL-22 production from group 3 innate lymphoid cells. Consistent with the key role of immune-derived IL-22 in activating STAT3 signaling during normal and pathological intestinal epithelial cell (IEC) proliferation, Card9 -/- mice also exhibit impaired tumor cell intrinsic STAT3 activation. Our results imply a Card9-controlled, ILC3-mediated mechanism regulating healthy and malignant IEC proliferation and demonstrates a role of Card9-mediated innate immunity in inflammation-associated carcinogenesis. © 2017 The Authors. European Journal of Immunology published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Phosphorylation of Dgk1 Diacylglycerol Kinase by Casein Kinase II Regulates Phosphatidic Acid Production in Saccharomyces cerevisiae.

Science.gov (United States)

Qiu, Yixuan; Hassaninasab, Azam; Han, Gil-Soo; Carman, George M

2016-12-16

In the yeast Saccharomyces cerevisiae, Dgk1 diacylglycerol (DAG) kinase catalyzes the CTP-dependent phosphorylation of DAG to form phosphatidic acid (PA). The enzyme in conjunction with Pah1 PA phosphatase controls the levels of PA and DAG for the synthesis of triacylglycerol and membrane phospholipids, the growth of the nuclear/endoplasmic reticulum membrane, and the formation of lipid droplets. Little is known about how DAG kinase activity is regulated by posttranslational modification. In this work, we examined the phosphorylation of Dgk1 DAG kinase by casein kinase II (CKII). When phosphate groups were globally reduced using nonspecific alkaline phosphatase, Triton X-100-solubilized membranes from DGK1-overexpressing cells showed a 7.7-fold reduction in DAG kinase activity; the reduced enzyme activity could be increased 5.5-fold by treatment with CKII. Dgk1(1-77) expressed heterologously in Escherichia coli was phosphorylated by CKII on a serine residue, and its phosphorylation was dependent on time as well as on the concentrations of CKII, ATP, and Dgk1(1-77). We used site-specific mutagenesis, coupled with phosphorylation analysis and phosphopeptide mapping, to identify Ser-45 and Ser-46 of Dgk1 as the CKII target sites, with Ser-46 being the major phosphorylation site. In vivo, the S46A and S45A/S46A mutations of Dgk1 abolished the stationary phase-dependent stimulation of DAG kinase activity. In addition, the phosphorylation-deficient mutations decreased Dgk1 function in PA production and in eliciting pah1Δ phenotypes, such as the expansion of the nuclear/endoplasmic reticulum membrane, reduced lipid droplet formation, and temperature sensitivity. This work demonstrates that the CKII-mediated phosphorylation of Dgk1 regulates its function in the production of PA. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Phosphorylation of Dgk1 Diacylglycerol Kinase by Casein Kinase II Regulates Phosphatidic Acid Production in Saccharomyces cerevisiae*

Science.gov (United States)

Qiu, Yixuan; Hassaninasab, Azam; Han, Gil-Soo; Carman, George M.

2016-01-01

In the yeast Saccharomyces cerevisiae, Dgk1 diacylglycerol (DAG) kinase catalyzes the CTP-dependent phosphorylation of DAG to form phosphatidic acid (PA). The enzyme in conjunction with Pah1 PA phosphatase controls the levels of PA and DAG for the synthesis of triacylglycerol and membrane phospholipids, the growth of the nuclear/endoplasmic reticulum membrane, and the formation of lipid droplets. Little is known about how DAG kinase activity is regulated by posttranslational modification. In this work, we examined the phosphorylation of Dgk1 DAG kinase by casein kinase II (CKII). When phosphate groups were globally reduced using nonspecific alkaline phosphatase, Triton X-100-solubilized membranes from DGK1-overexpressing cells showed a 7.7-fold reduction in DAG kinase activity; the reduced enzyme activity could be increased 5.5-fold by treatment with CKII. Dgk1(1–77) expressed heterologously in Escherichia coli was phosphorylated by CKII on a serine residue, and its phosphorylation was dependent on time as well as on the concentrations of CKII, ATP, and Dgk1(1–77). We used site-specific mutagenesis, coupled with phosphorylation analysis and phosphopeptide mapping, to identify Ser-45 and Ser-46 of Dgk1 as the CKII target sites, with Ser-46 being the major phosphorylation site. In vivo, the S46A and S45A/S46A mutations of Dgk1 abolished the stationary phase-dependent stimulation of DAG kinase activity. In addition, the phosphorylation-deficient mutations decreased Dgk1 function in PA production and in eliciting pah1Δ phenotypes, such as the expansion of the nuclear/endoplasmic reticulum membrane, reduced lipid droplet formation, and temperature sensitivity. This work demonstrates that the CKII-mediated phosphorylation of Dgk1 regulates its function in the production of PA. PMID:27834677

Nuclear regulation and safety

International Nuclear Information System (INIS)

Hendrie, J.M.

1982-01-01

Nuclear regulation and safety are discussed from the standpoint of a hypothetical country that is in the process of introducing a nuclear power industry and setting up a regulatory system. The national policy is assumed to be in favor of nuclear power. The regulators will have responsibility for economic, reliable electric production as well as for safety. Reactor safety is divided into three parts: shut it down, keep it covered, take out the afterheat. Emergency plans also have to be provided. Ways of keeping the core covered with water are discussed

Advances of orbital gas tungsten arc welding for Brazilian space applications – experimental setup

Directory of Open Access Journals (Sweden)

José A. Orlowski de Garcia

2010-08-01

Full Text Available The present work describes details of the several steps of the technology involved for the orbital Gas Tungsten Arc Welding (GTAW process of pure commercially titanium tubes. These pieces will be used to connect the several components of the propulsion system of the China-Brazilian Satellite CBERS, and is part of the Brazilian aerospace industry development. The implantation involved the steps of environment control; cut and facing of the base metal; cleaning procedures; piece alignment; choice of the type, geometry and installation of the tungsten electrode; system for the pressure of the purge gas; manual tack welding; choice of the welding parameters; and, finally, the qualification of welding procedures. Three distinct welding programs were studied, using pulsed current with increasing speed, continuous current and pulsed current with decreasing amperage levels. The results showed that the high quality criteria required to the aerospace segment is such that usual welding operations must be carefully designed and executed. The three welding developed programs generated welds free of defects and with adequate morphology, allowing to select the condition that better fits the Brazilian aerospace segment, and to be implanted in the welding of the CBERS Satellite Propulsion System.

7 CFR 57.840 - Identification of inedible, unwholesome, or adulterated egg products.

Science.gov (United States)

2010-01-01

... adulterated egg products. 57.840 Section 57.840 Agriculture Regulations of the Department of Agriculture... AGRICULTURE (CONTINUED) REGULATIONS AND STANDARDS UNDER THE AGRICULTURAL MARKETING ACT OF 1946 AND THE EGG PRODUCTS INSPECTION ACT (CONTINUED) INSPECTION OF EGGS (EGG PRODUCTS INSPECTION ACT) Regulations Governing...

Regulation of the csgD promoter by global regulators HN-S, IHF, and RpoS in E. coli O157:H7 isolates

Science.gov (United States)

Introduction: Curli production is essential for the biofilm formation in E. coli and Salmonella. The control of expression of CsgD, the key regulator of the curli operon, is very complex, and has been shown to be regulated by several global regulators and is influenced by various growth and stress...

Glycine regulates the production of pro-inflammatory cytokines in lean and monosodium glutamate-obese mice.

Science.gov (United States)

Alarcon-Aguilar, F J; Almanza-Perez, Julio; Blancas, Gerardo; Angeles, Selene; Garcia-Macedo, Rebeca; Roman, Ruben; Cruz, Miguel

2008-12-03

Fat tissue plays an important role in the regulation of inflammatory processes. Increased visceral fat has been associated with a higher production of cytokines that triggers a low-grade inflammatory response, which eventually may contribute to the development of insulin resistance. In the present study, we investigated whether glycine, an amino acid that represses the expression in vitro of pro-inflammatory cytokines in Kupffer and 3T3-L1 cells, can affect in vivo cytokine production in lean and monosodium glutamate-induced obese mice (MSG/Ob mice). Our data demonstrate that glycine treatment in lean mice suppressed TNF-alpha transcriptional expression in fat tissue, and serum protein levels of IL-6 were suppressed, while adiponectin levels were increased. In MSG/Ob mice, glycine suppressed TNF-alpha and IL-6 gene expression in fat tissue and significantly reduced protein levels of IL-6, resistin and leptin. To determine the role of peroxisome proliferator-activated receptor-gamma (PPAR-gamma) in the modulation of this inflammatory response evoked by glycine, we examined its expression levels in fat tissue. Glycine clearly increased PPAR-gamma expression in lean mice but not in MSG/Ob mice. Finally, to identify alterations in glucose metabolism by glycine, we also examined insulin levels and other biochemical parameters during an oral glucose tolerance test. Glycine significantly reduced glucose tolerance and raised insulin levels in lean but not in obese mice. In conclusion, our findings suggest that glycine suppresses the pro-inflammatory cytokines production and increases adiponectin secretion in vivo through the activation of PPAR-gamma. Glycine might prevent insulin resistance and associated inflammatory diseases.

The challenge of legitimizing spatially differentiated regulation

DEFF Research Database (Denmark)

Thorsøe, Martin Hvarregaard; Graversgaard, Morten; Noe, Egon

2017-01-01

Differentiating regulation is a promising approach to agri-environmental regulation that may potentially reduce the environmental impact of agriculture at the lowest possible costs for the farmers and society, but also possesses a number of challenges. In this article, we explore the challenges...... to the legitimacy of agri-environmental regulation that occurs when the regulatory regime changes from general regulation to differentiated regulation. The analysis is based on a case study of the implementation of the Buffer zone act in Denmark – a regulation that prevents agricultural production in a 10 (later 9......) meter fringe around selected waterbodies. We distinguish between two different ways of legitimizing: Producing knowledge and participation. We conclude that to harvest some of the obvious benefits of differentiated regulation a number of challenges must be resolved, 1) ensuring legitimacy...

Effect of plant growth regulators on production of alpha-linolenic ...

Indian Academy of Sciences (India)

Sujana Kokkiligadda

2017-10-05

Oct 5, 2017 ... MS received 13 October 2016; revised 22 March 2017; accepted 30 May 2017; ... Plant growth regulators; microalgae; Chlorella pyrenoidosa; alpha-linolenic acid. 1. ... the growth period by flocculation method [9] using alum.

What to consider when regulating electronic cigarettes: Pros, cons and unintended consequences.

Science.gov (United States)

Caponnetto, Pasquale; Saitta, Daniela; Sweanor, David; Polosa, Riccardo

2015-06-01

Many public health experts, medical research societies, large health organizations and policy makers have expressed concerns about the increased popularity of electronic cigarettes and have pushed for more restrictive measures ranging from complete bans to tight regulations of these products either as medicines or as tobacco products. But these concerns have never been adequately qualified nor quantified. Without judicious assessment and thorough evaluation, regulations may have unintended consequences that can do more damage than good in public health terms. In this article, we will appraise the existing prominent regulatory frameworks for e-cigarettes, namely, general consumer product, medicinal product and tobacco product regulation, to highlight their pros and cons. Moreover, we provide concrete examples of the unintended consequences which may arise from inappropriate regulatory action. Copyright © 2015 Elsevier B.V. All rights reserved.

[Present regulation on infant and follow-on formula].

Science.gov (United States)

Angulo Lucena, R; Gallego Domínguez, M C; Bentabol Manzanares, A; Jodral Villarejo, M

1995-01-01

The commercialization of breast milk substitutes has had great economic transcendence, sometimes without considering the sanitary and nutritional consequences for the customer. The sanitary authorities have been implied in this matter both in the International and European fields, issuing standards and regulations for the commercialization of breast milk substitutes which have been adopted by the Spanish Regulation. The aim of this paper is comment the regulations that affect foods for breast-feeding and short age children. This report analyzes and comments on the contents of international, european and national regulation on infant and follow-on formula. The regulations about Infant formula and Follow-on formula, banning the term of "humanized milk" and remarking the preference for breast feeding, which could only be substituted by sanitary professionals. This regulation deals with the appropriate chemical composition of these products, qualitative and quantitative. It includes standards for correct labeling, which should contain the appropriate information without idealizing the product Drawings and pictures showing the correct preparation are allowed. It provides for distribution and sales, as well as for correct advertising, which should be under control. This regulation also bans free samples and any other donation to particular customers or sanitary institutions. The present regulation on "Infant and Follow-on formulas" pursues the adequate nutrition of breast-feeding and short age children, being the protection of this kind of customers everyone's responsibility.

7 CFR 301.53-2 - Regulated articles.

Science.gov (United States)

2010-01-01

... 7 Agriculture 5 2010-01-01 2010-01-01 false Regulated articles. 301.53-2 Section 301.53-2... articles. The following are regulated articles: (a) The emerald ash borer; firewood of all hardwood (non... article, product, or means of conveyance not listed in paragraph (a) of this section may be designated as...

Sustainable recycling of automotive products in China: Technology and regulation

Science.gov (United States)

Chen, Ming

2006-08-01

The Chinese economy is growing rapidly, but accompanyingsuch growth are issues of environmental protection and social inequity which must be addressed. With the Automobile Industry Development Policy and the Motor Vehicle Product Recovery Technology Policy, an automobile products recoverability target has been established and will be incorporated into an automobile products authentication management system in China. By 2010, for all end-of-life automobile products, reuse and recovery shall be increased to a minimum of 85% by average weight per vehicle, and the use of lead, mercury, cadmium, and hexavalent chromium is prohibited. This paper will address the sustainable recycling of Chinese automobile products within the period of 2006 2010.

This Article Makes You Smarter! (Or, Regulating Health and Wellness Claims).

Science.gov (United States)

Duranske, Sarah

2017-03-01

Information has power - to inspire, to transform, and to harm. Recent technological advancements have enabled the creation of products that offer consumers direct access to a level of personal health information unprecedented in history. But how are we to balance the promise of health and wellness information with its risks? Two agencies are tasked with protecting consumers from false claims of health products: the FDA and the FTC. This Article investigates if they are up to the task. In part a study of agency policymaking choices, and in part a prescription for more thoughtful and focused regulation, this Article compares both intra-agency and inter-agency regulation of informational health and wellness products. Certain procedural and substantive characteristics of FDA regulation are unsuited to informational health and wellness products, rendering comprehensive regulation by the FDA unrealistic. This gap creates an opportunity for the FTC to use its distinct and well-tailored enforcement tools to police harmful product claims that escape the FDA's purview. I posit that by tailoring the FDA's responsibility and sustaining the FTC's engagement with health claims, the agencies can dovetail into a cohesive and comprehensive regulatory regime.

Regulated software meets DevOps

DEFF Research Database (Denmark)

Laukkarinen, Teemu; Kuusinen, Kati; Mikkonen, Tommi

2018-01-01

Context: Regulatory authorities require proofs from critical systems manufacturers that the software in their products is developed in accordance to prescribed development practices before accepting the product to the markets. This is challenging when using DevOps, where continuous integration...... and deployment are the default practices, which are not a good match with the regulatory software development standards. Objective: We aim to bring DevOps and regulated software development closer to each other. First, we want to make it easier for developers to develop regulated software with tools...... and practices they are familiar with. Second, we want to allow regulatory authorities to build confidence on solutions provided by manufacturers by defining a mapping between DevOps and regulatory software development. Method: We performed a literature survey and created research suggestions using exploratory...

Capital regulation: Less really can be more when incentives are socially aligned. Comments on Richard J. Herring "The Evolving Complexity of Capital Regulation". "The Interplay of Financial Regulations, Resilience, and Growth", Federal Reserve Bank of Philadelphia June 16-17, 2016

OpenAIRE

Hughes, Joseph P.

2017-01-01

Capital regulation has become increasingly complex as the largest financial institutions arbitrage differences in requirements across financial products to increase expected return for any given amount of regulatory capital, as financial regulators amend regulations to reduce arbitrage opportunities, and as financial institutions innovate to escape revised regulations - a regulatory dialectic. This increasing complexity makes monitoring bank risk-taking by markets and regulators more difficul...

77 FR 48992 - Tobacco Product Manufacturing Facility Visits

Science.gov (United States)

2012-08-15

... manufacture, preproduction design validation (including a process to assess the performance of a tobacco... about the manufacturing practices and processes unique to your facility and regulated tobacco products... process, package, label, and distribute different types of regulated tobacco products (cigarettes...

Becoming a law to regulate the production and use of chemicals: the problems of technical regulation

Directory of Open Access Journals (Sweden)

О. С. Бабенко

2013-10-01

Full Text Available The system of legal regulation of the management of chemicals in Ukraine, although it has become a development, but is very imperfect. The main problems concerning technical legislation, the resolution of which will improve the systems of standardization and certification focused on European practice.

PR-957, a selective inhibitor of immunoproteasome subunit low-MW polypeptide 7, attenuates experimental autoimmune neuritis by suppressing Th17-cell differentiation and regulating cytokine production.

Science.gov (United States)

Liu, Haijie; Wan, Chunxiao; Ding, Yanan; Han, Ranran; He, Yating; Xiao, Jinting; Hao, Junwei

2017-04-01

Experimental autoimmune neuritis (EAN) is a CD4 + T-cell-mediated autoimmune inflammatory demyelinating disease of the peripheral nervous system. It has been replicated in an animal model of human inflammatory demyelinating polyradiculoneuropathy, Guillain-Barré syndrome. In this study, we evaluated the therapeutic efficacy of a selective inhibitor of the immunoproteasome subunit, low-MW polypeptide 7 (PR-957) in rats with EAN. Our results showed that PR-957 significantly delayed onset day, reduced severity and shortened duration of EAN, and alleviated demyelination and inflammatory infiltration in sciatic nerves. In addition to significantly regulating expression of the cytokine profile, PR-957 treatment down-regulated the proportion of proinflammatory T-helper (T h )17 cells in sciatic nerves and spleens of rats with EAN. Data presented show the role of PR-957 in the signal transducer and activator of transcription 3 (STAT3) pathway. PR-957 not only decreased expression of IL-6 and IL-23 but also led to down-regulation of STAT3 phosphorylation in CD4 + T cells. Regulation of the STAT3 pathway led to a reduction in retinoid-related orphan nuclear receptor γ t and IL-17 production. Furthermore, reduction of STAT3 phosphorylation may have directly suppressed T h 17-cell differentiation. Therefore, our study demonstrates that PR-957 could potently alleviate inflammation in rats with EAN and that it may be a likely candidate for treating Guillain-Barré syndrome.-Liu, H., Wan, C., Ding, Y., Han, R., He, Y., Xiao, J., Hao, J. PR-957, a selective inhibitor of immunoproteasome subunit low-MW polypeptide 7, attenuates experimental autoimmune neuritis by suppressing T h 17-cell differentiation and regulating cytokine production. © FASEB.

Group 2 innate lymphoid cell production of IL-5 is regulated by NKT cells during influenza virus infection.

Directory of Open Access Journals (Sweden)

Stacey Ann Gorski

2013-09-01

Full Text Available Respiratory virus infections, such as influenza, typically induce a robust type I (pro-inflammatory cytokine immune response, however, the production of type 2 cytokines has been observed. Type 2 cytokine production during respiratory virus infection is linked to asthma exacerbation; however, type 2 cytokines may also be tissue protective. Interleukin (IL-5 is a prototypical type 2 cytokine that is essential for eosinophil maturation and egress out of the bone marrow. However, little is known about the cellular source and underlying cellular and molecular basis for the regulation of IL-5 production during respiratory virus infection. Using a mouse model of influenza virus infection, we found a robust transient release of IL-5 into infected airways along with a significant and progressive accumulation of eosinophils into the lungs, particularly during the recovery phase of infection, i.e. following virus clearance. The cellular source of the IL-5 was group 2 innate lymphoid cells (ILC2 infiltrating the infected lungs. Interestingly, the progressive accumulation of eosinophils following virus clearance is reflected in the rapid expansion of c-kit⁺ IL-5 producing ILC2. We further demonstrate that the enhanced capacity for IL-5 production by ILC2 during recovery is concomitant with the enhanced expression of the IL-33 receptor subunit, ST2, by ILC2. Lastly, we show that NKT cells, as well as alveolar macrophages (AM, are endogenous sources of IL-33 that enhance IL-5 production from ILC2. Collectively, these results reveal that c-kit⁺ ILC2 interaction with IL-33 producing NKT and AM leads to abundant production of IL-5 by ILC2 and accounts for the accumulation of eosinophils observed during the recovery phase of influenza infection.

Characterization of the SigD regulon of C. difficile and its positive control of toxin production through the regulation of tcdR.

Directory of Open Access Journals (Sweden)

Imane El Meouche

Full Text Available Clostridium difficile intestinal disease is mediated largely by the actions of toxins A (TcdA and B (TcdB, whose production occurs after the initial steps of colonization involving different surface or flagellar proteins. In B. subtilis, the sigma factor SigD controls flagellar synthesis, motility, and vegetative autolysins. A homolog of SigD encoding gene is present in the C.difficile 630 genome. We constructed a sigD mutant in C. difficile 630 ∆erm to analyze the regulon of SigD using a global transcriptomic approach. A total of 103 genes were differentially expressed between the wild-type and the sigD mutant, including genes involved in motility, metabolism and regulation. In addition, the sigD mutant displayed decreased expression of genes involved in flagellar biosynthesis, and also of genes encoding TcdA and TcdB as well as TcdR, the positive regulator of the toxins. Genomic analysis and RACE-PCR experiments allowed us to characterize promoter sequences of direct target genes of SigD including tcdR and to identify the SigD consensus. We then established that SigD positively regulates toxin expression via direct control of tcdR transcription. Interestingly, the overexpression of FlgM, a putative anti-SigD factor, inhibited the positive regulation of motility and toxin synthesis by SigD. Thus, SigD appears to be the first positive regulator of the toxin synthesis in C. difficile.

Advanced glycation end products-modified proteins and oxidized LDL mediate down-regulation of leptin in mouse adipocytes via CD36

International Nuclear Information System (INIS)

Unno, Yuka; Sakai, Masakazu; Sakamoto, Yu-ichiro; Kuniyasu, Akihiko; Nakayama, Hitoshi; Nagai, Ryoji; Horiuchi, Seikoh

2004-01-01

Advanced glycation end products (AGE)-modified proteins as well as oxidized-LDL (Ox-LDL) undergo receptor-mediated endocytosis by CHO cells overexpressing CD36, a member of class B scavenger receptor family. The purpose of the present study was to examine the effects of glycolaldehyde-modified BSA (GA-BSA) as an AGE-ligand and Ox-LDL on leptin expression in adipocytes. GA-BSA decreased leptin expression at both protein and mRNA levels in 3T3-L1 adipocytes and mouse epididymal adipocytes. Ox-LDL showed a similar inhibitory effect on leptin expression in 3T3-L1 adipocytes, which effect was protected by N-acetylcysteine, a reactive oxygen species (ROS) inhibitor. Binding of 125 I-GA-BSA or 125 I-Ox-LDL to 3T3-L1 adipocytes and subsequent endocytic degradation were inhibited by a neutralizing anti-CD36 antibody. Furthermore, this antibody also suppressed Ox-LDL-induced leptin down-regulation. These results clarify that the interaction of GA-BSA and Ox-LDL with CD36 leads to down-regulation of leptin expression via ROS system(s) in 3T3-L1 adipocytes, suggesting that a potential link of AGE- and/or Ox-LDL-induced leptin down-regulation might be linked to insulin-sensitivity in metabolic syndrome

Regulation of Meiotic Recombination

Energy Technology Data Exchange (ETDEWEB)

Gregory p. Copenhaver

2011-11-09

Meiotic recombination results in the heritable rearrangement of DNA, primarily through reciprocal exchange between homologous chromosome or gene conversion. In plants these events are critical for ensuring proper chromosome segregation, facilitating DNA repair and providing a basis for genetic diversity. Understanding this fundamental biological mechanism will directly facilitate trait mapping, conventional plant breeding, and development of genetic engineering techniques that will help support the responsible production and conversion of renewable resources for fuels, chemicals, and the conservation of energy (1-3). Substantial progress has been made in understanding the basal recombination machinery, much of which is conserved in organisms as diverse as yeast, plants and mammals (4, 5). Significantly less is known about the factors that regulate how often and where that basal machinery acts on higher eukaryotic chromosomes. One important mechanism for regulating the frequency and distribution of meiotic recombination is crossover interference - or the ability of one recombination event to influence nearby events. The MUS81 gene is thought to play an important role in regulating the influence of interference on crossing over. The immediate goals of this project are to use reverse genetics to identify mutants in two putative MUS81 homologs in the model plant Arabidopsis thaliana, characterize those mutants and initiate a novel forward genetic screen for additional regulators of meiotic recombination. The long-term goal of the project is to understand how meiotic recombination is regulated in higher eukaryotes with an emphasis on the molecular basis of crossover interference. The ability to monitor recombination in all four meiotic products (tetrad analysis) has been a powerful tool in the arsenal of yeast geneticists. Previously, the qrt mutant of Arabidopsis, which causes the four pollen products of male meiosis to remain attached, was developed as a facile system

The R2R3-MYB-like regulatory factor EOBI, acting downstream of EOBII, regulates scent production by activating ODO1 and structural scent-related genes in petunia.

Science.gov (United States)

Spitzer-Rimon, Ben; Farhi, Moran; Albo, Boaz; Cna'ani, Alon; Ben Zvi, Michal Moyal; Masci, Tania; Edelbaum, Orit; Yu, Yixun; Shklarman, Elena; Ovadis, Marianna; Vainstein, Alexander

2012-12-01

Flower scent is a highly dynamic trait, under developmental, spatial, and diurnal regulation. The mechanism governing scent production is only beginning to be unraveled. In petunia (Petunia hybrida), EMISSION OF BENZENOIDS II (EOBII) controls transcription of both the shikimate pathway-regulating MYB factor ODORANT1 (ODO1) and phenylpropanoid scent-related structural genes. A promoter-activation screen identified an R2R3-MYB-like regulatory factor of phenylpropanoid volatile biosynthesis acting downstream of EOBII, designated EOBI. EOBI silencing led to downregulation of ODO1 and numerous structural scent-related genes from both the shikimate and phenylpropanoid pathways. The ability of EOBI to directly activate ODO1, as revealed by electrophoretic mobility shift assay and yeast one-hybrid analysis, place EOBI upstream of ODO1 in regulating substrate availability for volatile biosynthesis. Interestingly, ODO1-silenced transgenic petunia flowers accumulated higher EOBI transcript levels than controls, suggesting a complex feedback loop between these regulatory factors. The accumulation pattern of EOBI transcript relative to EOBII and ODO1, and the effect of up/downregulation of EOBII on transcript levels of EOBI and ODO1, further support these factors' hierarchical relationships. The dependence of scent production on EOBI expression and its direct interaction with both regulatory and structural genes provide evidence for EOBI's wide-ranging involvement in the production of floral volatiles.

75 FR 71344 - Uniform Compliance Date for Food Labeling Regulations

Science.gov (United States)

2010-11-23

.... FSIS-2010-0031] RIN 0583-AD Uniform Compliance Date for Food Labeling Regulations AGENCY: Food Safety... regulations that require changes in the labeling of meat and poultry food products. Many meat and poultry... for new food labeling regulations is consistent with FDA's approach in this regard. FDA is also...

The myeloid receptor PILRβ mediates the balance of inflammatory responses through regulation of IL-27 production.

Directory of Open Access Journals (Sweden)

Cristina M Tato

Full Text Available Paired immunoglobulin-like receptors beta, PILRβ, and alpha, PILRα, are related to the Siglec family of receptors and are expressed primarily on cells of the myeloid lineage. PILRβ is a DAP12 binding partner expressed on both human and mouse myeloid cells. The potential ligand, CD99, is found on many cell types, such as epithelial cells where it plays a role in migration of immune cells to sites of inflammation. Pilrb deficient mice were challenged with the parasite Toxoplasma gondii in two different models of infection induced inflammation; one involving the establishment of chronic encephalitis and a second mimicking inflammatory bowel disease in order to understand the potential role of this receptor in persistent inflammatory responses. It was found that in the absence of activating signals from PILRβ, antigen-presenting cells (APCs produced increased amounts of IL-27, p28 and promoted IL-10 production in effector T cells. The sustained production of IL-27 led ultimately to enhanced survival after challenge due to dampened immune pathology in the gut. Similar protection was also observed in the CNS during chronic T. gondii infection after i.p. challenge again providing evidence that PILRβ is important for regulating aberrant inflammatory responses.

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

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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.

In vitro production of growth regulators and phosphatase activity by ...

African Journals Online (AJOL)

The result showed that the population levels of phosphobacteria were higher in the rhizosphere soil of groundnut plant. Further, all the strains of phosphobacteria were able to produce phytohormones and phosphatase enzyme under in vitro conditions. Keywords: In vitro, phosphobacteria, growth regulators ...

Regulation and Control of Hazardous Wastes

OpenAIRE

Hans W. Gottinger

1994-01-01

Hazardous waste regulations require disposal in approved dumpsites, where environmental consequences are minimal but entry may be privately very costly. Imperfect policing of regulations makes the socially more costly option illicit disposal preferable form the perspective of the private decision maker. The existence of the waste disposal decision, its economic nature, production independence, and the control over environmental damage are key issues in the economics of hazardous waste managem...

Biosynthesis of the antimicrobial cyclic lipopeptides nunamycin and nunapeptin by Pseudomonas fluorescens strain In5 is regulated by the LuxR-type transcriptional regulator NunF

DEFF Research Database (Denmark)

Hennessy, Rosanna Catherine; Phippen, Christopher; Nielsen, Kristian Fog

2017-01-01

-producing pseudomonads except for the border regions where putative LuxR-type regulators are located. This study focuses on understanding the regulatory role of the LuxR-type-encoding gene nunF in CLP production of P. fluorescens In5. Functional analysis of nunF coupled with liquid chromatography-high-resolution mass...... spectrometry (LC-HRMS) showed that CLP biosynthesis is regulated by nunF. Quantitative real-time PCR analysis indicated that transcription of the NRPS genes catalyzing CLP production is strongly reduced when nunF is mutated indicating that nunF is part of the nun-nup regulon. Swarming and biofilm formation...... that environmental elicitors may also influence nunF expression which upon activation regulates nunamycin and nunapeptin production required for the growth inhibition of phytopathogens....

Future directions in water quality regulations

International Nuclear Information System (INIS)

Pontius, F.W.

1997-01-01

The Safe Drinking Water Act amendments of 1996 have imposed new requirements on the US Environmental Protection Agency (USEPA) to establish drinking water regulations. The regulatory process has been revised and now requires the use of sound science. Costs, benefits, and competing risks may also be considered. Current regulations for fluoride, volatile organic chemicals, total coliforms, surface water treatment, Phase 2 and Phase 5 synthetic organic and inorganic contaminants, and lead and copper remain basically unchanged. New deadlines are established for the regulation of arsenic, sulfate, radon, disinfectants and disinfection by-products, enhanced surface water treatment, and groundwater disinfection

Human ketone body production and utilization studied using tracer techniques: Regulation by free fatty acids, insulin, catecholamines, and thyroid hormones

Energy Technology Data Exchange (ETDEWEB)

Keller, U.; Lustenberger, M.; Mueller-Brand, J.G.; Gerber, P.P.; Stauffacher, W.

1989-05-01

Ketone body concentrations fluctuate markedly during physiological and pathological conditions. Tracer techniques have been developed in recent years to study production, utilization, and the metabolic clearance rate of ketone bodies. This review describes data on the roles of insulin, catecholamines, and thyroid hormones in the regulation of ketone body kinetics. The data indicate that insulin lowers ketone body concentrations by three independent mechanisms: first, it inhibits lipolysis, and thus lowers free fatty acid availability for ketogenesis; second, it restrains ketone body production within the liver; third, it enhances peripheral ketone body utilization. To assess these effects in humans in vivo, experimental models were developed to study insulin effects with controlled concentrations of free fatty acids, insulin, glucagon, and ketone bodies. Presently available data also support an important role of catecholamines in increasing ketone body concentrations. Evidence was presented that norepinephrine increases ketogenesis not only by stimulating lipolysis, and thus releasing free fatty acids, but also by increasing intrahepatic ketogenesis. Thyroid hormone availability was associated with lipolysis and ketogenesis. Ketone body concentrations after an overnight fast were only modestly elevated in hyperthyroidism resulting from increased peripheral ketone body clearance. There was a significant correlation between serum triiodothyronine levels and the ketone body metabolic clearance rate. Thus, ketone body homeostasis in human subjects resulted from the interaction of hormones such as insulin, catecholamines, and thyroid hormones regulating lipolysis, intrahepatic ketogenesis, and peripheral ketone body utilization. 58 references.

Human ketone body production and utilization studied using tracer techniques: Regulation by free fatty acids, insulin, catecholamines, and thyroid hormones

International Nuclear Information System (INIS)

Keller, U.; Lustenberger, M.; Mueller-Brand, J.G.; Gerber, P.P.; Stauffacher, W.

1989-01-01

Ketone body concentrations fluctuate markedly during physiological and pathological conditions. Tracer techniques have been developed in recent years to study production, utilization, and the metabolic clearance rate of ketone bodies. This review describes data on the roles of insulin, catecholamines, and thyroid hormones in the regulation of ketone body kinetics. The data indicate that insulin lowers ketone body concentrations by three independent mechanisms: first, it inhibits lipolysis, and thus lowers free fatty acid availability for ketogenesis; second, it restrains ketone body production within the liver; third, it enhances peripheral ketone body utilization. To assess these effects in humans in vivo, experimental models were developed to study insulin effects with controlled concentrations of free fatty acids, insulin, glucagon, and ketone bodies. Presently available data also support an important role of catecholamines in increasing ketone body concentrations. Evidence was presented that norepinephrine increases ketogenesis not only by stimulating lipolysis, and thus releasing free fatty acids, but also by increasing intrahepatic ketogenesis. Thyroid hormone availability was associated with lipolysis and ketogenesis. Ketone body concentrations after an overnight fast were only modestly elevated in hyperthyroidism resulting from increased peripheral ketone body clearance. There was a significant correlation between serum triiodothyronine levels and the ketone body metabolic clearance rate. Thus, ketone body homeostasis in human subjects resulted from the interaction of hormones such as insulin, catecholamines, and thyroid hormones regulating lipolysis, intrahepatic ketogenesis, and peripheral ketone body utilization. 58 references

High efficiency cell-recycle continuous sodium gluconate production by Aspergillus niger using on-line physiological parameters association analysis to regulate feed rate rationally.

Science.gov (United States)

Lu, Fei; Li, Chao; Wang, Zejian; Zhao, Wei; Chu, Ju; Zhuang, Yingping; Zhang, Siliang

2016-11-01

In this paper, a system of cell-recycle continuous fermentation for sodium gluconate (SG) production by Aspergillus niger (A. niger) was established. Based on initial continuous fermentation result (100.0h) with constant feed rate, an automatic feedback strategy to regulate feed rate using on-line physiological parameters (OUR and DO) was proposed and applied successfully for the first time in the improved continuous fermentation (240.5h). Due to less auxiliary time, highest SG production rate (31.05±0.29gL(-1)h(-1)) and highest yield (0.984±0.067molmol(-1)), overall SG production capacity (975.8±5.8gh(-1)) in 50-L fermentor of improved continuous fermentation increased more than 300.0% compared to that of batch fermentation. Improvement of mass transfer and dispersed mycelia morphology were the two major reasons responsible for the high SG production rate. This system had been successfully applied to industrial fermentation and SG production was greatly improved. Copyright © 2016 Elsevier Ltd. All rights reserved.

No sisyphean task: how the FDA can regulate electronic cigarettes.

Science.gov (United States)

Paradise, Jordan

2013-01-01

The adverse effects of smoking have fostered a natural market for smoking cessation and smoking reduction products. Smokers attempting to quit or reduce consumption have tried everything: "low" or "light" cigarettes; nicotine-infused chewing gum, lozenges, and lollipops; dermal patches; and even hypnosis. The latest craze in the quest to find a safer source of nicotine is the electronic cigarette. Electronic cigarettes (e-cigarettes) have swept the market, reaching a rapidly expanding international consumer base. Boasting nicotine delivery and the tactile feel of a traditional cigarette without the dozens of other chemical constituents that contribute to carcinogenicity, e-cigarettes are often portrayed as less risky, as a smoking reduction or even a complete smoking cessation product, and perhaps most troubling for its appeal to youth, as a flavorful, trendy, and convenient accessory. The sensationalism associated with e-cigarettes has spurred outcry from health and medical professional groups, as well as the Food and Drug Administration (FDA), because of the unknown effects on public health. Inhabiting a realm of products deemed "tobacco products" under recent 2009 legislation, e-cigarettes pose new challenges to FDA regulation because of their novel method of nicotine delivery, various mechanical and electrical parts, and nearly nonexistent safety data. Consumer use, marketing and promotional claims, and technological characteristics of e-cigarettes have also raised decades old questions of when the FDA can assert authority over products as drugs or medical devices. Recent case law restricting FDA enforcement efforts against e-cigarettes further confounds the distinction among drugs and medical devices, emerging e-cigarette products, and traditional tobacco products such as cigarettes, cigars, and smokeless tobacco. This Article investigates the e-cigarette phenomenon in the wake of the recently enacted Family Smoking Prevention and Tobacco Control Act of 2009