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Sample records for activities regulations statutes

  1. 32 CFR 516.29 - Federal statutes and regulations.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... AUTHORITIES AND PUBLIC RELATIONS LITIGATION Individual Liability § 516.29 Federal statutes and regulations. (a... health care provider. (d) 28 CFR 50.15 (Representation of Federal officials and employees by Department... and procedures for requesting representation in individual liability cases. See also 28 CFR part...

  2. Youth Camp Safety & Health. Suggested State Statute & Regulations.

    ERIC Educational Resources Information Center

    Center for Disease Control (DHEW/PHS), Atlanta, GA.

    To assist state regulatory agencies in development of comprehensive youth camp safety programs, this publication contains a brief suggested statute that could be used for initiation or modification of any state's youth camp safety programs and it outlines minimal regulations. Various categories of camps are covered--day, primitive, residential,…

  3. 75 FR 17708 - Enforcement of Statutes, Orders, Rules and Regulations; Second Notice of Workshops on Penalty...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-07

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF ENERGY Federal Energy Regulatory Commission Enforcement of Statutes, Orders, Rules and Regulations; Second Notice of... call 703- 993-3100. \\1\\ Enforcement of Statutes, Orders, Rules, and Regulations, 130 FERC ]...

  4. 14 CFR 223.21 - Free and reduced-rate transportation authorized by statute or regulation.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 14 Aeronautics and Space 4 2010-01-01 2010-01-01 false Free and reduced-rate transportation authorized by statute or regulation. 223.21 Section 223.21 Aeronautics and Space OFFICE OF THE SECRETARY... International Travel § 223.21 Free and reduced-rate transportation authorized by statute or regulation. (a)...

  5. 14 CFR 223.21 - Free and reduced-rate transportation authorized by statute or regulation.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 14 Aeronautics and Space 4 2013-01-01 2013-01-01 false Free and reduced-rate transportation authorized by statute or regulation. 223.21 Section 223.21 Aeronautics and Space OFFICE OF THE SECRETARY... International Travel § 223.21 Free and reduced-rate transportation authorized by statute or regulation. (a)...

  6. 14 CFR 223.21 - Free and reduced-rate transportation authorized by statute or regulation.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 14 Aeronautics and Space 4 2011-01-01 2011-01-01 false Free and reduced-rate transportation authorized by statute or regulation. 223.21 Section 223.21 Aeronautics and Space OFFICE OF THE SECRETARY... International Travel § 223.21 Free and reduced-rate transportation authorized by statute or regulation. (a)...

  7. 14 CFR 223.21 - Free and reduced-rate transportation authorized by statute or regulation.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 14 Aeronautics and Space 4 2012-01-01 2012-01-01 false Free and reduced-rate transportation authorized by statute or regulation. 223.21 Section 223.21 Aeronautics and Space OFFICE OF THE SECRETARY... International Travel § 223.21 Free and reduced-rate transportation authorized by statute or regulation. (a)...

  8. 14 CFR 223.21 - Free and reduced-rate transportation authorized by statute or regulation.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 14 Aeronautics and Space 4 2014-01-01 2014-01-01 false Free and reduced-rate transportation authorized by statute or regulation. 223.21 Section 223.21 Aeronautics and Space OFFICE OF THE SECRETARY... International Travel § 223.21 Free and reduced-rate transportation authorized by statute or regulation. (a)...

  9. 75 FR 16100 - Enforcement of Statutes, Orders, Rules and Regulations; Notice of Workshops on Penalty Guidelines

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-31

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF ENERGY Federal Energy Regulatory Commission Enforcement of Statutes, Orders, Rules and Regulations; Notice of Workshops... registration list or registration fee to attend. \\1\\ Enforcement of Statutes, Orders, Rules, and...

  10. 29 CFR 794.110 - Activities excluded from the enterprise by the statute.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 29 Labor 3 2011-07-01 2011-07-01 false Activities excluded from the enterprise by the statute. 794... âenterpriseâ § 794.110 Activities excluded from the enterprise by the statute. The circumstances under which certain activities will be excluded from the “enterprise” referred to in the Act are made clear by...

  11. 29 CFR 794.110 - Activities excluded from the enterprise by the statute.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 29 Labor 3 2012-07-01 2012-07-01 false Activities excluded from the enterprise by the statute. 794... âenterpriseâ § 794.110 Activities excluded from the enterprise by the statute. The circumstances under which certain activities will be excluded from the “enterprise” referred to in the Act are made clear by...

  12. 29 CFR 794.110 - Activities excluded from the enterprise by the statute.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 29 Labor 3 2014-07-01 2014-07-01 false Activities excluded from the enterprise by the statute. 794... âenterpriseâ § 794.110 Activities excluded from the enterprise by the statute. The circumstances under which certain activities will be excluded from the “enterprise” referred to in the Act are made clear by...

  13. 29 CFR 794.110 - Activities excluded from the enterprise by the statute.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 29 Labor 3 2013-07-01 2013-07-01 false Activities excluded from the enterprise by the statute. 794... âenterpriseâ § 794.110 Activities excluded from the enterprise by the statute. The circumstances under which certain activities will be excluded from the “enterprise” referred to in the Act are made clear by...

  14. 45 CFR 1180.51 - Compliance with statutes, regulations, and its approved grant application.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 45 Public Welfare 3 2010-10-01 2010-10-01 false Compliance with statutes, regulations, and its approved grant application. 1180.51 Section 1180.51 Public Welfare Regulations Relating to Public Welfare (Continued) NATIONAL FOUNDATION ON THE ARTS AND THE HUMANITIES INSTITUTE OF MUSEUM AND LIBRARY...

  15. 28 CFR Appendix B to Subpart I of... - Age Distinctions in Federal Statutes or Regulations Affecting Financial Assistance Administered...

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... current regulations pertaining to formula grants under this statute are set forth at 28 CFR part 31 (CFDA... concerning block grants authorized under this statute are set forth at 28 CFR part 33. These regulations... assistance under the Victims of Crime Act of 1984, as amended (42 U.S.C. 10601-10604). Among other things,...

  16. 28 CFR Appendix B to Subpart I of... - Age Distinctions in Federal Statutes or Regulations Affecting Financial Assistance Administered...

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... current regulations pertaining to formula grants under this statute are set forth at 28 CFR part 31 (CFDA... concerning block grants authorized under this statute are set forth at 28 CFR part 33. These regulations... assistance under the Victims of Crime Act of 1984, as amended (42 U.S.C. 10601-10604). Among other things,...

  17. 28 CFR Appendix B to Subpart I of... - Age Distinctions in Federal Statutes or Regulations Affecting Financial Assistance Administered...

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... current regulations pertaining to formula grants under this statute are set forth at 28 CFR part 31 (CFDA... concerning block grants authorized under this statute are set forth at 28 CFR part 33. These regulations... assistance under the Victims of Crime Act of 1984, as amended (42 U.S.C. 10601-10604). Among other things,...

  18. 28 CFR Appendix B to Subpart I of... - Age Distinctions in Federal Statutes or Regulations Affecting Financial Assistance Administered...

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... current regulations pertaining to formula grants under this statute are set forth at 28 CFR part 31 (CFDA... concerning block grants authorized under this statute are set forth at 28 CFR part 33. These regulations... assistance under the Victims of Crime Act of 1984, as amended (42 U.S.C. 10601-10604). Among other things,...

  19. 28 CFR Appendix B to Subpart I of... - Age Distinctions in Federal Statutes or Regulations Affecting Financial Assistance Administered...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... current regulations pertaining to formula grants under this statute are set forth at 28 CFR part 31 (CFDA... concerning block grants authorized under this statute are set forth at 28 CFR part 33. These regulations... assistance under the Victims of Crime Act of 1984, as amended (42 U.S.C. 10601-10604). Among other things,...

  20. 42 CFR 68.17 - What other regulations and statutes apply?

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 42 Public Health 1 2014-10-01 2014-10-01 false What other regulations and statutes apply? 68.17 Section 68.17 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES FELLOWSHIPS, INTERNSHIPS, TRAINING NATIONAL INSTITUTES OF HEALTH (NIH) LOAN REPAYMENT PROGRAMS (LRPs) § 68.17 What...

  1. 42 CFR 68a.16 - What other regulations and statutes apply?

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 42 Public Health 1 2012-10-01 2012-10-01 false What other regulations and statutes apply? 68a.16 Section 68a.16 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES FELLOWSHIPS, INTERNSHIPS, TRAINING NATIONAL INSTITUTES OF HEALTH (NIH) CLINICAL RESEARCH LOAN REPAYMENT PROGRAM...

  2. 42 CFR 68.17 - What other regulations and statutes apply?

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 42 Public Health 1 2013-10-01 2013-10-01 false What other regulations and statutes apply? 68.17 Section 68.17 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES FELLOWSHIPS, INTERNSHIPS, TRAINING NATIONAL INSTITUTES OF HEALTH (NIH) LOAN REPAYMENT PROGRAMS (LRPs) § 68.17 What...

  3. 42 CFR 68a.16 - What other regulations and statutes apply?

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 1 2010-10-01 2010-10-01 false What other regulations and statutes apply? 68a.16 Section 68a.16 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES FELLOWSHIPS, INTERNSHIPS, TRAINING NATIONAL INSTITUTES OF HEALTH (NIH) CLINICAL RESEARCH LOAN REPAYMENT PROGRAM...

  4. 42 CFR 68a.16 - What other regulations and statutes apply?

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 42 Public Health 1 2011-10-01 2011-10-01 false What other regulations and statutes apply? 68a.16 Section 68a.16 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES FELLOWSHIPS, INTERNSHIPS, TRAINING NATIONAL INSTITUTES OF HEALTH (NIH) CLINICAL RESEARCH LOAN REPAYMENT PROGRAM...

  5. 42 CFR 68c.16 - What other regulations and statutes apply?

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 42 Public Health 1 2011-10-01 2011-10-01 false What other regulations and statutes apply? 68c.16 Section 68c.16 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES FELLOWSHIPS, INTERNSHIPS, TRAINING NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT CONTRACEPTION AND...

  6. 42 CFR 68c.16 - What other regulations and statutes apply?

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 42 Public Health 1 2012-10-01 2012-10-01 false What other regulations and statutes apply? 68c.16 Section 68c.16 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES FELLOWSHIPS, INTERNSHIPS, TRAINING NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT CONTRACEPTION AND...

  7. 42 CFR 68c.16 - What other regulations and statutes apply?

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 1 2010-10-01 2010-10-01 false What other regulations and statutes apply? 68c.16 Section 68c.16 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES FELLOWSHIPS, INTERNSHIPS, TRAINING NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT CONTRACEPTION AND...

  8. 7 CFR 4285.93 - Other Federal statutes and regulations that apply.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... BUSINESS-COOPERATIVE SERVICE AND RURAL UTILITIES SERVICE, DEPARTMENT OF AGRICULTURE COOPERATIVE AGREEMENTS Federal-State Research on Cooperatives Program § 4285.93 Other Federal statutes and regulations that apply... review or to agreements awarded under this part. These include but are not limited to: (a) 7 CFR Part...

  9. 1 CFR 2.5 - Publication of statutes, regulations, and related documents.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... “Federal Register Index,” and the “LSA (List of CFR Sections Affected).” ... 1 General Provisions 1 2012-01-01 2012-01-01 false Publication of statutes, regulations, and related documents. 2.5 Section 2.5 General Provisions ADMINISTRATIVE COMMITTEE OF THE FEDERAL...

  10. 1 CFR 2.5 - Publication of statutes, regulations, and related documents.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... “Federal Register Index,” and the “LSA (List of CFR Sections Affected).” ... 1 General Provisions 1 2014-01-01 2012-01-01 true Publication of statutes, regulations, and related documents. 2.5 Section 2.5 General Provisions ADMINISTRATIVE COMMITTEE OF THE FEDERAL...

  11. 1 CFR 2.5 - Publication of statutes, regulations, and related documents.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... “Federal Register Index,” and the “LSA (List of CFR Sections Affected).” ... 1 General Provisions 1 2013-01-01 2012-01-01 true Publication of statutes, regulations, and related documents. 2.5 Section 2.5 General Provisions ADMINISTRATIVE COMMITTEE OF THE FEDERAL...

  12. 1 CFR 2.5 - Publication of statutes, regulations, and related documents.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... “Federal Register Index,” and the “LSA (List of CFR Sections Affected).” ... 1 General Provisions 1 2011-01-01 2011-01-01 false Publication of statutes, regulations, and related documents. 2.5 Section 2.5 General Provisions ADMINISTRATIVE COMMITTEE OF THE FEDERAL...

  13. 1 CFR 2.5 - Publication of statutes, regulations, and related documents.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... “Federal Register Index,” and the “LSA (List of CFR Sections Affected).” ... 1 General Provisions 1 2010-01-01 2010-01-01 false Publication of statutes, regulations, and related documents. 2.5 Section 2.5 General Provisions ADMINISTRATIVE COMMITTEE OF THE FEDERAL...

  14. 7 CFR 3430.4 - Other applicable statutes and regulations.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... Bioterrorism Protection Act of 2002. 7 CFR Part 3015—USDA Uniform Federal Assistance Regulations, implementing... CSREES Federal assistance programs. These include, but are not limited to: 7 CFR Part 1, subpart A—USDA implementation of the Freedom of Information Act. 7 CFR Part 3—USDA implementation of OMB Circular No....

  15. 49 CFR Appendix E to Part 99 - Statutes Regulating Post-Employment Responsibilities of Government and Special Government Employees

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 49 Transportation 1 2012-10-01 2012-10-01 false Statutes Regulating Post-Employment Responsibilities of Government and Special Government Employees E Appendix E to Part 99 Transportation Office of the Secretary of Transportation EMPLOYEE RESPONSIBILITIES AND CONDUCT Pt. 99, App. E Appendix E...

  16. 49 CFR Appendix E to Part 99 - Statutes Regulating Post-Employment Responsibilities of Government and Special Government Employees

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 1 2010-10-01 2010-10-01 false Statutes Regulating Post-Employment Responsibilities of Government and Special Government Employees E Appendix E to Part 99 Transportation Office of the Secretary of Transportation EMPLOYEE RESPONSIBILITIES AND CONDUCT Pt. 99, App. E Appendix E...

  17. 40 CFR 1700.6 - Effect on State and local statutes and regulations.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 32 2010-07-01 2010-07-01 false Effect on State and local statutes and... STANDARDS FOR VESSELS OF THE ARMED FORCES Effect on States § 1700.6 Effect on State and local statutes and... practicable to require use of a Marine Pollution Control Device regarding a particular discharge incidental...

  18. Environmental laws regulating chemicals: Uses of information in decision making under environmental statutes

    SciTech Connect

    Gaba, J.M.

    1990-12-31

    Three areas are addressed in this paper: generic issues that arise simply in the process of decision-making under environmental statutes; different decision-making standards under various environmental statutes; and efforts to legislate a {open_quotes}safe{close_quotes} or {open_quotes}acceptable{close_quotes} risk from exposure to carcinogenic chemicals.

  19. 7 CFR 3401.10 - Other Federal statutes and regulations that apply.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ..., Rehabilitation Act of 1973) and 7 CFR Part 15B (USDA implementation of statute)—prohibiting discrimination based... awarded under this part. These include but are not limited to: 7 CFR Part 1c—USDA implementation of the Federal Policy for the Protection of Human Subjects; 7 CFR Part 1.1—USDA implementation of Freedom...

  20. 7 CFR 3411.8 - Other Federal statutes and regulations that apply.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... Drug-Free Workplace (Grants); 7 CFR part 3018—USDA implementation of New Restrictions on Lobbying... 7 CFR part 15B (USDA implementation of statute), prohibiting discrimination based upon physical or... under this part. These include but are not limited to: 7 CFR 1.1—USDA implementation of Freedom...

  1. BPA Statutes.

    SciTech Connect

    United States. Bonneville Power Administration.

    1999-08-01

    This report contains the Bonneville Power Administration's (BPA's) authorizing statutes--the Bonneville Project Act, the Federal Columbia River Transmission System Act, the Pacific Northwest Electric Power Planning and Conservation Act and other laws that contain provisions that define BPA's mission and affect the way it is carried out.

  2. 45 CFR 1180.51 - Compliance with statutes, regulations, and its approved grant application.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... (Continued) NATIONAL FOUNDATION ON THE ARTS AND THE HUMANITIES INSTITUTE OF MUSEUM AND LIBRARY SERVICES... regulation unless the regulation specifically provides for waiver. (c) No act or failure to act by...

  3. 45 CFR 1180.51 - Compliance with statutes, regulations, and its approved grant application.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... (Continued) NATIONAL FOUNDATION ON THE ARTS AND THE HUMANITIES INSTITUTE OF MUSEUM AND LIBRARY SERVICES... regulation unless the regulation specifically provides for waiver. (c) No act or failure to act by...

  4. 45 CFR 1180.51 - Compliance with statutes, regulations, and its approved grant application.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... (Continued) NATIONAL FOUNDATION ON THE ARTS AND THE HUMANITIES INSTITUTE OF MUSEUM AND LIBRARY SERVICES... regulation unless the regulation specifically provides for waiver. (c) No act or failure to act by...

  5. 34 CFR 222.19 - What other statutes and regulations apply to this part?

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 1964 (Pub. L. 88-352) (prohibition of discrimination on the basis of race, color or national origin), and the implementing regulations (34 CFR part 100). (Authority: 42 U.S.C. 2000d—2000d-4) (2) The... the basis of sex), and the implementing regulations (34 CFR part 106). (Authority: 20 U.S.C....

  6. 34 CFR 222.19 - What other statutes and regulations apply to this part?

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 1964 (Pub. L. 88-352) (prohibition of discrimination on the basis of race, color or national origin), and the implementing regulations (34 CFR part 100). (Authority: 42 U.S.C. 2000d—2000d-4) (2) The... the basis of sex), and the implementing regulations (34 CFR part 106). (Authority: 20 U.S.C....

  7. 34 CFR 222.19 - What other statutes and regulations apply to this part?

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 1964 (Pub. L. 88-352) (prohibition of discrimination on the basis of race, color or national origin), and the implementing regulations (34 CFR part 100). (Authority: 42 U.S.C. 2000d—2000d-4) (2) The... the basis of sex), and the implementing regulations (34 CFR part 106). (Authority: 20 U.S.C....

  8. 34 CFR 222.19 - What other statutes and regulations apply to this part?

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 1964 (Pub. L. 88-352) (prohibition of discrimination on the basis of race, color or national origin), and the implementing regulations (34 CFR part 100). (Authority: 42 U.S.C. 2000d—2000d-4) (2) The... the basis of sex), and the implementing regulations (34 CFR part 106). (Authority: 20 U.S.C....

  9. 34 CFR 222.19 - What other statutes and regulations apply to this part?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 1964 (Pub. L. 88-352) (prohibition of discrimination on the basis of race, color or national origin), and the implementing regulations (34 CFR part 100). (Authority: 42 U.S.C. 2000d—2000d-4) (2) The... the basis of sex), and the implementing regulations (34 CFR part 106). (Authority: 20 U.S.C....

  10. 32 CFR 26.625 - Criminal drug statute.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 32 National Defense 1 2014-07-01 2014-07-01 false Criminal drug statute. 26.625 Section 26.625... REGULATIONS GOVERNMENTWIDE REQUIREMENTS FOR DRUG-FREE WORKPLACE (FINANCIAL ASSISTANCE) Definitions § 26.625 Criminal drug statute. Criminal drug statute means a Federal or non-Federal criminal statute involving...

  11. 32 CFR 26.625 - Criminal drug statute.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 32 National Defense 1 2012-07-01 2012-07-01 false Criminal drug statute. 26.625 Section 26.625... REGULATIONS GOVERNMENTWIDE REQUIREMENTS FOR DRUG-FREE WORKPLACE (FINANCIAL ASSISTANCE) Definitions § 26.625 Criminal drug statute. Criminal drug statute means a Federal or non-Federal criminal statute involving...

  12. 32 CFR 26.625 - Criminal drug statute.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 32 National Defense 1 2010-07-01 2010-07-01 false Criminal drug statute. 26.625 Section 26.625... REGULATIONS GOVERNMENTWIDE REQUIREMENTS FOR DRUG-FREE WORKPLACE (FINANCIAL ASSISTANCE) Definitions § 26.625 Criminal drug statute. Criminal drug statute means a Federal or non-Federal criminal statute involving...

  13. 32 CFR 26.625 - Criminal drug statute.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 32 National Defense 1 2011-07-01 2011-07-01 false Criminal drug statute. 26.625 Section 26.625... REGULATIONS GOVERNMENTWIDE REQUIREMENTS FOR DRUG-FREE WORKPLACE (FINANCIAL ASSISTANCE) Definitions § 26.625 Criminal drug statute. Criminal drug statute means a Federal or non-Federal criminal statute involving...

  14. 32 CFR 26.625 - Criminal drug statute.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 32 National Defense 1 2013-07-01 2013-07-01 false Criminal drug statute. 26.625 Section 26.625... REGULATIONS GOVERNMENTWIDE REQUIREMENTS FOR DRUG-FREE WORKPLACE (FINANCIAL ASSISTANCE) Definitions § 26.625 Criminal drug statute. Criminal drug statute means a Federal or non-Federal criminal statute involving...

  15. 42 CFR 9.13 - Other federal laws, regulations, and statutes that apply to the sanctuary.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ...) Animal Welfare Act (7 U.S.C. 2131-2159). (b) Animal Welfare Regulations, 9 CFR, subchapter A, parts 1 and... HUMAN SERVICES GENERAL PROVISIONS STANDARDS OF CARE FOR CHIMPANZEES HELD IN THE FEDERALLY...

  16. 42 CFR 9.13 - Other federal laws, regulations, and statutes that apply to the sanctuary.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ...) Animal Welfare Act (7 U.S.C. 2131-2159). (b) Animal Welfare Regulations, 9 CFR, subchapter A, parts 1 and... HUMAN SERVICES GENERAL PROVISIONS STANDARDS OF CARE FOR CHIMPANZEES HELD IN THE FEDERALLY...

  17. 42 CFR 9.13 - Other federal laws, regulations, and statutes that apply to the sanctuary.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ...) Animal Welfare Act (7 U.S.C. 2131-2159). (b) Animal Welfare Regulations, 9 CFR, subchapter A, parts 1 and... HUMAN SERVICES GENERAL PROVISIONS STANDARDS OF CARE FOR CHIMPANZEES HELD IN THE FEDERALLY...

  18. 42 CFR 9.13 - Other federal laws, regulations, and statutes that apply to the sanctuary.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ...) Animal Welfare Act (7 U.S.C. 2131-2159). (b) Animal Welfare Regulations, 9 CFR, subchapter A, parts 1 and... HUMAN SERVICES GENERAL PROVISIONS STANDARDS OF CARE FOR CHIMPANZEES HELD IN THE FEDERALLY...

  19. 42 CFR 9.13 - Other federal laws, regulations, and statutes that apply to the sanctuary.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ...) Animal Welfare Act (7 U.S.C. 2131-2159). (b) Animal Welfare Regulations, 9 CFR, subchapter A, parts 1 and... HUMAN SERVICES GENERAL PROVISIONS STANDARDS OF CARE FOR CHIMPANZEES HELD IN THE FEDERALLY...

  20. 45 CFR 1180.44 - Federal statutes and regulations on nondiscrimination.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... applies the regulations in 45 CFR part 1170, issued by the National Endowment for the Humanities and...) NATIONAL FOUNDATION ON THE ARTS AND THE HUMANITIES INSTITUTE OF MUSEUM AND LIBRARY SERVICES...

  1. 45 CFR 1180.44 - Federal statutes and regulations on nondiscrimination.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ...) NATIONAL FOUNDATION ON THE ARTS AND THE HUMANITIES INSTITUTE OF MUSEUM AND LIBRARY SERVICES GRANTS.... 2000d through 2000d-4) Discrimination on the basis of sex Title IX of the Education Amendments of 1972... applies the regulations in 45 CFR part 1170, issued by the National Endowment for the Humanities...

  2. 45 CFR 1180.44 - Federal statutes and regulations on nondiscrimination.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ...) NATIONAL FOUNDATION ON THE ARTS AND THE HUMANITIES INSTITUTE OF MUSEUM AND LIBRARY SERVICES GRANTS.... 2000d through 2000d-4) Discrimination on the basis of sex Title IX of the Education Amendments of 1972... applies the regulations in 45 CFR part 1170, issued by the National Endowment for the Humanities...

  3. 7 CFR 4285.93 - Other Federal statutes and regulations that apply.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... involves a college or university; (e) 7 CFR Part 3015—USDA Uniform Federal Assistance Regulations... review or to agreements awarded under this part. These include but are not limited to: (a) 7 CFR Part 1, Subpart A—USDA implementation of the Freedom of Information Act; (b) 7 CFR Part 3—USDA implementation...

  4. 42 CFR 480.109 - Applicability of other statutes and regulations.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... DISCLOSURE OF QUALITY IMPROVEMENT ORGANIZATION REVIEW INFORMATION Utilization and Quality Control Quality.... The provisions of 42 U.S.C. 290dd-3 and 290ee-3 governing confidentiality of alcohol and drug abuse patients' records, and the implementing regulations at 42 CFR part 2, are applicable to QIO...

  5. 34 CFR 222.55 - What other statutes and regulations are applicable to this subpart?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... Section 8003(d) of the Act for Local Educational Agencies That Serve Children With Disabilities § 222.55... receiving funds under section 8003(d) are subject to the requirements of the Individuals with Disabilities Education Act, and related regulations (20 U.S.C. 1401 et seq. and 34 CFR part 300). (Authority: 20...

  6. 25 CFR 900.216 - What other statutes and regulations apply to contract disputes?

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ...) The Equal Access to Justice Act, 5 U.S.C. 504 and 28 U.S.C. 2412 and regulations at 43 CFR 4.601... disputes? 900.216 Section 900.216 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR, AND INDIAN... contract disputes? (a) The Contract Disputes Act of 1978 (CDA), Public Law 95-563 (41 U.S.C. 601 as...

  7. Shuttered Shutters: The Photographic Statutes and Their Faithful Companion, 18 USC 1382--An Examination of Photographic Access to Military Areas.

    ERIC Educational Resources Information Center

    Dykhouse, Caroline Dow

    The United States federal government, through a combination of statutes and regulations, has imposed restrictions on the activities of photojournalists that are not equally applicable to those of their print colleagues. For example, two statutes of the United States Code prohibit the photographing of defense installations and military equipment…

  8. 10 CFR 607.625 - Criminal drug statute.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 10 Energy 4 2010-01-01 2010-01-01 false Criminal drug statute. 607.625 Section 607.625 Energy DEPARTMENT OF ENERGY (CONTINUED) ASSISTANCE REGULATIONS GOVERNMENTWIDE REQUIREMENTS FOR DRUG-FREE WORKPLACE (FINANCIAL ASSISTANCE) Definitions § 607.625 Criminal drug statute. Criminal drug statute means a Federal...

  9. 38 CFR Appendix B to Subpart E of... - List of Age Distinctions Contained in Statutes and Regulations Governing Federal Financial...

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... Section 90.31(f) of the governmentwide regulations (45 CFR part 90) requires each Federal agency to... Regulation Section and Age Distinction CFDA Veterans' Benefits Adjudication (38 CFR part 3) Section 3.57... death. . . .” Survivors' and Dependents' Educational Assistance Adjudication (38 CFR part 3) Section...

  10. 38 CFR Appendix B to Subpart E of... - List of Age Distinctions Contained in Statutes and Regulations Governing Federal Financial...

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... Section 90.31(f) of the governmentwide regulations (45 CFR part 90) requires each Federal agency to... Regulation Section and Age Distinction CFDA Veterans' Benefits Adjudication (38 CFR part 3) Section 3.57... death. . . .” Survivors' and Dependents' Educational Assistance Adjudication (38 CFR part 3) Section...

  11. 10 CFR Appendix A to Part 603 - Applicable Federal Statutes, Executive Orders, and Government-wide Regulations

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... Government-wide common rule that the DOE has codified at 10 CFR part 601. The “List of Certifications and... Act of 1964 (42 U.S.C. 2000d, et seq.) as implemented by DOE regulations at 10 CFR part 1040. These... Discrimination Act of 1975 (42 U.S.C. 6101, et seq.) as implemented by DOE regulations at 10 CFR part 1040....

  12. 10 CFR Appendix A to Part 603 - Applicable Federal Statutes, Executive Orders, and Government-wide Regulations

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ..., Department of Agriculture rules and rules of the Department of Interior at 50 CFR parts 10 through 24 and... Government-wide common rule that the DOE has codified at 10 CFR part 601. The “List of Certifications and... Act of 1964 (42 U.S.C. 2000d, et seq.) as implemented by DOE regulations at 10 CFR part 1040....

  13. 38 CFR Appendix B to Subpart E of... - List of Age Distinctions Contained in Statutes and Regulations Governing Federal Financial...

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... Section 90.31(f) of the governmentwide regulations (45 CFR part 90) requires each Federal agency to... Adjudication (38 CFR part 3) Section 3.57 defines the term “child” of a veteran as, “. . . an unmarried person... Adjudication (38 CFR part 3) Section 3.807(d) sets forth basic eligibility criteria for the program...

  14. 38 CFR Appendix B to Subpart E of... - List of Age Distinctions Contained in Statutes and Regulations Governing Federal Financial...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... Section 90.31(f) of the governmentwide regulations (45 CFR part 90) requires each Federal agency to... Adjudication (38 CFR part 3) Section 3.57 defines the term “child” of a veteran as, “. . . an unmarried person... Adjudication (38 CFR part 3) Section 3.807(d) sets forth basic eligibility criteria for the program...

  15. 38 CFR Appendix B to Subpart E of... - List of Age Distinctions Contained in Statutes and Regulations Governing Federal Financial...

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... Section 90.31(f) of the governmentwide regulations (45 CFR part 90) requires each Federal agency to... Adjudication (38 CFR part 3) Section 3.57 defines the term “child” of a veteran as, “. . . an unmarried person... Adjudication (38 CFR part 3) Section 3.807(d) sets forth basic eligibility criteria for the program...

  16. Connecticut's new abortion statute.

    PubMed

    Healey, J M

    1990-08-01

    Amid the raging controversy on whether minors should have the same access to abortion as adults, the Connecticut legislature has passed a compromise statues that recognizes a minor's right seek an abortion, while imposing certain requirements. Those who seek to regulate access argue that because minors may lack the maturity to make a valid decision, parental notification is necessary; advocates of minors' right to access hold that it should be the minor who makes such personal decision. In an effort to resolve the conflict, Connecticut's law says that young women under the age of 16 must receive pregnancy-related information before an abortion can take place. Specifically., a physician or counselor is required to: 1) explain to the minor that the information provided is not intended to coerce or persuade her into making a particular choice; 2) explain that she may consider her decision any time prior to the operation or during the time period when abortion is legally permitted; 3) explain the alternatives of either carrying out the pregnancy or getting an abortion, including information on public and private agencies that may assist in carrying out the decision; 4) inform her that pubic and private agencies provide information on birth control; 5) discuss the possibility of involving the minor's parents(s), guardian(s), or other adult family member in the decision; and 6) allow the minor to ask questions and to obtain useful information. After the completion of the process, the minor must sign a form that attests that the requirements have been met, and -- if applicable -- that the minor has decided to involve a parent or relative. In cases where the health or safety of a minor requires and abortion, the Connecticut statute allows for the provisions to be waived.

  17. Nebraska Social Studies Statutes.

    ERIC Educational Resources Information Center

    Nebraska State Dept. of Education, Lincoln.

    This booklet lists the laws that relate to Nebraska social studies. The volume is intended for administrators, teachers, and curriculum planners to assist them to do a more thorough job of planning social studies programs. The Nebraska Social Studies Statutes are designed to be a primary tool in developing a district's curriculum, as they speak to…

  18. 45 CFR 607.10 - Statute of limitations.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 45 Public Welfare 3 2012-10-01 2012-10-01 false Statute of limitations. 607.10 Section 607.10 Public Welfare Regulations Relating to Public Welfare (Continued) NATIONAL SCIENCE FOUNDATION SALARY OFFSET § 607.10 Statute of limitations. If a debt has been outstanding for more than 10 years after...

  19. 45 CFR 607.10 - Statute of limitations.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 45 Public Welfare 3 2011-10-01 2011-10-01 false Statute of limitations. 607.10 Section 607.10 Public Welfare Regulations Relating to Public Welfare (Continued) NATIONAL SCIENCE FOUNDATION SALARY OFFSET § 607.10 Statute of limitations. If a debt has been outstanding for more than 10 years after...

  20. 45 CFR 607.10 - Statute of limitations.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 45 Public Welfare 3 2014-10-01 2014-10-01 false Statute of limitations. 607.10 Section 607.10 Public Welfare Regulations Relating to Public Welfare (Continued) NATIONAL SCIENCE FOUNDATION SALARY OFFSET § 607.10 Statute of limitations. If a debt has been outstanding for more than 10 years after...

  1. 45 CFR 607.10 - Statute of limitations.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 45 Public Welfare 3 2013-10-01 2013-10-01 false Statute of limitations. 607.10 Section 607.10 Public Welfare Regulations Relating to Public Welfare (Continued) NATIONAL SCIENCE FOUNDATION SALARY OFFSET § 607.10 Statute of limitations. If a debt has been outstanding for more than 10 years after...

  2. 32 CFR 1697.10 - Statute of Limitations.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 32 National Defense 6 2010-07-01 2010-07-01 false Statute of Limitations. 1697.10 Section 1697.10 National Defense Other Regulations Relating to National Defense SELECTIVE SERVICE SYSTEM SALARY OFFSET § 1697.10 Statute of Limitations. If a debt has been outstanding for more than 10 years after the agency's right to collect the debt first...

  3. 12 CFR 711.4 - Interlocking relationships permitted by statute.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 12 Banks and Banking 6 2010-01-01 2010-01-01 false Interlocking relationships permitted by statute. 711.4 Section 711.4 Banks and Banking NATIONAL CREDIT UNION ADMINISTRATION REGULATIONS AFFECTING CREDIT UNIONS MANAGEMENT OFFICIAL INTERLOCKS § 711.4 Interlocking relationships permitted by statute....

  4. 48 CFR 25.504-1 - Buy American statute.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 48 Federal Acquisition Regulations System 1 2014-10-01 2014-10-01 false Buy American statute. 25... SOCIOECONOMIC PROGRAMS FOREIGN ACQUISITION Evaluating Foreign Offers-Supply Contracts 25.504-1 Buy American... business concerns. The Buy American statute applies. Since the acquisition value is less than $25,000...

  5. 45 CFR 1179.10 - Statute of limitations.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 45 Public Welfare 3 2011-10-01 2011-10-01 false Statute of limitations. 1179.10 Section 1179.10 Public Welfare Regulations Relating to Public Welfare (Continued) NATIONAL FOUNDATION ON THE ARTS AND THE HUMANITIES NATIONAL ENDOWMENT FOR THE HUMANITIES SALARY OFFSET § 1179.10 Statute of limitations. If a...

  6. 45 CFR 1179.10 - Statute of limitations.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 45 Public Welfare 3 2010-10-01 2010-10-01 false Statute of limitations. 1179.10 Section 1179.10 Public Welfare Regulations Relating to Public Welfare (Continued) NATIONAL FOUNDATION ON THE ARTS AND THE HUMANITIES NATIONAL ENDOWMENT FOR THE HUMANITIES SALARY OFFSET § 1179.10 Statute of limitations. If a...

  7. 45 CFR 302.17 - Inclusion of State statutes.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 45 Public Welfare 2 2012-10-01 2012-10-01 false Inclusion of State statutes. 302.17 Section 302.17 Public Welfare Regulations Relating to Public Welfare OFFICE OF CHILD SUPPORT ENFORCEMENT (CHILD SUPPORT... PLAN REQUIREMENTS § 302.17 Inclusion of State statutes. The State plan shall provide a copy of...

  8. 45 CFR 302.17 - Inclusion of State statutes.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 45 Public Welfare 2 2014-10-01 2012-10-01 true Inclusion of State statutes. 302.17 Section 302.17 Public Welfare Regulations Relating to Public Welfare OFFICE OF CHILD SUPPORT ENFORCEMENT (CHILD SUPPORT... PLAN REQUIREMENTS § 302.17 Inclusion of State statutes. The State plan shall provide a copy of...

  9. 45 CFR 302.17 - Inclusion of State statutes.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 45 Public Welfare 2 2011-10-01 2011-10-01 false Inclusion of State statutes. 302.17 Section 302.17 Public Welfare Regulations Relating to Public Welfare OFFICE OF CHILD SUPPORT ENFORCEMENT (CHILD SUPPORT... PLAN REQUIREMENTS § 302.17 Inclusion of State statutes. The State plan shall provide a copy of...

  10. 45 CFR 302.17 - Inclusion of State statutes.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 45 Public Welfare 2 2013-10-01 2012-10-01 true Inclusion of State statutes. 302.17 Section 302.17 Public Welfare Regulations Relating to Public Welfare OFFICE OF CHILD SUPPORT ENFORCEMENT (CHILD SUPPORT... PLAN REQUIREMENTS § 302.17 Inclusion of State statutes. The State plan shall provide a copy of...

  11. 36 CFR 67.8 - Certifications of statutes.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... regulation, a State or local statute is a law of the State or local government designating, or providing a... jurisdiction of the review body. (b) When the certification of State statutes will have an impact on districts in specific localities, the Secretary encourages State governments to notify and consult...

  12. 36 CFR 67.8 - Certifications of statutes.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... regulation, a State or local statute is a law of the State or local government designating, or providing a... jurisdiction of the review body. (b) When the certification of State statutes will have an impact on districts in specific localities, the Secretary encourages State governments to notify and consult...

  13. 45 CFR 302.17 - Inclusion of State statutes.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 45 Public Welfare 2 2010-10-01 2010-10-01 false Inclusion of State statutes. 302.17 Section 302.17 Public Welfare Regulations Relating to Public Welfare OFFICE OF CHILD SUPPORT ENFORCEMENT (CHILD SUPPORT... PLAN REQUIREMENTS § 302.17 Inclusion of State statutes. The State plan shall provide a copy of...

  14. 45 CFR 1179.10 - Statute of limitations.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 45 Public Welfare 3 2013-10-01 2013-10-01 false Statute of limitations. 1179.10 Section 1179.10 Public Welfare Regulations Relating to Public Welfare (Continued) NATIONAL FOUNDATION ON THE ARTS AND THE HUMANITIES NATIONAL ENDOWMENT FOR THE HUMANITIES SALARY OFFSET § 1179.10 Statute of limitations. If a...

  15. 45 CFR 1179.10 - Statute of limitations.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 45 Public Welfare 3 2012-10-01 2012-10-01 false Statute of limitations. 1179.10 Section 1179.10 Public Welfare Regulations Relating to Public Welfare (Continued) NATIONAL FOUNDATION ON THE ARTS AND THE HUMANITIES NATIONAL ENDOWMENT FOR THE HUMANITIES SALARY OFFSET § 1179.10 Statute of limitations. If a...

  16. 45 CFR 1179.10 - Statute of limitations.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 45 Public Welfare 3 2014-10-01 2014-10-01 false Statute of limitations. 1179.10 Section 1179.10 Public Welfare Regulations Relating to Public Welfare (Continued) NATIONAL FOUNDATION ON THE ARTS AND THE HUMANITIES NATIONAL ENDOWMENT FOR THE HUMANITIES SALARY OFFSET § 1179.10 Statute of limitations. If a...

  17. 24 CFR 1007.45 - Applicability of civil rights statutes.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 24 Housing and Urban Development 4 2011-04-01 2011-04-01 false Applicability of civil rights statutes. 1007.45 Section 1007.45 Housing and Urban Development REGULATIONS RELATING TO HOUSING AND URBAN... civil rights statutes. To the extent that the requirements of title VI of the Civil Rights Act of...

  18. 24 CFR 1007.45 - Applicability of civil rights statutes.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 24 Housing and Urban Development 4 2014-04-01 2014-04-01 false Applicability of civil rights statutes. 1007.45 Section 1007.45 Housing and Urban Development REGULATIONS RELATING TO HOUSING AND URBAN... civil rights statutes. To the extent that the requirements of title VI of the Civil Rights Act of...

  19. 24 CFR 1007.45 - Applicability of civil rights statutes.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 24 Housing and Urban Development 4 2010-04-01 2010-04-01 false Applicability of civil rights statutes. 1007.45 Section 1007.45 Housing and Urban Development Regulations Relating to Housing and Urban... civil rights statutes. To the extent that the requirements of title VI of the Civil Rights Act of...

  20. 24 CFR 1007.45 - Applicability of civil rights statutes.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 24 Housing and Urban Development 4 2012-04-01 2012-04-01 false Applicability of civil rights statutes. 1007.45 Section 1007.45 Housing and Urban Development REGULATIONS RELATING TO HOUSING AND URBAN... civil rights statutes. To the extent that the requirements of title VI of the Civil Rights Act of...

  1. 24 CFR 1007.45 - Applicability of civil rights statutes.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 24 Housing and Urban Development 4 2013-04-01 2013-04-01 false Applicability of civil rights statutes. 1007.45 Section 1007.45 Housing and Urban Development REGULATIONS RELATING TO HOUSING AND URBAN... civil rights statutes. To the extent that the requirements of title VI of the Civil Rights Act of...

  2. The bribery statute: a new weapon against Medicare fraud.

    PubMed

    Cozort, L A

    2001-03-01

    A May 2000 U.S. Supreme Court decision determining when a Federal bribery statute can be used to fight Medicare fraud has ramifications for healthcare providers. In Fischer v. United States, the Court concluded that healthcare providers that participate in Medicare are considered to receive benefits as set forth in the bribery statute and thus can be prosecuted for fraudulent activities against the government under the statute. The statute mandates a fine, imprisonment for up to 10 years, or both for anyone convicted under it. Provider organizations that receive Medicare payments and business associates of such organizations should be aware that the government may step up its use of the bribery law in prosecuting fraudulent activity. In addition, although the case pertained specifically to healthcare providers that participate in Medicare, providers that do not participate in Medicare may wish to evaluate the advisability of accepting other Federal funding because of the possible reach of the bribery statute. PMID:11258271

  3. Environmental statutes. 1999 edition

    SciTech Connect

    1999-04-01

    Important changes in the environmental laws have come about under the 105th Congress. To ensure that you have the most current information available on the new acts and amendments, this book contains the up-to-date and complete text of each statute as currently amended. Both softcover book and new CD ROM contain the complete text for: Clean Air Act and Amendments of 1990; Clean Water Act; CERCLA/Superfund; Pollution Prevention Act of 1990; Emergency Planning and Community; Right-to-Know Act; Resource Conservation and Recovery Act; Federal Insecticide, Fungicide, and Rodenticide Act; Federal Water Pollution Control Act; Oil Pollution Act of 1990; Safe Drinking Water Act; National Environmental Policy Act; and Occupational Safety and Health Act.

  4. 42 CFR 2.21 - Relationship to Federal statutes protecting research subjects against compulsory disclosure of...

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... DRUG ABUSE PATIENT RECORDS General Provisions § 2.21 Relationship to Federal statutes protecting... implementing regulations at 42 CFR part 2a); or section 502(c) of the Controlled Substances Act (21 U.S.C. 872(c) and the implementing regulations at 21 CFR 1316.21). These “research privilege” statutes...

  5. 42 CFR 2.21 - Relationship to Federal statutes protecting research subjects against compulsory disclosure of...

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... DRUG ABUSE PATIENT RECORDS General Provisions § 2.21 Relationship to Federal statutes protecting... implementing regulations at 42 CFR part 2a); or section 502(c) of the Controlled Substances Act (21 U.S.C. 872(c) and the implementing regulations at 21 CFR 1316.21). These “research privilege” statutes...

  6. 42 CFR 2.21 - Relationship to Federal statutes protecting research subjects against compulsory disclosure of...

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... DRUG ABUSE PATIENT RECORDS General Provisions § 2.21 Relationship to Federal statutes protecting... implementing regulations at 42 CFR part 2a); or section 502(c) of the Controlled Substances Act (21 U.S.C. 872(c) and the implementing regulations at 21 CFR 1316.21). These “research privilege” statutes...

  7. Regulation of inflammasome activation

    PubMed Central

    Man, Si Ming; Kanneganti, Thirumala-Devi

    2015-01-01

    Summary Inflammasome biology is one of the most exciting and rapidly growing areas in immunology. Over the past 10 years, inflammasomes have been recognized for their roles in the host defense against invading pathogens and in the development of cancer, autoinflammatory, metabolic, and neurodegenerative diseases. Assembly of an inflammasome complex requires cytosolic sensing of pathogen-associated molecular patterns or danger-associated molecular patterns by a nucleotide-binding domain and leucine-rich repeat receptor (NLR) or absent in melanoma 2-like receptor (ALR). NLRs and ALRs engage caspase-1, in most cases requiring the adapter protein apoptosis-associated speck-like protein containing a CARD (ASC), to catalyze proteolytic cleavage of pro-interleukin-1β (pro-IL-1β) and pro-IL-18 and drive pyroptosis. Recent studies indicate that caspase-8, caspase-11, IL-1R–associated kinases (IRAK), and receptor-interacting protein (RIP) kinases contribute to inflammasome functions. In addition, post-translational modifications, including ubiquitination, deubiquitination, phosphorylation, and degradation, control almost every aspect of inflammasome activities. Genetic studies indicate that mutations in NLRP1, NLRP3, NLRC4, and AIM2 are linked to the development of autoinflammatory diseases, enterocolitis, and cancer. Overall, these findings transform our understanding of the basic biology and clinical relevance of inflammasomes. In this review, we provide an overview of the latest development of inflammasome research and discuss how inflammasome activities govern health and disease. PMID:25879280

  8. 45 CFR 5.64 - Exemption three: Records exempted by other statutes.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 45 Public Welfare 1 2010-10-01 2010-10-01 false Exemption three: Records exempted by other statutes. 5.64 Section 5.64 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION FREEDOM OF INFORMATION REGULATIONS Reasons for Withholding Some Records § 5.64 Exemption three: Records exempted by other statutes. We are not...

  9. 43 CFR 5511.3-1 - Free use of timber under other statutes.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 43 Public Lands: Interior 2 2011-10-01 2011-10-01 false Free use of timber under other statutes...) BUREAU OF LAND MANAGEMENT, DEPARTMENT OF THE INTERIOR FOREST MANAGEMENT (5000) FREE USE OF TIMBER Free Use Regulations § 5511.3-1 Free use of timber under other statutes. Free use will be allowed under...

  10. 48 CFR 33.205 - Relationship of the Disputes statute to Pub. L. 85-804.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... Disputes statute to Pub. L. 85-804. 33.205 Section 33.205 Federal Acquisition Regulations System FEDERAL... 33.205 Relationship of the Disputes statute to Pub. L. 85-804. (a) Requests for relief under Pub. L..., relief formerly available only under Pub. L. 85-804; i.e., legal entitlement to rescission or...

  11. 12 CFR 348.4 - Interlocking relationships permitted by statute.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 12 Banks and Banking 4 2010-01-01 2010-01-01 false Interlocking relationships permitted by statute. 348.4 Section 348.4 Banks and Banking FEDERAL DEPOSIT INSURANCE CORPORATION REGULATIONS AND STATEMENTS OF GENERAL POLICY MANAGEMENT OFFICIAL INTERLOCKS § 348.4 Interlocking relationships permitted...

  12. 36 CFR 67.8 - Certifications of statutes.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... INTERIOR HISTORIC PRESERVATION CERTIFICATIONS PURSUANT TO SEC. 48(g) AND SEC. 170(h) OF THE INTERNAL... certified by the Secretary. For the purpose of this regulation, a State or local statute is a law of the... or districts. This includes any by-laws or ordinances that contain information necessary for...

  13. 45 CFR 630.625 - Criminal drug statute.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 45 Public Welfare 3 2014-10-01 2014-10-01 false Criminal drug statute. 630.625 Section 630.625 Public Welfare Regulations Relating to Public Welfare (Continued) NATIONAL SCIENCE FOUNDATION GOVERNMENTWIDE REQUIREMENTS FOR DRUG-FREE WORKPLACE (FINANCIAL ASSISTANCE) Definitions § 630.625 Criminal...

  14. 45 CFR 607.10 - Statute of limitations.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 45 Public Welfare 3 2010-10-01 2010-10-01 false Statute of limitations. 607.10 Section 607.10 Public Welfare Regulations Relating to Public Welfare (Continued) NATIONAL SCIENCE FOUNDATION SALARY... material to the Government's right to collect were not known and could not reasonably have been known...

  15. Surface owner's estate becomes dominant: Wyoming's surface owner consent statute

    SciTech Connect

    Reese, T.

    1981-01-01

    This comment discusses the constitutionality of Wyoming's surface owner consent law in three areas. The first is whether Wyoming's statute is an unconstitutional taking without compensation of the dominant position of the mineral estate holder. The second theory will be that the federal government has preempted the area of mineral lands regulation and therefore Wyoming's statute is void. The third theory is that Wyoming's statute is unconstitutional because it denies equal protection of the law under the fourteenth amendment to the US Constitution. This comment will deal primarily with the reservations of mineral rights under lands the federal government disposed of to private interests. It will not deal with reservations of mineral estates by private parties.

  16. National Energy Act statutes and solar energy

    SciTech Connect

    Howard, J.

    1980-02-01

    The National Energy Act of 1978 contains many provisions that will significantly affect solar technology commercialization and solar energy users. Four of the five statutes that comprise the National Energy Act deserve close attention. The National Energy Conservation Policy Act will promote residential solar installations. The Energy Tax Act will accelerate both residential and commercial solar system applications. The Public Utilities Regulatory Policies Act promotes efficient use of utility resources as well as decentralized power production. And, the Power Plan and Industrial Fuel Use Act places severe restrictions on future burning of petroleum and natural gas, which should lead some operators to build or convert to solar energy systems. Each of the preceding acts are considered in separate sections of this report. Federal regulations issued pursuant to the various provisions are also identified and discussed, and some of the problems with the provisions and regulations are noted.

  17. Adrenocortical Activity and Emotion Regulation.

    ERIC Educational Resources Information Center

    Stansbury, Kathy; Gunnar, Megan R.

    1994-01-01

    This essay argues that the activity of the hypothalamic-pituitary-adrenocortical (HPA) system does not appear to be related to emotion regulation processes in children, although individual differences in emotion processes related to negative emotion temperaments appear to be associated with individual differences in HPA reactivity among normally…

  18. 7 CFR 1.29 - Subpoenas relating to investigations under statutes administered by the Secretary of Agriculture.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 1 2010-01-01 2010-01-01 false Subpoenas relating to investigations under statutes administered by the Secretary of Agriculture. 1.29 Section 1.29 Agriculture Office of the Secretary of Agriculture ADMINISTRATIVE REGULATIONS Departmental Proceedings § 1.29 Subpoenas relating to investigations under statutes administered by...

  19. US statutes for enforcement by security inspectors

    SciTech Connect

    Cadwell, J.J.; Ruger, C.J.

    1995-12-01

    This document is one of a three volume set. BNL 52201 is titled `Selected Text of Atomic Energy Act Executive Orders and Other Laws of General Interest to Safeguards and Security Executives`, and it contains detailed information for use by executives. BNL 52202 is titled `U.S. Statutes of General Interest to Safeguards and Security Officers`, and contains less detail than BNL 52201. It is intended for use by officers. BNL 52203 is titled `U.S. Statutes for Enforcement by Security Inspectors`, and it contains statutes to be applied by uniformed security inspectors.

  20. 14 CFR 1267.625 - Criminal drug statute.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 14 Aeronautics and Space 5 2011-01-01 2010-01-01 true Criminal drug statute. 1267.625 Section 1267... FOR DRUG-FREE WORKPLACE (FINANCIAL ASSISTANCE) Definitions § 1267.625 Criminal drug statute. Criminal drug statute means a Federal or non-Federal criminal statute involving the manufacture,...

  1. 2 CFR 1401.225 - Criminal drug statute.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 2 Grants and Agreements 1 2012-01-01 2012-01-01 false Criminal drug statute. 1401.225 Section 1401... INTERIOR REQUIREMENTS FOR DRUG-FREE WORKPLACE (FINANCIAL ASSISTANCE) Definitions § 1401.225 Criminal drug statute. Criminal drug statute means a Federal or non-Federal criminal statute involving the...

  2. 31 CFR 20.625 - Criminal drug statute.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 31 Money and Finance: Treasury 1 2010-07-01 2010-07-01 false Criminal drug statute. 20.625 Section... REQUIREMENTS FOR DRUG-FREE WORKPLACE (FINANCIAL ASSISTANCE) Definitions § 20.625 Criminal drug statute. Criminal drug statute means a Federal or non-Federal criminal statute involving the...

  3. 14 CFR 1267.625 - Criminal drug statute.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 14 Aeronautics and Space 5 2013-01-01 2013-01-01 false Criminal drug statute. 1267.625 Section... REQUIREMENTS FOR DRUG-FREE WORKPLACE (FINANCIAL ASSISTANCE) Definitions § 1267.625 Criminal drug statute. Criminal drug statute means a Federal or non-Federal criminal statute involving the...

  4. 38 CFR 48.625 - Criminal drug statute.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 2 2013-07-01 2013-07-01 false Criminal drug statute. 48...) GOVERNMENTWIDE REQUIREMENTS FOR DRUG-FREE WORKPLACE (FINANCIAL ASSISTANCE) Definitions § 48.625 Criminal drug statute. Criminal drug statute means a Federal or non-Federal criminal statute involving the...

  5. 24 CFR 21.625 - Criminal drug statute.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 24 Housing and Urban Development 1 2010-04-01 2010-04-01 false Criminal drug statute. 21.625... Development GOVERNMENTWIDE REQUIREMENTS FOR DRUG-FREE WORKPLACE (GRANTS) Definitions § 21.625 Criminal drug statute. Criminal drug statute means a Federal or non-Federal criminal statute involving the...

  6. 38 CFR 48.625 - Criminal drug statute.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 2 2011-07-01 2011-07-01 false Criminal drug statute. 48...) GOVERNMENTWIDE REQUIREMENTS FOR DRUG-FREE WORKPLACE (FINANCIAL ASSISTANCE) Definitions § 48.625 Criminal drug statute. Criminal drug statute means a Federal or non-Federal criminal statute involving the...

  7. 14 CFR 1267.625 - Criminal drug statute.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 14 Aeronautics and Space 5 2012-01-01 2012-01-01 false Criminal drug statute. 1267.625 Section... REQUIREMENTS FOR DRUG-FREE WORKPLACE (FINANCIAL ASSISTANCE) Definitions § 1267.625 Criminal drug statute. Criminal drug statute means a Federal or non-Federal criminal statute involving the...

  8. 38 CFR 48.625 - Criminal drug statute.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 2 2012-07-01 2012-07-01 false Criminal drug statute. 48...) GOVERNMENTWIDE REQUIREMENTS FOR DRUG-FREE WORKPLACE (FINANCIAL ASSISTANCE) Definitions § 48.625 Criminal drug statute. Criminal drug statute means a Federal or non-Federal criminal statute involving the...

  9. 45 CFR 630.625 - Criminal drug statute.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 45 Public Welfare 3 2010-10-01 2010-10-01 false Criminal drug statute. 630.625 Section 630.625... GOVERNMENTWIDE REQUIREMENTS FOR DRUG-FREE WORKPLACE (FINANCIAL ASSISTANCE) Definitions § 630.625 Criminal drug statute. Criminal drug statute means a Federal or non-Federal criminal statute involving the...

  10. 2 CFR 1401.225 - Criminal drug statute.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 2 Grants and Agreements 1 2013-01-01 2013-01-01 false Criminal drug statute. 1401.225 Section 1401... INTERIOR REQUIREMENTS FOR DRUG-FREE WORKPLACE (FINANCIAL ASSISTANCE) Definitions § 1401.225 Criminal drug statute. Criminal drug statute means a Federal or non-Federal criminal statute involving the...

  11. 29 CFR 1472.625 - Criminal drug statute.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 29 Labor 4 2011-07-01 2011-07-01 false Criminal drug statute. 1472.625 Section 1472.625 Labor... REQUIREMENTS FOR DRUG-FREE WORKPLACE (FINANCIAL ASSISTANCE) Definitions § 1472.625 Criminal drug statute. Criminal drug statute means a Federal or non-Federal criminal statute involving the...

  12. 2 CFR 182.625 - Criminal drug statute.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 2 Grants and Agreements 1 2012-01-01 2012-01-01 false Criminal drug statute. 182.625 Section 182... GOVERNMENTWIDE REQUIREMENTS FOR DRUG-FREE WORKPLACE (FINANCIAL ASSISTANCE) Definitions § 182.625 Criminal drug statute. Criminal drug statute means a Federal or non-Federal criminal statute involving the...

  13. 45 CFR 630.625 - Criminal drug statute.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 45 Public Welfare 3 2011-10-01 2011-10-01 false Criminal drug statute. 630.625 Section 630.625... GOVERNMENTWIDE REQUIREMENTS FOR DRUG-FREE WORKPLACE (FINANCIAL ASSISTANCE) Definitions § 630.625 Criminal drug statute. Criminal drug statute means a Federal or non-Federal criminal statute involving the...

  14. 29 CFR 1472.625 - Criminal drug statute.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 29 Labor 4 2012-07-01 2012-07-01 false Criminal drug statute. 1472.625 Section 1472.625 Labor... REQUIREMENTS FOR DRUG-FREE WORKPLACE (FINANCIAL ASSISTANCE) Definitions § 1472.625 Criminal drug statute. Criminal drug statute means a Federal or non-Federal criminal statute involving the...

  15. 24 CFR 21.625 - Criminal drug statute.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 24 Housing and Urban Development 1 2011-04-01 2011-04-01 false Criminal drug statute. 21.625... Development GOVERNMENTWIDE REQUIREMENTS FOR DRUG-FREE WORKPLACE (GRANTS) Definitions § 21.625 Criminal drug statute. Criminal drug statute means a Federal or non-Federal criminal statute involving the...

  16. 45 CFR 630.625 - Criminal drug statute.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 45 Public Welfare 3 2013-10-01 2013-10-01 false Criminal drug statute. 630.625 Section 630.625... GOVERNMENTWIDE REQUIREMENTS FOR DRUG-FREE WORKPLACE (FINANCIAL ASSISTANCE) Definitions § 630.625 Criminal drug statute. Criminal drug statute means a Federal or non-Federal criminal statute involving the...

  17. 31 CFR 20.625 - Criminal drug statute.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 31 Money and Finance: Treasury 1 2014-07-01 2014-07-01 false Criminal drug statute. 20.625 Section... REQUIREMENTS FOR DRUG-FREE WORKPLACE (FINANCIAL ASSISTANCE) Definitions § 20.625 Criminal drug statute. Criminal drug statute means a Federal or non-Federal criminal statute involving the...

  18. 45 CFR 630.625 - Criminal drug statute.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 45 Public Welfare 3 2012-10-01 2012-10-01 false Criminal drug statute. 630.625 Section 630.625... GOVERNMENTWIDE REQUIREMENTS FOR DRUG-FREE WORKPLACE (FINANCIAL ASSISTANCE) Definitions § 630.625 Criminal drug statute. Criminal drug statute means a Federal or non-Federal criminal statute involving the...

  19. 40 CFR 36.625 - Criminal drug statute.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 1 2010-07-01 2010-07-01 false Criminal drug statute. 36.625 Section... GOVERNMENTWIDE REQUIREMENTS FOR DRUG-FREE WORKPLACE (FINANCIAL ASSISTANCE) Definitions § 36.625 Criminal drug statute. Criminal drug statute means a Federal or non-Federal criminal statute involving the...

  20. 14 CFR 1267.625 - Criminal drug statute.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 14 Aeronautics and Space 5 2010-01-01 2010-01-01 false Criminal drug statute. 1267.625 Section... REQUIREMENTS FOR DRUG-FREE WORKPLACE (FINANCIAL ASSISTANCE) Definitions § 1267.625 Criminal drug statute. Criminal drug statute means a Federal or non-Federal criminal statute involving the...

  1. 38 CFR 48.625 - Criminal drug statute.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 2 2010-07-01 2010-07-01 false Criminal drug statute. 48...) GOVERNMENTWIDE REQUIREMENTS FOR DRUG-FREE WORKPLACE (FINANCIAL ASSISTANCE) Definitions § 48.625 Criminal drug statute. Criminal drug statute means a Federal or non-Federal criminal statute involving the...

  2. 29 CFR 1472.625 - Criminal drug statute.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 29 Labor 4 2010-07-01 2010-07-01 false Criminal drug statute. 1472.625 Section 1472.625 Labor... REQUIREMENTS FOR DRUG-FREE WORKPLACE (FINANCIAL ASSISTANCE) Definitions § 1472.625 Criminal drug statute. Criminal drug statute means a Federal or non-Federal criminal statute involving the...

  3. 29 CFR 1472.625 - Criminal drug statute.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 29 Labor 4 2013-07-01 2013-07-01 false Criminal drug statute. 1472.625 Section 1472.625 Labor... REQUIREMENTS FOR DRUG-FREE WORKPLACE (FINANCIAL ASSISTANCE) Definitions § 1472.625 Criminal drug statute. Criminal drug statute means a Federal or non-Federal criminal statute involving the...

  4. 2 CFR 182.625 - Criminal drug statute.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 2 Grants and Agreements 1 2013-01-01 2013-01-01 false Criminal drug statute. 182.625 Section 182... GOVERNMENTWIDE REQUIREMENTS FOR DRUG-FREE WORKPLACE (FINANCIAL ASSISTANCE) Definitions § 182.625 Criminal drug statute. Criminal drug statute means a Federal or non-Federal criminal statute involving the...

  5. 38 CFR 48.625 - Criminal drug statute.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 2 2014-07-01 2014-07-01 false Criminal drug statute. 48...) GOVERNMENTWIDE REQUIREMENTS FOR DRUG-FREE WORKPLACE (FINANCIAL ASSISTANCE) Definitions § 48.625 Criminal drug statute. Criminal drug statute means a Federal or non-Federal criminal statute involving the...

  6. 14 CFR § 1267.625 - Criminal drug statute.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 14 Aeronautics and Space 5 2014-01-01 2014-01-01 false Criminal drug statute. § 1267.625 Section... REQUIREMENTS FOR DRUG-FREE WORKPLACE (FINANCIAL ASSISTANCE) Definitions § 1267.625 Criminal drug statute. Criminal drug statute means a Federal or non-Federal criminal statute involving the...

  7. 29 CFR 1472.625 - Criminal drug statute.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 29 Labor 4 2014-07-01 2014-07-01 false Criminal drug statute. 1472.625 Section 1472.625 Labor... REQUIREMENTS FOR DRUG-FREE WORKPLACE (FINANCIAL ASSISTANCE) Definitions § 1472.625 Criminal drug statute. Criminal drug statute means a Federal or non-Federal criminal statute involving the...

  8. 31 CFR 20.625 - Criminal drug statute.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 31 Money and Finance: Treasury 1 2013-07-01 2013-07-01 false Criminal drug statute. 20.625 Section... REQUIREMENTS FOR DRUG-FREE WORKPLACE (FINANCIAL ASSISTANCE) Definitions § 20.625 Criminal drug statute. Criminal drug statute means a Federal or non-Federal criminal statute involving the...

  9. 38 CFR 14.809 - Demands or requests in legal proceedings for records protected by confidentiality statutes.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... regulations, such as 38 CFR 1.511, before the records may be provided or testimony given. Accordingly, the... an applicable confidentiality statute mandates disclosure, §§ 14.800 through 14.810 will not...

  10. 48 CFR 1506.302-5 - Authorized or required by statute.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 48 Federal Acquisition Regulations System 6 2012-10-01 2012-10-01 false Authorized or required by statute. 1506.302-5 Section 1506.302-5 Federal Acquisition Regulations System ENVIRONMENTAL PROTECTION... other than full and open competition to acquire the services of experts for use in preparing...

  11. 48 CFR 1506.302-5 - Authorized or required by statute.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 48 Federal Acquisition Regulations System 6 2014-10-01 2014-10-01 false Authorized or required by statute. 1506.302-5 Section 1506.302-5 Federal Acquisition Regulations System ENVIRONMENTAL PROTECTION... other than full and open competition to acquire the services of experts for use in preparing...

  12. Public Rules on Private Schools: Measuring the Regulatory Impact of State Statutes and School Choice Programs

    ERIC Educational Resources Information Center

    Catt, Andrew D.

    2014-01-01

    This report provides a framework for understanding the impacts of state government statutes regulating private schools, regulations distinct to a given school choice program, and any regulatory growth over a program's lifespan. Examining school choice programs in operation for at least a few years provides important context and comparisons for…

  13. 15 CFR 744.19 - Licensing policy regarding persons sanctioned pursuant to specified statutes.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 15 Commerce and Foreign Trade 2 2012-01-01 2012-01-01 false Licensing policy regarding persons sanctioned pursuant to specified statutes. 744.19 Section 744.19 Commerce and Foreign Trade Regulations Relating to Commerce and Foreign Trade (Continued) BUREAU OF INDUSTRY AND SECURITY, DEPARTMENT OF COMMERCE EXPORT ADMINISTRATION REGULATIONS...

  14. 48 CFR 1506.302-5 - Authorized or required by statute.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 48 Federal Acquisition Regulations System 6 2011-10-01 2011-10-01 false Authorized or required by statute. 1506.302-5 Section 1506.302-5 Federal Acquisition Regulations System ENVIRONMENTAL PROTECTION... prosecuting a civil or criminal action under SARA whether or not the expert is expected to testify at...

  15. 42 CFR 2.21 - Relationship to Federal statutes protecting research subjects against compulsory disclosure of...

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... implementing regulations at 42 CFR part 2a); or section 502(c) of the Controlled Substances Act (21 U.S.C. 872(c) and the implementing regulations at 21 CFR 1316.21). These “research privilege” statutes confer.... However, the research privilage granted under 21 CFR 291.505(g) to treatment programs using methadone...

  16. 42 CFR 2.21 - Relationship to Federal statutes protecting research subjects against compulsory disclosure of...

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    .... However, the research privilage granted under 21 CFR 291.505(g) to treatment programs using methadone for... implementing regulations at 42 CFR part 2a); or section 502(c) of the Controlled Substances Act (21 U.S.C. 872(c) and the implementing regulations at 21 CFR 1316.21). These “research privilege” statutes...

  17. Improving the regulation and management of low-activity radioactive wastes.

    PubMed

    Leroy, David H; Ryan, Michael T; Wiley, John R

    2006-11-01

    This paper summarizes the first phase of a study in progress by a committee of the National Research Council's Board on Radioactive Waste Management. The Board initiated the study after observing that statutes and regulations administered by the federal and state agencies that control low-activity radioactive wastes have developed as a patchwork over almost 60 y. These controls usually reflect the enterprise or process that produced the waste rather than the waste's radiological hazard. Inconsistencies in the regulatory patchwork or its application may have led to overly restrictive controls for some low-activity wastes while others were neglected in comparison. In the first phase of this study, the committee reviewed current low-activity waste inventories, regulations, and management practices. This led the committee to develop five categories that encompass the spectrum of low-activity wastes and serve to illustrate gaps and inconsistencies in current regulations and management practices. The committee completed its first phase with four findings that will lead into the final phase of the study. This paper is excerpted from the committee's interim report that was issued in October 2003.

  18. 45 CFR 91.3 - To what programs or activities do these regulations apply?

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... regulations apply? 91.3 Section 91.3 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL... apply to: (1) An age distinction contained in that part of a Federal, State, or local statute or ordinance adopted by an elected, general purpose legislative body which: (i) Provides any benefits...

  19. 77 FR 76938 - Defense Federal Acquisition Regulation Supplement: Contracting Activity Updates (DFARS Case 2012...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-12-31

    ... Federal Acquisition Regulation. Paragraph (a)(1) of the statute requires that a procurement policy... 13563 Executive Orders (E.O.s) 12866 and 13563 direct agencies to assess all costs and benefits of..., distributive impacts, and equity). E.O. 13563 emphasizes the importance of quantifying both costs and...

  20. [Molecular mechanisms regulating the activity of macrophages].

    PubMed

    Onoprienko, L V

    2011-01-01

    This article reviews modern concepts of the most common types of macrophage activation: classical, alternative, and type II. Molecular mechanisms of induction and regulation of these three types of activation are discussed. Any population of macrophages was shown to change its properties depending on its microenvironment and concrete biological situation (the "functional plasticity of macrophages"). Many intermediate states of macrophages were described along with the most pronounced and well-known activation types (classical activation, alternative activation, and type II activation). These intermediate states are characterized by a variety of combinations of their biological properties, including elements of the three afore mentioned types of activation. Macrophage activity is regulated by a complex network of interrelated cascade mechanisms.

  1. 22 CFR 1509.625 - Criminal drug statute.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 22 Foreign Relations 2 2010-04-01 2010-04-01 true Criminal drug statute. 1509.625 Section 1509.625 Foreign Relations AFRICAN DEVELOPMENT FOUNDATION GOVERNMENTWIDE REQUIREMENTS FOR DRUG-FREE WORKPLACE (FINANCIAL ASSISTANCE) Definitions § 1509.625 Criminal drug statute. Criminal drug statute means a Federal...

  2. 20 CFR 439.625 - Criminal drug statute.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 20 Employees' Benefits 2 2010-04-01 2010-04-01 false Criminal drug statute. 439.625 Section 439.625 Employees' Benefits SOCIAL SECURITY ADMINISTRATION GOVERNMENTWIDE REQUIREMENTS FOR DRUG-FREE WORKPLACE (FINANCIAL ASSISTANCE) Definitions § 439.625 Criminal drug statute. Criminal drug statute means...

  3. 22 CFR 1008.625 - Criminal drug statute.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 22 Foreign Relations 2 2010-04-01 2010-04-01 true Criminal drug statute. 1008.625 Section 1008.625 Foreign Relations INTER-AMERICAN FOUNDATION GOVERNMENTWIDE REQUIREMENTS FOR DRUG-FREE WORKPLACE (FINANCIAL ASSISTANCE) Definitions § 1008.625 Criminal drug statute. Criminal drug statute means a Federal or...

  4. 22 CFR 312.625 - Criminal drug statute.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 22 Foreign Relations 2 2010-04-01 2010-04-01 true Criminal drug statute. 312.625 Section 312.625 Foreign Relations PEACE CORPS GOVERNMENTWIDE REQUIREMENTS FOR DRUG-FREE WORKPLACE (FINANCIAL ASSISTANCE) Definitions § 312.625 Criminal drug statute. Criminal drug statute means a Federal or non-Federal...

  5. 49 CFR 32.625 - Criminal drug statute.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 1 2011-10-01 2011-10-01 false Criminal drug statute. 32.625 Section 32.625 Transportation Office of the Secretary of Transportation GOVERNMENTWIDE REQUIREMENTS FOR DRUG-FREE WORKPLACE (FINANCIAL ASSISTANCE) Definitions § 32.625 Criminal drug statute. Criminal drug statute means a Federal...

  6. 45 CFR 1155.625 - Criminal drug statute.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 45 Public Welfare 3 2013-10-01 2013-10-01 false Criminal drug statute. 1155.625 Section 1155.625... HUMANITIES NATIONAL ENDOWMENT FOR THE ARTS GOVERNMENTWIDE REQUIREMENTS FOR DRUG-FREE WORKPLACE (FINANCIAL ASSISTANCE) Definitions § 1155.625 Criminal drug statute. Criminal drug statute means a Federal or...

  7. 22 CFR 1008.625 - Criminal drug statute.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 22 Foreign Relations 2 2011-04-01 2009-04-01 true Criminal drug statute. 1008.625 Section 1008.625 Foreign Relations INTER-AMERICAN FOUNDATION GOVERNMENTWIDE REQUIREMENTS FOR DRUG-FREE WORKPLACE (FINANCIAL ASSISTANCE) Definitions § 1008.625 Criminal drug statute. Criminal drug statute means a Federal or...

  8. 49 CFR 32.625 - Criminal drug statute.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 49 Transportation 1 2012-10-01 2012-10-01 false Criminal drug statute. 32.625 Section 32.625 Transportation Office of the Secretary of Transportation GOVERNMENTWIDE REQUIREMENTS FOR DRUG-FREE WORKPLACE (FINANCIAL ASSISTANCE) Definitions § 32.625 Criminal drug statute. Criminal drug statute means a Federal...

  9. 22 CFR 1509.625 - Criminal drug statute.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 22 Foreign Relations 2 2012-04-01 2009-04-01 true Criminal drug statute. 1509.625 Section 1509.625 Foreign Relations AFRICAN DEVELOPMENT FOUNDATION GOVERNMENTWIDE REQUIREMENTS FOR DRUG-FREE WORKPLACE (FINANCIAL ASSISTANCE) Definitions § 1509.625 Criminal drug statute. Criminal drug statute means a Federal...

  10. 21 CFR 1405.625 - Criminal drug statute.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 9 2013-04-01 2013-04-01 false Criminal drug statute. 1405.625 Section 1405.625 Food and Drugs OFFICE OF NATIONAL DRUG CONTROL POLICY GOVERNMENTWIDE REQUIREMENTS FOR DRUG-FREE WORKPLACE (FINANCIAL ASSISTANCE) Definitions § 1405.625 Criminal drug statute. Criminal drug statute means...

  11. 21 CFR 1405.625 - Criminal drug statute.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 9 2012-04-01 2012-04-01 false Criminal drug statute. 1405.625 Section 1405.625 Food and Drugs OFFICE OF NATIONAL DRUG CONTROL POLICY GOVERNMENTWIDE REQUIREMENTS FOR DRUG-FREE WORKPLACE (FINANCIAL ASSISTANCE) Definitions § 1405.625 Criminal drug statute. Criminal drug statute means...

  12. 41 CFR 105-74.625 - Criminal drug statute.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 41 Public Contracts and Property Management 3 2012-01-01 2012-01-01 false Criminal drug statute... Administration 74-GOVERNMENTWIDE REQUIREMENTS FOR DRUG-FREE WORKPLACE (FINANCIAL ASSISTANCE) Definitions § 105-74.625 Criminal drug statute. Criminal drug statute means a Federal or non-Federal criminal...

  13. 45 CFR 1155.625 - Criminal drug statute.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 45 Public Welfare 3 2011-10-01 2011-10-01 false Criminal drug statute. 1155.625 Section 1155.625... HUMANITIES NATIONAL ENDOWMENT FOR THE ARTS GOVERNMENTWIDE REQUIREMENTS FOR DRUG-FREE WORKPLACE (FINANCIAL ASSISTANCE) Definitions § 1155.625 Criminal drug statute. Criminal drug statute means a Federal or...

  14. 45 CFR 1173.625 - Criminal drug statute.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 45 Public Welfare 3 2010-10-01 2010-10-01 false Criminal drug statute. 1173.625 Section 1173.625... HUMANITIES NATIONAL ENDOWMENT FOR THE HUMANITIES GOVERNMENTWIDE REQUIREMENTS FOR DRUG-FREE WORKPLACE (FINANCIAL ASSISTANCE) Definitions § 1173.625 Criminal drug statute. Criminal drug statute means a Federal...

  15. 7 CFR 3021.625 - Criminal drug statute.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 15 2011-01-01 2011-01-01 false Criminal drug statute. 3021.625 Section 3021.625..., DEPARTMENT OF AGRICULTURE GOVERNMENTWIDE REQUIREMENTS FOR DRUG-FREE WORKPLACE (FINANCIAL ASSISTANCE) Definitions § 3021.625 Criminal drug statute. Criminal drug statute means a Federal or non-Federal...

  16. 22 CFR 133.625 - Criminal drug statute.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 22 Foreign Relations 1 2013-04-01 2013-04-01 false Criminal drug statute. 133.625 Section 133.625 Foreign Relations DEPARTMENT OF STATE MISCELLANEOUS GOVERNMENTWIDE REQUIREMENTS FOR DRUG-FREE WORKPLACE (FINANCIAL ASSISTANCE) Definitions § 133.625 Criminal drug statute. Criminal drug statute means a Federal...

  17. 22 CFR 1008.625 - Criminal drug statute.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 22 Foreign Relations 2 2012-04-01 2009-04-01 true Criminal drug statute. 1008.625 Section 1008.625 Foreign Relations INTER-AMERICAN FOUNDATION GOVERNMENTWIDE REQUIREMENTS FOR DRUG-FREE WORKPLACE (FINANCIAL ASSISTANCE) Definitions § 1008.625 Criminal drug statute. Criminal drug statute means a Federal or...

  18. 36 CFR 1212.625 - Criminal drug statute.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 36 Parks, Forests, and Public Property 3 2011-07-01 2011-07-01 false Criminal drug statute. 1212... GENERAL RULES GOVERNMENTWIDE REQUIREMENTS FOR DRUG-FREE WORKPLACE (FINANCIAL ASSISTANCE) Definitions § 1212.625 Criminal drug statute. Criminal drug statute means a Federal or non-Federal criminal...

  19. 22 CFR 133.625 - Criminal drug statute.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Criminal drug statute. 133.625 Section 133.625 Foreign Relations DEPARTMENT OF STATE MISCELLANEOUS GOVERNMENTWIDE REQUIREMENTS FOR DRUG-FREE WORKPLACE (FINANCIAL ASSISTANCE) Definitions § 133.625 Criminal drug statute. Criminal drug statute means a Federal...

  20. 22 CFR 312.625 - Criminal drug statute.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 22 Foreign Relations 2 2012-04-01 2009-04-01 true Criminal drug statute. 312.625 Section 312.625 Foreign Relations PEACE CORPS GOVERNMENTWIDE REQUIREMENTS FOR DRUG-FREE WORKPLACE (FINANCIAL ASSISTANCE) Definitions § 312.625 Criminal drug statute. Criminal drug statute means a Federal or non-Federal...

  1. 49 CFR 32.625 - Criminal drug statute.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 49 Transportation 1 2014-10-01 2014-10-01 false Criminal drug statute. 32.625 Section 32.625 Transportation Office of the Secretary of Transportation GOVERNMENTWIDE REQUIREMENTS FOR DRUG-FREE WORKPLACE (FINANCIAL ASSISTANCE) Definitions § 32.625 Criminal drug statute. Criminal drug statute means a Federal...

  2. 22 CFR 133.625 - Criminal drug statute.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 22 Foreign Relations 1 2011-04-01 2011-04-01 false Criminal drug statute. 133.625 Section 133.625 Foreign Relations DEPARTMENT OF STATE MISCELLANEOUS GOVERNMENTWIDE REQUIREMENTS FOR DRUG-FREE WORKPLACE (FINANCIAL ASSISTANCE) Definitions § 133.625 Criminal drug statute. Criminal drug statute means a Federal...

  3. 41 CFR 105-74.625 - Criminal drug statute.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 41 Public Contracts and Property Management 3 2011-01-01 2011-01-01 false Criminal drug statute... Administration 74-GOVERNMENTWIDE REQUIREMENTS FOR DRUG-FREE WORKPLACE (FINANCIAL ASSISTANCE) Definitions § 105-74.625 Criminal drug statute. Criminal drug statute means a Federal or non-Federal criminal...

  4. 22 CFR 312.625 - Criminal drug statute.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 22 Foreign Relations 2 2011-04-01 2009-04-01 true Criminal drug statute. 312.625 Section 312.625 Foreign Relations PEACE CORPS GOVERNMENTWIDE REQUIREMENTS FOR DRUG-FREE WORKPLACE (FINANCIAL ASSISTANCE) Definitions § 312.625 Criminal drug statute. Criminal drug statute means a Federal or non-Federal...

  5. 36 CFR 1212.625 - Criminal drug statute.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 36 Parks, Forests, and Public Property 3 2012-07-01 2012-07-01 false Criminal drug statute. 1212... GENERAL RULES GOVERNMENTWIDE REQUIREMENTS FOR DRUG-FREE WORKPLACE (FINANCIAL ASSISTANCE) Definitions § 1212.625 Criminal drug statute. Criminal drug statute means a Federal or non-Federal criminal...

  6. 21 CFR 1405.625 - Criminal drug statute.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 9 2014-04-01 2014-04-01 false Criminal drug statute. 1405.625 Section 1405.625 Food and Drugs OFFICE OF NATIONAL DRUG CONTROL POLICY GOVERNMENTWIDE REQUIREMENTS FOR DRUG-FREE WORKPLACE (FINANCIAL ASSISTANCE) Definitions § 1405.625 Criminal drug statute. Criminal drug statute means...

  7. 22 CFR 210.625 - Criminal drug statute.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Criminal drug statute. 210.625 Section 210.625 Foreign Relations AGENCY FOR INTERNATIONAL DEVELOPMENT GOVERNMENTWIDE REQUIREMENTS FOR DRUG-FREE WORKPLACE (FINANCIAL ASSISTANCE) Definitions § 210.625 Criminal drug statute. Criminal drug statute means a Federal...

  8. 28 CFR 83.625 - Criminal drug statute.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 28 Judicial Administration 2 2011-07-01 2011-07-01 false Criminal drug statute. 83.625 Section 83.625 Judicial Administration DEPARTMENT OF JUSTICE (CONTINUED) GOVERNMENT-WIDE REQUIREMENTS FOR DRUG-FREE WORKPLACE (GRANTS) Definitions § 83.625 Criminal drug statute. Criminal drug statute means...

  9. 29 CFR 94.625 - Criminal drug statute.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 29 Labor 1 2014-07-01 2013-07-01 true Criminal drug statute. 94.625 Section 94.625 Labor Office of the Secretary of Labor GOVERNMENTWIDE REQUIREMENTS FOR DRUG-FREE WORKPLACE (FINANCIAL ASSISTANCE) Definitions § 94.625 Criminal drug statute. Criminal drug statute means a Federal or non-Federal...

  10. 34 CFR 84.625 - Criminal drug statute.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 34 Education 1 2011-07-01 2011-07-01 false Criminal drug statute. 84.625 Section 84.625 Education Office of the Secretary, Department of Education GOVERNMENTWIDE REQUIREMENTS FOR DRUG-FREE WORKPLACE (FINANCIAL ASSISTANCE) Definitions § 84.625 Criminal drug statute. Criminal drug statute means a Federal...

  11. 36 CFR 1212.625 - Criminal drug statute.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 36 Parks, Forests, and Public Property 3 2014-07-01 2014-07-01 false Criminal drug statute. 1212... GENERAL RULES GOVERNMENTWIDE REQUIREMENTS FOR DRUG-FREE WORKPLACE (FINANCIAL ASSISTANCE) Definitions § 1212.625 Criminal drug statute. Criminal drug statute means a Federal or non-Federal criminal...

  12. 45 CFR 1155.625 - Criminal drug statute.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 45 Public Welfare 3 2010-10-01 2010-10-01 false Criminal drug statute. 1155.625 Section 1155.625... HUMANITIES NATIONAL ENDOWMENT FOR THE ARTS GOVERNMENTWIDE REQUIREMENTS FOR DRUG-FREE WORKPLACE (FINANCIAL ASSISTANCE) Definitions § 1155.625 Criminal drug statute. Criminal drug statute means a Federal or...

  13. 22 CFR 133.625 - Criminal drug statute.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 22 Foreign Relations 1 2014-04-01 2014-04-01 false Criminal drug statute. 133.625 Section 133.625 Foreign Relations DEPARTMENT OF STATE MISCELLANEOUS GOVERNMENTWIDE REQUIREMENTS FOR DRUG-FREE WORKPLACE (FINANCIAL ASSISTANCE) Definitions § 133.625 Criminal drug statute. Criminal drug statute means a Federal...

  14. 22 CFR 210.625 - Criminal drug statute.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 22 Foreign Relations 1 2011-04-01 2011-04-01 false Criminal drug statute. 210.625 Section 210.625 Foreign Relations AGENCY FOR INTERNATIONAL DEVELOPMENT GOVERNMENTWIDE REQUIREMENTS FOR DRUG-FREE WORKPLACE (FINANCIAL ASSISTANCE) Definitions § 210.625 Criminal drug statute. Criminal drug statute means a Federal...

  15. 34 CFR 84.625 - Criminal drug statute.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 34 Education 1 2010-07-01 2010-07-01 false Criminal drug statute. 84.625 Section 84.625 Education Office of the Secretary, Department of Education GOVERNMENTWIDE REQUIREMENTS FOR DRUG-FREE WORKPLACE (FINANCIAL ASSISTANCE) Definitions § 84.625 Criminal drug statute. Criminal drug statute means a Federal...

  16. 36 CFR 1212.625 - Criminal drug statute.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 36 Parks, Forests, and Public Property 3 2013-07-01 2012-07-01 true Criminal drug statute. 1212... GENERAL RULES GOVERNMENTWIDE REQUIREMENTS FOR DRUG-FREE WORKPLACE (FINANCIAL ASSISTANCE) Definitions § 1212.625 Criminal drug statute. Criminal drug statute means a Federal or non-Federal criminal...

  17. 21 CFR 1405.625 - Criminal drug statute.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 9 2011-04-01 2011-04-01 false Criminal drug statute. 1405.625 Section 1405.625 Food and Drugs OFFICE OF NATIONAL DRUG CONTROL POLICY GOVERNMENTWIDE REQUIREMENTS FOR DRUG-FREE WORKPLACE (FINANCIAL ASSISTANCE) Definitions § 1405.625 Criminal drug statute. Criminal drug statute means...

  18. 28 CFR 83.625 - Criminal drug statute.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 28 Judicial Administration 2 2010-07-01 2010-07-01 false Criminal drug statute. 83.625 Section 83.625 Judicial Administration DEPARTMENT OF JUSTICE (CONTINUED) GOVERNMENT-WIDE REQUIREMENTS FOR DRUG-FREE WORKPLACE (GRANTS) Definitions § 83.625 Criminal drug statute. Criminal drug statute means...

  19. 41 CFR 105-74.625 - Criminal drug statute.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 41 Public Contracts and Property Management 3 2014-01-01 2014-01-01 false Criminal drug statute... Administration 74-GOVERNMENTWIDE REQUIREMENTS FOR DRUG-FREE WORKPLACE (FINANCIAL ASSISTANCE) Definitions § 105-74.625 Criminal drug statute. Criminal drug statute means a Federal or non-Federal criminal...

  20. 28 CFR 83.625 - Criminal drug statute.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 28 Judicial Administration 2 2012-07-01 2012-07-01 false Criminal drug statute. 83.625 Section 83.625 Judicial Administration DEPARTMENT OF JUSTICE (CONTINUED) GOVERNMENT-WIDE REQUIREMENTS FOR DRUG-FREE WORKPLACE (GRANTS) Definitions § 83.625 Criminal drug statute. Criminal drug statute means...

  1. 28 CFR 83.625 - Criminal drug statute.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 28 Judicial Administration 2 2014-07-01 2014-07-01 false Criminal drug statute. 83.625 Section 83.625 Judicial Administration DEPARTMENT OF JUSTICE (CONTINUED) GOVERNMENT-WIDE REQUIREMENTS FOR DRUG-FREE WORKPLACE (GRANTS) Definitions § 83.625 Criminal drug statute. Criminal drug statute means...

  2. 45 CFR 1155.625 - Criminal drug statute.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 45 Public Welfare 3 2012-10-01 2012-10-01 false Criminal drug statute. 1155.625 Section 1155.625... HUMANITIES NATIONAL ENDOWMENT FOR THE ARTS GOVERNMENTWIDE REQUIREMENTS FOR DRUG-FREE WORKPLACE (FINANCIAL ASSISTANCE) Definitions § 1155.625 Criminal drug statute. Criminal drug statute means a Federal or...

  3. 34 CFR 84.625 - Criminal drug statute.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 34 Education 1 2013-07-01 2013-07-01 false Criminal drug statute. 84.625 Section 84.625 Education Office of the Secretary, Department of Education GOVERNMENTWIDE REQUIREMENTS FOR DRUG-FREE WORKPLACE (FINANCIAL ASSISTANCE) Definitions § 84.625 Criminal drug statute. Criminal drug statute means a Federal...

  4. 34 CFR 84.625 - Criminal drug statute.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 34 Education 1 2014-07-01 2014-07-01 false Criminal drug statute. 84.625 Section 84.625 Education Office of the Secretary, Department of Education GOVERNMENTWIDE REQUIREMENTS FOR DRUG-FREE WORKPLACE (FINANCIAL ASSISTANCE) Definitions § 84.625 Criminal drug statute. Criminal drug statute means a Federal...

  5. 22 CFR 1509.625 - Criminal drug statute.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 22 Foreign Relations 2 2011-04-01 2009-04-01 true Criminal drug statute. 1509.625 Section 1509.625 Foreign Relations AFRICAN DEVELOPMENT FOUNDATION GOVERNMENTWIDE REQUIREMENTS FOR DRUG-FREE WORKPLACE (FINANCIAL ASSISTANCE) Definitions § 1509.625 Criminal drug statute. Criminal drug statute means a Federal...

  6. 28 CFR 83.625 - Criminal drug statute.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 28 Judicial Administration 2 2013-07-01 2013-07-01 false Criminal drug statute. 83.625 Section 83.625 Judicial Administration DEPARTMENT OF JUSTICE (CONTINUED) GOVERNMENT-WIDE REQUIREMENTS FOR DRUG-FREE WORKPLACE (GRANTS) Definitions § 83.625 Criminal drug statute. Criminal drug statute means...

  7. 45 CFR 1155.625 - Criminal drug statute.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 45 Public Welfare 3 2014-10-01 2014-10-01 false Criminal drug statute. 1155.625 Section 1155.625... HUMANITIES NATIONAL ENDOWMENT FOR THE ARTS GOVERNMENTWIDE REQUIREMENTS FOR DRUG-FREE WORKPLACE (FINANCIAL ASSISTANCE) Definitions § 1155.625 Criminal drug statute. Criminal drug statute means a Federal or...

  8. 49 CFR 32.625 - Criminal drug statute.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 1 2013-10-01 2013-10-01 false Criminal drug statute. 32.625 Section 32.625 Transportation Office of the Secretary of Transportation GOVERNMENTWIDE REQUIREMENTS FOR DRUG-FREE WORKPLACE (FINANCIAL ASSISTANCE) Definitions § 32.625 Criminal drug statute. Criminal drug statute means a Federal...

  9. 22 CFR 312.625 - Criminal drug statute.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 22 Foreign Relations 2 2013-04-01 2009-04-01 true Criminal drug statute. 312.625 Section 312.625 Foreign Relations PEACE CORPS GOVERNMENTWIDE REQUIREMENTS FOR DRUG-FREE WORKPLACE (FINANCIAL ASSISTANCE) Definitions § 312.625 Criminal drug statute. Criminal drug statute means a Federal or non-Federal...

  10. 41 CFR 105-74.625 - Criminal drug statute.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 41 Public Contracts and Property Management 3 2013-07-01 2013-07-01 false Criminal drug statute... Administration 74-GOVERNMENTWIDE REQUIREMENTS FOR DRUG-FREE WORKPLACE (FINANCIAL ASSISTANCE) Definitions § 105-74.625 Criminal drug statute. Criminal drug statute means a Federal or non-Federal criminal...

  11. 29 CFR 94.625 - Criminal drug statute.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 29 Labor 1 2013-07-01 2013-07-01 false Criminal drug statute. 94.625 Section 94.625 Labor Office of the Secretary of Labor GOVERNMENTWIDE REQUIREMENTS FOR DRUG-FREE WORKPLACE (FINANCIAL ASSISTANCE) Definitions § 94.625 Criminal drug statute. Criminal drug statute means a Federal or non-Federal...

  12. 15 CFR 744.19 - Licensing policy regarding persons sanctioned pursuant to specified statutes.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... EXPORT ADMINISTRATION REGULATIONS CONTROL POLICY: END-USER AND END-USE BASED § 744.19 Licensing policy regarding persons sanctioned pursuant to specified statutes. Notwithstanding any other licensing policy... 15 Commerce and Foreign Trade 2 2010-01-01 2010-01-01 false Licensing policy regarding...

  13. 32 CFR 22.310 - Statutes concerning certain research, development, and facilities construction grants.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... OFFICE OF THE SECRETARY OF DEFENSE DoD GRANT AND AGREEMENT REGULATIONS DoD GRANTS AND AGREEMENTS-AWARD... higher education for the performance of research and development or for the construction of research or... institutions of higher education by other than merit-based competitive procedures. (c) Subsequent statutes....

  14. 32 CFR 22.310 - Statutes concerning certain research, development, and facilities construction grants.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... OFFICE OF THE SECRETARY OF DEFENSE DoD GRANT AND AGREEMENT REGULATIONS DoD GRANTS AND AGREEMENTS-AWARD... higher education for the performance of research and development or for the construction of research or... institutions of higher education by other than merit-based competitive procedures. (c) Subsequent statutes....

  15. [Palliative care regulation and assisted death].

    PubMed

    Cossío-Díaz, José Ramón; Franco González-Salas, José Fernando; Kershenobich-Stalnikowitz, David; Goslinga-Remírez, Lorena; Montes de Oca-Arboleya, Rodrigo; Torres-Morán, Laura Estela; Calderón-Vidal, Mariana

    2015-01-01

    This article analyzes the Mexican regulation on palliative care and its relationship with the public debate on assisted death or suicide. This paper focuses on the rights that people with incurable diseases have, given the current contents of the General Health Statute and other applicable rules. Its main purpose is to activate the public debate on these matters. PMID:25739492

  16. [Palliative care regulation and assisted death].

    PubMed

    Cossío-Díaz, José Ramón; Franco González-Salas, José Fernando; Kershenobich-Stalnikowitz, David; Goslinga-Remírez, Lorena; Montes de Oca-Arboleya, Rodrigo; Torres-Morán, Laura Estela; Calderón-Vidal, Mariana

    2015-01-01

    This article analyzes the Mexican regulation on palliative care and its relationship with the public debate on assisted death or suicide. This paper focuses on the rights that people with incurable diseases have, given the current contents of the General Health Statute and other applicable rules. Its main purpose is to activate the public debate on these matters.

  17. 50 CFR 665.964 - Regulated activities.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 50 Wildlife and Fisheries 13 2014-10-01 2014-10-01 false Regulated activities. 665.964 Section 665.964 Wildlife and Fisheries FISHERY CONSERVATION AND MANAGEMENT, NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE (CONTINUED) FISHERIES IN THE WESTERN PACIFIC Rose Atoll Marine...

  18. 50 CFR 665.964 - Regulated activities.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 50 Wildlife and Fisheries 13 2013-10-01 2013-10-01 false Regulated activities. 665.964 Section 665.964 Wildlife and Fisheries FISHERY CONSERVATION AND MANAGEMENT, NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE (CONTINUED) FISHERIES IN THE WESTERN PACIFIC Rose Atoll Marine...

  19. Buckman extended: federal preemption of state fraud-on-the-FDA statutes.

    PubMed

    Gaddis, Christine A

    2014-01-01

    A number of states have enacted statutes that provide protection to drug manufacturers in product liability actions. Additionally, several of these states have enacted "fraud-on-the-FDA" statutory provisions, which remove statutory protection afforded to drug manufacturers in product liability actions if plaintiffs can provide evidence that the drug manufacturer made misrepresentations to the FDA during the process of obtaining marketing approval for the drug. Currently, the federal circuits are in disagreement over whether these state "fraud-on-the-FDA" statutes should be federally preempted. This issue warrants resolution for drug manufacturers, private citizens, and state legislatures. This Comment will discuss the history and role of the FDA's authority in drug and medical device regulation; federal preemption generally and the Supreme Court's decisions that considered whether state law failure to warn claims are federally preempted in the context of drugs and medical devices; the Supreme Court's decision in Buckman v. Plaintiffs' Legal Committee, where the Court held that claims that a medical device manufacturer made fraudulent representations to the FDA were federally preempted because such claims interfered with the relationship between the FDA and the entities it regulated, state fraud-on-the-FDA statutory provisions, and the existing circuit split regarding whether those statutes should be federally preempted; the potential resolutions to the circuit split; and will conclude and advocate that the Supreme Court's Buckman holding be applied to federally preempt state fraud-on-the-FDA statutes because such statutes involve the relationship between a federal agency and the entity it regulates and thus undermine the FDA's authority.

  20. Src regulates the activity of SIRT2

    SciTech Connect

    Choi, You Hee; Kim, Hangun; Lee, Sung Ho; Jin, Yun-Hye; Lee, Kwang Youl

    2014-07-25

    Highlights: • Src decreases the protein levels of Sirt2. • Src inhibitor and knockdown of Src increase the protein levels of Sirt2. • Src interacts with and phosphorylates Sirt2. • Src regulate the activity of Sirt2. - Abstract: SIRT2 is a mammalian member of the Sirtuin family of NAD{sup +}-dependent protein deacetylases. The tyrosine kinase Src is involved in a variety of cellular signaling pathways, leading to the induction of DNA synthesis, cell proliferation, and cytoskeletal reorganization. The function of SIRT2 is modulated by post-translational modifications; however, the precise molecular signaling mechanism of SIRT2 through interactions with c-Src has not yet been established. In this study, we investigated the potential regulation of SIRT2 function by c-Src. We found that the protein levels of SIRT2 were decreased by c-Src, and subsequently rescued by the addition of a Src specific inhibitor, SU6656, or by siRNA-mediated knockdown of c-Src. The c-Src interacts with and phosphorylates SIRT2 at Tyr104. c-Src also showed the ability to regulate the deacetylation activity of SIRT2. Investigation on the phosphorylation of SIRT2 suggested that this was the method of c-Src-mediated SIRT2 regulation.

  1. The Illinois HIV transmission statute: unconstitutionally vague or politically vogue?

    PubMed

    Kwiatt, K L

    1991-01-01

    This article does not challenge the prudence of enacting statutes criminalizing the transmission of the HIV virus. Instead, the author asks whether a particular statute, one already enacted in Illinois, is unconstitutionally vague because it does not give adequate warning to individuals that certain behavior is proscribed or because it is overbroad in that it prohibits constitutionally protected conduct. The author also offers a redrafted Illinois statute that she believes will pass constitutional muster.

  2. Regulators of Slc4 bicarbonate transporter activity

    PubMed Central

    Thornell, Ian M.; Bevensee, Mark O.

    2015-01-01

    The Slc4 family of transporters is comprised of anion exchangers (AE1-4), Na+-coupled bicarbonate transporters (NCBTs) including electrogenic Na/bicarbonate cotransporters (NBCe1 and NBCe2), electroneutral Na/bicarbonate cotransporters (NBCn1 and NBCn2), and the electroneutral Na-driven Cl-bicarbonate exchanger (NDCBE), as well as a borate transporter (BTR1). These transporters regulate intracellular pH (pHi) and contribute to steady-state pHi, but are also involved in other physiological processes including CO2 carriage by red blood cells and solute secretion/reabsorption across epithelia. Acid-base transporters function as either acid extruders or acid loaders, with the Slc4 proteins moving HCO−3 either into or out of cells. According to results from both molecular and functional studies, multiple Slc4 proteins and/or associated splice variants with similar expected effects on pHi are often found in the same tissue or cell. Such apparent redundancy is likely to be physiologically important. In addition to regulating pHi, a HCO−3 transporter contributes to a cell's ability to fine tune the intracellular regulation of the cotransported/exchanged ion(s) (e.g., Na+ or Cl−). In addition, functionally similar transporters or splice variants with different regulatory profiles will optimize pH physiology and solute transport under various conditions or within subcellular domains. Such optimization will depend on activated signaling pathways and transporter expression profiles. In this review, we will summarize and discuss both well-known and more recently identified regulators of the Slc4 proteins. Some of these regulators include traditional second messengers, lipids, binding proteins, autoregulatory domains, and less conventional regulators. The material presented will provide insight into the diversity and physiological significance of multiple members within the Slc4 gene family. PMID:26124722

  3. Team Regulation, Regulation of Social Activities or Co-Regulation: Different Labels for Effective Regulation of Learning in CSCL

    ERIC Educational Resources Information Center

    Saab, Nadira

    2012-01-01

    Computer-supported collaborative learning (CSCL) is an approach to learning in which learners can actively and collaboratively construct knowledge by means of interaction and joint problem solving. Regulation of learning is especially important in the domain of CSCL. Next to the regulation of task performance, the interaction between learners who…

  4. Activities and regulation of peptidoglycan synthases

    PubMed Central

    Egan, Alexander J. F.; Biboy, Jacob; van't Veer, Inge; Breukink, Eefjan; Vollmer, Waldemar

    2015-01-01

    Peptidoglycan (PG) is an essential component in the cell wall of nearly all bacteria, forming a continuous, mesh-like structure, called the sacculus, around the cytoplasmic membrane to protect the cell from bursting by its turgor. Although PG synthases, the penicillin-binding proteins (PBPs), have been studied for 70 years, useful in vitro assays for measuring their activities were established only recently, and these provided the first insights into the regulation of these enzymes. Here, we review the current knowledge on the glycosyltransferase and transpeptidase activities of PG synthases. We provide new data showing that the bifunctional PBP1A and PBP1B from Escherichia coli are active upon reconstitution into the membrane environment of proteoliposomes, and that these enzymes also exhibit DD-carboxypeptidase activity in certain conditions. Both novel features are relevant for their functioning within the cell. We also review recent data on the impact of protein–protein interactions and other factors on the activities of PBPs. As an example, we demonstrate a synergistic effect of multiple protein–protein interactions on the glycosyltransferase activity of PBP1B, by its cognate lipoprotein activator LpoB and the essential cell division protein FtsN. PMID:26370943

  5. Molecular mechanisms regulating NLRP3 inflammasome activation

    PubMed Central

    Jo, Eun-Kyeong; Kim, Jin Kyung; Shin, Dong-Min; Sasakawa, Chihiro

    2016-01-01

    Inflammasomes are multi-protein signaling complexes that trigger the activation of inflammatory caspases and the maturation of interleukin-1β. Among various inflammasome complexes, the NLRP3 inflammasome is best characterized and has been linked with various human autoinflammatory and autoimmune diseases. Thus, the NLRP3 inflammasome may be a promising target for anti-inflammatory therapies. In this review, we summarize the current understanding of the mechanisms by which the NLRP3 inflammasome is activated in the cytosol. We also describe the binding partners of NLRP3 inflammasome complexes activating or inhibiting the inflammasome assembly. Our knowledge of the mechanisms regulating NLRP3 inflammasome signaling and how these influence inflammatory responses offers further insight into potential therapeutic strategies to treat inflammatory diseases associated with dysregulation of the NLRP3 inflammasome. PMID:26549800

  6. Magnetoreception Regulates Male Courtship Activity in Drosophila.

    PubMed

    Wu, Chia-Lin; Fu, Tsai-Feng; Chiang, Meng-Hsuan; Chang, Yu-Wei; Her, Jim-Long; Wu, Tony

    2016-01-01

    The possible neurological and biophysical effects of magnetic fields on animals is an area of active study. Here, we report that courtship activity of male Drosophila increases in a magnetic field and that this effect is regulated by the blue light-dependent photoreceptor cryptochrome (CRY). Naïve male flies exhibited significantly increased courtship activities when they were exposed to a ≥ 20-Gauss static magnetic field, compared with their behavior in the natural environment (0 Gauss). CRY-deficient flies, cryb and crym, did not show an increased courtship index in a magnetic field. RNAi-mediated knockdown of cry in cry-GAL4-positive neurons disrupted the increased male courtship activity in a magnetic field. Genetically expressing cry under the control of cry-GAL4 in the CRY-deficient flies restored the increase in male courtship index that occurred in a magnetic field. Interestingly, artificially activating cry-GAL4-expressing neurons, which include large ventral lateral neurons and small ventral lateral neurons, via expression of thermosensitive cation channel dTrpA1, also increased the male courtship index. This enhancement was abolished by the addition of the cry-GAL80 transgene. Our results highlight the phenomenon of increased male courtship activity caused by a magnetic field through CRY-dependent magnetic sensation in CRY expression neurons in Drosophila. PMID:27195955

  7. Magnetoreception Regulates Male Courtship Activity in Drosophila

    PubMed Central

    Wu, Chia-Lin; Fu, Tsai-Feng; Chiang, Meng-Hsuan; Chang, Yu-Wei; Her, Jim-Long; Wu, Tony

    2016-01-01

    The possible neurological and biophysical effects of magnetic fields on animals is an area of active study. Here, we report that courtship activity of male Drosophila increases in a magnetic field and that this effect is regulated by the blue light-dependent photoreceptor cryptochrome (CRY). Naïve male flies exhibited significantly increased courtship activities when they were exposed to a ≥ 20-Gauss static magnetic field, compared with their behavior in the natural environment (0 Gauss). CRY-deficient flies, cryb and crym, did not show an increased courtship index in a magnetic field. RNAi-mediated knockdown of cry in cry-GAL4-positive neurons disrupted the increased male courtship activity in a magnetic field. Genetically expressing cry under the control of cry-GAL4 in the CRY-deficient flies restored the increase in male courtship index that occurred in a magnetic field. Interestingly, artificially activating cry-GAL4-expressing neurons, which include large ventral lateral neurons and small ventral lateral neurons, via expression of thermosensitive cation channel dTrpA1, also increased the male courtship index. This enhancement was abolished by the addition of the cry-GAL80 transgene. Our results highlight the phenomenon of increased male courtship activity caused by a magnetic field through CRY-dependent magnetic sensation in CRY expression neurons in Drosophila. PMID:27195955

  8. Regulation of pokemon 1 activity by sumoylation.

    PubMed

    Roh, Hee-Eun; Lee, Min-Nyung; Jeon, Bu-Nam; Choi, Won-Il; Kim, Yoo-Jin; Yu, Mi-Young; Hur, Man-Wook

    2007-01-01

    Pokemon 1 is a proto-oncogenic transcriptional regulator that contains a POZ domain at the N-terminus and four Kruppel-like zinc fingers at the C-terminus. Pokemon 1 plays an important role in adipogenesis, osteogenesis, oncogenesis, and transcription of NF-kB responsive genes. Recent reports have shown that biological activities of transcription factors are regulated by sumolylation. We investigated whether Pokemon 1 is post-translationally modified by sumoylation and whether the modification affects Pokemon 1's transcriptional properties. We found that Pokemon 1 is sumoylated in vitro and in vivo. Upon careful analysis of the amino acid sequence of Pokemon 1, we found ten potential sumoylation sites located at lysines 61, 354, 371, 379, 383, 396, 486, 487, 536 and 539. We mutated each of these amino acids into arginine and tested whether the mutation could affect the transcriptional properties of Pokemon 1 on the Pokemon 1 responsive genes, such as ADH5/FDH and pG5-FRE-Luc. Wild-type Pokemon 1 potently represses transcription of ADH5/FDH. Most of the mutants, however, were weaker transcription repressors and repressed transcription 1.3-3.3 fold less effective. Although potential sumoylation sites were located close to the DNA binding domain or the nuclear localization sequence, the mutations did not alter nuclear localization or DNA binding activity. In addition, on the pG5-FRE-Luc test promoter construct, ectopic SUMO-1 repressed transcription in the presence of Pokemon 1. The sumoylation target lysine residue at amino acid 61, which is located in the middle of the POZ-domain, is important because K61R mutation resulted in a much weaker molecular interaction with corepressors. Our data suggest that Pokemon 1's activity as a transcription factor may involve sumoylation, and that sumoylation might be important in the regulation of transcription by Pokemon 1. PMID:17595526

  9. Regulation of pokemon 1 activity by sumoylation.

    PubMed

    Roh, Hee-Eun; Lee, Min-Nyung; Jeon, Bu-Nam; Choi, Won-Il; Kim, Yoo-Jin; Yu, Mi-Young; Hur, Man-Wook

    2007-01-01

    Pokemon 1 is a proto-oncogenic transcriptional regulator that contains a POZ domain at the N-terminus and four Kruppel-like zinc fingers at the C-terminus. Pokemon 1 plays an important role in adipogenesis, osteogenesis, oncogenesis, and transcription of NF-kB responsive genes. Recent reports have shown that biological activities of transcription factors are regulated by sumolylation. We investigated whether Pokemon 1 is post-translationally modified by sumoylation and whether the modification affects Pokemon 1's transcriptional properties. We found that Pokemon 1 is sumoylated in vitro and in vivo. Upon careful analysis of the amino acid sequence of Pokemon 1, we found ten potential sumoylation sites located at lysines 61, 354, 371, 379, 383, 396, 486, 487, 536 and 539. We mutated each of these amino acids into arginine and tested whether the mutation could affect the transcriptional properties of Pokemon 1 on the Pokemon 1 responsive genes, such as ADH5/FDH and pG5-FRE-Luc. Wild-type Pokemon 1 potently represses transcription of ADH5/FDH. Most of the mutants, however, were weaker transcription repressors and repressed transcription 1.3-3.3 fold less effective. Although potential sumoylation sites were located close to the DNA binding domain or the nuclear localization sequence, the mutations did not alter nuclear localization or DNA binding activity. In addition, on the pG5-FRE-Luc test promoter construct, ectopic SUMO-1 repressed transcription in the presence of Pokemon 1. The sumoylation target lysine residue at amino acid 61, which is located in the middle of the POZ-domain, is important because K61R mutation resulted in a much weaker molecular interaction with corepressors. Our data suggest that Pokemon 1's activity as a transcription factor may involve sumoylation, and that sumoylation might be important in the regulation of transcription by Pokemon 1.

  10. 32 CFR 644.112 - Applicable statutes in condemnation proceedings.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 32 National Defense 4 2013-07-01 2013-07-01 false Applicable statutes in condemnation proceedings. 644.112 Section 644.112 National Defense Department of Defense (Continued) DEPARTMENT OF THE ARMY (CONTINUED) REAL PROPERTY REAL ESTATE HANDBOOK Acquisition Acquisition by Condemnation Proceedings § 644.112 Applicable statutes in...

  11. 32 CFR 536.47 - Statute of limitations.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 32 National Defense 3 2010-07-01 2010-07-01 true Statute of limitations. 536.47 Section 536.47 National Defense Department of Defense (Continued) DEPARTMENT OF THE ARMY CLAIMS AND ACCOUNTS CLAIMS AGAINST THE UNITED STATES Investigation and Processing of Claims § 536.47 Statute of limitations. To...

  12. 12 CFR 26.4 - Interlocking relationships permitted by statute.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 12 Banks and Banking 1 2010-01-01 2010-01-01 false Interlocking relationships permitted by statute. 26.4 Section 26.4 Banks and Banking COMPTROLLER OF THE CURRENCY, DEPARTMENT OF THE TREASURY MANAGEMENT OFFICIAL INTERLOCKS § 26.4 Interlocking relationships permitted by statute. The prohibitions...

  13. 12 CFR 563f.4 - Interlocking relationships permitted by statute.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 12 Banks and Banking 5 2010-01-01 2010-01-01 false Interlocking relationships permitted by statute. 563f.4 Section 563f.4 Banks and Banking OFFICE OF THRIFT SUPERVISION, DEPARTMENT OF THE TREASURY MANAGEMENT OFFICIAL INTERLOCKS § 563f.4 Interlocking relationships permitted by statute. The prohibitions...

  14. 13 CFR 147.625 - Criminal drug statute.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 13 Business Credit and Assistance 1 2013-01-01 2013-01-01 false Criminal drug statute. 147.625 Section 147.625 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION GOVERNMENTWIDE REQUIREMENTS FOR DRUG-FREE WORKPLACE (NONPROCUREMENT) Definitions § 147.625 Criminal drug statute. Criminal...

  15. 15 CFR 29.625 - Criminal drug statute.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 15 Commerce and Foreign Trade 1 2014-01-01 2014-01-01 false Criminal drug statute. 29.625 Section 29.625 Commerce and Foreign Trade Office of the Secretary of Commerce GOVERNMENTWIDE REQUIREMENTS FOR DRUG-FREE WORKPLACE (FINANCIAL ASSISTANCE) Definitions § 29.625 Criminal drug statute. Criminal...

  16. 15 CFR 29.625 - Criminal drug statute.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 15 Commerce and Foreign Trade 1 2010-01-01 2010-01-01 false Criminal drug statute. 29.625 Section 29.625 Commerce and Foreign Trade Office of the Secretary of Commerce GOVERNMENTWIDE REQUIREMENTS FOR DRUG-FREE WORKPLACE (FINANCIAL ASSISTANCE) Definitions § 29.625 Criminal drug statute. Criminal...

  17. 15 CFR 29.625 - Criminal drug statute.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 15 Commerce and Foreign Trade 1 2013-01-01 2013-01-01 false Criminal drug statute. 29.625 Section 29.625 Commerce and Foreign Trade Office of the Secretary of Commerce GOVERNMENTWIDE REQUIREMENTS FOR DRUG-FREE WORKPLACE (FINANCIAL ASSISTANCE) Definitions § 29.625 Criminal drug statute. Criminal...

  18. 13 CFR 147.625 - Criminal drug statute.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 13 Business Credit and Assistance 1 2014-01-01 2014-01-01 false Criminal drug statute. 147.625 Section 147.625 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION GOVERNMENTWIDE REQUIREMENTS FOR DRUG-FREE WORKPLACE (NONPROCUREMENT) Definitions § 147.625 Criminal drug statute. Criminal...

  19. 15 CFR 29.625 - Criminal drug statute.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 15 Commerce and Foreign Trade 1 2011-01-01 2011-01-01 false Criminal drug statute. 29.625 Section 29.625 Commerce and Foreign Trade Office of the Secretary of Commerce GOVERNMENTWIDE REQUIREMENTS FOR DRUG-FREE WORKPLACE (FINANCIAL ASSISTANCE) Definitions § 29.625 Criminal drug statute. Criminal...

  20. 43 CFR 43.625 - Criminal drug statute.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Criminal drug statute. 43.625 Section 43.625 Public Lands: Interior Office of the Secretary of the Interior GOVERNMENTWIDE REQUIREMENTS FOR DRUG-FREE WORKPLACE (FINANCIAL ASSISTANCE) Definitions § 43.625 Criminal drug statute. Criminal...

  1. 22 CFR 1007.10 - Statute of limitations.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 22 Foreign Relations 2 2010-04-01 2010-04-01 true Statute of limitations. 1007.10 Section 1007.10 Foreign Relations INTER-AMERICAN FOUNDATION SALARY OFFSET § 1007.10 Statute of limitations. If a debt has been outstanding for more than 10 years after the agency's right to collect the debt first accrued,...

  2. 22 CFR 1007.10 - Statute of limitations.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 22 Foreign Relations 2 2011-04-01 2009-04-01 true Statute of limitations. 1007.10 Section 1007.10 Foreign Relations INTER-AMERICAN FOUNDATION SALARY OFFSET § 1007.10 Statute of limitations. If a debt has been outstanding for more than 10 years after the agency's right to collect the debt first accrued,...

  3. 22 CFR 1007.10 - Statute of limitations.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 22 Foreign Relations 2 2014-04-01 2014-04-01 false Statute of limitations. 1007.10 Section 1007.10 Foreign Relations INTER-AMERICAN FOUNDATION SALARY OFFSET § 1007.10 Statute of limitations. If a debt has been outstanding for more than 10 years after the agency's right to collect the debt first accrued,...

  4. 22 CFR 1007.10 - Statute of limitations.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 22 Foreign Relations 2 2012-04-01 2009-04-01 true Statute of limitations. 1007.10 Section 1007.10 Foreign Relations INTER-AMERICAN FOUNDATION SALARY OFFSET § 1007.10 Statute of limitations. If a debt has been outstanding for more than 10 years after the agency's right to collect the debt first accrued,...

  5. 22 CFR 1007.10 - Statute of limitations.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 22 Foreign Relations 2 2013-04-01 2009-04-01 true Statute of limitations. 1007.10 Section 1007.10 Foreign Relations INTER-AMERICAN FOUNDATION SALARY OFFSET § 1007.10 Statute of limitations. If a debt has been outstanding for more than 10 years after the agency's right to collect the debt first accrued,...

  6. 48 CFR 25.602-2 - Buy American statute.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ...-Construction Materials 25.602-2 Buy American statute. Except as provided in 25.603, use only unmanufactured construction material mined or produced in the United States, as required by the Buy American statute or, if trade agreements apply, unmanufactured construction material mined or produced in a designated...

  7. Regulation of Aicda expression and AID activity.

    PubMed

    Zan, Hong; Casali, Paolo

    2013-03-01

    Activation-induced cytidine deaminase (AID) is expressed in a B cell differentiation stage-specific fashion and is essential for immunoglobulin (Ig) gene class switch DNA recombination (CSR) and somatic hypermutation (SHM). CSR and SHM play a central role in the maturation of antibody and autoantibody responses. AID displays a mutagenic activity by catalyzing targeted deamination of deoxycytidine (dC) residues in DNA resulting in dU:dG mismatches, which are processed into point-mutations in SHM or double-strand breaks (DSBs) in CSR. Although AID specifically targets the Ig gene loci (IgH, Igκ and Igλ), it can also home into a wide array of non-Ig genes in B-and non-B-cell backgrounds. Aberrant expression of AID is associated with multiple diseases such as allergy, inflammation, autoimmunity and cancer. In autoimmune systemic lupus erythematosus, dysregulated AID expression underpins increased CSR, SHM and autoantibody production. As a potent mutator, AID is under stringent transcriptional, post-transcriptional and post-translational regulation. AID is also regulated in its targeting and enzymatic function. In resting naïve or memory B cells, AID transcripts and protein are undetectable. These, however, are readily and significantly up-regulated in B cells induced to undergo CSR and/or SHM. Transcription factors, such as HoxC4 and NF-κB, which are up-regulated in a B cell lineage-and/or differentiation stage-specific manner, regulate the induction of AID. HoxC4 induces AID expression by directly binding to the AID gene promoter through an evolutionarily conserved 5'-ATTT-3' motif. HoxC4 is induced by the same stimuli that induce AID and CSR. It is further up-regulated by estrogen through three estrogen responsive elements in its promoter region. The targeting of AID to switch (S) regions is mediated by 14-3-3 adaptor proteins, which specifically bind to 5'-AGCT-3' repeats that are exist at high frequency in S region cores. Like HoxC4, 14-3-3 adaptors are induced

  8. State, federal statutes guide organ donation procedures.

    PubMed

    Sipes, D D

    1987-06-01

    To assist in improving the network of organ donors and recipients and in raising public awareness, Congress enacted the National Organ Transplant Act of 1984. The act established an Organ Procurement and Transplantation Network, created a Task Force on Organ Transplantation, and made in unlawful to sell or buy human organs for transplantation for "valuable consideration." At the state level, legislation has closely followed the procedures outlined in the Uniform Anatomical Gift Act. But despite the state and federal statutes, a critical shortage of organs and tissues for transplantation persists. Addressing this problem, approximately 31 states have passed legislation that requires hospitals to request approval for donations from the relatives of potential donors. A generally positive public attitude toward organ transplantation suggests that eventually such legislation could help to increase the supply of organs. In the meantime, however, organ selection and prioritizing processes, particularly those which relate to geographic distribution, will continue to be closely scrutinized.

  9. Regulation of polymorphonuclear cell activation by thrombopoietin.

    PubMed Central

    Brizzi, M F; Battaglia, E; Rosso, A; Strippoli, P; Montrucchio, G; Camussi, G; Pegoraro, L

    1997-01-01

    Thrombopoietin (TPO) regulates early and late stages of platelet formation as well as platelet activation. TPO exerts its effects by binding to the receptor, encoded by the protooncogene c-mpl, that is expressed in a large number of cells of hematopoietic origin. In this study, we evaluated the expression of c-Mpl and the effects of TPO on human polymorphonuclear cells (PMN). We demonstrate that PMN express the TPO receptor c-Mpl and that TPO induces STAT1 tyrosine phosphorylation and the formation of a serum inducible element complex containing STAT1. The analysis of biological effects of TPO on PMN demonstrated that TPO, at concentrations of 1-10 ng/ml, primes the response of PMN to n-formyl-met-leu-phe (FMLP) by inducing an early oxidative burst. TPO-induced priming on FMLP-stimulated PMN was also detected on the tyrosine phosphorylation of a protein with a molecular mass of approximately 28 kD. Moreover, we demonstrated that TPO by itself was able to stimulate, at doses ranging from 0.05 to 10 ng/ml, early release and delayed synthesis of interleukin 8 (IL-8). Thus, our data indicate that, in addition to sustaining megakaryocytopoiesis, TPO may have an important role in regulating PMN activation. PMID:9120001

  10. Redox regulation of methionine aminopeptidase 2 activity.

    PubMed

    Chiu, Joyce; Wong, Jason W H; Hogg, Philip J

    2014-05-23

    Protein translation is initiated with methionine in eukaryotes, and the majority of proteins have their N-terminal methionine removed by methionine aminopeptidases (MetAP1 and MetAP2) prior to action. Methionine removal can be important for protein function, localization, or stability. No mechanism of regulation of MetAP activity has been identified. MetAP2, but not MetAP1, contains a single Cys(228)-Cys(448) disulfide bond that has an -RHStaple configuration and links two β-loop structures, which are hallmarks of allosteric disulfide bonds. From analysis of crystal structures and using mass spectrometry and activity assays, we found that the disulfide bond exists in oxidized and reduced states in the recombinant enzyme. The disulfide has a standard redox potential of -261 mV and is efficiently reduced by the protein reductant, thioredoxin, with a rate constant of 16,180 m(-1) s(-1). The MetAP2 disulfide bond also exists in oxidized and reduced states in glioblastoma tumor cells, and stressing the cells by oxygen or glucose deprivation results in more oxidized enzyme. The Cys(228)-Cys(448) disulfide is at the rim of the active site and is only three residues distant from the catalytic His(231), which suggested that cleavage of the bond would influence substrate hydrolysis. Indeed, oxidized and reduced isoforms have different catalytic efficiencies for hydrolysis of MetAP2 peptide substrates. These findings indicate that MetAP2 is post-translationally regulated by an allosteric disulfide bond, which controls substrate specificity and catalytic efficiency.

  11. Endoglin regulates cyclooxygenase-2 expression and activity.

    PubMed

    Jerkic, Mirjana; Rivas-Elena, Juan V; Santibanez, Juan F; Prieto, Marta; Rodríguez-Barbero, Alicia; Perez-Barriocanal, Fernando; Pericacho, Miguel; Arévalo, Miguel; Vary, Calvin P H; Letarte, Michelle; Bernabeu, Carmelo; López-Novoa, Jose M

    2006-08-01

    The endoglin heterozygous (Eng(+/-)) mouse, which serves as a model of hereditary hemorrhagic telangiectasia (HHT), was shown to express reduced levels of endothelial NO synthase (eNOS) with impaired activity. Because of intricate changes in vasomotor function in the Eng(+/-) mice and the potential interactions between the NO- and prostaglandin-producing pathways, we assessed the expression and function of cyclooxygenase (COX) isoforms. A specific upregulation of COX-2 in the vascular endothelium and increased urinary excretion of prostaglandin E(2) were observed in the Eng(+/-) mice. Specific COX-2 inhibition with parecoxib transiently increased arterial pressure in Eng(+/-) but not in Eng(+/+) mice. Transfection of endoglin in L6E9 myoblasts, shown previously to stimulate eNOS expression, led to downregulation of COX-2 with no change in COX-1. In addition, COX-2 promoter activity and protein levels were inversely correlated with endoglin levels, in doxycyclin-inducible endothelial cells. Chronic NO synthesis inhibition with N(omega)-nitro-l-arginine methyl ester induced a marked increase in COX-2 only in the normal Eng(+/+) mice. N(omega)-nitro-l-arginine methyl ester also increased COX-2 expression and promoter activity in doxycyclin-inducible endoglin expressing endothelial cells, but not in control cells. The level of COX-2 expression following transforming growth factor-beta1 treatment was less in endoglin than in mock transfected L6E9 myoblasts and was higher in human endothelial cells silenced for endoglin expression. Our results indicate that endoglin is involved in the regulation of COX-2 activity. Furthermore, reduced endoglin levels and associated impaired NO production may be responsible, at least in part, for augmented COX-2 expression and activity in the Eng(+/-) mice. PMID:16840721

  12. 7 CFR 1.29 - Subpoenas relating to investigations under statutes administered by the Secretary of Agriculture.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 1 2011-01-01 2011-01-01 false Subpoenas relating to investigations under statutes administered by the Secretary of Agriculture. 1.29 Section 1.29 Agriculture Office of the Secretary of Agriculture ADMINISTRATIVE REGULATIONS Departmental Proceedings § 1.29 Subpoenas relating to...

  13. 7 CFR 1.29 - Subpoenas relating to investigations under statutes administered by the Secretary of Agriculture.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 1 2012-01-01 2012-01-01 false Subpoenas relating to investigations under statutes administered by the Secretary of Agriculture. 1.29 Section 1.29 Agriculture Office of the Secretary of Agriculture ADMINISTRATIVE REGULATIONS Departmental Proceedings § 1.29 Subpoenas relating to...

  14. 7 CFR 1.29 - Subpoenas relating to investigations under statutes administered by the Secretary of Agriculture.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 1 2013-01-01 2013-01-01 false Subpoenas relating to investigations under statutes administered by the Secretary of Agriculture. 1.29 Section 1.29 Agriculture Office of the Secretary of Agriculture ADMINISTRATIVE REGULATIONS Departmental Proceedings § 1.29 Subpoenas relating to...

  15. 7 CFR 1.29 - Subpoenas relating to investigations under statutes administered by the Secretary of Agriculture.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 1 2014-01-01 2014-01-01 false Subpoenas relating to investigations under statutes administered by the Secretary of Agriculture. 1.29 Section 1.29 Agriculture Office of the Secretary of Agriculture ADMINISTRATIVE REGULATIONS Departmental Proceedings § 1.29 Subpoenas relating to...

  16. 49 CFR 1302.42 - Further suspension of statute.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... SHIPMENTS; RAILROADS Charges for Rail Transportation When Water Transportation Performed in Vessels Not Documented Under Laws of the United States § 1302.42 Further suspension of statute. (a) Order of March...

  17. 49 CFR 1302.42 - Further suspension of statute.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... SHIPMENTS; RAILROADS Charges for Rail Transportation When Water Transportation Performed in Vessels Not Documented Under Laws of the United States § 1302.42 Further suspension of statute. (a) Order of March...

  18. 49 CFR 1302.42 - Further suspension of statute.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... SHIPMENTS; RAILROADS Charges for Rail Transportation When Water Transportation Performed in Vessels Not Documented Under Laws of the United States § 1302.42 Further suspension of statute. (a) Order of March...

  19. 49 CFR 1302.42 - Further suspension of statute.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... SHIPMENTS; RAILROADS Charges for Rail Transportation When Water Transportation Performed in Vessels Not Documented Under Laws of the United States § 1302.42 Further suspension of statute. (a) Order of March...

  20. 49 CFR 1302.42 - Further suspension of statute.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... SHIPMENTS; RAILROADS Charges for Rail Transportation When Water Transportation Performed in Vessels Not Documented Under Laws of the United States § 1302.42 Further suspension of statute. (a) Order of March...

  1. Cyfip1 Regulates Presynaptic Activity during Development

    PubMed Central

    Hsiao, Kuangfu; Harony-Nicolas, Hala; Buxbaum, Joseph D.

    2016-01-01

    Copy number variations encompassing the gene encoding Cyfip1 have been associated with a variety of human diseases, including autism and schizophrenia. Here we show that juvenile mice hemizygous for Cyfip1 have altered presynaptic function, enhanced protein translation, and increased levels of F-actin. In developing hippocampus, reduced Cyfip1 levels serve to decrease paired pulse facilitation and increase miniature EPSC frequency without a change in amplitude. Higher-resolution examination shows these changes to be caused primarily by an increase in presynaptic terminal size and enhanced vesicle release probability. Short hairpin-mediated knockdown of Cyfip1 coupled with expression of mutant Cyfip1 proteins indicates that the presynaptic alterations are caused by dysregulation of the WAVE regulatory complex. Such dysregulation occurs downstream of Rac1 as acute exposure to Rac1 inhibitors rescues presynaptic responses in culture and in hippocampal slices. The data serve to highlight an early and essential role for Cyfip1 in the generation of normally functioning synapses and suggest a means by which changes in Cyfip1 levels could impact the generation of neural networks and contribute to abnormal and maladaptive behaviors. SIGNIFICANCE STATEMENT Several developmental brain disorders have been associated with gene duplications and deletions that serve to increase or decrease levels of encoded proteins. Cyfip1 is one such protein, but the role it plays in brain development is poorly understood. We asked whether decreased Cyfip1 levels altered the function of developing synapses. The data show that synapses with reduced Cyfip1 are larger and release neurotransmitter more rapidly. These effects are due to Cyfip1's role in actin polymerization and are reversed by expression of a Cyfip1 mutant protein retaining actin regulatory function or by inhibiting Rac1. Thus, Cyfip1 has a more prominent early role regulating presynaptic activity during a stage of development when

  2. Activity and Regulation of Archaeal DNA Alkyltransferase

    PubMed Central

    Perugino, Giuseppe; Vettone, Antonella; Illiano, Giuseppina; Valenti, Anna; Ferrara, Maria C.; Rossi, Mosè; Ciaramella, Maria

    2012-01-01

    Agents that form methylation adducts in DNA are highly mutagenic and carcinogenic, and organisms have evolved specialized cellular pathways devoted to their repair, including DNA alkyltransferases. These are proteins conserved in eucarya, bacteria and archaea, acting by a unique reaction mechanism, which leads to direct repair of DNA alkylation damage and irreversible protein alkylation. The alkylated form of DNA alkyltransferases is inactive, and in eukaryotes, it is rapidly directed to degradation. We report here in vitro and in vivo studies on the DNA alkyltransferase from the thermophilic archaeon Sulfolobus solfataricus (SsOGT). The development of a novel, simple, and sensitive fluorescence-based assay allowed a careful characterization of the SsOGT biochemical and DNA binding activities. In addition, transcriptional and post-translational regulation of SsOGT by DNA damage was studied. We show that although the gene transcription is induced by alkylating agent treatment, the protein is degraded in vivo by an alkylation-dependent mechanism. These experiments suggest a striking conservation, from archaea to humans, of this important pathway safeguarding genome stability. PMID:22167184

  3. 76 FR 12364 - Agency Information Collection Activities: Bonded Warehouse Regulations

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-03-07

    ... SECURITY U.S. Customs and Border Protection Agency Information Collection Activities: Bonded Warehouse... Bonded Warehouse Regulations. This request for comment is being made pursuant to the Paperwork Reduction... concerning the following information collection: Title: Bonded Warehouse Regulations. OMB Number:...

  4. 7 CFR 2903.21 - Applicable Federal statutes and regulations.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ..., but are not limited to: 7 CFR Part 1, subpart A—USDA implementation of the Freedom of Information Act. 7 CFR Part 3—USDA implementation of OMB Circular No. A-129 regarding debt collection. 7 CFR Part 15, subpart A—USDA implementation of Title VI of the Civil Rights Act of 1964, as amended. 7 CFR Part...

  5. 7 CFR 2903.21 - Applicable Federal statutes and regulations.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ..., but are not limited to: 7 CFR Part 1, subpart A—USDA implementation of the Freedom of Information Act. 7 CFR Part 3—USDA implementation of OMB Circular No. A-129 regarding debt collection. 7 CFR Part 15, subpart A—USDA implementation of Title VI of the Civil Rights Act of 1964, as amended. 7 CFR Part...

  6. 7 CFR 3430.4 - Other applicable statutes and regulations.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... Part 331 and 9 CFR Part 121—USDA implementation of the Agricultural Bioterrorism Protection Act of 2002.... These include, but are not limited to: 7 CFR Part 1, subpart A—USDA implementation of the Freedom of Information Act. 7 CFR Part 3—USDA implementation of OMB Circular No. A-129, regarding debt management. 7...

  7. 7 CFR 3430.4 - Other applicable statutes and regulations.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 331 and 9 CFR Part 121—USDA implementation of the Agricultural Bioterrorism Protection Act of 2002. 7... include, but are not limited to: 7 CFR Part 1, subpart A—USDA implementation of the Freedom of Information Act. 7 CFR Part 3—USDA implementation of OMB Circular No. A-129, regarding debt management. 7 CFR...

  8. 7 CFR 3430.4 - Other applicable statutes and regulations.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 331 and 9 CFR Part 121—USDA implementation of the Agricultural Bioterrorism Protection Act of 2002. 7... include, but are not limited to: 7 CFR Part 1, subpart A—USDA implementation of the Freedom of Information Act. 7 CFR Part 3—USDA implementation of OMB Circular No. A-129, regarding debt management. 7 CFR...

  9. 7 CFR 3430.4 - Other applicable statutes and regulations.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 331 and 9 CFR Part 121—USDA implementation of the Agricultural Bioterrorism Protection Act of 2002. 7... include, but are not limited to: 7 CFR Part 1, subpart A—USDA implementation of the Freedom of Information Act. 7 CFR Part 3—USDA implementation of OMB Circular No. A-129, regarding debt management. 7 CFR...

  10. 32 CFR 516.29 - Federal statutes and regulations.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ...). FELRTCA, by amending the Federal Tort Claims Act, makes the FTCA the exclusive remedy for common law tort claims arising from actions taken by Federal employees acting within the scope of employment. The law was... health care provider. (d) 28 CFR 50.15 (Representation of Federal officials and employees by...

  11. 32 CFR 516.29 - Federal statutes and regulations.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ...). FELRTCA, by amending the Federal Tort Claims Act, makes the FTCA the exclusive remedy for common law tort claims arising from actions taken by Federal employees acting within the scope of employment. The law was... health care provider. (d) 28 CFR 50.15 (Representation of Federal officials and employees by...

  12. 32 CFR 516.29 - Federal statutes and regulations.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ...). FELRTCA, by amending the Federal Tort Claims Act, makes the FTCA the exclusive remedy for common law tort claims arising from actions taken by Federal employees acting within the scope of employment. The law was... health care provider. (d) 28 CFR 50.15 (Representation of Federal officials and employees by...

  13. 32 CFR 516.29 - Federal statutes and regulations.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ...). FELRTCA, by amending the Federal Tort Claims Act, makes the FTCA the exclusive remedy for common law tort claims arising from actions taken by Federal employees acting within the scope of employment. The law was... health care provider. (d) 28 CFR 50.15 (Representation of Federal officials and employees by...

  14. 7 CFR 2500.003 - Other applicable statutes and regulations.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... Governmentwide Requirements for Drug-Free Workplace (Financial Assistance). (j) 7 CFR Part 3052—USDA... grants and cooperative agreements awarded by OAO. These include, but are not limited to: (a) 7 CFR Part 1, Subpart A—USDA implementation of the Freedom of Information Act; (b) 7 CFR Part 3—USDA implementation...

  15. 7 CFR 2500.003 - Other applicable statutes and regulations.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... Governmentwide Requirements for Drug-Free Workplace (Financial Assistance). (j) 7 CFR Part 3052—USDA... grants and cooperative agreements awarded by OAO. These include, but are not limited to: (a) 7 CFR Part 1, Subpart A—USDA implementation of the Freedom of Information Act; (b) 7 CFR Part 3—USDA implementation...

  16. 7 CFR 2500.003 - Other applicable statutes and regulations.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... Governmentwide Requirements for Drug-Free Workplace (Financial Assistance). (j) 7 CFR Part 3052—USDA... grants and cooperative agreements awarded by OAO. These include, but are not limited to: (a) 7 CFR Part 1, Subpart A—USDA implementation of the Freedom of Information Act; (b) 7 CFR Part 3—USDA implementation...

  17. Statutes of limitations: the special problem of DES suits.

    PubMed

    Feigin, C A

    1981-01-01

    In 1971, medical studies determined that DES causes a rare type of vaginal cancer in a small number of daughters of mothers who took DES during pregnancy. Subsequently, medical studies determined that exposure to DES can cause other vaginal abnormalities in the daughters, some of which may be precancerous. As a result of these discoveries, many lawsuits have been filed by these daughters against DES manufacturers. Many DES suits may be barred by statutes of limitations, both because the number of years between the daughters' exposure to DES in utero and the discovery that DES can cause injuries exceeds the statutory period, and because the cancer or other injuries caused by DES may not develop for many additional years. This Note discusses two methods that DES plaintiffs may be able to use to overcome the potential statutes of limitations bar: the discovery rule, and state provisions which toll the statute of limitations for minors. The Note contends that courts should apply an expanded discovery rule to DES suits to avoid the unfair result of barring a claim before the plaintiff could have known that she had a cause of action. In addition, the Note argues that the injury which causes the statute of limitations to begin to run in DES suits should not be rigidly defined. Finally, the Note urges that courts allow eligible DES plaintiffs to take advantage of applicable state provisions that toll the statute of limitations for minors.

  18. Sex Hormones' Regulation of Rodent Physical Activity: A Review

    PubMed Central

    Lightfoot, J. Timothy

    2008-01-01

    There is a large body of emerging literature suggesting that physical activity is regulated to a varying extent by biological factors. Available animal data strongly suggests that there is a differential regulation of physical activity by sex and that the majority of this differential regulation is mediated by estrogen/testosterone pathways with females in many animal species having higher daily activity levels than males. The purpose of this manuscript is to review the mechanisms by which estrogen, progesterone, and testosterone affect the regulation of physical daily activity. This review lays the foundation for future investigations in humans as well as discussions about relative disease risk mediated by differential biological regulation of physical activity by sex. PMID:18449357

  19. 5 CFR 9303.102 - Prior approval for certain outside activities.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... activity; and (iii) The employee has read subpart H (“Outside Activities”) of 5 CFR part 2635. (3) Upon a... to involve conduct prohibited by statute or Federal regulation, including 5 CFR part 2635. (d) Definitions. For purposes of this section: (1) Active participant has the meaning set forth in 5 CFR...

  20. 5 CFR 9303.102 - Prior approval for certain outside activities.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... activity; and (iii) The employee has read subpart H (“Outside Activities”) of 5 CFR part 2635. (3) Upon a... to involve conduct prohibited by statute or Federal regulation, including 5 CFR part 2635. (d) Definitions. For purposes of this section: (1) Active participant has the meaning set forth in 5 CFR...

  1. 5 CFR 5101.103 - Outside employment and activities.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... employment and activities. (a) Subject to the restrictions and requirements contained in 5 CFR part 2635 and... Commission; or (3) Is prohibited by section 2(a)(7) of the Commodity Exchange Act, as incorporated in 17 CFR... not expected to involve conduct prohibited by statute or Federal regulation, including 5 CFR part...

  2. 75 FR 30031 - Proposed Information Collection Activity; Comment Request

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-05-28

    ... Final Rule (45 FR parts 98 and 99). Tribal Lead Agencies (TLAs) are required to submit annual aggregate.... The CCDF statute and regulations also require TLAs to submit a supplemental narrative as part of the ACF-700 report. This narrative describes child care activities and actions in the TLA's service...

  3. Cysteine cathepsin activity regulation by glycosaminoglycans.

    PubMed

    Novinec, Marko; Lenarčič, Brigita; Turk, Boris

    2014-01-01

    Cysteine cathepsins are a group of enzymes normally found in the endolysosomes where they are primarily involved in intracellular protein turnover but also have a critical role in MHC II-mediated antigen processing and presentation. However, in a number of pathologies cysteine cathepsins were found to be heavily upregulated and secreted into extracellular milieu, where they were found to degrade a number of extracellular proteins. A major role in modulating cathepsin activities play glycosaminoglycans, which were found not only to facilitate their autocatalytic activation including at neutral pH, but also to critically modulate their activities such as in the case of the collagenolytic activity of cathepsin K. The interaction between cathepsins and glycosaminoglycans will be discussed in more detail.

  4. Overview of Complement Activation and Regulation

    PubMed Central

    Noris, Marina; Remuzzi, Giuseppe

    2013-01-01

    Summary Complement is an important component of the innate immune system that is crucial for defense from microbial infections and for clearance of immune complexes and injured cells. In normal conditions complement is tightly controlled by a number of fluid-phase and cell surface proteins to avoid injury to autologous tissues. When complement is hyperactivated, as occurs in autoimmune diseases or in subjects with dysfunctional regulatory proteins, it drives a severe inflammatory response in numerous organs. The kidney appears to be particularly vulnerable to complement-mediated inflammatory injury. Injury may derive from deposition of circulating active complement fragments in glomeruli, but complement locally produced and activated in the kidney also may have a role. Many kidney disorders have been linked to abnormal complement activation, including immune-complex–mediated glomerulonephritis and rare genetic kidney diseases, but also tubulointerstitial injury associated with progressive proteinuric diseases or ischemia-reperfusion. PMID:24161035

  5. Dietary Methanol Regulates Human Gene Activity

    PubMed Central

    Komarova, Tatiana V.; Sheshukova, Ekaterina V.; Kosorukov, Vyacheslav S.; Kiryanov, Gleb I.; Dorokhov, Yuri L.

    2014-01-01

    Methanol (MeOH) is considered to be a poison in humans because of the alcohol dehydrogenase (ADH)-mediated conversion of MeOH to formaldehyde (FA), which is toxic. Our recent genome-wide analysis of the mouse brain demonstrated that an increase in endogenous MeOH after ADH inhibition led to a significant increase in the plasma MeOH concentration and a modification of mRNA synthesis. These findings suggest endogenous MeOH involvement in homeostasis regulation by controlling mRNA levels. Here, we demonstrate directly that study volunteers displayed increasing concentrations of MeOH and FA in their blood plasma when consuming citrus pectin, ethanol and red wine. A microarray analysis of white blood cells (WBC) from volunteers after pectin intake showed various responses for 30 significantly differentially regulated mRNAs, most of which were somehow involved in the pathogenesis of Alzheimer's disease (AD). There was also a decreased synthesis of hemoglobin mRNA, HBA and HBB, the presence of which in WBC RNA was not a result of red blood cells contamination because erythrocyte-specific marker genes were not significantly expressed. A qRT-PCR analysis of volunteer WBCs after pectin and red wine intake confirmed the complicated relationship between the plasma MeOH content and the mRNA accumulation of both genes that were previously identified, namely, GAPDH and SNX27, and genes revealed in this study, including MME, SORL1, DDIT4, HBA and HBB. We hypothesized that human plasma MeOH has an impact on the WBC mRNA levels of genes involved in cell signaling. PMID:25033451

  6. 15 CFR 922.102 - Prohibited or otherwise regulated activities.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 15 Commerce and Foreign Trade 3 2012-01-01 2012-01-01 false Prohibited or otherwise regulated activities. 922.102 Section 922.102 Commerce and Foreign Trade Regulations Relating to Commerce and Foreign Trade (Continued) NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE OCEAN AND COASTAL RESOURCE MANAGEMENT NATIONAL...

  7. 15 CFR 922.193 - Prohibited or otherwise regulated activities.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 15 Commerce and Foreign Trade 3 2011-01-01 2011-01-01 false Prohibited or otherwise regulated activities. 922.193 Section 922.193 Commerce and Foreign Trade Regulations Relating to Commerce and Foreign Trade (Continued) NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE OCEAN AND COASTAL RESOURCE MANAGEMENT NATIONAL...

  8. Physical Activity and Self-Regulation Strategy Use in Adolescents

    ERIC Educational Resources Information Center

    Matthews, James; Moran, Aidan

    2011-01-01

    Objective: To examine the degree to which the use of selected theoretically derived self-regulation strategies (eg, goal setting) could predict adolescents' self-reported leisure-time physical activity behavior. Method: Two hundred thirty-three (M age = 15.88) high school students completed measures assessing their self-regulation strategy use and…

  9. 12 CFR 590.101 - State criminal usury statutes.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 12 Banks and Banking 5 2011-01-01 2011-01-01 false State criminal usury statutes. 590.101 Section 590.101 Banks and Banking OFFICE OF THRIFT SUPERVISION, DEPARTMENT OF THE TREASURY PREEMPTION OF STATE... constitution or laws of any state expressly limiting the rate or amount of interest, discount points,...

  10. 12 CFR 348.4 - Interlocking relationships permitted by statute.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... authorized on an emergency basis in accordance with section 13(k) of the Federal Deposit Insurance Act (12 U... 12 Banks and Banking 4 2011-01-01 2011-01-01 false Interlocking relationships permitted by statute... function; (b) A corporation operating under section 25 or section 25A of the Federal Reserve Act (12...

  11. 12 CFR 348.4 - Interlocking relationships permitted by statute.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... authorized on an emergency basis in accordance with section 13(k) of the Federal Deposit Insurance Act (12 U... 12 Banks and Banking 5 2014-01-01 2014-01-01 false Interlocking relationships permitted by statute... function; (b) A corporation operating under section 25 or section 25A of the Federal Reserve Act (12...

  12. 12 CFR 348.4 - Interlocking relationships permitted by statute.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... authorized on an emergency basis in accordance with section 13(k) of the Federal Deposit Insurance Act (12 U... 12 Banks and Banking 5 2013-01-01 2013-01-01 false Interlocking relationships permitted by statute... function; (b) A corporation operating under section 25 or section 25A of the Federal Reserve Act (12...

  13. 12 CFR 348.4 - Interlocking relationships permitted by statute.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... authorized on an emergency basis in accordance with section 13(k) of the Federal Deposit Insurance Act (12 U... 12 Banks and Banking 5 2012-01-01 2012-01-01 false Interlocking relationships permitted by statute... function; (b) A corporation operating under section 25 or section 25A of the Federal Reserve Act (12...

  14. Bidding Statutes and Minority Business Set-Aside Plans.

    ERIC Educational Resources Information Center

    Ottosen, Karl R.; Nathan, Robert

    1989-01-01

    Discusses the requirements of a typical bidding statute and explores the ramifications of the U.S. Supreme Court's "City of Richmond v. Crosan Company" decision for minority business (MBE) set-aside programs. School districts with MBE set-aside plans should determine whether these plans are constitutionally sufficient before beginning a public…

  15. 45 CFR 73.735-1003 - Conflicts of interest statutes.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 45 Public Welfare 1 2011-10-01 2011-10-01 false Conflicts of interest statutes. 73.735-1003 Section 73.735-1003 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION... a direct and predictable effect upon the financial interests covered by the section. However,...

  16. 10 CFR 16.19 - Statute of limitations.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... REGULATORY COMMISSION SALARY OFFSET PROCEDURES FOR COLLECTING DEBTS OWED BY FEDERAL EMPLOYEES TO THE FEDERAL GOVERNMENT § 16.19 Statute of limitations. If a debt has been outstanding for more than 10 years after the... facts material to the Government's right to collect were not known and could not reasonably have...

  17. 10 CFR 16.19 - Statute of limitations.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... REGULATORY COMMISSION SALARY OFFSET PROCEDURES FOR COLLECTING DEBTS OWED BY FEDERAL EMPLOYEES TO THE FEDERAL GOVERNMENT § 16.19 Statute of limitations. If a debt has been outstanding for more than 10 years after the... facts material to the Government's right to collect were not known and could not reasonably have...

  18. 10 CFR 16.19 - Statute of limitations.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... REGULATORY COMMISSION SALARY OFFSET PROCEDURES FOR COLLECTING DEBTS OWED BY FEDERAL EMPLOYEES TO THE FEDERAL GOVERNMENT § 16.19 Statute of limitations. If a debt has been outstanding for more than 10 years after the... facts material to the Government's right to collect were not known and could not reasonably have...

  19. 10 CFR 16.19 - Statute of limitations.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... REGULATORY COMMISSION SALARY OFFSET PROCEDURES FOR COLLECTING DEBTS OWED BY FEDERAL EMPLOYEES TO THE FEDERAL GOVERNMENT § 16.19 Statute of limitations. If a debt has been outstanding for more than 10 years after the... facts material to the Government's right to collect were not known and could not reasonably have...

  20. 10 CFR 16.19 - Statute of limitations.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... REGULATORY COMMISSION SALARY OFFSET PROCEDURES FOR COLLECTING DEBTS OWED BY FEDERAL EMPLOYEES TO THE FEDERAL GOVERNMENT § 16.19 Statute of limitations. If a debt has been outstanding for more than 10 years after the... facts material to the Government's right to collect were not known and could not reasonably have...

  1. 46 CFR 502.63 - Statute of limitations for reparations.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 9 2010-10-01 2010-10-01 false Statute of limitations for reparations. 502.63 Section 502.63 Shipping FEDERAL MARITIME COMMISSION GENERAL AND ADMINISTRATIVE PROVISIONS RULES OF PRACTICE.... (a) Complaints seeking reparation pursuant to section 11 of the Shipping Act of 1984 (46 U.S.C....

  2. Review of the Alaska Statutes for Sex Discrimination.

    ERIC Educational Resources Information Center

    Gleason, Sharon L.

    Findings of a project to review Alaska statutes for evidence of sex discrimination is divided into 14 sections. An introduction provides an overview of the project scope, history, organization, and research procedure. A section on insurance looks at gender-based insurance rates and conversion and continuation of health benefits. Under the category…

  3. 32 CFR 842.105 - Statute of limitations.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... filed after the statute has run is considered if the United States is at war or in an armed conflict when the claim accrues; or if the United States enters a war or armed conflict after the claim accrues... exist or the war or armed conflict ends. Congress or the President establishes the beginning and end...

  4. 32 CFR 644.112 - Applicable statutes in condemnation proceedings.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 32 National Defense 4 2010-07-01 2010-07-01 true Applicable statutes in condemnation proceedings. 644.112 Section 644.112 National Defense Department of Defense (Continued) DEPARTMENT OF THE ARMY (CONTINUED) REAL PROPERTY REAL ESTATE HANDBOOK Acquisition Acquisition by Condemnation Proceedings §...

  5. Renalase regulates peripheral and central dopaminergic activities

    PubMed Central

    Serrão, Maria Paula; Soares-Silva, Isabel; Fernandes-Cerqueira, Cátia; Simões-Silva, Liliana; Pinho, Maria João; Remião, Fernando; Sampaio-Maia, Benedita; Desir, Gary V.; Pestana, Manuel

    2014-01-01

    Renalase is a recently identified FAD/NADH-dependent amine oxidase mainly expressed in kidney that is secreted into blood and urine where it was suggested to metabolize catecholamines. The present study evaluated central and peripheral dopaminergic activities in the renalase knockout (KO) mouse model and examined the changes induced by recombinant renalase (RR) administration on plasma and urine catecholamine levels. Compared with wild-type (WT) mice, KO mice presented increased plasma levels of epinephrine (Epi), norepinephrine (NE), and dopamine (DA) that were accompanied by increases in the urinary excretion of Epi, NE, DA. In addition, the KO mice presented an increase in urinary DA-to-l-3,4-dihydroxyphenylalanine (l-DOPA) ratios without changes in renal tubular aromatic-l-amino acid decarboxylase (AADC) activity. By contrast, the in vivo administration of RR (1.5 mg/kg sc) to KO mice was accompanied by significant decreases in plasma levels of Epi, DA, and l-DOPA as well as in urinary excretion of Epi, DA, and DA-to-l-DOPA ratios notwithstanding the accompanied increase in renal AADC activity. In addition, the increase in renal DA output observed in renalase KO mice was accompanied by an increase in the expression of the L-type amino acid transporter like (LAT) 1 that is reversed by the administration of RR in these animals. These results suggest that the overexpression of LAT1 in the renal cortex of the renalase KO mice might contribute to the enhanced l-DOPA availability/uptake and consequently to the activation of the renal dopaminergic system in the presence of renalase deficiency. PMID:25411385

  6. Temperature Regulator for Actively Cooled Structures

    NASA Technical Reports Server (NTRS)

    Blosser, Max (Inventor); Kelly, H. Neale (Inventor)

    1995-01-01

    In active cooling of a structure it is beneficial to use a plurality of passages for conducting coolant to various portions of the structure. Since most structures do not undergo isotropic thermal loads it is desirable to allow for variation in coolant flow to each area of the structure. The present invention allows for variable flow by a variation of the area of a portion of each of the coolant passages. Shape memory alloys and bi-material springs are used to produce passages that change flow area as a function of temperature.

  7. Kinase active Misshapen regulates Notch signaling in Drosophila melanogaster.

    PubMed

    Mishra, Abhinava K; Sachan, Nalani; Mutsuddi, Mousumi; Mukherjee, Ashim

    2015-11-15

    Notch signaling pathway represents a principal cellular communication system that plays a pivotal role during development of metazoans. Drosophila misshapen (msn) encodes a protein kinase, which is related to the budding yeast Ste20p (sterile 20 protein) kinase. In a genetic screen, using candidate gene approach to identify novel kinases involved in Notch signaling, we identified msn as a novel regulator of Notch signaling. Data presented here suggest that overexpression of kinase active form of Msn exhibits phenotypes similar to Notch loss-of-function condition and msn genetically interacts with components of Notch signaling pathway. Kinase active form of Msn associates with Notch receptor and regulate its signaling activity. We further show that kinase active Misshapen leads to accumulation of membrane-tethered form of Notch. Moreover, activated Msn also depletes Armadillo and DE-Cadherin from adherens junctions. Thus, this study provides a yet unknown mode of regulation of Notch signaling by Misshapen. PMID:26431585

  8. Negative regulation of mTOR activation by diacylglycerol kinases

    PubMed Central

    Gorentla, Balachandra K.; Wan, Chi-Keung

    2011-01-01

    The engagement of TCR induces T-cell activation, which initiates multiple characteristic changes such as increase in cell size, cell division, and the production of cytokines and other effector molecules. The mammalian target of rapamycin (mTOR) regulates protein synthesis, transcription, cell survival, and autophagy. Critical roles of mTOR in T-cell activation and effector/memory differentiation have been revealed using chemical inhibitors or by genetic ablation of mTOR in T cells. However, the connection between mTOR signaling and other signaling cascades downstream of TCR is unclear. We demonstrate that diacylglycerol (DAG) and TCR engagement activate signaling in both mTOR complexes 1 and 2 through the activation of the Ras–mitogen-activated protein kinase/extracellular signal–regulated kinase 1/2 (Mek1/2)–extracellular signal–regulated kinase 1/2 (Erk1/2)–activator protein 1 (AP-1), known collectively as the Ras-Mek1/2-Erk1/2-AP-1 pathway. Deficiency of RasGRP1 or inhibition of Mek1/2 activity drastically decreases TCR-induced mTOR activation, whereas constitutively active Ras or Mek1 promotes mTOR activation. Although constitutively active Akt promotes TCR-induced mTOR activation, such activation is attenuated by Mek1/2 inhibition. We demonstrated further that DAG kinases (DGKs) α and ζ, which terminate DAG-mediated signaling, synergistically inhibit TCR-induced mTOR activation by inhibiting the Ras-Mek1/2-Erk/12 pathway. These observations provide novel insights into the regulation of mTOR activation. PMID:21310925

  9. Regulation of Activation Induced Deaminase (AID) by Estrogen.

    PubMed

    Pauklin, Siim

    2016-01-01

    Regulation of Activation Induced Deaminase (AID) by the hormone estrogen has important implications for understanding adaptive immune responses as well as the involvement of AID in autoimmune diseases and tumorigenesis. This chapter describes the general laboratory techniques for analyzing AID expression and activity induced by estrogen, focusing on the isolation and preparation of cells for hormone treatment and the subsequent analysis of AID responsiveness to estrogen at the RNA level and for determining the regulation of AID activity via estrogen by analyzing Ig switch circle transcripts and mutations in switch region loci.

  10. Absence of canonical active chromatin marks in developmentally regulated genes

    PubMed Central

    Ruiz-Romero, Marina; Corominas, Montserrat; Guigó, Roderic

    2015-01-01

    The interplay of active and repressive histone modifications is assumed to play a key role in the regulation of gene expression. In contrast to this generally accepted view, we show that transcription of genes temporally regulated during fly and worm development occurs in the absence of canonically active histone modifications. Conversely, strong chromatin marking is related to transcriptional and post-transcriptional stability, an association that we also observe in mammals. Our results support a model in which chromatin marking is associated to stable production of RNA, while unmarked chromatin would permit rapid gene activation and de-activation during development. In this case, regulation by transcription factors would play a comparatively more important regulatory role. PMID:26280901

  11. MMP-10 Regulates Collagenolytic Activity of Alternatively Activated Resident Macrophages

    PubMed Central

    Rohani, Maryam G.; McMahan, Ryan S.; Razumova, Maria V.; Hertz, Angie L.; Cieslewicz, Maryelise; Pun, Suzie H.; Regnier, Michael; Wang, Ying; Birkland, Timothy P.; Parks, William C.

    2015-01-01

    MMP-10 is expressed by macrophages and epithelium in response to injury, but its functions in wound repair are unknown. We observed increased collagen deposition and skin stiffness in Mmp10−/− wounds with no difference in collagen expression or re-epithelialization. Increased collagen deposition in Mmp10−/− wounds was accompanied by less collagenolytic activity and reduced expression of specific metallocollagenases, particularly MMP-8 and MMP-13, where MMP-13 was the key collagenase. Ablation and adoptive transfer approaches and cell-based models demonstrated that the MMP-10-dependent collagenolytic activity was a product of alternatively activated (M2) resident macrophages. These data demonstrate a critical role for macrophage MMP-10 in controlling the tissue remodeling activity of macrophages and moderating scar formation during wound repair. PMID:25927164

  12. Chromatin Remodeling Inactivates Activity Genes and Regulates Neural Coding

    PubMed Central

    Hill, Kelly K.; Hemberg, Martin; Reddy, Naveen C.; Cho, Ha Y.; Guthrie, Arden N.; Oldenborg, Anna; Heiney, Shane A.; Ohmae, Shogo; Medina, Javier F.; Holy, Timothy E.; Bonni, Azad

    2016-01-01

    Activity-dependent transcription influences neuronal connectivity, but the roles and mechanisms of inactivation of activity-dependent genes have remained poorly understood. Genome-wide analyses in the mouse cerebellum revealed that the nucleosome remodeling and deacetylase (NuRD) complex deposits the histone variant H2A.z at promoters of activity-dependent genes, thereby triggering their inactivation. Purification of translating mRNAs from synchronously developing granule neurons (Sync-TRAP) showed that conditional knockout of the core NuRD subunit Chd4 impairs inactivation of activity-dependent genes when neurons undergo dendrite pruning. Chd4 knockout or expression of NuRD-regulated activity genes impairs dendrite pruning. Imaging of behaving mice revealed hyperresponsivity of granule neurons to sensorimotor stimuli upon Chd4 knockout. Our findings define an epigenetic mechanism that inactivates activity-dependent transcription and regulates dendrite patterning and sensorimotor encoding in the brain. PMID:27418512

  13. Developmental regulation of aromatase activity in the rat hypothalamus

    SciTech Connect

    Lephart, E.D.

    1989-01-01

    The brain of all mammalian species studied thus far contain an enzymatic activity (aromatase) that catalyzes the conversion of androgens to estrogens. The activity is highest during prenatal development and contributes to the establishment of sex differences which determine adult gonadotropin secretion patterns and reproductive behavior. The studies presented in this dissertation represent a systematic effort to elucidate the mechanism(s) that control the initiation of and contribute to maintaining rat hypothalamic aromatase activity during pre- and postnatal development. Aromatase enzyme activity was measured by the {sup 3}H{sub 2}O release assay or by traditional estrogen product isolation. Brain aromatase mRNA was detected by hybridization to a cDNA encoding rat aromatase cytochrome P-450. In both males and females the time of puberty was associated with a decline in hypothalamic aromatase activity. This decline may represent a factor underlying the peri-pubertal decrease in the sensitivity to gonadal steroid feedback that accompanies completion of puberty. The results also indicate that androgens regulate brain aromatase levels during both the prepubertal and peri-pubertal stages of sexual development and that this regulation is transiently lost in young adults. Utilizing a hypothalamic organotypic culture system, aromatase activity in vitro was maintained for as long as two days. The results of studies of a variety of hormonal and metabolic regulators suggest that prenatal aromatase activity is regulated by factor(s) that function independently from the classical cyclic AMP and protein kinase C trans-membrane signaling pathways.

  14. 5 CFR 6301.102 - Prior approval for certain outside activities.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... involve conduct prohibited by statute or Federal regulations, including 5 CFR part 2635. (e) For the purposes of this section: (1) “Active participant” has the meaning set forth in 5 CFR 2635.502(b)(1)(v). (2) “Prohibited source” has the meaning set forth in 5 CFR 2635.203(d). (3) “Relates to the employee's...

  15. 5 CFR 6301.102 - Prior approval for certain outside activities.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... involve conduct prohibited by statute or Federal regulations, including 5 CFR part 2635. (e) For the purposes of this section: (1) “Active participant” has the meaning set forth in 5 CFR 2635.502(b)(1)(v). (2) “Prohibited source” has the meaning set forth in 5 CFR 2635.203(d). (3) “Relates to the employee's...

  16. 5 CFR 6301.102 - Prior approval for certain outside activities.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... involve conduct prohibited by statute or Federal regulations, including 5 CFR part 2635. (e) For the purposes of this section: (1) “Active participant” has the meaning set forth in 5 CFR 2635.502(b)(1)(v). (2) “Prohibited source” has the meaning set forth in 5 CFR 2635.203(d). (3) “Relates to the employee's...

  17. 5 CFR 6301.102 - Prior approval for certain outside activities.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... involve conduct prohibited by statute or Federal regulations, including 5 CFR part 2635. (e) For the purposes of this section: (1) “Active participant” has the meaning set forth in 5 CFR 2635.502(b)(1)(v). (2) “Prohibited source” has the meaning set forth in 5 CFR 2635.203(d). (3) “Relates to the employee's...

  18. 5 CFR 6301.102 - Prior approval for certain outside activities.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... involve conduct prohibited by statute or Federal regulations, including 5 CFR part 2635. (e) For the purposes of this section: (1) “Active participant” has the meaning set forth in 5 CFR 2635.502(b)(1)(v). (2) “Prohibited source” has the meaning set forth in 5 CFR 2635.203(d). (3) “Relates to the employee's...

  19. Judging maturity in the courts: the Massachusetts consent statute.

    PubMed

    Yates, S; Pliner, A J

    1988-06-01

    This study examined the Case Summary Questionnaires completed by attorneys representing minors at judicial consent for abortion hearings in Massachusetts and filed with the Women's Bar Association. The 477 Case Summaries filed between December 1981 and June 1985 were analyzed to provide a more systematic account of how the judicial consent statute is applied in the courtroom. After hearings which typically lasted 12 minutes, only nine minors were judged immature. No evidence for a discernible pattern justifying these rulings emerged from an examination of petitioner and court characteristics such as age, length of hearing, number of weeks pregnant, or presiding judge. Further, 11 lawyers privately reported they found their clients immature. In only one instance, however, did the lawyer and judge identify the same adolescent. The findings add to a growing body or research that calls into question the ability of the consent statute to protect the best interest of the minors involved.

  20. Adoption activities on the Internet: a call for regulation.

    PubMed

    Roby, Jini L; White, Holly

    2010-07-01

    There is a growing practice of adoption services on the Internet with varying degrees of regulation, depending on whether it is domestic infant adoption, public foster care adoption, or international adoption. Regulation is particularly lacking in domestic infant adoptions, with Web sites connecting prospective birth and adoptive parents, sometimes through an adoption brokerage service. International adoptions can also be plagued by unethical practices as the Internet has become available in both developed and developing countries. These activities, although offering the benefits of privacy and convenience, also pose serious problems of potential fraud, exploitation, and, most important, lack of professional consideration of the child's best interest. In this article, the authors review the landscape of current Internet-based adoption activities, examine the benefits and risks of Internet-based adoption activities, and call for social work self-regulation and leadership. PMID:20632655

  1. Adoption activities on the Internet: a call for regulation.

    PubMed

    Roby, Jini L; White, Holly

    2010-07-01

    There is a growing practice of adoption services on the Internet with varying degrees of regulation, depending on whether it is domestic infant adoption, public foster care adoption, or international adoption. Regulation is particularly lacking in domestic infant adoptions, with Web sites connecting prospective birth and adoptive parents, sometimes through an adoption brokerage service. International adoptions can also be plagued by unethical practices as the Internet has become available in both developed and developing countries. These activities, although offering the benefits of privacy and convenience, also pose serious problems of potential fraud, exploitation, and, most important, lack of professional consideration of the child's best interest. In this article, the authors review the landscape of current Internet-based adoption activities, examine the benefits and risks of Internet-based adoption activities, and call for social work self-regulation and leadership.

  2. Epigenetic regulator Lid maintains germline stem cells through regulating JAK-STAT signaling pathway activity

    PubMed Central

    Tarayrah, Lama; Li, Yuping; Gan, Qiang; Chen, Xin

    2015-01-01

    ABSTRACT Signaling pathways and epigenetic mechanisms have both been shown to play essential roles in regulating stem cell activity. While the role of either mechanism in this regulation is well established in multiple stem cell lineages, how the two mechanisms interact to regulate stem cell activity is not as well understood. Here we report that in the Drosophila testis, an H3K4me3-specific histone demethylase encoded by little imaginal discs (lid) maintains germline stem cell (GSC) mitotic index and prevents GSC premature differentiation. Lid is required in germ cells for proper expression of the Stat92E transcription factor, the downstream effector of the Janus kinase signal transducer and activator of transcription (JAK-STAT) signaling pathway. Our findings support a germ cell autonomous role for the JAK-STAT pathway in maintaining GSCs and place Lid as an upstream regulator of this pathway. Our study provides new insights into the biological functions of a histone demethylase in vivo and sheds light on the interaction between epigenetic mechanisms and signaling pathways in regulating stem cell activities. PMID:26490676

  3. Phosphatidylinositol-3-kinase regulates PKCtheta activity in cytotoxic T cells.

    PubMed

    Puente, Lawrence G; Mireau, Laura R; Lysechko, Tara L; Ostergaard, Hanne L

    2005-06-01

    Protein kinase C (PKC) theta plays a crucial role in T cell activation. We, therefore, examined the regulation of PKCtheta activity in cytotoxic T lymphocytes (CTL). We demonstrated that PMA did not stimulate PKCtheta activation and phospholipase C inhibition did not block anti-CD3-stimulated PKCtheta activation in a CTL clone. This suggests that diacylglycerol is neither sufficient nor required for PKCtheta activation. Furthermore, PKCtheta was only activated in a CTL clone stimulated with plate-bound anti-CD3 but not soluble anti-CD3. However, PMA or cross-linked anti-CD3 stimulated phosphorylation of PKCtheta as measured by a migratory shift, suggesting that phosphorylation was not sufficient for activity. Phosphatidylinositol 3-kinase activity was required for anti-CD3, but not PMA, stimulated phosphorylation and for immobilized anti-CD3-triggered PKCtheta activity. A substantial fraction of PKCtheta was constitutively membrane associated and PMA or CD3 stimulation did not significantly increase membrane association. Our data indicate that phosphorylation of PKCtheta is not a suitable surrogate measurement for PKCtheta activity and that additional, yet to be defined steps, are required for the regulation of PKCtheta enzymatic activity in CTL.

  4. Extracellular Matrix Stiffness Regulates Osteogenic Differentiation through MAPK Activation

    PubMed Central

    Hwang, Jun-Ha; Byun, Mi Ran; Kim, A. Rum; Kim, Kyung Min; Cho, Hang Jun; Lee, Yo Han; Kim, Juwon; Jeong, Mi Gyeong; Hwang, Eun Sook; Hong, Jeong-Ho

    2015-01-01

    Mesenchymal stem cell (MSC) differentiation is regulated by the extracellular matrix (ECM) through activation of intracellular signaling mediators. The stiffness of the ECM was shown to be an important regulatory factor for MSC differentiation, and transcriptional coactivator with PDZ-binding motif (TAZ) was identified as an effector protein for MSC differentiation. However, the detailed underlying mechanism regarding the role of ECM stiffness and TAZ in MSC differentiation is not yet fully understood. In this report, we showed that ECM stiffness regulates MSC fate through ERK or JNK activation. Specifically, a stiff hydrogel matrix stimulates osteogenic differentiation concomitant with increased nuclear localization of TAZ, but inhibits adipogenic differentiation. ERK and JNK activity was significantly increased in cells cultured on a stiff hydrogel. TAZ activation was induced by ERK or JNK activation on a stiff hydrogel because exposure to an ERK or JNK inhibitor significantly decreased the nuclear localization of TAZ, indicating that ECM stiffness-induced ERK or JNK activation is important for TAZ-driven osteogenic differentiation. Taken together, these results suggest that ECM stiffness regulates MSC differentiation through ERK or JNK activation. PMID:26262877

  5. Extracellular Matrix Stiffness Regulates Osteogenic Differentiation through MAPK Activation.

    PubMed

    Hwang, Jun-Ha; Byun, Mi Ran; Kim, A Rum; Kim, Kyung Min; Cho, Hang Jun; Lee, Yo Han; Kim, Juwon; Jeong, Mi Gyeong; Hwang, Eun Sook; Hong, Jeong-Ho

    2015-01-01

    Mesenchymal stem cell (MSC) differentiation is regulated by the extracellular matrix (ECM) through activation of intracellular signaling mediators. The stiffness of the ECM was shown to be an important regulatory factor for MSC differentiation, and transcriptional coactivator with PDZ-binding motif (TAZ) was identified as an effector protein for MSC differentiation. However, the detailed underlying mechanism regarding the role of ECM stiffness and TAZ in MSC differentiation is not yet fully understood. In this report, we showed that ECM stiffness regulates MSC fate through ERK or JNK activation. Specifically, a stiff hydrogel matrix stimulates osteogenic differentiation concomitant with increased nuclear localization of TAZ, but inhibits adipogenic differentiation. ERK and JNK activity was significantly increased in cells cultured on a stiff hydrogel. TAZ activation was induced by ERK or JNK activation on a stiff hydrogel because exposure to an ERK or JNK inhibitor significantly decreased the nuclear localization of TAZ, indicating that ECM stiffness-induced ERK or JNK activation is important for TAZ-driven osteogenic differentiation. Taken together, these results suggest that ECM stiffness regulates MSC differentiation through ERK or JNK activation.

  6. Minimal regulation of platelet activity by PECAM-1.

    PubMed

    Dhanjal, Tarvinder S; Ross, Ewan A; Auger, Jocelyn M; McCarty, Owen J T; Hughes, Craig E; Senis, Yotis A; Buckley, Chris D; Watson, Steve P

    2007-02-01

    PECAM-1 is a member of the superfamily of immunoglobulins (Ig) and is expressed on platelets at moderate level. PECAM-1 has been reported to have contrasting effects on platelet activation by the collagen receptor GPVI and the integrin, alphaIIbbeta3, even though both receptors signal through Src-kinase regulation of PLCgamma2. The present study compares the role of PECAM-1 on platelet activation by these two receptors and by the lectin receptor, CLEC-2, which also signals via PLCgamma2. Studies using PECAM-1 knockout-mice and cross-linking of PECAM-1 using specific antibodies demonstrated a minor inhibitory role on platelet responses to the above three receptors and also under some conditions to the G-protein agonist thrombin. The degree of inhibition was considerably less than that produced by PGI2, which elevates cAMP. There was no significant difference in thrombus formation on collagen in PECAM-1-/- platelets relative to litter-matched controls. The very weak inhibitory effect of PECAM-1 on platelet activation relative to that of PGI2 indicate that the Ig-receptor is not a major regulator of platelet activation. PECAM-1 has been reported to have contrasting effects on platelet activation. The present study demonstrates a very mild or negligible effect on platelet activation in response to stimulation by a variety of agonists, thereby questioning the physiological role of the immunoglobulin receptor as a major regulator of platelet activation. PMID:17365855

  7. Spectrin regulates Hippo signaling by modulating cortical actomyosin activity

    PubMed Central

    Deng, Hua; Wang, Wei; Yu, Jianzhong; Zheng, Yonggang; Qing, Yun; Pan, Duojia

    2015-01-01

    The Hippo pathway controls tissue growth through a core kinase cascade that impinges on the transcription of growth-regulatory genes. Understanding how this pathway is regulated in development remains a major challenge. Recent studies suggested that Hippo signaling can be modulated by cytoskeletal tension through a Rok-myosin II pathway. How cytoskeletal tension is regulated or its relationship to the other known upstream regulators of the Hippo pathway remains poorly defined. In this study, we identify spectrin, a contractile protein at the cytoskeleton-membrane interface, as an upstream regulator of the Hippo signaling pathway. We show that, in contrast to canonical upstream regulators such as Crumbs, Kibra, Expanded, and Merlin, spectrin regulates Hippo signaling in a distinct way by modulating cortical actomyosin activity through non-muscle myosin II. These results uncover an essential mediator of Hippo signaling by cytoskeleton tension, providing a new entry point to dissecting how mechanical signals regulate Hippo signaling in living tissues. DOI: http://dx.doi.org/10.7554/eLife.06567.001 PMID:25826608

  8. Myths and facts about Minnesota's new safe patient handling statute and your dental practice.

    PubMed

    Shuman, Stephen; Simonson, Peggy; Tschida, Breca; Owen, Mary; Ofstehage, John; Glasrud, Patricia

    2011-01-01

    With the passage of a safe patient handling statute in 2009, Minnesota became one of a growing number of states requiring health care providers to become more aware and accountable about providing appropriate assistance during the movement of patients in clinical care settings. The Minnesota Department of Labor and Industry and the Minnesota Dental Association have been working together to ensure that Minnesota's SPH regulations are as practical as possible for dental providers while still achieving the objectives of the statute. A template Safe Patient Handling Program for Clinics has been developed with substantial input from MDA's ESNA Committee and is now available on the DLI website: www.dli.mn.gov/WSC/SPHlegislation.asp. All Minnesota dental practices should use this template to develop their own safe patient handling program as soon as possible. Additional background information and resources related to Minnesota's SPH regulations are also available on the DLI website. MDA and DLI are currently also developing a hazard assessment tool for dental practices to assess their specific risks associated with patient movement. This hazard assessment will, in turn, guide decisions about what type of safe patient handling equipment and staff training will be necessary for total compliance with the new statute. MDA, in cooperation with DLI, will continue to keep dental professionals informed about when these materials will be available. Additionally, MDA is working to ensure appropriate training options will be available for compliance with SPH regulations. The University of Minnesota's School of Dentistry's Oral Health Services for Older Adults Program and Department of Continuing Dental Education have been regularly providing such training in conjunction with the school's "Miniresidency in Nursing Home and Long-term Care for the Dental Team," and efforts are now underway at the dental school to create stand-alone training options for Minnesota's dental professionals

  9. Myths and facts about Minnesota's new safe patient handling statute and your dental practice.

    PubMed

    Shuman, Stephen; Simonson, Peggy; Tschida, Breca; Owen, Mary; Ofstehage, John; Glasrud, Patricia

    2011-01-01

    With the passage of a safe patient handling statute in 2009, Minnesota became one of a growing number of states requiring health care providers to become more aware and accountable about providing appropriate assistance during the movement of patients in clinical care settings. The Minnesota Department of Labor and Industry and the Minnesota Dental Association have been working together to ensure that Minnesota's SPH regulations are as practical as possible for dental providers while still achieving the objectives of the statute. A template Safe Patient Handling Program for Clinics has been developed with substantial input from MDA's ESNA Committee and is now available on the DLI website: www.dli.mn.gov/WSC/SPHlegislation.asp. All Minnesota dental practices should use this template to develop their own safe patient handling program as soon as possible. Additional background information and resources related to Minnesota's SPH regulations are also available on the DLI website. MDA and DLI are currently also developing a hazard assessment tool for dental practices to assess their specific risks associated with patient movement. This hazard assessment will, in turn, guide decisions about what type of safe patient handling equipment and staff training will be necessary for total compliance with the new statute. MDA, in cooperation with DLI, will continue to keep dental professionals informed about when these materials will be available. Additionally, MDA is working to ensure appropriate training options will be available for compliance with SPH regulations. The University of Minnesota's School of Dentistry's Oral Health Services for Older Adults Program and Department of Continuing Dental Education have been regularly providing such training in conjunction with the school's "Miniresidency in Nursing Home and Long-term Care for the Dental Team," and efforts are now underway at the dental school to create stand-alone training options for Minnesota's dental professionals

  10. Regulation of APC Activity by Phosphorylation and Regulatory Factors

    PubMed Central

    Kotani, Shuji; Tanaka, Hirofumi; Yasuda, Hideyo; Todokoro, Kazuo

    1999-01-01

    Ubiquitin-dependent proteolysis of Cut2/Pds1 and Cyclin B is required for sister chromatid separation and exit from mitosis, respectively. Anaphase-promoting complex/cyclosome (APC) specifically ubiquitinates Cut2/Pds1 at metaphase–anaphase transition, and ubiquitinates Cyclin B in late mitosis and G1 phase. However, the exact regulatory mechanism of substrate-specific activation of mammalian APC with the right timing remains to be elucidated. We found that not only the binding of the activators Cdc20 and Cdh1 and the inhibitor Mad2 to APC, but also the phosphorylation of Cdc20 and Cdh1 by Cdc2-Cyclin B and that of APC by Polo-like kinase and cAMP-dependent protein kinase, regulate APC activity. The cooperation of the phosphorylation/dephosphorylation and the regulatory factors in regulation of APC activity may thus control the precise progression of mitosis. PMID:10459014

  11. Active Inference, homeostatic regulation and adaptive behavioural control

    PubMed Central

    Pezzulo, Giovanni; Rigoli, Francesco; Friston, Karl

    2015-01-01

    We review a theory of homeostatic regulation and adaptive behavioural control within the Active Inference framework. Our aim is to connect two research streams that are usually considered independently; namely, Active Inference and associative learning theories of animal behaviour. The former uses a probabilistic (Bayesian) formulation of perception and action, while the latter calls on multiple (Pavlovian, habitual, goal-directed) processes for homeostatic and behavioural control. We offer a synthesis these classical processes and cast them as successive hierarchical contextualisations of sensorimotor constructs, using the generative models that underpin Active Inference. This dissolves any apparent mechanistic distinction between the optimization processes that mediate classical control or learning. Furthermore, we generalize the scope of Active Inference by emphasizing interoceptive inference and homeostatic regulation. The ensuing homeostatic (or allostatic) perspective provides an intuitive explanation for how priors act as drives or goals to enslave action, and emphasises the embodied nature of inference. PMID:26365173

  12. Active Inference, homeostatic regulation and adaptive behavioural control.

    PubMed

    Pezzulo, Giovanni; Rigoli, Francesco; Friston, Karl

    2015-11-01

    We review a theory of homeostatic regulation and adaptive behavioural control within the Active Inference framework. Our aim is to connect two research streams that are usually considered independently; namely, Active Inference and associative learning theories of animal behaviour. The former uses a probabilistic (Bayesian) formulation of perception and action, while the latter calls on multiple (Pavlovian, habitual, goal-directed) processes for homeostatic and behavioural control. We offer a synthesis these classical processes and cast them as successive hierarchical contextualisations of sensorimotor constructs, using the generative models that underpin Active Inference. This dissolves any apparent mechanistic distinction between the optimization processes that mediate classical control or learning. Furthermore, we generalize the scope of Active Inference by emphasizing interoceptive inference and homeostatic regulation. The ensuing homeostatic (or allostatic) perspective provides an intuitive explanation for how priors act as drives or goals to enslave action, and emphasises the embodied nature of inference. PMID:26365173

  13. Neural progenitor cells regulate microglia functions and activity.

    PubMed

    Mosher, Kira I; Andres, Robert H; Fukuhara, Takeshi; Bieri, Gregor; Hasegawa-Moriyama, Maiko; He, Yingbo; Guzman, Raphael; Wyss-Coray, Tony

    2012-11-01

    We found mouse neural progenitor cells (NPCs) to have a secretory protein profile distinct from other brain cells and to modulate microglial activation, proliferation and phagocytosis. NPC-derived vascular endothelial growth factor was necessary and sufficient to exert at least some of these effects in mice. Thus, neural precursor cells may not only be shaped by microglia, but also regulate microglia functions and activity.

  14. Regulation of p53 and MDM2 Activity by MTBP

    PubMed Central

    Brady, Mark; Vlatković, Nikolina; Boyd, Mark T.

    2005-01-01

    p53 is a critical coordinator of a wide range of stress responses. To facilitate a rapid response to stress, p53 is produced constitutively but is negatively regulated by MDM2. MDM2 can inhibit p53 in multiple independent ways: by binding to its transcription activation domain, inhibiting p53 acetylation, promoting nuclear export, and probably most importantly by promoting proteasomal degradation of p53. The latter is achieved via MDM2's E3 ubiquitin ligase activity harbored within the MDM2 RING finger domain. We have discovered that MTBP promotes MDM2-mediated ubiquitination and degradation of p53 and also MDM2 stabilization in an MDM2 RING finger-dependent manner. Moreover, using small interfering RNA to down-regulate endogenous MTBP in unstressed cells, we have found that MTBP significantly contributes to MDM2-mediated regulation of p53 levels and activity. However, following exposure of cells to UV, but not γ-irradiation, MTBP is destabilized as part of the coordinated cellular response. Our findings suggest that MTBP differentially regulates the E3 ubiquitin ligase activity of MDM2 towards two of its most critical targets (itself and p53) and in doing so significantly contributes to MDM2-dependent p53 homeostasis in unstressed cells. PMID:15632057

  15. 15 CFR 922.193 - Prohibited or otherwise regulated activities.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... Sanctuary and Underwater Preserve § 922.193 Prohibited or otherwise regulated activities. (a) Except as..., destroying, possessing, or attempting to recover, alter, destroy, or possess an underwater cultural resource. (2) Drilling into, dredging or otherwise altering the lakebottom associated with underwater...

  16. 76 FR 19120 - Agency Information Collection Activities: Drawback Process Regulations

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-04-06

    ... SECURITY U.S. Customs and Border Protection Agency Information Collection Activities: Drawback Process... Drawback Process Regulations (CBP Forms 7551, 7552 and 7553). This request for comment is being made... CBP is soliciting comments concerning the following information collection: Title: Drawback...

  17. 76 FR 44350 - Agency Information Collection Activities: Drawback Process Regulations

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-07-25

    ... collection was previously published in the Federal Register (76 FR 19120) on April 6, 2011, allowing for a 60... SECURITY U.S. CUSTOMS AND BORDER PROTECTION Agency Information Collection Activities: Drawback Process... approval in accordance with the Paperwork Reduction Act: Drawback Process Regulations (CBP Forms 7551,...

  18. Signal integration by Ca2+ regulates intestinal stem cell activity

    PubMed Central

    Deng, Hansong; Gerencser, Akos A.; Jasper, Heinrich

    2015-01-01

    Summary Somatic stem cells (SCs) maintain tissue homeostasis by dynamically adjusting proliferation and differentiation in response to stress and metabolic cues. Here, we identify Ca2+ signaling as a central regulator of intestinal SC (ISC) activity in Drosophila. We find that dietary L-glutamate stimulates ISC division and gut growth. The metabotropic glutamate receptor (mGluR) is required in ISCs for this response and for an associated modulation of cytosolic Ca2+ oscillations that results in sustained high cytosolic Ca2+ concentrations. High cytosolic Ca2+ induces ISC proliferation by regulating Calcineurin and CREB - regulated transcriptional co-activator (CRTC). In response to a wide range of dietary and stress stimuli, ISCs reversibly transition between Ca2+ oscillation states that represent poised or activated modes of proliferation, respectively. We propose that the dynamic regulation of intracellular Ca2+ levels allows effective integration of diverse mitogenic signals in ISCs to tailor their proliferative activity to the needs of the tissue. PMID:26633624

  19. 76 FR 28801 - Agency Information Collection Activities: Bonded Warehouse Regulations

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-05-18

    ... Federal Register (76 FR 11254) on March 1, 2011, allowing for a 60-day comment period. This notice allows... SECURITY U.S. Customs and Border Protection Agency Information Collection Activities: Bonded Warehouse... approval in accordance with the Paperwork Reduction Act: Bonded Warehouse Regulations. This is a...

  20. Structural basis of AMPK regulation by small molecule activators

    NASA Astrophysics Data System (ADS)

    Xiao, Bing; Sanders, Matthew J.; Carmena, David; Bright, Nicola J.; Haire, Lesley F.; Underwood, Elizabeth; Patel, Bhakti R.; Heath, Richard B.; Walker, Philip A.; Hallen, Stefan; Giordanetto, Fabrizio; Martin, Stephen R.; Carling, David; Gamblin, Steven J.

    2013-12-01

    AMP-activated protein kinase (AMPK) plays a major role in regulating cellular energy balance by sensing and responding to increases in AMP/ADP concentration relative to ATP. Binding of AMP causes allosteric activation of the enzyme and binding of either AMP or ADP promotes and maintains the phosphorylation of threonine 172 within the activation loop of the kinase. AMPK has attracted widespread interest as a potential therapeutic target for metabolic diseases including type 2 diabetes and, more recently, cancer. A number of direct AMPK activators have been reported as having beneficial effects in treating metabolic diseases, but there has been no structural basis for activator binding to AMPK. Here we present the crystal structure of human AMPK in complex with a small molecule activator that binds at a site between the kinase domain and the carbohydrate-binding module, stabilising the interaction between these two components. The nature of the activator-binding pocket suggests the involvement of an additional, as yet unidentified, metabolite in the physiological regulation of AMPK. Importantly, the structure offers new opportunities for the design of small molecule activators of AMPK for treatment of metabolic disorders.

  1. Activity-dependent regulation of astrocyte GAT levels during synaptogenesis

    PubMed Central

    Muthukumar, Allie K.; Stork, Tobias; Freeman, Marc R.

    2014-01-01

    Astrocytic uptake of GABA through GABA transporters (GATs) is an important mechanism regulating excitatory/inhibitory balance in the nervous system, however mechanisms by which astrocytes regulate GAT levels are undefined. Here we show at mid-pupal stages the Drosophila CNS neuropil is devoid of astrocyte membranes and synapses. Astrocyte membranes subsequently infiltrate the neuropil coordinate with synaptogenesis and a strocyte ablation reduces synapse numbers by half, indicating that Drosophila astrocytes are pro-synaptogenic. Shortly after synapses form in earnest, the GABA transporter, GAT, is up-regulated in astrocytes. Ablation or silencing of GABAergic neurons or disruption of metabotropic GABA receptor (GABABR1/2) signaling in astrocytes leads to decreased astrocytic GAT levels. Interestingly, developmental depletion of astrocytic GABABR1/2 signaling suppresses mechanosensory-induced seizure activity in mutants with hyperexcitable neurons. These data reveal astrocytes actively modulate GAT expression via metabotropic GABA receptor signaling, and highlight the importance of precise regulation of astrocytic GAT in modulation of seizure activity. PMID:25151265

  2. Tetraspanin CD9 regulates osteoclastogenesis via regulation of p44/42 MAPK activity

    SciTech Connect

    Yi, TacGhee; Kim, Hye-Jin; Cho, Je-Yoel; Woo, Kyung Mi; Ryoo, Hyun-Mo; Kim, Gwan-Shik; Baek, Jeong-Hwa . E-mail: baekjh@snu.ac.kr

    2006-08-18

    Tetraspanin CD9 has been shown to regulate cell-cell fusion in sperm-egg fusion and myotube formation. However, the role of CD9 in osteoclast, another multinucleated cell type, is not still clear. Therefore, we investigated the role of CD9 in osteoclast differentiation. CD9 was expressed in osteoclast lineage cells and its expression level increased during the progression of RANKL-induced osteoclastogenesis. KMC8, a neutralizing antibody specific to CD9, significantly suppressed RANKL-induced multinucleated osteoclast formation and the mRNA expression of osteoclast differentiation marker genes. To define CD9-regulated osteoclastogenic signaling pathway, MAPK pathways were examined. KMC8 induced long-term phosphorylation of p44/42 MAPK, but not of p38 MAPK. Constitutive activation of p44/42 MAPK by overexpressing constitutive-active mutant of MEK1 almost completely blocked osteoclast differentiation. Taken together, these results suggest that CD9 expressed on osteoclast lineage cells might positively regulate osteoclastogenesis via the regulation of p44/42 MAPK activity.

  3. Regulation of different human NFAT isoforms by neuronal activity.

    PubMed

    Vihma, Hanna; Luhakooder, Mirjam; Pruunsild, Priit; Timmusk, Tõnis

    2016-05-01

    Nuclear factor of activated T-cells (NFAT) is a family of transcription factors comprising four calcium-regulated members: NFATc1, NFATc2, NFATc3, and NFATc4. Upon activation by the calcium-dependent phosphatase calcineurin (CaN), NFATs translocate from cytosol to the nucleus and regulate their target genes, which in the nervous system are involved in axon growth, synaptic plasticity, and neuronal survival. We have shown previously that there are a number of different splice variants of NFAT genes expressed in the brain. Here, we studied the subcellular localizations and transactivation capacities of alternative human NFAT isoforms in rat primary cortical or hippocampal neurons in response to membrane depolarization and compared the induced transactivation levels in neurons to those obtained from HEK293 cells in response to calcium signaling. We confirm that in neurons the translocation to the nucleus of all NFAT isoforms is reliant on the activity of CaN. However, our results suggest that both the regulation of subcellular localization and transcriptional activity of NFAT proteins in neurons is isoform specific. We show that in primary hippocampal neurons NFATc2 isoforms have very fast translocation kinetics, whereas NFATc4 isoforms translocate relatively slowly to the nucleus. Moreover, we demonstrate that the strongest transcriptional activators in HEK293 cells are NFATc1 and NFATc3, but in neurons NFATc3 and NFATc4 lead to the highest induction, and NFATc2 and NFATc1 display isoform-specific transcription activation capacities. Altogether, our results indicate that the effects of calcium signaling on the action of NFAT proteins are isoform-specific and can differ between cell types. We show that the effects of calcium signaling on the action of NFAT proteins are isoform-specific and differ between cell types. Although nuclear localization of all NFAT isoforms in neurons requires calcineurin, the subcellular distributions, neuronal activity-induced nuclear

  4. Bassoon and piccolo regulate ubiquitination and link presynaptic molecular dynamics with activity-regulated gene expression.

    PubMed

    Ivanova, Daniela; Dirks, Anika; Fejtova, Anna

    2016-10-01

    Release of neurotransmitter is executed by complex multiprotein machinery, which is assembled around the presynaptic cytomatrix at the active zone. One well-established function of this proteinaceous scaffold is the spatial organization of synaptic vesicle cluster, the protein complexes that execute membrane fusion and compensatory endocytosis, and the transmembrane molecules important for alignment of pre- and postsynaptic structures. The presynaptic cytomatrix proteins function also in processes other than the formation of a static frame for assembly of the release apparatus and synaptic vesicle cycling. They actively contribute to the regulation of multiple steps in this process and are themselves an important subject of regulation during neuronal plasticity. We are only beginning to understand the mechanisms and signalling pathways controlling these regulations. They are mainly dependent on posttranslational modifications, including phosphorylation and small-molecules conjugation, such as ubiquitination. Ubiquitination of presynaptic proteins might lead to their degradation by proteasomes, but evidence is growing that this modification also affects their function independently of their degradation. Signalling from presynapse to nucleus, which works on a much slower time scale and more globally, emerged as an important mechanism for persistent usage-dependent and homeostatic neuronal plasticity. Recently, two new functions for the largest presynaptic scaffolding proteins bassoon and piccolo emerged. They were implied (1) in the regulation of specific protein ubiquitination and proteasome-mediated proteolysis that potentially contributes to short-term plasticity at the presynapse and (2) in the coupling of activity-induced molecular rearrangements at the presynapse with reprogramming of expression of neuronal activity-regulated genes.

  5. Interleukin 2 activates extracellular signal-regulated protein kinase 2

    PubMed Central

    1993-01-01

    Interleukin 2 (IL-2) stimulated activation of the 42-kD extracellular signal-regulated kinase 2 (Erk2) in murine IL-3-dependent cells, expressing either high or intermediate affinity IL-2 receptors. Activation was both rapid, occurring within 5 min of IL-2 addition, and prolonged, remaining elevated for 30 min. Activation of Erk2 appeared to be necessary for IL-2 stimulation of proliferation, as deletion of a region of the cytoplasmic domain of the IL-2 receptor beta chain, essential for IL-2 stimulation of proliferation, abolished Erk2 activation by IL-2. Furthermore, cells that had been deprived of cytokine for 24 h were then refractory to IL-2 stimulation of both Erk2 activity and proliferation. However, elevation of Erk2 activity was not sufficient to stimulate proliferation, as protein kinase C activation stimulated Erk2 activity but not DNA synthesis. Also, cells exposed to IL-2 in the presence of rapamycin showed full Erk2 activation but not DNA synthesis. These data suggest that IL-2 must stimulate both Erk2 activity and a further pathway(s) to trigger cell proliferation. PMID:8376945

  6. Alexithymia influences brain activation during emotion perception but not regulation

    PubMed Central

    Gromann, Paula M.; Swart, Marte; Wiersma, Durk; de Haan, Lieuwe; Bruggeman, Richard; Krabbendam, Lydia; Aleman, André

    2015-01-01

    Alexithymia is a psychological construct that can be divided into a cognitive and affective dimension. The cognitive dimension is characterized by difficulties in identifying, verbalizing and analysing feelings. The affective dimension comprises reduced levels of emotional experience and imagination. Alexithymia is widely regarded to arise from an impairment of emotion regulation. This is the first functional magnetic resonance imaging (fMRI) study to critically evaluate this by investigating the neural correlates of emotion regulation as a function of alexithymia levels. The aim of the current study was to investigate the neural correlates underlying the two alexithymia dimensions during emotion perception and emotion regulation. Using fMRI, we scanned 51 healthy subjects while viewing, reappraising or suppressing negative emotional pictures. The results support the idea that cognitive alexithymia, but not affective alexithymia, is associated with lower activation in emotional attention and recognition networks during emotion perception. However, in contrast with several theories, no alexithymia-related differences were found during emotion regulation (neither reappraisal nor suppression). These findings suggest that alexithymia may result from an early emotion processing deficit rather than compromised frontal circuits subserving higher-order emotion regulation processes. PMID:24760016

  7. Flavonoids as dietary regulators of nuclear receptor activity

    PubMed Central

    Avior, Yishai; Bomze, David; Ramon, Ory

    2013-01-01

    Metabolic diseases such as obesity, type II diabetes, and dyslipidemia are a rising cause of mortality worldwide. The progression of many metabolic diseases is fundamentally regulated on the transcriptional level by a family of ligand-activated transcription factors, called nuclear receptors, which detect and respond to metabolic changes. Their role in maintaining metabolic homeostasis makes nuclear receptors an important pharmaceutical and dietary target. This review will present the growing evidence that flavonoids, natural secondary plant metabolites, are important regulators of nuclear receptor activity. Structural similarities between flavonoids and cholesterol derivatives combined with the promiscuous nature of most nuclear receptors provide a wealth of possibilities for pharmaceutical and dietary modulation of metabolism. While the challenges of bringing flavonoid-derived therapeutics to the market are significant, we consider this rapidly growing field to be an essential aspect of the functional food initiative and an important mine for pharmaceutical compounds. PMID:23598551

  8. Commercial Activities in Schools: Use of Student Data Is Limited and Additional Dissemination of Guidance Could Help Districts Develop Policies. Report to Congressional Requesters. GAO-04-810.

    ERIC Educational Resources Information Center

    Shaul, Marnie S.

    2004-01-01

    This study examined (1) the extent to which, since 2000, states have enacted and proposed statutes and regulations to govern commercial activities in schools; (2) the extent to which districts have developed policies implementing amended provisions of the Protection of Pupil Rights Amendment (PPRA) in the No Child Left Behind Act on the use of…

  9. Harvester ants use interactions to regulate forager activation and availability

    PubMed Central

    Pinter-Wollman, Noa; Bala, Ashwin; Merrell, Andrew; Queirolo, Jovel; Stumpe, Martin C.; Holmes, Susan; Gordon, Deborah M.

    2013-01-01

    Social groups balance flexibility and robustness in their collective response to environmental changes using feedback between behavioural processes that operate at different timescales. Here we examine how behavioural processes operating at two timescales regulate the foraging activity of colonies of the harvester ant, Pogonomyrmex barbatus, allowing them to balance their response to food availability and predation. Previous work showed that the rate at which foragers return to the nest with food influences the rate at which foragers leave the nest. To investigate how interactions inside the nest link the rates of returning and outgoing foragers, we observed outgoing foragers inside the nest in field colonies using a novel observation method. We found that the interaction rate experienced by outgoing foragers inside the nest corresponded to forager return rate, and that the interactions of outgoing foragers were spatially clustered. Activation of a forager occurred on the timescale of seconds: a forager left the nest 3–8 s after a substantial increase in interactions with returning foragers. The availability of outgoing foragers to become activated was adjusted on the timescale of minutes: when forager return was interrupted for more than 4–5 min, available foragers waiting near the nest entrance went deeper into the nest. Thus, forager activation and forager availability both increased with the rate at which foragers returned to the nest. This process was checked by negative feedback between forager activation and forager availability. Regulation of foraging activation on the timescale of seconds provides flexibility in response to fluctuations in food abundance, whereas regulation of forager availability on the timescale of minutes provides robustness in response to sustained disturbance such as predation. PMID:24031094

  10. Harvester ants use interactions to regulate forager activation and availability.

    PubMed

    Pinter-Wollman, Noa; Bala, Ashwin; Merrell, Andrew; Queirolo, Jovel; Stumpe, Martin C; Holmes, Susan; Gordon, Deborah M

    2013-07-01

    Social groups balance flexibility and robustness in their collective response to environmental changes using feedback between behavioural processes that operate at different timescales. Here we examine how behavioural processes operating at two timescales regulate the foraging activity of colonies of the harvester ant, Pogonomyrmex barbatus, allowing them to balance their response to food availability and predation. Previous work showed that the rate at which foragers return to the nest with food influences the rate at which foragers leave the nest. To investigate how interactions inside the nest link the rates of returning and outgoing foragers, we observed outgoing foragers inside the nest in field colonies using a novel observation method. We found that the interaction rate experienced by outgoing foragers inside the nest corresponded to forager return rate, and that the interactions of outgoing foragers were spatially clustered. Activation of a forager occurred on the timescale of seconds: a forager left the nest 3-8 s after a substantial increase in interactions with returning foragers. The availability of outgoing foragers to become activated was adjusted on the timescale of minutes: when forager return was interrupted for more than 4-5 min, available foragers waiting near the nest entrance went deeper into the nest. Thus, forager activation and forager availability both increased with the rate at which foragers returned to the nest. This process was checked by negative feedback between forager activation and forager availability. Regulation of foraging activation on the timescale of seconds provides flexibility in response to fluctuations in food abundance, whereas regulation of forager availability on the timescale of minutes provides robustness in response to sustained disturbance such as predation.

  11. Activity-dependent regulation of astrocyte GAT levels during synaptogenesis.

    PubMed

    Muthukumar, Allie K; Stork, Tobias; Freeman, Marc R

    2014-10-01

    Astrocytic uptake of GABA through GABA transporters (GATs) is an important mechanism regulating excitatory/inhibitory balance in the nervous system; however, mechanisms by which astrocytes regulate GAT levels are undefined. We found that at mid-pupal stages the Drosophila melanogaster CNS neuropil was devoid of astrocyte membranes and synapses. Astrocyte membranes subsequently infiltrated the neuropil coordinately with synaptogenesis, and astrocyte ablation reduced synapse numbers by half, indicating that Drosophila astrocytes are pro-synaptogenic. Shortly after synapses formed in earnest, GAT was upregulated in astrocytes. Ablation or silencing of GABAergic neurons or disruption of metabotropic GABA receptor 1 and 2 (GABA(B)R1/2) signaling in astrocytes led to a decrease in astrocytic GAT. Notably, developmental depletion of astrocytic GABA(B)R1/2 signaling suppressed mechanosensory-induced seizure activity in mutants with hyperexcitable neurons. These data reveal that astrocytes actively modulate GAT expression via metabotropic GABA receptor signaling and highlight the importance of precise regulation of astrocytic GAT in modulation of seizure activity.

  12. Myocardin Regulates Vascular Smooth Muscle Cell Inflammatory Activation and Disease

    PubMed Central

    Ackers-Johnson, Matthew; Talasila, Amarnath; Sage, Andrew P; Long, Xiaochun; Bot, Ilze; Morrell, Nicholas W; Bennett, Martin R; Miano, Joseph M.; Sinha, Sanjay

    2015-01-01

    Objective Atherosclerosis, the cause of 50% of deaths in westernised societies, is widely regarded as a chronic vascular inflammatory disease. Vascular smooth muscle cell (VSMC) inflammatory activation in response to local pro-inflammatory stimuli contributes to disease progression and is a pervasive feature in developing atherosclerotic plaques. Therefore, it is of considerable therapeutic importance to identify mechanisms that regulate the VSMC inflammatory response. Approach and Results We report that myocardin, a powerful myogenic transcriptional coactivator, negatively regulates VSMC inflammatory activation and vascular disease. Myocardin levels are reduced during atherosclerosis, in association with phenotypic switching of smooth muscle cells. Myocardin deficiency accelerates atherogenesis in hypercholesterolemic ApoE−/− mice. Conversely, increased myocardin expression potently abrogates the induction of an array of inflammatory cytokines, chemokines and adhesion molecules in VSMCs. Expression of myocardin in VSMCs reduces lipid uptake, macrophage interaction, chemotaxis and macrophage-endothelial tethering in vitro, and attenuates monocyte accumulation within developing lesions in vivo. These results demonstrate that endogenous levels of myocardin are a critical regulator of vessel inflammation. Conclusions We propose myocardin as a guardian of the contractile, non-inflammatory VSMC phenotype, with loss of myocardin representing a critical permissive step in the process of phenotypic transition and inflammatory activation, at the onset of vascular disease. PMID:25614278

  13. Disorders of regulation of cognitive activity in autistic children.

    PubMed

    Adrien, J L; Martineau, J; Barthélémy, C; Bruneau, N; Garreau, B; Sauvage, D

    1995-06-01

    Infantile autism is a pervasive developmental disorder characterized by disturbances concerning not only the areas of socialization and communication ("aloneness") but also the ability to modify and change behavior ("need for sameness"). In most recent studies, various abnormal and deviant cognitive activities, such as the ability to regulate one's behavior, were considered as accounting for these signs. In this report, we examined the regulation of cognitive activity, from a developmental perspective in comparing autistic with mentally retarded children matched in a pairwise manner by global, verbal, and nonverbal developmental ages. All children were tested with tasks adapted from the Object Permanence Test which corresponds to Piaget's sensorimotor development Stages IV to VI. Results showed that autistic children had a pervasive difficulty in maintenance set, made more perseverative errors when the abstraction degree of task was higher, and were more variable in their behavioral strategies. Discussion is focused on the interests and limits of these tasks for the examination of regulation activity from diagnostic and developmental perspectives. Finally, interpretations about recent neuropsychological and neurophysiological works, and additional interdisciplinary studies are suggested. PMID:7559291

  14. AKT mediated glycolytic shift regulates autophagy in classically activated macrophages.

    PubMed

    Matta, Sumit Kumar; Kumar, Dhiraj

    2015-09-01

    Autophagy is considered as an innate defense mechanism primarily due to its role in the targeting of intracellular pathogens for lysosomal degradation. Here we report inhibition of autophagy as an adaptive response in classically activated macrophages that helps achieve high cellular ROS production and cell death-another hallmark of innate mechanisms. We show prolonged classical activation of Raw 264.7 macrophages by treating them with IFN-γ and LPS inhibited autophagy. The inhibition of autophagy was dependent on nitric oxide (NO) production which activated the AKT-mTOR signaling, the known negative regulators of autophagy. Autophagy inhibition in these cells was accompanied with a shift to aerobic glycolysis along with a decline in the mitochondrial membrane potential (MOMP). The decline in MOMP coupled with autophagy inhibition led to increased mitochondrial content and considerably elevated cellular ROS, eventually causing cell death. Next, using specific siRNA mediated knockdowns we show AKT was responsible for the glycolytic shift and autophagy inhibition in activated macrophages. Surprisingly, AKT knockdown in activated macrophages also rescued them from cell death. Finally we show that AKT mediated autophagy inhibition in the activated macrophages correlated with the depletion of glucose from the extracellular medium, and glucose supplementation not only rescued autophagy levels and reversed other phenotypes of activated macrophages, but also inhibited cell death. Thus we report here a novel link between AKT mediated glycolytic metabolism and autophagy in the activated macrophages, and provide a possible mechanism for sustained macrophage activation in vivo.

  15. Antithrombin Regulates Matriptase Activity Involved in Plasmin Generation, Syndecan Shedding, and HGF Activation in Keratinocytes

    PubMed Central

    Chen, Ya-Wen; Xu, Zhenghong; Baksh, Adrienne N. H.; Wang, Jehng-Kang; Chen, Chiu-Yuan; Swanson, Richard; Olson, Steve T.; Kataoka, Hiroaki; Johnson, Michael D.; Lin, Chen-Yong

    2013-01-01

    Matriptase, a membrane-associated serine protease, plays an essential role in epidermal barrier function through activation of the glycosylphosphatidylinositol (GPI)-anchored serine protease prostasin. The matriptase-prostasin proteolytic cascade is tightly regulated by hepatocyte growth factor activator inhibitor (HAI)-1 such that matriptase autoactivation and prostasin activation occur simultaneously and are followed immediately by the inhibition of both enzymes by HAI-1. However, the mechanisms whereby matriptase acts on extracellular substrates remain elusive. Here we report that some active matriptase can escape HAI-1 inhibition by being rapidly shed from the cell surface. In the pericellular environment, shed active matriptase is able to activate hepatocyte growth factor (HGF), accelerate plasminogen activation, and shed syndecan 1. The amount of active matriptase shed is inversely correlated with the amount of antithrombin (AT) bound to the surface of the keratinocytes. Binding of AT to the surface of keratinocytes is dependent on a functional heparin binding site, Lys-125, and that the N-glycosylation site Asn-135 be unglycosylated. This suggests that β-AT, and not α-AT, is responsible for regulation of pericellular matriptase activity in keratinocytes. Keratinocytes appear to rely on AT to regulate the level of pericellular active matriptase much more than breast and prostate epithelial cells in which AT regulation of matriptase activity occurs at much lower levels than keratinocytes. These results suggest that keratinocytes employ two distinct serine protease inhibitors to control the activation and processing of two different sets of matriptase substrates leading to different biological events: 1) HAI-1 for prostasin activation/inhibition, and 2) AT for the pericellular proteolysis involved in HGF activation, accelerating plasminogen activation, and shedding of syndecans. PMID:23675430

  16. Regulation of transcription and activity of Rhizobium etli glutaminase A.

    PubMed

    Huerta-Saquero, Alejandro; Calderón-Flores, Arturo; Díaz-Villaseñor, Andrea; Du Pont, Gisela; Durán, Socorro

    2004-08-01

    The present study determines the regulatory mechanisms that operate on Rhizobium etli glutaminase A. glsA gene expression levels were evaluated under several metabolic conditions by fusions of the glsA gene promoter and the transcriptional reporter cassette uidA2-aad. glsA expression was directly correlated to the glutaminase A activity found under the tested growth conditions, reaching its maximum level in the presence of glutamine and during exponential growth phase. Glutamine induces glsA expression. The influence of allosteric metabolites on glutaminase A activity was also determined. The purified enzyme was inhibited by 2-oxoglutarate and pyruvate, whereas oxaloacetate and glyoxylate modulate it positively. Glutaminase A is not inhibited by glutamate and is activated by ammonium. Glutaminase A participates in an ATP-consuming cycle where glutamine is continually degraded and resynthesized by glutamine synthetase (GS). GS and glutaminase A activities appear simultaneously during bacterial growth under different metabolic conditions and their control mechanisms are not reciprocal. Slight overproduction in glutaminase A expression causes a reduction in growth yield and a dramatic decrease in bacterial growth. We propose a model for regulation of glutaminase A, and discuss its contribution to glutamine cycle regulation. PMID:15279892

  17. Mycoplasma arthritidis mitogen up-regulates human NK cell activity.

    PubMed Central

    D'Orazio, J A; Cole, B C; Stein-Streilein, J

    1996-01-01

    While the effects of superantigens on T lymphocytes are well characterized, how superantigens interact with other immune cells is less clear. This report examines the effects of Mycoplasma arthritidis mitogen (MAM) on human natural killer (NK) cell activity. Incubation of peripheral blood mononuclear cells (PBMC) with MAM for 16 to 20 h augmented NK cytotoxicity (against K562) in a dose-dependent manner (P < or = 0.05). Superantigen-dependent cellular cytotoxicity, an activity of superantigen-activated cytotoxic T cells, was not involved in lysis of K562 cells because the erythroleukemic tumor target cells expressed no class II major histocompatibility complex by fluorescence-activated cell sorter analysis. Kinetic experiments showed that the largest increase in NK activity induced by MAM occurred within 48 h. Incubation with MAM caused a portion of NK cells to become adherent to tissue culture flasks, a quality associated with activation, and augmented NK activity was found in both adherent and nonadherent subpopulations. Experiments using cytokine-specific neutralizing antibodies showed that interleukin-2 contributed to enhancement of the NK activity observed in superantigen-stimulated PBMC. Interestingly, MAM was able to augment NK lysis of highly purified NK (CD56+) cells in the absence of other immune cells in 9 of 12 blood specimens, with the augmented lytic activity ranging from 110 to 170% of unstimulated NK activity. In summary, data presented in this report show for the first time that MAM affects human NK cells directly by increasing their lytic capacity and indirectly in PBMC as a consequence of cytokines produced by T cells. Results of this work suggest that, in vivo, one consequence of interaction with superantigen-secreting microorganisms may be up-regulation of NK lytic activity. These findings may have clinical application as a means of generating augmented NK effector cells useful in the immunotherapy of parasitic infections or neoplasms. PMID

  18. Calcium and cargoes as regulators of myosin 5a activity

    SciTech Connect

    Sellers, James R. Thirumurugan, Kavitha; Sakamoto, Takeshi; Hammer, John A.; Knight, Peter J.

    2008-04-25

    Myosin 5a is a two-headed actin-dependent motor that transports various cargoes in cells. Its enzymology and mechanochemistry have been extensively studied in vitro. It is a processive motor that takes multiple 36 nm steps on actin. The enzymatic activity of myosin 5 is regulated by an intramolecular folding mechanism whereby its lever arms fold back against the coiled-coil tail such that the motor domains directly bind the globular tail domains. We show that the structure seen in individual folded molecules is consistent with electron density map of two-dimensional crystals of the molecule. In this compact state, the actin-activated MgATPase activity of the molecule is markedly inhibited and the molecule cannot move processively on surface bound actin filaments. The actin-activated MgATPase activity of myosin 5a is activated by increasing the calcium concentration or by binding of a cargo-receptor molecule, melanophilin, in vitro. However, calcium binding to the calmodulin light chains results in dissociation of some of the calmodulin which disrupts the ability of myosin 5a to move on actin filaments in vitro. Thus we propose that the physiologically relevant activation pathway in vivo involves binding of cargo-receptor proteins.

  19. Regulation of Proteome Maintenance Gene Expression by Activators of Peroxisome Proliferator-Activated Receptor a (PPARa)

    EPA Science Inventory

    The nuclear receptor peroxisome proliferator-activated receptor alpha (PPARa) is activated by a large number of xenobiotic and hypolipidemic compounds called peroxisome proliferator chemicals (PPC). One agonist of PPARa (WY-14,643) regulates responses in the mouse liver to chemic...

  20. Inhibitory neurotransmission regulates vagal efferent activity and gastric motility.

    PubMed

    McMenamin, Caitlin A; Travagli, R Alberto; Browning, Kirsteen N

    2016-06-01

    The gastrointestinal tract receives extrinsic innervation from both the sympathetic and parasympathetic nervous systems, which regulate and modulate the function of the intrinsic (enteric) nervous system. The stomach and upper gastrointestinal tract in particular are heavily influenced by the parasympathetic nervous system, supplied by the vagus nerve, and disruption of vagal sensory or motor functions results in disorganized motility patterns, disrupted receptive relaxation and accommodation, and delayed gastric emptying, amongst others. Studies from several laboratories have shown that the activity of vagal efferent motoneurons innervating the upper GI tract is inhibited tonically by GABAergic synaptic inputs from the adjacent nucleus tractus solitarius. Disruption of this influential central GABA input impacts vagal efferent output, hence gastric functions, significantly. The purpose of this review is to describe the development, physiology, and pathophysiology of this functionally dominant inhibitory synapse and its role in regulating vagally determined gastric functions. PMID:27302177

  1. Beyond the anti-kickback statute: new entities, new theories in healthcare fraud prosecutions.

    PubMed

    Sheehan, James G; Goldner, Jesse A

    2007-01-01

    The authors analyze existing and developing trends in healthcare fraud litigation. They first review the traditional use of the Medicare-Medicaid Anti-Kickback Statute to prosecute such fraudulent activity. They then consider newer theories that have been employed, or may be employed, in cases involving payors, middlemen, agents, and fiduciaries. These include the use of the Civil False Claims Act, the Federal Travel Act, and the Public Contracts Anti-Kickback (sometimes incorporating violations under state commercial bribery and similar state legislation to form the basis of a federal claim or prosecution). The Article then turns to a discussion and warning of attorneys' potential liability for a client's kickback arrangements. Finally, the Article takes a very brief look at relationships under Medicare Part D that may well prove to be a fertile area of problematic conduct, public and congressional scrutiny, and prosecutions utilizing some of these theories.

  2. Beyond the anti-kickback statute: new entities, new theories in healthcare fraud prosecutions.

    PubMed

    Sheehan, James G; Goldner, Jesse A

    2007-01-01

    The authors analyze existing and developing trends in healthcare fraud litigation. They first review the traditional use of the Medicare-Medicaid Anti-Kickback Statute to prosecute such fraudulent activity. They then consider newer theories that have been employed, or may be employed, in cases involving payors, middlemen, agents, and fiduciaries. These include the use of the Civil False Claims Act, the Federal Travel Act, and the Public Contracts Anti-Kickback (sometimes incorporating violations under state commercial bribery and similar state legislation to form the basis of a federal claim or prosecution). The Article then turns to a discussion and warning of attorneys' potential liability for a client's kickback arrangements. Finally, the Article takes a very brief look at relationships under Medicare Part D that may well prove to be a fertile area of problematic conduct, public and congressional scrutiny, and prosecutions utilizing some of these theories. PMID:17849827

  3. Caveolin-1 regulates shear stress-dependent activation of extracellular signal-regulated kinase

    NASA Technical Reports Server (NTRS)

    Park, H.; Go, Y. M.; Darji, R.; Choi, J. W.; Lisanti, M. P.; Maland, M. C.; Jo, H.

    2000-01-01

    Fluid shear stress activates a member of the mitogen-activated protein (MAP) kinase family, extracellular signal-regulated kinase (ERK), by mechanisms dependent on cholesterol in the plasma membrane in bovine aortic endothelial cells (BAEC). Caveolae are microdomains of the plasma membrane that are enriched with cholesterol, caveolin, and signaling molecules. We hypothesized that caveolin-1 regulates shear activation of ERK. Because caveolin-1 is not exposed to the outside, cells were minimally permeabilized by Triton X-100 (0.01%) to deliver a neutralizing, polyclonal caveolin-1 antibody (pCav-1) inside the cells. pCav-1 then bound to caveolin-1 and inhibited shear activation of ERK but not c-Jun NH(2)-terminal kinase. Epitope mapping studies showed that pCav-1 binds to caveolin-1 at two regions (residues 1-21 and 61-101). When the recombinant proteins containing the epitopes fused to glutathione-S-transferase (GST-Cav(1-21) or GST-Cav(61-101)) were preincubated with pCav-1, only GST-Cav(61-101) reversed the inhibitory effect of the antibody on shear activation of ERK. Other antibodies, including m2234, which binds to caveolin-1 residues 1-21, had no effect on shear activation of ERK. Caveolin-1 residues 61-101 contain the scaffolding and oligomerization domains, suggesting that binding of pCav-1 to these regions likely disrupts the clustering of caveolin-1 or its interaction with signaling molecules involved in the shear-sensitive ERK pathway. We suggest that caveolae-like domains play a critical role in the mechanosensing and/or mechanosignal transduction of the ERK pathway.

  4. 32 CFR 22.310 - Statutes concerning certain research, development, and facilities construction grants.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... the period of execution of a multi-year award. (2) New grant. A grant that is not a follow-on grant... statute meeting the criteria in paragraph (c)(1) of this section; (ii) In the case of a follow-on grant..., there is a statute meeting the criteria in paragraph (c)(2) of this section; and (iii) The Secretary...

  5. 33 CFR 401.202 - Statute providing for assessment, mitigation or remission of civil penalties.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 33 Navigation and Navigable Waters 3 2013-07-01 2013-07-01 false Statute providing for assessment, mitigation or remission of civil penalties. 401.202 Section 401.202 Navigation and Navigable Waters SAINT... Assessment, Mitigation or Remission of Penalties § 401.202 Statute providing for assessment, mitigation...

  6. 33 CFR 401.202 - Statute providing for assessment, mitigation or remission of civil penalties.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 33 Navigation and Navigable Waters 3 2012-07-01 2012-07-01 false Statute providing for assessment, mitigation or remission of civil penalties. 401.202 Section 401.202 Navigation and Navigable Waters SAINT... Assessment, Mitigation or Remission of Penalties § 401.202 Statute providing for assessment, mitigation...

  7. 33 CFR 401.202 - Statute providing for assessment, mitigation or remission of civil penalties.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 33 Navigation and Navigable Waters 3 2010-07-01 2010-07-01 false Statute providing for assessment, mitigation or remission of civil penalties. 401.202 Section 401.202 Navigation and Navigable Waters SAINT... Assessment, Mitigation or Remission of Penalties § 401.202 Statute providing for assessment, mitigation...

  8. 33 CFR 401.202 - Statute providing for assessment, mitigation or remission of civil penalties.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 33 Navigation and Navigable Waters 3 2014-07-01 2014-07-01 false Statute providing for assessment, mitigation or remission of civil penalties. 401.202 Section 401.202 Navigation and Navigable Waters SAINT... Assessment, Mitigation or Remission of Penalties § 401.202 Statute providing for assessment, mitigation...

  9. 33 CFR 401.202 - Statute providing for assessment, mitigation or remission of civil penalties.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 33 Navigation and Navigable Waters 3 2011-07-01 2011-07-01 false Statute providing for assessment, mitigation or remission of civil penalties. 401.202 Section 401.202 Navigation and Navigable Waters SAINT... Assessment, Mitigation or Remission of Penalties § 401.202 Statute providing for assessment, mitigation...

  10. Florida School Laws. Chapters 228-246 Florida Statutes. 1998 Edition.

    ERIC Educational Resources Information Center

    Florida State Dept. of Education, Tallahassee.

    This volume of Florida School Laws contains chapters 228 through 246 of the Florida Statutes, which comprise "The Florida School Code." The laws contain those statutes specifically applicable to public schools, community colleges, postsecondary institutions, all other institutions and agencies included as a part of the state system of education,…

  11. [The oldest statutes of the Faculty of Medicine of the University of Rostock].

    PubMed

    Michael, Susi-Hilde

    2015-01-01

    The statutes of the Faculties of Medicine of the Universities Rostock and Bützow are in the process of being edited and translated from Latin in to German. This article gives the first critical examination of the oldest statutes of the Faculty of Medicine of the Alma Mater Rostochiensis.

  12. Negative regulation of lymphocyte activation by the adaptor protein LAX.

    PubMed

    Zhu, Minghua; Granillo, Olivia; Wen, Renren; Yang, Kaiyong; Dai, Xuezhi; Wang, Demin; Zhang, Weiguo

    2005-05-01

    The membrane-associated adaptor protein LAX is a linker for activation of T cells (LAT)-like molecule that is expressed in lymphoid tissues. Upon stimulation of T or B cells, it is phosphorylated and interacts with Grb2 and the p85 subunit of PI3K. LAX, however, is not capable of replacing LAT in the TCR signaling pathway. In this study we report that upon T or B cell activation, the LAX protein was up-regulated dramatically. Although disruption of the LAX gene by homologous recombination had no major impact on lymphocyte development, it caused a significant reduction in CD23 expression on mature B cells. Interestingly, naive LAX(-/-) mice had spontaneous germinal center formation. Compared with normal T and B cells, LAX(-/-) T and B cells were hyperresponsive and had enhanced calcium flux, protein tyrosine phosphorylation, MAPK and Akt activation, and cell survival upon engagement of the T or B AgRs. Our data demonstrate that LAX functions as a negative regulator in lymphocyte signaling.

  13. Deconstructing GSK-3: The Fine Regulation of Its Activity

    PubMed Central

    Medina, Miguel; Wandosell, Francisco

    2011-01-01

    Glycogen synthase kinase-3 (GSK-3) unique position in modulating the function of a diverse series of proteins in combination with its association with a wide variety of human disorders has attracted significant attention to the protein both as a therapeutic target and as a means to understand the molecular basis of these disorders. GSK-3 is ubiquitously expressed and, unusually, constitutively active in resting, unstimulated cells. In mammals, GSK-3α and β are each expressed widely at both the RNA and protein levels although some tissues show preferential levels of some of the two proteins. Neither gene appears to be acutely regulated at the transcriptional level, whereas the proteins are controlled posttranslationally, largely through protein-protein interactions or by posttranslational regulation. Control of GSK-3 activity thus occurs by complex mechanisms that are each dependent upon specific signalling pathways. Furthermore, GSK-3 appears to be a cellular nexus, integrating several signalling systems, including several second messengers and a wide selection of cellular stimulants. This paper will focus on the different ways to control GSK-3 activity (phosphorylation, protein complex formation, truncation, subcellular localization, etc.), the main signalling pathways involved in its control, and its pathological deregulation. PMID:21629747

  14. Epac Activation Regulates Human Mesenchymal Stem Cells Migration and Adhesion.

    PubMed

    Yu, Jiao-Le; Deng, Ruixia; Chung, Sookja K; Chan, Godfrey Chi-Fung

    2016-04-01

    How to enhance the homing of human mesenchymal stem cells (hMSCs) to the target tissues remains a clinical challenge nowadays. To overcome this barrier, the mechanism responsible for the hMSCs migration and engraftment has to be defined. Currently, the exact mechanism involved in migration and adhesion of hMSCs remains unknown. Exchange protein directly activated by cAMP (Epac), a novel protein discovered in cAMP signaling pathway, may have a potential role in regulating cells adhesion and migration by triggering the downstream Rap family signaling cascades. However, the exact role of Epac in cells homing is elusive. Our study evaluated the role of Epac in the homing of hMSCs. We confirmed that hMSCs expressed functional Epac and its activation enhanced the migration and adhesion of hMSCs significantly. The Epac activation was further found to be contributed directly to the chemotactic responses induced by stromal cell derived factor-1 (SDF-1) which is a known chemokine in regulating hMSCs homing. These findings suggested Epac is connected to the SDF-1 signaling cascades. In conclusion, our study revealed that Epac plays a role in hMSCs homing by promoting adhesion and migration. Appropriate manipulation of Epac may enhance the homing of hMSCs and facilitate their future clinical applications. PMID:26727165

  15. How Phosphorylation and ATPase Activity Regulate Anion Flux though the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR).

    PubMed

    Zwick, Matthias; Esposito, Cinzia; Hellstern, Manuel; Seelig, Anna

    2016-07-01

    The cystic fibrosis transmembrane conductance regulator (CFTR, ABCC7), mutations of which cause cystic fibrosis, belongs to the ATP-binding cassette (ABC) transporter family and works as a channel for small anions, such as chloride and bicarbonate. Anion channel activity is known to depend on phosphorylation by cAMP-dependent protein kinase A (PKA) and CFTR-ATPase activity. Whereas anion channel activity has been extensively investigated, phosphorylation and CFTR-ATPase activity are still poorly understood. Here, we show that the two processes can be measured in a label-free and non-invasive manner in real time in live cells, stably transfected with CFTR. This study reveals three key findings. (i) The major contribution (≥90%) to the total CFTR-related ATP hydrolysis rate is due to phosphorylation by PKA and the minor contribution (≤10%) to CFTR-ATPase activity. (ii) The mutant CFTR-E1371S that is still conductive, but defective in ATP hydrolysis, is not phosphorylated, suggesting that phosphorylation requires a functional nucleotide binding domain and occurs in the post-hydrolysis transition state. (iii) CFTR-ATPase activity is inversely related to CFTR anion flux. The present data are consistent with a model in which CFTR is in a closed conformation with two ATPs bound. The open conformation is induced by ATP hydrolysis and corresponds to the post-hydrolysis transition state that is stabilized by phosphorylation and binding of chloride channel potentiators. PMID:27226582

  16. Regulation of epithelial sodium channels in urokinase plasminogen activator deficiency

    PubMed Central

    Chen, Zaixing; Zhao, Runzhen; Zhao, Meimi; Liang, Xinrong; Bhattarai, Deepa; Dhiman, Rohan; Shetty, Sreerama; Idell, Steven

    2014-01-01

    Epithelial sodium channels (ENaC) govern transepithelial salt and fluid homeostasis. ENaC contributes to polarization, apoptosis, epithelial-mesenchymal transformation, etc. Fibrinolytic proteases play a crucial role in virtually all of these processes and are elaborated by the airway epithelium. We hypothesized that urokinase-like plasminogen activator (uPA) regulates ENaC function in airway epithelial cells and tested that possibility in primary murine tracheal epithelial cells (MTE). Both basal and cAMP-activated Na+ flow through ENaC were significantly reduced in monolayers of uPA-deficient cells. The reduction in ENaC activity was further confirmed in basolateral membrane-permeabilized cells. A decrease in the Na+-K+-ATPase activity in the basolateral membrane could contribute to the attenuation of ENaC function in intact monolayer cells. Dysfunctional fluid resolution was seen in uPA-disrupted cells. Administration of uPA and plasmin partially restores ENaC activity and fluid reabsorption by MTEs. ERK1/2, but not Akt, phosphorylation was observed in the cells and lungs of uPA-deficient mice. On the other hand, cleavage of γ ENaC is significantly depressed in the lungs of uPA knockout mice vs. those of wild-type controls. Expression of caspase 8, however, did not differ between wild-type and uPA−/− mice. In addition, uPA deficiency did not alter transepithelial resistance. Taken together, the mechanisms for the regulation of ENaC by uPA in MTEs include augmentation of Na+-K+-ATPase, proteolysis, and restriction of ERK1/2 phosphorylation. We demonstrate for the first time that ENaC may serve as a downstream signaling target by which uPA controls the biophysical profiles of airway fluid and epithelial function. PMID:25172911

  17. Dynamic regulation of Polycomb group activity during plant development.

    PubMed

    Bemer, Marian; Grossniklaus, Ueli

    2012-11-01

    Polycomb group (PcG) complexes play important roles in phase transitions and cell fate determination in plants and animals, by epigenetically repressing sets of genes that promote either proliferation or differentiation. The continuous differentiation of new organs in plants, such as leaves or flowers, requires a highly dynamic PcG function, which can be induced, modulated, or repressed when necessary. In this review, we discuss the recent advance in understanding PcG function in plants and focus on the diverse molecular mechanisms that have been described to regulate and counteract PcG activity in Arabidopsis.

  18. Dynamic regulation of Polycomb group activity during plant development.

    PubMed

    Bemer, Marian; Grossniklaus, Ueli

    2012-11-01

    Polycomb group (PcG) complexes play important roles in phase transitions and cell fate determination in plants and animals, by epigenetically repressing sets of genes that promote either proliferation or differentiation. The continuous differentiation of new organs in plants, such as leaves or flowers, requires a highly dynamic PcG function, which can be induced, modulated, or repressed when necessary. In this review, we discuss the recent advance in understanding PcG function in plants and focus on the diverse molecular mechanisms that have been described to regulate and counteract PcG activity in Arabidopsis. PMID:22999383

  19. Lipoprotein electrostatic properties regulate hepatic lipase association and activity.

    PubMed

    Boucher, Jonathan G; Nguyen, Trang; Sparks, Daniel L

    2007-12-01

    The effect of lipoprotein electrostatic properties on the catalytic regulation of hepatic lipase (HL) was investigated. Enrichment of serum or very low density lipoprotein (VLDL) with oleic acid increased lipoprotein negative charge and stimulated lipid hydrolysis by HL. Similarly, enrichment of serum or isolated lipoproteins with the anionic phospholipids phosphatidylinositol (PI), phosphatidic acid, or phosphatidylserine also increased lipoprotein negative charge and stimulated hydrolysis by HL. Anionic lipids had a small effect on phospholipid hydrolysis, but significantly stimulated triacylglyceride (TG) hydrolysis. High density lipoprotein (HDL) charge appears to have a specific effect on lipolysis. Enrichment of HDL with PI significantly stimulated VLDL-TG hydrolysis by HL. To determine whether HDL charge affects the association of HL with HDL and VLDL, HL-lipoprotein interactions were probed immunochemically. Under normal circumstances, HL associates with HDL particles, and only small amounts bind to VLDL. PI enrichment of HDL blocked the binding of HL with HDL. These data indicate that increasing the negative charge of HDL stimulates VLDL-TG hydrolysis by reducing the association of HL with HDL. Therefore, HDL controls the hydrolysis of VLDL by affecting the interlipoprotein association of HL. Lipoprotein electrostatic properties regulate lipase association and are an important regulator of the binding and activity of lipolytic enzymes.

  20. Motor unit regulation of mammalian pharyngeal dilator muscle activity.

    PubMed Central

    van Lunteren, E; Dick, T E

    1989-01-01

    The present study examined the cellular regulation of one of the pharyngeal dilator muscles, the geniohyoid, by assessing its motor unit (MU) behavior in anesthetized cats. During spontaneous breathing, MU that (a) were active during inspiration only (I-MU) and (b) were active during both inspiration and expiration (I/E-MU) were identified. I-MU had a later inspiratory onset time and a shorter duration of inspiratory firing than did I/E-MU (P less than 0.002 and P less than 0.0001, respectively). I-MU were usually quiescent whereas I/E-MU were usually active during the last 20% of inspiration. I/E-MU fired more rapidly (P less than 0.00001) and for relatively longer periods of time (P less than 0.00001) during inspiration than during expiration. End-expiratory airway occlusion (preventing lung expansion during inspiration) augmented the inspiratory activity of both I-MU and I/E-MU. Conversely, end-expiratory airway occlusion reduced the absolute and relative firing durations (P less than 0.002 and P less than 0.00002, respectively) and the firing frequency (P less than 0.001) of I/E-MU activity during expiration. These results indicate that (a) the complex pattern of pharyngeal dilator muscle activity is due to the integrated activity of a heterogeneous group of MU, (b) changes in the degree to which pharyngeal dilator muscles are active result from combinations of MU recruitment/decruitment and modulations of the frequency and duration of MU firing, and (c) gating of lung-volume afferent information occurs during the respiratory cycle. PMID:2760202

  1. Hypoxic regulation of osteoclast differentiation and bone resorption activity

    PubMed Central

    Knowles, Helen J

    2015-01-01

    Bone integrity is maintained throughout life via the homeostatic actions of bone cells, namely, osteoclasts, which resorb bone, and osteoblasts, which produce bone. Disruption of this balance in favor of osteoclast activation results in pathological bone loss, which occurs in conditions including osteoporosis, rheumatoid arthritis, primary bone cancer, and cancer metastasis to bone. Hypoxia also plays a major role in these conditions, where it is associated with disease progression and poor prognosis. In recent years, considerable interest has arisen in the mechanisms whereby hypoxia and the hypoxia-inducible transcription factors, HIF-1α and HIF-2α, affect bone remodeling and bone pathologies. This review summarizes the current evidence for hypoxia-mediated regulation of osteoclast differentiation and bone resorption activity. Role(s) of HIF and HIF target genes in the formation of multinucleated osteoclasts from cells of the monocyte–macrophage lineage and in the activation of bone resorption by mature osteoclasts will be discussed. Specific attention will be paid to hypoxic metabolism and generation of ATP by osteoclasts. Hypoxia-driven increases in both glycolytic flux and mitochondrial metabolic activity, along with consequent generation of mitochondrial reactive oxygen species, have been found to be essential for osteoclast formation and resorption activity. Finally, evidence for the use of HIF inhibitors as potential therapeutic agents targeting bone resorption in osteolytic disease will be discussed. PMID:27774484

  2. Iron regulates xanthine oxidase activity in the lung.

    PubMed

    Ghio, Andrew J; Kennedy, Thomas P; Stonehuerner, Jacqueline; Carter, Jacqueline D; Skinner, Kelly A; Parks, Dale A; Hoidal, John R

    2002-09-01

    The iron chelator deferoxamine has been reported to inhibit both xanthine oxidase (XO) and xanthine dehydrogenase activity, but the relationship of this effect to the availability of iron in the cellular and tissue environment remains unexplored. XO and total xanthine oxidoreductase activity in cultured V79 cells was increased with exposure to ferric ammonium sulfate and inhibited by deferoxamine. Lung XO and total xanthine oxidoreductase activities were reduced in rats fed an iron-depleted diet and increased in rats supplemented with iron, without change in the ratio of XO to total oxidoreductase. Intratracheal injection of an iron salt or silica-iron, but not aluminum salts or silica-zinc, significantly increased rat lung XO and total xanthine oxidoreductase activities, immunoreactive xanthine oxidoreductase, and the concentration of urate in bronchoalveolar fluid. These results suggest the possibility that the production of uric acid, a major chelator of iron in extracellular fluid, is directly influenced by iron-mediated regulation of the expression and/or activity of its enzymatic source, xanthine oxidase.

  3. Comparative Analysis of Protein Tyrosine Phosphatases Regulating Microglial Activation

    PubMed Central

    Song, Gyun Jee; Kim, Jaehong; Kim, Jong-Heon; Song, Seungeun; Park, Hana; Zhang, Zhong-Yin

    2016-01-01

    Protein tyrosine phosphatases (PTPs) are key regulatory factors in inflammatory signaling pathways. Although PTPs have been extensively studied, little is known about their role in neuroinflammation. In the present study, we examined the expression of 6 different PTPs (PTP1B, TC-PTP, SHP2, MEG2, LYP, and RPTPβ) and their role in glial activation and neuroinflammation. All PTPs were expressed in brain and glia. The expression of PTP1B, SHP2, and LYP was enhanced in the inflamed brain. The expression of PTP1B, TC-PTP, and LYP was increased after treating microglia cells with lipopolysaccharide (LPS). To examine the role of PTPs in microglial activation and neuroinflammation, we used specific pharmacological inhibitors of PTPs. Inhibition of PTP1B, TC-PTP, SHP2, LYP, and RPTPβ suppressed nitric oxide production in LPS-treated microglial cells in a dose-dependent manner. Furthermore, intracerebroventricular injection of PTP1B, TC-PTP, SHP2, and RPTPβ inhibitors downregulated microglial activation in an LPS-induced neuroinflammation model. Our results indicate that multiple PTPs are involved in regulating microglial activation and neuroinflammation, with different expression patterns and specific functions. Thus, PTP inhibitors can be exploited for therapeutic modulation of microglial activation in neuroinflammatory diseases. PMID:27790059

  4. Regulation of Seasonal Reproduction by Hypothalamic Activation of Thyroid Hormone

    PubMed Central

    Shinomiya, Ai; Shimmura, Tsuyoshi; Nishiwaki-Ohkawa, Taeko; Yoshimura, Takashi

    2014-01-01

    Organisms living outside the tropics measure the changes in the length of the day to adapt to seasonal changes in the environment. Animals that breed during spring and summer are called long-day breeders, while those that breed during fall are called short-day breeders. Although the influence of thyroid hormone in the regulation of seasonal reproduction has been known for several decades, its precise mechanism remained unknown. Recent studies revealed that the activation of thyroid hormone within the mediobasal hypothalamus plays a key role in this phenomenon. This localized activation of the thyroid hormone is controlled by thyrotropin (thyroid-stimulating hormone) secreted from the pars tuberalis of the pituitary gland. Although seasonal reproduction is a rate-limiting factor in animal production, genes involved in photoperiodic signal transduction pathway could emerge as potential targets to facilitate domestication. PMID:24600435

  5. Neuroligin-1 links neuronal activity to sleep-wake regulation

    PubMed Central

    El Helou, Janine; Bélanger-Nelson, Erika; Freyburger, Marlène; Dorsaz, Stéphane; Curie, Thomas; La Spada, Francesco; Gaudreault, Pierre-Olivier; Beaumont, Éric; Pouliot, Philippe; Lesage, Frédéric; Frank, Marcos G.; Franken, Paul; Mongrain, Valérie

    2013-01-01

    Maintaining wakefulness is associated with a progressive increase in the need for sleep. This phenomenon has been linked to changes in synaptic function. The synaptic adhesion molecule Neuroligin-1 (NLG1) controls the activity and synaptic localization of N-methyl-d-aspartate receptors, which activity is impaired by prolonged wakefulness. We here highlight that this pathway may underlie both the adverse effects of sleep loss on cognition and the subsequent changes in cortical synchrony. We found that the expression of specific Nlg1 transcript variants is changed by sleep deprivation in three mouse strains. These observations were associated with strain-specific changes in synaptic NLG1 protein content. Importantly, we showed that Nlg1 knockout mice are not able to sustain wakefulness and spend more time in nonrapid eye movement sleep than wild-type mice. These changes occurred with modifications in waking quality as exemplified by low theta/alpha activity during wakefulness and poor preference for social novelty, as well as altered delta synchrony during sleep. Finally, we identified a transcriptional pathway that could underlie the sleep/wake-dependent changes in Nlg1 expression and that involves clock transcription factors. We thus suggest that NLG1 is an element that contributes to the coupling of neuronal activity to sleep/wake regulation. PMID:23716671

  6. Rac1 activity regulates proliferation of aggressive metastatic melanoma

    SciTech Connect

    Bauer, Natalie N. Chen Yihwen; Samant, Rajeev S.; Shevde, Lalita A.; Fodstad, Oystein

    2007-11-01

    Molecular mechanisms underlying the different capacity of two in vivo selected human melanoma cell variants to form experimental metastases were studied. The doubling times of the FEMX-I and FEMX-V cell sublines in vitro were 15 and 25 h, respectively. The invasive capacity of FEMX-I cells was 8-fold higher than FEMX-V cells, and the time to form approximately 10 mm s.c. tumors in nude mice was 21 versus 35 days. FEMX-I displayed a spindle-like formation in vitro, whereas FEMX-V cells had a rounded shape. Hence, we examined known determinants of cell shape and proliferation, the small GTPases. The four studied showed equal expression in both cell types, but Rac1 activity was significantly decreased in FEMX-V cells. Rac1 stimulates NF{kappa}B, and we found that endogenous NF{kappa}B activity of FEMX-V cells was 2% of that of FEMX-I cells. Inhibition of Rac1 resulted in blocked NF{kappa}B activity. Specific inhibition of either Rac1 or NF{kappa}B significantly reduced proliferation and invasion of FEMX-I cells, the more pronounced effects observed with Rac1 inhibition. These data indicate that Rac1 activity in FEMX cells regulates cell proliferation and invasion, in part via its effect on NF{kappa}B, signifying Rac1 as a key molecule in melanoma progression and metastasis.

  7. EGFR regulates macrophage activation and function in bacterial infection.

    PubMed

    Hardbower, Dana M; Singh, Kshipra; Asim, Mohammad; Verriere, Thomas G; Olivares-Villagómez, Danyvid; Barry, Daniel P; Allaman, Margaret M; Washington, M Kay; Peek, Richard M; Piazuelo, M Blanca; Wilson, Keith T

    2016-09-01

    EGFR signaling regulates macrophage function, but its role in bacterial infection has not been investigated. Here, we assessed the role of macrophage EGFR signaling during infection with Helicobacter pylori, a bacterial pathogen that causes persistent inflammation and gastric cancer. EGFR was phosphorylated in murine and human macrophages during H. pylori infection. In human gastric tissues, elevated levels of phosphorylated EGFR were observed throughout the histologic cascade from gastritis to carcinoma. Deleting Egfr in myeloid cells attenuated gastritis and increased H. pylori burden in infected mice. EGFR deficiency also led to a global defect in macrophage activation that was associated with decreased cytokine, chemokine, and NO production. We observed similar alterations in macrophage activation and disease phenotype in the Citrobacter rodentium model of murine infectious colitis. Mechanistically, EGFR signaling activated NF-κB and MAPK1/3 pathways to induce cytokine production and macrophage activation. Although deletion of Egfr had no effect on DC function, EGFR-deficient macrophages displayed impaired Th1 and Th17 adaptive immune responses to H. pylori, which contributed to decreased chronic inflammation in infected mice. Together, these results indicate that EGFR signaling is central to macrophage function in response to enteric bacterial pathogens and is a potential therapeutic target for infection-induced inflammation and associated carcinogenesis.

  8. EGFR regulates macrophage activation and function in bacterial infection.

    PubMed

    Hardbower, Dana M; Singh, Kshipra; Asim, Mohammad; Verriere, Thomas G; Olivares-Villagómez, Danyvid; Barry, Daniel P; Allaman, Margaret M; Washington, M Kay; Peek, Richard M; Piazuelo, M Blanca; Wilson, Keith T

    2016-09-01

    EGFR signaling regulates macrophage function, but its role in bacterial infection has not been investigated. Here, we assessed the role of macrophage EGFR signaling during infection with Helicobacter pylori, a bacterial pathogen that causes persistent inflammation and gastric cancer. EGFR was phosphorylated in murine and human macrophages during H. pylori infection. In human gastric tissues, elevated levels of phosphorylated EGFR were observed throughout the histologic cascade from gastritis to carcinoma. Deleting Egfr in myeloid cells attenuated gastritis and increased H. pylori burden in infected mice. EGFR deficiency also led to a global defect in macrophage activation that was associated with decreased cytokine, chemokine, and NO production. We observed similar alterations in macrophage activation and disease phenotype in the Citrobacter rodentium model of murine infectious colitis. Mechanistically, EGFR signaling activated NF-κB and MAPK1/3 pathways to induce cytokine production and macrophage activation. Although deletion of Egfr had no effect on DC function, EGFR-deficient macrophages displayed impaired Th1 and Th17 adaptive immune responses to H. pylori, which contributed to decreased chronic inflammation in infected mice. Together, these results indicate that EGFR signaling is central to macrophage function in response to enteric bacterial pathogens and is a potential therapeutic target for infection-induced inflammation and associated carcinogenesis. PMID:27482886

  9. Hydrogen Peroxide-Induced Akt Phosphorylation Regulates Bax Activation

    PubMed Central

    Sadidi, Mahdieh; Lentz, Stephen I.; Feldman, Eva L.

    2009-01-01

    Reactive oxygen species such as hydrogen peroxide (H2O2) are involved in many cellular processes that positively and negatively regulate cell fate. H2O2, acting as an intracellular messenger, activates phosphatidylinositol-3 kinase (PI3K) and its downstream target Akt, and promotes cell survival. The aim of the current study was to understand the mechanism by which PI3K/Akt signaling promotes survival in SH-SY5Y neuroblastoma cells. We demonstrate that PI3K/Akt mediates phosphorylation of the pro-apoptotic Bcl-2 family member Bax. This phosphorylation suppresses apoptosis and promotes cell survival. Increased survival in the presence of H2O2 was blocked by LY294002, an inhibitor of PI3K activation. LY294002 prevented Bax phosphorylation and resulted in Bax translocation to the mitochondria, cytochrome c release, caspase-3 activation, and cell death. Collectively, these findings reveal a mechanism by which H2O2-induced activation of PI3K/Akt influences posttranslational modification of Bax and inactivate a key component of the cell death machinery. PMID:19278624

  10. The regulation and biological activity of interleukin 12.

    PubMed

    Lee, S M; Suen, Y; Qian, J; Knoppel, E; Cairo, M S

    1998-05-01

    Interleukin 12 (IL-12) is a pleiotropic cytokine and mediates several biological activities on human T and natural killer (NK) cells, including induction of IFN-gamma production, enhancement of cell-mediated cytotoxicity and comitogenic effects on resting T-cells. The major cellular sources producing IL-12 are antigen-stimulated monocytes, macrophages, and B-cells isolated from peripheral blood mononuclear cells (PBMC). Our laboratory has investigated the regulation of IL-12 gene expression in both cord blood and adult PBMC, and the effects of IL-12 on induction of IFN-gamma production, NK, and lymphokine-activated killer (LAK) cytotoxicity. IL-12 mRNA expression and protein production in LPS-stimulated cord blood MNC were 3-4 fold decreased when compared with adult PBMC. There were no differences between cord blood and adult PBMC in both basal levels of transcription or the degree of transcriptional activation of the IL-12 gene. Additionally, the half-life of IL-12 p40 mRNA was 3-fold lower in activated cord blood compared to adult PBMC. Exogenous IL-12 induced a significant increase of IFN-gamma from both cord and adult PBMC. Cord MNC has significantly reduced levels of NK activity, and IL-12 significantly enhanced cord blood NK cytotoxicity up to similar levels in adult PBMC. IL-12 also significantly enhanced cord blood NK and LAK activities against a broad range of neuroblastoma, leukemia, and lymphoma cell lines. Lower doses of IL-12 and IL-15 concomitantly generated either synergistic or additive effects on cord blood NK and LAK cytotoxicities. In light of the important biological functions of IL-12, reduced expression and production of IL-12 from activated cord blood may contribute to the immaturity of cord blood cellular immunity and contribute, in part, to decreased severe graft vs. host disease following unrelated cord blood stem cell transplantation. IL-12 enhancement of IFN-gamma, NK, and LAK activity in activated cord blood MNC up to comparable levels

  11. Regulation of TLR3 Activation by S100A9.

    PubMed

    Tsai, Su-Yu; Segovia, Jesus A; Chang, Te-Hung; Shil, Niraj K; Pokharel, Swechha M; Kannan, T R; Baseman, Joel B; Defrêne, Joan; Pagé, Nathalie; Cesaro, Annabelle; Tessier, Philippe A; Bose, Santanu

    2015-11-01

    Recognition of viral dsRNA by endosomal TLR3 activates innate immune response during virus infection. Trafficking of TLR3 to the endolysosomal compartment arising from fusion of late endosome (LE) with lysosome is required for recognition and detection of pathogen associated molecular patterns, which results in activation of the TLR3-dependent signaling cascade. Existing knowledge about the mechanism(s) and cellular factor(s) governing TLR3 trafficking is limited. In the current study, we identified intracellular S100A9 protein as a critical regulator of TLR3 trafficking. S100A9 was required for maturation of TLR3 containing early endosome (EE) into LE, the compartment that fuses with lysosome to form the endolysosomal compartment. A drastic reduction in cytokine production was observed in S100A9-knockout (KO) primary macrophages following RNA virus infection and treatment of cells with polyinosinic-polycytidylic acid (polyIC; a dsRNA mimetic that acts as a TLR3 agonist). Mechanistic studies revealed colocalization and interaction of S100A9 with TLR3 following polyIC treatment. S100A9-TLR3 interaction was critical for maturation of TLR3 containing EE into LE because TLR3 could not be detected in the LE of polyIC-treated S100A9-KO macrophages. Subsequently, TLR3 failed to colocalize with its agonist (i.e., biotin-labeled polyIC) in S100A9-deficient macrophages. The in vivo physiological role of S100A9 was evident from loss of cytokine production in polyIC-treated S100A9-KO mice. Thus, we identified intracellular S100A9 as a regulator of TLR3 signaling and demonstrated that S100A9 functions during pre-TLR3 activation stages by facilitating maturation of TLR3 containing EE into LE. PMID:26385519

  12. Topographic regulation of kinase activity in Alzheimer's disease brains.

    PubMed

    Grant, Philip; Pant, Harish C

    2002-08-01

    At autopsy, a most distinctive pathology seen in Alzheimer's disease (AD) brains is numerous abnormal neurons filled with neurofibrillary tangles (NFTs) containing stable complexes of hyperphosphorylated tau (PHF), neurofilaments and various kinases, among other proteins. Though these neuronal aggregates have been actively studied, their nature and origin are still poorly understood. Our studies of regulation of phosphorylation in neurons of the squid giant fiber system, using P13(suc1) affinity chromatography, suggest that neuronal phosphorylation of cytoskeletal proteins is compartmentalized into active axonal and inactive cell body-specific multimeric complexes of kinases, substrates and phosphatases. To determine whether such compartment-specific phosphorylation complexes are present in human brains, we separated gray matter (enriched in cell bodies) and white matter (enriched in axons) from normal and AD brains and studied the total kinase activities in lysates, pellets and P13(suc1) complexes. In addition, Western blot analysis was used to characterize the proteins associated with P13(suc1) multimeric complexes extracted from gray and white matter. We tested the hypothesis that P13 phosphorylation complexes were abnormally compartmentalized in AD neurons with the more active complexes shifted to cell bodies (gray matter) instead of axons (white matter). We found that (1) endogenous and exogenous substrate-dependent kinase activities of AD and control brain extracts were similar in both gray and white matter. (2) Long post mortem times tend to erase any differences in kinase activity between control and AD extracts. In contrast to shorter post mortem times (4.5-10 hrs), long post mortem times (13-34 hrs) significantly minimize the variances in kinase activities between control and AD brain extracts suggesting that cell death and proteolysis may eliminate any intrinsic differences in enzyme activities. (3) Except for the significantly higher level of histone

  13. CONSTANS is a photoperiod regulated activator of flowering in sorghum

    PubMed Central

    2014-01-01

    Background Sorghum genotypes used for grain production in temperate regions are photoperiod insensitive and flower early avoiding adverse environments during the reproductive phase. In contrast, energy sorghum hybrids are highly photoperiod sensitive with extended vegetative phases in long days, resulting in enhanced biomass accumulation. SbPRR37 and SbGHD7 contribute to photoperiod sensitivity in sorghum by repressing expression of SbEHD1 and FT-like genes, thereby delaying flowering in long days with minimal influence in short days (PNAS_108:16469-16474, 2011; Plant Genome_in press, 2014). The GIGANTEA (GI)-CONSTANS (CO)-FLOWERING LOCUS T (FT) pathway regulates flowering time in Arabidopsis and the grasses (J Exp Bot_62:2453-2463, 2011). In long day flowering plants, such as Arabidopsis and barley, CONSTANS activates FT expression and flowering in long days. In rice, a short day flowering plant, Hd1, the ortholog of CONSTANS, activates flowering in short days and represses flowering in long days. Results Quantitative trait loci (QTL) that modify flowering time in sorghum were identified by screening Recombinant Inbred Lines (RILs) derived from BTx642 and Tx7000 in long days, short days, and under field conditions. Analysis of the flowering time QTL on SBI-10 revealed that BTx642 encodes a recessive CONSTANS allele containing a His106Tyr substitution in B-box 2 known to inactivate CONSTANS in Arabidopsis thaliana. Genetic analysis characterized sorghum CONSTANS as a floral activator that promotes flowering by inducing the expression of EARLY HEADING DATE 1 (SbEHD1) and sorghum orthologs of the maize FT genes ZCN8 (SbCN8) and ZCN12 (SbCN12). The floral repressor PSEUDORESPONSE REGULATOR PROTEIN 37 (PRR37) inhibits sorghum CONSTANS activity and flowering in long days. Conclusion Sorghum CONSTANS is an activator of flowering that is repressed post-transcriptionally in long days by the floral inhibitor PRR37, contributing to photoperiod sensitive flowering in Sorghum

  14. Regulation of Akt/PKB activity by P21-activated kinase in cardiomyocytes.

    PubMed

    Mao, Kai; Kobayashi, Satoru; Jaffer, Zahara M; Huang, Yuan; Volden, Paul; Chernoff, Jonathan; Liang, Qiangrong

    2008-02-01

    Akt/PKB is a critical regulator of cardiac function and morphology, and its activity is governed by dual phosphorylation at active loop (Thr308) by phosphoinositide-dependent protein kinase-1 (PDK1) and at carboxyl-terminal hydrophobic motif (Ser473) by a putative PDK2. P21-activated kinase-1 (Pak1) is a serine/threonine protein kinase implicated in the regulation of cardiac hypertrophy and contractility and was shown previously to activate Akt through an undefined mechanism. Here we report Pak1 as a potential PDK2 that is essential for Akt activity in cardiomyocytes. Both Pak1 and Akt can be activated by multiple hypertrophic stimuli or growth factors in a phosphatidylinositol-3-kinase (PI3K)-dependent manner. Pak1 overexpression induces Akt phosphorylation at both Ser473 and Thr308 in cardiomyocytes. Conversely, silencing or inactivating Pak1 gene diminishes Akt phosphorylation in vitro and in vivo. Purified Pak1 can directly phosphorylate Akt only at Ser473, suggesting that Pak1 may be a relevant PDK2 responsible for AKT Ser473 phosphorylation in cardiomyocytes. In addition, Pak1 protects cardiomyocytes from cell death, which is blocked by Akt inhibition. Our results connect two important regulators of cellular physiological functions and provide a potential mechanism for Pak1 signaling in cardiomyocytes. PMID:18054038

  15. Activation and Regulation of Purinergic P2X Receptor Channels

    PubMed Central

    Coddou, Claudio; Yan, Zonghe; Obsil, Tomas; Huidobro-Toro, J. Pablo

    2011-01-01

    Mammalian ATP-gated nonselective cation channels (P2XRs) can be composed of seven possible subunits, denoted P2X1 to P2X7. Each subunit contains a large ectodomain, two transmembrane domains, and intracellular N and C termini. Functional P2XRs are organized as homomeric and heteromeric trimers. This review focuses on the binding sites involved in the activation (orthosteric) and regulation (allosteric) of P2XRs. The ectodomains contain three ATP binding sites, presumably located between neighboring subunits and formed by highly conserved residues. The detection and coordination of three ATP phosphate residues by positively charged amino acids are likely to play a dominant role in determining agonist potency, whereas an AsnPheArg motif may contribute to binding by coordinating the adenine ring. Nonconserved ectodomain histidines provide the binding sites for trace metals, divalent cations, and protons. The transmembrane domains account not only for the formation of the channel pore but also for the binding of ivermectin (a specific P2X4R allosteric regulator) and alcohols. The N- and C- domains provide the structures that determine the kinetics of receptor desensitization and/or pore dilation and are critical for the regulation of receptor functions by intracellular messengers, kinases, reactive oxygen species and mercury. The recent publication of the crystal structure of the zebrafish P2X4.1R in a closed state provides a major advance in the understanding of this family of receptor channels. We will discuss data obtained from numerous site-directed mutagenesis experiments accumulated during the last 15 years with reference to the crystal structure, allowing a structural interpretation of the molecular basis of orthosteric and allosteric ligand actions. PMID:21737531

  16. Inflammatory and Immune Activation in Intestinal Myofibroblasts Is Developmentally Regulated

    PubMed Central

    Zawahir, Sharmila; Li, Guanghui; Banerjee, Aditi; Shiu, Jessica; Blanchard, Thomas G.

    2015-01-01

    We previously demonstrated that intestinal myofibroblasts from immature tissue produce excessive IL-8 in response to Escherichia coli lipopolysaccharide (LPS) compared to cells from mature tissue. However, it is unknown whether other cytokines and TLR agonists contribute to this developmentally regulated response. The aim of this study was to further characterize differences in inflammatory signaling in human primary intestinal fibroblasts from fetal (FIF) and infant (IIF) tissue and examine their potential to activate the adaptive immune response in vitro. Cytokine profiles of LPS-stimulated FIF and IIF were assessed by cytokine profile array. IL-8, IL-6, and IL-10 production in response to TLR2, TLR2/6, TLR4, and TLR5 agonists was determined by quantitative ELISA. The potential of activated myofibroblasts to activate adaptive immunity was determined by measuring surface class II MHC expression using flow cytometry. LPS-stimulated FIF produced a distinct proinflammatory cytokine profile consisting of MCP-1, GRO-alpha, IL-6, and IL-8 expression. FIF produced significant IL-8 and IL-6 in response to TLR4 agonist. IIF produced significant levels of IL-8 and IL-6 in the presence of TLR5 and TLR2 agonists. IFN-γ-treated FIF expressed greater HLA-DR levels compared to unstimulated controls and IFN-γ- and LPS-treated IIF. Activated FIF produce a more diverse inflammatory cytokine profile and greater levels of IL-8 and IL-6 in response to TLR4 stimulation compared to IIF. FIF express class II MHC proteins associated with activation of the adaptive immune response. These data suggest that FIF may contribute to bacterial-associated gut inflammation in the immature intestine. PMID:26101946

  17. Vimentin regulates activation of the NLRP3 inflammasome

    NASA Astrophysics Data System (ADS)

    Dos Santos, Gimena; Rogel, Micah R.; Baker, Margaret A.; Troken, James R.; Urich, Daniela; Morales-Nebreda, Luisa; Sennello, Joseph A.; Kutuzov, Mikhail A.; Sitikov, Albert; Davis, Jennifer M.; Lam, Anna P.; Cheresh, Paul; Kamp, David; Shumaker, Dale K.; Budinger, G. R. Scott; Ridge, Karen M.

    2015-03-01

    Activation of the NLRP3 inflammasome and subsequent maturation of IL-1β have been implicated in acute lung injury (ALI), resulting in inflammation and fibrosis. We investigated the role of vimentin, a type III intermediate filament, in this process using three well-characterized murine models of ALI known to require NLRP3 inflammasome activation. We demonstrate that central pathophysiologic events in ALI (inflammation, IL-1β levels, endothelial and alveolar epithelial barrier permeability, remodelling and fibrosis) are attenuated in the lungs of Vim-/- mice challenged with LPS, bleomycin and asbestos. Bone marrow chimeric mice lacking vimentin have reduced IL-1β levels and attenuated lung injury and fibrosis following bleomycin exposure. Furthermore, decreased active caspase-1 and IL-1β levels are observed in vitro in Vim-/- and vimentin-knockdown macrophages. Importantly, we show direct protein-protein interaction between NLRP3 and vimentin. This study provides insights into lung inflammation and fibrosis and suggests that vimentin may be a key regulator of the NLRP3 inflammasome.

  18. Vimentin regulates activation of the NLRP3 inflammasome

    PubMed Central

    dos Santos, Gimena; Rogel, Micah R.; Baker, Margaret A.; Troken, James R.; Urich, Daniela; Morales-Nebreda, Luisa; Sennello, Joseph A.; Kutuzov, Mikhail A.; Sitikov, Albert; Davis, Jennifer M.; Lam, Anna P.; Cheresh, Paul; Kamp, David; Shumaker, Dale K.; Budinger, G.R. Scott; Ridge, Karen M.

    2015-01-01

    Activation of the NLRP3 inflammasome and subsequent maturation of IL-1β have been implicated in acute lung injury (ALI), resulting in inflammation and fibrosis. We investigated the role of vimentin, a type III intermediate filament, in this process using three well-characterized murine models of ALI known to require NLRP3 inflammasome activation. We demonstrate that central pathophysiologic events in ALI (inflammation, IL-1β levels, endothelial and alveolar epithelial barrier permeability, remodeling, and fibrosis) are attenuated in the lungs of Vim-/- mice challenged with LPS, bleomycin, and asbestos. Bone marrow chimeric mice lacking vimentin have reduced IL-1β levels and attenuated lung injury and fibrosis following bleomycin exposure. Furthermore, decreased active caspase-1 and IL-1β levels are observed in vitro in Vim-/- and vimentin-knockdown macrophages. Importantly, we show direct protein-protein interaction between NLRP3 and vimentin. This study provides insights into lung inflammation and fibrosis and suggests vimentin may be a key regulator of the NLRP3 inflammasome. PMID:25762200

  19. Serotonin transporter genotype modulates amygdala activity during mood regulation

    PubMed Central

    Rao, Hengyi; Wang, Jiongjiong; Detre, John A.; Breland, Jessica; Sankoorikal, Geena Mary V.; Brodkin, Edward S.; Farah, Martha J.

    2010-01-01

    Recent studies have implicated the short allele of the serotonin transporter-linked polymorphic region (5-HTTLPR) in depression vulnerability, particularly in the context of stress. Several neuroimaging studies have shown that 5-HTTLPR genotype predicts amygdala reactivity to negatively valenced stimuli, suggesting a mechanism whereby the short allele confers depression risk. The current study investigated whether 5-HTTLPR genotype similarly affects neural activity during an induced sad mood and during recovery from sad mood. Participants were 15 homozygous short (S) and 15 homozygous long (L) individuals. Regional cerebral blood flow was measured with perfusion functional magnetic resonance imaging during four scanning blocks: baseline, sad mood, mood recovery and following return to baseline. Comparing mood recovery to baseline, both whole brain analyses and template-based region-of-interest analyses revealed greater amygdala activity for the S vs the L-group. There were no significant amygdala differences found during the induced sad mood. These results demonstrate the effect of the S allele on amygdala activity during intentional mood regulation and suggest that amygdala hyperactivity during recovery from a sad mood may be one mechanism by which the S allele confers depression risk. PMID:19858108

  20. Pharmacological activation of lysophosphatidic acid receptors regulates erythropoiesis

    PubMed Central

    Lin, Kuan-Hung; Ho, Ya-Hsuan; Chiang, Jui-Chung; Li, Meng-Wei; Lin, Shi-Hung; Chen, Wei-Min; Chiang, Chi-Ling; Lin, Yu-Nung; Yang, Ya-Jan; Chen, Chiung-Nien; Lu, Jenher; Huang, Chang-Jen; Tigyi, Gabor; Yao, Chao-Ling; Lee, Hsinyu

    2016-01-01

    Lysophosphatidic acid (LPA), a growth factor-like phospholipid, regulates numerous physiological functions, including cell proliferation and differentiation. In a previous study, we have demonstrated that LPA activates erythropoiesis by activating the LPA 3 receptor subtype (LPA3) under erythropoietin (EPO) induction. In the present study, we applied a pharmacological approach to further elucidate the functions of LPA receptors during red blood cell (RBC) differentiation. In K562 human erythroleukemia cells, knockdown of LPA2 enhanced erythropoiesis, whereas knockdown of LPA3 inhibited RBC differentiation. In CD34+ human hematopoietic stem cells (hHSC) and K526 cells, the LPA3 agonist 1-oleoyl-2-methyl-sn-glycero-3-phosphothionate (2S-OMPT) promoted erythropoiesis, whereas the LPA2 agonist dodecyl monophosphate (DMP) and the nonlipid specific agonist GRI977143 (GRI) suppressed this process. In zebrafish embryos, hemoglobin expression was significantly increased by 2S-OMPT treatment but was inhibited by GRI. Furthermore, GRI treatment decreased, whereas 2S-OMPT treatment increased RBC counts and amount of hemoglobin level in adult BALB/c mice. These results indicate that LPA2 and LPA3 play opposing roles during RBC differentiation. The pharmacological activation of LPA receptor subtypes represent a novel strategies for augmenting or inhibiting erythropoiesis. PMID:27244685

  1. p47 GTPases Regulate Toxoplasma gondii Survival in Activated Macrophages

    PubMed Central

    Butcher, Barbara A.; Greene, Robert I.; Henry, Stanley C.; Annecharico, Kimberly L.; Weinberg, J. Brice; Denkers, Eric Y.; Sher, Alan; Taylor, Gregory A.

    2005-01-01

    The cytokine gamma interferon (IFN-γ) is critical for resistance to Toxoplasma gondii. IFN-γ strongly activates macrophages and nonphagocytic host cells to limit intracellular growth of T. gondii; however, the cellular factors that are required for this effect are largely unknown. We have shown previously that IGTP and LRG-47, members of the IFN-γ-regulated family of p47 GTPases, are required for resistance to acute T. gondii infections in vivo. In contrast, IRG-47, another member of this family, is not required. In the present work, we addressed whether these GTPases are required for IFN-γ-induced suppression of T. gondii growth in macrophages in vitro. Bone marrow macrophages that lacked IGTP or LRG-47 displayed greatly attenuated IFN-γ-induced inhibition of T. gondii growth, while macrophages that lacked IRG-47 displayed normal inhibition. Thus, the ability of the p47 GTPases to limit acute infection in vivo correlated with their ability to suppress intracellular growth in macrophages in vitro. Using confocal microscopy and sucrose density fractionation, we demonstrated that IGTP largely colocalizes with endoplasmic reticulum markers, while LRG-47 was mainly restricted to the Golgi. Although both IGTP and LRG-47 localized to vacuoles containing latex beads, neither protein localized to vacuoles containing live T. gondii. These results suggest that IGTP and LRG-47 are able to regulate host resistance to acute T. gondii infections through their ability to inhibit parasite growth within the macrophage. PMID:15908352

  2. Serum cholesterol selectively regulates glucocorticoid sensitivity through activation of JNK.

    PubMed

    Yang, Nan; Caratti, Giorgio; Ince, Louise M; Poolman, Toryn M; Trebble, Peter J; Holt, Cathy M; Ray, David W; Matthews, Laura C

    2014-11-01

    Glucocorticoids (Gc) are potent anti-inflammatory agents with wide clinical application. We have previously shown that increased serum concentration significantly attenuates regulation of a simple Gc-responsive reporter. We now find that glucocorticoid receptor (GR) regulation of some endogenous transactivated but not transrepressed genes is impaired, suggesting template specificity. Serum did not directly affect GR expression, activity or trafficking, implicating GR crosstalk with other signalling pathways. Indeed, a JNK inhibitor completely abolished the serum effect. We identified the Gc modulating serum component as cholesterol. Cholesterol loading mimicked the serum effect, which was readily reversed by JNK inhibition. Chelation of serum cholesterol with methyl-β-cyclodextrin or inhibition of cellular cholesterol synthesis with simvastatin potentiated the Gc response. To explore the effect in vivo we used ApoE(-/-) mice, a model of hypercholesterolaemia. Consistent with our in vitro studies, we find no impact of elevated cholesterol on the expression of GR, or on the hypothalamic-pituitary-adrenal axis, measured by dexamethasone suppression test. Instead we find selective Gc resistance on some hepatic target genes in ApoE(-/-) mice. Therefore, we have discovered an unexpected role for cholesterol as a selective modulator of Gc action in vivo. Taken together these findings reveal a new environmental constraint on Gc action with relevance to both inflammation and cancer.

  3. SUMOylation of Pancreatic Glucokinase Regulates Its Cellular Stability and Activity*

    PubMed Central

    Aukrust, Ingvild; Bjørkhaug, Lise; Negahdar, Maria; Molnes, Janne; Johansson, Bente B.; Müller, Yvonne; Haas, Wilhelm; Gygi, Steven P.; Søvik, Oddmund; Flatmark, Torgeir; Kulkarni, Rohit N.; Njølstad, Pål R.

    2013-01-01

    Glucokinase is the predominant hexokinase expressed in hepatocytes and pancreatic β-cells, with a pivotal role in regulating glucose-stimulated insulin secretion, illustrated by glucokinase gene mutations causing monogenic diabetes and congenital hyperinsulinemic hypoglycemia. A complex tissue-specific network of mechanisms regulates this enzyme, and a major unanswered question in glucokinase biology is how post-translational modifications control the function of the enzyme. Here, we show that the pancreatic isoform of human glucokinase is SUMOylated in vitro, using recombinant enzymes, and in insulin-secreting model cells. Three N-terminal lysines unique for the pancreatic isoform (Lys-12/Lys-13 and/or Lys-15) may represent one SUMOylation site, with an additional site (Lys-346) common for the pancreatic and the liver isoform. SUMO-1 and E2 overexpression stabilized preferentially the wild-type human pancreatic enzyme in MIN6 β-cells, and SUMOylation increased the catalytic activity of recombinant human glucokinase in vitro and also of glucokinase in target cells. Small ubiquitin-like modifier conjugation represents a novel form of post-translational modification of the enzyme, and it may have an important regulatory function in pancreatic β-cells. PMID:23297408

  4. Multi-site Phosphorylation Regulates Bim Stability and Apoptotic Activity

    PubMed Central

    Hübner, Anette; Barrett, Tamera; Flavell, Richard A.; Davis, Roger J.

    2008-01-01

    The pro-apoptotic BH3-only protein Bim is established to be an important mediator of signaling pathways that induce cell death. Multi-site phosphorylation of Bim by several members of the MAP kinase group is implicated as a regulatory mechanism that controls the apoptotic activity of Bim. To test the role of Bim phosphorylation in vivo, we constructed mice with a series of mutant alleles that express phosphorylation-defective Bim proteins. We show that mutation of the phosphorylation site Thr-112 causes decreased binding of Bim to the anti-apoptotic protein Bcl2 and can increase cell survival. In contrast, mutation of the phosphorylation sites Ser-55, Ser-65, and Ser-73 can cause increased apoptosis because of reduced proteasomal degradation of Bim. Together, these data indicate that phosphorylation can regulate Bim by multiple mechanisms and that the phosphorylation of Bim on different sites can contribute to the sensitivity of cellular apoptotic responses. PMID:18498746

  5. Parkin Regulates the Activity of Pyruvate Kinase M2*

    PubMed Central

    Liu, Kun; Li, Fanzhou; Han, Haichao; Chen, Yue; Mao, Zebin; Luo, Jianyuan; Zhao, Yingming; Zheng, Bin; Gu, Wei; Zhao, Wenhui

    2016-01-01

    Parkin, a ubiquitin E3 ligase, is mutated in most cases of autosomal recessive early onset Parkinson disease. It was discovered that Parkin is also mutated in glioblastoma and other human malignancies and that it inhibits tumor cell growth. Here, we identified pyruvate kinase M2 (PKM2) as a unique substrate for parkin through biochemical purification. We found that parkin interacts with PKM2 both in vitro and in vivo, and this interaction dramatically increases during glucose starvation. Ubiquitylation of PKM2 by parkin does not affect its stability but decreases its enzymatic activity. Parkin regulates the glycolysis pathway and affects the cell metabolism. Our studies revealed the novel important roles of parkin in tumor cell metabolism and provided new insight for therapy of Parkinson disease. PMID:26975375

  6. Effects of Online Self-Regulation Activities on Physical Activity Among Pregnant and Early Postpartum Women.

    PubMed

    Kim, Hye Kyung; Niederdeppe, Jeff; Graham, Meredith; Olson, Christine; Gay, Geri

    2015-01-01

    Physical and psychological changes that occur during pregnancy present a unique challenge for women's physical activity. Using a theory-based prospective design, this study examines the effects of pregnant women's (a) physical activity cognitions (self-efficacy, outcome expectancy, and safety beliefs) and (b) online self-regulation activities (goal-setting and self-monitoring) on subsequent changes in their physical activity intentions and behavior during pregnancy and immediately postpartum. The authors used data from three panel surveys administered to pregnant women enrolled in a web-based intervention to promote healthy pregnancy and postpartum weight, as well as log data on their use of self-regulatory features on the intervention website. Perceived self-efficacy and perceived safety of physical activity in pregnancy enhanced subsequent intentions to be physically active. Repeated goal-setting and monitoring of those goals helped to maintain positive intentions during pregnancy, but only repeated self-monitoring transferred positive intentions into actual behavior. Theoretically, this study offers a better understanding of the roles of self-regulation activities in the processes of goal-striving. The authors also discuss practical implications for encouraging physical activity among pregnant and early postpartum women.

  7. Hepatic triacylglycerol hydrolysis regulates peroxisome proliferator-activated receptor alpha activity.

    PubMed

    Sapiro, Jessica M; Mashek, Mara T; Greenberg, Andrew S; Mashek, Douglas G

    2009-08-01

    Recent evidence suggests that fatty acids generated from intracellular triacylglycerol (TAG) hydrolysis may have important roles in intracellular signaling. This study was conducted to determine if fatty acids liberated from TAG hydrolysis regulate peroxisome proliferator-activated receptor alpha (PPARalpha). Primary rat hepatocyte cultures were treated with adenoviruses overexpressing adipose differentiation-related protein (ADRP) or adipose triacylglycerol lipase (ATGL) or treated with short interfering RNA (siRNA) targeted against ADRP. Subsequent effects on TAG metabolism and PPARalpha activity and target gene expression were determined. Overexpressing ADRP attenuated TAG hydrolysis, whereas siRNA-mediated knockdown of ADRP or ATGL overexpression resulted in enhanced TAG hydrolysis. Results from PPARalpha reporter activity assays demonstrated that decreasing TAG hydrolysis by ADRP overexpression resulted in a 35-60% reduction in reporter activity under basal conditions or in the presence of fatty acids. As expected, PPARalpha target genes were also decreased in response to ADRP overexpression. However, the PPARalpha ligand, WY-14643, was able to restore PPARalpha activity following ADRP overexpression. Despite its effects on PPARalpha, overexpressing ADRP did not affect PPARgamma activity. Enhancing TAG hydrolysis through ADRP knockdown or ATGL overexpression increased PPARalpha activity. These results indicate that TAG hydrolysis and the consequential release of fatty acids regulate PPARalpha activity.

  8. Regulation of sucrose metabolism in higher plants: localization and regulation of activity of key enzymes

    NASA Technical Reports Server (NTRS)

    Winter, H.; Huber, S. C.; Brown, C. S. (Principal Investigator)

    2000-01-01

    Sucrose (Suc) plays a central role in plant growth and development. It is a major end product of photosynthesis and functions as a primary transport sugar and in some cases as a direct or indirect regulator of gene expression. Research during the last 2 decades has identified the pathways involved and which enzymes contribute to the control of flux. Availability of metabolites for Suc synthesis and 'demand' for products of sucrose degradation are important factors, but this review specifically focuses on the biosynthetic enzyme sucrose-phosphate synthase (SPS), and the degradative enzymes, sucrose synthase (SuSy), and the invertases. Recent progress has included the cloning of genes encoding these enzymes and the elucidation of posttranslational regulatory mechanisms. Protein phosphorylation is emerging as an important mechanism controlling SPS activity in response to various environmental and endogenous signals. In terms of Suc degradation, invertase-catalyzed hydrolysis generally has been associated with cell expansion, whereas SuSy-catalyzed metabolism has been linked with biosynthetic processes (e.g., cell wall or storage products). Recent results indicate that SuSy may be localized in multiple cellular compartments: (1) as a soluble enzyme in the cytosol (as traditionally assumed); (2) associated with the plasma membrane; and (3) associated with the actin cytoskeleton. Phosphorylation of SuSy has been shown to occur and may be one of the factors controlling localization of the enzyme. The purpose of this review is to summarize some of the recent developments relating to regulation of activity and localization of key enzymes involved in sucrose metabolism in plants.

  9. Characterization of murine BATF: a negative regulator of activator protein-1 activity in the thymus.

    PubMed

    Williams, K L; Nanda, I; Lyons, G E; Kuo, C T; Schmid, M; Leiden, J M; Kaplan, M H; Taparowsky, E J

    2001-05-01

    BATF belongs to the AP-1/ATF superfamily of transcription factors and forms heterodimers with Jun proteins to bind AP-1 consensus DNA. Unlike Fos/Jun heterodimers which stimulate gene transcription, BATF/Jun heterodimers are transcriptionally inert and inhibit biological processes that are associated with the overstimulation of AP-1 activity. Here, we describe the murine BATF cDNA and genomic clones and map the BATF locus to chromosome 12 D2-3. Using in situ hybridization of BATF mRNA, we show that BATF gene expression is highly restricted, with the most prominent signals detected in the thymus. BATF mRNA levels are regulated differentially during discrete stages of T cell development and are up-regulated following activation of T cells in the periphery. To demonstrate the impact of BATF on AP-1 activity in vivo, AP-1 luciferase reporter mice were crossed to transgenic mice overexpressing BATF exclusively in thymic T cells. Results show that elevated levels of BATF protein correlate with reduced transactivation by AP-1. Since the differential regulation of AP-1 activity is linked to key transitions in the developing immune system, our observations support a critical role for BATF in determining the overall level of AP-1 activity, and thus AP-1 target gene expression, in specific T cell subtypes.

  10. Regulation of RYR1 activity by Ca(2+) and calmodulin

    NASA Technical Reports Server (NTRS)

    Rodney, G. G.; Williams, B. Y.; Strasburg, G. M.; Beckingham, K.; Hamilton, S. L.

    2000-01-01

    The skeletal muscle calcium release channel (RYR1) is a Ca(2+)-binding protein that is regulated by another Ca(2+)-binding protein, calmodulin. The functional consequences of calmodulin's interaction with RYR1 are dependent on Ca(2+) concentration. At nanomolar Ca(2+) concentrations, calmodulin is an activator, but at micromolar Ca(2+) concentrations, calmodulin is an inhibitor of RYR1. This raises the question of whether the Ca(2+)-dependent effects of calmodulin on RYR1 function are due to Ca(2+) binding to calmodulin, RYR1, or both. To distinguish the effects of Ca(2+) binding to calmodulin from those of Ca(2+) binding to RYR1, a mutant calmodulin that cannot bind Ca(2+) was used to evaluate the effects of Ca(2+)-free calmodulin on Ca(2+)-bound RYR1. We demonstrate that Ca(2+)-free calmodulin enhances the affinity of RYR1 for Ca(2+) while Ca(2+) binding to calmodulin converts calmodulin from an activator to an inhibitor. Furthermore, Ca(2+) binding to RYR1 enhances its affinity for both Ca(2+)-free and Ca(2+)-bound calmodulin.

  11. OASIS modulates hypoxia pathway activity to regulate bone angiogenesis.

    PubMed

    Cui, Min; Kanemoto, Soshi; Cui, Xiang; Kaneko, Masayuki; Asada, Rie; Matsuhisa, Koji; Tanimoto, Keiji; Yoshimoto, Yuki; Shukunami, Chisa; Imaizumi, Kazunori

    2015-11-12

    OASIS/CREB3L1, an endoplasmic reticulum (ER)-resident transcription factor, plays important roles in osteoblast differentiation. In this study, we identified new crosstalk between OASIS and the hypoxia signaling pathway, which regulates vascularization during bone development. RT-PCR and real-time PCR analyses revealed significant decreases in the expression levels of hypoxia-inducible factor-1α (HIF-1α) target genes such as vascular endothelial growth factor A (VEGFA) in OASIS-deficient (Oasis(-/-)) mouse embryonic fibroblasts. In coimmunoprecipitation experiments, the N-terminal fragment of OASIS (OASIS-N; activated form of OASIS) bound to HIF-1α through the bZIP domain. Luciferase assays showed that OASIS-N promoted the transcription activities of a reporter gene via a hypoxia-response element (HRE). Furthermore, the expression levels of an angiogenic factor Vegfa was decreased in Oasis(-/-) osteoblasts. Immunostaining and metatarsal angiogenesis assay showed retarded vascularization in bone tissue of Oasis(-/-) mice. These results suggest that OASIS affects the expression of HIF-1α target genes through the protein interaction with HIF-1α, and that OASIS-HIF-1α complexes may play essential roles in angiogenesis during bone development.

  12. OASIS modulates hypoxia pathway activity to regulate bone angiogenesis

    PubMed Central

    Cui, Min; Kanemoto, Soshi; Cui, Xiang; Kaneko, Masayuki; Asada, Rie; Matsuhisa, Koji; Tanimoto, Keiji; Yoshimoto, Yuki; Shukunami, Chisa; Imaizumi, Kazunori

    2015-01-01

    OASIS/CREB3L1, an endoplasmic reticulum (ER)-resident transcription factor, plays important roles in osteoblast differentiation. In this study, we identified new crosstalk between OASIS and the hypoxia signaling pathway, which regulates vascularization during bone development. RT-PCR and real-time PCR analyses revealed significant decreases in the expression levels of hypoxia-inducible factor-1α (HIF-1α) target genes such as vascular endothelial growth factor A (VEGFA) in OASIS-deficient (Oasis−/−) mouse embryonic fibroblasts. In coimmunoprecipitation experiments, the N-terminal fragment of OASIS (OASIS-N; activated form of OASIS) bound to HIF-1α through the bZIP domain. Luciferase assays showed that OASIS-N promoted the transcription activities of a reporter gene via a hypoxia-response element (HRE). Furthermore, the expression levels of an angiogenic factor Vegfa was decreased in Oasis−/− osteoblasts. Immunostaining and metatarsal angiogenesis assay showed retarded vascularization in bone tissue of Oasis−/− mice. These results suggest that OASIS affects the expression of HIF-1α target genes through the protein interaction with HIF-1α, and that OASIS-HIF-1α complexes may play essential roles in angiogenesis during bone development. PMID:26558437

  13. Sucking pump activity in feeding behaviour regulation in carpenter ants.

    PubMed

    Falibene, Agustina; Gontijo, Alberto de Figueiredo; Josens, Roxana

    2009-06-01

    Modulation of liquid feeding-rate would allow insects to ingest more food in the same time when this was required. Ants can vary nectar intake rate by increasing sucking pump frequency according to colony requirements. We analysed electrical signals generated by sucking pump activity of ants during drinking solutions of different sucrose concentrations and under different carbohydrate-deprivation levels. Our aim was to define parameters that characterize the recordings and analyse their relationship with feeding behaviour. Signals showed that the initial and final frequencies of sucking pump activity, as well as the difference between them were higher in sugar-deprived ants. However, these parameters were not influenced by sucrose solution concentration, which affected the number of pump contractions and the volume per contraction. Unexpectedly, we found two different responses in feeding behaviour of starved and non-starved ants depending on concentration. Starved ants drank dilute solutions for the same length of time as non-starved ants but ingested higher volumes. While drinking the concentrated solutions, starved ants drank the same volume, but did so in a shorter time than the non-starved ones. Despite these differences, for each analysed concentration the total number of pump contractions remained constant independently of sugar-deprivation level. These results are discussed in the frame of feeding regulation and decision making in ant foraging behaviour. PMID:19217950

  14. Sucking pump activity in feeding behaviour regulation in carpenter ants.

    PubMed

    Falibene, Agustina; Gontijo, Alberto de Figueiredo; Josens, Roxana

    2009-06-01

    Modulation of liquid feeding-rate would allow insects to ingest more food in the same time when this was required. Ants can vary nectar intake rate by increasing sucking pump frequency according to colony requirements. We analysed electrical signals generated by sucking pump activity of ants during drinking solutions of different sucrose concentrations and under different carbohydrate-deprivation levels. Our aim was to define parameters that characterize the recordings and analyse their relationship with feeding behaviour. Signals showed that the initial and final frequencies of sucking pump activity, as well as the difference between them were higher in sugar-deprived ants. However, these parameters were not influenced by sucrose solution concentration, which affected the number of pump contractions and the volume per contraction. Unexpectedly, we found two different responses in feeding behaviour of starved and non-starved ants depending on concentration. Starved ants drank dilute solutions for the same length of time as non-starved ants but ingested higher volumes. While drinking the concentrated solutions, starved ants drank the same volume, but did so in a shorter time than the non-starved ones. Despite these differences, for each analysed concentration the total number of pump contractions remained constant independently of sugar-deprivation level. These results are discussed in the frame of feeding regulation and decision making in ant foraging behaviour.

  15. Notch1 regulated autophagy controls survival and suppressor activity of activated murine T-regulatory cells

    PubMed Central

    Marcel, Nimi; Sarin, Apurva

    2016-01-01

    Cell survival is one of several processes regulated by the Notch pathway in mammalian cells. Here we report functional outcomes of non-nuclear Notch signaling to activate autophagy, a conserved cellular response to nutrient stress, regulating survival in murine natural T-regulatory cells (Tregs), an immune subset controlling tolerance and inflammation. Induction of autophagy required ligand-dependent, Notch intracellular domain (NIC) activity, which controlled mitochondrial organization and survival of activated Tregs. Consistently, NIC immune-precipitated Beclin and Atg14, constituents of the autophagy initiation complex. Further, ectopic expression of an effector of autophagy (Atg3) or recombinant NIC tagged to a nuclear export signal (NIC-NES), restored autophagy and suppressor function in Notch1-/- Tregs. Furthermore, Notch1 deficiency in the Treg lineage resulted in immune hyperactivity, implicating Notch activity in Treg homeostasis. Notch1 integration with autophagy, revealed in these experiments, holds implications for Notch regulated cell-fate decisions governing differentiation. DOI: http://dx.doi.org/10.7554/eLife.14023.001 PMID:27267497

  16. The regulation and activation of lupus-associated B cells.

    PubMed

    Fields, Michele L; Hondowicz, Brian D; Wharton, Gina N; Adair, Brigette S; Metzgar, Michele H; Alexander, Shawn T; Caton, Andrew J; Erikson, Jan

    2005-04-01

    Anti-double-stranded DNA (anti-dsDNA) B cells are regulated in non-autoimmune mice. While some are deleted or undergo receptor editing, a population of anti-dsDNA (VH3H9/V lambda 1) B cells that emigrate into the periphery has also been identified. These cells have an altered phenotype relative to normal B cells in that they have a reduced lifespan, appear developmentally arrested, and localize primarily to the T/B-cell interface in the spleen. This phenotype may be the consequence of immature B cells encountering antigen in the absence of T-cell help. When provided with T-cell help, the anti-dsDNA B cells differentiate into antibody-forming cells. In the context of the autoimmune-prone lpr/lpr or gld/gld mutations, the VH3H9/V lambda 1 anti-dsDNA B cells populate the B-cell follicle and by 12 weeks of age produce serum autoantibodies. The early event of anti-dsDNA B-cell follicular entry, in the absence of autoantibody production, is dependent upon CD4(+) T cells. We hypothesize that control of autoantibody production in young autoimmune-prone mice may be regulated by the counterbalancing effect of T-regulatory (T(reg)) cells. Consistent with this model, we have demonstrated that T(reg) cells are able to prevent autoantibody production induced by T-cell help. Additional studies are aimed at investigating the mechanisms of this suppression as well as probing the impact of distinct forms of T-cell-dependent and -independent activation on anti-dsDNA B cells.

  17. Measuring Self-Regulation: A Focus on Activity

    ERIC Educational Resources Information Center

    Turner, Julianne C.

    2006-01-01

    Ainley and Patrick describe an assessment process designed to "identify self-regulation in action." In the spirit of this goal, the author offers three suggestions for providing a more holistic and contextual view of self-regulation. These suggestions include (a) expanding the definition of self-regulation used in their studies; (b) measuring…

  18. 33 CFR 148.737 - What environmental statutes must an applicant follow?

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... statutes and Executive Orders (E.O.s) that may apply includes but is not limited to: Abandoned Shipwreck...; Protection of Children from Environmental Health and Safety Risks, E.O. 13045, 62 FR 19885; Protection...

  19. 33 CFR 148.737 - What environmental statutes must an applicant follow?

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... statutes and Executive Orders (E.O.s) that may apply includes but is not limited to: Abandoned Shipwreck...; Protection of Children from Environmental Health and Safety Risks, E.O. 13045, 62 FR 19885; Protection...

  20. Regulation of AMP-activated protein kinase by natural and synthetic activators

    PubMed Central

    Grahame Hardie, David

    2015-01-01

    The AMP-activated protein kinase (AMPK) is a sensor of cellular energy status that is almost universally expressed in eukaryotic cells. While it appears to have evolved in single-celled eukaryotes to regulate energy balance in a cell-autonomous manner, during the evolution of multicellular animals its role has become adapted so that it also regulates energy balance at the whole body level, by responding to hormones that act primarily on the hypothalamus. AMPK monitors energy balance at the cellular level by sensing the ratios of AMP/ATP and ADP/ATP, and recent structural analyses of the AMPK heterotrimer that have provided insight into the complex mechanisms for these effects will be discussed. Given the central importance of energy balance in diseases that are major causes of morbidity or death in humans, such as type 2 diabetes, cancer and inflammatory disorders, there has been a major drive to develop pharmacological activators of AMPK. Many such activators have been described, and the various mechanisms by which these activate AMPK will be discussed. A particularly large class of AMPK activators are natural products of plants derived from traditional herbal medicines. While the mechanism by which most of these activate AMPK has not yet been addressed, I will argue that many of them may be defensive compounds produced by plants to deter infection by pathogens or grazing by insects or herbivores, and that many of them will turn out to be inhibitors of mitochondrial function. PMID:26904394

  1. Regulation of AMP-activated protein kinase by natural and synthetic activators.

    PubMed

    Grahame Hardie, David

    2016-01-01

    The AMP-activated protein kinase (AMPK) is a sensor of cellular energy status that is almost universally expressed in eukaryotic cells. While it appears to have evolved in single-celled eukaryotes to regulate energy balance in a cell-autonomous manner, during the evolution of multicellular animals its role has become adapted so that it also regulates energy balance at the whole body level, by responding to hormones that act primarily on the hypothalamus. AMPK monitors energy balance at the cellular level by sensing the ratios of AMP/ATP and ADP/ATP, and recent structural analyses of the AMPK heterotrimer that have provided insight into the complex mechanisms for these effects will be discussed. Given the central importance of energy balance in diseases that are major causes of morbidity or death in humans, such as type 2 diabetes, cancer and inflammatory disorders, there has been a major drive to develop pharmacological activators of AMPK. Many such activators have been described, and the various mechanisms by which these activate AMPK will be discussed. A particularly large class of AMPK activators are natural products of plants derived from traditional herbal medicines. While the mechanism by which most of these activate AMPK has not yet been addressed, I will argue that many of them may be defensive compounds produced by plants to deter infection by pathogens or grazing by insects or herbivores, and that many of them will turn out to be inhibitors of mitochondrial function. PMID:26904394

  2. Regulation of Hyperpolarization-activated Cyclic Nucleotide-gated (HCN) Channel Activity by cCMP*

    PubMed Central

    Zong, Xiangang; Krause, Stefanie; Chen, Cheng-Chang; Krüger, Jens; Gruner, Christian; Cao-Ehlker, Xiaochun; Fenske, Stefanie; Wahl-Schott, Christian; Biel, Martin

    2012-01-01

    Activation of hyperpolarization-activated cyclic nucleotide-gated (HCN) channels is facilitated in vivo by direct binding of the second messenger cAMP. This process plays a fundamental role in the fine-tuning of HCN channel activity and is critical for the modulation of cardiac and neuronal rhythmicity. Here, we identify the pyrimidine cyclic nucleotide cCMP as another regulator of HCN channels. We demonstrate that cCMP shifts the activation curves of two members of the HCN channel family, HCN2 and HCN4, to more depolarized voltages. Moreover, cCMP speeds up activation and slows down deactivation kinetics of these channels. The two other members of the HCN channel family, HCN1 and HCN3, are not sensitive to cCMP. The modulatory effect of cCMP is reversible and requires the presence of a functional cyclic nucleotide-binding domain. We determined an EC50 value of ∼30 μm for cCMP compared with 1 μm for cAMP. Notably, cCMP is a partial agonist of HCN channels, displaying an efficacy of ∼0.6. cCMP increases the frequency of pacemaker potentials from isolated sinoatrial pacemaker cells in the presence of endogenous cAMP concentrations. Electrophysiological recordings indicated that this increase is caused by a depolarizing shift in the activation curve of the native HCN current, which in turn leads to an enhancement of the slope of the diastolic depolarization of sinoatrial node cells. In conclusion, our findings establish cCMP as a gating regulator of HCN channels and indicate that this cyclic nucleotide has to be considered in HCN channel-regulated processes. PMID:22715094

  3. Regulation of platelet activating factor receptor coupled phosphoinositide-specific phospholipase C activity

    SciTech Connect

    Morrison, W.J.

    1988-01-01

    The major objectives of this study were two-fold. The first was to establish whether binding of platelet activating factor (PAF) to its receptor was integral to the stimulation of polyphosphoinositide-specific phospholipase C (PLC) in rabbit platelets. The second was to determine regulatory features of this receptor-coupled mechanism. ({sup 3}H)PAF binding demonstrated two binding sites, a high affinity site with a inhibitory constant (Ki) of 2.65 nM and a low affinity site with a Ki of 0.80 {mu}M. PAF receptor coupled activation of phosphoinositide-specific PLC was studied in platelets which were made refractory, by short term pretreatments, to either PAF or thrombin. Saponin-permeabilized rabbit platelets continue to regulate the mechanism(s) coupling PAF receptors to PLC stimulation. However, TRP{gamma}S and GDP{beta}S, which affect guanine nucleotide regulatory protein functions, were unable to modulate the PLC activity to any appreciable extent as compared to PAF. The possible involvement of protein kinase C (PKC) activation in regulating PAF-stimulated PLC activity was studied in rabbit platelets pretreated with staurosporine followed by pretreatments with PAF or phorbol 12-myristate 13-acetate (PMA).

  4. Apical constriction and epithelial invagination are regulated by BMP activity

    PubMed Central

    Jidigam, Vijay K.; Srinivasan, Raghuraman C.; Patthey, Cedric; Gunhaga, Lena

    2015-01-01

    ABSTRACT Epithelial invagination is a morphological process in which flat cell sheets transform into three-dimensional structures through bending of the tissue. It is accompanied by apical constriction, in which the apical cell surface is reduced in relation to the basal cell surface. Although much is known about the intra-cellular molecular machinery driving apical constriction and epithelial invagination, information of how extra-cellular signals affect these processes remains insufficient. In this study we have established several in vivo assays of placodal invagination to explore whether the external signal BMP regulates processes connected to epithelial invagination. By inhibiting BMP activity in prospective cranial placodes, we provide evidence that BMP signals are required for RhoA and F-actin rearrangements, apical constriction, cell elongation and epithelial invagination. The failure of placode invagination after BMP inhibition appears to be a direct consequence of disrupted apical accumulation of RhoA and F-actin, rather than changes in cell death or proliferation. In addition, our results show that epithelial invagination and acquisition of placode-specific identities are two distinct and separable developmental processes. In summary, our results provide evidence that BMP signals promote epithelial invagination by acting upstream of the intracellular molecular machinery that drives apical constriction and cell elongation. PMID:26621830

  5. Tonic PKA Activity Regulates SK Channel Nanoclustering and Somatodendritic Distribution.

    PubMed

    Abiraman, Krithika; Sah, Megha; Walikonis, Randall S; Lykotrafitis, George; Tzingounis, Anastasios V

    2016-06-01

    Small-conductance calcium-activated potassium (SK) channels mediate a potassium conductance in the brain and are involved in synaptic plasticity, learning, and memory. SK channels show a distinct subcellular localization that is crucial for their neuronal functions. However, the mechanisms that control this spatial distribution are unknown. We imaged SK channels labeled with fluorophore-tagged apamin and monitored SK channel nanoclustering at the single molecule level by combining atomic force microscopy and toxin (i.e., apamin) pharmacology. Using these two complementary approaches, we found that native SK channel distribution in pyramidal neurons, across the somatodendritic domain, depends on ongoing cyclic adenosine monophosphate (cAMP)-protein kinase A (PKA) levels, strongly limiting SK channel expression at the pyramidal neuron soma. Furthermore, tonic cAMP-PKA levels also controlled whether SK channels were expressed in nanodomains as single entities or as a group of multiple channels. Our study reveals a new level of regulation of SK channels by cAMP-PKA and suggests that ion channel topography and nanoclustering might be under the control of second messenger cascades. PMID:27107637

  6. German National Galileo Public Regulated Service (PRS) Testing Activities

    NASA Astrophysics Data System (ADS)

    Habrich, Heinz; Söhne, Wolfgang

    2013-04-01

    The European Global Navigation System (GNSS) Galileo is going to be established in the near future. Currently, four satellites are in place forming the In-Orbit-Testing (IOT) phase. Within the next years, the constellation will be filled. Full Operational Capability (FOC) will be reached 2019. Beside the Open Service (OS) which is comparable to other OS of existing GNSS, e.g., GPS C/A, there is a so-called Public Regulated Service (PRS) included in the IOT satellites already. The PRS will have improved robustness, i.e. robust signals which will be resistant against involuntary interferences, jamming and spoofing. The PRS signal is encrypted and there will be a restricted access to authorized users, e.g. safety and emergency services, authorities with security task, critical infrastructure organizations etc. The access to the PRS which will be controlled through a special key management will be managed and supervised within the European Union (EU) Member States (MS) by national authorities, the Competent PRS Authority (CPA). But a set of Common Minimum Standards (CMS) will define the minimum requirements applicable to each PRS participant. Nevertheless, each MS is responsible for its national key management. This presentation will inform about the testing activities for Galileo PRS in Germany. The coarse concept for the testing is explained, the schedule is outlined. Finally, the paper will formulate some expectations to the Galileo PRS, e.g. for international cooperation.

  7. Kisspeptin Regulation of Neuronal Activity throughout the Central Nervous System

    PubMed Central

    Liu, Xinhuai

    2016-01-01

    Kisspeptin signaling at the gonadotropin-releasing hormone (GnRH) neuron is now relatively well characterized and established as being critical for the neural control of fertility. However, kisspeptin fibers and the kisspeptin receptor (KISS1R) are detected throughout the brain suggesting that kisspeptin is involved in regulating the activity of multiple neuronal circuits. We provide here a review of kisspeptin actions on neuronal populations throughout the brain including the magnocellular oxytocin and vasopressin neurons, and cells within the arcuate nucleus, hippocampus, and amygdala. The actions of kisspeptin in these brain regions are compared to its effects upon GnRH neurons. Two major themes arise from this analysis. First, it is apparent that kisspeptin signaling through KISS1R at the GnRH neuron is a unique, extremely potent form or neurotransmission whereas kisspeptin actions through KISS1R in other brain regions exhibit neuromodulatory actions typical of other neuropeptides. Second, it is becoming increasingly likely that kisspeptin acts as a neuromodulator not only through KISS1R but also through other RFamide receptors such as the neuropeptide FF receptors (NPFFRs). We suggest likely locations of kisspeptin signaling through NPFFRs but note that only limited tools are presently available for examining kisspeptin cross-signaling within the RFamide family of neuropeptides. PMID:27246282

  8. 43 CFR 17.302 - To what programs or activities do these regulations apply?

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... regulations apply to each DOI recipient and to each program or activity operated by the recipient which receives Federal financial assistance provided by DOI. (b) The Act and these regulations do not apply...

  9. Miro1 Regulates Activity-Driven Positioning of Mitochondria within Astrocytic Processes Apposed to Synapses to Regulate Intracellular Calcium Signaling.

    PubMed

    Stephen, Terri-Leigh; Higgs, Nathalie F; Sheehan, David F; Al Awabdh, Sana; López-Doménech, Guillermo; Arancibia-Carcamo, I Lorena; Kittler, Josef T

    2015-12-01

    It is fast emerging that maintaining mitochondrial function is important for regulating astrocyte function, although the specific mechanisms that govern astrocyte mitochondrial trafficking and positioning remain poorly understood. The mitochondrial Rho-GTPase 1 protein (Miro1) regulates mitochondrial trafficking and detachment from the microtubule transport network to control activity-dependent mitochondrial positioning in neurons. However, whether Miro proteins are important for regulating signaling-dependent mitochondrial dynamics in astrocytic processes remains unclear. Using live-cell confocal microscopy of rat organotypic hippocampal slices, we find that enhancing neuronal activity induces transient mitochondrial remodeling in astrocytes, with a concomitant, transient reduction in mitochondrial trafficking, mediated by elevations in intracellular Ca(2+). Stimulating neuronal activity also induced mitochondrial confinement within astrocytic processes in close proximity to synapses. Furthermore, we show that the Ca(2+)-sensing EF-hand domains of Miro1 are important for regulating mitochondrial trafficking in astrocytes and required for activity-driven mitochondrial confinement near synapses. Additionally, activity-dependent mitochondrial positioning by Miro1 reciprocally regulates the levels of intracellular Ca(2+) in astrocytic processes. Thus, the regulation of intracellular Ca(2+) signaling, dependent on Miro1-mediated mitochondrial positioning, could have important consequences for astrocyte Ca(2+) wave propagation, gliotransmission, and ultimately neuronal function. PMID:26631479

  10. Cystatin F regulates proteinase activity in IL-2-activated natural killer cells.

    PubMed

    Maher, Katarina; Konjar, Spela; Watts, Colin; Turk, Boris; Kopitar-Jerala, Natasa

    2014-01-01

    Cystatin F is a unique member of the cystatin family of cysteine protease inhibitors, which is synthesized as an inactive dimer and it is activated by N-terminal cleavage in the endolysosomes. It is expressed in the cells of the immune system: myeloid cells and the cells involved in target cell killing: natural killer (NK) cells and cytotoxic T cells (CTLs). Upon activation of the NK cells with interleukin 2 (IL-2), cystatin F was found upregulated and co-localized in cytotoxic granules with cathepsin C (CatC) and CatV. However, cystatin F inhibits the CatC in cells only when its N-terminal part is processed. Although cystatin F could inhibit both CatV and CatC, the IL-2 stimulation of the YT cells resulted in an increased CatV activity, while the CatC activity was unchanged. The incubation of IL-2 activated NK cells with a cysteine proteinase inhibitor E-64d increased the cystatin F dimer formation. Our results suggest that cystatin F not only inhibits CatV, but it is processed by the CatV in order to inhibit the CatC activity in cytotoxic granules. The regulation of the CatC activity in the cytotoxic granules of the NK cells by the cystatin F could be important for the processing and activation of granule-associated serine proteases - granzymes.

  11. Regulation of Prolactin in Mice with Altered Hypothalamic Melanocortin Activity

    PubMed Central

    Dutia, Roxanne; Kim, Andrea J.; Mosharov, Eugene; Savontaus, Eriika; Chua, Streamson C.; Wardlaw, Sharon L.

    2012-01-01

    This study used two mouse models with genetic manipulation of the melanocortin system to investigate prolactin regulation. Mice with overexpression of the melanocortin receptor (MC-R) agonist, α-melanocyte-stimulating hormone (Tg-MSH) or deletion of the MC-R antagonist agouti-related protein (AgRP KO) were studied. Male Tg-MSH mice had lower blood prolactin levels at baseline (2.9±0.3 vs 4.7±0.7 ng/ml) and after restraint stress(68 ±6.5 vs 117±22 ng/ml) versus WT (p<0.05); however, pituitary prolactin content was not different. Blood prolactin was also decreased in male AgRP KO mice at baseline (4.2±0.5 vs 7.6±1.3 ng/ml) and after stress (60±4.5 vs 86.1±5.7 ng/ml) vs WT (p <0.001). Pituitary prolactin content was lower in male AgRP KO mice (4.3±0.3 vs 6.7±0.5 μg/pituitary, p <0.001) versus WT. No differences in blood or pituitary prolactin levels were observed in female AgRP KO mice versus WT. Hypothalamic dopamine activity was assessed as the potential mechanism responsible for changes in prolactin levels. Hypothalamic tyrosine hydroxylase mRNA was measured in both genetic models versus WT mice and hypothalamic dopamine and 3,4-dihydroxyphenylacetic acid (DOPAC) content were measured in male AgRP KO and WT mice but neither were significantly different. However, these results do not preclude changes in dopamine activity as dopamine turnover was not directly investigated. This is the first study to show that baseline and stress-induced prolactin release and pituitary prolactin content are reduced in mice with genetic alterations of the melanocortin system and suggests that changes in hypothalamic melanocortin activity may be reflected in measurements of serum prolactin levels. PMID:22800691

  12. Regulation of prolactin in mice with altered hypothalamic melanocortin activity.

    PubMed

    Dutia, Roxanne; Kim, Andrea J; Mosharov, Eugene; Savontaus, Eriika; Chua, Streamson C; Wardlaw, Sharon L

    2012-09-01

    This study used two mouse models with genetic manipulation of the melanocortin system to investigate prolactin regulation. Mice with overexpression of the melanocortin receptor (MC-R) agonist, α-melanocyte-stimulating hormone (Tg-MSH) or deletion of the MC-R antagonist agouti-related protein (AgRP KO) were studied. Male Tg-MSH mice had lower blood prolactin levels at baseline (2.9±0.3 vs. 4.7±0.7ng/ml) and after restraint stress (68±6.5 vs. 117±22ng/ml) vs. WT (p<0.05); however, pituitary prolactin content was not different. Blood prolactin was also decreased in male AgRP KO mice at baseline (4.2±0.5 vs. 7.6±1.3ng/ml) and after stress (60±4.5 vs. 86.1±5.7ng/ml) vs. WT (p<0.001). Pituitary prolactin content was lower in male AgRP KO mice (4.3±0.3 vs. 6.7±0.5μg/pituitary, p<0.001) vs. WT. No differences in blood or pituitary prolactin levels were observed in female AgRP KO mice vs. WT. Hypothalamic dopamine activity was assessed as the potential mechanism responsible for changes in prolactin levels. Hypothalamic tyrosine hydroxylase mRNA was measured in both genetic models vs. WT mice and hypothalamic dopamine and 3,4-dihydroxyphenylacetic acid (DOPAC) content were measured in male AgRP KO and WT mice but neither were significantly different. However, these results do not preclude changes in dopamine activity as dopamine turnover was not directly investigated. This is the first study to show that baseline and stress-induced prolactin release and pituitary prolactin content are reduced in mice with genetic alterations of the melanocortin system and suggests that changes in hypothalamic melanocortin activity may be reflected in measurements of serum prolactin levels.

  13. Transcriptional Regulation in Saccharomyces cerevisiae: Transcription Factor Regulation and Function, Mechanisms of Initiation, and Roles of Activators and Coactivators

    PubMed Central

    Hahn, Steven; Young, Elton T.

    2011-01-01

    Here we review recent advances in understanding the regulation of mRNA synthesis in Saccharomyces cerevisiae. Many fundamental gene regulatory mechanisms have been conserved in all eukaryotes, and budding yeast has been at the forefront in the discovery and dissection of these conserved mechanisms. Topics covered include upstream activation sequence and promoter structure, transcription factor classification, and examples of regulated transcription factor activity. We also examine advances in understanding the RNA polymerase II transcription machinery, conserved coactivator complexes, transcription activation domains, and the cooperation of these factors in gene regulatory mechanisms. PMID:22084422

  14. NMDA receptor activation regulates sociability by its effect on mTOR signaling activity.

    PubMed

    Burket, Jessica A; Benson, Andrew D; Tang, Amy H; Deutsch, Stephen I

    2015-07-01

    Tuberous Sclerosis Complex is one example of a syndromic form of autism spectrum disorder associated with disinhibited activity of mTORC1 in neurons (e.g., cerebellar Purkinje cells). mTORC1 is a complex protein possessing serine/threonine kinase activity and a key downstream molecule in a signaling cascade beginning at the cell surface with the transduction of neurotransmitters (e.g., glutamate and acetylcholine) and nerve growth factors (e.g., Brain-Derived Neurotrophic Factor). Interestingly, the severity of the intellectual disability in Tuberous Sclerosis Complex may relate more to this metabolic disturbance (i.e., overactivity of mTOR signaling) than the density of cortical tubers. Several recent reports showed that rapamycin, an inhibitor of mTORC1, improved sociability and other symptoms in mouse models of Tuberous Sclerosis Complex and autism spectrum disorder, consistent with mTORC1 overactivity playing an important pathogenic role. NMDA receptor activation may also dampen mTORC1 activity by at least two possible mechanisms: regulating intraneuronal accumulation of arginine and the phosphorylation status of a specific extracellular signal regulating kinase (i.e., ERK1/2), both of which are "drivers" of mTORC1 activity. Conceivably, the prosocial effects of targeting the NMDA receptor with agonists in mouse models of autism spectrum disorders result from their ability to dampen mTORC1 activity in neurons. Strategies for dampening mTORC1 overactivity by NMDA receptor activation may be preferred to its direct inhibition in chronic neurodevelopmental disorders, such as autism spectrum disorders.

  15. Endothelial cell activation and proliferation modulate NKG2D activity by regulating MICA expression and shedding.

    PubMed

    Chauveau, Annabelle; Tonnerre, Pierre; Pabois, Angélique; Gavlovsky, Pierre-Jean; Chatelais, Mathais; Coupel, Stéphanie; Charreau, Béatrice

    2014-01-01

    MICA are major histocompatibility complex class I-related molecules, expressed by endothelial cells (ECs), that may be targets for alloantibodies and NKG2D-expressing natural killer (NK) and T effector cells in organ allografts. This study shows that basal levels of MICA expressed on vascular ECs is sufficient to functionally modulate the expression and activity of the immunoreceptor NKG2D in allogeneic NK cells. We found that MICA expression is differentially regulated at the EC surface in response to cytokines. TNFα upregulates MICA while IFNγ significantly decreases MICA at the EC surface. Both cytokines induce the release of soluble MICA by ECs. Modulation of NKG2D correlates with the MICA level on the EC surface. Glycosylation and metalloproteinase activities account for major post-transcriptional mechanisms controlling MICA level and the function in ECs. Our results indicate that, in addition to the NFκB pathway, the mitogen-activated protein kinase pathways JNK, ERK1/2 and p38 are key signaling pathways in the control of MICA by the cytokines. Finally, we show that EC proliferation mediated by FGF-2 or wound healing increases the MICA level. Together, our data suggest that inflammation and proliferation regulate endothelial MICA expression and shedding, enabling ECs to modulate NKG2D activity on effector NK and T cells, and provide further evidence of a role for ECs in immunoregulation.

  16. Adoption Activities on the Internet: A Call for Regulation

    ERIC Educational Resources Information Center

    Roby, Jini L.; White, Holly

    2010-01-01

    There is a growing practice of adoption services on the Internet with varying degrees of regulation, depending on whether it is domestic infant adoption, public foster care adoption, or international adoption. Regulation is particularly lacking in domestic infant adoptions, with Web sites connecting prospective birth and adoptive parents,…

  17. Detection of Neu1 Sialidase Activity in Regulating TOLL-like Receptor Activation

    PubMed Central

    Abdulkhalek, Samar

    2010-01-01

    Mammalian Toll-like receptors (TLRs) are a family of receptors that recognize pathogen-associated molecular patterns. Not only are TLRs crucial sensors of microbial (e.g., viruses, bacteria and parasite) infections, they also play an important role in the pathophysiology of infectious diseases, inflammatory diseases, and possibly in autoimmune diseases. Thus, the intensity and duration of TLR responses against infectious diseases must be tightly controlled. It follows that understanding the structural integrity of sensor receptors, their ligand interactions and signaling components is essential for subsequent immunological protection. It would also provide important opportunities for disease modification through sensor manipulation. Although the signaling pathways of TLR sensors are well characterized, the parameters controlling interactions between the sensors and their ligands still remain poorly defined. We have recently identified a novel mechanism of TLR activation by its natural ligand, which has not been previously observed 1,2. It suggests that ligand-induced TLR activation is tightly controlled by Neu1 sialidase activation. We have also reported that Neu1 tightly regulates neurotrophin receptors like TrkA and TrkB 3, which involve Neu1 and matrix metalloproteinase-9 (MMP-9) cross-talk in complex with the receptors 4. The sialidase assay has been initially use to find a novel ligand, thymoquinone, in the activation of Neu4 sialidase on the cell surface of macrophages, dendritic cells and fibroblast cells via GPCR Gαi proteins and MMP-9 5. For TLR receptors, our data indicate that Neu1 sialidase is already in complex with TLR-2, -3 and -4 receptors, and is induced upon ligand binding to either receptor. Activated Neu1 sialidase hydrolyzes sialyl α-2,3-linked β-galactosyl residues distant from ligand binding to remove steric hinderance to TLR-4 dimerization, MyD88/TLR4 complex recruitment, NFkB activation and pro-inflammatory cell responses. In a

  18. Vinculin contributes to Cell Invasion by Regulating Contractile Activation

    NASA Astrophysics Data System (ADS)

    Mierke, Claudia Tanja

    2008-07-01

    Vinculin is a component of the focal adhesion complex and is described as a mechano-coupling protein connecting the integrin receptor and the actin cytoskeleton. Vinculin knock-out (k.o.) cells (vin-/-) displayed increased migration on a 2-D collagen- or fibronectin-coated substrate compared to wildtype cells, but the role of vinculin in cell migration through a 3-D connective tissue is unknown. We determined the invasiveness of established tumor cell lines using a 3-D collagen invasion assay. Gene expression analysis of 4 invasive and 4 non-invasive tumor cell lines revealed that vinculin expression was significantly increased in invasive tumor cell lines. To analyze the mechanisms by which vinculin increased cell invasion in a 3-D gel, we studied mouse embryonic fibroblasts wildtype and vin-/- cells. Wildtype cells were 3-fold more invasive compared vin-/- cells. We hypothesized that the ability to generate sufficient traction forces is a prerequisite for tumor cell migration in a 3-D connective tissue matrix. Using traction microscopy, we found that wildtype exerted 3-fold higher tractions on fibronectin-coated polyacrylamide gels compared to vin-/- cells. These results show that vinculin controls two fundamental functions that lead to opposite effects on cell migration in a 2-D vs. a 3-D environment: On the one hand, vinculin stabilizes the focal adhesions (mechano-coupling function) and thereby reduces motility in 2-D. On the other hand, vinculin is also a potent activator of traction generation (mechano-regulating function) that is important for cell invasion in a 3-D environment.

  19. The regulation of rat activity following exposure to hyperdynamic fields

    NASA Technical Reports Server (NTRS)

    Fuller, Charles A.; Ishihama, Linda M.; Murakami, Dean M.

    1993-01-01

    The microgravity of space flight and the hyperdynamic fields produced via centrifugation have allowed researchers to examine the effect of altered gravitational environments on the regulation of physiological systems. In this study, a high frequency light/dark cycle was provided for 24 hours as an environmental challenge to assess the recovery of homeostatic and circadian components of physiological regulation in rats. For example, the nocturnal rat exhibited a homeostatic increase in body temperature during the dark periods and a decrease during the light periods. In addition, the magnitude of the body temperature response exhibits a time of day variation demonstrating the effect on circadian regulation.

  20. Public health problems in the medieval statutes of Croatian Adriatic coastal towns: from public morality to public health.

    PubMed

    Petaros, Anja; Skrobonja, Ante; Culina, Tatjana; Bosnar, Alan; Frkovic, Vedran; Azman, Josip

    2013-06-01

    The article seeks out the regulations about public health in the oldest medieval statutes of fourteen cities of the eastern Croatian Adriatic coast, between the thirteenth and sixteenth century. The research revealed numerous examples of direct or indirect ways of protecting public health. Through the analyzed documents, a noteworthy relationship between public morality and public health can be noted. The described rules are important as a reflection of awareness about public health as a condition of survival and progress in the past. They witness a progressive transition from an original common law into a written law as well as the impact that religion had in influencing people's general opinion and lifestyle in light of public health problems.

  1. Activity-induced regulation of myosin isoform distribution - Comparison of two contractile activity programs

    NASA Technical Reports Server (NTRS)

    Diffee, Gary M.; Caiozzo, Vince J.; Mccue, Samuel A.; Herrick, Robert E.; Baldwin, Kenneth M.

    1993-01-01

    This study examined the role of specific types of contractile activity in regulating myosin heavy chain (MHC) isoform expression in rodent soleus. A combination of hindlimb suspension (SN) and two programmed contractile training activity paradigms, either isometric contractile activity (ST-IM) or high-load slowly shortening isovelocity activity, were utilized. Both training paradigms increased muscle mass compared with SN alone. However, only ST-IM resulted in a partial prevention of the suspension-induced decrease in type I MHC. With the use of a fluorescently labeled antibody to type IIa MHC, the distribution of MHCs among fibers was examined immunohistochemically. In SN, the percentage of cells staining positive for type IIa MHC was increased but the staining intensity of the positively staining cells was unchanged compared with control cells. In the ST-IM soleus, the percentage of positively staining fibers was unchanged but the intensity of the positively staining cells was decreased compared with SN values. These results suggest that 1) isometric contractile activity is more effective than isovelocity activity in preventing suspension-induced shifts in soleus MHC distribution and 2) changes associated with both suspension and training occur in only a small number of fibers, with the majority of fibers apparently unresponsive to these interventions.

  2. Calcium-Oxidant Signaling Network Regulates AMP-activated Protein Kinase (AMPK) Activation upon Matrix Deprivation*

    PubMed Central

    Sundararaman, Ananthalakshmy; Amirtham, Usha; Rangarajan, Annapoorni

    2016-01-01

    The AMP-activated protein kinase (AMPK) has recently been implicated in anoikis resistance. However, the molecular mechanisms that activate AMPK upon matrix detachment remain unexplored. In this study, we show that AMPK activation is a rapid and sustained phenomenon upon matrix deprivation, whereas re-attachment to the matrix leads to its dephosphorylation and inactivation. Because matrix detachment leads to loss of integrin signaling, we investigated whether integrin signaling negatively regulates AMPK activation. However, modulation of focal adhesion kinase or Src, the major downstream components of integrin signaling, failed to cause a corresponding change in AMPK signaling. Further investigations revealed that the upstream AMPK kinases liver kinase B1 (LKB1) and Ca2+/calmodulin-dependent protein kinase kinase β (CaMKKβ) contribute to AMPK activation upon detachment. In LKB1-deficient cells, we found AMPK activation to be predominantly dependent on CaMKKβ. We observed no change in ATP levels under detached conditions at early time points suggesting that rapid AMPK activation upon detachment was not triggered by energy stress. We demonstrate that matrix deprivation leads to a spike in intracellular calcium as well as oxidant signaling, and both these intracellular messengers contribute to rapid AMPK activation upon detachment. We further show that endoplasmic reticulum calcium release-induced store-operated calcium entry contributes to intracellular calcium increase, leading to reactive oxygen species production, and AMPK activation. We additionally show that the LKB1/CaMKK-AMPK axis and intracellular calcium levels play a critical role in anchorage-independent cancer sphere formation. Thus, the Ca2+/reactive oxygen species-triggered LKB1/CaMKK-AMPK signaling cascade may provide a quick, adaptable switch to promote survival of metastasizing cancer cells. PMID:27226623

  3. Arabidopsis PROTEASOME REGULATOR1 is required for auxin-mediated suppression of proteasome activity and regulates auxin signalling

    PubMed Central

    Yang, Bao-Jun; Han, Xin-Xin; Yin, Lin-Lin; Xing, Mei-Qing; Xu, Zhi-Hong; Xue, Hong-Wei

    2016-01-01

    The plant hormone auxin is perceived by the nuclear F-box protein TIR1 receptor family and regulates gene expression through degradation of Aux/IAA transcriptional repressors. Several studies have revealed the importance of the proteasome in auxin signalling, but details on how the proteolytic machinery is regulated and how this relates to degradation of Aux/IAA proteins remains unclear. Here we show that an Arabidopsis homologue of the proteasome inhibitor PI31, which we name PROTEASOME REGULATOR1 (PTRE1), is a positive regulator of the 26S proteasome. Loss-of-function ptre1 mutants are insensitive to auxin-mediated suppression of proteasome activity, show diminished auxin-induced degradation of Aux/IAA proteins and display auxin-related phenotypes. We found that auxin alters the subcellular localization of PTRE1, suggesting this may be part of the mechanism by which it reduces proteasome activity. Based on these results, we propose that auxin regulates proteasome activity via PTRE1 to fine-tune the homoeostasis of Aux/IAA repressor proteins thus modifying auxin activity. PMID:27109828

  4. Arabidopsis PROTEASOME REGULATOR1 is required for auxin-mediated suppression of proteasome activity and regulates auxin signalling.

    PubMed

    Yang, Bao-Jun; Han, Xin-Xin; Yin, Lin-Lin; Xing, Mei-Qing; Xu, Zhi-Hong; Xue, Hong-Wei

    2016-01-01

    The plant hormone auxin is perceived by the nuclear F-box protein TIR1 receptor family and regulates gene expression through degradation of Aux/IAA transcriptional repressors. Several studies have revealed the importance of the proteasome in auxin signalling, but details on how the proteolytic machinery is regulated and how this relates to degradation of Aux/IAA proteins remains unclear. Here we show that an Arabidopsis homologue of the proteasome inhibitor PI31, which we name PROTEASOME REGULATOR1 (PTRE1), is a positive regulator of the 26S proteasome. Loss-of-function ptre1 mutants are insensitive to auxin-mediated suppression of proteasome activity, show diminished auxin-induced degradation of Aux/IAA proteins and display auxin-related phenotypes. We found that auxin alters the subcellular localization of PTRE1, suggesting this may be part of the mechanism by which it reduces proteasome activity. Based on these results, we propose that auxin regulates proteasome activity via PTRE1 to fine-tune the homoeostasis of Aux/IAA repressor proteins thus modifying auxin activity. PMID:27109828

  5. 77 FR 42305 - Agency Information Collection Activities; Proposed Collection; Comment Request; Regulations.gov...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-07-18

    ... AGENCY Agency Information Collection Activities; Proposed Collection; Comment Request; Regulations.gov... Collection Request (ICR): Regulations.gov Information Collection, OMB Control Number 2025-0008, EPA ICR...-OEI- 2012-0547, to (1) EPA online using www.regulations.gov (our preferred method), by email...

  6. Individual Differences for Self-Regulating Task-Oriented Reading Activities

    ERIC Educational Resources Information Center

    Vidal-Abarca, Eduardo; Mana, Amelia; Gil, Laura

    2010-01-01

    The goal of this study is to analyze the self-regulation processes present in task-oriented reading activities. In the 1st experiment, we examined the following self-regulation processes in the context of answering questions about an available text: (a) monitoring the comprehension of the question, (b) self-regulating the search process, and (c)…

  7. Robust, synergistic regulation of human gene expression using TALE activators.

    PubMed

    Maeder, Morgan L; Linder, Samantha J; Reyon, Deepak; Angstman, James F; Fu, Yanfang; Sander, Jeffry D; Joung, J Keith

    2013-03-01

    Artificial activators designed using transcription activator-like effector (TALE) technology have broad utility, but previous studies suggest that these monomeric proteins often exhibit low activities. Here we demonstrate that TALE activators can robustly function individually or in synergistic combinations to increase expression of endogenous human genes over wide dynamic ranges. These findings will encourage applications of TALE activators for research and therapy, and guide design of monomeric TALE-based fusion proteins.

  8. Miro1 Regulates Activity-Driven Positioning of Mitochondria within Astrocytic Processes Apposed to Synapses to Regulate Intracellular Calcium Signaling

    PubMed Central

    Stephen, Terri-Leigh; Higgs, Nathalie F.; Sheehan, David F.; Al Awabdh, Sana; López-Doménech, Guillermo; Arancibia-Carcamo, I. Lorena

    2015-01-01

    It is fast emerging that maintaining mitochondrial function is important for regulating astrocyte function, although the specific mechanisms that govern astrocyte mitochondrial trafficking and positioning remain poorly understood. The mitochondrial Rho-GTPase 1 protein (Miro1) regulates mitochondrial trafficking and detachment from the microtubule transport network to control activity-dependent mitochondrial positioning in neurons. However, whether Miro proteins are important for regulating signaling-dependent mitochondrial dynamics in astrocytic processes remains unclear. Using live-cell confocal microscopy of rat organotypic hippocampal slices, we find that enhancing neuronal activity induces transient mitochondrial remodeling in astrocytes, with a concomitant, transient reduction in mitochondrial trafficking, mediated by elevations in intracellular Ca2+. Stimulating neuronal activity also induced mitochondrial confinement within astrocytic processes in close proximity to synapses. Furthermore, we show that the Ca2+-sensing EF-hand domains of Miro1 are important for regulating mitochondrial trafficking in astrocytes and required for activity-driven mitochondrial confinement near synapses. Additionally, activity-dependent mitochondrial positioning by Miro1 reciprocally regulates the levels of intracellular Ca2+ in astrocytic processes. Thus, the regulation of intracellular Ca2+ signaling, dependent on Miro1-mediated mitochondrial positioning, could have important consequences for astrocyte Ca2+ wave propagation, gliotransmission, and ultimately neuronal function. SIGNIFICANCE STATEMENT Mitochondria are key cellular organelles that play important roles in providing cellular energy and buffering intracellular calcium ions. The mechanisms that control mitochondrial distribution within the processes of glial cells called astrocytes and the impact this may have on calcium signaling remains unclear. We show that activation of glutamate receptors or increased neuronal

  9. Self-Regulated Learning and Perceived Health among University Students Participating in Physical Activity Classes

    ERIC Educational Resources Information Center

    McBride, Ron E.; Altunsöz, Irmak Hürmeriç; Su, Xiaoxia; Xiang, Ping; Demirhan, Giyasettin

    2016-01-01

    The purpose of this study was to explore motivational indicators of self-regulated learning (SRL) and the relationship between self-regulation (SR) and perceived health among university students enrolled in physical activity (PA) classes. One hundred thirty-one Turkish students participating in physical education activity classes at two…

  10. Physical Activity, Self-Regulation, and Early Academic Achievement in Preschool Children

    ERIC Educational Resources Information Center

    Becker, Derek R.; McClelland, Megan M.; Loprinzi, Paul; Trost, Stewart G.

    2014-01-01

    Research Findings: The present study investigated whether active play during recess was associated with self-regulation and academic achievement in a prekindergarten sample. A total of 51 children in classes containing approximately half Head Start children were assessed on self-regulation, active play, and early academic achievement. Path…

  11. Structural plasticity of GABAergic axons is regulated by network activity and GABAA receptor activation

    PubMed Central

    Schuemann, Anne; Klawiter, Agnieszka; Bonhoeffer, Tobias; Wierenga, Corette J.

    2013-01-01

    Coordinated changes at excitatory and inhibitory synapses are essential for normal brain development and function. It is well established that excitatory neurons undergo structural changes, but our knowledge about inhibitory structural plasticity is rather scarce. Here we present a quantitative analysis of the dynamics of GABAergic boutons in the dendritic region of the hippocampal CA1 area using time-lapse two-photon imaging in organotypic hippocampal cultures from GAD65-GFP mice. We show that ~20% of inhibitory boutons are not stable. They are appearing, disappearing and reappearing at specific locations along the inhibitory axon and reflect immature or incomplete synapses. Furthermore, we observed that persistent boutons show large volume fluctuations over several hours, suggesting that presynaptic content of inhibitory synapses is not constant. Our data show that inhibitory boutons are highly dynamic structures and suggest that inhibitory axons are continuously probing potential locations for inhibitory synapse formation by redistributing presynaptic material along the axon. In addition, we found that neuronal activity affects the exploratory dynamics of inhibitory axons. Blocking network activity rapidly reduces the number of transient boutons, whereas enhancing activity reduces the number of persistent inhibitory boutons, possibly reflecting enhanced competition between boutons along the axon. The latter effect requires signaling through GABAA receptors. We propose that activity-dependent regulation of bouton dynamics contributes to inhibitory synaptic plasticity. PMID:23805077

  12. 18.6-year Earth tide regulates geyser activity.

    PubMed

    Rinehart, J S

    1972-07-28

    Over 40 years of records from Yellowstone National Park, Wyoming, show that the 18.6-year tidal component strongly regulates the frequencies of eruption of Grand and Steamboat geysers. The frequency of Grand Geyser increases with increasing tidal force and that of Steamboat Geyser decreases, which suggests that tidal dilatation is one factor affecting heat flow to a geyser.

  13. 18.6-year Earth tide regulates geyser activity.

    PubMed

    Rinehart, J S

    1972-07-28

    Over 40 years of records from Yellowstone National Park, Wyoming, show that the 18.6-year tidal component strongly regulates the frequencies of eruption of Grand and Steamboat geysers. The frequency of Grand Geyser increases with increasing tidal force and that of Steamboat Geyser decreases, which suggests that tidal dilatation is one factor affecting heat flow to a geyser. PMID:17813197

  14. Polyphosphate - an ancient energy source and active metabolic regulator

    PubMed Central

    2011-01-01

    There are a several molecules on Earth that effectively store energy within their covalent bonds, and one of these energy-rich molecules is polyphosphate. In microbial cells, polyphosphate granules are synthesised for both energy and phosphate storage and are degraded to produce nucleotide triphosphate or phosphate. Energy released from these energetic carriers is used by the cell for production of all vital molecules such as amino acids, nucleobases, sugars and lipids. Polyphosphate chains directly regulate some processes in the cell and are used as phosphate donors in gene regulation. These two processes, energetic metabolism and regulation, are orchestrated by polyphosphate kinases. Polyphosphate kinases (PPKs) can currently be categorized into three groups (PPK1, PPK2 and PPK3) according their functionality; they can also be divided into three groups according their homology (EcPPK1, PaPPK2 and ScVTC). This review discusses historical information, similarities and differences, biochemical characteristics, roles in stress response regulation and possible applications in the biotechnology industry of these enzymes. At the end of the review, a hypothesis is discussed in view of synthetic biology applications that states polyphosphate and calcium-rich organelles have endosymbiotic origins from ancient protocells that metabolized polyphosphate. PMID:21816086

  15. Laser Activated Flow Regulator for Glaucoma Drainage Devices

    PubMed Central

    Olson, Jeffrey L.; Velez-Montoya, Raul; Bhandari, Ramanath

    2014-01-01

    Purpose To assess the capabilities of a new glaucoma drainage device regulator in controlling fluid flow as well as to demonstrate that this effect may be titratable by noninvasive means. Methods A rigid eye model with two main ports was used. On the first port, we placed a saline solution column. On the second, we placed a glaucoma shunt. We then measured the flow and flow rate through the system. After placing the regulator device on the tip of the tube, we measured again with the intact membrane and with the membrane open 50% and 100%. For the ex vivo testing we used a similar setting, using a cadaveric porcine eye, we measured again the flow and flow rate. However, this time we opened the membrane gradually using laser shots. A one-way analysis of variance and a Fisher's Least Significant Difference test were used for statistical significance. We also calculated the correlation between the numbers of laser shots applied and the main outcomes. Results The flow through the system with the glaucoma drainage device regulator (membrane intact and 50% open) was statistically lower than with the membrane open 100% and without device (P < 0.05). The flow was successfully controlled by the number of laser shots applied, and showed a positive correlation (+ 0.9). The flow rate was almost doubled every 10 shots and statistically lower than without device at all time (P < 0.05). Conclusions The glaucoma drainage device regulator can be controlled noninvasively with laser, and allows titratable control of aqueous flow. Translational Relevance Initial results and evidence from this experiment will justify the initiation of in vivo animal trials with the glaucoma drainage device regulator; which brings us closer to possible human trials and the chance to significantly improve the existing technology to treat glaucoma surgically. PMID:25374772

  16. Membrane lipids regulate ganglioside GM2 catabolism and GM2 activator protein activity[S

    PubMed Central

    Anheuser, Susi; Breiden, Bernadette; Schwarzmann, Günter; Sandhoff, Konrad

    2015-01-01

    Ganglioside GM2 is the major lysosomal storage compound of Tay-Sachs disease. It also accumulates in Niemann-Pick disease types A and B with primary storage of SM and with cholesterol in type C. Reconstitution of GM2 catabolism with β-hexosaminidase A and GM2 activator protein (GM2AP) at uncharged liposomal surfaces carrying GM2 as substrate generated only a physiologically irrelevant catabolic rate, even at pH 4.2. However, incorporation of anionic phospholipids into the GM2 carrying liposomes stimulated GM2 hydrolysis more than 10-fold, while the incorporation of plasma membrane stabilizing lipids (SM and cholesterol) generated a strong inhibition of GM2 hydrolysis, even in the presence of anionic phospholipids. Mobilization of membrane lipids by GM2AP was also inhibited in the presence of cholesterol or SM, as revealed by surface plasmon resonance studies. These lipids also reduced the interliposomal transfer rate of 2-NBD-GM1 by GM2AP, as observed in assays using Förster resonance energy transfer. Our data raise major concerns about the usage of recombinant His-tagged GM2AP compared with untagged protein. The former binds more strongly to anionic GM2-carrying liposomal surfaces, increases GM2 hydrolysis, and accelerates intermembrane transfer of 2-NBD-GM1, but does not mobilize membrane lipids. PMID:26175473

  17. Activation of TRPV4 Regulates Respiration through Indirect Activation of Bronchopulmonary Sensory Neurons

    PubMed Central

    Gu, Qihai (David); Moss, Charles R.; Kettelhut, Kristen L.; Gilbert, Carolyn A.; Hu, Hongzhen

    2016-01-01

    Transient receptor potential vanilloid receptor 4 (TRPV4) is a calcium-permeable non-selective cation channel implicated in numerous physiological and pathological functions. This study aimed to investigate the effect of TRPV4 activation on respiration and to explore the potential involvement of bronchopulmonary sensory neurons. Potent TRPV4 agonist GSK1016790A was injected into right atrium in anesthetized spontaneously breathing rats and the changes in breathing were measured. Patch-clamp recording was performed to investigate the effect of GSK1016790A or another TRPV4 activator 4α-PDD on cultured rat vagal bronchopulmonary sensory neurons. Immunohistochemistry was carried out to determine the TRPV4-expressing cells in lung slices obtained from TRPV4-EGFP mice. Our results showed, that right-atrial injection of GSK1016790A evoked a slow-developing, long-lasting rapid shallow breathing in anesthetized rats. Activation of TRPV4 also significantly potentiated capsaicin-evoked chemoreflex responses. The alteration in ventilation induced by GSK1016790A was abolished by cutting or perineural capsaicin treatment of both vagi, indicating the involvement of bronchopulmonary afferent neurons. The stimulating and sensitizing effects of GSK1016790A were abolished by a selective TRPV4 antagonist GSK2193874 and also by inhibiting cyclooxygenase with indomethacin. Surprising, GSK1016790A or 4α-PDD did not activate isolated bronchopulmonary sensory neurons, nor did they modulate capsaicin-induced inward currents in these neurons. Furthermore, TRPV4 expression was found in alveolar macrophages, alveolar epithelial, and vascular endothelial cells. Collectively, our results suggest that GSK1016790A regulates the respiration through an indirect activation of bronchopulmonary sensory neurons, likely via its stimulation of other TRPV4-expressing cells in the lungs and airways. PMID:26973533

  18. Activity-Dependent Regulation of Synapses by Retrograde Messengers

    PubMed Central

    Regehr, Wade G.; Carey, Megan R.; Best, Aaron R.

    2011-01-01

    Summary Throughout the brain postsynaptic neurons release substances from their cell bodies and dendrites that regulate the strength of the synapses they receive. Diverse chemical messengers have been implicated in retrograde signaling from postsynaptic neurons to presynaptic boutons. Here we provide an overview of the signaling systems that lead to rapid changes in synaptic strength. We consider the capabilities, specializations and physiological roles of each type of signaling system. PMID:19640475

  19. mTORC1-Induced HK1-Dependent Glycolysis Regulates NLRP3 Inflammasome Activation.

    PubMed

    Moon, Jong-Seok; Hisata, Shu; Park, Mi-Ae; DeNicola, Gina M; Ryter, Stefan W; Nakahira, Kiichi; Choi, Augustine M K

    2015-07-01

    The mammalian target of rapamycin complex 1 (mTORC1) regulates activation of immune cells and cellular energy metabolism. Although glycolysis has been linked to immune functions, the mechanisms by which glycolysis regulates NLRP3 inflammasome activation remain unclear. Here, we demonstrate that mTORC1-induced glycolysis provides an essential mechanism for NLRP3 inflammasome activation. Moreover, we demonstrate that hexokinase 1 (HK1)-dependent glycolysis, under the regulation of mTORC1, represents a critical metabolic pathway for NLRP3 inflammasome activation. Downregulation of glycolysis by inhibition of Raptor/mTORC1 or HK1 suppressed both pro-IL-1β maturation and caspase-1 activation in macrophages in response to LPS and ATP. These results suggest that upregulation of HK1-dependent glycolysis by mTORC1 regulates NLRP3 inflammasome activation.

  20. Protein oxidation mediated by heme-induced active site conversion specific for heme-regulated transcription factor, iron response regulator

    PubMed Central

    Kitatsuji, Chihiro; Izumi, Kozue; Nambu, Shusuke; Kurogochi, Masaki; Uchida, Takeshi; Nishimura, Shin-Ichiro; Iwai, Kazuhiro; O’Brian, Mark R.; Ikeda-Saito, Masao; Ishimori, Koichiro

    2016-01-01

    The Bradyrhizobium japonicum transcriptional regulator Irr (iron response regulator) is a key regulator of the iron homeostasis, which is degraded in response to heme binding via a mechanism that involves oxidative modification of the protein. Here, we show that heme-bound Irr activates O2 to form highly reactive oxygen species (ROS) with the “active site conversion” from heme iron to non-heme iron to degrade itself. In the presence of heme and reductant, the ROS scavenging experiments show that Irr generates H2O2 from O2 as found for other hemoproteins, but H2O2 is less effective in oxidizing the peptide, and further activation of H2O2 is suggested. Interestingly, we find a time-dependent decrease of the intensity of the Soret band and appearance of the characteristic EPR signal at g = 4.3 during the oxidation, showing the heme degradation and the successive formation of a non-heme iron site. Together with the mutational studies, we here propose a novel “two-step self-oxidative modification” mechanism, during which O2 is activated to form H2O2 at the heme regulatory motif (HRM) site and the generated H2O2 is further converted into more reactive species such as ·OH at the non-heme iron site in the His-cluster region formed by the active site conversion. PMID:26729068

  1. Astragaloside II triggers T cell activation through regulation of CD45 protein tyrosine phosphatase activity

    PubMed Central

    Wan, Chun-ping; Gao, Li-xin; Hou, Li-fei; Yang, Xiao-qian; He, Pei-lan; Yang, Yi-fu; Tang, Wei; Yue, Jian-min; Li, Jia; Zuo, Jian-ping

    2013-01-01

    Aim: To investigate the immunomodulating activity of astragalosides, the active compounds from a traditional tonic herb Astragalus membranaceus Bge, and to explore the molecular mechanisms underlying the actions, focusing on CD45 protein tyrosine phosphatase (CD45 PTPase), which plays a critical role in T lymphocyte activation. Methods: Primary splenocytes and T cells were prepared from mice. CD45 PTPase activity was assessed using a colorimetric assay. Cell proliferation was measured using a [3H]-thymidine incorporation assay. Cytokine proteins and mRNAs were examined with ELISA and RT-PCR, respectively. Activation markers, including CD25 and CD69, were analyzed using flow cytometry. Activation of LCK (Tyr505) was detected using Western blot analysis. Mice were injected with the immunosuppressant cyclophosphamide (CTX, 80 mg/kg), and administered astragaloside II (50 mg/kg). Results: Astragaloside I, II, III, and IV concentration-dependently increased the CD45-mediated of pNPP/OMFP hydrolysis with the EC50 values ranged from 3.33 to 10.42 μg/mL. Astragaloside II (10 and 30 nmol/L) significantly enhanced the proliferation of primary splenocytes induced by ConA, alloantigen or anti-CD3. Astragaloside II (30 nmol/L) significantly increased IL-2 and IFN-γ secretion, upregulated the mRNA levels of IFN-γ and T-bet in primary splenocytes, and promoted CD25 and CD69 expression on primary CD4+ T cells upon TCR stimulation. Furthermore, astragaloside II (100 nmol/L) promoted CD45-mediated dephosphorylation of LCK (Tyr505) in primary T cells, which could be blocked by a specific CD45 PTPase inhibitor. In CTX-induced immunosuppressed mice, oral administration of astragaloside II restored the proliferation of splenic T cells and the production of IFN-γ and IL-2. However, astragaloside II had no apparent effects on B cell proliferation. Conclusion: Astragaloside II enhances T cell activation by regulating the activity of CD45 PTPase, which may explain why Astragalus

  2. Examining "Active" Procrastination from a Self-Regulated Learning Perspective

    ERIC Educational Resources Information Center

    Cao, Li

    2012-01-01

    This study examined the notion that active procrastinators are a positive type of procrastinators who possess desirable characteristics similar to non-procrastinators, but different from the traditional passive procrastinators. A two-step procedure was followed to categorise university students (N = 125) as active procrastinators, passive…

  3. Light and dark active phosphodiesterase regulation in salamander rods

    PubMed Central

    1991-01-01

    We studied the activation of 3',5'-cyclic guanosine monophosphate (cGMP) phosphodiesterase (PDE) by using a cell-permeant enzyme inhibitor. Rods of Ambystoma tigrinum held in a suction electrode were jumped into a stream of 3-isobutyl-1-methylxanthine (IBMX), 0.01-1 mM. Initial transient light-sensitive currents fit the notion that dark and light-activated forms of PDE contributed independently to metabolic activity and were equivalently inhibited by IBMX (apparent Ki 30 microns). Inhibition developed within 50 ms, producing a step decrease of enzyme velocity, which could be offset by activation with flashes or steps of light. The dark PDE activity was equivalent to light activation of enzyme by 1,000 isomerization rod-1s-1, sufficient to hydrolyze the free cGMP pool (1/e) in 0.6 s. Steady light activated PDE in linear proportion to isomerization rate, the range from darkness to current saturation amounting to a 10-fold increase. The conditions for simultaneous onset of inhibitor and illumination to produce no net change of membrane current defined the apparent lifetime of light- activated PDE, TPDE* = 0.9 s, which was independent of both background illumination and current over the range 0-3 x 10(5) isomerization s-1, from 50 to 0 pA. Adaptation was a function of current rather than isomerization: jumps with different proportions of IBMX concentration to steady light intensity produced equal currents, and followed the same course of adaptation in maintained light, despite a 10-fold difference of illumination. Judged from the delay between IBMX- and light-induced currents, the dominant feedback regulatory site comes after PDE on the signal path. The dark active PDE affects the hydrolytic flux and cytoplasmic diffusion of cGMP, as well as the proportional range of the cGMP activity signal in response to light. PMID:1722240

  4. Abstracts of State Authorizing and Oversight Laws and Regulations. A Study of State Oversight in Postsecondary Education.

    ERIC Educational Resources Information Center

    Helliwell, Carolyn B.; And Others

    Herein are contained abstracts of state laws and regulations governing postsecondary education in three sectors: public, private degree-granting, and private nondegree-granting. With some exceptions, all obtainable statutes having the force of law are included. The statutes are arranged by state. Each abstract includes basic identifying data,…

  5. Autonomy, Accountability, and the Values of Public Education: A Comparative Assessment of Charter School Statutes Leading to Model Legislation.

    ERIC Educational Resources Information Center

    Millot, Marc Dean

    This report analyzes state statutes authorizing a new approach to the organization of elementary and secondary education in the public sector, the "outcome-based,""contract," or, as it is now commonly called, "charter school." Charter school statutes create an alternative legal framework for the formation of public schools by permitting a state…

  6. The Stark truth: what your physician clients should know about Stark Law and the Anti-Kickback Statute.

    PubMed

    Taormina, Melissa

    2013-01-01

    This article summarizes key features of Stark Law and the Anti-Kickback Statute, statutes used to fight health care fraud and abuse within Medicare and Medicaid, and explains how attorneys can help health care providers comply with these laws. PMID:23614270

  7. 34 CFR 99.38 - What conditions apply to disclosure of information as permitted by State statute adopted after...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... permitted by State statute adopted after November 19, 1974, concerning the juvenile justice system? 99.38... adopted after November 19, 1974, concerning the juvenile justice system? (a) If reporting or disclosure allowed by State statute concerns the juvenile justice system and the system's ability to...

  8. Simulated shift work in rats perturbs multiscale regulation of locomotor activity

    PubMed Central

    Hsieh, Wan-Hsin; Escobar, Carolina; Yugay, Tatiana; Lo, Men-Tzung; Pittman-Polletta, Benjamin; Salgado-Delgado, Roberto; Scheer, Frank A. J. L.; Shea, Steven A.; Buijs, Ruud M.; Hu, Kun

    2014-01-01

    Motor activity possesses a multiscale regulation that is characterized by fractal activity fluctuations with similar structure across a wide range of timescales spanning minutes to hours. Fractal activity patterns are disturbed in animals after ablating the master circadian pacemaker (suprachiasmatic nucleus, SCN) and in humans with SCN dysfunction as occurs with aging and in dementia, suggesting the crucial role of the circadian system in the multiscale activity regulation. We hypothesized that the normal synchronization between behavioural cycles and the SCN-generated circadian rhythms is required for multiscale activity regulation. To test the hypothesis, we studied activity fluctuations of rats in a simulated shift work protocol that was designed to force animals to be active during the habitual resting phase of the circadian/daily cycle. We found that these animals had gradually decreased mean activity level and reduced 24-h activity rhythm amplitude, indicating disturbed circadian and behavioural cycles. Moreover, these animals had disrupted fractal activity patterns as characterized by more random activity fluctuations at multiple timescales from 4 to 12 h. Intriguingly, these activity disturbances exacerbated when the shift work schedule lasted longer and persisted even in the normal days (without forced activity) following the shift work. The disrupted circadian and fractal patterns resemble those of SCN-lesioned animals and of human patients with dementia, suggesting a detrimental impact of shift work on multiscale activity regulation. PMID:24829282

  9. Simulated shift work in rats perturbs multiscale regulation of locomotor activity.

    PubMed

    Hsieh, Wan-Hsin; Escobar, Carolina; Yugay, Tatiana; Lo, Men-Tzung; Pittman-Polletta, Benjamin; Salgado-Delgado, Roberto; Scheer, Frank A J L; Shea, Steven A; Buijs, Ruud M; Hu, Kun

    2014-07-01

    Motor activity possesses a multiscale regulation that is characterized by fractal activity fluctuations with similar structure across a wide range of timescales spanning minutes to hours. Fractal activity patterns are disturbed in animals after ablating the master circadian pacemaker (suprachiasmatic nucleus, SCN) and in humans with SCN dysfunction as occurs with aging and in dementia, suggesting the crucial role of the circadian system in the multiscale activity regulation. We hypothesized that the normal synchronization between behavioural cycles and the SCN-generated circadian rhythms is required for multiscale activity regulation. To test the hypothesis, we studied activity fluctuations of rats in a simulated shift work protocol that was designed to force animals to be active during the habitual resting phase of the circadian/daily cycle. We found that these animals had gradually decreased mean activity level and reduced 24-h activity rhythm amplitude, indicating disturbed circadian and behavioural cycles. Moreover, these animals had disrupted fractal activity patterns as characterized by more random activity fluctuations at multiple timescales from 4 to 12 h. Intriguingly, these activity disturbances exacerbated when the shift work schedule lasted longer and persisted even in the normal days (without forced activity) following the shift work. The disrupted circadian and fractal patterns resemble those of SCN-lesioned animals and of human patients with dementia, suggesting a detrimental impact of shift work on multiscale activity regulation.

  10. [Studies on regulation of glutamine synthetase activity from Streptomyces lincolnensis].

    PubMed

    Jin, Z; Jiao, R; Mao, Y

    2001-08-01

    Glutamine synthetase in crude extracts from Streptomyces lincolnensis growing under different nitrogen sources were studied. The results showed that NH4+ in high concentration repressed the biosynthesis of the enzyme. To determine whether Streptomyces lincolnensis has undergone covalent modification, a comparison of the glutamine synthetase isolated from cells grown on different nitrogen sources was made. No significant difference was observed in specific activity, pH optima, divalent cation response, and ultraviolet absorption spectra. Glutamine synthetase activity was not influenced by ammonia shock or snake venom phosphodiesterase treatment. Under these conditions, the activity of glutamine synthetase from K. aerogenes was markedly changed. There was therefore no evidence for enzymatic adenylylation of glutamine synthetase from Streptomyces lincolnensis. Glutamine synthetase was subject to feedback inhibition by end products of glutamine metabolism. Cumulative feedback inhibition of the Mn(2+)-dependent glutamine synthetase activity was demonstrated. These results suggest that glutamine synthetase from Streptomyces lincolnensis is an allosteric enzyme. PMID:12552916

  11. [Regulation of glucosamine synthetase activity by cholesterol and hydrocortisone].

    PubMed

    Sharaev, P N; Ivanov, V G; Bogdanov, N G

    1988-09-01

    The effects of cholesterol and hydrocortisone (cortisol) on the activity of purified glucosamine synthetase from rat liver was studied in vitro. It was found that the enzyme activity is increased by cholesterol and inhibited by hydrocortisone. These steroids block the allosteric effect of vitamin K1 on the enzyme. There is evidence testifying to the allosteric type of cholesterol and hydrocortisone effects on glucosamine synthetase. PMID:3203113

  12. Differential regulation of protein subdomain activity with caged bivalent ligands.

    PubMed

    Mayer, Günter; Müller, Jens; Mack, Timo; Freitag, Daniel F; Höver, Thomas; Pötzsch, Bernd; Heckel, Alexander

    2009-03-01

    Subtle change: Spatiotemporal modulation of individual protein subdomains with light as the trigger signal becomes possible by using bivalent aptamers and introducing photolabile "caging groups" to switch individual aptamer modules ON or OFF differentially. To the best of our knowledge, this is the first study to show that it is possible to modulate individual domain activity in aptamers, and thus also domain activity in proteins, with light.

  13. Regulation of Autophagic Activation by Rta of Epstein-Barr Virus via the Extracellular Signal-Regulated Kinase Pathway

    PubMed Central

    Chen, Lee-Wen; Wang, Wen-Hung; Chang, Pey-Jium; Chiu, Ya-Fang; Hung, Chen-Chia; Lin, Ying-Ju; Liou, Jieh-Yuan; Tsai, Wan-Ju; Hung, Chia-Ling

    2014-01-01

    ABSTRACT Autophagy is an intracellular degradation pathway that provides a host defense mechanism against intracellular pathogens. However, many viruses exploit this mechanism to promote their replication. This study shows that lytic induction of Epstein-Barr virus (EBV) increases the membrane-bound form of LC3 (LC3-II) and LC3-containing punctate structures in EBV-positive cells. Transfecting 293T cells with a plasmid that expresses Rta also induces autophagy, revealing that Rta is responsible for autophagic activation. The activation involves Atg5, a key component of autophagy, but not the mTOR pathway. The expression of Rta also activates the transcription of the genes that participate in the formation of autophagosomes, including LC3A, LC3B, and ATG9B genes, as well as those that are involved in the regulation of autophagy, including the genes TNF, IRGM, and TRAIL. Additionally, treatment with U0126 inhibits the Rta-induced autophagy and the expression of autophagy genes, indicating that the autophagic activation is caused by the activation of extracellular signal-regulated kinase (ERK) signaling by Rta. Finally, the inhibition of autophagic activity by an autophagy inhibitor, 3-methyladenine, or Atg5 small interfering RNA, reduces the expression of EBV lytic proteins and the production of viral particles, revealing that autophagy is critical to EBV lytic progression. This investigation reveals how an EBV-encoded transcription factor promotes autophagy to affect viral lytic development. PMID:25122800

  14. Regulation of Mec1 kinase activity by the SWI/SNF chromatin remodeling complex.

    PubMed

    Kapoor, Prabodh; Bao, Yunhe; Xiao, Jing; Luo, Jie; Shen, Jianfeng; Persinger, Jim; Peng, Guang; Ranish, Jeff; Bartholomew, Blaine; Shen, Xuetong

    2015-03-15

    ATP-dependent chromatin remodeling complexes alter chromatin structure through interactions with chromatin substrates such as DNA, histones, and nucleosomes. However, whether chromatin remodeling complexes have the ability to regulate nonchromatin substrates remains unclear. Saccharomyces cerevisiae checkpoint kinase Mec1 (ATR in mammals) is an essential master regulator of genomic integrity. Here we found that the SWI/SNF chromatin remodeling complex is capable of regulating Mec1 kinase activity. In vivo, Mec1 activity is reduced by the deletion of Snf2, the core ATPase subunit of the SWI/SNF complex. SWI/SNF interacts with Mec1, and cross-linking studies revealed that the Snf2 ATPase is the main interaction partner for Mec1. In vitro, SWI/SNF can activate Mec1 kinase activity in the absence of chromatin or known activators such as Dpb11. The subunit requirement of SWI/SNF-mediated Mec1 regulation differs from that of SWI/SNF-mediated chromatin remodeling. Functionally, SWI/SNF-mediated Mec1 regulation specifically occurs in S phase of the cell cycle. Together, these findings identify a novel regulator of Mec1 kinase activity and suggest that ATP-dependent chromatin remodeling complexes can regulate nonchromatin substrates such as a checkpoint kinase.

  15. Neuronal activity regulates remyelination via glutamate signalling to oligodendrocyte progenitors

    PubMed Central

    Gautier, Hélène O. B.; Evans, Kimberley A.; Volbracht, Katrin; James, Rachel; Sitnikov, Sergey; Lundgaard, Iben; James, Fiona; Lao-Peregrin, Cristina; Reynolds, Richard; Franklin, Robin J. M.; Káradóttir, Ragnhildur T

    2015-01-01

    Myelin regeneration can occur spontaneously in demyelinating diseases such as multiple sclerosis (MS). However, the underlying mechanisms and causes of its frequent failure remain incompletely understood. Here we show, using an in-vivo remyelination model, that demyelinated axons are electrically active and generate de novo synapses with recruited oligodendrocyte progenitor cells (OPCs), which, early after lesion induction, sense neuronal activity by expressing AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid)/kainate receptors. Blocking neuronal activity, axonal vesicular release or AMPA receptors in demyelinated lesions results in reduced remyelination. In the absence of neuronal activity there is a ∼6-fold increase in OPC number within the lesions and a reduced proportion of differentiated oligodendrocytes. These findings reveal that neuronal activity and release of glutamate instruct OPCs to differentiate into new myelinating oligodendrocytes that recover lost function. Co-localization of OPCs with the presynaptic protein VGluT2 in MS lesions implies that this mechanism may provide novel targets to therapeutically enhance remyelination. PMID:26439639

  16. Histone acetyltransferases regulate HIV-1 enhancer activity in vitro

    PubMed Central

    Sheridan, Philip L.; Mayall, Timothy P.; Verdin, Eric; Jones, Katherine A.

    1997-01-01

    Specific inhibitors of histone deacetylase, such as trichostatin A (TSA) and trapoxin (TPX), are potent inducers of HIV-1 transcription in latently infected T-cell lines. Activation of the integrated HIV-1 promoter is accompanied by the loss or rearrangement of a positioned nucleosome (nuc-1) near the viral RNA start site. Here we show that TSA strongly induces HIV-1 transcription on chromatin in vitro, concomitant with an enhancer factor-assisted increase in the level of acetylated histone H4. TSA treatment, however, did not detectably alter enhancer factor binding or the positioning of nuc-1 on the majority of the chromatin templates indicating that protein acetylation and chromatin remodeling may be limiting steps that occur only on transcriptionally competent templates, or that remodeling of nuc-1 requires additional factors. To assess the number of active chromatin templates in vitro, transcription was limited to a single round with low levels of the detergent Sarkosyl. Remarkably, HIV-1 transcription on chromatin was found to arise from a small number of active templates that can each support nearly 100 rounds of transcription, and TSA increased the number of active templates in each round. In contrast, transcription on naked DNA was limited to only a few rounds and was not responsive to TSA. We conclude that HIV-1 enhancer complexes greatly facilitate transcription reinitiation on chromatin in vitro, and act at a limiting step to promote the acetylation of histones or other transcription factors required for HIV-1 enhancer activity. PMID:9407026

  17. Serum thymus and activation-regulated chemokine as disease activity and response biomarker in alopecia areata.

    PubMed

    Inui, Shigeki; Noguchi, Fumihito; Nakajima, Takeshi; Itami, Satoshi

    2013-11-01

    Serum thymus and activation-regulated chemokine/CCL17 (sTARC) is known as a good indicator for atopic dermatitis severity. Herein, we investigate whether sTARC correlates with severity and therapeutic response for alopecia areata (AA) in our 121 patients. The sTARC mean of AA totalis and universalis was significantly higher than mild AA. Next, we compared sTARC of diffuse AA (n = 14) and severity-controlled patchy AA (n = 32) and found that sTARC in diffuse AA (564.2 ± 400.0 pg/mL) was significantly higher than that of the patchy type (344.0 ± 239.8 pg/mL), suggesting a potential role of TARC in active progression of diffuse AA. Ten patients with diffuse AA were treated with i.v. corticosteroid pulse therapy. Then, we tested whether sTARC can predict prognosis after the pulse therapy and found that baseline sTARC in the poor responders (1025.5 ± 484.8 pg/mL) was significantly higher than that in the good responders (complete remission at 24 months after the pulse therapy, 347.8 ± 135.7 pg/mL), indicating sTARC as a response biomarker in the corticosteroid pulse therapy for diffuse AA. Finally, to investigate TARC production in the affected hair follicles, we performed immunohistochemical double staining of TARC and CD68 using scalp skin specimens of diffuse AA with high titers of sTARC. The results showed their co-localization in the infiltrating cells around the AA hair follicles, suggesting that TARC is mainly produced from CD68(+) histiocytes. In conclusion, sTARC is a disease activity and response biomarker in AA, providing new insight beyond the T-helper 1/2 paradigm to solve the immunological pathogenesis of AA.

  18. 77 FR 45247 - Implementation of Statute of Limitations Provisions for Office Disciplinary Proceedings

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-07-31

    ... Statute of Limitations Provisions for Office Disciplinary Proceedings, 77 FR 457 (January 5, 2012). Prior... disciplinary complaints: Complaints predicated on the receipt of a probable cause determination from the... investigated case to the Committee on Discipline for a determination of whether there is probable cause...

  19. A Comparison of the States' Child Abuse and Neglect Reporting Statutes. Report No. 84.

    ERIC Educational Resources Information Center

    Education Commission of the States, Denver, CO.

    Each of the 50 states has a child abuse and neglect reporting law. An overview of these various statutes is provided in table form, giving the following information: citation; year enacted; effective date; requirement for mandatory reporting; reportable age; definitions of child abuse; requirement for education/school report; immunity, civil and…

  20. 20 CFR 402.85 - Exemption three for withholding records: Records exempted by other statutes.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 20 Employees' Benefits 2 2010-04-01 2010-04-01 false Exemption three for withholding records: Records exempted by other statutes. 402.85 Section 402.85 Employees' Benefits SOCIAL SECURITY ADMINISTRATION AVAILABILITY OF INFORMATION AND RECORDS TO THE PUBLIC § 402.85 Exemption three for...

  1. 36 CFR 1256.50 - Information exempted from disclosure by statute.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 36 Parks, Forests, and Public Property 3 2010-07-01 2010-07-01 false Information exempted from disclosure by statute. 1256.50 Section 1256.50 Parks, Forests, and Public Property NATIONAL ARCHIVES AND RECORDS ADMINISTRATION PUBLIC AVAILABILITY AND USE ACCESS TO RECORDS AND DONATED HISTORICAL...

  2. 77 FR 74025 - Federated Indians of Graton Rancheria-Liquor Control Statute

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-12-12

    ... Rancheria (``Reservation''), in order to permit alcohol sales by tribally owned and operated enterprises and...: ] 2.1 Definitions. As used in this Statute, the terms below are defined as follows: (a) Alcohol means ethyl alcohol, hydrated oxide of ethyl, or spirit of wine, in any form, and regardless of source or...

  3. A Summary and Analysis of Warrantless Arrest Statutes for Domestic Violence in the United States

    ERIC Educational Resources Information Center

    Zeoli, April M.; Norris, Alexis; Brenner, Hannah

    2011-01-01

    In the United States, all 50 states and the District of Columbia have enacted statutes that allow police officers to make warrantless arrests for domestic violence given probable cause; however, state laws differ from one another in multiple, important ways. Research on domestic violence warrantless arrest laws rarely describe them as anything…

  4. 48 CFR 1506.302-5 - Authorized or required by statute.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... AGENCY ACQUISITION PLANNING COMPETITION REQUIREMENTS Other Than Full and Open Competition 1506.302-5 Authorized or required by statute. (a) Authority. Section 109(e) of the Superfund Amendments and... expert services under the authority of section 109(e) of SARA. The contracting officer shall document...

  5. 20 CFR 1002.311 - Is there a statute of limitations in an action under USERRA?

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... EMPLOYMENT AND REEMPLOYMENT RIGHTS ACT OF 1994 Compliance Assistance, Enforcement and Remedies Enforcement of... unreasonably delays asserting his or her rights, and that unreasonable delay causes prejudice to the employer... applicability of the Federal statute of limitations has been resolved and, in any event, act promptly...

  6. 40 CFR 35.935-5 - Davis-Bacon and related statutes.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 1 2010-07-01 2010-07-01 false Davis-Bacon and related statutes. 35.935-5 Section 35.935-5 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY GRANTS AND OTHER FEDERAL ASSISTANCE STATE AND LOCAL ASSISTANCE Grants for Construction of Treatment Works-Clean Water...

  7. 40 CFR 35.935-5 - Davis-Bacon and related statutes.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 1 2013-07-01 2013-07-01 false Davis-Bacon and related statutes. 35.935-5 Section 35.935-5 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY GRANTS AND OTHER FEDERAL ASSISTANCE STATE AND LOCAL ASSISTANCE Grants for Construction of Treatment Works-Clean Water...

  8. 40 CFR 35.935-5 - Davis-Bacon and related statutes.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 1 2012-07-01 2012-07-01 false Davis-Bacon and related statutes. 35.935-5 Section 35.935-5 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY GRANTS AND OTHER FEDERAL ASSISTANCE STATE AND LOCAL ASSISTANCE Grants for Construction of Treatment Works-Clean Water...

  9. 40 CFR 35.935-5 - Davis-Bacon and related statutes.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 1 2014-07-01 2014-07-01 false Davis-Bacon and related statutes. 35.935-5 Section 35.935-5 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY GRANTS AND OTHER FEDERAL ASSISTANCE STATE AND LOCAL ASSISTANCE Grants for Construction of Treatment Works-Clean Water...

  10. 40 CFR 35.935-5 - Davis-Bacon and related statutes.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 1 2011-07-01 2011-07-01 false Davis-Bacon and related statutes. 35.935-5 Section 35.935-5 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY GRANTS AND OTHER FEDERAL ASSISTANCE STATE AND LOCAL ASSISTANCE Grants for Construction of Treatment Works-Clean Water...

  11. [The law of March 4th, 2002 - the Patient's Rights Statute].

    PubMed

    Thouvenin, Dominique

    2015-06-01

    With regards to the health professionals-patients relationships, this Statute marked a transition from a system to another : from the "knowing" professional one to the patient-actor one. The rights granted to patients are designed to given them the means to become such a player.

  12. 45 CFR 30.4 - Compromise, waiver, or disposition under other statutes not precluded.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 45 Public Welfare 1 2010-10-01 2010-10-01 false Compromise, waiver, or disposition under other statutes not precluded. 30.4 Section 30.4 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION CLAIMS COLLECTION General Provisions § 30.4 Compromise, waiver, or disposition under...

  13. Caspase activation regulates the extracellular export of autophagic vacuoles.

    PubMed

    Sirois, Isabelle; Groleau, Jessika; Pallet, Nicolas; Brassard, Nathalie; Hamelin, Katia; Londono, Irène; Pshezhetsky, Alexey V; Bendayan, Moise; Hébert, Marie-Josée

    2012-06-01

    The endothelium plays a central role in the regulation of vascular wall cellularity and tone by secreting an array of mediators of importance in intercellular communication. Nutrient deprivation of human endothelial cells (EC) evokes unconventional forms of secretion leading to the release of nanovesicles distinct from apoptotic bodies and bearing markers of multivesicular bodies (MVB). Nutrient deficiency is also a potent inducer of autophagy and vesicular transport pathways can be assisted by autophagy. Nutrient deficiency induced a significant and rapid increase in autophagic features, as imaged by electron microscopy and immunoblotting analysis of LC3-II/LC3-I ratios. Increased autophagic flux was confirmed by exposing serum-starved cells to bafilomycin A 1. Induction of autophagy was followed by indices of an apoptotic response, as assessed by microscopy and poly (ADP-ribose) polymerase cleavage in absence of cell membrane permeabilization indicative of necrosis. Pan-caspase inhibition with ZVAD-FMK did not prevent the development of autophagy but negatively impacted autophagic vacuole (AV) maturation. Adopting a multidimensional proteomics approach with validation by immunoblotting, we determined that nutrient-deprived EC released AV components (LC3I, LC3-II, ATG16L1 and LAMP2) whereas pan-caspase inhibition with ZVAD-FMK blocked AV release. Similarly, nutrient deprivation in aortic murine EC isolated from CASP3/caspase 3-deficient mice induced an autophagic response in absence of apoptosis and failed to prompt LC3 release. Collectively, the present results demonstrate the release of autophagic components by nutrient-deprived apoptotic human cells in absence of cell membrane permeabilization. These results also identify caspase-3 as a novel regulator of AV release. PMID:22692030

  14. 32 CFR 536.34 - Determination of correct statute.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... noncombat activities or brought by soldiers for incident-to-service property losses sustained within the... claims resulting from Army firing and demolition activities must be forwarded to the Commander USARCS for... rental vehicles will be processed in the same manner as NAFI commercially insured activities...

  15. 32 CFR 536.34 - Determination of correct statute.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... noncombat activities or brought by soldiers for incident-to-service property losses sustained within the... claims resulting from Army firing and demolition activities must be forwarded to the Commander USARCS for... rental vehicles will be processed in the same manner as NAFI commercially insured activities...

  16. 32 CFR 536.34 - Determination of correct statute.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... noncombat activities or brought by soldiers for incident-to-service property losses sustained within the... claims resulting from Army firing and demolition activities must be forwarded to the Commander USARCS for... rental vehicles will be processed in the same manner as NAFI commercially insured activities...

  17. 32 CFR 536.34 - Determination of correct statute.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... noncombat activities or brought by soldiers for incident-to-service property losses sustained within the... claims resulting from Army firing and demolition activities must be forwarded to the Commander USARCS for... rental vehicles will be processed in the same manner as NAFI commercially insured activities...

  18. 32 CFR 536.34 - Determination of correct statute.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... noncombat activities or brought by soldiers for incident-to-service property losses sustained within the... claims resulting from Army firing and demolition activities must be forwarded to the Commander USARCS for... rental vehicles will be processed in the same manner as NAFI commercially insured activities...

  19. 76 FR 28852 - Agency Information Collection (Regulation for Submission of Evidence); Activity Under OMB Review

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-05-18

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF VETERANS AFFAIRS Agency Information Collection (Regulation for Submission of Evidence); Activity Under OMB Review... INFORMATION: Title: Regulation for Submission of Evidence--Title 38 CFR 17.101(a)(4). OMB Control Number:...

  20. 78 FR 43969 - Agency Information Collection (Regulation for Reconsideration of Denied Claims) Activity Under...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-07-22

    ....Regulations.gov or to VA's OMB Desk Officer, OMB Human Resources and Housing Branch, New Executive Office... AFFAIRS Agency Information Collection (Regulation for Reconsideration of Denied Claims) Activity Under OMB... collection of information abstracted below to the Office of Management and Budget (OMB) for review...