Exclusions, exemptions and low specific activity material in the 1996 edition of the IAEA regulations for the safe transport of radioactive material

International Nuclear Information System (INIS)

Baekelandt, L.

1997-01-01

Exclusions and exemptions, total as well as partial, have always been part of the IAEA transport regulations, but these provisions were dispersed over various sections. In the 1996 edition of these regulations, some of these exclusions and exemptions have been kept unchanged, others have been changed and also, new ones have been added. This paper gives an overview of the exclusions and exemptions in the 1996 edition, the most important change with respect to the previous edition being the departure from the single exemption value of 70 Bq/g for all radionuclides to the radionuclide specific exemption values as specified in the IAEA Basic Safety Standards. As a consequence of this change, a new category of Low Specific Activity (LSA) material has been introduced. This paper also discusses the rationale of these changes to the regulations. (author)

A walk into the LuxR regulators of Actinobacteria: phylogenomic distribution and functional diversity.

Directory of Open Access Journals (Sweden)

Catarina Lopes Santos

Full Text Available LuxR regulators are a widely studied group of bacterial helix-turn-helix (HTH transcription factors involved in the regulation of many genes coding for important traits at an ecological and medical level. This regulatory family is particularly known by their involvement in quorum-sensing (QS mechanisms, i.e., in the bacterial ability to communicate through the synthesis and binding of molecular signals. However, these studies have been mainly focused on gram-negative organisms, and the presence of LuxR regulators in the gram-positive Actinobacteria phylum is still poorly explored. In this manuscript, the presence of LuxR regulators among Actinobacteria was assayed using a domain-based strategy. A total of 991 proteins having one LuxR domain were identified in 53 genome-sequenced actinobacterial species, of which 59% had an additional domain. In most cases (53% this domain was REC (receiver domain, suggesting that LuxR regulators in Actinobacteria may either function as single transcription factors or as part of two-component systems. The frequency, distribution and evolutionary stability of each of these sub-families of regulators was analyzed and contextualized regarding the ecological niche occupied by each organism. The results show that the presence of extra-domains in the LuxR-regulators was likely driven by a general need to physically uncouple the signal sensing from the signal transduction. Moreover, the total frequency of LuxR regulators was shown to be dependent on genetic, metabolic and ecological variables. Finally, the functional annotation of the LuxR regulators revealed that the bacterial ecological niche has biased the specialization of these proteins. In the case of pathogens, our results suggest that LuxR regulators can be involved in virulence and are therefore promising targets for future studies in the health-related biotechnology field.

A Walk into the LuxR Regulators of Actinobacteria: Phylogenomic Distribution and Functional Diversity

Science.gov (United States)

Santos, Catarina Lopes; Correia-Neves, Margarida; Moradas-Ferreira, Pedro; Mendes, Marta Vaz

2012-01-01

LuxR regulators are a widely studied group of bacterial helix-turn-helix (HTH) transcription factors involved in the regulation of many genes coding for important traits at an ecological and medical level. This regulatory family is particularly known by their involvement in quorum-sensing (QS) mechanisms, i.e., in the bacterial ability to communicate through the synthesis and binding of molecular signals. However, these studies have been mainly focused on Gram-negative organisms, and the presence of LuxR regulators in the Gram-positive Actinobacteria phylum is still poorly explored. In this manuscript, the presence of LuxR regulators among Actinobacteria was assayed using a domain-based strategy. A total of 991 proteins having one LuxR domain were identified in 53 genome-sequenced actinobacterial species, of which 59% had an additional domain. In most cases (53%) this domain was REC (receiver domain), suggesting that LuxR regulators in Actinobacteria may either function as single transcription factors or as part of two-component systems. The frequency, distribution and evolutionary stability of each of these sub-families of regulators was analyzed and contextualized regarding the ecological niche occupied by each organism. The results show that the presence of extra-domains in the LuxR-regulators was likely driven by a general need to physically uncouple the signal sensing from the signal transduction. Moreover, the total frequency of LuxR regulators was shown to be dependent on genetic, metabolic and ecological variables. Finally, the functional annotation of the LuxR regulators revealed that the bacterial ecological niche has biased the specialization of these proteins. In the case of pathogens, our results suggest that LuxR regulators can be involved in virulence and are therefore promising targets for future studies in the health-related biotechnology field. PMID:23056438

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.

Trout Stream Special Regulations

Data.gov (United States)

Minnesota Department of Natural Resources — This layer shows Minnesota trout streams that have a special regulation as described in the 2006 Minnesota Fishing Regulations. Road crossings were determined using...

77 FR 30588 - R.J. Corman Railroad Company/Pennsylvania Lines Inc.-Construction and Operation Exemption-In...

Science.gov (United States)

2012-05-23

... DEPARTMENT OF TRANSPORTATION Surface Transportation Board [Docket No. FD 35116] R.J. Corman Railroad Company/Pennsylvania Lines Inc.-- Construction and Operation Exemption--In Clearfield County, PA.... 10901 for R.J. Corman Railroad Company/Pennsylvania Lines Inc. (RJCP) to construct and operate 10.8...

Exclusion, exemption and clearance in the mining and minerals industry - A review of the concepts from a South African perspective

International Nuclear Information System (INIS)

Selby, J.H.

1997-01-01

The risks from mining and processing of ores is reviewed on a generic basis with particular reference to some of the confusions which can arise due to lack of consistency or common logic in the use of exclusion, exemption and clearance. The difference in exclusion and exemption are challenged by comparing doses received in high background radiation areas and the doses received from a mining practice. The common principle of risk to the human species is not applied consistently. The differences between IAEA recommendations and local regulatory conditions are compared, and the use of exemption levels as clearance levels is considered. A case study on management of mine tailings is presented with special focus on the use of clearance levels. In all areas of review the interpretation of regulation is subject to confusion resulting from inconsistencies which can distort free market economics. (author)

76 FR 31415 - Federal Acquisition Regulation; Buy American Exemption for Commercial Information Technology...

Science.gov (United States)

2011-05-31

... 9000-AL62 Federal Acquisition Regulation; Buy American Exemption for Commercial Information Technology... from the Buy American Act for acquisition of information technology that is a commercial item. DATES: Effective Date: May 31, 2011. FOR FURTHER INFORMATION CONTACT: Ms. Cecelia L. Davis, Procurement Analyst, at...

21 CFR 1002.50 - Special exemptions.

Science.gov (United States)

2010-04-01

... and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... exemptions. (a) Manufacturers of electronic products may submit to the Director a request, together with... following criteria: (1) The products cannot emit electronic product radiation in sufficient intensity or of...

Basis for applying for exemption according to species protection regulation. Final repository for spent nuclear fuel at Forsmark

International Nuclear Information System (INIS)

2011-02-01

SKB will submit applications for permits and admissibility under the Environmental Act and under the Nuclear Activities Act to construct and operate a disposal facility for spent nuclear fuel at Forsmark. In the final repository the spent nuclear fuel from Swedish nuclear power plants is placed in order to protect human health and the environment against harmful effects of ionizing radiation. Construction and operation of the disposal facility in Forsmark will make an impact, give effects and consequences for the natural environment. Utilization of land for the construction of the facility and the impact on ground water as a result of groundwater drainage is expected to have negative consequences for the species included in species protection regulation. Thus, the planned activity require exemption from species protection regulation (SFS 2007:845). The purpose of this document is to provide a basis for an application for exemption under 14 paragraph species protection regulation from the prohibitions of 4, 6, 7 and 8 paragraph species protection regulation. A basis for the exemption application is that the proposed activity is considered to have an 'overriding public interest' prescribed in 14 paragraph species protection regulation. The document reports the impact, effects and consequences of the planned activities on species covered in the species protection regulation. The impact on protected species can be divided into two categories: - Direct effects on protected species and their habitats by utilization of the land. - Indirect effects on protected species and their habitats in the drainage of groundwater and the effect on groundwater levels. The document also includes a description of planned actions to prevent, restrict and compensate for the effects and consequences that the activity may cause. By applying for an exemption under 14 paragraph species protection regulation in a separate order from the application for permit according to chapters 9 and 11

The exemption from the requirement of registration and/or licensing of some sources. machines and devices emitting ionizing and /or on ionizing radiation: a proposed draft for Israeli regulations

Energy Technology Data Exchange (ETDEWEB)

Schlesinger, T; Margaliot, M [Israel Atomic Energy Commission, Yavne (Israel). Soreq Nuclear Research Center

1997-11-16

The licensing and authorization of the import, purchase, distribution, transportation and application of radioactive materials and devices emitting ionizing and/or non-ionizing radiation are carried out in Israel by the Ministries of the Environment and of Health. The legal basis for file authority of these Ministries in radiation protection matters is file {sup P}harmacists Regulation- Radioactive Elements and Products Thereof, 1981 (revision 1994) (PRREPT). Licenses are issued by the Chief Radiation Executive (CUE) appointed by the Minister of the Environment and the Minister of Health. The Regulations include a clause which enables the CUE to exempt certain amounts of radioactive materials from file requirements laid down in the PRREPT. The exemption clause is general and does not indicate the types and amounts of radioactive material may be exempted. The proposed draft Israeli regulations are related to exemption of some sources, machines and devices emitting ionizing and non-ionizing radiation, wife a suggestion to extend file above mentioned exemption clause to include some machines and devices and to provide an explicit and detailed list of materials, sources and devices to be exempted. Among these are the following: (authors)

The exemption from the requirement of registration and/or licensing of some sources. machines and devices emitting ionizing and /or on ionizing radiation: a proposed draft for Israeli regulations

International Nuclear Information System (INIS)

Schlesinger, T.; Margaliot, M.

1997-01-01

The licensing and authorization of the import, purchase, distribution, transportation and application of radioactive materials and devices emitting ionizing and/or non-ionizing radiation are carried out in Israel by the Ministries of the Environment and of Health. The legal basis for file authority of these Ministries in radiation protection matters is file P harmacists Regulation- Radioactive Elements and Products Thereof, 1981 (revision 1994) (PRREPT). Licenses are issued by the Chief Radiation Executive (CUE) appointed by the Minister of the Environment and the Minister of Health. The Regulations include a clause which enables the CUE to exempt certain amounts of radioactive materials from file requirements laid down in the PRREPT. The exemption clause is general and does not indicate the types and amounts of radioactive material may be exempted. The proposed draft Israeli regulations are related to exemption of some sources, machines and devices emitting ionizing and non-ionizing radiation, wife a suggestion to extend file above mentioned exemption clause to include some machines and devices and to provide an explicit and detailed list of materials, sources and devices to be exempted. Among these are the following: (authors)

29 CFR 570.72 - Exemptions.

Science.gov (United States)

2010-07-01

... 29 Labor 3 2010-07-01 2010-07-01 false Exemptions. 570.72 Section 570.72 Labor Regulations Relating to Labor (Continued) WAGE AND HOUR DIVISION, DEPARTMENT OF LABOR REGULATIONS CHILD LABOR... the Employment of Children Below the Age of 16 § 570.72 Exemptions. (a) Student-learners. The findings...

48 CFR 2804.506 - Exemptions.

Science.gov (United States)

2010-10-01

... 48 Federal Acquisition Regulations System 6 2010-10-01 2010-10-01 true Exemptions. 2804.506 Section 2804.506 Federal Acquisition Regulations System DEPARTMENT OF JUSTICE General ADMINISTRATIVE MATTERS Electronic Commerce in Contracting 2804.506 Exemptions. Pursuant to FAR 4.506(b), all...

43 CFR 24.7 - Exemptions.

Science.gov (United States)

2010-10-01

... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Exemptions. 24.7 Section 24.7 Public Lands...-FEDERAL RELATIONSHIPS § 24.7 Exemptions. (a) Exempted from this policy are the following: (1) The control and regulation by the United States, in the area in which an international convention or treaty...

76 FR 30890 - Special Local Regulations; Sabine River, Orange, TX

Science.gov (United States)

2011-05-27

...-AA08 Special Local Regulations; Sabine River, Orange, TX AGENCY: Coast Guard, DHS. ACTION: Notice of... the Port Arthur Captain of the Port Zone on the Sabine River, Orange, Texas on September 24-25, 2011... race in conjunction with the Orange, TX S.P.O.R.T. boat races. The powerboat race and associated...

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.

29 CFR 2580.412-30 - Conditions of exemption.

Science.gov (United States)

2010-07-01

... BONDING RULES Exemptions Savings and Loan Associations Subject to Federal Regulation § 2580.412-30 Conditions of exemption. This exemption applies only to those savings and loan associations (including building and loan associations, cooperative banks and homestead associations) subject to regulation and...

40 CFR 90.908 - National security exemption.

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 20 2010-07-01 2010-07-01 false National security exemption. 90.908... Exemption of Nonroad Engines from Regulations § 90.908 National security exemption. (a)(1) Any nonroad... defense, will be considered exempt from this part for purposes of national security. No request for...

75 FR 66686 - Defense Federal Acquisition Regulation Supplement; Balance of Payments Program Exemption for...

Science.gov (United States)

2010-10-29

... Federal Acquisition Regulation Supplement; Balance of Payments Program Exemption for Commercial... Balance of Payments Program for construction material that is commercial information technology. DATES... the Balance of Payments Program for commercial information technology to be used in overseas...

29 CFR 2580.412-29 - Exemption.

Science.gov (United States)

2010-07-01

... Exemptions Savings and Loan Associations Subject to Federal Regulation § 2580.412-29 Exemption. An exemption... Act is granted whereby savings and loan associations (including building and loan associations... for the benefit of their own employees, where such a savings and loan association is the administrator...

48 CFR 53.301-1094A - SF 1094A, Tax Exemption Certificates Accountability Record.

Science.gov (United States)

2010-10-01

... 48 Federal Acquisition Regulations System 2 2010-10-01 2010-10-01 false SF 1094A, Tax Exemption Certificates Accountability Record. 53.301-1094A Section 53.301-1094A Federal Acquisition Regulations System... 1094A, Tax Exemption Certificates Accountability Record. ER02JA97.013 ER02JA97.014 [62 FR 247, Jan. 2...

78 FR 79285 - Home Mortgage Disclosure (Regulation C): Adjustment to Asset-Size Exemption Threshold

Science.gov (United States)

2013-12-30

... for Urban Wage Earners and Clerical Workers (CPI-W). The exemption threshold is adjusted to increase... of $1 million dollars. The definition of ``financial institution'' in Regulation C provides that the... good cause found and published with the rule. 5 U.S.C. 553(d). At a minimum, the Bureau believes the...

45 CFR 2508.19 - What Privacy Act exemptions or control of systems of records are exempt from disclosure?

Science.gov (United States)

2010-10-01

... 45 Public Welfare 4 2010-10-01 2010-10-01 false What Privacy Act exemptions or control of systems of records are exempt from disclosure? 2508.19 Section 2508.19 Public Welfare Regulations Relating to... ACT OF 1974 § 2508.19 What Privacy Act exemptions or control of systems of records are exempt from...

77 FR 29450 - Actions on Special Permit Applications

Science.gov (United States)

2012-05-17

............ Conference of 49 CFR To modify the Radiation 172.203(d); special permit add Control Part 172, 49 CFR Part 172..., KY. the list of regulations exempted in paragraph 4. 11406-M......... Conference of 49 CFR Part To... mode of Berlin 173.345; transportation Packaging 173.346; (cargo vessel.) (Former 173.359; Grantee All...

DR2539 is a novel DtxR-like regulator of Mn/Fe ion homeostasis and antioxidant enzyme in Deinococcus radiodurans

International Nuclear Information System (INIS)

Chen, Huan; Wu, Rongrong; Xu, Guangzhi; Fang, Xu; Qiu, Xiaoli; Guo, Hongyin; Tian, Bing; Hua, Yuejin

2010-01-01

Transcriptional regulators of the diphtheria toxin repressor (DtxR) family control the expression of genes involved in the uptake of iron and manganese, which is not only necessitous nutrients but also was suggested to be essential for intracellular redox cycling of microorganisms. We identified a unique DtxR homologue (DR2539) with special characteristics from Deinococcus radiodurans, which is known for its extreme resistance to radiation and oxidants. The dr2539 mutant showed higher resistance to hydrogen peroxide than the wild-type strain R1. Intracellular catalase activity assay and semiquantitative PCR analysis demonstrated that this DtxR is a negative regulator of catalase (katE). Furthermore, quantitative real-time PCR, global transcription profile and inductively coupled plasma-mass spectrometry analysis showed that the DtxR is involved in the regulation of antioxidant system by maintaining the intracellular Mn/Fe ion homeostasis of D. radiodurans. However, unlike the other DtxR homologues, the DtxR of D. radiodurans acts as a negative regulator of a Mn transporter gene (dr2283) and as a positive regulator of Fe-dependent transporter genes (dr1219, drb0125) in D. radiodurans.

DR2539 is a novel DtxR-like regulator of Mn/Fe ion homeostasis and antioxidant enzyme in Deinococcus radiodurans

Energy Technology Data Exchange (ETDEWEB)

Chen, Huan [Key Laboratory for Nuclear-Agricultural Sciences of Chinese Ministry of Agriculture and Zhejiang Province, Institute of Nuclear-Agricultural Sciences, Zhejiang University, Hangzhou 310029 (China); Zhejiang Institute of Microbiology, Zhejiang Province, Hangzhou 310012 (China); Wu, Rongrong [Department of Cardiology, Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310009 (China); Xu, Guangzhi [Key Laboratory for Nuclear-Agricultural Sciences of Chinese Ministry of Agriculture and Zhejiang Province, Institute of Nuclear-Agricultural Sciences, Zhejiang University, Hangzhou 310029 (China); Fang, Xu; Qiu, Xiaoli; Guo, Hongyin [Zhejiang Institute of Microbiology, Zhejiang Province, Hangzhou 310012 (China); Tian, Bing, E-mail: tianbing@zju.edu.cn [Key Laboratory for Nuclear-Agricultural Sciences of Chinese Ministry of Agriculture and Zhejiang Province, Institute of Nuclear-Agricultural Sciences, Zhejiang University, Hangzhou 310029 (China); Hua, Yuejin, E-mail: yjhua@zju.edu.cn [Key Laboratory for Nuclear-Agricultural Sciences of Chinese Ministry of Agriculture and Zhejiang Province, Institute of Nuclear-Agricultural Sciences, Zhejiang University, Hangzhou 310029 (China)

2010-05-28

Transcriptional regulators of the diphtheria toxin repressor (DtxR) family control the expression of genes involved in the uptake of iron and manganese, which is not only necessitous nutrients but also was suggested to be essential for intracellular redox cycling of microorganisms. We identified a unique DtxR homologue (DR2539) with special characteristics from Deinococcus radiodurans, which is known for its extreme resistance to radiation and oxidants. The dr2539 mutant showed higher resistance to hydrogen peroxide than the wild-type strain R1. Intracellular catalase activity assay and semiquantitative PCR analysis demonstrated that this DtxR is a negative regulator of catalase (katE). Furthermore, quantitative real-time PCR, global transcription profile and inductively coupled plasma-mass spectrometry analysis showed that the DtxR is involved in the regulation of antioxidant system by maintaining the intracellular Mn/Fe ion homeostasis of D. radiodurans. However, unlike the other DtxR homologues, the DtxR of D. radiodurans acts as a negative regulator of a Mn transporter gene (dr2283) and as a positive regulator of Fe-dependent transporter genes (dr1219, drb0125) in D. radiodurans.

40 CFR 89.908 - National security exemption.

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 20 2010-07-01 2010-07-01 false National security exemption. 89.908... Provisions § 89.908 National security exemption. (a)(1) Any nonroad engine, otherwise subject to this part... regulations for purposes of national security. No request for exemption is necessary. (2) Manufacturers may...

41 CFR 109-38.204-1 - Unlimited exemptions.

Science.gov (United States)

2010-07-01

... 41 Public Contracts and Property Management 3 2010-07-01 2010-07-01 false Unlimited exemptions... Regulations System (Continued) DEPARTMENT OF ENERGY PROPERTY MANAGEMENT REGULATIONS AVIATION, TRANSPORTATION... § 109-38.204-1 Unlimited exemptions. (a)-(f) [Reserved] (g) The Director, Office of Administrative...

7 CFR 930.162 - Exemptions.

Science.gov (United States)

2010-01-01

... MICHIGAN, NEW YORK, PENNSYLVANIA, OREGON, UTAH, WASHINGTON, AND WISCONSIN Administrative Rules and Regulations § 930.162 Exemptions. (a) General. Tart cherries which are used for the purpose of new product... and/or new markets for tart cherry products. Any exemption for experimental work shall be limited in...

Preliminary report. Preliminary findings and views concerning the exemption of aviation gasoline from the Mandatory Petroleum Allocation and Price Regulations

Energy Technology Data Exchange (ETDEWEB)

None

1978-01-01

Preliminary findings indicate that: the fuel is not in short supply; exemption will not have an adverse impact on supply of any other petroleum product subject to the Emergency Petroleum allocation Act of 1973; competition and market force are adequate; exemption will not result in inequitable prices; and exemption will not have adverse state or regional impacts or any other adverse impacts. Chapter II provides background information on the use, production, and distribution of aviation gasoline. Chapter III analyzes the historical interaction of supply, demand, and price, and explores the market structure for aviation gasoline during 1968 to 1976, prior to and during imposition of allocation and price controls. Chapter IV examines aviation gasoline supply, demand, price, and market structure impacts of exempting aviation gasoline from controls. In Chapter V, the potential economic impacts of exemption are evaluated. Chapter VI provides a final summary of the DOE's findings and views in support of its preliminary judgment that aviation gasoline should be exempted from allocation and price regulations. (MCW)

40 CFR 94.908 - National security exemption.

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 20 2010-07-01 2010-07-01 false National security exemption. 94.908... § 94.908 National security exemption. (a)(1) Any marine engine, otherwise subject to this part, that is... regulations in this subpart for reasons of national security. No request for this exemption is necessary. (2...

12 CFR 218.741 - Exemption for banks effecting transactions in money market funds.

Science.gov (United States)

2010-01-01

... money market funds. 218.741 Section 218.741 Banks and Banking FEDERAL RESERVE SYSTEM BOARD OF GOVERNORS... EXCHANGE ACT OF 1934 (REGULATION R) § 218.741 Exemption for banks effecting transactions in money market... issued by a money market fund, provided that: (1) The bank either (i) Provides the customer, directly or...

75 FR 44049 - Qualification of Drivers; Exemption Applications; Diabetes Mellitus

Science.gov (United States)

2010-07-27

.... Koegel, Nicholas J. Niemerg, Dereck J. Oliveira, Paul J. O'Neil, Jr., Worden T. Price, Frankie R. Ramey... the twenty-five exemption applications, FMCSA exempts, Calvin R. Adams, Michael R. Amstutz, Clinton R. Carlson, II, Brandon L. Cheek, Michael J. Drake, Richard A. Dufton, Jr., Kenneth Dunn, Robert J. Dyxin...

78 FR 24303 - Qualification of Drivers; Exemption Applications; Diabetes Mellitus

Science.gov (United States)

2013-04-24

... exemption applications, FMCSA exempts Christopher R. Anderson (MN), Brent T. Applebury (MO), Joseph A.... Torklidson (WI), Terry R. Washa (NE), Alfred J. Williams (VA), Scott B. Wood (ND), and James L. Zore (IN...

45 CFR 5b.11 - Exempt systems.

Science.gov (United States)

2010-10-01

... 45 Public Welfare 1 2010-10-01 2010-10-01 false Exempt systems. 5b.11 Section 5b.11 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION PRIVACY ACT REGULATIONS § 5b.11 Exempt systems. (a) General policy. The Act permits certain types of specific systems of records to be exempt from...

Regulation of Specialized Metabolism by WRKY Transcription Factors

Science.gov (United States)

Schluttenhofer, Craig; Yuan, Ling

2015-01-01

WRKY transcription factors (TFs) are well known for regulating plant abiotic and biotic stress tolerance. However, much less is known about how WRKY TFs affect plant-specialized metabolism. Analysis of WRKY TFs regulating the production of specialized metabolites emphasizes the values of the family outside of traditionally accepted roles in stress tolerance. WRKYs with conserved roles across plant species seem to be essential in regulating specialized metabolism. Overall, the WRKY family plays an essential role in regulating the biosynthesis of important pharmaceutical, aromatherapy, biofuel, and industrial components, warranting considerable attention in the forthcoming years. PMID:25501946

48 CFR 252.229-7005 - Tax exemptions (Spain).

Science.gov (United States)

2010-10-01

... 48 Federal Acquisition Regulations System 3 2010-10-01 2010-10-01 false Tax exemptions (Spain... of Provisions And Clauses 252.229-7005 Tax exemptions (Spain). As prescribed in 229.402-70(e), use the following clause: Tax Exemptions (Spain) (JUN 1997) (a) The Contractor represents that the...

Negative regulation of NOD1 mediated angiogenesis by PPARγ-regulated miR-125a

International Nuclear Information System (INIS)

Kang, Hyesoo; Park, Youngsook; Lee, Aram; Seo, Hyemin; Kim, Min Jung; Choi, Jihea; Jo, Ha-neul; Jeong, Ha-neul; Cho, Jin Gu; Chang, Woochul; Lee, Myeong-Sok; Jeon, Raok; Kim, Jongmin

2017-01-01

Infection with pathogens activates the endothelial cell and its sustained activation may result in impaired endothelial function. Endothelial dysfunction contributes to the pathologic angiogenesis that is characteristic of infection-induced inflammatory pathway activation. Nucleotide-binding oligomerization domain-containing protein 1 (NOD1) is a protein receptor which recognizes bacterial molecules and stimulates an immune reaction in various cells; however, the underlying molecular mechanisms in the regulation of inflammation-triggered angiogenesis are not fully understood. Here we report that peroxisome proliferator-activated receptor gamma (PPARγ)-mediated miR-125a serves as an important regulator of NOD1 agonist-mediated angiogenesis in endothelial cells by directly targeting NOD1. Treatment of human umbilical vein endothelial cells with natural PPARγ ligand, 15-Deoxy-Delta12,14-prostaglandin J2, led to inhibition of NOD1 expression; contrarily, protein levels of NOD1 were significantly increased by PPARγ knockdown. We report that PPARγ regulation of NOD1 expression is a novel microRNA-mediated regulation in endothelial cells. MiR-125a expression was markedly decreased in human umbilical vein endothelial cells subjected to PPARγ knockdown while 15-Deoxy-Delta12,14-prostaglandin J2 treatment increased the level of miR-125a. In addition, NOD1 is closely regulated by miR-125a, which directly targets the 3′ untranslated region of NOD1. Moreover, both overexpression of miR-125a and PPARγ activation led to inhibition of NOD1 agonist-induced tube formation in endothelial cells. Finally, NOD1 agonist increased the formation of cranial and subintestinal vessel plexus in zebrafish, and this effect was abrogated by concurrent PPARγ activation. Overall, these findings identify a PPARγ-miR-125a-NOD1 signaling axis in endothelial cells that is critical in the regulation of inflammation-mediated angiogenesis. - Highlights: • Expression of NOD1 is regulated by

29 CFR 779.388 - Exemption provided for food or beverage service employees.

Science.gov (United States)

2010-07-01

... 29 Labor 3 2010-07-01 2010-07-01 false Exemption provided for food or beverage service employees... Service Establishments Restaurants and Establishments Providing Food and Beverage Service § 779.388 Exemption provided for food or beverage service employees. (a) A special exemption is provided in section 13...

Civilsamfundets ABC: R for Regulering

DEFF Research Database (Denmark)

Meyer, Gitte; Lund, Anker Brink

2016-01-01

Hvad er civilsamfundet? Anker Brink Lund og Gitte Meyer fra CBS Center for Civil Society Studies gennemgår civilsamfundet bogstav for bogstav. Vi er nået til R for Regulering.......Hvad er civilsamfundet? Anker Brink Lund og Gitte Meyer fra CBS Center for Civil Society Studies gennemgår civilsamfundet bogstav for bogstav. Vi er nået til R for Regulering....

77 FR 25865 - Amendment to the International Traffic in Arms Regulations: Exemption for Temporary Export of...

Science.gov (United States)

2012-05-02

... difficulties in certain instances (for example, departing on a U.S. military airplane from a U.S. military base). According to law and regulations, persons who claim this exemption must submit the articles for CBP...) for the individual to declare to CBP his intention of returning the articles upon each return to the...

A systems biology approach identifies a R2R3 MYB gene subfamily with distinct and overlapping functions in regulation of aliphatic glucosinolates.

Directory of Open Access Journals (Sweden)

Ida Elken Sønderby

Full Text Available BACKGROUND: Glucosinolates are natural metabolites in the order Brassicales that defend plants against both herbivores and pathogens and can attract specialized insects. Knowledge about the genes controlling glucosinolate regulation is limited. Here, we identify three R2R3 MYB transcription factors regulating aliphatic glucosinolate biosynthesis in Arabidopsis by combining several systems biology tools. METHODOLOGY/PRINCIPAL FINDINGS: MYB28 was identified as a candidate regulator of aliphatic glucosinolates based on its co-localization within a genomic region controlling variation both in aliphatic glucosinolate content (metabolite QTL and in transcript level for genes involved in the biosynthesis of aliphatic glucosinolates (expression QTL, as well as its co-expression with genes in aliphatic glucosinolate biosynthesis. A phylogenetic analysis with the R2R3 motif of MYB28 showed that it and two homologues, MYB29 and MYB76, were members of an Arabidopsis-specific clade that included three characterized regulators of indole glucosinolates. Over-expression of the individual MYB genes showed that they all had the capacity to increase the production of aliphatic glucosinolates in leaves and seeds and induce gene expression of aliphatic biosynthetic genes within leaves. Analysis of leaves and seeds of single knockout mutants showed that mutants of MYB29 and MYB76 have reductions in only short-chained aliphatic glucosinolates whereas a mutant in MYB28 has reductions in both short- and long-chained aliphatic glucosinolates. Furthermore, analysis of a double knockout in MYB28 and MYB29 identified an emergent property of the system since the absence of aliphatic glucosinolates in these plants could not be predicted by the chemotype of the single knockouts. CONCLUSIONS/SIGNIFICANCE: It seems that these cruciferous-specific MYB regulatory genes have evolved both overlapping and specific regulatory capacities. This provides a unique system within which to

Distinguishing community benefits: tax exemption versus organizational legitimacy.

Science.gov (United States)

Byrd, James D; Landry, Amy

2012-01-01

US policymakers continue to call into question the tax-exempt status of hospitals. As nonprofit tax-exempt entities, hospitals are required by the Internal Revenue Service (IRS) to report the type and cost of community benefits they provide. Institutional theory indicates that organizations derive organizational legitimacy from conforming to the expectations of their environment. Expectations from the state and federal regulators (the IRS, state and local taxing authorities in particular) and the community require hospitals to provide community benefits to achieve legitimacy. This article examines community benefit through an institutional theory framework, which includes regulative (laws and regulation), normative (certification and accreditation), and cultural-cognitive (relationship with the community including the provision of community benefits) pillars. Considering a review of the results of a 2006 IRS study of tax-exempt hospitals, the authors propose a model of hospital community benefit behaviors that distinguishes community benefits between cost-quantifiable activities appropriate for justifying tax exemption and unquantifiable activities that only contribute to hospitals' legitimacy.

29 CFR 516.11 - Employees exempt from both minimum wage and overtime pay requirements under section 13(a) (2), (3...

Science.gov (United States)

2010-07-01

... 29 Labor 3 2010-07-01 2010-07-01 false Employees exempt from both minimum wage and overtime pay... Exemptions Under the Act; Other Special Requirements § 516.11 Employees exempt from both minimum wage and.... With respect to each and every employee exempt from both the minimum wage and overtime pay requirements...

48 CFR 252.229-7002 - Customs exemptions (Germany).

Science.gov (United States)

2010-10-01

... 48 Federal Acquisition Regulations System 3 2010-10-01 2010-10-01 false Customs exemptions... of Provisions And Clauses 252.229-7002 Customs exemptions (Germany). As prescribed in 229.402-70(b), use the following clause: Customs Exemptions (Germany) (JUN 1997) Imported products required for the...

29 CFR 780.300 - Statutory exemptions in section 13(a)(6).

Science.gov (United States)

2010-07-01

... Employment in Agriculture That Is Exempted From the Minimum Wage and Overtime Pay Requirements Under Section... the Act exempts from the minimum wage requirements of section 6 and from the overtime pay requirements... 780.300 Labor Regulations Relating to Labor (Continued) WAGE AND HOUR DIVISION, DEPARTMENT OF LABOR...

The coming changes in tax-exempt health care finance.

Science.gov (United States)

Carlile, L L; Serchuk, B M

1995-01-01

On December 30, 1994, the Internal Revenue Service (IRS) published proposed regulations (Proposed Regulations) that if enacted would significantly change the climate and rules of federal income tax law controlling the issuance and maintenance of tax-exempt bonds for governmental and 501(c)(3) health care borrowers. This article (1) summarizes the aspects of the Proposed Regulations dealing with private activity tests, management contracts, allocation and accounting rules, change in use of financed facilities, and antiabuse rules, and (2) summarizes the possible interrelationship of the IRS's audit program for tax-exempt bonds and the Proposed Regulations. The article reviews features of the Proposed Regulations that will affect either the costs or administrative burdens of managing the federal tax compliance of future tax-exempt health care borrowings.

Preliminary report. Preliminary findings and views concerning the exemption of kerojet fuels from the Mandatory Petroleum Allocation and Price Regulations

Energy Technology Data Exchange (ETDEWEB)

None

1978-01-01

Preliminary findings indicate the following: kerojet fuel is not in short supply; it will not adversely impact on the supply of other petroleum products subject to the Emergency Petroleum Allocation Act; competition and market forces are adequate; and it will not result in inequitable prices for kerojet or other products. Chapter II provides background information on the use, production, and distribution of kerojet. Chapter III analyzes the historical interaction of supply, demand, and price, and explores the market structure for kerojet during 1968 to 1976, prior to and during imposition of allocation and price controls. Chapter IV examines the effect upon kerojet supply, demand, price, and market structure of exempting kerojet from controls and indicates the benefits to be derived from such exemption. In Chapter V, the potential economic impacts of exemption are evaluated. Chapter VI provides a final summary of the DOE's findings and views in support of its preliminary judgment that kerojet should be exempted from allocation and price regulations. (MCW)

75 FR 1453 - Qualification of Drivers; Exemption Renewals; Vision

Science.gov (United States)

2010-01-11

...; Exemption Renewals; Vision AGENCY: Federal Motor Carrier Safety Administration (FMCSA), DOT. ACTION: Notice... the vision requirement in the Federal Motor Carrier Safety Regulations for 23 individuals. FMCSA has statutory authority to exempt individuals from the vision requirement if the exemptions granted will not...

7 CFR 985.58 - Exempt oil.

Science.gov (United States)

2010-01-01

... 7 Agriculture 8 2010-01-01 2010-01-01 false Exempt oil. 985.58 Section 985.58 Agriculture... HANDLING OF SPEARMINT OIL PRODUCED IN THE FAR WEST Order Regulating Handling Volume Limitations § 985.58 Exempt oil. Oil held by a producer or handler on the effective date of this subpart shall not be...

PamR, a new MarR-like regulator affecting prophages and metabolic genes expression in Bacillus subtilis.

Directory of Open Access Journals (Sweden)

Alba De San Eustaquio-Campillo

Full Text Available B. subtilis adapts to changing environments by reprogramming its genetic expression through a variety of transcriptional regulators from the global transition state regulators that allow a complete resetting of the cell genetic expression, to stress specific regulators controlling only a limited number of key genes required for optimal adaptation. Among them, MarR-type transcriptional regulators are known to respond to a variety of stresses including antibiotics or oxidative stress, and to control catabolic or virulence gene expression. Here we report the characterization of the ydcFGH operon of B. subtilis, containing a putative MarR-type transcriptional regulator. Using a combination of molecular genetics and high-throughput approaches, we show that this regulator, renamed PamR, controls directly its own expression and influence the expression of large sets of prophage-related and metabolic genes. The extent of the regulon impacted by PamR suggests that this regulator reprograms the metabolic landscape of B. subtilis in response to a yet unknown signal.

The GlnR Regulon in Streptococcus mutans Is Differentially Regulated by GlnR and PmrA.

Directory of Open Access Journals (Sweden)

Yi-Ywan M Chen

Full Text Available GlnR-mediated repression of the GlnR regulon at acidic pH is required for optimal acid tolerance in Streptococcus mutans, the etiologic agent for dental caries. Unlike most streptococci, the GlnR regulon is also regulated by newly identified PmrA (SMUGS5_RS05810 at the transcriptional level in S. mutans GS5. Results from gel mobility shift assays confirmed that both GlnR and PmrA recognized the putative GlnR box in the promoter regions of the GlnR regulon genes. By using a chemostat culture system, we found that PmrA activated the expression of the GlnR regulon at pH 7, and that this activation was enhanced by excess glucose. Deletion of pmrA (strain ΔPmrA reduced the survival rate of S. mutans GS5 at pH 3 moderately, whereas the GlnR mutant (strain ΔGlnR exhibited an acid-sensitive phenotype in the acid killing experiments. Elevated biofilm formation in both ΔGlnR and ΔPmrA mutant strains is likely a result of indirect regulation of the GlnR regulon since GlnR and PmrA regulate the regulon differently. Taken together, it is suggested that activation of the GlnR regulon by PmrA at pH 7 ensures adequate biosynthesis of amino acid precursor, whereas repression by GlnR at acidic pH allows greater ATP generation for acid tolerance. The tight regulation of the GlnR regulon in response to pH provides an advantage for S. mutans to better survive in its primary niche, the oral cavity.

Exemption values and measurements in international comparison

International Nuclear Information System (INIS)

Neider, R.

1994-01-01

Activities are developed worldwide to systematically derive exemption limits or exemption values (IAEA, ICRP, Radiation Protection Ordinance) for different applications according to uniform principles. An important step in this regard is the adoption of the new guideline of the EU Council on radiation protection. Also regarding a uniform definition of the exemption of material from nuclear installations, agreement should be reached soon in Europe. Due to different concepts of ultimate disposal of radioactive wastes, in particular low level wastes, internationally there is no prospect of a uniform regulation concerning the exemption of very low level wastes, while in Germany a corresponding recommendation has already been made by the radiation protection commission. The exemption limits valid at present are mentioned. (orig./HP) [de

A review and comparison of international exemption and clearance levels

International Nuclear Information System (INIS)

Cooper, J.R.; Mobbs, S.F.

1997-01-01

The publication of new European Basic Safety Standards by the European Commission and of new International Basic Safety Standards by the IAEA together with other international agencies, has led to increased interest in the application of the concepts of exemption and clearance. This paper discusses the derivation of radionuclide-specific exemption and clearance values for application in various areas of the regulation of radioactive materials. (author)

The Exempt Market in Canada: Empirics, Observations and Recommendations

Directory of Open Access Journals (Sweden)

Vijay Jog

2015-03-01

Full Text Available There is a massive and vital capital market at work in Canada — possibly bigger than rough estimates have so far suggested — and it is one for which several market regulators are preparing new rules. Yet the remarkable thing is how little we know about it. Data about the so-called exempt market are so lacking that were regulators in Ontario and the other provinces contemplating new exempt-market regulations to proceed, they would be creating policies based on anecdotal, incomplete and, potentially, incorrect evidence. Even estimating the size of the Canadian exempt market has been an inexact science, given the incomplete data, but we can estimate that it provides in excess of $100 billion in gross capital flow every year, and that amount continues to grow. While it may be natural to assume that the exempt market is used primarily by small and medium-sized enterprises, it seems it is primarily used by the financial services industry. These institutions appear to rely on the exempt market to raise potentially short-term debt capital relatively free of particularly burdensome information-disclosure requirements. Unfortunately, we are forced to rely here again on deductions based on limited evidence: So incomplete are the data about the exempt market that we lack even complete information on the type of issuers, investors and securities, or the volume and duration of the securities and the level of redemptions. The exempt market exists for important reasons: it is a way out of the regulatory conundrum, wherein the regulator’s mandate to protect investors, through significant requirements for information disclosure, can put too large a burden on certain issuers. That is why it is essential that any new regulations are developed using a thorough understanding of how it operates. Yet the reality is that it is impossible to evaluate how individual investors and small firms are using the exempt market, or their experience in it. This is

41 CFR 128-1.8008 - Exemptions.

Science.gov (United States)

2010-07-01

... 41 Public Contracts and Property Management 3 2010-07-01 2010-07-01 false Exemptions. 128-1.8008 Section 128-1.8008 Public Contracts and Property Management Federal Property Management Regulations System (Continued) DEPARTMENT OF JUSTICE 1-INTRODUCTION 1.80-Seismic Safety Program § 128-1.8008 Exemptions. The...

The heterocyst differentiation transcriptional regulator HetR of the filamentous cyanobacterium Anabaena forms tetramers and can be regulated by phosphorylation.

Science.gov (United States)

Valladares, Ana; Flores, Enrique; Herrero, Antonia

2016-02-01

Many filamentous cyanobacteria respond to the external cue of nitrogen scarcity by the differentiation of heterocysts, cells specialized in the fixation of atmospheric nitrogen in oxic environments. Heterocysts follow a spatial pattern along the filament of two heterocysts separated by ca. 10-15 vegetative cells performing oxygenic photosynthesis. HetR is a transcriptional regulator that directs heterocyst differentiation. In the model strain Anabaena sp. PCC 7120, the HetR protein was observed in various oligomeric forms in vivo, including a tetramer that peaked with maximal hetR expression during differentiation. Tetramers were not detected in a hetR point mutant incapable of differentiation, but were conspicuous in an over-differentiating strain lacking the PatS inhibitor. In differentiated filaments the HetR tetramer was restricted to heterocysts, being undetectable in vegetative cells. HetR co-purified with RNA polymerase from Anabaena mainly as a tetramer. In vitro, purified recombinant HetR was distributed between monomers, dimers, trimers and tetramers, and it was phosphorylated when incubated with (γ-(32)P)ATP. Phosphorylation and PatS hampered the accumulation of HetR tetramers and impaired HetR binding to DNA. In summary, tetrameric HetR appears to represent a functionally relevant form of HetR, whose abundance in the Anabaena filament could be negatively regulated by phosphorylation and by PatS. © 2015 John Wiley & Sons Ltd.

7 CFR 1207.514 - Exemption for organic potatoes.

Science.gov (United States)

2010-01-01

... 7 Agriculture 10 2010-01-01 2010-01-01 false Exemption for organic potatoes. 1207.514 Section 1207... SERVICE (MARKETING AGREEMENTS AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE POTATO RESEARCH AND PROMOTION PLAN Rules and Regulations Assessments § 1207.514 Exemption for organic potatoes. (a...

15 CFR 30.36 - Exemption for shipments destined to Canada.

Science.gov (United States)

2010-01-01

... 15 Commerce and Foreign Trade 1 2010-01-01 2010-01-01 false Exemption for shipments destined to Canada. 30.36 Section 30.36 Commerce and Foreign Trade Regulations Relating to Commerce and Foreign Trade BUREAU OF THE CENSUS, DEPARTMENT OF COMMERCE FOREIGN TRADE REGULATIONS Exemptions From the Requirements...

29 CFR 1625.11 - Exemption for employees serving under a contract of unlimited tenure.

Science.gov (United States)

2010-07-01

... 29 Labor 4 2010-07-01 2010-07-01 false Exemption for employees serving under a contract of unlimited tenure. 1625.11 Section 1625.11 Labor Regulations Relating to Labor (Continued) EQUAL EMPLOYMENT... within the exemption can lawfully be forced to retire on account of age at age 70 (see paragraph (a)(1...

miR-29b and miR-125a Regulate Podoplanin and Suppress Invasion in Glioblastoma

Science.gov (United States)

Cortez, Maria Angelica; Nicoloso, Milena Sabrina; Shimizu, Masayoshi; Rossi, Simona; Gopisetty, Gopal; Molina, Jennifer R.; Carlotti, Carlos; Tirapelli, Daniela; Neder, Luciano; Brassesco, Maria Sol; Scrideli, Carlos Alberto; Tone, Luiz Gonzaga; Georgescu, Maria-Magdalena; Zhang, Wei; Puduvalli, Vinay; Calin, George Adrian

2017-01-01

Glioblastoma is the most frequent and malignant brain tumor, characterized by an elevated capacity for cellular proliferation and invasion. Recently, it was demonstrated that podoplanin membrane sialo-glycoprotein encoded by PDPN gene is over-expressed and related to cellular invasion in astrocytic tumors; however the mechanisms of regulation are still unknown. MicroRNAs are noncoding RNAs that regulate gene expression and several biological processes and diseases, including cancer. Nevertheless, their roles in invasion, proliferation, and apoptosis of glioblastoma are not completely understood. In this study, we focused on miR-29b and miR-125a, which were predicted to regulate PDPN, and demonstrated that these microRNAs directly target the 3′ untranslated region of PDPN and inhibit invasion, apoptosis, and proliferation of glioblastomas. Furthermore, we report that miR-29b and miR-125a are downregulated in glioblastomas and also in CD133-positive cells. Taken together, these results suggest that miR-29b and miR-125a represent potential therapeutic targets in glioblastoma. PMID:20665731

A R2R3-MYB transcription factor from Epimedium sagittatum regulates the flavonoid biosynthetic pathway.

Directory of Open Access Journals (Sweden)

Wenjun Huang

Full Text Available Herba epimedii (Epimedium, a traditional Chinese medicine, has been widely used as a kidney tonic and antirheumatic medicine for thousands of years. The bioactive components in herba epimedii are mainly prenylated flavonol glycosides, end-products of the flavonoid pathway. Epimedium species are also used as garden plants due to the colorful flowers and leaves. Many R2R3-MYB transcription factors (TFs have been identified to regulate the flavonoid and anthocyanin biosynthetic pathways. However, little is known about the R2R3-MYB TFs involved in regulation of the flavonoid pathway in Epimedium. Here, we reported the isolation and functional characterization of the first R2R3-MYB TF (EsMYBA1 from Epimedium sagittatum (Sieb. Et Zucc. Maxim. Conserved domains and phylogenetic analysis showed that EsMYBA1 belonged to the subgroup 6 clade (anthocyanin-related MYB clade of R2R3-MYB family, which includes Arabidopsis AtPAP1, apple MdMYB10 and legume MtLAP1. EsMYBA1 was preferentially expressed in leaves, especially in red leaves that contain higher content of anthocyanin. Alternative splicing of EsMYBA1 resulted in three transcripts and two of them encoded a MYB-related protein. Yeast two-hybrid and transient luciferase expression assay showed that EsMYBA1 can interact with several bHLH regulators of the flavonoid pathway and activate the promoters of dihydroflavonol 4-reductase (DFR and anthocyanidin synthase (ANS. In both transgenic tobacco and Arabidopsis, overexpression of EsMYBA1 induced strong anthocyanin accumulation in reproductive and/or vegetative tissues via up-regulation of the main flavonoid-related genes. Furthermore, transient expression of EsMYBA1 in E. sagittatum leaves by Agrobacterium infiltration also induced anthocyanin accumulation in the wounded area. This first functional characterization of R2R3-MYB TFs in Epimedium species will promote further studies of the flavonoid biosynthesis and regulation in medicinal plants.

A R2R3-MYB transcription factor from Epimedium sagittatum regulates the flavonoid biosynthetic pathway.

Science.gov (United States)

Huang, Wenjun; Sun, Wei; Lv, Haiyan; Luo, Ming; Zeng, Shaohua; Pattanaik, Sitakanta; Yuan, Ling; Wang, Ying

2013-01-01

Herba epimedii (Epimedium), a traditional Chinese medicine, has been widely used as a kidney tonic and antirheumatic medicine for thousands of years. The bioactive components in herba epimedii are mainly prenylated flavonol glycosides, end-products of the flavonoid pathway. Epimedium species are also used as garden plants due to the colorful flowers and leaves. Many R2R3-MYB transcription factors (TFs) have been identified to regulate the flavonoid and anthocyanin biosynthetic pathways. However, little is known about the R2R3-MYB TFs involved in regulation of the flavonoid pathway in Epimedium. Here, we reported the isolation and functional characterization of the first R2R3-MYB TF (EsMYBA1) from Epimedium sagittatum (Sieb. Et Zucc.) Maxim. Conserved domains and phylogenetic analysis showed that EsMYBA1 belonged to the subgroup 6 clade (anthocyanin-related MYB clade) of R2R3-MYB family, which includes Arabidopsis AtPAP1, apple MdMYB10 and legume MtLAP1. EsMYBA1 was preferentially expressed in leaves, especially in red leaves that contain higher content of anthocyanin. Alternative splicing of EsMYBA1 resulted in three transcripts and two of them encoded a MYB-related protein. Yeast two-hybrid and transient luciferase expression assay showed that EsMYBA1 can interact with several bHLH regulators of the flavonoid pathway and activate the promoters of dihydroflavonol 4-reductase (DFR) and anthocyanidin synthase (ANS). In both transgenic tobacco and Arabidopsis, overexpression of EsMYBA1 induced strong anthocyanin accumulation in reproductive and/or vegetative tissues via up-regulation of the main flavonoid-related genes. Furthermore, transient expression of EsMYBA1 in E. sagittatum leaves by Agrobacterium infiltration also induced anthocyanin accumulation in the wounded area. This first functional characterization of R2R3-MYB TFs in Epimedium species will promote further studies of the flavonoid biosynthesis and regulation in medicinal plants.

75 FR 32661 - Special Local Regulation; Hydroplane Exhibition, Detroit River, Detroit, MI

Science.gov (United States)

2010-06-09

...; Detroit River; Detroit, MI. (a) Location. The following is a temporary special local regulation area: All...-AA08 Special Local Regulation; Hydroplane Exhibition, Detroit River, Detroit, MI AGENCY: Coast Guard, DHS. ACTION: Temporary final rule. SUMMARY: The Coast Guard will enforce a temporary special local...

7 CFR 1210.516 - Exemption for organic watermelons.

Science.gov (United States)

2010-01-01

... 7 Agriculture 10 2010-01-01 2010-01-01 false Exemption for organic watermelons. 1210.516 Section... SERVICE (MARKETING AGREEMENTS AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE WATERMELON RESEARCH AND PROMOTION PLAN Rules and Regulations Assessments § 1210.516 Exemption for organic watermelons...

76 FR 12558 - Amendment to Special Use Airspace Restricted Areas R-2203, and R-2205; Alaska

Science.gov (United States)

2011-03-08

...-0055; Airspace Docket No. 11-AAL-2] Amendment to Special Use Airspace Restricted Areas R-2203, and R... amendment. SUMMARY: This action amends the using agency of Restricted Areas R-2203 A, B, & C; Eagle River, AK, and R-2205, Stuart Creek, AK. These changes reflect the U.S. Army's current organization in...

15 CFR 30.35 - Procedure for shipments exempt from filing requirements.

Science.gov (United States)

2010-01-01

... 15 Commerce and Foreign Trade 1 2010-01-01 2010-01-01 false Procedure for shipments exempt from filing requirements. 30.35 Section 30.35 Commerce and Foreign Trade Regulations Relating to Commerce and Foreign Trade BUREAU OF THE CENSUS, DEPARTMENT OF COMMERCE FOREIGN TRADE REGULATIONS Exemptions From the...

29 CFR 780.506 - Dependence of exemption on shade-grown tobacco operations.

Science.gov (United States)

2010-07-01

... 29 Labor 3 2010-07-01 2010-07-01 false Dependence of exemption on shade-grown tobacco operations. 780.506 Section 780.506 Labor Regulations Relating to Labor (Continued) WAGE AND HOUR DIVISION....506 Dependence of exemption on shade-grown tobacco operations. The exemption provided by section 13(a...

29 CFR 570.126 - Parental exemption.

Science.gov (United States)

2010-07-01

... 29 Labor 3 2010-07-01 2010-07-01 false Parental exemption. 570.126 Section 570.126 Labor Regulations Relating to Labor (Continued) WAGE AND HOUR DIVISION, DEPARTMENT OF LABOR REGULATIONS CHILD LABOR REGULATIONS, ORDERS AND STATEMENTS OF INTERPRETATION General Statements of Interpretation of the Child Labor...

The Institutionalised and Non-Institutionalised Exemptions from EU Public Procurement Law: Towards a More Coherent Approach?

Directory of Open Access Journals (Sweden)

Willem A. Janssen

2014-12-01

Full Text Available From a EU public procurement law perspective, contracting authorities have a discretionary power to decide upon who is allowed and best suited to provide public services to the public. When public authorities deem the in-house performance of a service to be the most suitable, the Court of Justice of the EU has allowed these authorities to rely on the institutionalised and non-institutionalised exemptions, which exempt a possible duty to contract out a public contract. The first part of this contribution discusses the recent codification of these exemptions in Article 12 Directive 2014/24/EU on public procurement. It concludes that this codification creates some legal certainty, but it mostly expands the scope of these exemptions from public procurement law. The second part of this contribution proposes a more coherent approach for these exemptions by discussing the challenges of regulating and enforcing the pre-procurement phase (the make-or-buy decision in which a public authority decides to favour the internal or external performance of a service. It concludes by providing legal perspectives to regulate and enforce this decision-making phase.

29 CFR 780.318 - Exemption for nonlocal minors.

Science.gov (United States)

2010-07-01

... Employment in Agriculture That Is Exempted From the Minimum Wage and Overtime Pay Requirements Under Section... 1966 Amendments to the Fair Labor Standards Act exempts from the minimum wage and overtime provisions... Labor Regulations Relating to Labor (Continued) WAGE AND HOUR DIVISION, DEPARTMENT OF LABOR STATEMENTS...

Experience in the application of exemption principles. Proceedings of a specialists meeting held in Vienna, 2-4 November 1993

Energy Technology Data Exchange (ETDEWEB)

NONE

1995-07-01

The Proceedings presentations have been grouped in 4 Sessions: International developments on principles and standards (3 papers), Exemption principles in national regulations (8 papers), Derived exemption and clearance levels (6 papers) and Practical application of exemption and clearance concepts (5 papers). A separate abstract was prepared for each paper. Refs, figs and tabs.

Experience in the application of exemption principles. Proceedings of a specialists meeting held in Vienna, 2-4 November 1993

International Nuclear Information System (INIS)

1995-07-01

The Proceedings presentations have been grouped in 4 Sessions: International developments on principles and standards (3 papers), Exemption principles in national regulations (8 papers), Derived exemption and clearance levels (6 papers) and Practical application of exemption and clearance concepts (5 papers). A separate abstract was prepared for each paper. Refs, figs and tabs

7 CFR 1219.202 - Exemption for organic Hass avocados.

Science.gov (United States)

2010-01-01

... defined in the Organic Act, a signed certification that the applicant meets all of the requirements... 7 Agriculture 10 2010-01-01 2010-01-01 false Exemption for organic Hass avocados. 1219.202 Section... AVOCADO PROMOTION, RESEARCH, AND INFORMATION Rules and Regulations § 1219.202 Exemption for organic Hass...

29 CFR 780.307 - Exemption for employer's immediate family.

Science.gov (United States)

2010-07-01

... Employment in Agriculture That Is Exempted From the Minimum Wage and Overtime Pay Requirements Under Section...) of the Fair Labor Standards Amendments of 1966 provides a minimum wage and overtime exemption in the... 780.307 Labor Regulations Relating to Labor (Continued) WAGE AND HOUR DIVISION, DEPARTMENT OF LABOR...

Research Article Special Issue

African Journals Online (AJOL)

pc

2018-03-07

Mar 7, 2018 ... Eurostat and the Ministry of Economic Development. 4. .... regard to the application of special national schemes for small enterprises. ... 2013) mentions a two-year exemption from the tax on joint stock companies and local taxes. ... specialized support programs are developed, such as the introduction of the ...

Resignation from the VAT exemption of sales of residential premises by the developer

Directory of Open Access Journals (Sweden)

Joanna Koziollek

2016-09-01

Full Text Available Tax institutions should be construed in a rational manner, in order so as to not restrict economic turnover excessively. The regulations concerning the possibility to resign from the VAT exemption of sales of residential premises by the developer characterizes by the high level of formalism which affects in a negative manner the sales process performed by the developer. This paper is devoted to the fragment of the polish Act on the goods and services tax governing the issue of resignation from the VAT exemption of sales of residential premises, which implies in a certain extent to appeal to the regulation of exemptions stipulated in this Act. The subject matter of this analysis is to examine the correctness of transposition of the Directive 112 into polish legal system in the field of real estate exemptions from VAT, the conditions for exercising the optional exemption, as well as the benefit of the resignation from the VAT exemption by the taxpayer.

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.

40 CFR 89.909 - Export exemptions.

Science.gov (United States)

2010-07-01

... Enforcement Auditing Section, Manufacturers Operations Division (6405-J), Environmental Protection Agency... comply with EPA certification regulations. (d) It is a condition of any exemption for the purpose of...

Department of Transportation -- Exemption for using the Transuranic Package Transporter-I (TRUPACT-I) at the Idaho National Engineering Laboratory (Code of Federal Regulations, Title 49, Part 107, Subpart B -- Exemptions, 107-103 Application for Exemption)

International Nuclear Information System (INIS)

Tyacke, M.J.; Macdonald, R.J.

1992-08-01

Exemption from specific regulations is being sought for the Transuranic Package Transporter Model I (TRUPACT-I) container. The design has successfully undergone extensive testing of a quarter-scale model and a full-scale prototype of the container. Results from the analysis and testing are in the TRUPACT-1 Safely Analysis Report for Packaging (SARP), GA-Al8695/SAND 87-7104 (TTC0735), April 1987 (see Attachment 1). The container was never certified or used because of questions raised during the certification process. Two features of the container design failed to satisfy the regulations for Type B packaging. First, the design utilizes a venting system to control internal and external pressures; this venting system is not allowed by the Code of Federal Regulations, Title 10, Parts 71(h) and 71.51(b) [10 CFR 71.(h) and 71.51(b)]. Second, the maximum quantity fissile material proposed to be hauled in TRUPACT-I exceeded the limits in 10 CFR 71.63(b) for a single-containment container. To correct these design deficiencies, the vents would be plugged during transport, and the maximum quantity of fissile material would be limited to the allowables for a single-containment container. An engineering analysis showed that the container could safely transport radioactive material within the boundaries of the Idaho National Engineering Laboratory (INEL) with the vent system plugged (see Attachment 2). However, some of the requirements for determining pressure on a container need to be changed (i.e., exempted) to reflect conditions unique to the INEL. The following are the requirements needing to be changed for INEL conditions, variances being sought, and justifications for the variances

45 CFR 5.68 - Exemption seven: Law enforcement.

Science.gov (United States)

2010-10-01

... 45 Public Welfare 1 2010-10-01 2010-10-01 false Exemption seven: Law enforcement. 5.68 Section 5... INFORMATION REGULATIONS Reasons for Withholding Some Records § 5.68 Exemption seven: Law enforcement. We are not required to disclose information or records that the government has compiled for law enforcement...

75 FR 55968 - Special Local Regulations, Sabine River; Orange, TX

Science.gov (United States)

2010-09-15

...-AA08 Special Local Regulations, Sabine River; Orange, TX AGENCY: Coast Guard, DHS. ACTION: Temporary... Arthur Captain of the Port Zone on the Sabine River, Orange, Texas. This Special Local Regulation is... River, Orange, TX in the Federal Register (75 FR 41119). We received no comments on the proposed rule...

45 CFR 5.67 - Exemption six: Clearly unwarranted invasion of personal privacy.

Science.gov (United States)

2010-10-01

... 45 Public Welfare 1 2010-10-01 2010-10-01 false Exemption six: Clearly unwarranted invasion of... ADMINISTRATION FREEDOM OF INFORMATION REGULATIONS Reasons for Withholding Some Records § 5.67 Exemption six... the lines” or piece together items that would constitute information that normally would be exempt...

78 FR 1919 - Qualification of Drivers; Exemption Applications; Vision

Science.gov (United States)

2013-01-09

...-0339] Qualification of Drivers; Exemption Applications; Vision AGENCY: Federal Motor Carrier Safety... announces receipt of applications from 14 individuals for exemption from the vision requirement in the Federal Motor Carrier Safety Regulations. They are unable to meet the vision requirement in one eye for...

MDRL lncRNA regulates the processing of miR-484 primary transcript by targeting miR-361.

Directory of Open Access Journals (Sweden)

Kun Wang

2014-07-01

Full Text Available Long noncoding RNAs (lncRNAs are emerging as new players in gene regulation, but whether lncRNAs operate in the processing of miRNA primary transcript is unclear. Also, whether lncRNAs are involved in the regulation of the mitochondrial network remains to be elucidated. Here, we report that a long noncoding RNA, named mitochondrial dynamic related lncRNA (MDRL, affects the processing of miR-484 primary transcript in nucleus and regulates the mitochondrial network by targeting miR-361 and miR-484. The results showed that miR-361 that predominantly located in nucleus can directly bind to primary transcript of miR-484 (pri-miR-484 and prevent its processing by Drosha into pre-miR-484. miR-361 is able to regulate mitochondrial fission and apoptosis by regulating miR-484 levels. In exploring the underlying molecular mechanism by which miR-361 is regulated, we identified MDRL and demonstrated that it could directly bind to miR-361 and downregulate its expression levels, which promotes the processing of pri-miR-484. MDRL inhibits mitochondrial fission and apoptosis by downregulating miR-361, which in turn relieves inhibition of miR-484 processing by miR-361. Our present study reveals a novel regulating model of mitochondrial fission program which is composed of MDRL, miR-361 and miR-484. Our work not only expands the function of the lncRNA pathway in gene regulation but also establishes a new mechanism for controlling miRNA expression.

49 CFR 525.11 - Termination of exemption; amendment of alternative average fuel economy standard.

Science.gov (United States)

2010-10-01

... average fuel economy standard. 525.11 Section 525.11 Transportation Other Regulations Relating to... EXEMPTIONS FROM AVERAGE FUEL ECONOMY STANDARDS § 525.11 Termination of exemption; amendment of alternative average fuel economy standard. (a) Any exemption granted under this part for an affected model year does...

75 FR 60266 - Federal Acquisition Regulation; Buy American Exemption for Commercial Information Technology...

Science.gov (United States)

2010-09-29

...). Section 615 authorizes exemption from the Buy American Act for acquisition of information technology that... acquisition of information technology that is a commercial item. This same exemption has appeared every year... applies. ``Information technology'' and ``Commercial item'' are already defined in FAR part 2. This is a...

Assessment of the U.S. regulations for fissile exemptions and fissile material general licenses

International Nuclear Information System (INIS)

Parks, C.V.; Hopper, C.M.; Lichtenwalter, J.J.; Easton, E.P.; Brochman, P.G.

1998-05-01

The paragraphs for general licenses for fissile material and exemptions (often termed exceptions in the international community) for fissile material have long been a part of the US Code of Federal Regulations (CFR) 10 CFR Part 71, Packaging and Transportation of Radioactive Material. More recently, the Nuclear Regulatory Commission (NRC) issued a final rule on Part 71 via emergency rule-making procedures in order to address an identified deficiency related to one of the fissile exemptions. To address the specified deficiency in a general fashion, the emergency rule adopted the approach of the 1996 Edition of the IAEA: Regulations for the Safe Transport of Radioactive Material (IAEA 1996), which places restrictions on certain moderating materials and limits the quantity of fissile material in a consignment. The public comments received by the NRC indicated general agreement with the need for restrictions on certain moderators (beryllium, deuterium, and graphite). The comments indicated concern relative to both the degree of restriction imposed (not more than 0.1% of fissile material mass) and the need to limit the fissile material mass of the consignment, particularly in light of the subsequent NRC staff position that the true intent was to provide control for limiting the fissile mass of the conveyance. The purpose of the review is to identify potential deficiencies that might be adverse to maintaining adequate subcriticality under normal conditions of transport and hypothetical accident conditions. In addition, ORNL has been asked to identify changes that would address any identified safety issues, enable inherently safe packages to continue to be unencumbered in transport, and seek to minimize the impact on current safe practices

7 CFR 3565.6 - Inclusion of tax-exempt debt.

Science.gov (United States)

2010-01-01

... 7 Agriculture 15 2010-01-01 2010-01-01 false Inclusion of tax-exempt debt. 3565.6 Section 3565.6 Agriculture Regulations of the Department of Agriculture (Continued) RURAL HOUSING SERVICE, DEPARTMENT OF AGRICULTURE GUARANTEED RURAL RENTAL HOUSING PROGRAM General Provisions § 3565.6 Inclusion of tax-exempt debt...

GntR family of regulators in Mycobacterium smegmatis: a sequence and structure based characterization

Directory of Open Access Journals (Sweden)

Ranjan Akash

2007-08-01

Full Text Available Abstract Background Mycobacterium smegmatis is fast growing non-pathogenic mycobacteria. This organism has been widely used as a model organism to study the biology of other virulent and extremely slow growing species like Mycobacterium tuberculosis. Based on the homology of the N-terminal DNA binding domain, the recently sequenced genome of M. smegmatis has been shown to possess several putative GntR regulators. A striking characteristic feature of this family of regulators is that they possess a conserved N-terminal DNA binding domain and a diverse C-terminal domain involved in the effector binding and/or oligomerization. Since the physiological role of these regulators is critically dependent upon effector binding and operator sites, we have analysed and classified these regulators into their specific subfamilies and identified their potential binding sites. Results The sequence analysis of M. smegmatis putative GntRs has revealed that FadR, HutC, MocR and the YtrA-like regulators are encoded by 45, 8, 8 and 1 genes respectively. Further out of 45 FadR-like regulators, 19 were classified into the FadR group and 26 into the VanR group. All these proteins showed similar secondary structural elements specific to their respective subfamilies except MSMEG_3959, which showed additional secondary structural elements. Using the reciprocal BLAST searches, we further identified the orthologs of these regulators in Bacillus subtilis and other mycobacteria. Since the expression of many regulators is auto-regulatory, we have identified potential operator sites for a number of these GntR regulators by analyzing the upstream sequences. Conclusion This study helps in extending the annotation of M. smegmatis GntR proteins. It identifies the GntR regulators of M. smegmatis that could serve as a model for studying orthologous regulators from virulent as well as other saprophytic mycobacteria. This study also sheds some light on the nucleotide preferences in the

An approach to the exemption of materials from regulation as radioactive wastes

International Nuclear Information System (INIS)

Chatterjee, R.M.; Coady, J.R.; Wagstaff, K.P.

1982-01-01

Staff of the Canadian Atomic Energy Control Board are proposing to establish a general framework for assessing the radiological impact of radioactive waste management practices. This framework features, in addition to the familiar radiation protection principles concerning dose limits and optimization, the concept of trivial doses that are so low that for practical purposes they may be neglected. The rationale for the derivation of numerical criteria for trivial doses is based primarily on consideration of risks to individuals in small and large populations. The concept of trivial individual doses has wide application and significant implications for a variety of waste management practices, including the definition of contaminated materials that are exempt from regulations as radioactive wastes. Examples are given of the practical application of this approach to specific waste disposal issues

Measuring Individual Differences in Emotion Regulation: The Emotion Regulation Profile-Revised (ERP-R

Directory of Open Access Journals (Sweden)

Delphine Nelis

2011-02-01

Full Text Available The main purpose of this study was to validate a new instrument aimed to assess emotion regulation: the Emotion Regulation Profile-Revised (ERP-R. Exploratory factor analyses yielded two theoretically meaningful factors: down-regulation of negative emotions and up-regulation of positive emotions. Internal reliability scores of the two factors were good. Findings showed evidence of convergent/discriminant validity, with ERP-R scores being independent of non verbal reasoning and verbal skills while positively related to emotional intelligence and to relevant personality dimensions. There was also preliminary evidence of criterion validity. ERP-R scores also demonstrated incremental validity to predict a number of criteria over and above emotional intelligence and emotional stability. Overall, the results show a clear 2 factors solution for the ERP-R and high correlations with convergent and divergent scales as well as good criterion and incremental validities.

75 FR 16520 - James A. Fitzpatrick Nuclear Power Plant; Exemption

Science.gov (United States)

2010-04-01

... Power Plant; Exemption 1.0 Background Entergy Nuclear Operations, Inc. (the licensee) is the holder of Facility Operating License No. DPR-59, which authorizes operation of the James A. FitzPatrick Nuclear Power... date for all operating nuclear power plants, but noted that the Commission's regulations provide...

34 CFR 682.302 - Payment of special allowance on FFEL loans.

Science.gov (United States)

2010-07-01

... which special allowance is claimed under paragraph (f)(2)of this section, describes the role of such... section— (1) A tax-exempt obligation is an obligation the income of which is exempt from taxation under...

77 FR 69593 - Atlantic Highly Migratory Species; Exempted Fishing, Scientific Research, Display, and Chartering...

Science.gov (United States)

2012-11-20

... Highly Migratory Species; Exempted Fishing, Scientific Research, Display, and Chartering Permits; Letters... intent to issue Exempted Fishing Permits (EFPs), Scientific Research Permits (SRPs), Display Permits... public display and scientific research that is exempt from regulations (e.g., fishing seasons, prohibited...

75 FR 75458 - Atlantic Highly Migratory Species; Exempted Fishing, Scientific Research, Display, and Chartering...

Science.gov (United States)

2010-12-03

... Highly Migratory Species; Exempted Fishing, Scientific Research, Display, and Chartering Permits; Letters... intent to issue Exempted Fishing Permits (EFPs), Scientific Research Permits (SRPs), Display Permits... of HMS for public display and scientific research that is exempt from regulations (e.g., seasons...

Basis for applying for exemption according to species protection regulation. Final repository for spent nuclear fuel at Forsmark; Underlag till ansoekan om dispens enligt artskyddsfoerordningen. Slutfoervar foer anvaent kaernbraensle i Forsmark

Energy Technology Data Exchange (ETDEWEB)

2011-02-15

SKB will submit applications for permits and admissibility under the Environmental Act and under the Nuclear Activities Act to construct and operate a disposal facility for spent nuclear fuel at Forsmark. In the final repository the spent nuclear fuel from Swedish nuclear power plants is placed in order to protect human health and the environment against harmful effects of ionizing radiation. Construction and operation of the disposal facility in Forsmark will make an impact, give effects and consequences for the natural environment. Utilization of land for the construction of the facility and the impact on ground water as a result of groundwater drainage is expected to have negative consequences for the species included in species protection regulation. Thus, the planned activity require exemption from species protection regulation (SFS 2007:845). The purpose of this document is to provide a basis for an application for exemption under 14 paragraph species protection regulation from the prohibitions of 4, 6, 7 and 8 paragraph species protection regulation. A basis for the exemption application is that the proposed activity is considered to have an 'overriding public interest' prescribed in 14 paragraph species protection regulation. The document reports the impact, effects and consequences of the planned activities on species covered in the species protection regulation. The impact on protected species can be divided into two categories: - Direct effects on protected species and their habitats by utilization of the land. - Indirect effects on protected species and their habitats in the drainage of groundwater and the effect on groundwater levels. The document also includes a description of planned actions to prevent, restrict and compensate for the effects and consequences that the activity may cause. By applying for an exemption under 14 paragraph species protection regulation in a separate order from the application for permit according to chapters 9

Basis for applying for exemption according to species protection regulation. Final repository for spent nuclear fuel at Forsmark; Underlag till ansoekan om dispens enligt artskyddsfoerordningen. Slutfoervar foer anvaent kaernbraensle i Forsmark

Energy Technology Data Exchange (ETDEWEB)

2011-02-15

SKB will submit applications for permits and admissibility under the Environmental Act and under the Nuclear Activities Act to construct and operate a disposal facility for spent nuclear fuel at Forsmark. In the final repository the spent nuclear fuel from Swedish nuclear power plants is placed in order to protect human health and the environment against harmful effects of ionizing radiation. Construction and operation of the disposal facility in Forsmark will make an impact, give effects and consequences for the natural environment. Utilization of land for the construction of the facility and the impact on ground water as a result of groundwater drainage is expected to have negative consequences for the species included in species protection regulation. Thus, the planned activity require exemption from species protection regulation (SFS 2007:845). The purpose of this document is to provide a basis for an application for exemption under 14 paragraph species protection regulation from the prohibitions of 4, 6, 7 and 8 paragraph species protection regulation. A basis for the exemption application is that the proposed activity is considered to have an 'overriding public interest' prescribed in 14 paragraph species protection regulation. The document reports the impact, effects and consequences of the planned activities on species covered in the species protection regulation. The impact on protected species can be divided into two categories: - Direct effects on protected species and their habitats by utilization of the land. - Indirect effects on protected species and their habitats in the drainage of groundwater and the effect on groundwater levels. The document also includes a description of planned actions to prevent, restrict and compensate for the effects and consequences that the activity may cause. By applying for an exemption under 14 paragraph species protection regulation in a separate order from the application for permit according to chapters 9 and 11

29 CFR 553.216 - Other exemptions.

Science.gov (United States)

2010-07-01

... 29 Labor 3 2010-07-01 2010-07-01 false Other exemptions. 553.216 Section 553.216 Labor Regulations Relating to Labor (Continued) WAGE AND HOUR DIVISION, DEPARTMENT OF LABOR REGULATIONS APPLICATION OF THE FAIR LABOR STANDARDS ACT TO EMPLOYEES OF STATE AND LOCAL GOVERNMENTS Fire Protection and Law...

33 CFR 100.1302 - Special Local Regulation, Annual Dragon Boat Races, Portland, Oregon.

Science.gov (United States)

2010-07-01

... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Special Local Regulation, Annual Dragon Boat Races, Portland, Oregon. 100.1302 Section 100.1302 Navigation and Navigable Waters COAST... § 100.1302 Special Local Regulation, Annual Dragon Boat Races, Portland, Oregon. (a) Regulated area. All...

Tax Incentives to Businesses in the Areas of Special State Concern

Directory of Open Access Journals (Sweden)

Branimir Marković

2013-07-01

Full Text Available The legal and strategic framework for regional development in the Republic of Croatia, which includes the development of entrepreneurship, was established almost twenty years after Croatia had gained independence. Until then, less developed areas, i.e., areas with a special status in terms of certain reliefs and exemptions granted to citizens and economic entities had been supported through individual laws. Today, government authorities stimulate entrepreneurial activity through individual regulations in force, by corporate income tax exemptions. The state gives back corporate income tax (tax liability not subject to exemptions that taxpayers engaged in entrepreneurial activities had paid up to the state budget, to local self-government units as assistance from the state budget. By doing so, the government aims to reduce the gap between the developed and underdeveloped parts of the Republic of Croatia and encourage entrepreneurial activity in the smaller and less developed regions. The indicators of entrepreneurial activity in the area supported by the state: the number of enterprises, number of employees in an enterprise, the total revenue generated by entrepreneurial activities, profit and loss after tax and net operating profit/loss, provide insight into the performance of enterprises. In view of the above, the authors have analyzed the performance of enterprises entitled to tax relief in the areas of special state concern and provided an overview of financial resources (tax revenue which state authorities have waived to facilitate a more competitive business performance.

77 FR 65831 - Polymers; exemptions from the requirement of a tolerance.

Science.gov (United States)

2012-10-31

...]-Nonylphenyl)poly(oxypropylene) Block Polymer With Poly(oxyethylene); Tolerance Exemption AGENCY: Environmental... requirement of a tolerance for residues of [alpha]-([rho]-Nonylphenyl)poly(oxypropylene) block polymer with... polymer with poly(oxyethylene) on food or feed commodities. DATES: This regulation is effective October 31...

Regulation of a Glycerol-Induced Quinoprotein Alcohol Dehydrogenase by σ54 and a LuxR-Type Regulator in Azospirillum brasilense Sp7.

Science.gov (United States)

Singh, Vijay Shankar; Dubey, Ashutosh Prakash; Gupta, Ankush; Singh, Sudhir; Singh, Bhupendra Narain; Tripathi, Anil Kumar

2017-07-01

Azospirillum brasilense Sp7 uses glycerol as a carbon source for growth and nitrogen fixation. When grown in medium containing glycerol as a source of carbon, it upregulates the expression of a protein which was identified as quinoprotein alcohol dehydrogenase (ExaA). Inactivation of exaA adversely affects the growth of A. brasilense on glycerol. A determination of the transcription start site of exaA revealed an RpoN-dependent -12/-24 promoter consensus. The expression of an exaA :: lacZ fusion was induced maximally by glycerol and was dependent on σ 54 Bioinformatic analysis of the sequence flanking the -12/-24 promoter revealed a 17-bp sequence motif with a dyad symmetry of 6 nucleotides upstream of the promoter, the disruption of which caused a drastic reduction in promoter activity. The electrophoretic mobility of a DNA fragment containing the 17-bp sequence motif was retarded by purified EraR, a LuxR-type transcription regulator that is transcribed divergently from exaA EraR also showed a positive interaction with RpoN in two-hybrid and pulldown assays. IMPORTANCE Quinoprotein alcohol dehydrogenase (ExaA) plays an important role in the catabolism of alcohols in bacteria. Although exaA expression is thought to be regulated by a two-component system consisting of EraS and EraR, the mechanism of regulation was not known. This study shows the details of the regulation of expression of the exaA gene in A. brasilense We have shown here that exaA of A. brasilense is maximally induced by glycerol and harbors a σ 54 -dependent promoter. The response regulator EraR binds to an inverted repeat located upstream of the exaA promoter. This study shows that a LuxR-type response regulator (EraR) binds upstream of the exaA gene and physically interacts with σ 54 The unique feature of this regulation is that EraR is a LuxR-type transcription regulator that lacks the GAFTGA motif, a characteristic feature of the enhancer binding proteins that are known to interact with σ 54

76 FR 52563 - Special Local Regulations; Sabine River, Orange, TX

Science.gov (United States)

2011-08-23

...-AA08 Special Local Regulations; Sabine River, Orange, TX AGENCY: Coast Guard, DHS. ACTION: Temporary... Regulations; Sabine River, Orange, TX in the Federal Register (76 FR 103). We received no comments on the... Regulations for Marine Events; Sabine River, Orange, TX. (a) Definitions. As used in this section...

49 CFR 605.11 - Exemptions.

Science.gov (United States)

2010-10-01

...) That private school bus operators in the urban area are unable to provide adequate transportation, at a... 49 Transportation 7 2010-10-01 2010-10-01 false Exemptions. 605.11 Section 605.11 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL TRANSIT ADMINISTRATION, DEPARTMENT OF...

MiR-210 disturbs mitotic progression through regulating a group of mitosis-related genes.

Science.gov (United States)

He, Jie; Wu, Jiangbin; Xu, Naihan; Xie, Weidong; Li, Mengnan; Li, Jianna; Jiang, Yuyang; Yang, Burton B; Zhang, Yaou

2013-01-07

MiR-210 is up-regulated in multiple cancer types but its function is disputable and further investigation is necessary. Using a bioinformatics approach, we identified the putative target genes of miR-210 in hypoxia-induced CNE cells from genome-wide scale. Two functional gene groups related to cell cycle and RNA processing were recognized as the major targets of miR-210. Here, we investigated the molecular mechanism and biological consequence of miR-210 in cell cycle regulation, particularly mitosis. Hypoxia-induced up-regulation of miR-210 was highly correlated with the down-regulation of a group of mitosis-related genes, including Plk1, Cdc25B, Cyclin F, Bub1B and Fam83D. MiR-210 suppressed the expression of these genes by directly targeting their 3'-UTRs. Over-expression of exogenous miR-210 disturbed mitotic progression and caused aberrant mitosis. Furthermore, miR-210 mimic with pharmacological doses reduced tumor formation in a mouse metastatic tumor model. Taken together, these results implicate that miR-210 disturbs mitosis through targeting multi-genes involved in mitotic progression, which may contribute to its inhibitory role on tumor formation.

A R2R3-MYB transcription factor regulates the flavonol biosynthetic pathway in a traditional Chinese medicinal plant, Epimedium sagittatum

Directory of Open Access Journals (Sweden)

Wenjun Huang

2016-07-01

Full Text Available Flavonols as plant secondary metabolites with vital roles in plant development and defense against UV light, have been demonstrated to be the main bioactive components in the genus Epimedium plants, several species of which are used as materials for Herba Epimedii, an important traditional Chinese medicine. The flavonol biosynthetic pathway genes had been already isolated from E. sagittatum, but a R2R3-MYB transcription factor regulating the flavonol synthesis has not been functionally characterized so far in Epimedium plants. In this study, we isolated and characterized the R2R3-MYB transcription factor EsMYBF1 involved in regulation of the flavonol biosynthetic pathway from E. sagittatum. Sequence analysis indicated that EsMYBF1 belongs to the subgroup 7 of R2R3-MYB family which contains the flavonol-specific MYB regulators identified to date. Transient reporter assay showed that EsMYBF1 strongly activated the promoters of EsF3H (flavanone 3-hydroxylase and EsFLS (flavonol synthase, but not the promoters of EsDFRs (dihydroflavonol 4-reductase and EsANS (anthocyanidin synthase in transiently transformed Nicotiana benthamiana leaves. Both yeast two-hybrid assay and transient reporter assay validated EsMYBF1 to be independent of EsTT8, or AtTT8 bHLH regulators of the flavonoid pathway as cofactors. Ectopic expression of EsMYBF1 in transgenic tobacco resulted in the increased flavonol content and the decreased anthocyanin content in flowers. Correspondingly, the structural genes involved in flavonol synthesis were upregulated in the EsMYBF1 overexpression lines, including NtCHS (chalcone synthase, NtCHI (chalcone isomerase, NtF3H and NtFLS, whereas the late biosynthetic genes of the anthocyanin pathway (NtDFR and NtANS were remarkably downregulated, compared to the controls. These results suggest that EsMYBF1 is a flavonol-specific R2R3-MYB regulator, and involved in regulation of the biosynthesis of the flavonol-derived bioactive components in E

76 FR 27284 - Special Local Regulation; Partnership in Education, Dragon Boat Race; Maumee River, Toledo, OH

Science.gov (United States)

2011-05-11

...-AA08 Special Local Regulation; Partnership in Education, Dragon Boat Race; Maumee River, Toledo, OH... establishing a permanent Special Local Regulation on the Maumee River, Toledo, Ohio. This regulation is... place during the third or fourth weekend in July each year. This special local regulated area is...

77 FR 55436 - Special Local Regulation; Partnership in Education, Dragon Boat Race; Maumee River, Toledo, OH

Science.gov (United States)

2012-09-10

...-AA08 Special Local Regulation; Partnership in Education, Dragon Boat Race; Maumee River, Toledo, OH.... Add Sec. 100.921 to read as follows: Sec. 100.921 Special Local Regulations, Partnership in Education... establishing a permanent Special Local Regulation on the Maumee River, Toledo, Ohio. This regulation is...

miR-193b Regulates Mcl-1 in Melanoma.

Science.gov (United States)

Chen, Jiamin; Zhang, Xiao; Lentz, Cindy; Abi-Daoud, Marie; Paré, Geneviève C; Yang, Xiaolong; Feilotter, Harriet E; Tron, Victor A

2011-11-01

MicroRNAs play important roles in gene regulation, and their expression is frequently dysregulated in cancer cells. In a previous study, we reported that miR-193b represses cell proliferation and regulates cyclin D1 in melanoma cells, suggesting that miR-193b could act as a tumor suppressor. Herein, we demonstrate that miR-193b also down-regulates myeloid cell leukemia sequence 1 (Mcl-1) in melanoma cells. MicroRNA microarray profiling revealed that miR-193b is expressed at a significantly lower level in malignant melanoma than in benign nevi. Consistent with this, Mcl-1 is detected at a higher level in malignant melanoma than in benign nevi. In a survey of melanoma samples, the level of Mcl-1 is inversely correlated with the level of miR-193b. Overexpression of miR-193b in melanoma cells represses Mcl-1 expression. Previous studies showed that Mcl-1 knockdown cells are hypersensitive to ABT-737, a small-molecule inhibitor of Bcl-2, Bcl-X(L), and Bcl-w. Similarly, overexpression of miR-193b restores ABT-737 sensitivity to ABT-737-resistant cells. Furthermore, the effect of miR-193b on the expression of Mcl-1 seems to be mediated by direct interaction between miR-193b and seed and seedless pairing sequences in the 3' untranslated region of Mcl-1 mRNA. Thus, this study provides evidence that miR-193b directly regulates Mcl-1 and that down-regulation of miR-193b in vivo could be an early event in melanoma progression. Copyright © 2011 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

8 CFR 103.22 - Records exempt in whole or in part.

Science.gov (United States)

2010-01-01

... 8 Aliens and Nationality 1 2010-01-01 2010-01-01 false Records exempt in whole or in part. 103.22 Section 103.22 Aliens and Nationality DEPARTMENT OF HOMELAND SECURITY IMMIGRATION REGULATIONS POWERS AND... exemptions cited. If the disclosure of the existence of a criminal law enforcement proceeding record could...

PfsR is a key regulator of iron homeostasis in Synechocystis PCC 6803.

Directory of Open Access Journals (Sweden)

Dan Cheng

Full Text Available Iron is an essential cofactor in numerous cellular processes. The iron deficiency in the oceans affects the primary productivity of phytoplankton including cyanobacteria. In this study, we examined the function of PfsR, a TetR family transcriptional regulator, in iron homeostasis of the cyanobacterium Synechocystis PCC 6803. Compared with the wild type, the pfsR deletion mutant displayed stronger tolerance to iron limitation and accumulated significantly more chlorophyll a, carotenoid, and phycocyanin under iron-limiting conditions. The mutant also maintained more photosystem I and photosystem II complexes than the wild type after iron deprivation. In addition, the activities of photosystem I and photosystem II were much higher in pfsR deletion mutant than in wild-type cells under iron-limiting conditions. The transcripts of pfsR were enhanced by iron limitation and inactivation of the gene affected pronouncedly expression of fut genes (encoding a ferric iron transporter, feoB (encoding a ferrous iron transporter, bfr genes (encoding bacterioferritins, ho genes (encoding heme oxygenases, isiA (encoding a chlorophyll-binding protein, and furA (encoding a ferric uptake regulator. The iron quota in pfsR deletion mutant cells was higher than in wild-type cells both before and after exposure to iron limitation. Electrophoretic mobility shift assays showed that PfsR bound to its own promoter and thereby auto-regulated its own expression. These data suggest that PfsR is a critical regulator of iron homeostasis.

Spearmint R2R3-MYB transcription factor MsMYB negatively regulates monoterpene production and suppresses the expression of geranyl diphosphate synthase large subunit (MsGPPS.LSU).

Science.gov (United States)

Reddy, Vaishnavi Amarr; Wang, Qian; Dhar, Niha; Kumar, Nadimuthu; Venkatesh, Prasanna Nori; Rajan, Chakravarthy; Panicker, Deepa; Sridhar, Vishweshwaran; Mao, Hui-Zhu; Sarojam, Rajani

2017-09-01

Many aromatic plants, such as spearmint, produce valuable essential oils in specialized structures called peltate glandular trichomes (PGTs). Understanding the regulatory mechanisms behind the production of these important secondary metabolites will help design new approaches to engineer them. Here, we identified a PGT-specific R2R3-MYB gene, MsMYB, from comparative RNA-Seq data of spearmint and functionally characterized it. Analysis of MsMYB-RNAi transgenic lines showed increased levels of monoterpenes, and MsMYB-overexpressing lines exhibited decreased levels of monoterpenes. These results suggest that MsMYB is a novel negative regulator of monoterpene biosynthesis. Ectopic expression of MsMYB, in sweet basil and tobacco, perturbed sesquiterpene- and diterpene-derived metabolite production. In addition, we found that MsMYB binds to cis-elements of MsGPPS.LSU and suppresses its expression. Phylogenetic analysis placed MsMYB in subgroup 7 of R2R3-MYBs whose members govern phenylpropanoid pathway and are regulated by miR858. Analysis of transgenic lines showed that MsMYB is more specific to terpene biosynthesis as it did not affect metabolites derived from phenylpropanoid pathway. Further, our results indicate that MsMYB is probably not regulated by miR858, like other members of subgroup 7. © 2017 The Authors. Plant Biotechnology Journal published by Society for Experimental Biology and The Association of Applied Biologists and John Wiley & Sons Ltd.

7 CFR 1210.521 - Reports of disposition of exempted watermelons.

Science.gov (United States)

2010-01-01

... 7 Agriculture 10 2010-01-01 2010-01-01 false Reports of disposition of exempted watermelons. 1210... WATERMELON RESEARCH AND PROMOTION PLAN Rules and Regulations Assessments § 1210.521 Reports of disposition of exempted watermelons. The Board may require reports by handlers or importers on the handling/importing and...

29 CFR 780.323 - Exemption for range production of livestock.

Science.gov (United States)

2010-07-01

... STANDARDS ACT Employment in Agriculture That Is Exempted From the Minimum Wage and Overtime Pay Requirements... exemption from the minimum wage and overtime requirements of the Act for any employee “employed in... Section 780.323 Labor Regulations Relating to Labor (Continued) WAGE AND HOUR DIVISION, DEPARTMENT OF...

77 FR 6784 - Proposed Information Collection; Comment Request; Scientific Research, Exempted Fishing, and...

Science.gov (United States)

2012-02-09

... Collection; Comment Request; Scientific Research, Exempted Fishing, and Exempted Activity Submissions AGENCY... collection. Fishery regulations do not generally affect scientific research activities conducted by a scientific research vessel. Persons planning to conduct such research are encouraged to submit a scientific...

12 CFR 760.4 - Exemptions.

Science.gov (United States)

2010-01-01

... 12 Banks and Banking 6 2010-01-01 2010-01-01 false Exemptions. 760.4 Section 760.4 Banks and Banking NATIONAL CREDIT UNION ADMINISTRATION REGULATIONS AFFECTING CREDIT UNIONS LOANS IN AREAS HAVING... apply with respect to: (a) Any State-owned property covered under a policy of self-insurance...

Modern aspects of tax regulation of investment activity

Directory of Open Access Journals (Sweden)

E.S. Podakov

2016-03-01

Full Text Available The article investigates the tax regulation of investment activity in modern conditions. Scientists studied different views about the impact of tax regulations on the investment activity in the country. The author determines that the tax regulation of investment activity involves the use of state mechanisms taxation of certain measures to improve investment conditions. The subject is the state tax regulations, and the object is the investment activity of individual and institutional investors of any form of ownership including organizational and legal forms. Such regulation is performed by using complex special tools. The possible methods of tax stimulation of investment processes are described. The article deals with the current results of tax reform in Ukraine and predicts its possible consequences for agricultural producers. The rating positions of Ukraine according to international organizations are showed. The systematic analysis has been carried out and the impact of differential tax rates, tax exemption for a specified period, reducing the tax base, elimination of double taxation on investment activity in certain areas have been researched. The special instruments of investment activity tax regulation are considered. The options for improving investment activity by introducing effective tax regulation are determined.

78 FR 6213 - Styrene-2-Ethylhexyl Acrylate Copolymer; Tolerance Exemption

Science.gov (United States)

2013-01-30

...This regulation establishes an exemption from the requirement of a tolerance for residues of 2-propenoic acid, 2-ethylhexyl ester, polymer with ethenylbenzene; also known as styrene-2-ethylhexyl acrylate copolymer when used as an inert ingredient in a pesticide chemical formulation. H. B. Fuller Company submitted a petition to EPA under the Federal Food, Drug, and Cosmetic Act (FFDCA), requesting an exemption from the requirement of a tolerance. This regulation eliminates the need to establish a maximum permissible level for residues of 2-propenoic acid, 2-Ethylhexyl Ester, Polymer with Ethenylbenzene on food or feed commodities.

76 FR 16654 - Austin Western Railroad, L.L.C.-Lease and Operation Exemption-Capital Metropolitan Transportation...

Science.gov (United States)

2011-03-24

... DEPARTMENT OF TRANSPORTATION Surface Transportation Board [Docket No. FD 35456] Austin Western Railroad, L.L.C.--Lease and Operation Exemption-- Capital Metropolitan Transportation Authority Austin... be leased since 2007, pursuant to an operating agreement. See Austin W. R.R.--Operation Exemption...

Down-regulated miR-448 relieves spinal cord ischemia/reperfusion injury by up-regulating SIRT1

Directory of Open Access Journals (Sweden)

Yun Wang

2018-03-01

Full Text Available MicroRNAs play a crucial role in the progression of spinal cord ischemia/reperfusion injury (SCII. The role of miR-448 and SIRT1 in SCII was investigated in this study, to provide further insights into prevention and improvement of this disorder. In this study, expressions of miR-448 and SIRT1 protein were determined by qRT-PCR and western blot, respectively. Flow cytometry was used to analyze cell apoptosis. The endogenous expression of genes was modulated by recombinant plasmids and cell transfection. Dual-luciferase reporter assay was performed to determine the interaction between miR-448 and SIRT1. The Basso, Beattie, and Bresnahan score was used to measure the hind-limb function of rat. The spinal cord ischemia reperfusion injury model of adult rats was developed by abdominal aorta clamping, and the nerve function evaluation was completed by motor deficit index score. In SCII tissues and cells treated with hypoxia, miR-448 was up-regulated while SIRT1 was down-regulated. Hypoxia treatment reduced the expression of SIRT1 through up-regulating miR-448 in nerve cells. Up-regulation of miR-448 induced by hypoxia promoted apoptosis of nerve cells through down-regulating SIRT1. Down-regulated miR-448 improved neurological function and hind-limb motor function of rats with SCII by up-regulating SIRT1. Down-regulated miR-448 inhibited apoptosis of nerve cells and improved neurological function by up-regulating SIRT1, which contributes to relieving SCII.

17 CFR 240.36a1-2 - Exemption from SIPA for OTC derivatives dealers.

Science.gov (United States)

2010-04-01

... 17 Commodity and Securities Exchanges 3 2010-04-01 2010-04-01 false Exemption from SIPA for OTC derivatives dealers. 240.36a1-2 Section 240.36a1-2 Commodity and Securities Exchanges SECURITIES AND EXCHANGE COMMISSION (CONTINUED) GENERAL RULES AND REGULATIONS, SECURITIES EXCHANGE ACT OF 1934 Rules and Regulations...

31 CFR 595.206 - Exempt transactions.

Science.gov (United States)

2010-07-01

... FOREIGN ASSETS CONTROL, DEPARTMENT OF THE TREASURY TERRORISM SANCTIONS REGULATIONS Prohibitions § 595.206 Exempt transactions. (a) Personal communications. The prohibitions contained in this part do not apply to any postal, telegraphic, telephonic, or other personal communication, which does not involve the...

MiR-29c regulates the expression of miR-34c and miR-449a by targeting DNA methyltransferase 3a and 3b in nasopharyngeal carcinoma

International Nuclear Information System (INIS)

Niu, Man; Gao, Dan; Wen, Qiuyuan; Wei, Pingpin; Pan, Suming; Shuai, Cijun; Ma, Huiling; Xiang, Juanjuan; Li, Zheng; Fan, Songqing; Li, Guiyuan; Peng, Shuping

2016-01-01

Nasopharyngeal carcinoma (NPC) is prevalent in South East Asia and Southern China particularly, despite the reported 5-year survival ratio is relative higher than other deadly cancers such as liver, renal, pancreas cancer, the lethality is characterized by high metastatic potential in the early stage and high recurrence rate after radiation treatment. MicroRNA-29c was found to be down-regulated in the serum as well as in the tissue of nasopharyngeal carcinoma tissue. In this study, we found accidentally that the transfection of pre-miR-29c or miR-29c mimics significantly increases the expression level of miR-34c and miR-449a but doesn’t affect that of miR-222 using real-time quantitative PCR in nasopharyngeal carcinoma cell lines. To explore the molecular mechanism of the regulatory role, the cells are treated with 5-Aza-2-deoxycytidine (5-Aza-CdR) treatment and the level of miR-34c and miR-449a but not miR-222 accumulated by the treatment. DNA methyltransferase 3a, 3b were down-regulated by the 5-Aza-CdR treatment with western blot and real-time quantitative PCR. We found that pre-miR-29c or miR-29c mimics significantly increases the expression level of miR-34c and miR-449a. We further found DNA methyltransferase 3a and 3b are the target gene of miR-29c. Restoration of miR-29c in NPC cells down-regulated DNA methyltransferase 3a, 3b, but not DNA methyltransferase T1. The regulation of miR-29c/DNMTs/miR-34c/449a is an important molecular axis of NPC development and targeting DNMTs or restoring of miR-29c might be a promising therapy strategy for the prevention of NPC

78 FR 28492 - Special Local Regulation; Low Country Splash, Wando River, Cooper River, and Charleston Harbor...

Science.gov (United States)

2013-05-15

...-AA08 Special Local Regulation; Low Country Splash, Wando River, Cooper River, and Charleston Harbor... establishing a special local regulation on the waters of the Wando River, Cooper River, and Charleston Harbor... rulemaking (NPRM) entitled, ``Special Local Regulation; Low Country Splash, Wando River, Cooper River, and...

miR-9: a versatile regulator of neurogenesis

Directory of Open Access Journals (Sweden)

Marion Coolen

2013-11-01

Full Text Available Soon after its discovery, microRNA-9 (miR-9 attracted the attention of neurobiologists, since it is one of the most highly expressed microRNAs in the developing and adult vertebrate brain. Functional analyses in different vertebrate species have revealed a prominent role of this microRNA in balancing proliferation in embryonic neural progenitor populations. Key transcriptional regulators such as FoxG1, Hes1 or Tlx, were identified as direct targets of miR-9, placing it at the core of the gene network controlling the progenitor state. Recent data also suggest that this function could extend to adult neural stem cells. Other studies point to a role of miR-9 in differentiated neurons. Moreover miR-9 has been implicated in human brain pathologies, either displaying a protective role, such as in Progeria, or participating in disease progression in brain cancers. Altogether functional studies highlight a prominent feature of this highly conserved microRNA, its functional versatility, both along its evolutionary history and across cellular contexts.

The Involvement of miR-23a/APAF1 Regulation Axis in Colorectal Cancer

Directory of Open Access Journals (Sweden)

Fung Lin Yong

2014-07-01

Full Text Available Recent advances in microRNAome have made microRNAs (miRNAs a compelling novel class of biomarker in cancer biology. In the present study, the role of miR-23a in the carcinogenesis of colorectal cancer (CRC was investigated. Cell viability, apoptosis, and caspase 3/7 activation analyses were conducted to determine the potentiality of apoptosis resistance function of miR-23a in CRC. Luciferase assay was performed to verify a putative target site of miR-23a in the 3'-UTR of apoptosis protease activating factor 1 (APAF1 mRNA. The expression levels of miR-23a and APAF1 in CRC cell lines (SW480 and SW620 and clinical samples were assessed using reverse transcription-quantitative real-time PCR (RT-qPCR and Western blot. We found that the inhibition of miR-23a in SW480 and SW620 cell lines resulted in significant reduction of cell viability and promotion of cell apoptosis. Moreover, miR-23a up-regulation was coupled with APAF1 down-regulation in CRC tissue samples. Taken together, miR-23a was identified to regulate apoptosis in CRC. Our study highlights the potential application of miR-23a/APAF1 regulation axis in miRNA-based therapy and prognostication.

Xenosensor CAR mediates down-regulation of miR-122 and up-regulation of miR-122 targets in the liver

Energy Technology Data Exchange (ETDEWEB)

Kazantseva, Yuliya A.; Yarushkin, Andrei A.; Mostovich, Lyudmila A. [The Institute of Molecular Biology and Biophysics, Timakova str., 2/12, Novosibirsk 630117 (Russian Federation); Pustylnyak, Yuliya A. [Novosibirsk State University, Pirogova str., 2, Novosibirsk 630090 (Russian Federation); Pustylnyak, Vladimir O., E-mail: pustylnyak@ngs.ru [The Institute of Molecular Biology and Biophysics, Timakova str., 2/12, Novosibirsk 630117 (Russian Federation); Novosibirsk State University, Pirogova str., 2, Novosibirsk 630090 (Russian Federation); The Institute International Tomography Center of the Russian Academy of Sciences, Institutskaya str. 3-A, Novosibirsk 630090 (Russian Federation)

2015-10-01

MiR-122 is a major hepatic microRNA, accounting for more than 70% of the total liver miRNA population. It has been shown that miR-122 is associated with liver diseases, including hepatocellular carcinoma. Mir-122 is an intergenic miRNA with its own promoter. Pri-miR-122 expression is regulated by liver-enriched transcription factors, mainly by HNF4α, which mediates the expression via the interaction with a specific DR1 site. It has been shown that phenobarbital-mediated activation of constitutive androstane receptor (CAR), xenobiotic nuclear receptor, is associated with a decrease in miR-122 in the liver. In the present study, we investigated HNF4α–CAR cross-talk in the regulation of miR-122 levels and promitogenic signalling in mouse livers. The level of miR-122 was significantly repressed by treatment with 1,4-bis[2-(3,5-dichloropyridyloxy)]benzene (TCPOBOP), which is an agonist of mouse CAR. ChIP assays demonstrated that TCPOBOP-activated CAR inhibited HNF4α transactivation by competing with HNF4α for binding to the DR1 site in the pri-miR-122 promoter. Such transcription factor replacement was strongly correlated with miR-122 down-regulation. Additionally, the decrease in miR-122 levels produced by CAR activation is accompanied by an increase in mRNA and cellular protein levels of E2f1 and its accumulation on the target cMyc gene promoter. The increase in accumulation of E2f1 on the target cMyc gene promoter is accompanied by an increase in cMyc levels and transcriptional activity. Thus, our results provide evidence to support the conclusion that CAR activation decreases miR-122 levels through suppression of HNF4α transcriptional activity and indirectly regulates the promitogenic protein cMyc. HNF4α–CAR cross-talk may provide new opportunities for understanding liver diseases and developing more effective therapeutic approaches to better drug treatments. - Highlights: • CAR activation decreased the level of miR-122 in mouse livers. • CAR decreases

Xenosensor CAR mediates down-regulation of miR-122 and up-regulation of miR-122 targets in the liver

International Nuclear Information System (INIS)

Kazantseva, Yuliya A.; Yarushkin, Andrei A.; Mostovich, Lyudmila A.; Pustylnyak, Yuliya A.; Pustylnyak, Vladimir O.

2015-01-01

MiR-122 is a major hepatic microRNA, accounting for more than 70% of the total liver miRNA population. It has been shown that miR-122 is associated with liver diseases, including hepatocellular carcinoma. Mir-122 is an intergenic miRNA with its own promoter. Pri-miR-122 expression is regulated by liver-enriched transcription factors, mainly by HNF4α, which mediates the expression via the interaction with a specific DR1 site. It has been shown that phenobarbital-mediated activation of constitutive androstane receptor (CAR), xenobiotic nuclear receptor, is associated with a decrease in miR-122 in the liver. In the present study, we investigated HNF4α–CAR cross-talk in the regulation of miR-122 levels and promitogenic signalling in mouse livers. The level of miR-122 was significantly repressed by treatment with 1,4-bis[2-(3,5-dichloropyridyloxy)]benzene (TCPOBOP), which is an agonist of mouse CAR. ChIP assays demonstrated that TCPOBOP-activated CAR inhibited HNF4α transactivation by competing with HNF4α for binding to the DR1 site in the pri-miR-122 promoter. Such transcription factor replacement was strongly correlated with miR-122 down-regulation. Additionally, the decrease in miR-122 levels produced by CAR activation is accompanied by an increase in mRNA and cellular protein levels of E2f1 and its accumulation on the target cMyc gene promoter. The increase in accumulation of E2f1 on the target cMyc gene promoter is accompanied by an increase in cMyc levels and transcriptional activity. Thus, our results provide evidence to support the conclusion that CAR activation decreases miR-122 levels through suppression of HNF4α transcriptional activity and indirectly regulates the promitogenic protein cMyc. HNF4α–CAR cross-talk may provide new opportunities for understanding liver diseases and developing more effective therapeutic approaches to better drug treatments. - Highlights: • CAR activation decreased the level of miR-122 in mouse livers. • CAR decreases

The "common sense" of the nonprofit hospital tax exemption: a policy analysis.

Science.gov (United States)

Sanders, S M

1995-01-01

Although rarely discussed prior to the 1985 Utah Supreme Court ruling against Intermountain Health Care Inc., the question of whether to grant tax exemptions to nonprofit hospitals is currently being debated by federal, state, and local legislators, and by the courts. Changes to current policy seem likely. This policy analysis: (1) presents the historical and legal background; (2) examines the economic, political, and organizational implications of current tax-exemption policy; and (3) offers three alternatives to this current policy. The analysis indicates that the current policy provides little incentive for nonprofit hospitals to make contributions of charity care. Of the alternatives, eliminating the exemption is not politically feasible at this time; regulating hospital operations and outputs portends an implementation nightmare; and tying tax subsidy levels to output levels of charity care--perhaps the strongest and most efficient incentive--would require an unlikely political consensus on what constitute valid and reliable measures of charity care. If there is a movement toward subsidies, then linking subsidy amounts to levels of charity care will depend on whether policy analysts can design satisfactory empirical measures. With the advent of universal health coverage, the demand for charity care will decrease. The problem for tax-exempt hospitals will then become justifying the exemption by demonstrating the extent to which they generate community benefits at no or reduced cost to society.

Demethoxycurcumin inhibited human epithelia ovarian cancer cells' growth via up-regulating miR-551a.

Science.gov (United States)

Du, Zhenhua; Sha, Xianqun

2017-03-01

Curcumin is a natural agent that has ability to dampen tumor cells' growth. However, the natural form of curcumin is prone to degrade and unstable in vitro. Here, we demonstrated that demethoxycurcumin (a curcumin-related demethoxy compound) could inhibit cell proliferation and induce apoptosis of ovarian cancer cells. Moreover, IRS2/PI3K/Akt axis was inactivated in cells treated with demethoxycurcumin. Quantitative real-time reverse transcription polymerase chain reaction demonstrated that miR-551a was down-regulated in ovarian cancer tissues and ovarian cancer cell lines. Over-expression of miR-551a inhibited cell proliferation and induced apoptosis of ovarian cancer cells, whereas down-regulation of miR-551a exerted the opposite function. Luciferase assays confirmed that there was a binding site of miR-551a in IRS2, and we found that miR-551a exerted tumor-suppressive function by targeting IRS2 in ovarian cancer cells. Remarkably, miR-551a was up-regulated in the cells treated with demethoxycurcumin, and demethoxycurcumin suppressed IRS2 by restoration of miR-551a. In conclusion, demethoxycurcumin hindered ovarian cancer cells' malignant progress via up-regulating miR-551a.

Pharmaceutical regulation in Europe and its impact on corporate R&D.

Science.gov (United States)

Eger, Stephan; Mahlich, Jörg C

2014-12-01

Many European countries regulate the markets for prescription drugs in order to cope with rising health expenditures. On the other hand, regulation distorts incentives to invest in pharmaceutical R&D. This study aims at empirically assessing the impact of regulation on pharmaceutical R&D expenditures. We analyze a sample of 20 leading pharmaceutical companies between 2000 and 2008. The share of sales in Europe serves as a proxy for the degree of pharmaceutical regulation. We control for other firm specific determinants of R&D such as cash flow, company size, leverage ratio, growth rate, and Tobin's q. Our results suggest a nonlinear relationship between European sales ratio and R&D intensity. Beyond a threshold of 33% of sales generated in Europe, a higher presence in Europe is associated with lower R&D investments. The results can be interpreted as further evidence of the deteriorating effect of regulation on firm's incentives to invest in R&D.

77 FR 39393 - Special Local Regulation; Upper Mississippi River, Mile 842.0 to 840.0

Science.gov (United States)

2012-07-03

... is establishing a temporary special local regulation for all waters of the Upper Mississippi River... 1625-AA00 Special Local Regulation; Upper Mississippi River, Mile 842.0 to 840.0 AGENCY: Coast Guard, DHS. ACTION: Temporary final rule. SUMMARY: The Coast Guard is establishing a temporary special local...

The FDA Food Safety and Modernization Act and the Exemption for Small Firms

OpenAIRE

Pouliot, Sebastien

2011-01-01

The FDA Food Safety Modernization Act of 2010 is new legislation that mandates, among other things, new food safety standards. The act includes a clause that exempts small firms from new regulatory requirements. This paper investigates the effects of a small firm exemption from more stringent food safety standards. The model compares food safety, total output and the number of market participants for different food safety regulation with and without an exemption for small firms. The numerical...

48 CFR 9904.402-62 - Exemption.

Science.gov (United States)

2010-10-01

... Section 9904.402-62 Federal Acquisition Regulations System COST ACCOUNTING STANDARDS BOARD, OFFICE OF FEDERAL PROCUREMENT POLICY, OFFICE OF MANAGEMENT AND BUDGET PROCUREMENT PRACTICES AND COST ACCOUNTING STANDARDS COST ACCOUNTING STANDARDS 9904.402-62 Exemption. None for this Standard. ...

48 CFR 9904.407-62 - Exemption.

Science.gov (United States)

2010-10-01

... Section 9904.407-62 Federal Acquisition Regulations System COST ACCOUNTING STANDARDS BOARD, OFFICE OF FEDERAL PROCUREMENT POLICY, OFFICE OF MANAGEMENT AND BUDGET PROCUREMENT PRACTICES AND COST ACCOUNTING STANDARDS COST ACCOUNTING STANDARDS 9904.407-62 Exemption. None for this Standard. ...

48 CFR 9904.404-62 - Exemption.

Science.gov (United States)

2010-10-01

... Section 9904.404-62 Federal Acquisition Regulations System COST ACCOUNTING STANDARDS BOARD, OFFICE OF FEDERAL PROCUREMENT POLICY, OFFICE OF MANAGEMENT AND BUDGET PROCUREMENT PRACTICES AND COST ACCOUNTING STANDARDS COST ACCOUNTING STANDARDS 9904.404-62 Exemption. None for this Standard. ...

48 CFR 9904.406-62 - Exemption.

Science.gov (United States)

2010-10-01

... Section 9904.406-62 Federal Acquisition Regulations System COST ACCOUNTING STANDARDS BOARD, OFFICE OF FEDERAL PROCUREMENT POLICY, OFFICE OF MANAGEMENT AND BUDGET PROCUREMENT PRACTICES AND COST ACCOUNTING STANDARDS COST ACCOUNTING STANDARDS 9904.406-62 Exemption. None for this Standard. ...

48 CFR 9904.401-62 - Exemption.

Science.gov (United States)

2010-10-01

... Section 9904.401-62 Federal Acquisition Regulations System COST ACCOUNTING STANDARDS BOARD, OFFICE OF FEDERAL PROCUREMENT POLICY, OFFICE OF MANAGEMENT AND BUDGET PROCUREMENT PRACTICES AND COST ACCOUNTING STANDARDS COST ACCOUNTING STANDARDS 9904.401-62 Exemption. None for this Standard. ...

48 CFR 9904.405-62 - Exemption.

Science.gov (United States)

2010-10-01

... Section 9904.405-62 Federal Acquisition Regulations System COST ACCOUNTING STANDARDS BOARD, OFFICE OF FEDERAL PROCUREMENT POLICY, OFFICE OF MANAGEMENT AND BUDGET PROCUREMENT PRACTICES AND COST ACCOUNTING STANDARDS COST ACCOUNTING STANDARDS 9904.405-62 Exemption. None for this Standard. ...

GlnR-Mediated Regulation of ectABCD Transcription Expands the Role of the GlnR Regulon to Osmotic Stress Management.

Science.gov (United States)

Shao, ZhiHui; Deng, WanXin; Li, ShiYuan; He, JuanMei; Ren, ShuangXi; Huang, WeiRen; Lu, YinHua; Zhao, GuoPing; Cai, ZhiMing; Wang, Jin

2015-10-01

Ectoine and hydroxyectoine are excellent compatible solutes for bacteria to deal with environmental osmotic stress and temperature damages. The biosynthesis cluster of ectoine and hydroxyectoine is widespread among microorganisms, and its expression is activated by high salinity and temperature changes. So far, little is known about the mechanism of the regulation of the transcription of ect genes and only two MarR family regulators (EctR1 in methylobacteria and the EctR1-related regulator CosR in Vibrio cholerae) have been found to negatively regulate the expression of ect genes. Here, we characterize GlnR, the global regulator for nitrogen metabolism in actinomycetes, as a negative regulator for the transcription of ectoine/hydroxyectoine biosynthetic genes (ect operon) in Streptomyces coelicolor. The physiological role of this transcriptional repression by GlnR is proposed to protect the intracellular glutamate pool, which acts as a key nitrogen donor for both the nitrogen metabolism and the ectoine/hydroxyectoine biosynthesis. High salinity is deleterious, and cells must evolve sophisticated mechanisms to cope with this osmotic stress. Although production of ectoine and hydroxyectoine is one of the most frequently adopted strategies, the in-depth mechanism of regulation of their biosynthesis is less understood. So far, only two MarR family negative regulators, EctR1 and CosR, have been identified in methylobacteria and Vibrio, respectively. Here, our work demonstrates that GlnR, the global regulator for nitrogen metabolism, is a negative transcriptional regulator for ect genes in Streptomyces coelicolor. Moreover, a close relationship is found between nitrogen metabolism and osmotic resistance, and GlnR-mediated regulation of ect transcription is proposed to protect the intracellular glutamate pool. Meanwhile, the work reveals the multiple roles of GlnR in bacterial physiology. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

12 CFR 711.6 - General exemption.

Science.gov (United States)

2010-01-01

... 12 Banks and Banking 6 2010-01-01 2010-01-01 false General exemption. 711.6 Section 711.6 Banks and Banking NATIONAL CREDIT UNION ADMINISTRATION REGULATIONS AFFECTING CREDIT UNIONS MANAGEMENT... are members of a minority group or women; (3) Is a depository institution that has been chartered for...

MiR-210 disturbs mitotic progression through regulating a group of mitosis-related genes

OpenAIRE

He, Jie; Wu, Jiangbin; Xu, Naihan; Xie, Weidong; Li, Mengnan; Li, Jianna; Jiang, Yuyang; Yang, Burton B.; Zhang, Yaou

2012-01-01

MiR-210 is up-regulated in multiple cancer types but its function is disputable and further investigation is necessary. Using a bioinformatics approach, we identified the putative target genes of miR-210 in hypoxia-induced CNE cells from genome-wide scale. Two functional gene groups related to cell cycle and RNA processing were recognized as the major targets of miR-210. Here, we investigated the molecular mechanism and biological consequence of miR-210 in cell cycle regulation, particularly ...

A novel mode of regulation of the Staphylococcus aureus Vancomycin-resistance-associated response regulator VraR mediated by Stk1 protein phosphorylation.

Science.gov (United States)

Canova, Marc J; Baronian, Grégory; Brelle, Solène; Cohen-Gonsaud, Martin; Bischoff, Markus; Molle, Virginie

2014-04-25

The Staphylococcus aureus Vancomycin-resistance-associated response regulator VraR is known as an important response regulator, member of the VraTSR three-component signal transduction system that modulates the expression of the cell wall stress stimulon in response to a number of different cell wall active antibiotics. Given its crucial role in regulating gene expression in response to antibiotic challenges, VraR must be tightly regulated. We report here for the first time in S. aureus convergence of two major signal transduction systems, serine/threonine protein kinase and two (three)-component systems. We demonstrate that VraR can be phosphorylated by the staphylococcal Ser/Thr protein kinase Stk1 and that phosphorylation negatively affects its DNA-binding properties. Mass spectrometric analyses and site-directed mutagenesis identified Thr106, Thr119, Thr175 and Thr178 as phosphoacceptors. A S. aureus ΔvraR mutant expressing a VraR derivative that mimics constitutive phosphorylation, VraR_Asp, still exhibited markedly decreased antibiotic resistance against different cell wall active antibiotics, when compared to the wild-type, suggesting that VraR phosphorylation may represent a novel and presumably more general mechanism of regulation of the two (three)-component systems in staphylococci. Copyright © 2014 Elsevier Inc. All rights reserved.

A Novel TetR Family Transcriptional Regulator, CalR3, Negatively Controls Calcimycin Biosynthesis in Streptomyces chartreusis NRRL 3882

Directory of Open Access Journals (Sweden)

Lixia Gou

2017-11-01

Full Text Available Calcimycin is a unique ionophoric antibiotic that is widely used in biochemical and pharmaceutical applications, but the genetic basis underlying the regulatory mechanisms of calcimycin biosynthesis are unclear. Here, we identified the calR3 gene, which encodes a novel TetR family transcriptional regulator and exerts a negative effect on calcimycin biosynthesis. Disruption of calR3 in Streptomyces chartreusis NRRL 3882 led to significantly increased calcimycin and its intermediate cezomycin. Gene expression analysis showed that the transcription of calR3 and its adjacent calT gene were dramatically enhanced (30- and 171-fold, respectively in GLX26 (ΔcalR3 mutants compared with the wild-type strains. Two CalR3-binding sites within the bidirectional calR3-calT promoter region were identified using a DNase I footprinting assay, indicating that CalR3 directly repressed the transcription of its own gene and the calT gene. In vitro electrophoretic mobility shift assays suggested that both calcimycin and cezomycin can act as CalR3 ligands to induce CalR3 to dissociate from its binding sites. These findings indicate negative feedback for the regulation of CalR3 in calcimycin biosynthesis and suggest that calcimycin production can be improved by manipulating its biosynthetic machinery.

78 FR 77777 - Qualification of Drivers; Exemption Applications; Vision

Science.gov (United States)

2013-12-24

... vision requirement if the exemptions will provide a level of safety that is equivalent to or greater than... Alex M. Long Charles McDonald Kenneth C. Mead Abdelkhaleq R. Muhammad Eduardo Nunez Michael J... suspension during the 3-year period: Buck J. Barney Charles R. Edwards The following applicant, Victor A...

75 FR 38710 - Special Local Regulation, Fran Schnarr Open Water Championships, Huntington Bay, NY

Science.gov (United States)

2010-07-06

...-AA08 Special Local Regulation, Fran Schnarr Open Water Championships, Huntington Bay, NY AGENCY: Coast... Regulation on the navigable waters of Huntington Bay, New York due to the annual Fran Schnarr Open Water... ``Special Local Regulation, Fran Schnarr Open Water Championships, Huntington Bay, NY'' in the Federal...

European regulation for therapeutic use of stem cells.

Science.gov (United States)

Ferry, Nicolas

2017-01-01

The regulation for the use of stem cells has evolved during the past decade with the aim of ensuring a high standard of quality and safety for human derived products throughout Europe to comply with the provision of the Lisbon treaty. To this end, new regulations have been issued and the regulatory status of stem cells has been revised. Indeed, stem cells used for therapeutic purposes can now be classified as a cell preparation, or as advanced therapy medicinal products depending on the clinical indication and on the procedure of cell preparation. Furthermore, exemptions to the European regulation are applicable for stem cells prepared and used within the hospital. The aim of this review is to give the non-specialized reader a broad overview of this particular regulatory landscape.

75 FR 41119 - Special Local Regulations; Sabine River, Orange, TX

Science.gov (United States)

2010-07-15

...-AA08 Special Local Regulations; Sabine River, Orange, TX AGENCY: Coast Guard, DHS. ACTION: Notice of... the Port Arthur Captain of the Port Zone on the Sabine River, Orange, Texas. This Special Local... Orange, TX, Thunder on the Sabine boat races. The powerboat race and associated testing will occur...

10 CFR 9.19 - Segregation of exempt information and deletion of identifying details.

Science.gov (United States)

2010-01-01

... 10 Energy 1 2010-01-01 2010-01-01 false Segregation of exempt information and deletion of... Information Act Regulations § 9.19 Segregation of exempt information and deletion of identifying details. (a... deletions are made from parts of the record by computer, the amount of information deleted will be indicated...

Impact of the Application of Exemption Regulation to the Non-nuclear Industry in Indonesia

International Nuclear Information System (INIS)

Eri-Hiswara

2001-01-01

Nuclear Energy Control Board (BAPETEN) as a nuclear regulatory authority in Indonesia has published the exemption regulation that establishes the value of activity, activity concentration, and dose rate for practices that their operations do not require a licence. From an assessment it was found that the value of activity concentration and dose rate have been exceeded by technologically enhanced naturally occurring radioactive materials (TENORM) present in the raw material and product/waste of some mining and mineral industries known so far as non-nuclear industry. The result has the impact that those industries should be categorized as nuclear industry, with the implication that they need to have licence from regulatory authority, and their activities need to be inspected regularly from the radiation safety point of view by the authority. (author)

76 FR 39289 - Special Local Regulation; Detroit APBA Gold Cup, Detroit River, Detroit, MI

Science.gov (United States)

2011-07-06

...-AA08 Special Local Regulation; Detroit APBA Gold Cup, Detroit River, Detroit, MI AGENCY: Coast Guard... immediately after the Detroit APBA Gold Cup boat race. This special local regulation will establish... entry found in 33 CFR 100.918, Detroit APBA Gold Cup, Detroit, MI. Currently, the regulations located at...

17 CFR 270.22e-3 - Exemption for liquidation of money market funds.

Science.gov (United States)

2010-04-01

... money market funds. 270.22e-3 Section 270.22e-3 Commodity and Securities Exchanges SECURITIES AND... for liquidation of money market funds. (a) Exemption. A registered open-end management investment company or series thereof (“fund”) that is regulated as a money market fund under § 270.2a-7 is exempt...

29 CFR 794.103 - Dependence of exemption on engagement in described distribution.

Science.gov (United States)

2010-07-01

... 29 Labor 3 2010-07-01 2010-07-01 false Dependence of exemption on engagement in described distribution. 794.103 Section 794.103 Labor Regulations Relating to Labor (Continued) WAGE AND HOUR DIVISION... Act Scope and Application in General § 794.103 Dependence of exemption on engagement in described...

48 CFR 9904.409-62 - Exemption.

Science.gov (United States)

2010-10-01

... Section 9904.409-62 Federal Acquisition Regulations System COST ACCOUNTING STANDARDS BOARD, OFFICE OF FEDERAL PROCUREMENT POLICY, OFFICE OF MANAGEMENT AND BUDGET PROCUREMENT PRACTICES AND COST ACCOUNTING STANDARDS COST ACCOUNTING STANDARDS 9904.409-62 Exemption. This Standard shall not apply where compensation...

48 CFR 9904.408-62 - Exemption.

Science.gov (United States)

2010-10-01

... Section 9904.408-62 Federal Acquisition Regulations System COST ACCOUNTING STANDARDS BOARD, OFFICE OF FEDERAL PROCUREMENT POLICY, OFFICE OF MANAGEMENT AND BUDGET PROCUREMENT PRACTICES AND COST ACCOUNTING STANDARDS COST ACCOUNTING STANDARDS 9904.408-62 Exemption. This Standard shall not apply to contracts and...

The Control of Pollution (Special Waste) Regulations 1980 SI 1980 No. 1709

International Nuclear Information System (INIS)

1980-01-01

These Regulations give effect to certain provisions of Community Legislation in Council Directive No. 78/319/EEC concerned with toxic and dangerous waste which will be special waste. Regulation 3 deals with radioactive waste which will be special waste if it has dangerous properties other than radioactivity. Precautions against radioactivity are dealt with under the Radioactive Substances Act 1960. (NEA) [fr

76 FR 77709 - Butyl acrylate-methacrylic acid-styrene polymer; Tolerance Exemption

Science.gov (United States)

2011-12-14

...This regulation establishes an exemption from the requirement of a tolerance for residues of 2-Propenoic acid, 2-methyl-, polymer with butyl 2-propenoate and ethenylbenzene (CAS Reg. No. 25036-16-2); also known as butyl acrylate-methacrylic acid-styrene polymer when used as an inert ingredient in a pesticide chemical formulation. Momentive Performance Materials submitted a petition to EPA under the Federal Food, Drug, and Cosmetic Act (FFDCA), requesting an exemption from the requirement of a tolerance. This regulation eliminates the need to establish a maximum permissible level for residues of 2-Propenoic acid, 2-methyl-, polymer with butyl 2-propenoate and ethenylbenzene on food or feed commodities.

12 CFR 348.6 - General exemption.

Science.gov (United States)

2010-01-01

... 12 Banks and Banking 4 2010-01-01 2010-01-01 false General exemption. 348.6 Section 348.6 Banks and Banking FEDERAL DEPOSIT INSURANCE CORPORATION REGULATIONS AND STATEMENTS OF GENERAL POLICY... minority group, or women; (3) Is a depository institution that has been chartered for less than two years...

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.

miR-181a regulates multiple pathways in hypopharyngeal ...

African Journals Online (AJOL)

Expression of four pathway reporters were significantly increased (p53/DNA damage, TGFβ, MAPK/ERK and MAPK/JNK), while expression of two pathway reporters were decreased (Wnt and NFkB) upon miR-181a down-regulation. Notch, Myc/Max, hypoxia and cell cycle/pRB-E2F pathways were not significantly affected ...

76 FR 49365 - Cost Accounting Standards: Elimination of the Exemption From Cost Accounting Standards for...

Science.gov (United States)

2011-08-10

... Accounting Standards: Elimination of the Exemption From Cost Accounting Standards for Contracts and...: Office of Management and Budget (OMB), Office of Federal Procurement Policy (OFPP), Cost Accounting... Accounting Standards (CAS) Board, is publishing a final rule to eliminate the exemption from regulations...

29 CFR 780.704 - Dependence of exemption on nature of employing establishment.

Science.gov (United States)

2010-07-01

... 29 Labor 3 2010-07-01 2010-07-01 false Dependence of exemption on nature of employing establishment. 780.704 Section 780.704 Labor Regulations Relating to Labor (Continued) WAGE AND HOUR DIVISION... Elevator § 780.704 Dependence of exemption on nature of employing establishment. If an employee is to be...

A review of the justification for exemption orders, and for other low-level radioactive waste disposal practices

International Nuclear Information System (INIS)

Sumerling, T.J.; Sweeney, B.J.

1987-04-01

The historical background and philosophy underlying the Radioactive Substances Act (RSA) and the system of Authorisation and Exemption is examined and the radiological protection criteria contemporary with the introduction of the RSA and those now current are reviewed. The potential radiological impact (maximum individual doses and collective doses to disposal workers and to members of the public) from ''dustbin limit'' disposals, special precautions burial, disposal of demolition wastes, incineration of H-3 and C-14 and from disposals under each of the current Exemption Orders with waste disposal implications are calculated. (author)

78 FR 25572 - Special Local Regulation; Wy-Hi Rowing Regatta, Trenton Channel; Detroit River, Wyandotte, MI

Science.gov (United States)

2013-05-02

...-AA08 Special Local Regulation; Wy-Hi Rowing Regatta, Trenton Channel; Detroit River, Wyandotte, MI..., during, and immediately after the Wy-Hi Rowing Regatta. This special local regulation will establish... to read as follows: Sec. 100.T09-0287 Special Local Regulation; Wy-Hi Rowing Regatta, Wyandotte, MI...

MiR-34a regulates the invasive capacity of canine osteosarcoma cell lines.

Science.gov (United States)

Lopez, Cecilia M; Yu, Peter Y; Zhang, Xiaoli; Yilmaz, Ayse Selen; London, Cheryl A; Fenger, Joelle M

2018-01-01

Osteosarcoma (OSA) is the most common bone tumor in children and dogs; however, no substantial improvement in clinical outcome has occurred in either species over the past 30 years. MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression and play a fundamental role in cancer. The purpose of this study was to investigate the potential contribution of miR-34a loss to the biology of canine OSA, a well-established spontaneous model of the human disease. RT-qPCR demonstrated that miR-34a expression levels were significantly reduced in primary canine OSA tumors and canine OSA cell lines as compared to normal canine osteoblasts. In canine OSA cell lines stably transduced with empty vector or pre-miR-34a lentiviral constructs, overexpression of miR-34a inhibited cellular invasion and migration but had no effect on cell proliferation or cell cycle distribution. Transcriptional profiling of canine OSA8 cells possessing enforced miR-34a expression demonstrated dysregulation of numerous genes, including significant down-regulation of multiple putative targets of miR-34a. Moreover, gene ontology analysis of down-regulated miR-34a target genes showed enrichment of several biological processes related to cell invasion and motility. Lastly, we validated changes in miR-34a putative target gene expression, including decreased expression of KLF4, SEM3A, and VEGFA transcripts in canine OSA cells overexpressing miR-34a and identified KLF4 and VEGFA as direct target genes of miR-34a. Concordant with these data, primary canine OSA tumor tissues demonstrated increased expression levels of putative miR-34a target genes. These data demonstrate that miR-34a contributes to invasion and migration in canine OSA cells and suggest that loss of miR-34a may promote a pattern of gene expression contributing to the metastatic phenotype in canine OSA.

MiR-34a regulates the invasive capacity of canine osteosarcoma cell lines.

Directory of Open Access Journals (Sweden)

Cecilia M Lopez

Full Text Available Osteosarcoma (OSA is the most common bone tumor in children and dogs; however, no substantial improvement in clinical outcome has occurred in either species over the past 30 years. MicroRNAs (miRNAs are small non-coding RNAs that regulate gene expression and play a fundamental role in cancer. The purpose of this study was to investigate the potential contribution of miR-34a loss to the biology of canine OSA, a well-established spontaneous model of the human disease.RT-qPCR demonstrated that miR-34a expression levels were significantly reduced in primary canine OSA tumors and canine OSA cell lines as compared to normal canine osteoblasts. In canine OSA cell lines stably transduced with empty vector or pre-miR-34a lentiviral constructs, overexpression of miR-34a inhibited cellular invasion and migration but had no effect on cell proliferation or cell cycle distribution. Transcriptional profiling of canine OSA8 cells possessing enforced miR-34a expression demonstrated dysregulation of numerous genes, including significant down-regulation of multiple putative targets of miR-34a. Moreover, gene ontology analysis of down-regulated miR-34a target genes showed enrichment of several biological processes related to cell invasion and motility. Lastly, we validated changes in miR-34a putative target gene expression, including decreased expression of KLF4, SEM3A, and VEGFA transcripts in canine OSA cells overexpressing miR-34a and identified KLF4 and VEGFA as direct target genes of miR-34a. Concordant with these data, primary canine OSA tumor tissues demonstrated increased expression levels of putative miR-34a target genes.These data demonstrate that miR-34a contributes to invasion and migration in canine OSA cells and suggest that loss of miR-34a may promote a pattern of gene expression contributing to the metastatic phenotype in canine OSA.

Safety regulation for the design approval of special form radioactive sources

International Nuclear Information System (INIS)

Cho, Woon-Kap

2009-01-01

Several kinds of special form radioactive sources for industrial, medical applications are being produced in Korea. Special form radioactive sources should meet strict safety requirements specified in the domestic safety regulations and the design of the sources should be certified by the regulatory authority, the Ministry of Education, Science and Technology (MEST). Several safety tests such as impact, percussion, heating, and leak tests are performed on the sources according to the domestic regulations and the international safety standards such as ANSI N542-1977 and ISO 2919-1999(E). As a regulatory expert body, Korea Institute of Nuclear Safety (KINS) assesses various types of application documents, such as safety analysis report, quality assurance program, and other documents evidencing fulfillment of requirements for design approval of the special form radioactive sources, submitted by a legal person who intends to produce special form radioactive sources and then reports the assessment result to MEST. A design approval certificate is issued to the applicant by MEST on the basis of a technical evaluation report presented by KINS.

Regulation of Fanconi anemia protein FANCD2 monoubiquitination by miR-302

International Nuclear Information System (INIS)

Suresh, Bharathi; Kumar, A. Madhan; Jeong, Hoe-Su; Cho, Youl-Hee; Ramakrishna, Suresh; Kim, Kye-Seong

2015-01-01

Fanconi anemia (FA) is a recessively inherited multigene disease characterized by congenital defects, progressive bone marrow failure, and heightened cancer susceptibility. Monoubiquitination of the FA pathway member FANCD2 contributes to the repair of replication stalling DNA lesions. However, cellular regulation of FANCD2 monoubiquitination remains poorly understood. In the present study, we identified the miR-302 cluster as a potential regulator of FANCD2 by bioinformatics analysis. MicroRNAs (miRNAs) are the major posttranscriptional regulators of a wide variety of biological processes, and have been implicated in a number of diseases. Expression of the exogenous miR-302 cluster (without miR-367) reduced FANCD2 monoubiquitination and nuclear foci formation. Furthermore, miR-302 cells showed extensive chromosomal breakage upon MMC treatment when compared to mock control cells. Taken together, our results suggest that overexpression of miR-302 plays a critical role in the regulation of FANCD2 monoubiquitination, resulting in characteristic defects in DNA repair within cells. - Highlights: • miR-302 binds to the 3′UTR promoter of the FANCD2 gene to regulate gene expression. • miR-302 cluster down-regulates FANCD2 protein expression. • miR-302 cluster reduces FANCD2 monoubiquitination and nuclear foci formation. • miR-302 exhibits the characteristic defects in DNA repair in cells.

Regulation of Fanconi anemia protein FANCD2 monoubiquitination by miR-302

Energy Technology Data Exchange (ETDEWEB)

Suresh, Bharathi [Graduate School of Biomedical Science and Engineering, Hanyang University, Seoul (Korea, Republic of); College of Medicine, Hanyang University, Seoul (Korea, Republic of); Kumar, A. Madhan [Center of Research Excellence in Corrosion, Research Institute King Fahd University of Petroleum and Minerals, Dhahran (Saudi Arabia); Jeong, Hoe-Su [Graduate School of Biomedical Science and Engineering, Hanyang University, Seoul (Korea, Republic of); Cho, Youl-Hee [College of Medicine, Hanyang University, Seoul (Korea, Republic of); Ramakrishna, Suresh, E-mail: suresh.ramakris@gmail.com [Graduate School of Biomedical Science and Engineering, Hanyang University, Seoul (Korea, Republic of); College of Medicine, Hanyang University, Seoul (Korea, Republic of); Kim, Kye-Seong, E-mail: ks66kim@hanyang.ac.kr [Graduate School of Biomedical Science and Engineering, Hanyang University, Seoul (Korea, Republic of); College of Medicine, Hanyang University, Seoul (Korea, Republic of)

2015-10-16

Fanconi anemia (FA) is a recessively inherited multigene disease characterized by congenital defects, progressive bone marrow failure, and heightened cancer susceptibility. Monoubiquitination of the FA pathway member FANCD2 contributes to the repair of replication stalling DNA lesions. However, cellular regulation of FANCD2 monoubiquitination remains poorly understood. In the present study, we identified the miR-302 cluster as a potential regulator of FANCD2 by bioinformatics analysis. MicroRNAs (miRNAs) are the major posttranscriptional regulators of a wide variety of biological processes, and have been implicated in a number of diseases. Expression of the exogenous miR-302 cluster (without miR-367) reduced FANCD2 monoubiquitination and nuclear foci formation. Furthermore, miR-302 cells showed extensive chromosomal breakage upon MMC treatment when compared to mock control cells. Taken together, our results suggest that overexpression of miR-302 plays a critical role in the regulation of FANCD2 monoubiquitination, resulting in characteristic defects in DNA repair within cells. - Highlights: • miR-302 binds to the 3′UTR promoter of the FANCD2 gene to regulate gene expression. • miR-302 cluster down-regulates FANCD2 protein expression. • miR-302 cluster reduces FANCD2 monoubiquitination and nuclear foci formation. • miR-302 exhibits the characteristic defects in DNA repair in cells.

48 CFR 9904.403-62 - Exemption. [Reserved

Science.gov (United States)

2010-10-01

....403-62 Section 9904.403-62 Federal Acquisition Regulations System COST ACCOUNTING STANDARDS BOARD, OFFICE OF FEDERAL PROCUREMENT POLICY, OFFICE OF MANAGEMENT AND BUDGET PROCUREMENT PRACTICES AND COST ACCOUNTING STANDARDS COST ACCOUNTING STANDARDS 9904.403-62 Exemption. [Reserved] ...

The ties that bind. Proposed IRS regulations would put an organization's tax exemption at risk for the behavior of its executives and board.

Science.gov (United States)

Taylor, Mark

2005-09-19

Newly proposed IRS regulations have a simple message for not-for-profit hospitals: If you want to keep your tax-exempt status, don't engage in excess-benefit transactions. The proposals arrive as compliance officers are paying more attention to the issue. "I wouldn't say that tax awareness is high, but it's higher than ever before," says Lisa Murtha, right.

15 CFR 762.3 - Records exempt from recordkeeping requirements.

Science.gov (United States)

2010-01-01

... 15 Commerce and Foreign Trade 2 2010-01-01 2010-01-01 false Records exempt from recordkeeping requirements. 762.3 Section 762.3 Commerce and Foreign Trade Regulations Relating to Commerce and Foreign Trade (Continued) BUREAU OF INDUSTRY AND SECURITY, DEPARTMENT OF COMMERCE EXPORT ADMINISTRATION REGULATIONS...

78 FR 31627 - Thirteenth Meeting: RTCA Special Committee 222, Inmarsat AMS(R)S.

Science.gov (United States)

2013-05-24

... Committee 222, Inmarsat AMS(R)S. AGENCY: Federal Aviation Administration (FAA), U.S. Department of Transportation (DOT). ACTION: Meeting Notice of RTCA Special Committee 222, Inmarsat AMS(R)S. SUMMARY: The FAA is..., Inmarsat AMS(R)S DATES: The meeting will be held June 10-11 from 9:00 a.m.-5:00 p.m. ADDRESSES: The meeting...

78 FR 61446 - Fourteenth Meeting: RTCA Special Committee 222, Inmarsat AMS(R)S

Science.gov (United States)

2013-10-03

... Committee 222, Inmarsat AMS(R)S AGENCY: Federal Aviation Administration (FAA), U.S. Department of Transportation (DOT). ACTION: Meeting Notice of RTCA Special Committee 222, Inmarsat AMS(R)S. SUMMARY: The FAA is..., Inmarsat AMS(R)S DATES: The meeting will be held November 19, 2013 from 9:00 a.m.-5:00 p.m. ADDRESSES: The...

75 FR 51619 - Privacy Act of 1974: Implementation of Exemptions; Department of Homeland Security/United States...

Science.gov (United States)

2010-08-23

... regulations to exempt portions of a Department of Homeland Security/United States Citizenship and Immigration system of records entitled the ``United States Citizenship and Immigration Services--009 Compliance... of 1974: Implementation of Exemptions; Department of Homeland Security/United States Citizenship and...

Aryl hydrocarbon receptor-dependent regulation of miR-196a expression controls lung fibroblast apoptosis but not proliferation

International Nuclear Information System (INIS)

Hecht, Emelia; Zago, Michela; Sarill, Miles; Rico de Souza, Angela; Gomez, Alvin; Matthews, Jason; Hamid, Qutayba; Eidelman, David H.; Baglole, Carolyn J.

2014-01-01

The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor implicated in the regulation of apoptosis and proliferation. Although activation of the AhR by xenobiotics such as dioxin inhibits the cell cycle and control apoptosis, paradoxically, AhR expression also promotes cell proliferation and survival independent of exogenous ligands. The microRNA (miRNA) miR-196a has also emerged as a regulator of proliferation and apoptosis but a relationship between the AhR and miR-196a is not known. Therefore, we hypothesized that AhR-dependent regulation of endogenous miR-196a expression would promote cell survival and proliferation. Utilizing lung fibroblasts from AhR deficient (AhR −/− ) and wild-type (AhR +/+ ) mice, we show that there is ligand-independent regulation of miRNA, including low miR-196a in AhR −/− cells. Validation by qRT-PCR revealed a significant decrease in basal expression of miR-196a in AhR −/− compared to AhR +/+ cells. Exposure to AhR agonists benzo[a]pyrene (B[a]P) and FICZ as well as AhR antagonist CH-223191 decreased miR-196a expression in AhR +/+ fibroblasts concomitant with decreased AhR protein levels. There was increased proliferation only in AhR +/+ lung fibroblasts in response to serum, corresponding to a decrease in p27 KIP1 protein, a cyclin-dependent kinase inhibitor. Increasing the cellular levels of miR-196a had no effect on proliferation or expression of p27 KIP1 in AhR −/− fibroblasts but attenuated cigarette smoke-induced apoptosis. This study provides the first evidence that AhR expression is essential for the physiological regulation of cellular miRNA levels- including miR-196a. Future experiments designed to elucidate the functional relationship between the AhR and miR-196a may delineate additional novel ligand-independent roles for the AhR. - Highlights: • The AhR controls proliferation and apoptosis in lung cells. • The AhR regulates the expression of the microRNA miR-196a independent of

The Agrobacterium tumefaciens Transcription Factor BlcR Is Regulated via Oligomerization

Energy Technology Data Exchange (ETDEWEB)

Pan, Yi; Fiscus, Valena; Meng, Wuyi; Zheng, Zhida; Zhang, Lian-Hui; Fuqua, Clay; Chen, Lingling (IMCB-Singapore); (Indiana)

2012-02-08

The Agrobacterium tumefaciens BlcR is a member of the emerging isocitrate lyase transcription regulators that negatively regulates metabolism of {gamma}-butyrolactone, and its repressing function is relieved by succinate semialdehyde (SSA). Our crystal structure showed that BlcR folded into the DNA- and SSA-binding domains and dimerized via the DNA-binding domains. Mutational analysis identified residues, including Phe{sup 147}, that are important for SSA association; BlcR{sup F147A} existed as tetramer. Two BlcR dimers bound to target DNA and in a cooperative manner, and the distance between the two BlcR-binding sequences in DNA was critical for BlcR-DNA association. Tetrameric BlcR{sup F147A} retained DNA binding activity, and importantly, this activity was not affected by the distance separating the BlcR-binding sequences in DNA. SSA did not dissociate tetrameric BlcR{sup F147A} or BlcR{sup F147A}-DNA. As well as in the SSA-binding site, Phe{sup 147} is located in a structurally flexible loop that may be involved in BlcR oligomerization. We propose that SSA regulates BlcR DNA-binding function via oligomerization.

75 FR 50700 - Quarterly Listings; Safety Zones, Security Zones, Special Local Regulations, and Drawbridge...

Science.gov (United States)

2010-08-17

...] Quarterly Listings; Safety Zones, Security Zones, Special Local Regulations, and Drawbridge Operation... notice lists temporary safety zones, security zones, special local regulations, and drawbridge operation... responsive to the safety and security needs within their jurisdiction; therefore, District Commanders and...

5 CFR 551.207 - Professional exemption criteria.

Science.gov (United States)

2010-01-01

... Section 551.207 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT CIVIL SERVICE REGULATIONS PAY... criteria. To qualify for the professional exemption, an employee's primary duty must be the performance of work requiring knowledge of an advanced type in a field of science or learning customarily acquired by...

Multiple Myeloma-Derived Exosomes Regulate the Functions of Mesenchymal Stem Cells Partially via Modulating miR-21 and miR-146a

Directory of Open Access Journals (Sweden)

Qian Cheng

2017-01-01

Full Text Available Exosomes derived from cancer cells can affect various functions of mesenchymal stem cells (MSCs via conveying microRNAs (miRs. miR-21 and miR-146a have been demonstrated to regulate MSC proliferation and transformation. Interleukin-6 (IL-6 secreted from transformed MSCs in turn favors the survival of multiple myeloma (MM cells. However, the effects of MM exosomes on MSC functions remain largely unclear. In this study, we investigated the effects of OPM2 (a MM cell line exosomes (OPM2-exo on regulating the proliferation, cancer-associated fibroblast (CAF transformation, and IL-6 secretion of MSCs and determined the role of miR-21 and miR-146a in these effects. We found that OPM2-exo harbored high levels of miR-21 and miR-146a and that OPM2-exo coculture significantly increased MSC proliferation with upregulation of miR-21 and miR-146a. Moreover, OPM2-exo induced CAF transformation of MSCs, which was evidenced by increased fibroblast-activated protein (FAP, α-smooth muscle actin (α-SMA, and stromal-derived factor 1 (SDF-1 expressions and IL-6 secretion. Inhibition of miR-21 or miR-146a reduced these effects of OPM2-exo on MSCs. In conclusion, MM could promote the proliferation, CAF transformation, and IL-6 secretion of MSCs partially through regulating miR21 and miR146a.

40 CFR 180.1157 - Cytokinins; exemption from the requirement of a tolerance.

Science.gov (United States)

2010-07-01

... extract of seaweed meal and kinetin) in or on all food commodities when used as plant regulators on plants, seeds, or cuttings and on all food commodities after harvest in accordance with good agricultural... AGENCY (CONTINUED) PESTICIDE PROGRAMS TOLERANCES AND EXEMPTIONS FOR PESTICIDE CHEMICAL RESIDUES IN FOOD...

76 FR 43376 - Order Granting Temporary Exemptions From Certain Government Securities Act Provisions and...

Science.gov (United States)

2011-07-20

.../gsareg.htm . As noted in its request, on July 16, 2011, ICE Trust reorganized its corporate structure... DEPARTMENT OF THE TREASURY Order Granting Temporary Exemptions From Certain Government Securities... temporary exemptions from certain Government Securities Act of 1986 provisions and regulations regarding...

29 CFR 793.21 - Exempt and nonexempt work.

Science.gov (United States)

2010-07-01

... POLICY OR INTERPRETATION NOT DIRECTLY RELATED TO REGULATIONS EXEMPTION OF CERTAIN RADIO AND TELEVISION... explained in § 793.13, work which does not come within the occupational duties of an announcer, news editor...

Characterization of a Vibrio vulnificus LysR homologue, HupR, which regulates expression of the haem uptake outer membrane protein, HupA.

Science.gov (United States)

Litwin, C M; Quackenbush, J

2001-12-01

In Vibrio vulnificus, the ability to acquire iron from the host has been shown to correlate with virulence. Here, we show that the DNA upstream of hupA (haem uptake receptor) in V. vulnificus encodes a protein in the inverse orientation to hupA (named hupR). HupR shares homology with the LysR family of positive transcriptional activators. A hupA-lacZ fusion contained on a plasmid was transformed into Fur(-), Fur(+)and HupR(-)strains of V. vulnificus. The beta-galactosidase assays and Northern blot analysis showed that transcription of hupA is negatively regulated by iron and the Fur repressor in V. vulnificus. Under low-iron conditions with added haemin, the expression of hupA in the hupR mutant was significantly lower than in the wild-type. This diminished response to haem was detected by both Northern blot and hupA-lacZ fusion analysis. The haem response of hupA in the hupR mutant was restored to wild-type levels when complemented with hupR in trans. These studies suggest that HupR may act as a positive regulator of hupA transcription under low-iron conditions in the presence of haemin. Copyright 2001 Academic Press.

78 FR 19632 - Special Local Regulations; St. Thomas Carnival Watersport Activities, Charlotte Amalie Harbor; St...

Science.gov (United States)

2013-04-02

...-AA08 Special Local Regulations; St. Thomas Carnival Watersport Activities, Charlotte Amalie Harbor; St... proposes to establish a special local regulation on the waters of Charlotte Amalie Harbor in St Thomas, USVI during the St. Thomas Carnival Watersport Activities, a high speed boat race. The event is...

THE PROBLEMS OF USING EXEMPTION ACTIVITY VALUES FOR REGULATING THE MANAGEMENT OF SEALED RADIONUCLIDE SOURCES OF GAMMA-RADIATION

Directory of Open Access Journals (Sweden)

A. N. Barkovsky

2017-01-01

Full Text Available The article focuses on the procedure for exemption of the sealed and unsealed radionuclide sources of gamma radiation from regulatory control. The contradictory nature of the existing set of exemption criteria has been noted, leading, in some cases, to paradoxical situations. It is shown that the exempt activity values determined in NRB-99/2009 and in the international basic safety standards of the IAEA are significantly overestimated (in comparison with the activity values of a point source creating the ambient dose equivalent rate of 1 μSv / h at a distance of 0.1 m for a number of the most widely used gamma-emitting radionuclides, including 22Na, 54Mn, 75Se, 152Eu and 154Eu. It is proposed to revise the current values of exempt activity, bringing them in line with the dose rate criterion for the exempt of sealed radionuclide sources of gamma radiation, and to present them with one significant digit. The corrected values of exempt activity for  seven selected radionuclides are proposed for further use in the process of revision of the national radiation safety standards.

Variation in exemptions to school immunization requirements among New York State private and public schools.

Science.gov (United States)

Lai, Yun-Kuang; Nadeau, Jessica; McNutt, Louise-Anne; Shaw, Jana

2014-12-12

School immunization requirements have ensured high vaccination rates and have helped to control vaccine-preventable diseases. However, vaccine exemptions have increased in the last decade. This study compared New York State private versus public schools with respect to medical and religious exemption rates. This retrospective study utilizes New York State Department of Health Immunization Survey data from the 2003 through 2012 academic years. Schools were categorized as private or public, the former further categorized by religious affiliation. Rates of medical and religious vaccine exemptions were compared by school category. From 2003 to 2012, religious exemptions increased in private and public schools from 0.63% to 1.35% and 0.17% to 0.29% (Spearman's R: 0.89 and 0.81), respectively. Among private schools, increases in religious exemption rates during the study period were observed in Catholic/Eastern Orthodox, Protestant/Other Christian, Jewish, and secular schools (Spearman's R=0.66, 0.99, 0.89, and 0.93), respectively. Exemption rate ratios in private schools compared to public schools were 1.39 (95% CI 1.15-1.68) for medical and 3.94 (95% CI: 3.20-4.86) for religious exemptions. Among private school students, all school types except for Catholic/Eastern Orthodox and Episcopal affiliates were more likely to report religious exemptions compared to children in public schools. Medical and religious exemption rates increased over time and higher rates were observed among New York State private schools compared to public schools. Low exemption rates are critical to minimize disease outbreaks in the schools and their community. Copyright © 2014 Elsevier Ltd. All rights reserved.

29 CFR 780.405 - Exemption is direct and does not mean activities are agriculture.

Science.gov (United States)

2010-07-01

... agriculture. 780.405 Section 780.405 Labor Regulations Relating to Labor (Continued) WAGE AND HOUR DIVISION... EXEMPTIONS APPLICABLE TO AGRICULTURE, PROCESSING OF AGRICULTURAL COMMODITIES, AND RELATED SUBJECTS UNDER THE FAIR LABOR STANDARDS ACT Employment in Agriculture or Irrigation That Is Exempted From the Overtime Pay...

8 CFR 313.3 - Statutory exemptions.

Science.gov (United States)

2010-01-01

... 8 Aliens and Nationality 1 2010-01-01 2010-01-01 false Statutory exemptions. 313.3 Section 313.3 Aliens and Nationality DEPARTMENT OF HOMELAND SECURITY NATIONALITY REGULATIONS MEMBERSHIP IN THE... education will qualify as an essential of living only if the applicant can establish the existence of...

31 CFR 588.206 - Exempt transactions.

Science.gov (United States)

2010-07-01

... 31 Money and Finance: Treasury 3 2010-07-01 2010-07-01 false Exempt transactions. 588.206 Section 588.206 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF... assist in the creation of information or informational materials; and, with respect to information or...

31 CFR 560.210 - Exempt transactions.

Science.gov (United States)

2010-07-01

... 31 Money and Finance: Treasury 3 2010-07-01 2010-07-01 false Exempt transactions. 560.210 Section 560.210 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF... services to market, produce or co-produce, create or assist in the creation of information and...

31 CFR 545.208 - Exempt transactions.

Science.gov (United States)

2010-07-01

... 31 Money and Finance: Treasury 3 2010-07-01 2010-07-01 false Exempt transactions. 545.208 Section 545.208 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF... assist in the creation of information or informational materials; and, with respect to information or...

31 CFR 542.206 - Exempt transactions.

Science.gov (United States)

2010-07-01

... 31 Money and Finance: Treasury 3 2010-07-01 2010-07-01 false Exempt transactions. 542.206 Section 542.206 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF... assist in the creation of information or informational materials; and, with respect to information or...

31 CFR 587.206 - Exempt transactions.

Science.gov (United States)

2010-07-01

... 31 Money and Finance: Treasury 3 2010-07-01 2010-07-01 false Exempt transactions. 587.206 Section 587.206 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF...-produce, create, or assist in the creation of information or informational materials; and, with respect to...

31 CFR 586.206 - Exempt transactions.

Science.gov (United States)

2010-07-01

... 31 Money and Finance: Treasury 3 2010-07-01 2010-07-01 false Exempt transactions. 586.206 Section 586.206 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF... or assist in the creation of information and informational materials, and payment of royalties to...

31 CFR 537.210 - Exempt transactions.

Science.gov (United States)

2010-07-01

... 31 Money and Finance: Treasury 3 2010-07-01 2010-07-01 false Exempt transactions. 537.210 Section 537.210 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF... assist in the creation of information or informational materials; and, with respect to information or...

31 CFR 538.212 - Exempt transactions.

Science.gov (United States)

2010-07-01

... 31 Money and Finance: Treasury 3 2010-07-01 2010-07-01 false Exempt transactions. 538.212 Section 538.212 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF... services to market, produce or co-produce, create or assist in the creation of information and...

31 CFR 548.206 - Exempt transactions.

Science.gov (United States)

2010-07-01

... 31 Money and Finance: Treasury 3 2010-07-01 2010-07-01 false Exempt transactions. 548.206 Section 548.206 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF... assist in the creation of information or informational materials; and, with respect to information or...

31 CFR 544.206 - Exempt transactions.

Science.gov (United States)

2010-07-01

... 31 Money and Finance: Treasury 3 2010-07-01 2010-07-01 false Exempt transactions. 544.206 Section 544.206 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF...-produce, create, or assist in the creation of information or informational materials; and, with respect to...

31 CFR 541.206 - Exempt transactions.

Science.gov (United States)

2010-07-01

... 31 Money and Finance: Treasury 3 2010-07-01 2010-07-01 false Exempt transactions. 541.206 Section 541.206 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF... assist in the creation of information or informational materials; and, with respect to information or...

Aryl hydrocarbon receptor-dependent regulation of miR-196a expression controls lung fibroblast apoptosis but not proliferation

Energy Technology Data Exchange (ETDEWEB)

Hecht, Emelia [Department of Medicine, McGill University, Montreal, Quebec (Canada); Zago, Michela [Research Institute of the McGill University Health Centre, McGill University, Montreal, Quebec (Canada); Sarill, Miles [Department of Medicine, McGill University, Montreal, Quebec (Canada); Rico de Souza, Angela [Research Institute of the McGill University Health Centre, McGill University, Montreal, Quebec (Canada); Gomez, Alvin; Matthews, Jason [Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON (Canada); Hamid, Qutayba; Eidelman, David H. [Department of Medicine, McGill University, Montreal, Quebec (Canada); Research Institute of the McGill University Health Centre, McGill University, Montreal, Quebec (Canada); Baglole, Carolyn J., E-mail: Carolyn.baglole@McGill.ca [Department of Medicine, McGill University, Montreal, Quebec (Canada); Research Institute of the McGill University Health Centre, McGill University, Montreal, Quebec (Canada)

2014-11-01

The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor implicated in the regulation of apoptosis and proliferation. Although activation of the AhR by xenobiotics such as dioxin inhibits the cell cycle and control apoptosis, paradoxically, AhR expression also promotes cell proliferation and survival independent of exogenous ligands. The microRNA (miRNA) miR-196a has also emerged as a regulator of proliferation and apoptosis but a relationship between the AhR and miR-196a is not known. Therefore, we hypothesized that AhR-dependent regulation of endogenous miR-196a expression would promote cell survival and proliferation. Utilizing lung fibroblasts from AhR deficient (AhR{sup −/−}) and wild-type (AhR{sup +/+}) mice, we show that there is ligand-independent regulation of miRNA, including low miR-196a in AhR{sup −/−} cells. Validation by qRT-PCR revealed a significant decrease in basal expression of miR-196a in AhR{sup −/−} compared to AhR{sup +/+} cells. Exposure to AhR agonists benzo[a]pyrene (B[a]P) and FICZ as well as AhR antagonist CH-223191 decreased miR-196a expression in AhR{sup +/+} fibroblasts concomitant with decreased AhR protein levels. There was increased proliferation only in AhR{sup +/+} lung fibroblasts in response to serum, corresponding to a decrease in p27{sup KIP1} protein, a cyclin-dependent kinase inhibitor. Increasing the cellular levels of miR-196a had no effect on proliferation or expression of p27{sup KIP1} in AhR{sup −/−} fibroblasts but attenuated cigarette smoke-induced apoptosis. This study provides the first evidence that AhR expression is essential for the physiological regulation of cellular miRNA levels- including miR-196a. Future experiments designed to elucidate the functional relationship between the AhR and miR-196a may delineate additional novel ligand-independent roles for the AhR. - Highlights: • The AhR controls proliferation and apoptosis in lung cells. • The AhR regulates the

International recommendations on scope of radiological protection regulations - ICRP Publication 104

International Nuclear Information System (INIS)

Stanescu, Gabriel; Avadanei, Camelia; Ghilea, Simion

2011-01-01

The system of radiological protection applies, in principle, to all exposures to ionising radiation. Nevertheless, in practice, the measures taken in order to control these exposures should be limited for pragmatic reasons. ICRP Publication 104 deals with the scope of radiological protection control measures and describes the instruments that can be used for this purpose: exclusion, exemption, clearance. This paper aims to present the ICRP recommendations on scope of regulations in all types of exposure situations: planned, emergency and existing. Also, there are discussed the instruments available to regulators in different exposure situations. Exclusion refers to the deliberate omission of exposure situations from the scope of regulatory requirements, and exemption refers to waiving regulatory requirements if their application is not warranted. A special case of exemption, termed 'clearance', refers to the relinquishing of regulatory control if such a control becomes unwarranted. Societal attitudes to the control of exposure situations are taken into account in determining what can be excluded or exempted from regulatory control. People have higher demands for controlling 'artificial' exposure situations than for dealing with 'natural' exposure situations. Therefore, account should be taken not only of the justification and optimisation of controlling measures, but also of the different expectations of those affected by the exposure situations. The recommendations in this report are intended to assist in defining what needs to be the subject of regulatory requirements for radiological protection and what does not. The application of regulatory controls should achieve a net benefit in protection; otherwise, regulatory control is not justified. Similarly, regulatory requirements should be applied in a manner that optimises protection, otherwise the application of regulatory requirements is not warranted. (authors)

18 CFR 152.1 - Exemption applications and blanket certificates.

Science.gov (United States)

2010-04-01

... implementing the Natural Gas Act, “vehicular natural gas” or “VNG” means natural gas that will be used, in... Commission's regulations implementing the Natural Gas Act, vehicular natural gas, or VNG, is deemed to be... REGULATORY COMMISSION, DEPARTMENT OF ENERGY REGULATIONS UNDER NATURAL GAS ACT APPLICATION FOR EXEMPTION FROM...

A review of the concepts of exclusion and exemption

International Nuclear Information System (INIS)

Wrixon, A.D.

2004-01-01

The concept of exemption has been widely used in radiological protection. It is part of the regulator's arsenal for applying legislative requirements in a graded fashion, to avoid the expenditure of effort on situations where the return in terms of improvement in protection would otherwise be trivial. Nevertheless, it still remains a controversial matter. Perhaps somewhat surprisingly, it is not so much the dosimetric criteria for exemption that cause debate; it is more the way in which the concept is used; the scenarios employed to calculate derived activity concentrations, and its relationship to the somewhat analogous concept of exclusion. Much of the debate regarding the use of the concept and its relationship with exclusion finds its origin in the national legislative culture that has developed over the years in various countries and the inevitable resistance to keep pace with the evolution of the system of radiological protection as recommended by the International Commission on Radiological Protection and implemented through the International Basic Safety Standards for Protection against Ionizing Radiation and for the Safety of Radiation Sources. A particular problem has been the full integration into the legislative system of protection of exposures to radiation from sources of natural origin and the degree to which exemption is a relevant concept for dealing with such situations. The purpose of this paper is to attempt to provide some clarity on the two concepts and their practical implementation with a view to encouraging international harmonization and avoiding further unnecessary debate. (author)

A 3'-untranslated region (3'UTR) induces organ adhesion by regulating miR-199a* functions.

Science.gov (United States)

Lee, Daniel Y; Shatseva, Tatiana; Jeyapalan, Zina; Du, William W; Deng, Zhaoqun; Yang, Burton B

2009-01-01

Mature microRNAs (miRNAs) are single-stranded RNAs of 18-24 nucleotides that repress post-transcriptional gene expression. However, it is unknown whether the functions of mature miRNAs can be regulated. Here we report that expression of versican 3'UTR induces organ adhesion in transgenic mice by modulating miR-199a* activities. The study was initiated by the hypothesis that the non-coding 3'UTR plays a role in the regulation of miRNA function. Transgenic mice expressing a construct harboring the 3'UTR of versican exhibits the adhesion of organs. Computational analysis indicated that a large number of microRNAs could bind to this fragment potentially including miR-199a*. Expression of versican and fibronectin, two targets of miR-199a*, are up-regulated in transgenic mice, suggesting that the 3'UTR binds and modulates miR-199a* activities, freeing mRNAs of versican and fibronectin from being repressed by miR-199a*. Confirmation of the binding was performed by PCR using mature miR-199a* as a primer and the targeting was performed by luciferase assays. Enhanced adhesion by expression of the 3'UTR was confirmed by in vitro assays. Our results demonstrated that upon arrival in cytoplasm, miRNA activities can be modulated locally by the 3'UTR. Our assay may be developed as sophisticated approaches for studying the mutual regulation of miRNAs and mRNAs in vitro and in vivo. We anticipate that expression of the 3'UTR may be an approach in the development of gene therapy.

75 FR 13454 - Special Local Regulation, Fran Schnarr Open Water Championships, Huntington Bay, NY

Science.gov (United States)

2010-03-22

...-AA08 Special Local Regulation, Fran Schnarr Open Water Championships, Huntington Bay, NY AGENCY: Coast... navigable waters of Huntington Bay, New York due to the annual Fran Schnarr Open Water Championships. The..., ``Special Local Regulation, Fran Schnarr Open Water Championships, Huntington Bay, NY'' (Docket number USCG...

miR-181a and miR-630 regulate cisplatin-induced cancer cell death.

Science.gov (United States)

Galluzzi, Lorenzo; Morselli, Eugenia; Vitale, Ilio; Kepp, Oliver; Senovilla, Laura; Criollo, Alfredo; Servant, Nicolas; Paccard, Caroline; Hupé, Philippe; Robert, Thomas; Ripoche, Hugues; Lazar, Vladimir; Harel-Bellan, Annick; Dessen, Philippe; Barillot, Emmanuel; Kroemer, Guido

2010-03-01

MicroRNAs (miRNA) are noncoding RNAs that regulate multiple cellular processes, including proliferation and apoptosis. We used microarray technology to identify miRNAs that were upregulated by non-small cell lung cancer (NSCLC) A549 cells in response to cisplatin (CDDP). The corresponding synthetic miRNA precursors (pre-miRNAs) per se were not lethal when transfected into A549 cells yet affected cell death induction by CDDP, C2-ceramide, cadmium, etoposide, and mitoxantrone in an inducer-specific fashion. Whereas synthetic miRNA inhibitors (anti-miRNAs) targeting miR-181a and miR-630 failed to modulate the response of A549 to CDDP, pre-miR-181a and pre-miR-630 enhanced and reduced CDDP-triggered cell death, respectively. Pre-miR-181a and pre-miR-630 consistently modulated mitochondrial/postmitochondrial steps of the intrinsic pathway of apoptosis, including Bax oligomerization, mitochondrial transmembrane potential dissipation, and the proteolytic maturation of caspase-9 and caspase-3. In addition, pre-miR-630 blocked early manifestations of the DNA damage response, including the phosphorylation of the ataxia-telangiectasia mutated (ATM) kinase and of two ATM substrates, histone H2AX and p53. Pharmacologic and genetic inhibition of p53 corroborated the hypothesis that pre-miR-630 (but not pre-miR-181a) blocks the upstream signaling pathways that are ignited by DNA damage and converge on p53 activation. Pre-miR-630 arrested A549 cells in the G0-G1 phase of the cell cycle, correlating with increased levels of the cell cycle inhibitor p27(Kip1) as well as with reduced proliferation rates and resulting in greatly diminished sensitivity of A549 cells to the late S-G2-M cell cycle arrest mediated by CDDP. Altogether, these results identify miR-181a and miR-630 as novel modulators of the CDDP response in NSCLC.

29 CFR 794.119 - Dependence of exemption on sales volume of the enterprise.

Science.gov (United States)

2010-07-01

... 29 Labor 3 2010-07-01 2010-07-01 false Dependence of exemption on sales volume of the enterprise. 794.119 Section 794.119 Labor Regulations Relating to Labor (Continued) WAGE AND HOUR DIVISION... Act Annual Gross Volume of Sales § 794.119 Dependence of exemption on sales volume of the enterprise...

31 CFR 539.204 - Exempt transactions.

Science.gov (United States)

2010-07-01

... 31 Money and Finance: Treasury 3 2010-07-01 2010-07-01 false Exempt transactions. 539.204 Section 539.204 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF... of services to market, produce or co-produce, create, or assist in the creation of information or...

76 FR 15214 - Special Local Regulations for Marine Events; Potomac River, Charles County, MD

Science.gov (United States)

2011-03-21

...-AA08 Special Local Regulations for Marine Events; Potomac River, Charles County, MD AGENCY: Coast Guard... for Marine Events; Potomac River, Charles County, MD'' in the Federal Register (76 FR 1381). We... follows: Sec. 100.35-T05-1113 Special Local Regulations for Marine Events; Potomac River, Charles County...

MiR529a modulates panicle architecture through regulating SQUAMOSA PROMOTER BINDING-LIKE genes in rice (Oryza sativa).

Science.gov (United States)

Yue, Erkui; Li, Chao; Li, Yu; Liu, Zhen; Xu, Jian-Hong

2017-07-01

MiR529a affects rice panicle architecture by targeting OsSPL2,OsSPL14 and OsSPL17 genes that could regulate their downstream panicle related genes. The panicle architecture determines the grain yield and quality of rice, which could be regulated by many transcriptional factors. The SQUAMOSA PROMOTER BINDING-LIKE (SPL) transcription factors are involved in the regulation of panicle development, which are targeted by miR156 and miR529. The expression profile demonstrated that miR529a is preferentially expressed in the early panicle of rice and it might regulate panicle development in rice. However, the regulation mechanism of miR529-SPL is still not clear. In this study, we predicted five miR529a putative target genes, OsSPL2, OsSPL14, OsSPL16, OsSPL17 and OsSPL18, while only the expression of OsSPL2, OsSPL14, and OsSPL17 was regulated by miR529a in the rice panicle. Overexpression of miR529a dramatically affected panicle architecture, which was regulated by OsSPL2, OsSPL14, and OsSPL17. Furthermore, the 117, 35, and 25 pathway genes associated with OsSPL2, OsSPL14 and OsSPL17, respectively, were predicted, and they shared 20 putative pathway genes. Our results revealed that miR529a could play a vital role in the regulation of panicle architecture through regulating OsSPL2, OsSPL14, OsSPL17 and the complex networks formed by their pathway and downstream genes. These findings will provide new genetic resources for reshaping ideal plant architecture and breeding high yield rice varieties.

Implications for the management of R A materials transport

International Nuclear Information System (INIS)

Devine, I.R.

1997-01-01

This paper attempts to describe some Exclusions and Exemptions from the current and proposed transport regulations and describes those requirements applicable to low active material. It concludes that Clearance is the dominant issue and that within the UK nuclear sector, the current (1985 as amended 1990) transport regulations have no significant impact on the management of low active materials. Nor will the proposed (1996) Regulations. (author)

77 FR 42465 - Special Local Regulations, Cruce a Nado Internacional, Ponce Harbor; Ponce, PR

Science.gov (United States)

2012-07-19

... effect on the human environment. This proposed rule involves special local regulations issued in.... Dated: June 7, 2012. D.W. Pearson, Captain, U.S. Coast Guard, Captain of the Port San Juan. [FR Doc...

A 3'-untranslated region (3'UTR induces organ adhesion by regulating miR-199a* functions.

Directory of Open Access Journals (Sweden)

Daniel Y Lee

Full Text Available Mature microRNAs (miRNAs are single-stranded RNAs of 18-24 nucleotides that repress post-transcriptional gene expression. However, it is unknown whether the functions of mature miRNAs can be regulated. Here we report that expression of versican 3'UTR induces organ adhesion in transgenic mice by modulating miR-199a* activities. The study was initiated by the hypothesis that the non-coding 3'UTR plays a role in the regulation of miRNA function. Transgenic mice expressing a construct harboring the 3'UTR of versican exhibits the adhesion of organs. Computational analysis indicated that a large number of microRNAs could bind to this fragment potentially including miR-199a*. Expression of versican and fibronectin, two targets of miR-199a*, are up-regulated in transgenic mice, suggesting that the 3'UTR binds and modulates miR-199a* activities, freeing mRNAs of versican and fibronectin from being repressed by miR-199a*. Confirmation of the binding was performed by PCR using mature miR-199a* as a primer and the targeting was performed by luciferase assays. Enhanced adhesion by expression of the 3'UTR was confirmed by in vitro assays. Our results demonstrated that upon arrival in cytoplasm, miRNA activities can be modulated locally by the 3'UTR. Our assay may be developed as sophisticated approaches for studying the mutual regulation of miRNAs and mRNAs in vitro and in vivo. We anticipate that expression of the 3'UTR may be an approach in the development of gene therapy.

78 FR 8684 - Twelfth Meeting: RTCA Special Committee 222, Inmarsat AMS(R)S

Science.gov (United States)

2013-02-06

... Committee 222, Inmarsat AMS(R)S AGENCY: Federal Aviation Administration (FAA), U.S. Department of Transportation (DOT). ACTION: Meeting Notice of RTCA Special Committee 222, Inmarsat AMS(R)S. SUMMARY: The FAA is..., Inmarsat AMS(R)S. DATES: The meeting will be held February 20, 2013, from 1:00 p.m.--4:00 p.m. ADDRESSES...

76 FR 1381 - Special Local Regulations for Marine Events; Potomac River, Charles County, MD

Science.gov (United States)

2011-01-10

...-AA08 Special Local Regulations for Marine Events; Potomac River, Charles County, MD AGENCY: Coast Guard... Regulations for Marine Events; Potomac River, Charles County, MD. (a) Regulated area. The following location... local regulations during the ``Potomac River Sharkfest Swim'' amateur swim, a marine event to be held on...

Legislation for the countermeasures on special issues of nuclear safety regulations

International Nuclear Information System (INIS)

Cho, Byung Sun; Lee, Mo Sung; Chung, Gum Chun; Kim, Heon Jin; Oh, Ho Chul

2004-02-01

Since the present nuclear safety regulation has some legal problems that refer to special issues and contents of regulatory provisions, this report has preformed research on the legal basic theory of nuclear safety regulation to solve the problems. In addition, this report analyzed the problems of each provisions and suggested the revision drafts on the basis of analyzing problems and the undergoing theory of nuclear safety regulation

Legislation for the countermeasures on special issues of nuclear safety regulations

Energy Technology Data Exchange (ETDEWEB)

Cho, Byung Sun; Lee, Mo Sung; Chung, Gum Chun; Kim, Heon Jin; Oh, Ho Chul [Chongju Univ., Cheongju (Korea, Republic of)

2004-02-15

Since the present nuclear safety regulation has some legal problems that refer to special issues and contents of regulatory provisions, this report has preformed research on the legal basic theory of nuclear safety regulation to solve the problems. In addition, this report analyzed the problems of each provisions and suggested the revision drafts on the basis of analyzing problems and the undergoing theory of nuclear safety regulation.

77 FR 6708 - Special Local Regulations for Marine Events; Potomac River, Charles County, MD

Science.gov (United States)

2012-02-09

...-AA08 Special Local Regulations for Marine Events; Potomac River, Charles County, MD AGENCY: Coast Guard... River, Charles County, MD. (a) Regulated area. The following location is a regulated area: All waters of... local regulations during the ``Potomac River Sharkfest Swim'' amateur swim, a marine event to be held on...

29 CFR Non - Mandatory Appendix A to Subpart B of Part 1904-Partially Exempt Industries

Science.gov (United States)

2010-07-01

... Exempt Industries Non Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH... classification, must report to OSHA any workplace incident that results in a fatality or the hospitalization of... Agents, Brokers & Services 832 Individual and Family Services. 653 Real Estate Agents and Managers 835...

The NifA-RpoN regulon of Mesorhizobium loti strain R7A and its symbiotic activation by a novel LacI/GalR-family regulator.

Directory of Open Access Journals (Sweden)

John T Sullivan

Full Text Available Mesorhizobium loti is the microsymbiont of Lotus species, including the model legume L. japonicus. M. loti differs from other rhizobia in that it contains two copies of the key nitrogen fixation regulatory gene nifA, nifA1 and nifA2, both of which are located on the symbiosis island ICEMlSym(R7A. M. loti R7A also contains two rpoN genes, rpoN1 located on the chromosome outside of ICEMlSym(R7A and rpoN2 that is located on ICEMlSym(R7A. The aims of the current work were to establish how nifA expression was activated in M. loti and to characterise the NifA-RpoN regulon. The nifA2 and rpoN2 genes were essential for nitrogen fixation whereas nifA1 and rpoN1 were dispensable. Expression of nifA2 was activated, possibly in response to an inositol derivative, by a novel regulator of the LacI/GalR family encoded by the fixV gene located upstream of nifA2. Other than the well-characterized nif/fix genes, most NifA2-regulated genes were not required for nitrogen fixation although they were strongly expressed in nodules. The NifA-regulated nifZ and fixU genes, along with nifQ which was not NifA-regulated, were required in M. loti for a fully effective symbiosis although they are not present in some other rhizobia. The NifA-regulated gene msi158 that encodes a porin was also required for a fully effective symbiosis. Several metabolic genes that lacked NifA-regulated promoters were strongly expressed in nodules in a NifA2-dependent manner but again mutants did not have an overt symbiotic phenotype. In summary, many genes encoded on ICEMlSym(R7A were strongly expressed in nodules but not free-living rhizobia, but were not essential for symbiotic nitrogen fixation. It seems likely that some of these genes have functional homologues elsewhere in the genome and that bacteroid metabolism may be sufficiently plastic to adapt to loss of certain enzymatic functions.

26 CFR 1.501(a)-1 - Exemption from taxation.

Science.gov (United States)

2010-04-01

... 26 Internal Revenue 7 2010-04-01 2010-04-01 true Exemption from taxation. 1.501(a)-1 Section 1.501(a)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES (CONTINUED) Exempt Organizations § 1.501(a)-1 Exemption from taxation. (a) In...

26 CFR 1.923-1T - Temporary regulations; exempt foreign trade income.

Science.gov (United States)

2010-04-01

... be exempt foreign trade income. If a FSC has a non-corporate shareholder (shareholders), 16/23 of its foreign trade income attributable to the noncorporate shareholder's (shareholders') proportionate interest... attributable to the non-corporate shareholder's (shareholders') proportionate interest in the FSC will be...

Genetic versus Non-Genetic Regulation of miR-103, miR-143 and miR-483-3p Expression in Adipose Tissue and Their Metabolic Implications—A Twin Study

Directory of Open Access Journals (Sweden)

Jette Bork-Jensen

2014-07-01

Full Text Available Murine models suggest that the microRNAs miR-103 and miR-143 may play central roles in the regulation of subcutaneous adipose tissue (SAT and development of type 2 diabetes (T2D. The microRNA miR-483-3p may reduce adipose tissue expandability and cause ectopic lipid accumulation, insulin resistance and T2D. We aimed to explore the genetic and non-genetic factors that regulate these microRNAs in human SAT, and to investigate their impact on metabolism in humans. Levels of miR-103, miR-143 and miR-483-3p were measured in SAT biopsies from 244 elderly monozygotic and dizygotic twins using real-time PCR. Heritability estimates were calculated and multiple regression analyses were performed to study associations between these microRNAs and measures of metabolism, as well as between these microRNAs and possible regulating factors. We found that increased BMI was associated with increased miR-103 expression levels. In addition, the miR-103 levels were positively associated with 2 h plasma glucose levels and hemoglobin A1c independently of BMI. Heritability estimates for all three microRNAs were low. In conclusion, the expression levels of miR-103, miR-143 and miR-483-3p in adipose tissue are primarily influenced by non-genetic factors, and miR-103 may be involved in the development of adiposity and control of glucose metabolism in humans.

77 FR 39395 - Special Local Regulations; Ocean State Tall Ships Festival 2012, Narragansett Bay, RI

Science.gov (United States)

2012-07-03

...-AA08 Special Local Regulations; Ocean State Tall Ships Festival 2012, Narragansett Bay, RI AGENCY... Tall Ships Festival 2012. DATES: This rule is effective from July 6, 2012 until July 10, 2012... ``Special Local Regulations: Ocean State Tall Ships Festival 2012, Narragansett Bay, RI'' in the Federal...

Practical applications of the exemption principle in radiation protection

International Nuclear Information System (INIS)

Wrixon, A.D.

2004-01-01

The concept of exemption has been widely used in radiological protection. It is part of the regulator's arsenal for applying legislative requirements in a graded fashion, to avoid the expenditure of effort on situations where the return in terms of improvement in protection would otherwise be trivial. Nevertheless, it still remains a controversial matter. It is not so much the dosimetric criteria for exemption that cause debate; it is more the way in which the concept is used; the scenarios employed to calculate derived activity concentrations, and its relationship to the somewhat analogous concept of exclusion. A particular problem has been the full integration into the legislative system of protection of exposures to radiation from sources of natural origin and the degree to which exemption is a relevant concept for dealing with such situations. The purpose of this paper is to attempt to provide some clarity on the two concepts and their practical implementation with a view to encouraging international harmonization and avoiding further unnecessary debate. (orig.)

Diverse Genetic Regulon of the Virulence-Associated Transcriptional Regulator MucR in Brucella abortus 2308

Science.gov (United States)

Caswell, Clayton C.; Elhassanny, Ahmed E. M.; Planchin, Emilie E.; Roux, Christelle M.; Weeks-Gorospe, Jenni N.; Ficht, Thomas A.; Dunman, Paul M.

2013-01-01

The Ros-type regulator MucR is one of the few transcriptional regulators that have been linked to virulence in Brucella. Here, we show that a Brucella abortus in-frame mucR deletion strain exhibits a pronounced growth defect during in vitro cultivation and, more importantly, that the mucR mutant is attenuated in cultured macrophages and in mice. The genetic basis for the attenuation of Brucella mucR mutants has not been defined previously, but in the present study the genes regulated by MucR in B. abortus have been elucidated using microarray analysis and real-time reverse transcription-PCR (RT-PCR). In B. abortus 2308, MucR regulates a wide variety of genes whose products may function in establishing and maintaining cell envelope integrity, polysaccharide biosynthesis, iron homeostasis, genome plasticity, and transcriptional regulation. Particularly notable among the MucR-regulated genes identified is arsR6 (nolR), which encodes a transcriptional regulator previously linked to virulence in Brucella melitensis 16 M. Importantly, electrophoretic mobility shift assays (EMSAs) determined that a recombinant MucR protein binds directly to the promoter regions of several genes repressed by MucR (including arsR6 [nolR]), and in Brucella, as in other alphaproteobacteria, MucR binds to its own promoter to repress expression of the gene that encodes it. Overall, these studies have uncovered the diverse genetic regulon of MucR in Brucella, and in doing so this work has begun to define the MucR-controlled genetic circuitry whose misregulation contributes to the virulence defect of Brucella mucR mutants. PMID:23319565

7 CFR 1250.530 - Certification of exempt producers.

Science.gov (United States)

2010-01-01

... section 2103 of the Organic Foods Production Act of 1990 (7 U.S.C. 6502), a signed certification that the... 7 Agriculture 10 2010-01-01 2010-01-01 false Certification of exempt producers. 1250.530 Section... RESEARCH AND PROMOTION Rules and Regulations Registration, Certification and Reports § 1250.530...

15 CFR 303.3 - Determination of the total annual duty-exemption.

Science.gov (United States)

2010-01-01

... 15 Commerce and Foreign Trade 2 2010-01-01 2010-01-01 false Determination of the total annual duty-exemption. 303.3 Section 303.3 Commerce and Foreign Trade Regulations Relating to Commerce and Foreign Trade (Continued) INTERNATIONAL TRADE ADMINISTRATION, DEPARTMENT OF COMMERCE MISCELLANEOUS REGULATIONS WATCHES...

15 CFR 303.9 - Restrictions on the transfer of duty-exemptions.

Science.gov (United States)

2010-01-01

... 15 Commerce and Foreign Trade 2 2010-01-01 2010-01-01 false Restrictions on the transfer of duty-exemptions. 303.9 Section 303.9 Commerce and Foreign Trade Regulations Relating to Commerce and Foreign Trade (Continued) INTERNATIONAL TRADE ADMINISTRATION, DEPARTMENT OF COMMERCE MISCELLANEOUS REGULATIONS WATCHES...

Exemption of the use of radiation from the safety licence and reporting obligation

International Nuclear Information System (INIS)

1999-07-01

The primary means of controlling the use of radiation is the safety licence procedure. The safety licence, and the granting of the licence, are regulated in the section 16 of the Finnish Radiation Act (592/1991). In section 17 of the act, certain practices are exempted from the safety licence. In addition to these practices, the Radiation and Nuclear Safety (STUK) may (on the basis of the same legal clause) exempt other types of radiation use from the safety licence, if it is possible to ascertain with sufficient reliability that the use of the radiation will not cause damage or danger to health. This guide presents the conditions applying to exemption from the safety licence for the use of radiation and reporting obligation, and also the exemption values for radioactive substances which, if exceeded, will entail the application of the safety licence and notification procedure for the use of radiation in question. The guide also presents exemptions in the use of exemption values, and requirements associated with the exemption of radiation appliances. However, the guide does not apply to the use of nuclear energy

Exemption of the use of radiation from the safety licence and reporting obligation

Energy Technology Data Exchange (ETDEWEB)

NONE

1999-07-01

The primary means of controlling the use of radiation is the safety licence procedure. The safety licence, and the granting of the licence, are regulated in the section 16 of the Finnish Radiation Act (592/1991). In section 17 of the act, certain practices are exempted from the safety licence. In addition to these practices, the Radiation and Nuclear Safety (STUK) may (on the basis of the same legal clause) exempt other types of radiation use from the safety licence, if it is possible to ascertain with sufficient reliability that the use of the radiation will not cause damage or danger to health. This guide presents the conditions applying to exemption from the safety licence for the use of radiation and reporting obligation, and also the exemption values for radioactive substances which, if exceeded, will entail the application of the safety licence and notification procedure for the use of radiation in question. The guide also presents exemptions in the use of exemption values, and requirements associated with the exemption of radiation appliances. However, the guide does not apply to the use of nuclear energy.

Structure of the transcriptional regulator LmrR and its mechanism of multidrug recognition

NARCIS (Netherlands)

Madoori, Pramod Kumar; Agustiandari, Herfita; Driessen, Arnold J. M.; Thunnissen, Andy-Mark W. H.

2009-01-01

LmrR is a PadR-related transcriptional repressor that regulates the production of LmrCD, a major multidrug ABC transporter in Lactococcus lactis. Transcriptional regulation is presumed to follow a drug-sensitive induction mechanism involving the direct binding of transporter ligands to LmrR. Here,

CPC, a single-repeat R3 MYB, is a negative regulator of anthocyanin biosynthesis in Arabidopsis.

Science.gov (United States)

Zhu, Hui-Fen; Fitzsimmons, Karen; Khandelwal, Abha; Kranz, Robert G

2009-07-01

Single-repeat R3 MYB transcription factors like CPC (CAPRICE) are known to play roles in developmental processes such as root hair differentiation and trichome initiation. However, none of the six Arabidopsis single-repeat R3 MYB members has been reported to regulate flavonoid biosynthesis. We show here that CPC is a negative regulator of anthocyanin biosynthesis. In the process of using CPC to test GAL4-dependent driver lines, we observed a repression of anthocyanin synthesis upon GAL4-mediated CPC overexpression. We demonstrated that this is not due to an increase in nutrient uptake because of more root hairs. Rather, CPC expression level tightly controls anthocyanin accumulation. Microarray analysis on the whole genome showed that, of 37 000 features tested, 85 genes are repressed greater than three-fold by CPC overexpression. Of these 85, seven are late anthocyanin biosynthesis genes. Also, anthocyanin synthesis genes were shown to be down-regulated in 35S::CPC overexpression plants. Transient expression results suggest that CPC competes with the R2R3-MYB transcription factor PAP1/2, which is an activator of anthocyanin biosynthesis genes. This report adds anthocyanin biosynthesis to the set of programs that are under CPC control, indicating that this regulator is not only for developmental programs (e.g. root hairs, trichomes), but can influence anthocyanin pigment synthesis.

R-Ras regulates migration through an interaction with filamin A in melanoma cells.

Directory of Open Access Journals (Sweden)

Joanna E Gawecka

2010-06-01

Full Text Available Changes in cell adhesion and migration in the tumor microenvironment are key in the initiation and progression of metastasis. R-Ras is one of several small GTPases that regulate cell adhesion and migration on the extracellular matrix, however the mechanism has not been completely elucidated. Using a yeast two-hybrid approach we sought to identify novel R-Ras binding proteins that might mediate its effects on integrins.We identified Filamin A (FLNa as a candidate interacting protein. FLNa is an actin-binding scaffold protein that also binds to integrin beta1, beta2 and beta7 tails and is associated with diverse cell processes including cell migration. Indeed, M2 melanoma cells require FLNa for motility. We further show that R-Ras and FLNa interact in co-immunoprecipitations and pull-down assays. Deletion of FLNa repeat 3 (FLNaDelta3 abrogated this interaction. In M2 melanoma cells active R-Ras co-localized with FLNa but did not co-localize with FLNa lacking repeat 3. Thus, activated R-Ras binds repeat 3 of FLNa. The functional consequence of this interaction was that active R-Ras and FLNa coordinately increased cell migration. In contrast, co-expression of R-Ras and FLNaDelta3 had a significantly reduced effect on migration. While there was enhancement of integrin activation and fibronectin matrix assembly, cell adhesion was not altered. Finally, siRNA knockdown of endogenous R-Ras impaired FLNa-dependent fibronectin matrix assembly.These data support a model in which R-Ras functionally associates with FLNa and thereby regulates integrin-dependent migration. Thus in melanoma cells R-Ras and FLNa may cooperatively promote metastasis by enhancing cell migration.

78 FR 18277 - Special Local Regulation; Low Country Splash, Wando River, Cooper River, and Charleston Harbor...

Science.gov (United States)

2013-03-26

...-AA08 Special Local Regulation; Low Country Splash, Wando River, Cooper River, and Charleston Harbor... proposes to issue a special local regulation on the waters of the Wando River, Cooper River, and Charleston... Country Splash is scheduled to take place on the waters of the Wando River, Cooper River, and Charleston...

Identification of miR-185 as a regulator of de novo cholesterol biosynthesis and low density lipoprotein uptake

Science.gov (United States)

Yang, Muhua; Liu, Weidong; Pellicane, Christina; Sahyoun, Christine; Joseph, Biny K.; Gallo-Ebert, Christina; Donigan, Melissa; Pandya, Devanshi; Giordano, Caroline; Bata, Adam; Nickels, Joseph T.

2014-01-01

Dysregulation of cholesterol homeostasis is associated with various metabolic diseases, including atherosclerosis and type 2 diabetes. The sterol response element binding protein (SREBP)-2 transcription factor induces the expression of genes involved in de novo cholesterol biosynthesis and low density lipoprotein (LDL) uptake, thus it plays a crucial role in maintaining cholesterol homeostasis. Here, we found that overexpressing microRNA (miR)-185 in HepG2 cells repressed SREBP-2 expression and protein level. miR-185-directed inhibition caused decreased SREBP-2-dependent gene expression, LDL uptake, and HMG-CoA reductase activity. In addition, we found that miR-185 expression was tightly regulated by SREBP-1c, through its binding to a single sterol response element in the miR-185 promoter. Moreover, we found that miR-185 expression levels were elevated in mice fed a high-fat diet, and this increase correlated with an increase in total cholesterol level and a decrease in SREBP-2 expression and protein. Finally, we found that individuals with high cholesterol had a 5-fold increase in serum miR-185 expression compared with control individuals. Thus, miR-185 controls cholesterol homeostasis through regulating SREBP-2 expression and activity. In turn, SREBP-1c regulates miR-185 expression through a complex cholesterol-responsive feedback loop. Thus, a novel axis regulating cholesterol homeostasis exists that exploits miR-185-dependent regulation of SREBP-2 and requires SREBP-1c for function. PMID:24296663

The Pseudomonas transcriptional regulator AlgR controls LipA expression via the noncoding RNA RsmZ in Pseudomonas protegens Pf-5.

Science.gov (United States)

Li, Menggang; Yan, Jinyong; Yan, Yunjun

2017-05-20

Pseudomonas lipases are well studied enzymes. However, few studies have been conducted to explore the mechanism underlying the regulation of lipases expression. AlgR, a global regulator, controls the expression of multiple genes, regulates bacterial peristalsis, and participates in the regulation of quorum-sensing (QS) system, and so on. In this study, the effect of AlgR on lipase expression was investigated by knocking out the algR and rsmZ genes or overexpressing them. It is found out that AlgR can regulate the expression of lipA at both transcriptional and translational levels, but the transcriptional level was dominant. AlgR is also able to regulate the expression of rsmX/rsmY/rsmZ. Additionally, using algR/rsmZ double gene knock-out, it showed that AlgR could directly bind to the promoter sequence of rsmZ to regulate lipA activity. In conclusion, this study for the first time indicates that AlgR directly binds to rsmZ to regulates the expression of lipA via regulating transcription of rsmZ, and mainly regulates the expression of lipA at transcriptional level in P. protegens Pf-5. Copyright © 2017 Elsevier Inc. All rights reserved.

17 CFR 240.36a1-1 - Exemption from Section 7 for OTC derivatives dealers.

Science.gov (United States)

2010-04-01

... 17 Commodity and Securities Exchanges 3 2010-04-01 2010-04-01 false Exemption from Section 7 for OTC derivatives dealers. 240.36a1-1 Section 240.36a1-1 Commodity and Securities Exchanges SECURITIES AND EXCHANGE COMMISSION (CONTINUED) GENERAL RULES AND REGULATIONS, SECURITIES EXCHANGE ACT OF 1934...

77 FR 16974 - Special Local Regulations; Ocean State Tall Ships Festival 2012, Narragansett Bay, RI

Science.gov (United States)

2012-03-23

...-AA08 Special Local Regulations; Ocean State Tall Ships Festival 2012, Narragansett Bay, RI AGENCY... Island, for the Ocean State Tall Ships Festival 2012. This action is necessary to provide for the safety..., during the Ocean State Tall Ships Festival on July 6-9, 2012. These temporary special local regulations...

Epigenetic control of virulence gene expression in Pseudomonas aeruginosa by a LysR-type transcription regulator.

Directory of Open Access Journals (Sweden)

Keith H Turner

2009-12-01

Full Text Available Phenotypic variation within an isogenic bacterial population is thought to ensure the survival of a subset of cells in adverse conditions. The opportunistic pathogen Pseudomonas aeruginosa variably expresses several phenotypes, including antibiotic resistance, biofilm formation, and the production of CupA fimbriae. Here we describe a previously unidentified bistable switch in P. aeruginosa. This switch controls the expression of a diverse set of genes, including aprA, which encodes the secreted virulence factor alkaline protease. We present evidence that bistable expression of PA2432, herein named bexR (bistable expression regulator, which encodes a LysR-type transcription regulator, controls this switch. In particular, using DNA microarrays, quantitative RT-PCR analysis, chromatin immunoprecipitation, and reporter gene fusions, we identify genes directly under the control of BexR and show that these genes are bistably expressed. Furthermore, we show that bexR is itself bistably expressed and positively autoregulated. Finally, using single-cell analyses of a GFP reporter fusion, we present evidence that positive autoregulation of bexR is necessary for bistable expression of the BexR regulon. Our findings suggest that a positive feedback loop involving a LysR-type transcription regulator serves as the basis for an epigenetic switch that controls virulence gene expression in P. aeruginosa.

Roles of PucR, G1nR, and TnrA in regulating expression of the Bacillus subtilis ure p3 promoter

DEFF Research Database (Denmark)

Brandenburg, J.L.; Wray, L.V.; Beier, Lars

2002-01-01

consensus GlnR/TnrA binding sites located in the ure P3 promoter region were shown to be required for negative regulation by GlnR. Mutational analysis indicates that a cooperative interaction occurs between GlnR dimers bound at these two sites. B. subtilis is the first example where urease expression...

7 CFR 28.116 - Amounts of fees for classification; exemption.

Science.gov (United States)

2010-01-01

... Section 28.116 Agriculture Regulations of the Department of Agriculture AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing Practices), DEPARTMENT OF AGRICULTURE COMMODITY STANDARDS AND STANDARD... Standards Act Fees and Costs § 28.116 Amounts of fees for classification; exemption. (a) For the...

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.

40 CFR 80.81 - Enforcement exemptions for California gasoline.

Science.gov (United States)

2010-07-01

... gasoline. 80.81 Section 80.81 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) REGULATION OF FUELS AND FUEL ADDITIVES Reformulated Gasoline § 80.81 Enforcement exemptions for California gasoline. (a)(1) The requirements of subparts D, E, F, and J of this part are...

46 CFR 28.60 - Exemption letter.

Science.gov (United States)

2010-10-01

... VESSELS General Provisions § 28.60 Exemption letter. (a) Types of exemptions. (1) Specific exemption means... for an exemption of either type must be in writing, have specific reasons for the request, and be sent... vessel to which any exemption applies. (e) Right of appeal. Any person directly affected by a decision or...

77 FR 69929 - Western Carolina Railway Service Corporation, Steven C. Hawkins and Cheryl R. Hawkins-Continuance...

Science.gov (United States)

2012-11-21

... Railway Service Corporation, Steven C. Hawkins and Cheryl R. Hawkins--Continuance in Control Exemption--Aiken Railway Company, LLC Western Carolina Railway Service Corporation (WCRS) and Steven C. Hawkins and Cheryl R. Hawkins (the Hawkins) (collectively, Applicants) have filed a verified notice of exemption...

12 CFR 225.21 - Prohibited nonbanking activities and acquisitions; exempt bank holding companies.

Science.gov (United States)

2010-01-01

... CONTROL (REGULATION Y) Regulations Nonbanking Activities and Acquisitions by Bank Holding Companies § 225... company or a subsidiary may not engage in, or acquire or control, directly or indirectly, voting... Internal Revenue Code (26 U.S.C. 501(c)). (3) Companies granted hardship exemption. Any bank holding...

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.

75 FR 32983 - Commercial Driver's License (CDL) Standards: Exemption

Science.gov (United States)

2010-06-10

...-28480] Commercial Driver's License (CDL) Standards: Exemption AGENCY: Federal Motor Carrier Safety... commercial driver's license (CDL) as required by current regulations. FMCSA reviewed NAAA's application for... demonstrate alternatives its members would employ to ensure that their commercial motor vehicle (CMV) drivers...

76 FR 8942 - Poison Prevention Packaging Requirements; Proposed Exemption of Powder Formulations of...

Science.gov (United States)

2011-02-16

..., when a special packaging standard issued under the PPPA is in effect, ``no State or political... Product Safety Commission (``CPSC,'' ``Commission,'' or ``we'') is proposing to amend its child-resistant... would exempt these prescription drug products on the basis that child-resistant packaging is not needed...

Brucella BioR Regulator Defines a Complex Regulatory Mechanism for Bacterial Biotin Metabolism

Science.gov (United States)

Xu, Jie; Zhang, Huimin; Srinivas, Swaminath

2013-01-01

The enzyme cofactor biotin (vitamin H or B7) is an energetically expensive molecule whose de novo biosynthesis requires 20 ATP equivalents. It seems quite likely that diverse mechanisms have evolved to tightly regulate its biosynthesis. Unlike the model regulator BirA, a bifunctional biotin protein ligase with the capability of repressing the biotin biosynthetic pathway, BioR has been recently reported by us as an alternative machinery and a new type of GntR family transcriptional factor that can repress the expression of the bioBFDAZ operon in the plant pathogen Agrobacterium tumefaciens. However, quite unusually, a closely related human pathogen, Brucella melitensis, has four putative BioR-binding sites (both bioR and bioY possess one site in the promoter region, whereas the bioBFDAZ [bio] operon contains two tandem BioR boxes). This raised the question of whether BioR mediates the complex regulatory network of biotin metabolism. Here, we report that this is the case. The B. melitensis BioR ortholog was overexpressed and purified to homogeneity, and its solution structure was found to be dimeric. Functional complementation in a bioR isogenic mutant of A. tumefaciens elucidated that Brucella BioR is a functional repressor. Electrophoretic mobility shift assays demonstrated that the four predicted BioR sites of Brucella plus the BioR site of A. tumefaciens can all interact with the Brucella BioR protein. In a reporter strain that we developed on the basis of a double mutant of A. tumefaciens (the ΔbioR ΔbioBFDA mutant), the β-galactosidase (β-Gal) activity of three plasmid-borne transcriptional fusions (bioBbme-lacZ, bioYbme-lacZ, and bioRbme-lacZ) was dramatically decreased upon overexpression of Brucella bioR. Real-time quantitative PCR analyses showed that the expression of bioBFDA and bioY is significantly elevated upon removal of bioR from B. melitensis. Together, we conclude that Brucella BioR is not only a negative autoregulator but also a repressor of

miR-99 regulates normal and malignant hematopoietic stem cell self-renewal.

Science.gov (United States)

Khalaj, Mona; Woolthuis, Carolien M; Hu, Wenhuo; Durham, Benjamin H; Chu, S Haihua; Qamar, Sarah; Armstrong, Scott A; Park, Christopher Y

2017-07-21

The microRNA-99 ( miR-99 ) family comprises a group of broadly conserved microRNAs that are highly expressed in hematopoietic stem cells (HSCs) and acute myeloid leukemia stem cells (LSCs) compared with their differentiated progeny. Herein, we show that miR-99 regulates self-renewal in both HSCs and LSCs. miR-99 maintains HSC long-term reconstitution activity by inhibiting differentiation and cell cycle entry. Moreover, miR-99 inhibition induced LSC differentiation and depletion in an MLL-AF9-driven mouse model of AML, leading to reduction in leukemia-initiating activity and improved survival in secondary transplants. Confirming miR-99 's role in established AML, miR-99 inhibition induced primary AML patient blasts to undergo differentiation. A forward genetic shRNA library screen revealed Hoxa1 as a critical mediator of miR-99 function in HSC maintenance, and this observation was independently confirmed in both HSCs and LSCs. Together, these studies demonstrate the importance of noncoding RNAs in the regulation of HSC and LSC function and identify miR-99 as a critical regulator of stem cell self-renewal. © 2017 Khalaj et al.

Regulation of Metalloprotease Gene Expression in Vibrio vulnificus by a Vibrio harveyi LuxR Homologue

Science.gov (United States)

Shao, Chung-Ping; Hor, Lien-I

2001-01-01

Expression of the Vibrio vulnificus metalloprotease gene, vvp, was turned up rapidly when bacterial growth reached the late log phase. A similar pattern of expression has been found in the metalloprotease gene of Vibrio cholerae, and this has been shown to be regulated by a Vibrio harveyi LuxR-like transcriptional activator. To find out whether a LuxR homologue exists in V. vulnificus, a gene library of this organism was screened by colony hybridization using a probe derived from a sequence that is conserved in various luxR-like genes of vibrios. A gene containing a 618-bp open reading frame was identified and found to be identical to the smcR gene of V. vulnificus reported previously. An isogenic SmcR-deficient (RD) mutant was further constructed by an in vivo allelic exchange technique. This mutant exhibited an extremely low level of vvp transcription compared with that of the parent strain. On the other hand, the cytolysin gene, vvhA, was expressed at a higher level in the RD mutant than in the parent strain during the log phase of growth. These data suggested that SmcR might not only be a positive regulator of the protease gene but might also be involved in negative regulation of the cytolysin gene. Virulence of the RD mutant in either normal or iron-overloaded mice challenged by intraperitoneal injection was comparable to that of the parent strain, indicating that SmcR is not required for V. vulnificus virulence in mice. PMID:11157950

16 CFR 1061.6 - Contents of applications for exemption.

Science.gov (United States)

2010-01-01

....6 Section 1061.6 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION GENERAL APPLICATIONS FOR... include the information specified in §§ 1061.7 through 1061.10. More generally, a State or local... support of the findings the Commission is required to make in issuing an exemption regulation. If any of...

78 FR 75376 - Entergy Operations, Inc.; Combined License Application for River Bend Unit 3, Exemption From the...

Science.gov (United States)

2013-12-11

...) The exemption(s) are authorized by law, will not present an undue risk to public health or safety, and... only temporary relief from the applicable regulation and the licensee or applicant has made good faith.... ML11343A568), and December 3, 2012 (ADAMS Accession No. ML12342A231), EOI has made good faith efforts to...

MiR302 regulates SNAI1 expression to control mesangial cell plasticity

DEFF Research Database (Denmark)

De Chiara, L.; Andrews, D.; Watson, A.

2017-01-01

Cell fate decisions are controlled by the interplay of transcription factors and epigenetic modifiers, which together determine cellular identity. Here we elaborate on the role of miR302 in the regulation of cell plasticity. Overexpression of miR302 effected silencing of the TGFβ type II receptor...... and facilitated plasticity in a manner distinct from pluripotency, characterized by increased expression of Snail. miR302 overexpressing mesangial cells also exhibited enhanced expression of EZH2 coincident with Snail upregulation. esiRNA silencing of each component suggest that Smad3 and EZH2 are part...... of a complex that regulates plasticity and that miR302 regulates EZH2 and Snail independently. Subsequent manipulation of miR302 overexpressing cells demonstrated the potential of using this approach for reprogramming as evidenced by de novo expression of the tight junction components ZO-1 and E...

17 CFR 250.12 - Exemption of certain public utility companies from the definition of subsidiary companies of...

Science.gov (United States)

2010-04-01

... utility companies from the definition of subsidiary companies of holding companies. 250.12 Section 250.12... REGULATIONS, PUBLIC UTILITY HOLDING COMPANY ACT OF 1935 Registration and General Exemptions § 250.12 Exemption of certain public utility companies from the definition of subsidiary companies of holding companies...

Medical devices; exemption from premarket notification; class II devices; wheelchair elevator. Final order.

Science.gov (United States)

2013-03-04

The Food and Drug Administration (FDA) is publishing an order granting a petition requesting exemption from premarket notification requirements for wheelchair elevator devices commonly known as inclined platform lifts and vertical platform lifts. These devices are used to provide a means for a person with a mobility impairment caused by injury or other disease to move from one level to another, usually in a wheelchair. This order exempts wheelchair elevators, class II devices, from premarket notification and establishes conditions for exemption for this device that will provide a reasonable assurance of the safety and effectiveness of the device without submission of a premarket notification (510(k)). This exemption from 510(k), subject to these conditions, is immediately in effect for wheelchair elevators. All other devices classified under FDA's wheelchair elevator regulations, including attendant-operated stair climbing devices for wheelchairs and portable platform lifts, continue to require submission of 510(k)s. FDA is publishing this order in accordance with the section of the Food, Drug, and Cosmetic Act (the FD&C Act) permitting the exemption of a device from the requirement to submit a 510(k).

Introduction of hsa-miR-103a and hsa-miR-1827 and hsa-miR-137 as new regulators of Wnt signaling pathway and their relation to colorectal carcinoma.

Science.gov (United States)

Fasihi, Ali; M Soltani, Bahram; Atashi, Amir; Nasiri, Shirzad

2018-07-01

Wnt signaling is hyper-activated in most of human cancers including colorectal carcinoma (CRC). Therefore, the introduction of new regulators for Wnt pathway possesses promising diagnostic and therapeutic applications in cancer medicine. Bioinformatics analysis introduced hsa-miR-103a, hsa-miR-1827, and hsa-miR-137 as potential regulators of Wnt signaling pathway. Here, we intended to examine the effect of these human miRNAs on Wnt signaling pathway components, on the cell cycle progression in CRC originated cell lines and their expression in CRC tissues. RT-qPCR results indicated upregulation of hsa-miR-103a, hsa-miR-1827, and downregulation of hsa-miR-137 in CRC tissues. Overexpression of hsa-miR-103a and hsa-miR-1827 in SW480 cells resulted in elevated Wnt activity, detected by both Top/Flash assay and RT-qPCR analysis. Inhibition of Wnt signaling by using PNU-74654 or IWP-2 small molecules suggested that these miRNAs exerts their effect at the β-catenin degradation complex level. Then, RT-qPCR, dual luciferase assay, and western blotting analysis indicated that APC and APC2 transcripts were targeted by hsa-miR-103a, hsa-miR-1827 while, Wnt3a and β-catenin genes were upregulated. However, hsa-miR-137 downregulated Wnt3a and β-catenin genes. Further, hsa-miR-103a and hsa-miR-1827 overexpression resulted in cell cycle progression and reduced apoptotic rate in SW480 cells, unlike hsa-miR-137 overexpression which resulted in cell cycle suppression, detected by flowcytometry and Anexin analysis. Overall, our data introduced hsa-miR-103a, hsa-miR-1827 as onco-miRNAs and hsa-miR-137 as tumor suppressor which exert their effect through regulation of Wnt signaling pathway in CRC and introduced them as potential target for therapy. © 2017 Wiley Periodicals, Inc.

Market Share, R&D Cooperation, and EU Competition Policy

OpenAIRE

Richard Rubble; Bruno Versaevel

2009-01-01

Working Paper GATE 2009-10; Current EU policy exempts horizontal R&D agreements from antitrust con- cerns when the combined market shares of participants are low enough. This paper argues that existing theory does not support limiting the exemption to low market shares. This is done by introducing a set of non-innovating outside firms to the standard framework to assess what link might exist between the market share of innovating firms and the product market benefits of cooperation. With R&D out...

Risk Assessment for Current and Projected Uses of Source Material Under a U.S. NRC General License and Exemption Request

International Nuclear Information System (INIS)

Smith, Michael A.; Napier, Bruce A.; Strom, Daniel J.; Short, Steven M.; Beatty, Cassandra V.; Stoker, Natasha F.; Newman, Teridee

2006-01-01

Source material is used under specific license, general license, and various exemptions from licensing requirements in 10 CFR Part 40. Because the Atomic Energy Act of 1946 focused on source material primarily in terms of its significance to the production of special nuclear material, the initial regulation of source material did not, apparently, give much emphasis to public health and safety. This emphasis on the production of special nuclear material continued in later modifications to the regulations. Because the last major update of these regulations was over 40 years ago (1961), the NRC is concerned that the current regulations for source materials may not be consistent with current health and safety regulations. Current industrial trends indicate a general decline in the use of thorium and uranium. Thorium was traditionally used in ceramics for refractory purposes but now is primarily used in scientific research, in a few electrical applications, as a chemical catalyst, and in optical lenses. Uranium, once popular in pigments and glazes, is now almost entirely limited to military applications that require special licensure and in scientific research. Due to high-disposal costs, increasingly stringent regulations, and public concerns related to the natural radioactivity of source material, industry is rapidly developing substitutes and alternate processes that do not involve the use of uranium and thorium. For these reasons, the downward trend in the use of source material is expected to continue. Researchers at Pacific Northwest National Laboratory (PNNL) identified how source materials meeting the exemption and general license requirements of 10 CFR 40.13(a), 40.13(b), and 40.22 are currently being used in industry and by the public. Based on the results of an extensive literature and internet search, few ?truly? new uses of source material were discovered that were not already considered in or represented by previous NRC analyses. Exceptions were (1) the

Capture of microRNA-bound mRNAs identifies the tumor suppressor miR-34a as a regulator of growth factor signaling.

Directory of Open Access Journals (Sweden)

Ashish Lal

2011-11-01

Full Text Available A simple biochemical method to isolate mRNAs pulled down with a transfected, biotinylated microRNA was used to identify direct target genes of miR-34a, a tumor suppressor gene. The method reidentified most of the known miR-34a regulated genes expressed in K562 and HCT116 cancer cell lines. Transcripts for 982 genes were enriched in the pull-down with miR-34a in both cell lines. Despite this large number, validation experiments suggested that ~90% of the genes identified in both cell lines can be directly regulated by miR-34a. Thus miR-34a is capable of regulating hundreds of genes. The transcripts pulled down with miR-34a were highly enriched for their roles in growth factor signaling and cell cycle progression. These genes form a dense network of interacting gene products that regulate multiple signal transduction pathways that orchestrate the proliferative response to external growth stimuli. Multiple candidate miR-34a-regulated genes participate in RAS-RAF-MAPK signaling. Ectopic miR-34a expression reduced basal ERK and AKT phosphorylation and enhanced sensitivity to serum growth factor withdrawal, while cells genetically deficient in miR-34a were less sensitive. Fourteen new direct targets of miR-34a were experimentally validated, including genes that participate in growth factor signaling (ARAF and PIK3R2 as well as genes that regulate cell cycle progression at various phases of the cell cycle (cyclins D3 and G2, MCM2 and MCM5, PLK1 and SMAD4. Thus miR-34a tempers the proliferative and pro-survival effect of growth factor stimulation by interfering with growth factor signal transduction and downstream pathways required for cell division.

Capture of microRNA-bound mRNAs identifies the tumor suppressor miR-34a as a regulator of growth factor signaling.

Science.gov (United States)

Lal, Ashish; Thomas, Marshall P; Altschuler, Gabriel; Navarro, Francisco; O'Day, Elizabeth; Li, Xiao Ling; Concepcion, Carla; Han, Yoon-Chi; Thiery, Jerome; Rajani, Danielle K; Deutsch, Aaron; Hofmann, Oliver; Ventura, Andrea; Hide, Winston; Lieberman, Judy

2011-11-01

A simple biochemical method to isolate mRNAs pulled down with a transfected, biotinylated microRNA was used to identify direct target genes of miR-34a, a tumor suppressor gene. The method reidentified most of the known miR-34a regulated genes expressed in K562 and HCT116 cancer cell lines. Transcripts for 982 genes were enriched in the pull-down with miR-34a in both cell lines. Despite this large number, validation experiments suggested that ~90% of the genes identified in both cell lines can be directly regulated by miR-34a. Thus miR-34a is capable of regulating hundreds of genes. The transcripts pulled down with miR-34a were highly enriched for their roles in growth factor signaling and cell cycle progression. These genes form a dense network of interacting gene products that regulate multiple signal transduction pathways that orchestrate the proliferative response to external growth stimuli. Multiple candidate miR-34a-regulated genes participate in RAS-RAF-MAPK signaling. Ectopic miR-34a expression reduced basal ERK and AKT phosphorylation and enhanced sensitivity to serum growth factor withdrawal, while cells genetically deficient in miR-34a were less sensitive. Fourteen new direct targets of miR-34a were experimentally validated, including genes that participate in growth factor signaling (ARAF and PIK3R2) as well as genes that regulate cell cycle progression at various phases of the cell cycle (cyclins D3 and G2, MCM2 and MCM5, PLK1 and SMAD4). Thus miR-34a tempers the proliferative and pro-survival effect of growth factor stimulation by interfering with growth factor signal transduction and downstream pathways required for cell division.

Capture of MicroRNA–Bound mRNAs Identifies the Tumor Suppressor miR-34a as a Regulator of Growth Factor Signaling

Science.gov (United States)

O'Day, Elizabeth; Li, Xiao Ling; Concepcion, Carla; Han, Yoon-Chi; Thiery, Jerome; Rajani, Danielle K.; Deutsch, Aaron; Hofmann, Oliver; Ventura, Andrea; Hide, Winston; Lieberman, Judy

2011-01-01

A simple biochemical method to isolate mRNAs pulled down with a transfected, biotinylated microRNA was used to identify direct target genes of miR-34a, a tumor suppressor gene. The method reidentified most of the known miR-34a regulated genes expressed in K562 and HCT116 cancer cell lines. Transcripts for 982 genes were enriched in the pull-down with miR-34a in both cell lines. Despite this large number, validation experiments suggested that ∼90% of the genes identified in both cell lines can be directly regulated by miR-34a. Thus miR-34a is capable of regulating hundreds of genes. The transcripts pulled down with miR-34a were highly enriched for their roles in growth factor signaling and cell cycle progression. These genes form a dense network of interacting gene products that regulate multiple signal transduction pathways that orchestrate the proliferative response to external growth stimuli. Multiple candidate miR-34a–regulated genes participate in RAS-RAF-MAPK signaling. Ectopic miR-34a expression reduced basal ERK and AKT phosphorylation and enhanced sensitivity to serum growth factor withdrawal, while cells genetically deficient in miR-34a were less sensitive. Fourteen new direct targets of miR-34a were experimentally validated, including genes that participate in growth factor signaling (ARAF and PIK3R2) as well as genes that regulate cell cycle progression at various phases of the cell cycle (cyclins D3 and G2, MCM2 and MCM5, PLK1 and SMAD4). Thus miR-34a tempers the proliferative and pro-survival effect of growth factor stimulation by interfering with growth factor signal transduction and downstream pathways required for cell division. PMID:22102825

Functional specialization of the plant miR396 regulatory network through distinct microRNA-target interactions.

Directory of Open Access Journals (Sweden)

Juan M Debernardi

2012-01-01

Full Text Available MicroRNAs (miRNAs are ∼21 nt small RNAs that regulate gene expression in animals and plants. They can be grouped into families comprising different genes encoding similar or identical mature miRNAs. Several miRNA families are deeply conserved in plant lineages and regulate key aspects of plant development, hormone signaling, and stress response. The ancient miRNA miR396 regulates conserved targets belonging to the GROWTH-REGULATING FACTOR (GRF family of transcription factors, which are known to control cell proliferation in Arabidopsis leaves. In this work, we characterized the regulation of an additional target for miR396, the transcription factor bHLH74, that is necessary for Arabidopsis normal development. bHLH74 homologs with a miR396 target site could only be detected in the sister families Brassicaceae and Cleomaceae. Still, bHLH74 repression by miR396 is required for margin and vein pattern formation of Arabidopsis leaves. MiR396 contributes to the spatio-temporal regulation of GRF and bHLH74 expression during leaf development. Furthermore, a survey of miR396 sequences in different species showed variations in the 5' portion of the miRNA, a region known to be important for miRNA activity. Analysis of different miR396 variants in Arabidopsis thaliana revealed that they have an enhanced activity toward GRF transcription factors. The interaction between the GRF target site and miR396 has a bulge between positions 7 and 8 of the miRNA. Our data indicate that such bulge modulates the strength of the miR396-mediated repression and that this modulation is essential to shape the precise spatio-temporal pattern of GRF2 expression. The results show that ancient miRNAs can regulate conserved targets with varied efficiency in different species, and we further propose that they could acquire new targets whose control might also be biologically relevant.

Altered regulation of miR-34a and miR-483-3p in alcoholic hepatitis and DDC fed mice.

Science.gov (United States)

Liu, Hui; French, Barbara A; Li, Jun; Tillman, Brittany; French, Samuel W

2015-12-01

MicroRNAs are small noncoding RNAs that negatively regulate gene expression by binding to the untranslated regions of their target mRNAs. Deregulation of miRNAs is shown to play pivotal roles in tumorigenesis and progression. Mallory-Denk Bodies (MDBs) are prevalent in various liver diseases including alcoholic hepatitis (AH) and are formed in mice livers by feeding DDC. By comparing AH livers where MDBs had formed with normal livers, there were significant changes of miR-34a and miR-483-3p by RNA sequencing (RNA-Seq) analyses. Real-time PCR further shows a 3- and 6-fold upregulation (respectively) of miR-34a in the AH livers and in the livers of DDC re-fed mice, while miR-483-3p was significantly downregulated in AH and DDC re-fed mice livers. This indicates that miR-34a and miR-483-3p may be crucial for liver MDB formation. P53 mRNA was found to be significantly downregulated both in the AH livers and in the livers of DDC re-fed mice, indicating that the upregulation of miR-34a is permitted by the decrease of p53 in AH since miR-34a is a main target of p53. Overexpression of miR-34a leads to an increase of p53 targets such as p27, which inhibits the cell cycle leading to cell cycle arrest. Importantly, BRCA1 is a target gene of miR-483-3p by RNA-Seq analyses and the downregulation of miR-483-3p may be the mechanism for liver MDB formation since the BRCA1 signal was markedly upregulated in AH livers. These results constitute a demonstration of the altered regulation of miR-34a and miR-483-3p in the livers of AH and mice fed DDC where MDBs formed, providing further insight into the mechanism of MDB formation mediated by miR-34a and miR-483-3p in AH. Copyright © 2015 Elsevier Inc. All rights reserved.

77 FR 18984 - Special Local Regulation for Marine Events; Yorktown Parade of Sail, York River; Yorktown, VA

Science.gov (United States)

2012-03-29

...-AA08 Special Local Regulation for Marine Events; Yorktown Parade of Sail, York River; Yorktown, VA... proposes to establish special local regulation during the Yorktown Parade of Sail, a parade of five tall... sponsor the ``Yorktown Parade of Sail'' on the waters of York River. The event will consist of...

76 FR 9646 - Quarterly Listings; Safety Zones, Security Zones, Special Local Regulations, Drawbridge Operation...

Science.gov (United States)

2011-02-22

... DEPARTMENT OF HOMELAND SECURITY Coast Guard 33 CFR Parts 100, 117, 147, and 165 [USCG-2010-0399] Quarterly Listings; Safety Zones, Security Zones, Special Local Regulations, Drawbridge Operation Regulations and Regulated Navigation Areas AGENCY: Coast Guard, DHS. ACTION: Notice of expired temporary rules...

A central role for R7bp in the regulation of itch sensation.

Science.gov (United States)

Pandey, Mritunjay; Zhang, Jian-Hua; Mishra, Santosh K; Adikaram, Poorni R; Harris, Benjamin; Kahler, John F; Loshakov, Anna; Sholevar, Roxanne; Genis, Allison; Kittock, Claire; Kabat, Juraj; Ganesan, Sundar; Neubig, Richard R; Hoon, Mark A; Simonds, William F

2017-05-01

Itch is a protective sensation producing a desire to scratch. Pathologic itch can be a chronic symptom of illnesses such as uremia, cholestatic liver disease, neuropathies and dermatitis, however current therapeutic options are limited. Many types of cell surface receptors, including those present on cells in the skin, on sensory neurons and on neurons in the spinal cord, have been implicated in itch signaling. The role of G protein signaling in the regulation of pruriception is poorly understood. We identify here 2 G protein signaling components whose mutation impairs itch sensation. R7bp (a.k.a. Rgs7bp) is a palmitoylated membrane anchoring protein expressed in neurons that facilitates Gαi/o -directed GTPase activating protein activity mediated by the Gβ5/R7-RGS complex. Knockout of R7bp diminishes scratching responses to multiple cutaneously applied and intrathecally-administered pruritogens in mice. Knock-in to mice of a GTPase activating protein-insensitive mutant of Gαo (Gnao1 G184S/+) produces a similar pruriceptive phenotype. The pruriceptive defect in R7bp knockout mice was rescued in double knockout mice also lacking Oprk1, encoding the G protein-coupled kappa-opioid receptor whose activation is known to inhibit itch sensation. In a model of atopic dermatitis (eczema), R7bp knockout mice showed diminished scratching behavior and enhanced sensitivity to kappa opioid agonists. Taken together, our results indicate that R7bp is a key regulator of itch sensation and suggest the potential targeting of R7bp-dependent GTPase activating protein activity as a novel therapeutic strategy for pathological itch.

GlnR-Mediated Regulation of ectABCD Transcription Expands the Role of the GlnR Regulon to Osmotic Stress Management

OpenAIRE

Shao, ZhiHui; Deng, WanXin; Li, ShiYuan; He, JuanMei; Ren, ShuangXi; Huang, WeiRen; Lu, YinHua; Zhao, GuoPing; Cai, ZhiMing; Wang, Jin

2015-01-01

Ectoine and hydroxyectoine are excellent compatible solutes for bacteria to deal with environmental osmotic stress and temperature damages. The biosynthesis cluster of ectoine and hydroxyectoine is widespread among microorganisms, and its expression is activated by high salinity and temperature changes. So far, little is known about the mechanism of the regulation of the transcription of ect genes and only two MarR family regulators (EctR1 in methylobacteria and the EctR1-related regulator Co...

29 CFR 780.502 - Legislative history of exemption.

Science.gov (United States)

2010-07-01

... Employment or Agricultural Employees in Processing Shade-Grown Tobacco; Exemption From Minimum Wage and... Labor Regulations Relating to Labor (Continued) WAGE AND HOUR DIVISION, DEPARTMENT OF LABOR STATEMENTS... reported to the House (see H. Rept. No. 75, 87th Cong., first sess., p. 29) was to exclude from the minimum...

75 FR 66187 - Review of Commodity, Boxcar, and TOFC/COFC Exemptions

Science.gov (United States)

2010-10-27

... rail (and truck) operations provided in connection with intermodal (TOFC/COFC) services, under 49 CFR.... 2d 969 (1993); Exemption from Regulation--Rail Transp. Frozen Food, 367 I.C.C. 859 (1983); Liquid...

CytR Is a Global Positive Regulator of Competence, Type VI Secretion, and Chitinases in Vibrio cholerae.

Directory of Open Access Journals (Sweden)

Samit S Watve

Full Text Available The facultative pathogen Vibrio cholerae transitions between its human host and aquatic reservoirs where it colonizes chitinous surfaces. Growth on chitin induces expression of chitin utilization genes, genes involved in DNA uptake by natural transformation, and a type VI secretion system that allows contact-dependent killing of neighboring bacteria. We have previously shown that the transcription factor CytR, thought to primarily regulate the pyrimidine nucleoside scavenging response, is required for natural competence in V. cholerae. Through high-throughput RNA sequencing (RNA-seq, we show that CytR positively regulates the majority of competence genes, the three type VI secretion operons, and the four known or predicted chitinases. We used transcriptional reporters and phenotypic analysis to determine the individual contributions of quorum sensing, which is controlled by the transcription factors HapR and QstR; chitin utilization that is mediated by TfoX; and pyrimidine starvation that is orchestrated by CytR, toward each of these processes. We find that in V. cholerae, CytR is a global regulator of multiple behaviors affecting fitness and adaptability in the environment.

78 FR 25574 - Special Local Regulations; Third Annual Space Coast Super Boat Grand Prix, Atlantic Ocean; Cocoa...

Science.gov (United States)

2013-05-02

...-AA08 Special Local Regulations; Third Annual Space Coast Super Boat Grand Prix, Atlantic Ocean; Cocoa... establishing a special local regulation on the waters of the Atlantic Ocean east of Cocoa Beach, Florida during... event will be held on the waters of the Atlantic Ocean east of Cocoa Beach, Florida. Approximately 30...

40 CFR 180.1119 - Azadirachtin; exemption from the requirement of a tolerance.

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 23 2010-07-01 2010-07-01 false Azadirachtin; exemption from the... Exemptions From Tolerances § 180.1119 Azadirachtin; exemption from the requirement of a tolerance. An exemption from the requirement of a tolerance is established for the biochemical azadirachtin, which is...

miR-146a down-regulation alleviates H2O2-induced cytotoxicity of PC12 cells by regulating MCL1/JAK/STAT pathway : miR-146a down-regulation relieves H2O2-induced PC12 cells cytotoxicity by MCL1/JAK/STAT.

Science.gov (United States)

Yang, Xuecheng; Mao, Xin; Ding, Xuemei; Guan, Fengju; Jia, Yuefeng; Luo, Lei; Li, Bin; Tan, Hailin; Cao, Caixia

2018-02-26

Oxidative stress and miRNAs have been confirmed to play an important role in neurological diseases. The study aimed to explore the underlying effect and mechanisms of miR-146a in H 2 O 2 -induced injury of PC12 cells. Here, PC12 cells were stimulated with 200 μM of H 2 O 2 to construct oxidative injury model. Cell injury was evaluated on the basis of the changes in cell viability, migration, invasion, apoptosis, and DNA damage. Results revealed that miR-146a expression was up-regulated in H 2 O 2 -induced PC12 cells. Functional analysis showed that down-regulation of miR-146a alleviated H 2 O 2 -induced cytotoxicity in PC12 cells. Dual-luciferase reporter and western blot assay verified that MCL1 was a direct target gene of miR-146a. Moreover, anti-miR-146a-mediated suppression on cell cytotoxicity was abated following MCL1 knockdown in H 2 O 2 -induced PC12 cells. Furthermore, MCL1 activated JAK/STAT signaling pathway and MCL1 overexpression attenuated H 2 O 2 -induced cytotoxicity in PC12 cells by JAK/STAT signaling pathway. In conclusion, this study suggested that suppression of miR-146a abated H 2 O 2 -induced cytotoxicity in PC12 cells via regulating MCL1/JAK/STAT pathway.

Medical devices; exemption from premarket notification; Class II devices; optical impression systems for computer assisted design and manufacturing. Final rule.

Science.gov (United States)

2003-04-22

The Food and Drug Administration (FDA) is publishing an order granting a petition requesting exemption from the premarket notification requirements for data acquisition units for ceramic dental restoration systems. This rule exempts from premarket notification data acquisition units for ceramic dental restoration systems and establishes a guidance document as a special control for this device. FDA is publishing this order in accordance with the Food and Drug Administration Modernization Act of 1997 (FDAMA).

A functional microRNA library screen reveals miR-410 as a novel anti-apoptotic regulator of cholangiocarcinoma

International Nuclear Information System (INIS)

Palumbo, Tiziana; Poultsides, George A.; Kouraklis, Grigorios; Liakakos, Theodore; Drakaki, Alexandra; Peros, George; Hatziapostolou, Maria; Iliopoulos, Dimitrios

2016-01-01

Cholangiocarcinoma is characterized by late diagnosis and a poor survival rate. MicroRNAs have been involved in the pathogenesis of different cancer types, including cholangiocarcinoma. Our aim was to identify novel microRNAs regulating cholangiocarcinoma cell growth in vitro and in vivo. A functional microRNA library screen was performed in human cholangiocarcinoma cells to identify microRNAs that regulate cholangiocarcinoma cell growth. Real-time PCR analysis evaluated miR-9 and XIAP mRNA levels in cholangiocarcinoma cells and tumors. The screen identified 21 microRNAs that regulated >50 % cholangiocarcinoma cell growth. MiR-410 was identified as the top suppressor of growth, while its overexpression significantly inhibited the invasion and colony formation ability of cholangiocarcinoma cells. Bioinformatics analysis revealed that microRNA-410 exerts its effects through the direct regulation of the X-linked inhibitor of apoptosis protein (XIAP). Furthermore, overexpression of miR-410 significantly reduced cholangiocarcinoma tumor growth in a xenograft mouse model through induction of apoptosis. In addition, we identified an inverse relationship between miR-410 and XIAP mRNA levels in human cholangiocarcinomas. Taken together, our study revealed a novel microRNA signaling pathway involved in cholangiocarcinoma and suggests that manipulation of the miR-410/XIAP pathway could have a therapeutic potential for cholangiocarcinoma. The online version of this article (doi:10.1186/s12885-016-2384-0) contains supplementary material, which is available to authorized users

A 3′-Untranslated Region (3′UTR) Induces Organ Adhesion by Regulating miR-199a* Functions

Science.gov (United States)

Lee, Daniel Y.; Shatseva, Tatiana; Jeyapalan, Zina; Du, William W.; Deng, Zhaoqun; Yang, Burton B.

2009-01-01

Mature microRNAs (miRNAs) are single-stranded RNAs of 18–24 nucleotides that repress post-transcriptional gene expression. However, it is unknown whether the functions of mature miRNAs can be regulated. Here we report that expression of versican 3′UTR induces organ adhesion in transgenic mice by modulating miR-199a* activities. The study was initiated by the hypothesis that the non-coding 3′UTR plays a role in the regulation of miRNA function. Transgenic mice expressing a construct harboring the 3′UTR of versican exhibits the adhesion of organs. Computational analysis indicated that a large number of microRNAs could bind to this fragment potentially including miR-199a*. Expression of versican and fibronectin, two targets of miR-199a*, are up-regulated in transgenic mice, suggesting that the 3′UTR binds and modulates miR-199a* activities, freeing mRNAs of versican and fibronectin from being repressed by miR-199a*. Confirmation of the binding was performed by PCR using mature miR-199a* as a primer and the targeting was performed by luciferase assays. Enhanced adhesion by expression of the 3′UTR was confirmed by in vitro assays. Our results demonstrated that upon arrival in cytoplasm, miRNA activities can be modulated locally by the 3′UTR. Our assay may be developed as sophisticated approaches for studying the mutual regulation of miRNAs and mRNAs in vitro and in vivo. We anticipate that expression of the 3′UTR may be an approach in the development of gene therapy. PMID:19223980

77 FR 4248 - Cyazofamid; Pesticide Tolerances for Emergency Exemptions

Science.gov (United States)

2012-01-27

... basil, fresh and dried. This action is in response to EPA's granting of an emergency exemption under... pesticide on basil. This regulation establishes a maximum permissible level for residues of cyazofamid in or... of the fungicide cyazofamid, in or on fresh basil at 12 parts per million (ppm), and on dried basil...

MiR-130a regulates neurite outgrowth and dendritic spine density by targeting MeCP2

Directory of Open Access Journals (Sweden)

Yunjia Zhang

2016-06-01

Full Text Available ABSTRACT MicroRNAs (miRNAs are critical for both development and function of the central nervous system. Significant evidence suggests that abnormal expression of miRNAs is associated with neurodevelopmental disorders. MeCP2 protein is an epigenetic regulator repressing or activating gene transcription by binding to methylated DNA. Both loss-of-function and gain-of-function mutations in the MECP2 gene lead to neurodevelopmental disorders such as Rett syndrome, autism and MECP2 duplication syndrome. In this study, we demonstrate that miR-130a inhibits neurite outgrowth and reduces dendritic spine density as well as dendritic complexity. Bioinformatics analyses, cell cultures and biochemical experiments indicate that miR-130a targets MECP2 and down-regulates MeCP2 protein expression. Furthermore, expression of the wild-type MeCP2, but not a loss-of-function mutant, rescues the miR-130a-induced phenotype. Our study uncovers the MECP2 gene as a previous unknown target for miR-130a, supporting that miR-130a may play a role in neurodevelopment by regulating MeCP2. Together with data from other groups, our work suggests that a feedback regulatory mechanism involving both miR-130a and MeCP2 may serve to ensure their appropriate expression and function in neural development.

9 CFR 381.15 - Exemption from definition of “poultry product” of certain human food products containing poultry.

Science.gov (United States)

2010-01-01

... productâ of certain human food products containing poultry. 381.15 Section 381.15 Animals and Animal...; MANDATORY MEAT AND POULTRY PRODUCTS INSPECTION AND VOLUNTARY INSPECTION AND CERTIFICATION POULTRY PRODUCTS INSPECTION REGULATIONS Exemptions § 381.15 Exemption from definition of “poultry product” of certain human...

78 FR 35596 - Special Local Regulation; Long Beach Regatta, Powerboat Race, Atlantic Ocean, Long Beach, NY

Science.gov (United States)

2013-06-13

... 1625-AA08 Special Local Regulation; Long Beach Regatta, Powerboat Race, Atlantic Ocean, Long Beach, NY... temporary special local regulation on the navigable waters of the Atlantic Ocean off Long Beach, NY during... powerboat racing regatta. The event will be held on the Atlantic Ocean off Long Beach, NY and will feature...

29 CFR 780.104 - How modern specialization affects the scope of agriculture.

Science.gov (United States)

2010-07-01

... 29 Labor 3 2010-07-01 2010-07-01 false How modern specialization affects the scope of agriculture... EXEMPTIONS APPLICABLE TO AGRICULTURE, PROCESSING OF AGRICULTURAL COMMODITIES, AND RELATED SUBJECTS UNDER THE FAIR LABOR STANDARDS ACT General Scope of Agriculture Introductory § 780.104 How modern specialization...

The onion (Allium cepa L. R2R3-MYB gene MYB1 regulates anthocyanin biosynthesis

Directory of Open Access Journals (Sweden)

Kathy Schwinn

2016-12-01

Full Text Available Bulb colour is an important consumer trait for onion (Allium cepa L., Allioideae, Asparagales. The bulbs accumulate a range of flavonoid compounds, including anthocyanins (red, flavonols (pale yellow and chalcones (bright yellow. Flavonoid regulation is poorly characterised in onion and in other plants belonging to the Asparagales, despite being a major plant order containing many important crop and ornamental species. R2R3-MYB transcription factors associated with the regulation of distinct branches of the flavonoid pathway were isolated from onion. These belonged to sub-groups (SGs that commonly activate anthocyanin (SG6, MYB1 or flavonol (SG7, MYB29 production, or repress phenylpropanoid/flavonoid synthesis (SG4, MYB4, MYB5. MYB1 was demonstrated to be a positive regulator of anthocyanin biosynthesis by the induction of anthocyanin production in onion tissue when transiently overexpressd and by reduction of pigmentation when transiently repressed via RNAi. Furthermore, ectopic red pigmentation was observed in garlic (A. sativum L. plants stably transformed with a construct for co-overexpression of MYB1 and a bHLH partner. MYB1 also was able to complement the acyanic petal phenotype of a defined R2R3-MYB anthocyanin mutant in Antirrhinum majus of the asterid clade of eudicots. The availability of sequence information for flavonoid-related MYBs from onion enabled phylogenetic groupings to be determined across monocotyledonous and dicotyledonous species, including the identification of characteristic amino acid motifs. This analysis suggests that divergent evolution of the R2R3-MYB family has occurred between Poaceae/Orchidaceae and Allioideae species. The DNA sequences identified will be valuable for future analysis of classical flavonoid genetic loci in Allium crops and will assist the breeding of these important crop species.

29 CFR 1612.4 - Exemptions to open meeting policy.

Science.gov (United States)

2010-07-01

... 29 Labor 4 2010-07-01 2010-07-01 false Exemptions to open meeting policy. 1612.4 Section 1612.4 Labor Regulations Relating to Labor (Continued) EQUAL EMPLOYMENT OPPORTUNITY COMMISSION GOVERNMENT IN...) disclose investigative techniques and procedures, or (6) endanger the life of physical safety of law...

MiR-217 is down-regulated in psoriasis and promotes keratinocyte differentiation via targeting GRHL2

International Nuclear Information System (INIS)

Zhu, Haigang; Hou, Liyue; Liu, Jingjing; Li, Zhiming

2016-01-01

MiR-217 is a well-known tumor suppressor, and its down-regulation has been shown in a wide range of solid and leukaemic cancers. However, the biological role of miR-217 in psoriasis pathogenesis, especially in keratinocyte hyperproliferation and differentiation, is not clearly understood. In this study, we found the expression of miR-217 was markedly down-regulated in psoriasis keratinocytes of psoriatic patients. In addition, overexpression of miR-217 inhibited the proliferation and promoted the differentiation of primary human keratinocytes. On the contrary, inhibition of endogenous miR-217 increased cell proliferation and delayed differentiation. Furthermore, Grainyhead-like 2 (GRHL2) was identified as a direct target of miR-217 by luciferase reporter assay. The expression of miR-217 and GRHL2 was inversely correlated in both transfected keratinocytes and in psoriasis lesional skin. Moreover, knocking down GRHL2 expression by siRNA enhanced keratinocyte differentiation. Taken together, our results demonstrate a role for miR-217 in the regulation of keratinocyte differentiation, partially through the regulation of GRHL2. - Highlights: • miR-217 is down-regulated in psoriasis skin lesions. • miR-217 inhibits the proliferation and promotes differentiation of keratinocytes. • GRHL2 is a novel target of miR-217 in keratinocytes. • GRHL2 is up-regulated and inversely correlated with miR-217 in psoriasis skin lesions.

MiR-217 is down-regulated in psoriasis and promotes keratinocyte differentiation via targeting GRHL2

Energy Technology Data Exchange (ETDEWEB)

Zhu, Haigang; Hou, Liyue; Liu, Jingjing; Li, Zhiming, E-mail: lizm_1001@sina.com

2016-02-26

MiR-217 is a well-known tumor suppressor, and its down-regulation has been shown in a wide range of solid and leukaemic cancers. However, the biological role of miR-217 in psoriasis pathogenesis, especially in keratinocyte hyperproliferation and differentiation, is not clearly understood. In this study, we found the expression of miR-217 was markedly down-regulated in psoriasis keratinocytes of psoriatic patients. In addition, overexpression of miR-217 inhibited the proliferation and promoted the differentiation of primary human keratinocytes. On the contrary, inhibition of endogenous miR-217 increased cell proliferation and delayed differentiation. Furthermore, Grainyhead-like 2 (GRHL2) was identified as a direct target of miR-217 by luciferase reporter assay. The expression of miR-217 and GRHL2 was inversely correlated in both transfected keratinocytes and in psoriasis lesional skin. Moreover, knocking down GRHL2 expression by siRNA enhanced keratinocyte differentiation. Taken together, our results demonstrate a role for miR-217 in the regulation of keratinocyte differentiation, partially through the regulation of GRHL2. - Highlights: • miR-217 is down-regulated in psoriasis skin lesions. • miR-217 inhibits the proliferation and promotes differentiation of keratinocytes. • GRHL2 is a novel target of miR-217 in keratinocytes. • GRHL2 is up-regulated and inversely correlated with miR-217 in psoriasis skin lesions.

The Onion (Allium cepa L.) R2R3-MYB Gene MYB1 Regulates Anthocyanin Biosynthesis

Science.gov (United States)

Schwinn, Kathy E.; Ngo, Hanh; Kenel, Fernand; Brummell, David A.; Albert, Nick W.; McCallum, John A.; Pither-Joyce, Meeghan; Crowhurst, Ross N.; Eady, Colin; Davies, Kevin M.

2016-01-01

Bulb color is an important consumer trait for onion (Allium cepa L., Allioideae, Asparagales). The bulbs accumulate a range of flavonoid compounds, including anthocyanins (red), flavonols (pale yellow), and chalcones (bright yellow). Flavonoid regulation is poorly characterized in onion and in other plants belonging to the Asparagales, despite being a major plant order containing many important crop and ornamental species. R2R3-MYB transcription factors associated with the regulation of distinct branches of the flavonoid pathway were isolated from onion. These belonged to sub-groups (SGs) that commonly activate anthocyanin (SG6, MYB1) or flavonol (SG7, MYB29) production, or repress phenylpropanoid/flavonoid synthesis (SG4, MYB4, MYB5). MYB1 was demonstrated to be a positive regulator of anthocyanin biosynthesis by the induction of anthocyanin production in onion tissue when transiently overexpressed and by reduction of pigmentation when transiently repressed via RNAi. Furthermore, ectopic red pigmentation was observed in garlic (Allium sativum L.) plants stably transformed with a construct for co-overexpression of MYB1 and a bHLH partner. MYB1 also was able to complement the acyanic petal phenotype of a defined R2R3-MYB anthocyanin mutant in Antirrhinum majus of the asterid clade of eudicots. The availability of sequence information for flavonoid-related MYBs from onion enabled phylogenetic groupings to be determined across monocotyledonous and dicotyledonous species, including the identification of characteristic amino acid motifs. This analysis suggests that divergent evolution of the R2R3-MYB family has occurred between Poaceae/Orchidaceae and Allioideae species. The DNA sequences identified will be valuable for future analysis of classical flavonoid genetic loci in Allium crops and will assist the breeding of these important crop species. PMID:28018399

The Onion (Allium cepa L.) R2R3-MYB Gene MYB1 Regulates Anthocyanin Biosynthesis.

Science.gov (United States)

Schwinn, Kathy E; Ngo, Hanh; Kenel, Fernand; Brummell, David A; Albert, Nick W; McCallum, John A; Pither-Joyce, Meeghan; Crowhurst, Ross N; Eady, Colin; Davies, Kevin M

2016-01-01

Bulb color is an important consumer trait for onion ( Allium cepa L., Allioideae, Asparagales). The bulbs accumulate a range of flavonoid compounds, including anthocyanins (red), flavonols (pale yellow), and chalcones (bright yellow). Flavonoid regulation is poorly characterized in onion and in other plants belonging to the Asparagales, despite being a major plant order containing many important crop and ornamental species. R2R3-MYB transcription factors associated with the regulation of distinct branches of the flavonoid pathway were isolated from onion. These belonged to sub-groups (SGs) that commonly activate anthocyanin (SG6, MYB1) or flavonol (SG7, MYB29) production, or repress phenylpropanoid/flavonoid synthesis (SG4, MYB4, MYB5). MYB1 was demonstrated to be a positive regulator of anthocyanin biosynthesis by the induction of anthocyanin production in onion tissue when transiently overexpressed and by reduction of pigmentation when transiently repressed via RNAi. Furthermore, ectopic red pigmentation was observed in garlic ( Allium sativum L.) plants stably transformed with a construct for co-overexpression of MYB1 and a bHLH partner. MYB1 also was able to complement the acyanic petal phenotype of a defined R2R3-MYB anthocyanin mutant in Antirrhinum maju s of the asterid clade of eudicots. The availability of sequence information for flavonoid-related MYBs from onion enabled phylogenetic groupings to be determined across monocotyledonous and dicotyledonous species, including the identification of characteristic amino acid motifs. This analysis suggests that divergent evolution of the R2R3-MYB family has occurred between Poaceae/Orchidaceae and Allioideae species. The DNA sequences identified will be valuable for future analysis of classical flavonoid genetic loci in Allium crops and will assist the breeding of these important crop species.

Regulation of turkey myogenic satellite cell migration by MicroRNAs miR-128 and miR-24.

Science.gov (United States)

Velleman, S G; Harding, R L

2017-06-01

Myogenic satellite cells are an adult stem cell responsible for all post-hatch muscle growth in poultry. As a stem cell population, satellite cells are highly heterogeneous, but the origin of this heterogeneity remains unclear. Heterogeneity is, in part, regulated by gene expression. One method of endogenous gene regulation that may contribute to heterogeneity is microRNAs (miRNAs). Two miRNAs previously shown to regulate poultry myogenic satellite cell proliferation and differentiation, miR-128 and miR-24, were studied to determine if they also affected satellite cell migration. Satellite cell migration is an essential step for both proliferation and differentiation. During proliferation, satellite cells will migrate and align to form new myofibers or donate their nuclei to existing myofibers leading to muscle fiber hypertrophy or regeneration. Transient transfection of miRNA specific mimics to each miRNA reduced migration of satellite cells following a cell culture scratch at 72 h of proliferation when the cultures were 90 to 100% confluent. However, only the migration in cells transfected with miR-24 mimics at 24 and 30 h following the scratch was significantly reduced (P ≤ 0.05) to around 70% of the distance migrated by controls. Alternately, transfection with inhibitors specific to miR-128 or miR-24 significantly (P ≤ 0.05) increased migration between 147 and 252% compared to their controls between 24 and 48 h following the scratch. These data demonstrate that miR-128 and miR-24 play a role in myogenic satellite cell migration, which will impact muscle development and growth. © 2016 Poultry Science Association Inc.

77 FR 76542 - Millstone Power Station, Unit 2; Exemption

Science.gov (United States)

2012-12-28

... (CR) level indication, Condensate Storage Tank (CST) CR level indication, suction-side flow to the... and R-14. The fire areas included in the exemption request are not shop areas so hot work activities... provide for Decay Heat Removal and to restore Charging system flow to the RCS. 3.1.4 OMAs Credited for a...

Regulation by SoxR of mfsA, Which Encodes a Major Facilitator Protein Involved in Paraquat Resistance in Stenotrophomonas maltophilia.

Directory of Open Access Journals (Sweden)

Kriangsuk Srijaruskul

Full Text Available Stenotrophomonas maltophilia MfsA (Smlt1083 is an efflux pump in the major facilitator superfamily (MFS. Deletion of mfsA renders the strain more susceptible to paraquat, but no alteration in the susceptibility levels of other oxidants is observed. The expression of mfsA is inducible upon challenge with redox cycling/superoxide-generating drug (paraquat, menadione and plumbagin treatments and is directly regulated by SoxR, which is a transcription regulator and sensor of superoxide-generating agents. Analysis of mfsA expression patterns in wild-type and a soxR mutant suggests that oxidized SoxR functions as a transcription activator of the gene. soxR (smlt1084 is located in a head-to-head fashion with mfsA, and these genes share the -10 motif of their promoter sequences. Purified SoxR specifically binds to the putative mfsA promoter motifs that contain a region that is highly homologous to the consensus SoxR binding site, and mutation of the SoxR binding site abolishes binding of purified SoxR protein. The SoxR box is located between the putative -35 and -10 promoter motifs of mfsA; and this position is typical for a promoter in which SoxR acts as a transcriptional activator. At the soxR promoter, the SoxR binding site covers the transcription start site of the soxR transcript; thus, binding of SoxR auto-represses its own transcription. Taken together, our results reveal for the first time that mfsA is a novel member of the SoxR regulon and that SoxR binds and directly regulates its expression.

Introduction to the Special Volume on "Ecology and Ecological Modeling in R"

OpenAIRE

Kneib, Thomas; Petzoldt, Thomas

2007-01-01

The third special volume in the "Foometrics in R" series of the Journal of Statistical Software collects a number of contributions describing statistical methodology and corresponding implementations related to ecology and ecological modelling. The scope of the papers ranges from theoretical ecology and ecological modelling to statistical methodology relevant for data analyses in ecological applications.

40 CFR 152.20 - Exemptions for pesticides adequately regulated by another Federal agency.

Science.gov (United States)

2010-07-01

... Federal agency. (a) Certain biological control agents. (1) Except as provided by paragraphs (a)(3) and (a)(4) of this section, all biological control agents are exempt from FIFRA requirements. (2) If the Agency determines that an individual biological control agent or class of biological control agents is no...

In Vivo Delivery of miR-34a Sensitizes Lung Tumors to Radiation Through RAD51 Regulation

Directory of Open Access Journals (Sweden)

Maria Angelica Cortez

2015-01-01

Full Text Available MiR-34a, an important tumor-suppressing microRNA, is downregulated in several types of cancer; loss of its expression has been linked with unfavorable clinical outcomes in non-small-cell lung cancer (NSCLC, among others. MiR-34a represses several key oncogenic proteins, and a synthetic mimic of miR-34a is currently being tested in a cancer trial. However, little is known about the potential role of miR-34a in regulating DNA damage response and repair. Here, we demonstrate that miR-34a directly binds to the 3’ untranslated region of RAD51 and regulates homologous recombination, inhibiting double-strand-break repair in NSCLC cells. We further demonstrate the therapeutic potential of miR-34a delivery in combination with radiotherapy in mouse models of lung cancer. Collectively, our results suggest that administration of miR-34a in combination with radiotherapy may represent a novel strategy for treating NSCLC.

76 FR 70342 - Quarterly Listings; Safety Zones, Security Zones, Special Local Regulations, Drawbridge Operation...

Science.gov (United States)

2011-11-14

...] Quarterly Listings; Safety Zones, Security Zones, Special Local Regulations, Drawbridge Operation... published in the Federal Register. This notice lists temporary safety zones, security zones, special local... Commanders and Captains of the Port (COTP) must be immediately responsive to the safety and security needs...

MicroRNA miR-308 regulates dMyc through a negative feedback loop in Drosophila

Directory of Open Access Journals (Sweden)

Kaveh Daneshvar

2012-10-01

The abundance of Myc protein must be exquisitely controlled to avoid growth abnormalities caused by too much or too little Myc. An intriguing mode of regulation exists in which Myc protein itself leads to reduction in its abundance. We show here that dMyc binds to the miR-308 locus and increases its expression. Using our gain-of-function approach, we show that an increase in miR-308 causes a destabilization of dMyc mRNA and reduced dMyc protein levels. In vivo knockdown of miR-308 confirmed the regulation of dMyc levels in embryos. This regulatory loop is crucial for maintaining appropriate dMyc levels and normal development. Perturbation of the loop, either by elevated miR-308 or elevated dMyc, caused lethality. Combining elevated levels of both, therefore restoring balance between miR-308 and dMyc levels, resulted in lower apoptotic activity and suppression of lethality. These results reveal a sensitive feedback mechanism that is crucial to prevent the pathologies caused by abnormal levels of dMyc.

76 FR 44650 - Qualification of Drivers; Exemption Applications; Diabetes Mellitus

Science.gov (United States)

2011-07-26

...-2011-0143] Qualification of Drivers; Exemption Applications; Diabetes Mellitus AGENCY: Federal Motor... diabetes mellitus (ITDM) from operating commercial motor vehicles (CMVs) in interstate commerce. The... complying with the current regulation 49 CFR 391.41(b)(3). Diabetes Mellitus and Driving Experience of the...

76 FR 53707 - Qualification of Drivers; Exemption Applications; Diabetes Mellitus

Science.gov (United States)

2011-08-29

...-2011-0145] Qualification of Drivers; Exemption Applications; Diabetes Mellitus AGENCY: Federal Motor... diabetes mellitus (ITDM) from operating commercial motor vehicles (CMVs) in interstate commerce. The... complying with the current regulation 49 CFR 391.41(b)(3). Diabetes Mellitus and Driving Experience of the...

77 FR 25227 - Qualification of Drivers; Exemption Applications; Diabetes Mellitus

Science.gov (United States)

2012-04-27

...-2011-0383] Qualification of Drivers; Exemption Applications; Diabetes Mellitus AGENCY: Federal Motor... diabetes mellitus (ITDM) from operating commercial motor vehicles (CMVs) in interstate commerce. The... the current regulation 49 CFR 391.41(b)(3). Diabetes Mellitus and Driving Experience of the Applicants...

77 FR 75492 - Qualification of Drivers; Exemption Applications; Diabetes Mellitus

Science.gov (United States)

2012-12-20

...-2012-0283] Qualification of Drivers; Exemption Applications; Diabetes Mellitus AGENCY: Federal Motor... the current regulation 49 CFR 391.41(b)(3). Diabetes Mellitus and Driving Experience of the Applicants... person has no established medical history or clinical diagnosis of diabetes mellitus currently requiring...

77 FR 38383 - Qualification of Drivers; Exemption Applications; Diabetes Mellitus

Science.gov (United States)

2012-06-27

...-2012-0107] Qualification of Drivers; Exemption Applications; Diabetes Mellitus AGENCY: Federal Motor... current regulation 49 CFR 391.41(b)(3). Diabetes Mellitus and Driving Experience of the Applicants The... person has no established medical history or clinical diagnosis of diabetes mellitus currently requiring...

77 FR 64585 - Qualification of Drivers; Exemption Applications; Diabetes Mellitus

Science.gov (United States)

2012-10-22

...-2012-0218] Qualification of Drivers; Exemption Applications; Diabetes Mellitus AGENCY: Federal Motor... current regulation 49 CFR 391.41(b)(3). Diabetes Mellitus and Driving Experience of the Applicants The... person has no established medical history or clinical diagnosis of diabetes mellitus currently requiring...

76 FR 79759 - Qualification of Drivers; Exemption Applications; Diabetes Mellitus

Science.gov (United States)

2011-12-22

...-2011-0278] Qualification of Drivers; Exemption Applications; Diabetes Mellitus AGENCY: Federal Motor... diabetes mellitus (ITDM) from operating commercial motor vehicles (CMVs) in interstate commerce. The... complying with the current regulation 49 CFR 391.41(b)(3). Diabetes Mellitus and Driving Experience of the...

77 FR 59450 - Qualification of Drivers; Exemption Applications; Diabetes Mellitus

Science.gov (United States)

2012-09-27

...-2012-0164] Qualification of Drivers; Exemption Applications; Diabetes Mellitus AGENCY: Federal Motor... current regulation 49 CFR 391.41(b)(3). Diabetes Mellitus and Driving Experience of the Applicants The... person has no established medical history or clinical diagnosis of diabetes mellitus currently requiring...

76 FR 61139 - Qualification of Drivers; Exemption Applications; Diabetes Mellitus

Science.gov (United States)

2011-10-03

...-2011-0192] Qualification of Drivers; Exemption Applications; Diabetes Mellitus AGENCY: Federal Motor... diabetes mellitus (ITDM) from operating commercial motor vehicles (CMVs) in interstate commerce. The... complying with the current regulation 49 CFR 391.41(b)(3). Diabetes Mellitus and Driving Experience of the...

MiR-495 and miR-218 regulate the expression of the Onecut transcription factors HNF-6 and OC-2

Energy Technology Data Exchange (ETDEWEB)

Simion, Alexandru; Laudadio, Ilaria; Prevot, Pierre-Paul; Raynaud, Peggy; Lemaigre, Frederic P. [Universite catholique de Louvain, de Duve Institute, 75 Avenue Hippocrate 7529, B-1200 Brussels (Belgium); Jacquemin, Patrick, E-mail: patrick.jacquemin@uclouvain.be [Universite catholique de Louvain, de Duve Institute, 75 Avenue Hippocrate 7529, B-1200 Brussels (Belgium)

2010-01-01

MicroRNAs are small, non-coding RNAs that posttranscriptionally regulate gene expression mainly by binding to the 3'UTR of their target mRNAs. Recent data revealed that microRNAs have an important role in pancreas and liver development and physiology. Using cloning and microarray profiling approaches, we show that a unique repertoire of microRNAs is expressed at the onset of liver and pancreas organogenesis, and in pancreas and liver at key stages of cell fate determination. Among the microRNAs that are expressed at these stages, miR-495 and miR-218 were predicted to, respectively, target the Onecut (OC) transcription factors Hepatocyte Nuclear Factor-6 (HNF-6/OC-1) and OC-2, two important regulators of liver and pancreas development. MiR-495 and miR-218 are dynamically expressed in developing liver and pancreas, and by transient transfection, we show that they target HNF-6 and OC-2 3'UTRs. Moreover, when overexpressed in cultured cells, miR-495 and miR-218 decrease the endogenous levels of HNF-6 and OC-2 mRNA. These results indicate that the expression of regulators of liver and pancreas development is modulated by microRNAs. They also suggest a developmental role for miR-495 and miR-218.

MiR-495 and miR-218 regulate the expression of the Onecut transcription factors HNF-6 and OC-2

International Nuclear Information System (INIS)

Simion, Alexandru; Laudadio, Ilaria; Prevot, Pierre-Paul; Raynaud, Peggy; Lemaigre, Frederic P.; Jacquemin, Patrick

2010-01-01

MicroRNAs are small, non-coding RNAs that posttranscriptionally regulate gene expression mainly by binding to the 3'UTR of their target mRNAs. Recent data revealed that microRNAs have an important role in pancreas and liver development and physiology. Using cloning and microarray profiling approaches, we show that a unique repertoire of microRNAs is expressed at the onset of liver and pancreas organogenesis, and in pancreas and liver at key stages of cell fate determination. Among the microRNAs that are expressed at these stages, miR-495 and miR-218 were predicted to, respectively, target the Onecut (OC) transcription factors Hepatocyte Nuclear Factor-6 (HNF-6/OC-1) and OC-2, two important regulators of liver and pancreas development. MiR-495 and miR-218 are dynamically expressed in developing liver and pancreas, and by transient transfection, we show that they target HNF-6 and OC-2 3'UTRs. Moreover, when overexpressed in cultured cells, miR-495 and miR-218 decrease the endogenous levels of HNF-6 and OC-2 mRNA. These results indicate that the expression of regulators of liver and pancreas development is modulated by microRNAs. They also suggest a developmental role for miR-495 and miR-218.

SACE_0012, a TetR-Family Transcriptional Regulator, Affects the Morphogenesis of Saccharopolyspora erythraea

OpenAIRE

Yin, Xiaojuan; Xu, Xinqiang; Wu, Hang; Yuan, Li; Huang, Xunduan; Zhang, Buchang

2013-01-01

Saccharopolyspora erythraea, a mycelium-forming actinomycete, produces a clinically important antibiotic erythromycin. Extensive investigations have provided insights into erythromycin biosynthesis in S. erythraea, but knowledge of its morphogenesis remains limited. By gene inactivation and complementation strategies, the TetR-family transcriptional regulator SACE_0012 was identified to be a negative regulator of mycelium formation of S. erythraea A226. Detected by quantitative real-time PCR,...

Arabidopsis mutant sk156 reveals complex regulation of SPL15 in a miR156-controlled gene network.

Science.gov (United States)

Wei, Shu; Gruber, Margaret Y; Yu, Bianyun; Gao, Ming-Jun; Khachatourians, George G; Hegedus, Dwayne D; Parkin, Isobel A P; Hannoufa, Abdelali

2012-09-18

The Arabidopsis microRNA156 (miR156) regulates 11 members of the SQUAMOSA PROMOTER BINDING PROTEIN LIKE (SPL) family by base pairing to complementary target mRNAs. Each SPL gene further regulates a set of other genes; thus, miR156 controls numerous genes through a complex gene regulation network. Increased axillary branching occurs in transgenic Arabidopsis overexpressing miR156b, similar to that observed in loss-of-function max3 and max4 mutants with lesions in carotenoid cleavage dioxygenases. Arabidopsis miR156b was found to enhance carotenoid levels and reproductive shoot branching when expressed in Brassica napus, suggesting a link between miR156b expression and carotenoid metabolism. However, details of the miR156 regulatory network of SPL genes related to carotenoid metabolism are not known. In this study, an Arabidopsis T-DNA enhancer mutant, sk156, was identified due to its altered branching and trichome morphology and increased seed carotenoid levels compared to wild type (WT) ecovar Columbia. Enhanced miR156b expression due to the 35S enhancers present on the T-DNA insert was responsible for these phenotypes. Constitutive and leaf primodium-specific expression of a miR156-insensitive (mutated) SPL15 (SPL15m) largely restored WT seed carotenoid levels and plant morphology when expressed in sk156. The Arabidopsis native miR156-sensitive SPL15 (SPL15n) and SPL15m driven by a native SPL15 promoter did not restore the WT phenotype in sk156. Our findings suggest that SPL15 function is somewhat redundant with other SPL family members, which collectively affect plant phenotypes. Moreover, substantially decreased miR156b transcript levels in sk156 expressing SPL15m, together with the presence of multiple repeats of SPL-binding GTAC core sequence close to the miR156b transcription start site, suggested feedback regulation of miR156b expression by SPL15. This was supported by the demonstration of specific in vitro interaction between DNA-binding SBP domain of SPL15

miR-27 regulates mitochondrial networks by directly targeting the mitochondrial fission factor.

Science.gov (United States)

Tak, Hyosun; Kim, Jihye; Jayabalan, Aravinth Kumar; Lee, Heejin; Kang, Hoin; Cho, Dong-Hyung; Ohn, Takbum; Nam, Suk Woo; Kim, Wook; Lee, Eun Kyung

2014-11-28

Mitochondrial morphology is dynamically regulated by forming small, fragmented units or interconnected networks, and this is a pivotal process that is used to maintain mitochondrial homeostasis. Although dysregulation of mitochondrial dynamics is related to the pathogenesis of several human diseases, its molecular mechanism is not fully elucidated. In this study, we demonstrate the potential role of miR-27 in the regulation of mitochondrial dynamics. Mitochondrial fission factor (MFF) mRNA is a direct target of miR-27, whose ectopic expression decreases MFF expression through binding to its 3'-untranslated region. Expression of miR-27 results in the elongation of mitochondria as well as an increased mitochondrial membrane potential and mitochondrial ATP level. Our results suggest that miR-27 is a novel regulator affecting morphological mitochondrial changes by targeting MFF.

Multiple Copies of a Simple MYB-Binding Site Confers Trans-regulation by Specific Flavonoid-Related R2R3 MYBs in Diverse Species

Directory of Open Access Journals (Sweden)

Cyril Brendolise

2017-10-01

Full Text Available In apple, the MYB transcription factor MYB10 controls the accumulation of anthocyanins. MYB10 is able to auto-activate its expression by binding its own promoter at a specific motif, the R1 motif. In some apple accessions a natural mutation, termed R6, has more copies of this motif within the MYB10 promoter resulting in stronger auto-activation and elevated anthocyanins. Here we show that other anthocyanin-related MYBs selected from apple, pear, strawberry, petunia, kiwifruit and Arabidopsis are able to activate promoters containing the R6 motif. To examine the specificity of this motif, members of the R2R3 MYB family were screened against a promoter harboring the R6 mutation. Only MYBs from subgroups 5 and 6 activate expression by binding the R6 motif, with these MYBs sharing conserved residues in their R2R3 DNA binding domains. Insertion of the apple R6 motif into orthologous promoters of MYB10 in pear (PcMYB10 and Arabidopsis (AtMY75 elevated anthocyanin levels. Introduction of the R6 motif into the promoter region of an anthocyanin biosynthetic enzyme F3′5′H of kiwifruit imparts regulation by MYB10. This results in elevated levels of delphinidin in both tobacco and kiwifruit. Finally, an R6 motif inserted into the promoter the vitamin C biosynthesis gene GDP-L-Gal phosphorylase increases vitamin C content in a MYB10-dependent manner. This motif therefore provides a tool to re-engineer novel MYB-regulated responses in plants.

miR-21 may acts as an oncomir by targeting RECK, a matrix metalloproteinase regulator, in prostate cancer

Directory of Open Access Journals (Sweden)

Reis Sabrina

2012-05-01

Full Text Available Abstract Background Prognosis of prostate cancer (PCa is based mainly in histological aspects together with PSA serum levels that not always reflect the real aggressive potential of the neoplasia. The micro RNA (miRNA mir-21 has been shown to regulate invasiveness in cancer through translational repression of the Metaloproteinase (MMP inhibitor RECK. Our aim is to investigate the levels of expression of RECK and miR-21 in PCa comparing with classical prognostic factors and disease outcome and also test if RECK is a target of miR-21 in in vitro study using PCa cell line. Materials and methods To determine if RECK is a target of miR-21 in prostate cancer we performed an in vitro assay with PCa cell line DU-145 transfected with pre-miR-21 and anti-miR-21. To determine miR-21 and RECK expression levels in PCa samples we performed quantitative real-time polymerase chain reaction (qRT-PCR. Results The in vitro assays showed a decrease in expression levels of RECK after transfection with pre-miR-21, and an increase of MMP9 that is regulated by RECK compared to PCa cells treated with anti-miR-21. We defined three profiles to compare the prognostic factors. The first was characterized by miR-21 and RECK underexpression (N = 25 the second was characterized by miR-21 overexpression and RECK underexpression (N = 12, and the third was characterized by miR-21 underexpression and RECK overexpression (N = 16. From men who presented the second profile (miR-21 overexpression and RECK underexpression 91.7% were staged pT3. For the other two groups 48.0%, and 46.7% of patients were staged pT3 (p = 0.025. Conclusions Our results demonstrate RECK as a target of miR-21. We believe that miR-21 may be important in PCa progression through its regulation of RECK, a known regulator of tumor cell invasion.

77 FR 23120 - Special Local Regulations; Lowcountry Splash Open Water Swim, Wando River and Cooper River, Mount...

Science.gov (United States)

2012-04-18

...-AA08 Special Local Regulations; Lowcountry Splash Open Water Swim, Wando River and Cooper River, Mount... establishing special local regulations on the waters of the Wando River and Cooper River in Mount Pleasant... River and Cooper River along the shoreline of Mount Pleasant, South Carolina. The Lowcountry Splash...

Non-selective regulation of peroxide and superoxide resistance genes by PerR in Campylobacter jejuni

Directory of Open Access Journals (Sweden)

Jong-Chul eKim

2015-02-01

Full Text Available Campylobacter jejuni is an important foodborne pathogen. The molecular mechanisms for the regulation of oxidative stress resistance have not yet been understood fully in this bacterium. In this study, we investigated how PerR (peroxide stress regulator modulates the transcriptional regulation of both peroxide and superoxide resistance genes in C. jejuni, particularly under oxidative stress conditions. The transcriptional levels of ahpC, katA, and sodB were substantially increased by aeration and oxidant exposure. Interestingly, a perR mutation completely abrogated the transcriptional response of ahpC, katA and sodB to oxidants. Furthermore, we demonstrated that perR transcription was reduced by aeration and oxidant exposure. In contrast to the unique role of PerR homologs in peroxide stress regulation in other bacteria, interestingly, C. jejuni PerR directly regulates the transcription of sodB, the most important gene in superoxide defense, as evidenced by the alteration of sodB transcription by the perR mutation and direct binding of rPerR to the sodB promoter. In addition, we also observed notable morphological changes in C. jejuni from spiral rods to coccoid morphology under aerobic conditions. Based on the intracellular ATP levels, C. jejuni entered a viable-but-non-culturable state under aerobic conditions. These findings clearly demonstrate that C. jejuni possesses a unique regulatory mechanism of oxidative stress defense that does not specifically distinguish between peroxide and superoxide defense, and PerR plays a pivotal role in this non-selective regulation of oxidative stress resistance in C. jejuni.

40 CFR 180.1054 - Calcium hypochlorite; exemptions from the requirement of a tolerance.

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 23 2010-07-01 2010-07-01 false Calcium hypochlorite; exemptions from... FOOD Exemptions From Tolerances § 180.1054 Calcium hypochlorite; exemptions from the requirement of a tolerance. (a) Calcium hypochlorite is exempted from the requirement of a tolerance when used preharvest or...

System certification: An alternative to package certification?

International Nuclear Information System (INIS)

Luna, R.E.; Jefferson, R.J.

1991-01-01

One precept of the current radioactive material transportation regulations is that the package is the primary protection for the public. A packaging is chosen to provide containment, shielding, and criticality control suitable to the quantity and characteristics of the radionuclide being transported. Occasionally, radioactive materials requiring transport are not of a mass or size that would allow the materials to be shipped in an appropriate packaging. Where the shipment to be made is relatively infrequent, there may be economic and time penalties that may hamper shipment or force the shipper into uneconomic or high risk options. However, there is recognition of such situations in the International Atomic Energy Agency (IAEA) regulations under the provisions for Special Arrangement. The principal paragraphs defining Special Arrangement in Regulations for the Safe of Radioactive Material; Safety Series 6 (SS6) [IAEA, 1990a] are 141, 211, 720, and 727. In the US regulations the applicable term is ''Exemption.'' An exemption is obtained from either the United States Department of Transportation (USDOT) or the United States Nuclear Regulatory Commission (USNRC) depending on the character of the needed exemption. The essential concept is that some requirements of the regulations that apply in a given situation are not required if the shipment is subjected to other operational controls that provide an equivalent level of risk to that attained if the regulations were observed fully. This paper deals primarily with changing of packaging requirements in Special Arrangements, but it is also true that operational requirements also may be changed as a result of an Exemption or Special Arrangement approval by a regulatory authority

MiR-338-3p regulates neuronal maturation and suppresses glioblastoma proliferation.

Directory of Open Access Journals (Sweden)

James R Howe

Full Text Available Neurogenesis is a highly-regulated process occurring in the dentate gyrus that has been linked to learning, memory, and antidepressant efficacy. MicroRNAs (miRNAs have been previously shown to play an important role in the regulation of neuronal development and neurogenesis in the dentate gyrus via modulation of gene expression. However, this mode of regulation is both incompletely described in the literature thus far and highly multifactorial. In this study, we designed sensors and detected relative levels of expression of 10 different miRNAs and found miR-338-3p was most highly expressed in the dentate gyrus. Comparison of miR-338-3p expression with neuronal markers of maturity indicates miR-338-3p is expressed most highly in the mature neuron. We also designed a viral "sponge" to knock down in vivo expression of miR-338-3p. When miR-338-3p is knocked down, neurons sprout multiple primary dendrites that branch off of the soma in a disorganized manner, cellular proliferation is upregulated, and neoplasms form spontaneously in vivo. Additionally, miR-338-3p overexpression in glioblastoma cell lines slows their proliferation in vitro. Further, low miR-338-3p expression is associated with increased mortality and disease progression in patients with glioblastoma. These data identify miR-338-3p as a clinically relevant tumor suppressor in glioblastoma.

21 CFR 511.1 - New animal drugs for investigational use exempt from section 512(a) of the act.

Science.gov (United States)

2010-04-01

... in animals used only for laboratory research purposes under this exemption shall use due diligence to... diligence to assure that the new animal drug or animal feed containing a new animal drug will actually be... animal administered any unlicensed experimental veterinary biological product regulated under the viruses...

78 FR 20032 - Styrene-Ethylene-Propylene Block Copolymer; Tolerance Exemption

Science.gov (United States)

2013-04-03

...-Ethylene-Propylene Block Copolymer; Tolerance Exemption AGENCY: Environmental Protection Agency (EPA... for residues of styrene-ethylene-propylene block copolymer (CAS Reg. No. 108388-87-0) when used as an...-ethylene-propylene block copolymer on food or feed commodities. DATES: This regulation is effective April 3...

78 FR 37273 - Qualification of Drivers; Exemption Applications; Diabetes Mellitus

Science.gov (United States)

2013-06-20

...-2013-0016] Qualification of Drivers; Exemption Applications; Diabetes Mellitus AGENCY: Federal Motor... achieved by complying with the current regulation 49 CFR 391.41(b)(3). Diabetes Mellitus and Driving... mellitus currently requiring insulin for control'' (49 CFR 391.41(b)(3)). FMCSA established its diabetes...

77 FR 75493 - Qualification of Drivers; Exemption Applications; Diabetes Mellitus

Science.gov (United States)

2012-12-20

...-2012-0282] Qualification of Drivers; Exemption Applications; Diabetes Mellitus AGENCY: Federal Motor... complying with the current regulation 49 CFR 391.41(b)(3). Diabetes Mellitus and Driving Experience of the... person has no established medical history or clinical diagnosis of diabetes mellitus currently requiring...

78 FR 26422 - Qualification of Drivers; Exemption Applications; Diabetes Mellitus

Science.gov (United States)

2013-05-06

...-2013-0012] Qualification of Drivers; Exemption Applications; Diabetes Mellitus AGENCY: Federal Motor... achieved by complying with the current regulation 49 CFR 391.41(b)(3). Diabetes Mellitus and Driving... mellitus currently requiring insulin for control'' (49 CFR 391.41(b)(3)). FMCSA established its diabetes...

77 FR 65929 - Qualification of Drivers; Exemption Applications; Diabetes Mellitus

Science.gov (United States)

2012-10-31

...-2012-0219] Qualification of Drivers; Exemption Applications; Diabetes Mellitus AGENCY: Federal Motor... complying with the current regulation 49 CFR 391.41(b)(3). Diabetes Mellitus and Driving Experience of the... person has no established medical history or clinical diagnosis of diabetes mellitus currently requiring...

77 FR 70529 - Qualification of Drivers; Exemption Applications; Diabetes Mellitus

Science.gov (United States)

2012-11-26

...-2012-0281] Qualification of Drivers; Exemption Applications; Diabetes Mellitus AGENCY: Federal Motor... complying with the current regulation 49 CFR 391.41(b)(3). Diabetes Mellitus and Driving Experience of the... person has no established medical history or clinical diagnosis of diabetes mellitus currently requiring...

78 FR 35088 - Qualification of Drivers; Exemption Applications; Diabetes Mellitus

Science.gov (United States)

2013-06-11

...-2013-0015] Qualification of Drivers; Exemption Applications; Diabetes Mellitus AGENCY: Federal Motor... would be achieved by complying with the current regulation 49 CFR 391.41(b)(3). Diabetes Mellitus and... of diabetes mellitus currently requiring insulin for control'' (49 CFR 391.41(b)(3)). FMCSA...

77 FR 46791 - Qualification of Drivers; Exemption Applications; Diabetes Mellitus

Science.gov (United States)

2012-08-06

...-2012-0162] Qualification of Drivers; Exemption Applications; Diabetes Mellitus AGENCY: Federal Motor... complying with the current regulation 49 CFR 391.41(b)(3). Diabetes Mellitus and Driving Experience of the... person has no established medical history or clinical diagnosis of diabetes mellitus currently requiring...

78 FR 5559 - Qualification of Drivers; Exemption Applications; Diabetes Mellitus

Science.gov (United States)

2013-01-25

...-2012-0348] Qualification of Drivers; Exemption Applications; Diabetes Mellitus AGENCY: Federal Motor... complying with the current regulation 49 CFR 391.41(b)(3). Diabetes Mellitus and Driving Experience of the... person has no established medical history or clinical diagnosis of diabetes mellitus currently requiring...

77 FR 33264 - Qualification of Drivers; Exemption Applications; Diabetes Mellitus

Science.gov (United States)

2012-06-05

...-2012-0044] Qualification of Drivers; Exemption Applications; Diabetes Mellitus AGENCY: Federal Motor... complying with the current regulation 49 CFR 391.41(b)(3). Diabetes Mellitus and Driving Experience of the... person has no established medical history or clinical diagnosis of diabetes mellitus currently requiring...

77 FR 29446 - Qualification of Drivers; Exemption Applications; Diabetes Mellitus

Science.gov (United States)

2012-05-17

...-2012-0043] Qualification of Drivers; Exemption Applications; Diabetes Mellitus AGENCY: Federal Motor... current regulation 49 CFR 391.41(b)(3). Diabetes Mellitus and Driving Experience of the Applicants The... vehicle if that person has no established medical history or clinical diagnosis of diabetes mellitus...

78 FR 37272 - Qualification of Drivers; Exemption Applications; Diabetes Mellitus

Science.gov (United States)

2013-06-20

...-2013-0017] Qualification of Drivers; Exemption Applications; Diabetes Mellitus AGENCY: Federal Motor... achieved by complying with the current regulation 49 CFR 391.41(b)(3). Diabetes Mellitus and Driving... mellitus currently requiring insulin for control'' (49 CFR 391.41(b)(3)). FMCSA established its diabetes...

29 CFR 516.21 - Bulk petroleum employees partially exempt from overtime pay requirements pursuant to section 7(b...

Science.gov (United States)

2010-07-01

... 29 Labor 3 2010-07-01 2010-07-01 false Bulk petroleum employees partially exempt from overtime pay requirements pursuant to section 7(b)(3) of the Act. 516.21 Section 516.21 Labor Regulations Relating to Labor....21 Bulk petroleum employees partially exempt from overtime pay requirements pursuant to section 7(b...

40 CFR 180.1040 - Ethylene glycol; exemption from the requirement of a tolerance.

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 23 2010-07-01 2010-07-01 false Ethylene glycol; exemption from the... Exemptions From Tolerances § 180.1040 Ethylene glycol; exemption from the requirement of a tolerance. Ethylene glycol as a component of pesticide formulations is exempt from the requirement of a tolerance when...

40 CFR 180.1135 - Pasteuria penetrans; exemption from the requirement of a tolerance.

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 23 2010-07-01 2010-07-01 false Pasteuria penetrans; exemption from... FOOD Exemptions From Tolerances § 180.1135 Pasteuria penetrans; exemption from the requirement of a tolerance. The biological nematicide Pasteuria penetrans is exempted from the requirement of a tolerance in...

40 CFR 180.1145 - Pseudomonas syringae; exemption from the requirement of a tolerance.

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 23 2010-07-01 2010-07-01 false Pseudomonas syringae; exemption from... FOOD Exemptions From Tolerances § 180.1145 Pseudomonas syringae; exemption from the requirement of a tolerance. Pseudomonas syringae is exempted from the requirement of a tolerance on all raw agricultural...

77 FR 15006 - Special Local Regulations; Third Annual Space Coast Super Boat Grand Prix, Atlantic Ocean, Cocoa...

Science.gov (United States)

2012-03-14

...-AA08 Special Local Regulations; Third Annual Space Coast Super Boat Grand Prix, Atlantic Ocean, Cocoa... proposes to establish special local regulations on the waters of the Atlantic Ocean east of Cocoa Beach... waters of the Atlantic Ocean east of Cocoa Beach, Florida. Approximately 30 high- speed power boats are...

78 FR 71493 - Special Local Regulation; Lake Havasu City Christmas Boat Parade of Lights; Colorado River; Lake...

Science.gov (United States)

2013-11-29

...-AA00 Special Local Regulation; Lake Havasu City Christmas Boat Parade of Lights; Colorado River; Lake... temporarily modifying the dates for the special local regulation in support of the Lake Havasu City Christmas Boat Parade of Lights on the Colorado River. This modification is necessary to reflect the actual dates...

Lipopolysaccharide induces the migration of human dental pulp cells by up-regulating miR-146a.

Science.gov (United States)

Wang, Min-Ching; Hung, Pei-Shih; Tu, Hsi-Feng; Shih, Wen-Yu; Li, Wan-Chun; Chang, Kuo-Wei

2012-12-01

MicroRNAs are small noncoding RNAs that play crucial roles in regulating normal and pathologic functions. Bacterial lipopolysaccharide (LPS) is one of the key regulators of pulpal pathogenesis. This study investigated how LPS regulates microRNA expression and affects the phenotype of human dental pulp cells (DPCs). Primary DPCs were established and immortalized to achieve immortalized DPCs (I-DPCs). DPCs and I-DPCs were treated with LPS and examined to identify changes in microRNA expression, cell proliferation, and cell migration. Quantitative reverse-transcriptase polymerase chain reaction was used to detect changes in gene expression. Exogenous miR-146a expression was performed transfection with pre-mir-146a mimic. Knockdown of interleukin receptor-associated kinase (IRAK1) and tumor necrosis factor receptor-associated factor 6 (TRAF6) expression was performed by small interference oligonucleotide transfection. Western blot analysis was used to detect changes in the expression of the IRAK1 and TRAF6 proteins. The differentiation of DPCs was induced by osteogenic medium. I-DPCs had a higher level of human telomerase reverse transcriptase gene than the parental DPCs. Up-regulation of miR-146a expression and an increase in migration was induced by LPS treatment of DPCs and I-DPCs. Exogenous miR-146a expression increased the migration of DPCs and I-DPCs and down-regulated the expression of IRAK1 and TRAF6. Knockdown of IRAK1 and/or TRAF6 increased the migration of DPCs. The results suggested that LPS is able to increase the migration of DPCs by modulating the miR-146a-TRAF6/IRAK1 regulatory cascade. Copyright © 2012 American Association of Endodontists. All rights reserved.

40 CFR 180.1090 - Lactic acid; exemption from the requirement of a tolerance.

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 23 2010-07-01 2010-07-01 false Lactic acid; exemption from the... Exemptions From Tolerances § 180.1090 Lactic acid; exemption from the requirement of a tolerance. Lactic acid (2-hydroxypropanoic acid) is exempted from the requirement of a tolerance when used as a plant growth...

40 CFR 180.1241 - Eucalyptus oil; exemption from the requirement of a tolerance.

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 23 2010-07-01 2010-07-01 false Eucalyptus oil; exemption from the... Exemptions From Tolerances § 180.1241 Eucalyptus oil; exemption from the requirement of a tolerance. Time-limited exemptions from the requirement of a tolerance are established for residues of eucalyptus oil on...

Proteolysis of virulence regulator ToxR is associated with entry of Vibrio cholerae into a dormant state.

Directory of Open Access Journals (Sweden)

Salvador Almagro-Moreno