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Sample records for activities regulations statutes

  1. 32 CFR 516.29 - Federal statutes and regulations.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 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. 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...

  3. 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,…

  4. 34 CFR 222.19 - What other statutes and regulations apply to this part?

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 34 Education 1 2014-07-01 2014-07-01 false What other statutes and regulations apply to this part? 222.19 Section 222.19 Education Regulations of the Offices of the Department of Education OFFICE OF ELEMENTARY AND SECONDARY EDUCATION, DEPARTMENT OF EDUCATION IMPACT AID PROGRAMS General § 222.19 What other statutes and regulations apply to...

  5. 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)...

  6. 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)...

  7. 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)...

  8. 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)...

  9. 45 CFR Appendix I to Part 617 - List of Age Distinctions Provided in Federal Statutes or Regulations Affecting Federal Financial...

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... Statutes or Regulations Affecting Federal Financial Assistance Administered by NSF I Appendix I to Part 617... NONDISCRIMINATION ON THE BASIS OF AGE IN PROGRAMS OR ACTIVITIES RECEIVING FEDERAL FINANCIAL ASSISTANCE FROM NSF Pt... Regulations Affecting Federal Financial Assistance Administered by NSF I. Section 6 of Pub. L. 94-86, 42...

  10. 45 CFR Appendix I to Part 617 - List of Age Distinctions Provided in Federal Statutes or Regulations Affecting Federal Financial...

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... Statutes or Regulations Affecting Federal Financial Assistance Administered by NSF I Appendix I to Part 617... NONDISCRIMINATION ON THE BASIS OF AGE IN PROGRAMS OR ACTIVITIES RECEIVING FEDERAL FINANCIAL ASSISTANCE FROM NSF Pt... Regulations Affecting Federal Financial Assistance Administered by NSF I. Section 6 of Pub. L. 94-86, 42...

  11. 45 CFR Appendix I to Part 617 - List of Age Distinctions Provided in Federal Statutes or Regulations Affecting Federal Financial...

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... Statutes or Regulations Affecting Federal Financial Assistance Administered by NSF I Appendix I to Part 617... NONDISCRIMINATION ON THE BASIS OF AGE IN PROGRAMS OR ACTIVITIES RECEIVING FEDERAL FINANCIAL ASSISTANCE FROM NSF Pt... Regulations Affecting Federal Financial Assistance Administered by NSF I. Section 6 of Pub. L. 94-86, 42...

  12. 45 CFR Appendix I to Part 617 - List of Age Distinctions Provided in Federal Statutes or Regulations Affecting Federal Financial...

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... Statutes or Regulations Affecting Federal Financial Assistance Administered by NSF I Appendix I to Part 617... NONDISCRIMINATION ON THE BASIS OF AGE IN PROGRAMS OR ACTIVITIES RECEIVING FEDERAL FINANCIAL ASSISTANCE FROM NSF Pt... Regulations Affecting Federal Financial Assistance Administered by NSF I. Section 6 of Pub. L. 94-86, 42...

  13. 7 CFR 3430.4 - Other applicable statutes and regulations.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... for Drug-Free Workplace (Financial Assistance). 7 CFR Part 3052—USDA implementation of OMB Circular No..., Rehabilitation Act of 1973) and 7 CFR Part 15b (USDA implementation of statute)—prohibiting discrimination based... CSREES Federal assistance programs. These include, but are not limited to: 7 CFR Part 1, subpart...

  14. 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...

  15. 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...

  16. 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...

  17. 29 CFR 794.110 - Activities excluded from the enterprise by the statute.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 29 Labor 3 2010-07-01 2010-07-01 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...

  18. 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...

  19. 7 CFR 3402.20 - Other Federal statutes and regulations that apply.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 15 2011-01-01 2011-01-01 false Other Federal statutes and regulations that apply. 3402.20 Section 3402.20 Agriculture Regulations of the Department of Agriculture (Continued) NATIONAL INSTITUTE OF FOOD AND AGRICULTURE FOOD AND AGRICULTURAL SCIENCES NATIONAL NEEDS GRADUATE AND POSTGRADUATE FELLOWSHIP GRANTS PROGRAM...

  20. 45 CFR 1180.51 - Compliance with statutes, regulations, and its approved grant application.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 45 Public Welfare 3 2011-10-01 2011-10-01 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...

  1. 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...

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

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 45 Public Welfare 3 2014-10-01 2014-10-01 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...

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

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 45 Public Welfare 3 2013-10-01 2013-10-01 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...

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

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 45 Public Welfare 3 2012-10-01 2012-10-01 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...

  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, DEPARTMENT OF TRANSPORTATION (AVIATION PROCEEDINGS) ECONOMIC REGULATIONS FREE AND REDUCED-RATE TRANSPORTATION International Travel § 223.21 Free...

  6. 28 CFR 91.68 - Compliance with other Federal environmental statutes, regulations and executive orders.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... Historic Preservation Act, as well as the Advisory Council on Historic Preservation's regulations at 36 CFR... environmental statutes, regulations and executive orders. 91.68 Section 91.68 Judicial Administration DEPARTMENT OF JUSTICE (CONTINUED) GRANTS FOR CORRECTIONAL FACILITIES Environmental Impact Review Procedures...

  7. 28 CFR 91.68 - Compliance with other Federal environmental statutes, regulations and executive orders.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... Historic Preservation Act, as well as the Advisory Council on Historic Preservation's regulations at 36 CFR... environmental statutes, regulations and executive orders. 91.68 Section 91.68 Judicial Administration DEPARTMENT OF JUSTICE (CONTINUED) GRANTS FOR CORRECTIONAL FACILITIES Environmental Impact Review Procedures...

  8. 28 CFR 91.68 - Compliance with other Federal environmental statutes, regulations and executive orders.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... Historic Preservation Act, as well as the Advisory Council on Historic Preservation's regulations at 36 CFR... environmental statutes, regulations and executive orders. 91.68 Section 91.68 Judicial Administration DEPARTMENT OF JUSTICE (CONTINUED) GRANTS FOR CORRECTIONAL FACILITIES Environmental Impact Review Procedures...

  9. 28 CFR 91.68 - Compliance with other Federal environmental statutes, regulations and executive orders.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... Historic Preservation Act, as well as the Advisory Council on Historic Preservation's regulations at 36 CFR... environmental statutes, regulations and executive orders. 91.68 Section 91.68 Judicial Administration DEPARTMENT OF JUSTICE (CONTINUED) GRANTS FOR CORRECTIONAL FACILITIES Environmental Impact Review Procedures...

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

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 10 Energy 4 2014-01-01 2014-01-01 false Applicable Federal Statutes, Executive Orders, and Government-wide Regulations A Appendix A to Part 603 Energy DEPARTMENT OF ENERGY (CONTINUED) ASSISTANCE REGULATIONS TECHNOLOGY INVESTMENT AGREEMENTS Pt. 603, App. A Appendix A to Part 603—Applicable Federal Statutes, Executive Orders, and...

  11. 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

    ... Administered by the Department of Justice Section 90.31(f) of HHS' the general regulations (45 CFR part 90... 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...

  12. 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

    ... Administered by the Department of Justice Section 90.31(f) of HHS' the general regulations (45 CFR part 90... 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...

  13. 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

    ... Administered by the Department of Justice Section 90.31(f) of HHS' the general regulations (45 CFR part 90... 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...

  14. 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

    ... Administered by the Department of Justice Section 90.31(f) of HHS' the general regulations (45 CFR part 90... 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...

  15. 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

    ... Administered by the Department of Justice Section 90.31(f) of HHS' the general regulations (45 CFR part 90... 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...

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

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 49 Transportation 1 2014-10-01 2014-10-01 false Statutes Regulating Post-Employment... Part 99—Statutes Regulating Post-Employment Responsibilities of Government and Special Government Employees Note: This appendix applies only to employees who terminated government service before January...

  17. 49 CFR Appendix E to Part 99 - Statutes Regulating Post-Employment Responsibilities of Government and Special Government Employees

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 1 2011-10-01 2011-10-01 false Statutes Regulating Post-Employment... Part 99—Statutes Regulating Post-Employment Responsibilities of Government and Special Government Employees Note: This appendix applies only to employees who terminated government service before January...

  18. 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... Part 99—Statutes Regulating Post-Employment Responsibilities of Government and Special Government Employees Note: This appendix applies only to employees who terminated government service before January...

  19. 49 CFR Appendix E to Part 99 - Statutes Regulating Post-Employment Responsibilities of Government and Special Government Employees

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 1 2013-10-01 2013-10-01 false Statutes Regulating Post-Employment... Part 99—Statutes Regulating Post-Employment Responsibilities of Government and Special Government Employees Note: This appendix applies only to employees who terminated government service before January...

  20. 45 CFR Appendix I to Part 617 - List of Age Distinctions Provided in Federal Statutes or Regulations Affecting Federal Financial...

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... Statutes or Regulations Affecting Federal Financial Assistance Administered by NSF I Appendix I to Part 617.... 617, App. I Appendix I to Part 617—List of Age Distinctions Provided in Federal Statutes or Regulations Affecting Federal Financial Assistance Administered by NSF I. Section 6 of Pub. L. 94-86, 42...

  1. 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...

  2. 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...

  3. 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...

  4. 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...

  5. 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...

  6. 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...

  7. 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...

  8. 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...

  9. 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...

  10. 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...

  11. 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...

  12. 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...

  13. 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...

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

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... Administrative Requirements for Grants and Agreements with Institutions of Higher Education, Hospitals and Other... regulations are contained in 37 CFR part 401) (n) Title IX of the Education Amendment of 1972 (20 U.S.C. 1681... grants and cooperative agreements awarded by OAO. These include, but are not limited to: (a) 7 CFR Part...

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

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... Administrative Requirements for Grants and Agreements with Institutions of Higher Education, Hospitals and Other... regulations are contained in 37 CFR part 401) (n) Title IX of the Education Amendment of 1972 (20 U.S.C. 1681... grants and cooperative agreements awarded by OAO. These include, but are not limited to: (a) 7 CFR Part...

  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, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 33 2011-07-01 2011-07-01 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. 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...

  19. 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.

  20. 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...

  1. 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...

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

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 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 GRANTS... Federal financial assistance from the Institute. These regulations apply to each program or activity...

  3. 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.

  4. 30 CFR 250.1451 - What may BSEE do if I violate a statute, regulation, order, or lease term relating to a Federal...

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 30 Mineral Resources 2 2012-07-01 2012-07-01 false What may BSEE do if I violate a statute, regulation, order, or lease term relating to a Federal oil and gas lease? 250.1451 Section 250.1451 Mineral Resources BUREAU OF SAFETY AND ENVIRONMENTAL ENFORCEMENT, DEPARTMENT OF THE INTERIOR OFFSHORE OIL AND GAS AND SULPHUR OPERATIONS IN THE...

  5. 30 CFR 250.1451 - What may BSEE do if I violate a statute, regulation, order, or lease term relating to a Federal...

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 30 Mineral Resources 2 2013-07-01 2013-07-01 false What may BSEE do if I violate a statute, regulation, order, or lease term relating to a Federal oil and gas lease? 250.1451 Section 250.1451 Mineral Resources BUREAU OF SAFETY AND ENVIRONMENTAL ENFORCEMENT, DEPARTMENT OF THE INTERIOR OFFSHORE OIL AND GAS AND SULPHUR OPERATIONS IN THE...

  6. 30 CFR 250.1451 - What may BSEE do if I violate a statute, regulation, order, or lease term relating to a Federal...

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 30 Mineral Resources 2 2014-07-01 2014-07-01 false What may BSEE do if I violate a statute, regulation, order, or lease term relating to a Federal oil and gas lease? 250.1451 Section 250.1451 Mineral Resources BUREAU OF SAFETY AND ENVIRONMENTAL ENFORCEMENT, DEPARTMENT OF THE INTERIOR OFFSHORE OIL AND GAS AND SULPHUR OPERATIONS IN THE...

  7. 28 CFR 91.68 - Compliance with other Federal environmental statutes, regulations and executive orders.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... Historic Preservation Act, as well as the Advisory Council on Historic Preservation's regulations at 36 CFR... regulations, and the relevant executive orders: (1) Archeological and Historical Preservation Act, (2)...

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

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... the basis of sex), and the implementing regulations (34 CFR part 106). (Authority: 20 U.S.C. 1681-1683...), and the implementing regulations (34 CFR part 100). (Authority: 42 U.S.C. 2000d—2000d-4) (2) The... discrimination on the basis of disability), and the implementing regulations (34 CFR part 104). (Authority: 29...

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

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... discrimination on the basis of disability), and the implementing regulations (34 CFR part 104). (Authority: 29 U...), 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. 34 CFR 222.19 - What other statutes and regulations apply to this part?

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... the basis of sex), and the implementing regulations (34 CFR part 106). (Authority: 20 U.S.C. 1681-1683...), and the implementing regulations (34 CFR part 100). (Authority: 42 U.S.C. 2000d—2000d-4) (2) The... discrimination on the basis of disability), and the implementing regulations (34 CFR part 104). (Authority: 29...

  11. 34 CFR 222.19 - What other statutes and regulations apply to this part?

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... the basis of sex), and the implementing regulations (34 CFR part 106). (Authority: 20 U.S.C. 1681-1683...), and the implementing regulations (34 CFR part 100). (Authority: 42 U.S.C. 2000d—2000d-4) (2) The... discrimination on the basis of disability), and the implementing regulations (34 CFR part 104). (Authority: 29...

  12. 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...

  13. 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...

  14. 42 CFR 480.109 - Applicability of other statutes and regulations.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... AND HUMAN SERVICES (CONTINUED) QUALITY IMPROVEMENT ORGANIZATIONS ACQUISITION, PROTECTION, AND DISCLOSURE OF QUALITY IMPROVEMENT ORGANIZATION REVIEW INFORMATION Utilization and Quality Control Quality... patients' records, and the implementing regulations at 42 CFR part 2, are applicable to QIO...

  15. 45 CFR 1180.44 - Federal statutes and regulations on nondiscrimination.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 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...

  16. 45 CFR 1180.44 - Federal statutes and regulations on nondiscrimination.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 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...

  17. 45 CFR 1180.44 - Federal statutes and regulations on nondiscrimination.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 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...

  18. 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...

  19. 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...

  20. 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...

  1. 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...

  2. 42 CFR 480.109 - Applicability of other statutes and regulations.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... AND HUMAN SERVICES (CONTINUED) QUALITY IMPROVEMENT ORGANIZATIONS ACQUISITION, PROTECTION, AND DISCLOSURE OF QUALITY IMPROVEMENT ORGANIZATION REVIEW INFORMATION Utilization and Quality Control Quality... patients' records, and the implementing regulations at 42 CFR part 2, are applicable to QIO...

  3. 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...

  4. 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...

  5. 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...

  6. 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...

  7. 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...

  8. 25 CFR 900.216 - What other statutes and regulations apply to contract disputes?

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ...); (b) If the matter is submitted to the Interior Board of Contract Appeals, 43 CFR 4.110-126; and (c) The Equal Access to Justice Act, 5 U.S.C. 504 and 28 U.S.C. 2412 and regulations at 43 CFR 4.601 through 4.619 (DOI) and 45 CFR 13 (DHHS)....

  9. 7 CFR 4285.93 - Other Federal statutes and regulations that apply.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ..., cooperative agreements, and loans; (i) 7 CFR Part 3051—Audits of Institutions of Higher Education and Other... 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...

  10. 7 CFR 4285.93 - Other Federal statutes and regulations that apply.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ..., cooperative agreements, and loans; (i) 7 CFR Part 3051—Audits of Institutions of Higher Education and Other... 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...

  11. State Policies Regulating the Practice of Pain Management: Statutes, Rules, and Guidelines That Shape Pain Care.

    PubMed

    Twillman, Robert K; Gilson, Aaron M; Duensing, Kathryn N

    2016-06-01

    In response to increased awareness of prescription opioid misuse, abuse, addiction, diversion, and overdose, states have promulgated a large number of public policies intended to regulate the practice of pain medicine. Nearly every state now has at least 1 type of policy; others only provide recommendations to physicians. This article reviews the existing policies and extracts specific provisions within each of them. Although there are many similarities across policies, unique features are found in some and are specifically reviewed. This review can serve as a quick reference for policymakers and as a guide for researchers interested in the impacts of such policies. PMID:27208718

  12. Teacher Evaluation as a Policy Target for Improved Student Learning: A Fifty-State Review of Statute and Regulatory Action since NCLB

    ERIC Educational Resources Information Center

    Hazi, Helen M.; Rucinski, Daisy Arredondo

    2009-01-01

    This paper reports on the analysis of state statutes and department of education regulations in fifty states for changes in teacher evaluation in use since the passage of No Child Left Behind Act of 2001. We asked what the policy activity for teacher evaluation is in state statutes and department of education regulations, how these changes in…

  13. 7 CFR 3021.625 - Criminal drug statute.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 15 2012-01-01 2012-01-01 false Criminal drug statute. 3021.625 Section 3021.625 Agriculture Regulations of the Department of Agriculture (Continued) OFFICE OF THE CHIEF FINANCIAL OFFICER...) Definitions § 3021.625 Criminal drug statute. Criminal drug statute means a Federal or non-Federal...

  14. 7 CFR 3021.625 - Criminal drug statute.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 15 2010-01-01 2010-01-01 false Criminal drug statute. 3021.625 Section 3021.625 Agriculture Regulations of the Department of Agriculture (Continued) OFFICE OF THE CHIEF FINANCIAL OFFICER...) Definitions § 3021.625 Criminal drug statute. Criminal drug statute means a Federal or non-Federal...

  15. 48 CFR 25.602-2 - 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 American Recovery and Reinvestment Act-Buy American Statute-Construction Materials 25.602-2 Buy American statute. Except as provided in 25.603, use only...

  16. 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...

  17. 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...

  18. 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...

  19. 10 CFR Appendix A to Part 603 - Applicable Federal Statutes, Executive Orders, and Government-wide Regulations

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 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....

  20. 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....

  1. 10 CFR Appendix A to Part 603 - Applicable Federal Statutes, Executive Orders, and Government-wide Regulations

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 745 and rules on animal acquisition, transport, care, handling and use in 9 CFR parts 1 through 4... 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....

  2. 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

    ... 745 and rules on animal acquisition, transport, care, handling and use in 9 CFR parts 1 through 4... 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....

  3. 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...

  4. 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...

  5. 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

    ... veteran who meets the requirements of 38 CFR 3.57, except as to age or marital status 64.117 Survivors... 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...

  6. 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…

  7. 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...

  8. 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...

  9. 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 OFFSET § 607.10 Statute of limitations. If a debt has been outstanding for more than 10 years after...

  10. 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...

  11. 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...

  12. 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...

  13. 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...

  14. 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...

  15. 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...

  16. 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 by statute. The prohibitions of § 348.3 do...

  17. 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...

  18. 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...

  19. 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...

  20. 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...

  1. 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...

  2. Factors regulating microglia activation

    PubMed Central

    Kierdorf, Katrin; Prinz, Marco

    2013-01-01

    Microglia are resident macrophages of the central nervous system (CNS) that display high functional similarities to other tissue macrophages. However, it is especially important to create and maintain an intact tissue homeostasis to support the neuronal cells, which are very sensitive even to minor changes in their environment. The transition from the “resting” but surveying microglial phenotype to an activated stage is tightly regulated by several intrinsic (e.g., Runx-1, Irf8, and Pu.1) and extrinsic factors (e.g., CD200, CX3CR1, and TREM2). Under physiological conditions, minor changes of those factors are sufficient to cause fatal dysregulation of microglial cell homeostasis and result in severe CNS pathologies. In this review, we discuss recent achievements that gave new insights into mechanisms that ensure microglia quiescence. PMID:23630462

  3. Medical Emergency Exceptions in State Abortion Statutes: The Statistical Record.

    PubMed

    Linton, Paul Benjamin

    2016-01-01

    This article attempts to determine, first, whether emergency exceptions in statutes regulating abortion have been abused and, second, whether the standard used in such an exception--subjective or objective--makes a difference in the reported incidence of such emergencies. A review of the statistical data supports two conclusions. First, physicians who perform abortions and have complied with state reporting requirements have not relied upon the medical emergency exceptions in state abortion statutes to evade the requirements of those statutes. Second, the use of an objective standard for evaluating medical emergencies ("reasonable medical judgment") has not been associated with fewer reported emergencies (per number of abortions performed) than the use of a subjective standard ("good faith clinical judgment"). Both of these conclusions may be relevant in drafting other abortion statutes including prohibitions (e.g., post-viability abortions). PMID:27323547

  4. Indians and Southern Colonial Statutes

    ERIC Educational Resources Information Center

    Kawashima, Yasuhide

    1974-01-01

    Southern statutes, with their dual nature of uniformity and diversity, were doubtlessly an essential source of law for the examination of complex legal relations between American Indians and Anglo Americans in the colonial South. (FF)

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

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 48 Federal Acquisition Regulations System 6 2010-10-01 2010-10-01 true Authorized or required by statute. 1506.302-5 Section 1506.302-5 Federal Acquisition Regulations System ENVIRONMENTAL PROTECTION AGENCY ACQUISITION PLANNING COMPETITION REQUIREMENTS Other Than Full and Open Competition 1506.302-5 Authorized or required by statute....

  6. 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 AGENCY ACQUISITION PLANNING COMPETITION REQUIREMENTS Other Than Full and Open Competition 1506.302-5 Authorized or required by statute....

  7. 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 AGENCY ACQUISITION PLANNING COMPETITION REQUIREMENTS Other Than Full and Open Competition 1506.302-5 Authorized or required by statute....

  8. Regulation of inflammasome activation.

    PubMed

    Man, Si Ming; Kanneganti, Thirumala-Devi

    2015-05-01

    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, auto-inflammatory, 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 (AIM2)-like receptors (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 with the development of auto-inflammatory 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

  9. 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

  10. 15 CFR 922.61 - Prohibited or otherwise regulated activities.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... type, whether by an individual or by a submersible; (d) Lowering below the surface of the water any grappling, suction, conveyor, dredging or wrecking device; (e) Detonating below the surface of the water any... into the water in violation of any Federal statute or regulation....

  11. 15 CFR 922.61 - Prohibited or otherwise regulated activities.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... type, whether by an individual or by a submersible; (d) Lowering below the surface of the water any grappling, suction, conveyor, dredging or wrecking device; (e) Detonating below the surface of the water any... into the water in violation of any Federal statute or regulation....

  12. 15 CFR 922.61 - Prohibited or otherwise regulated activities.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... type, whether by an individual or by a submersible; (d) Lowering below the surface of the water any grappling, suction, conveyor, dredging or wrecking device; (e) Detonating below the surface of the water any... into the water in violation of any Federal statute or regulation....

  13. 15 CFR 922.61 - Prohibited or otherwise regulated activities.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... type, whether by an individual or by a submersible; (d) Lowering below the surface of the water any grappling, suction, conveyor, dredging or wrecking device; (e) Detonating below the surface of the water any... into the water in violation of any Federal statute or regulation....

  14. 15 CFR 922.61 - Prohibited or otherwise regulated activities.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... type, whether by an individual or by a submersible; (d) Lowering below the surface of the water any grappling, suction, conveyor, dredging or wrecking device; (e) Detonating below the surface of the water any... into the water in violation of any Federal statute or regulation....

  15. Molecular regulation of osteoclast activity.

    PubMed

    Bruzzaniti, Angela; Baron, Roland

    2006-06-01

    Osteoclasts are multinucleated cells derived from hematopoietic precursors that are primarily responsible for the degradation of mineralized bone during bone development, homeostasis and repair. In various skeletal disorders such as osteoporosis, hypercalcemia of malignancy, tumor metastases and Paget's disease, bone resorption by osteoclasts exceeds bone formation by osteoblasts leading to decreased bone mass, skeletal fragility and bone fracture. The overall rate of osteoclastic bone resorption is regulated either at the level of differentiation of osteoclasts from their monocytic/macrophage precursor pool or through the regulation of key functional proteins whose specific activities in the mature osteoclast control its attachment, migration and resorption. Thus, reducing osteoclast numbers and/or decreasing the bone resorbing activity of osteoclasts are two common therapeutic approaches for the treatment of hyper-resorptive skeletal diseases. In this review, several of the key functional players involved in the regulation of osteoclast activity will be discussed. PMID:16951988

  16. 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...

  17. 49 CFR 1302.42 - Further suspension of statute.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 9 2010-10-01 2010-10-01 false Further suspension of statute. 1302.42 Section 1302.42 Transportation Other Regulations Relating to Transportation (Continued) SURFACE TRANSPORTATION BOARD, DEPARTMENT OF TRANSPORTATION (CONTINUED) CARRIER RATES AND SERVICE TERMS EXPORT AND...

  18. 49 CFR 1302.41 - Suspension of statute.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 9 2010-10-01 2010-10-01 false Suspension of statute. 1302.41 Section 1302.41 Transportation Other Regulations Relating to Transportation (Continued) SURFACE TRANSPORTATION BOARD, DEPARTMENT OF TRANSPORTATION (CONTINUED) CARRIER RATES AND SERVICE TERMS EXPORT AND IMPORT SHIPMENTS;...

  19. 49 CFR 1302.42 - Further suspension of statute.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 9 2011-10-01 2011-10-01 false Further suspension of statute. 1302.42 Section 1302.42 Transportation Other Regulations Relating to Transportation (Continued) SURFACE TRANSPORTATION BOARD, DEPARTMENT OF TRANSPORTATION (CONTINUED) CARRIER RATES AND SERVICE TERMS EXPORT AND...

  20. 49 CFR 1302.41 - Suspension of statute.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 9 2011-10-01 2011-10-01 false Suspension of statute. 1302.41 Section 1302.41 Transportation Other Regulations Relating to Transportation (Continued) SURFACE TRANSPORTATION BOARD, DEPARTMENT OF TRANSPORTATION (CONTINUED) CARRIER RATES AND SERVICE TERMS EXPORT AND IMPORT SHIPMENTS;...

  1. 22 CFR 120.27 - U.S. criminal statutes.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 22 Foreign Relations 1 2012-04-01 2012-04-01 false U.S. criminal statutes. 120.27 Section 120.27 Foreign Relations DEPARTMENT OF STATE INTERNATIONAL TRAFFIC IN ARMS REGULATIONS PURPOSE AND DEFINITIONS... means: (1) Section 38 of the Arms Export Control Act (22 U.S.C. 2778); (2) Section 11 of the...

  2. 22 CFR 120.27 - U.S. criminal statutes.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 22 Foreign Relations 1 2013-04-01 2013-04-01 false U.S. criminal statutes. 120.27 Section 120.27 Foreign Relations DEPARTMENT OF STATE INTERNATIONAL TRAFFIC IN ARMS REGULATIONS PURPOSE AND DEFINITIONS... means: (1) Section 38 of the Arms Export Control Act (22 U.S.C. 2778); (2) Section 11 of the...

  3. 22 CFR 120.27 - U.S. criminal statutes.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 22 Foreign Relations 1 2011-04-01 2011-04-01 false U.S. criminal statutes. 120.27 Section 120.27 Foreign Relations DEPARTMENT OF STATE INTERNATIONAL TRAFFIC IN ARMS REGULATIONS PURPOSE AND DEFINITIONS... means: (1) Section 38 of the Arms Export Control Act (22 U.S.C. 2778); (2) Section 11 of the...

  4. 12 CFR 238.94 - Interlocking relationships permitted by statute.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 12 Banks and Banking 4 2013-01-01 2013-01-01 false Interlocking relationships permitted by statute. 238.94 Section 238.94 Banks and Banking FEDERAL RESERVE SYSTEM (CONTINUED) BOARD OF GOVERNORS OF THE FEDERAL RESERVE SYSTEM (CONTINUED) SAVINGS AND LOAN HOLDING COMPANIES (REGULATION LL) Management...

  5. 12 CFR 238.94 - Interlocking relationships permitted by statute.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 12 Banks and Banking 4 2012-01-01 2012-01-01 false Interlocking relationships permitted by statute. 238.94 Section 238.94 Banks and Banking FEDERAL RESERVE SYSTEM (CONTINUED) BOARD OF GOVERNORS OF THE FEDERAL RESERVE SYSTEM (CONTINUED) SAVINGS AND LOAN HOLDING COMPANIES (REGULATION LL) Management...

  6. 12 CFR 238.94 - Interlocking relationships permitted by statute.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 12 Banks and Banking 4 2014-01-01 2014-01-01 false Interlocking relationships permitted by statute. 238.94 Section 238.94 Banks and Banking FEDERAL RESERVE SYSTEM (CONTINUED) BOARD OF GOVERNORS OF THE FEDERAL RESERVE SYSTEM (CONTINUED) SAVINGS AND LOAN HOLDING COMPANIES (REGULATION LL) Management...

  7. 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.

  8. Phosphatase regulation of macrophage activation.

    PubMed

    Kozicky, Lisa K; Sly, Laura M

    2015-08-01

    Macrophages are innate immune cells that play critical roles in tissue homeostasis and the immune response to invading pathogens or tumor cells. A hallmark of macrophages is their "plasticity," that is, their ability to respond to cues in their local microenvironment and adapt their activation state or phenotype to mount an appropriate response. During the inflammatory response, macrophages may be required to mount a profound anti-bacterial or anti-tumor response, an anti-inflammatory response, an anti-parasitic response, or a wound healing response. To do so, macrophages express cell surface receptors for growth factors, chemokines and cytokines, as well pathogen and danger associated molecular patterns. Downstream of these cell surface receptors, cell signalling cascades are activated and deactivated by reversible and competing activities of lipid and protein kinases and phosphatases. While kinases drive the activation of cell signalling pathways critical for macrophage activation, the strength and duration of the signalling is regulated by phosphatases. Hence, gene knockout mouse models have revealed critical roles for lipid and protein phosphatases in macrophage activation. Herein, we describe our current understanding and the key roles of specific cellular phosphatases in the regulation of the quality of macrophage polarization as well as the quantity of cytokines produced by activated macrophages. PMID:26216598

  9. 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.

  10. [Evidence of health culture in medieval statute of Budva].

    PubMed

    Milovic Karic, Grozdana; Milovic, Dorde

    2010-01-01

    The Statute of Budva dates from the time of Nemanjics. This medieval document was approved at the time Budva was under venetian dominion and remained in force until the end of the Venetian Republic. During 17th century the Statute was translated into the Italian language. The document includes regulations which indicate a concern for the health of the public. Among the regulations is one which prohibit the sale of fisch outside the stalls of the fishmarket presumably to ensure the sale of only fresh fish. Another regulation prohibits the sale of dead animals, the sale of dog's meat instead od wether meat. There is also language indicating a concern for protecting the cleanliness of brooks, rivers and wells. Corporal punishment is mentioned but only with regard to whipping and beheading. PMID:21192114

  11. 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.

  12. 48 CFR 6.302-5 - Authorized or required by statute.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 48 Federal Acquisition Regulations System 1 2010-10-01 2010-10-01 false Authorized or required by statute. 6.302-5 Section 6.302-5 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION... a specified source or through another agency: (1) Federal Prison Industries (UNICOR)—18 U.S.C....

  13. 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...

  14. 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...

  15. 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... 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...

  16. 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...

  17. 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...

  18. 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...

  19. 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...

  20. 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...

  1. 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...

  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. 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...

  4. 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...

  5. 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...

  6. 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...

  7. 34 CFR 84.625 - Criminal drug statute.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 34 Education 1 2012-07-01 2012-07-01 false Criminal drug statute. 84.625 Section 84.625 Education... (FINANCIAL ASSISTANCE) Definitions § 84.625 Criminal drug statute. Criminal drug statute means a Federal or non-Federal criminal statute involving the manufacture, distribution, dispensing, use, or...

  8. 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,...

  9. 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...

  10. 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...

  11. 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...

  12. 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...

  13. 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...

  14. 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...

  15. 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...

  16. 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...

  17. 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...

  18. 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...

  19. 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...

  20. 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...

  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. 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...

  3. 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...

  4. Transportation legislative data base: State radioactive materials transportation statute compilation, 1989--1993

    SciTech Connect

    1994-04-01

    The Transportation Legislative Data Base (TLDB) is a computer-based information service containing summaries of federal, state and certain local government statutes and regulations relating to the transportation of radioactive materials in the United States. The TLDB has been operated by the National Conference of State Legislatures (NCSL) under cooperative agreement with the US Department of Energy`s (DOE) Office of Civilian Radioactive Waste Management since 1992. The data base system serves the legislative and regulatory information needs of federal, state, tribal and local governments, the affected private sector and interested members of the general public. Users must be approved by DOE and NCSL. This report is a state statute compilation that updates the 1989 compilation produced by Battelle Memorial Institute, the previous manager of the data base. This compilation includes statutes not included in the prior compilation, as well as newly enacted laws. Statutes not included in the prior compilation show an enactment date prior to 1989. Statutes that deal with low-level radioactive waste transportation are included in the data base as are statutes from the states of Alaska and Hawaii. Over 155 new entries to the data base are summarized in this compilation.

  5. 41 CFR Appendix A to Part 102 - 37-Miscellaneous Donation Statutes

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 41 Public Contracts and Property Management 3 2010-07-01 2010-07-01 false 37-Miscellaneous Donation Statutes A Appendix A to Part 102 Public Contracts and Property Management Federal Property Management Regulations System (Continued) FEDERAL MANAGEMENT REGULATION PERSONAL PROPERTY 37-DONATION...

  6. 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...

  7. 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...

  8. 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...

  9. 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…

  10. 42 CFR 2.21 - Relationship to Federal statutes protecting research subjects against compulsory disclosure of...

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    .... 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...

  11. 42 CFR 2.21 - Relationship to Federal statutes protecting research subjects against compulsory disclosure of...

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    .... 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...

  12. 42 CFR 2.21 - Relationship to Federal statutes protecting research subjects against compulsory disclosure of...

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    .... 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...

  13. 49 CFR 32.625 - Criminal drug statute.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 1 2010-10-01 2010-10-01 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...

  14. 22 CFR 133.625 - Criminal drug statute.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 22 Foreign Relations 1 2012-04-01 2012-04-01 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...

  15. 29 CFR 94.625 - Criminal drug statute.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 29 Labor 1 2010-07-01 2010-07-01 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...

  16. 12 CFR 590.101 - State criminal usury statutes.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... the federal statute preempts a state law which deems it a criminal offense to charge interest at a... 12 Banks and Banking 5 2010-01-01 2010-01-01 false State criminal usury statutes. 590.101 Section... USURY LAWS § 590.101 State criminal usury statutes. (a) Section 501 provides that “the provisions of...

  17. 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...

  18. 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...

  19. 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...

  20. 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...

  1. 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...

  2. 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...

  3. 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...

  4. 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...

  5. 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...

  6. 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...

  7. 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...

  8. 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...

  9. 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...

  10. 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...

  11. 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...

  12. 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...

  13. 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...

  14. 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...

  15. 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...

  16. 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...

  17. 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...

  18. 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...

  19. 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...

  20. 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...

  1. 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...

  2. 2 CFR 182.625 - Criminal drug statute.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 2 Grants and Agreements 1 2010-01-01 2010-01-01 false Criminal drug statute. 182.625 Section 182... AGREEMENTS Reserved GOVERNMENTWIDE REQUIREMENTS FOR DRUG-FREE WORKPLACE (FINANCIAL ASSISTANCE) Definitions § 182.625 Criminal drug statute. Criminal drug statute means a Federal or non-Federal criminal...

  3. 12 CFR 590.101 - State criminal usury statutes.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 12 Banks and Banking 6 2014-01-01 2012-01-01 true State criminal usury statutes. 590.101 Section... USURY LAWS § 590.101 State criminal usury statutes. (a) Section 501 provides that “the provisions of the... the federal statute preempts a state law which deems it a criminal offense to charge interest at...

  4. 12 CFR 190.101 - State criminal usury statutes.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 12 Banks and Banking 1 2013-01-01 2013-01-01 false State criminal usury statutes. 190.101 Section... USURY LAWS § 190.101 State criminal usury statutes. (a) Section 501 provides that “the provisions of the... the Federal statute preempts a state law which deems it a criminal offense to charge interest at...

  5. 12 CFR 190.101 - State criminal usury statutes.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 12 Banks and Banking 1 2014-01-01 2014-01-01 false State criminal usury statutes. 190.101 Section... USURY LAWS § 190.101 State criminal usury statutes. (a) Section 501 provides that “the provisions of the... the Federal statute preempts a state law which deems it a criminal offense to charge interest at...

  6. 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...

  7. 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...

  8. 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...

  9. 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...

  10. 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...

  11. 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...

  12. 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...

  13. 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...

  14. 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...

  15. 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...

  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. 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...

  18. 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...

  19. 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...

  20. 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...

  1. 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...

  2. 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...

  3. 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...

  4. 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...

  5. 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...

  6. 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...

  7. 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...

  8. 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...

  9. 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...

  10. 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...

  11. 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...

  12. Transglutaminase 2 Regulates the GTPase-activating Activity of Bcr*

    PubMed Central

    Yi, Sun-Ju; Groffen, John; Heisterkamp, Nora

    2009-01-01

    Transglutaminase 2 (TG2) is a multifunctional protein that has been implicated in numerous pathologies including that of neurodegeneration and celiac disease, but the molecular interactions that mediate its diverse activities are largely unknown. Bcr and the closely related Abr negatively regulate the small G-protein Rac: loss of their combined function in vivo results in increased reactivity of innate immune cells. Bcr and Abr are GTPase-activating proteins that catalyze the hydrolysis of the GTP bound to Rac. However, how the Bcr and Abr GTPase-activating activity is regulated is not precisely understood. We here report a novel mechanism of regulation through direct protein-protein interaction with TG2. TG2 bound to the Rac-binding pocket in the GTPase-activating domains of Bcr and Abr, blocked Bcr activity and, through this mechanism, increased levels of active GTP-bound Rac and EGF-stimulated membrane ruffling. TG2 exists in at least two different conformations. Interestingly, experiments using TG2 mutants showed that Bcr exhibits preferential binding to the non-compacted conformation of TG2, in which its catalytic domain is exposed, but transamidation is not needed for the interaction. Thus, TG2 regulates levels of cellular GTP-bound Rac and actin cytoskeletal reorganization through a new mechanism involving direct inhibition of Bcr GTPase-activating activity. PMID:19840940

  13. 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...

  14. 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...

  15. Regulation of ROCK activity in cancer.

    PubMed

    Morgan-Fisher, Marie; Wewer, Ulla M; Yoneda, Atsuko

    2013-03-01

    Cancer-associated changes in cellular behavior, such as modified cell-cell contact, increased migratory potential, and generation of cellular force, all require alteration of the cytoskeleton. Two homologous mammalian serine/threonine kinases, Rho-associated protein kinases (ROCK I and II), are key regulators of the actin cytoskeleton acting downstream of the small GTPase Rho. ROCK is associated with cancer progression, and ROCK protein expression is elevated in several types of cancer. ROCKs exist in a closed, inactive conformation under quiescent conditions, which is changed to an open, active conformation by the direct binding of guanosine triphosphate (GTP)-loaded Rho. In recent years, a number of ROCK isoform-specific binding partners have been found to modulate the kinase activity through direct interactions with the catalytic domain or via altered cellular localization of the kinases. Thus, these findings demonstrate additional modes to regulate ROCK activity. This review describes the molecular mechanisms of ROCK activity regulation in cancer, with emphasis on ROCK isoform-specific regulation and interaction partners, and discusses the potential of ROCKs as therapeutic targets in cancer. PMID:23204112

  16. Regulation of brain aromatase activity in rats

    SciTech Connect

    Roselli, C.E.; Ellinwood, W.E.; Resko, J.A.

    1984-01-01

    The distribution and regulation of aromatase activity in the adult rat brain with a sensitive in vitro assay that measures the amount of /sup 3/H/sub 2/O formed during the conversion of (1 beta-/sup 3/H)androstenedione to estrone. The rate of aromatase activity in the hypothalamus-preoptic area (HPOA) was linear with time up to 1 h, and with tissue concentrations up to 5 mgeq/200 microliters incubation mixture. The enzyme demonstrated a pH optimum of 7.4 and an apparent Michaelis-Menten constant (Km) of 0.04 microns. The greatest amount of aromatase activity was found in amygdala and HPOA from intact male rats. The hippocampus, midbrain tegmentum, cerebral cortex, cerebellum, and anterior pituitary all contained negligible enzymatic activity. Castration produced a significant decrease in aromatase activity in the HPOA, but not in the amygdala or cerebral cortex. The HPOAs of male rats contained significantly greater aromatase activity than the HPOAs of female rats. In females, this enzyme activity did not change during the estrous cycle or after ovariectomy. Administration of testosterone to gonadectomized male and female rats significantly enhanced HPOA aromatase activities to levels approximating those found in HPOA from intact males. Therefore, the results suggest that testosterone, or one of its metabolites, is a major steroidal regulator of HPOA aromatase activity in rats.

  17. 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 LAWRENCE SEAWAY DEVELOPMENT CORPORATION, DEPARTMENT OF TRANSPORTATION SEAWAY REGULATIONS AND RULES Assessment, Mitigation or Remission...

  18. 49 CFR 1302.43 - Applicable rates on shipments in transit when statute becomes effective.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 9 2011-10-01 2011-10-01 false Applicable rates on shipments in transit when statute becomes effective. 1302.43 Section 1302.43 Transportation Other Regulations Relating to Transportation (Continued) SURFACE TRANSPORTATION BOARD, DEPARTMENT OF TRANSPORTATION (CONTINUED) CARRIER...

  19. 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:...

  20. 32 CFR 22.310 - Statutes concerning certain research, development, and facilities construction grants.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 32 National Defense 1 2013-07-01 2013-07-01 false Statutes concerning certain research, development, and facilities construction grants. 22.310 Section 22.310 National Defense Department of Defense OFFICE OF THE SECRETARY OF DEFENSE DoD GRANT AND AGREEMENT REGULATIONS DoD GRANTS AND AGREEMENTS-AWARD AND ADMINISTRATION Competition §...

  1. 49 CFR 1302.43 - Applicable rates on shipments in transit when statute becomes effective.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 9 2010-10-01 2010-10-01 false Applicable rates on shipments in transit when statute becomes effective. 1302.43 Section 1302.43 Transportation Other Regulations Relating to Transportation (Continued) SURFACE TRANSPORTATION BOARD, DEPARTMENT OF TRANSPORTATION (CONTINUED) CARRIER RATES AND SERVICE TERMS EXPORT AND IMPORT...

  2. Regulating the regulators: modulators of transcription factor activity.

    PubMed

    Everett, Logan; Hansen, Matthew; Hannenhalli, Sridhar

    2010-01-01

    Gene transcription is largely regulated by DNA-binding transcription factors (TFs). However, the TF activity itself is modulated via, among other things, post-translational modifications (PTMs) by specific modification enzymes in response to cellular stimuli. TF-PTMs thus serve as "molecular switchboards" that map upstream signaling events to the downstream transcriptional events. An important long-term goal is to obtain a genome-wide map of "regulatory triplets" consisting of a TF, target gene, and a modulator gene that specifically modulates the regulation of the target gene by the TF. A variety of genome-wide data sets can be exploited by computational methods to obtain a rough map of regulatory triplets, which can guide directed experiments. However, a prerequisite to developing such computational tools is a systematic catalog of known instances of regulatory triplets. We first describe PTM-Switchboard, a recent database that stores triplets of genes such that the ability of one gene (the TF) to regulate a target gene is dependent on one or more PTMs catalyzed by a third gene, the modifying enzyme. We also review current computational approaches to infer regulatory triplets from genome-wide data sets and conclude with a discussion of potential future research. PTM-Switchboard is accessible at http://cagr.pcbi.upenn.edu/PTMswitchboard / PMID:20827600

  3. 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.

  4. 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

  5. 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…

  6. 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

  7. 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

  8. Regulation of Trichophyton rubrum proteolytic activity.

    PubMed Central

    Apodaca, G; McKerrow, J H

    1989-01-01

    Trichophyton rubrum is the most common dermatophyte of humans and normally colonizes the superficial layers of the epidermis (stratum corneum). Several proteinases with a possible role in the metabolism of host proteins have been purified from this fungus. The regulation of these enzymes and their role in fungal metabolism were studied at the biochemical level. General proteolytic (azocollytic) activity was repressed when log-phase cultures of T. rubrum were grown in a minimal medium that contained readily metabolized sources of carbon, nitrogen, sulfur, and phosphorus. When either carbon, nitrogen, or sulfur was deleted from this minimal medium, azocollytic activity was derepressed. In all cases a high-molecular-weight activity (Mr, greater than 200,000) was expressed. A 71,000-Mr proteinase was observed in nitrogen-depleted cultures, and proteolytic species of Mr 124,000 and 27,000 were secreted in sulfur-depleted cultures. The addition of either inorganic (MgSO4, Na2SO3, NaS2O3) or organic (methionine, cysteine) sulfur to the sulfur-depleted medium repressed the expression of azocollytic activity. In contrast, keratinolytic activity was not repressed by carbon, nitrogen, or sulfur but instead was induced when a protein source was included in the minimal medium. Stationary-phase cultures of T. rubrum secreted all proteolytic activities constitutively. Unlike log-phase cultures, the stationary-phase cultures secreted azocollytic, elastinolytic, and keratinolytic activity in minimal medium. These activities fell in the carbon-, nitrogen-, and phosphorous-depleted media but remained high in sulfur-depleted medium. The following model is proposed for the regulation of T. rubrum proteolytic activity. In the initial stages of infection, T. rubrum grows logarithmically. In this state, proteolytic activity is derepressed whenever carbon, nitrogen, or sulfur is lacking in the fungal milieu. The general proteinases produced would act on the nonkeratinous proteins in the

  9. 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

  10. 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

  11. 22 CFR 120.27 - U.S. criminal statutes.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false U.S. criminal statutes. 120.27 Section 120.27... § 120.27 U.S. criminal statutes. (a) For purposes of this subchapter, the phrase U.S. criminal statutes means: (1) Section 38 of the Arms Export Control Act (22 U.S.C. 2778); (2) Section 11 of the...

  12. 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

  13. 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

  14. Structural Basis for Plexin Activation and Regulation.

    PubMed

    Kong, Youxin; Janssen, Bert J C; Malinauskas, Tomas; Vangoor, Vamshidhar R; Coles, Charlotte H; Kaufmann, Rainer; Ni, Tao; Gilbert, Robert J C; Padilla-Parra, Sergi; Pasterkamp, R Jeroen; Jones, E Yvonne

    2016-08-01

    Class A plexins (PlxnAs) act as semaphorin receptors and control diverse aspects of nervous system development and plasticity, ranging from axon guidance and neuron migration to synaptic organization. PlxnA signaling requires cytoplasmic domain dimerization, but extracellular regulation and activation mechanisms remain unclear. Here we present crystal structures of PlxnA (PlxnA1, PlxnA2, and PlxnA4) full ectodomains. Domains 1-9 form a ring-like conformation from which the C-terminal domain 10 points away. All our PlxnA ectodomain structures show autoinhibitory, intermolecular "head-to-stalk" (domain 1 to domain 4-5) interactions, which are confirmed by biophysical assays, live cell fluorescence microscopy, and cell-based and neuronal growth cone collapse assays. This work reveals a 2-fold role of the PlxnA ectodomains: imposing a pre-signaling autoinhibitory separation for the cytoplasmic domains via intermolecular head-to-stalk interactions and supporting dimerization-based PlxnA activation upon ligand binding. More generally, our data identify a novel molecular mechanism for preventing premature activation of axon guidance receptors. PMID:27397516

  15. 21 CFR 20.67 - Records exempted by other statutes.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 1 2010-04-01 2010-04-01 false Records exempted by other statutes. 20.67 Section 20.67 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL... withheld from public disclosure if a statute specifically allows the Food and Drug Administration (FDA)...

  16. 15 CFR 29.625 - Criminal drug statute.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 15 Commerce and Foreign Trade 1 2012-01-01 2012-01-01 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. 13 CFR 147.625 - Criminal drug statute.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 13 Business Credit and Assistance 1 2011-01-01 2011-01-01 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...

  18. 2 CFR 182.625 - Criminal drug statute.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 2 Grants and Agreements 1 2014-01-01 2014-01-01 false Criminal drug statute. 182.625 Section 182.625 Grants and Agreements Office of Management and Budget Guidance for Grants and Agreements OFFICE OF... FOR DRUG-FREE WORKPLACE (FINANCIAL ASSISTANCE) Definitions § 182.625 Criminal drug statute....

  19. 2 CFR 182.625 - Criminal drug statute.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 2 Grants and Agreements 1 2011-01-01 2011-01-01 false Criminal drug statute. 182.625 Section 182.625 Grants and Agreements Office of Management and Budget Guidance for Grants and Agreements OFFICE OF...-FREE WORKPLACE (FINANCIAL ASSISTANCE) Definitions § 182.625 Criminal drug statute. Criminal...

  20. 36 CFR 67.8 - Certifications of statutes.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... or districts. This includes any by-laws or ordinances that contain information necessary for the... certification of the statute. (c) State enabling legislation which authorizes local governments to designate, or... statutes will be certified. If the State enabling legislation contains provisions which do not meet...

  1. 45 CFR 73.735-1003 - Conflicts of interest statutes.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 45 Public Welfare 1 2010-10-01 2010-10-01 false Conflicts of interest statutes. 73.735-1003...-1003 Conflicts of interest statutes. (a) Each consultant should acquaint himself or herself with... related to conflicts of interest. The restraints imposed by the four criminal sections are summarized...

  2. 26 CFR 1.9002-7 - Statute of limitations.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 26 Internal Revenue 13 2012-04-01 2012-04-01 false Statute of limitations. 1.9002-7 Section 1.9002-7 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES (CONTINUED) General Actuarial Valuations § 1.9002-7 Statute of limitations....

  3. 26 CFR 1.9004-3 - Statutes of limitation.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 26 Internal Revenue 13 2014-04-01 2014-04-01 false Statutes of limitation. 1.9004-3 Section 1.9004-3 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES (CONTINUED) General Actuarial Valuations § 1.9004-3 Statutes of limitation....

  4. 26 CFR 1.9004-3 - Statutes of limitation.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 13 2010-04-01 2010-04-01 false Statutes of limitation. 1.9004-3 Section 1.9004-3 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES General Actuarial Valuations § 1.9004-3 Statutes of limitation. The period...

  5. 26 CFR 1.9002-7 - Statute of limitations.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 13 2010-04-01 2010-04-01 false Statute of limitations. 1.9002-7 Section 1.9002-7 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES General Actuarial Valuations § 1.9002-7 Statute of limitations. (a) Extension...

  6. 26 CFR 1.9004-3 - Statutes of limitation.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 26 Internal Revenue 13 2013-04-01 2013-04-01 false Statutes of limitation. 1.9004-3 Section 1.9004-3 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES (CONTINUED) General Actuarial Valuations § 1.9004-3 Statutes of limitation....

  7. 26 CFR 1.9005-3 - Statutes of limitation.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 26 Internal Revenue 13 2013-04-01 2013-04-01 false Statutes of limitation. 1.9005-3 Section 1.9005-3 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES (CONTINUED) General Actuarial Valuations § 1.9005-3 Statutes of...

  8. 26 CFR 1.9003-3 - Statutes of limitation.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 26 Internal Revenue 13 2011-04-01 2011-04-01 false Statutes of limitation. 1.9003-3 Section 1.9003-3 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES (CONTINUED) General Actuarial Valuations § 1.9003-3 Statutes of limitation....

  9. 26 CFR 1.9002-7 - Statute of limitations.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 26 Internal Revenue 13 2011-04-01 2011-04-01 false Statute of limitations. 1.9002-7 Section 1.9002-7 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES (CONTINUED) General Actuarial Valuations § 1.9002-7 Statute of limitations....

  10. 26 CFR 1.9003-3 - Statutes of limitation.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 26 Internal Revenue 13 2014-04-01 2014-04-01 false Statutes of limitation. 1.9003-3 Section 1.9003-3 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES (CONTINUED) General Actuarial Valuations § 1.9003-3 Statutes of limitation....

  11. 26 CFR 1.9003-3 - Statutes of limitation.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 26 Internal Revenue 13 2013-04-01 2013-04-01 false Statutes of limitation. 1.9003-3 Section 1.9003-3 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES (CONTINUED) General Actuarial Valuations § 1.9003-3 Statutes of limitation....

  12. 26 CFR 1.9005-3 - Statutes of limitation.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 26 Internal Revenue 13 2012-04-01 2012-04-01 false Statutes of limitation. 1.9005-3 Section 1.9005-3 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES (CONTINUED) General Actuarial Valuations § 1.9005-3 Statutes of...

  13. 26 CFR 1.9002-7 - Statute of limitations.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 26 Internal Revenue 13 2013-04-01 2013-04-01 false Statute of limitations. 1.9002-7 Section 1.9002-7 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES (CONTINUED) General Actuarial Valuations § 1.9002-7 Statute of limitations....

  14. 26 CFR 1.9005-3 - Statutes of limitation.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 26 Internal Revenue 13 2014-04-01 2014-04-01 false Statutes of limitation. 1.9005-3 Section 1.9005-3 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES (CONTINUED) General Actuarial Valuations § 1.9005-3 Statutes of...

  15. 26 CFR 1.9004-3 - Statutes of limitation.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 26 Internal Revenue 13 2011-04-01 2011-04-01 false Statutes of limitation. 1.9004-3 Section 1.9004-3 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES (CONTINUED) General Actuarial Valuations § 1.9004-3 Statutes of limitation....

  16. 26 CFR 1.9002-7 - Statute of limitations.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 26 Internal Revenue 13 2014-04-01 2014-04-01 false Statute of limitations. 1.9002-7 Section 1.9002-7 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES (CONTINUED) General Actuarial Valuations § 1.9002-7 Statute of limitations....

  17. 26 CFR 1.9003-3 - Statutes of limitation.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 13 2010-04-01 2010-04-01 false Statutes of limitation. 1.9003-3 Section 1.9003-3 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES General Actuarial Valuations § 1.9003-3 Statutes of limitation. Under section...

  18. 26 CFR 1.9005-3 - Statutes of limitation.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 13 2010-04-01 2010-04-01 false Statutes of limitation. 1.9005-3 Section 1.9005-3 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES General Actuarial Valuations § 1.9005-3 Statutes of limitation. Notwithstanding...

  19. 26 CFR 1.9004-3 - Statutes of limitation.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 26 Internal Revenue 13 2012-04-01 2012-04-01 false Statutes of limitation. 1.9004-3 Section 1.9004-3 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES (CONTINUED) General Actuarial Valuations § 1.9004-3 Statutes of limitation....

  20. 26 CFR 1.9003-3 - Statutes of limitation.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 26 Internal Revenue 13 2012-04-01 2012-04-01 false Statutes of limitation. 1.9003-3 Section 1.9003-3 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES (CONTINUED) General Actuarial Valuations § 1.9003-3 Statutes of limitation....

  1. 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...

  2. 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...

  3. 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...

  4. 19 CFR 171.64 - Waiver of statute of limitations.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 19 Customs Duties 2 2010-04-01 2010-04-01 false Waiver of statute of limitations. 171.64 Section 171.64 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY; DEPARTMENT....64 Waiver of statute of limitations. The deciding Customs official always reserves the right...

  5. 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,...

  6. 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,...

  7. 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,...

  8. 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,...

  9. 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,...

  10. 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...

  11. 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...

  12. 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...

  13. 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...

  14. 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

  15. 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

  16. 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:...

  17. 48 CFR 552.212-72 - Contract Terms and Conditions Required To Implement Statutes or Executive Orders Applicable to...

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 48 Federal Acquisition Regulations System 4 2010-10-01 2010-10-01 false Contract Terms and... ADMINISTRATION CLAUSES AND FORMS SOLICITATION PROVISIONS AND CONTRACT CLAUSES Text of Provisions and Clauses 552.212-72 Contract Terms and Conditions Required To Implement Statutes or Executive Orders Applicable...

  18. 48 CFR 52.225-7 - Waiver of Buy American Statute for Civil Aircraft and Related Articles.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 48 Federal Acquisition Regulations System 2 2014-10-01 2014-10-01 false Waiver of Buy American... CLAUSES Text of Provisions and Clauses 52.225-7 Waiver of Buy American Statute for Civil Aircraft and Related Articles. As prescribed in 25.1101(d), insert the following provision: Waiver of Buy...

  19. 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...

  20. 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...

  1. 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...

  2. 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...

  3. 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...

  4. 12 CFR Appendix to Part 215 - Section 5200 of the Revised Statutes Total Loans and Extensions of Credit

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 12 Banks and Banking 2 2010-01-01 2010-01-01 false Section 5200 of the Revised Statutes Total Loans and Extensions of Credit Appendix to Part 215 Banks and Banking FEDERAL RESERVE SYSTEM BOARD OF GOVERNORS OF THE FEDERAL RESERVE SYSTEM LOANS TO EXECUTIVE OFFICERS, DIRECTORS, AND PRINCIPAL SHAREHOLDERS OF MEMBER BANKS (REGULATION O) Pt. 215,...

  5. 12 CFR Appendix to Part 215 - Section 5200 of the Revised Statutes Total Loans and Extensions of Credit

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 12 Banks and Banking 2 2012-01-01 2012-01-01 false Section 5200 of the Revised Statutes Total Loans and Extensions of Credit Appendix to Part 215 Banks and Banking FEDERAL RESERVE SYSTEM BOARD OF GOVERNORS OF THE FEDERAL RESERVE SYSTEM LOANS TO EXECUTIVE OFFICERS, DIRECTORS, AND PRINCIPAL SHAREHOLDERS OF MEMBER BANKS (REGULATION O) Pt. 215,...

  6. 12 CFR Appendix to Part 215 - Section 5200 of the Revised Statutes Total Loans and Extensions of Credit

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 12 Banks and Banking 2 2014-01-01 2014-01-01 false Section 5200 of the Revised Statutes Total Loans and Extensions of Credit Appendix to Part 215 Banks and Banking FEDERAL RESERVE SYSTEM BOARD OF GOVERNORS OF THE FEDERAL RESERVE SYSTEM LOANS TO EXECUTIVE OFFICERS, DIRECTORS, AND PRINCIPAL SHAREHOLDERS OF MEMBER BANKS (REGULATION O) Pt. 215,...

  7. 12 CFR Appendix to Part 215 - Section 5200 of the Revised Statutes Total Loans and Extensions of Credit

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 12 Banks and Banking 2 2013-01-01 2013-01-01 false Section 5200 of the Revised Statutes Total Loans and Extensions of Credit Appendix to Part 215 Banks and Banking FEDERAL RESERVE SYSTEM BOARD OF GOVERNORS OF THE FEDERAL RESERVE SYSTEM LOANS TO EXECUTIVE OFFICERS, DIRECTORS, AND PRINCIPAL SHAREHOLDERS OF MEMBER BANKS (REGULATION O) Pt. 215,...

  8. 8 CFR 319.5 - Public international organizations in which the U.S. participates by treaty or statute.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 8 Aliens and Nationality 1 2010-01-01 2010-01-01 false Public international organizations in which the U.S. participates by treaty or statute. 319.5 Section 319.5 Aliens and Nationality DEPARTMENT OF HOMELAND SECURITY NATIONALITY REGULATIONS SPECIAL CLASSES OF PERSONS WHO MAY BE NATURALIZED: SPOUSES...

  9. 8 CFR 319.5 - Public international organizations in which the U.S. participates by treaty or statute.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 8 Aliens and Nationality 1 2011-01-01 2011-01-01 false Public international organizations in which the U.S. participates by treaty or statute. 319.5 Section 319.5 Aliens and Nationality DEPARTMENT OF HOMELAND SECURITY NATIONALITY REGULATIONS SPECIAL CLASSES OF PERSONS WHO MAY BE NATURALIZED: SPOUSES...

  10. 22 CFR 1008.625 - 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. 1008.625 Section 1008.625 Foreign Relations INTER-AMERICAN FOUNDATION GOVERNMENTWIDE REQUIREMENTS FOR DRUG-FREE WORKPLACE (FINANCIAL... controlled substance....

  11. 22 CFR 312.625 - Criminal drug statute.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 22 Foreign Relations 2 2014-04-01 2014-04-01 false Criminal drug statute. 312.625 Section 312.625 Foreign Relations PEACE CORPS GOVERNMENTWIDE REQUIREMENTS FOR DRUG-FREE WORKPLACE (FINANCIAL ASSISTANCE... substance....

  12. 22 CFR 1008.625 - Criminal drug statute.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 22 Foreign Relations 2 2014-04-01 2014-04-01 false Criminal drug statute. 1008.625 Section 1008.625 Foreign Relations INTER-AMERICAN FOUNDATION GOVERNMENTWIDE REQUIREMENTS FOR DRUG-FREE WORKPLACE... of any controlled substance....

  13. 22 CFR 1509.625 - Criminal drug statute.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 22 Foreign Relations 2 2014-04-01 2014-04-01 false Criminal drug statute. 1509.625 Section 1509.625 Foreign Relations AFRICAN DEVELOPMENT FOUNDATION GOVERNMENTWIDE REQUIREMENTS FOR DRUG-FREE... possession of any controlled substance....

  14. 22 CFR 1509.625 - 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. 1509.625 Section 1509.625 Foreign Relations AFRICAN DEVELOPMENT FOUNDATION GOVERNMENTWIDE REQUIREMENTS FOR DRUG-FREE WORKPLACE... of any controlled substance....

  15. 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...

  16. 32 CFR 516.29 - Federal statutes and regulations.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 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 15 (Defense of Certain Suits Against Federal Employees, etc.). (e) 28 CFR 50.16 (Representation of...

  17. 7 CFR 2500.003 - Other applicable statutes and regulations.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 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 of... origin, and 7 CFR part 15, subpart A (USDA implementation); (d) 7 CFR Part 3015—USDA Uniform...

  18. 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...

  19. 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...

  20. 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...

  1. 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...

  2. 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...

  3. 7 CFR 2903.21 - Applicable Federal statutes and regulations.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ..., 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...

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

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ..., 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, 2013 CFR

    2013-01-01

    ..., 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. Mechanisms of specificity in neuronal activity-regulated gene transcription

    PubMed Central

    Lyons, Michelle R.; West, Anne E.

    2011-01-01

    The brain is a highly adaptable organ that is capable of converting sensory information into changes in neuronal function. This plasticity allows behavior to be accommodated to the environment, providing an important evolutionary advantage. Neurons convert environmental stimuli into long-lasting changes in their physiology in part through the synaptic activity-regulated transcription of new gene products. Since the neurotransmitter-dependent regulation of Fos transcription was first discovered nearly 25 years ago, a wealth of studies have enriched our understanding of the molecular pathways that mediate activity-regulated changes in gene transcription. These findings show that a broad range of signaling pathways and transcriptional regulators can be engaged by neuronal activity to sculpt complex programs of stimulus-regulated gene transcription. However, the shear scope of the transcriptional pathways engaged by neuronal activity raises the question of how specificity in the nature of the transcriptional response is achieved in order to encode physiologically relevant responses to divergent stimuli. Here we summarize the general paradigms by which neuronal activity regulates transcription while focusing on the molecular mechanisms that confer differential stimulus-, cell-type-, and developmental-specificity upon activity-regulated programs of neuronal gene transcription. In addition, we preview some of the new technologies that will advance our future understanding of the mechanisms and consequences of activity-regulated gene transcription in the brain. PMID:21620929

  7. Cysteine Cathepsin Activity Regulation by Glycosaminoglycans

    PubMed Central

    Lenarčič, Brigita

    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. PMID:25587532

  8. [Regulation of peptide hydrolase activity in psoriasis].

    PubMed

    Suworow, A P

    1990-01-01

    Clinico-biological examination of 154 patients with psoriasis resulted in data showing high activity of endo- and exopeptidases in efflorescences of that dermatosis. This was accompanied by depressed activity of trypsin inhibitor. At the same time magnesium deficiency, polysaccharide decrease and leucocyte increase were stated to be in the focus of skin damage. That character of interrelation, which play an important role in the pathogenesis of this widespread skin disease, is demonstrated. PMID:2257941

  9. Dietary methanol regulates human gene activity.

    PubMed

    Shindyapina, Anastasia V; Petrunia, Igor V; 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

  10. Endogenous Methanol Regulates Mammalian Gene Activity

    PubMed Central

    Komarova, Tatiana V.; Petrunia, Igor V.; Shindyapina, Anastasia V.; Silachev, Denis N.; Sheshukova, Ekaterina V.; Kiryanov, Gleb I.; Dorokhov, Yuri L.

    2014-01-01

    We recently showed that methanol emitted by wounded plants might function as a signaling molecule for plant-to-plant and plant-to-animal communications. In mammals, methanol is considered a poison because the enzyme alcohol dehydrogenase (ADH) converts methanol into toxic formaldehyde. However, the detection of methanol in the blood and exhaled air of healthy volunteers suggests that methanol may be a chemical with specific functions rather than a metabolic waste product. Using a genome-wide analysis of the mouse brain, we demonstrated that an increase in blood methanol concentration led to a change in the accumulation of mRNAs from genes primarily involved in detoxification processes and regulation of the alcohol/aldehyde dehydrogenases gene cluster. To test the role of ADH in the maintenance of low methanol concentration in the plasma, we used the specific ADH inhibitor 4-methylpyrazole (4-MP) and showed that intraperitoneal administration of 4-MP resulted in a significant increase in the plasma methanol, ethanol and formaldehyde concentrations. Removal of the intestine significantly decreased the rate of methanol addition to the plasma and suggested that the gut flora may be involved in the endogenous production of methanol. ADH in the liver was identified as the main enzyme for metabolizing methanol because an increase in the methanol and ethanol contents in the liver homogenate was observed after 4-MP administration into the portal vein. Liver mRNA quantification showed changes in the accumulation of mRNAs from genes involved in cell signalling and detoxification processes. We hypothesized that endogenous methanol acts as a regulator of homeostasis by controlling the mRNA synthesis. PMID:24587296

  11. 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

  12. 15 CFR 922.102 - 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. 922.102 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...

  13. 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…

  14. 15 CFR 922.152 - 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. 922.152 Section 922.152 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...

  15. 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...

  16. 5 CFR 9303.102 - Prior approval for certain outside activities.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 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 2635.502... activity; and (iii) The employee has read subpart H (“Outside Activities”) of 5 CFR part 2635. (3) Upon...

  17. 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

  18. 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...

  19. 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...

  20. 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

  1. 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

  2. 38 CFR 17.502 - Applicability of other statutes.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2013-07-01 2013-07-01 false Applicability of other statutes. 17.502 Section 17.502 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS....S.C. 7332 (drug and alcohol abuse, sickle cell anemia, HIV infection), and 38 U.S.C. 5701...

  3. 38 CFR 17.502 - Applicability of other statutes.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2011-07-01 2011-07-01 false Applicability of other statutes. 17.502 Section 17.502 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS....S.C. 7332 (drug and alcohol abuse, sickle cell anemia, HIV infection), and 38 U.S.C. 5701...

  4. 38 CFR 17.502 - Applicability of other statutes.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2010-07-01 2010-07-01 false Applicability of other statutes. 17.502 Section 17.502 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS....S.C. 7332 (drug and alcohol abuse, sickle cell anemia, HIV infection), and 38 U.S.C. 5701...

  5. 38 CFR 17.502 - Applicability of other statutes.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2014-07-01 2014-07-01 false Applicability of other statutes. 17.502 Section 17.502 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS....S.C. 7332 (drug and alcohol abuse, sickle cell anemia, HIV infection), and 38 U.S.C. 5701...

  6. 38 CFR 17.502 - Applicability of other statutes.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2012-07-01 2012-07-01 false Applicability of other statutes. 17.502 Section 17.502 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS....S.C. 7332 (drug and alcohol abuse, sickle cell anemia, HIV infection), and 38 U.S.C. 5701...

  7. An Economic Analysis of the California Art Royalty Statute.

    ERIC Educational Resources Information Center

    Bolch, Ben W.; And Others

    1978-01-01

    The probable economic impact on the art market, museums, and the artist of California's "droit de suite" legislation, designed to yield to artists a portion of the resale value of their works, is examined. It is argued that only a few living artists will benefit. The statute, California Civil Code 986, is appended. (JMD)

  8. 5 CFR 734.702 - Related statutes and Executive orders.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ...-15162; 3 CFR 1989 Comp. 215-218) as modified by Executive Order 12731 (55 FR 42547-42550; 3 CFR 1990... Orders § 734.702 Related statutes and Executive orders. (a) The prohibition against offering anything of.... 210). (b) The prohibition against solicitation or acceptance of anything of value to obtain...

  9. 12 CFR 212.4 - Interlocking relationships permitted by statute.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    .... 212.4 Section 212.4 Banks and Banking FEDERAL RESERVE SYSTEM BOARD OF GOVERNORS OF THE FEDERAL RESERVE SYSTEM MANAGEMENT OFFICIAL INTERLOCKS § 212.4 Interlocking relationships permitted by statute. The... subsidiary thereof: (a) A depository organization that has been placed formally in liquidation, or which...

  10. 31 CFR 20.625 - Criminal drug statute.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 31 Money and Finance: Treasury 1 2012-07-01 2012-07-01 false Criminal drug statute. 20.625 Section 20.625 Money and Finance: Treasury Office of the Secretary of the Treasury GOVERNMENTWIDE REQUIREMENTS FOR DRUG-FREE WORKPLACE (FINANCIAL ASSISTANCE) Definitions § 20.625 Criminal drug...

  11. 31 CFR 20.625 - Criminal drug statute.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 31 Money and Finance: Treasury 1 2011-07-01 2011-07-01 false Criminal drug statute. 20.625 Section 20.625 Money and Finance: Treasury Office of the Secretary of the Treasury GOVERNMENTWIDE REQUIREMENTS FOR DRUG-FREE WORKPLACE (FINANCIAL ASSISTANCE) Definitions § 20.625 Criminal drug...

  12. 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...

  13. 5 CFR 1215.10 - Statute of limitations.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 1215.10 Administrative Personnel MERIT SYSTEMS PROTECTION BOARD ORGANIZATION AND PROCEDURES DEBT MANAGEMENT Salary Offset § 1215.10 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, the agency may not collect by...

  14. 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…

  15. 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…

  16. 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

  17. 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.

  18. Bacterial differentiation via gradual activation of global regulators.

    PubMed

    Kovács, Ákos T

    2016-02-01

    Bacteria have evolved to adapt to various conditions and respond to certain stress conditions. The ability to sense and efficiently reply to these environmental effects involve versatile array of sensors and global or specific regulators. Interestingly, modulation of the levels of active global regulators enables bacteria to respond to diverse signals via a single central transcriptional regulator and to activate or repress certain differentiation pathways at a spatio-temporal manner. The Gram-positive Bacillus subtilis is an ideal bacterium to study how membrane bound and cytoplasmic sensor kinases affect the level of phosphorylated global regulator, Spo0A which in response activates genes related to sliding, biofilm formation, and sporulation. In addition, other global regulators, including the two-component system DegS-DegU, modulate overlapping and complementary genes in B. subtilis related to surface colonization and biofilm formation. The intertwinement of global regulatory systems also allows the accurate modulation of differentiation pathways. Studies in the last decade enable us to get a deeper insight into the role of global regulators on the smooth transition of developmental processes in B. subtilis. PMID:26458398

  19. 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

  20. 34 CFR 110.2 - To what programs or activities do these regulations apply?

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... labor-management joint apprenticeship training program, except any program or activity receiving Federal... regulations apply? (a) These regulations apply to any program or activity receiving Federal...

  1. 34 CFR 110.2 - To what programs or activities do these regulations apply?

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... labor-management joint apprenticeship training program, except any program or activity receiving Federal... regulations apply? (a) These regulations apply to any program or activity receiving Federal...

  2. 34 CFR 110.2 - To what programs or activities do these regulations apply?

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... labor-management joint apprenticeship training program, except any program or activity receiving Federal... regulations apply? (a) These regulations apply to any program or activity receiving Federal...

  3. 34 CFR 110.2 - To what programs or activities do these regulations apply?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... labor-management joint apprenticeship training program, except any program or activity receiving Federal... regulations apply? (a) These regulations apply to any program or activity receiving Federal...

  4. 34 CFR 110.2 - To what programs or activities do these regulations apply?

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... labor-management joint apprenticeship training program, except any program or activity receiving Federal... regulations apply? (a) These regulations apply to any program or activity receiving Federal...

  5. 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

  6. Platelet activating factor: regulation by mast cells and aspirin.

    PubMed

    Denburg, J A; Williams, D B; Kinlough-Rathbone, R L; Cazenave, J P; Bienenstock, J

    1984-02-01

    We have investigated some aspects of the regulation of production of rat platelet activating factor (PAF)2 in vitro. Suspensions of unseparated (PLC1), mast cell-depleted (PLC2), or mast cell (MC)-enriched rat peritoneal lavage cells (PLC) were analyzed for PAF content by extraction at alkaline pH. PAF activity extracted from PLC1 varied inversely with viable cell concentration: at 1 X 10(6) cells/ml, 32 +/- 9.3 PAF units, decreasing to 11.2 +/- 9.5 units at 10 X 10(6) cells/ml, and no activity at higher concentrations. Incubation of PLC1 in Tyrode's buffer or acetylsalicylic acid (ASA), but not salicylate, resulted in a time-dependent loss of PAF activity. Mean PAF activity of PLC2 was similar to that in PLC1, while no PAF activity was extractable from MC. Co-incubation with MC extracts inhibited PAF activity of PLC1 extracts in a dose-dependent fashion. Ultracentrifugation of PAF-containing samples led to a loss of all PAF activity in PLC1 extracts, suggesting the association of PAF activity with subcellular components. PAF appears to be derived from a non-MC population of rat PLC, is not extractable from rat PLC in the presence of ASA and is inhibited by MC extracts. These studies suggest that ASA regulates PAF availability unrelated to its effect on cyclooxygenase and that MC membrane products directly inhibit PAF activity from rat PLC. PMID:6711391

  7. Intracerebroventricular injection of adiponectin regulates locomotor activity in rats.

    PubMed

    Miyatake, Yumiko; Shiuchi, Tetsuya; Ueta, Tomoyo; Taniguchi, Yasuko; Futami, Akari; Sato, Fukiko; Kitamura, Tadahiro; Tsutsumi, Rie; Harada, Nagakatsu; Nakaya, Yutaka; Sakaue, Hiroshi

    2015-01-01

    Enhancing exercise motivation is the best way to prevent obesity and diabetes. In this study, we examined whether adiponectin affects locomotion activity in Wister and Spontaneously-Running Tokushima-Shikoku (SPORTS) rats using two types of behavioral assays: home cage and wheel running activity. SPORTS rats were established from an original line from Wister strain that had shown high level of wheel running activity in our laboratory. Injection of adiponectin into the lateral ventricle of Wister rats and SPORTS rats decreased home cage activity, but no change was observed in the food intake and oxygen consumption. This result indicates the possibility that adiponectin can reduce non-exercise activity thermogenesis (NEAT) and physical activity via the central nervous system. In contrast, injection of adiponectin did not change wheel running activity in SPORTS rats. We produced hypothalamus-destructed model rat using monosodium glutamate (MSG) to elucidate the regulation site of adiponectin. Injection of adiponectin into MSG-treated SPORTS rats did not change amount of home cage activity and food intake, suggesting that adiponectin action on home cage activity was in the hypothalamic area. These results suggest that adiponectin regulates locomotion activity through mediobasal hypothalamus. PMID:26399348

  8. 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

  9. 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

  10. 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...

  11. 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...

  12. 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...

  13. 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...

  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. Regulation of the extracellular ligand binding activity of integrins.

    PubMed

    Fernandez, C; Clark, K; Burrows, L; Schofield, N R; Humphries, M J

    1998-07-01

    Integrins are a large heterodimeric family of cell surface adhesion receptors that bind extracellular matrix and cell surface ligands. The extracellular ligand binding activity of integrins is a dynamic and highly regulated event involving the induction of conformational changes within the integrin structure. The adhesive properties of integrins can be controlled by altering the activation state of the integrin, either through conformational change or receptor clustering, using mechanisms that are regulated by intracellular proteins. In this review, we will discuss what is currently known about integrin structure and the ligand binding sites present within the receptor. In addition, the mechanisms by which the ligand binding event is regulated through conformational change will be addressed, and the potential role of intracellular cytoplasmic proteins will be discussed. PMID:9637803

  16. 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

  17. Primary cilia and Gli3 activity regulate cerebral cortical size

    PubMed Central

    Wilson, Sandra L.; Wilson, John P.; Wang, Chengbing; Wang, Baolin; McConnell, Susan K.

    2012-01-01

    During neural development, patterning, neurogenesis and overall growth are highly regulated and coordinated between different brain regions. Here, we show that primary cilia and the regulation of Gli activity, are necessary for the normal expansion of the cerebral cortex. We show that loss of Kif3a, an important functional component of primary cilia, leads to the degeneration of primary cilia, marked overgrowth of the cortex, and altered cell cycle kinetics within cortical progenitors. The G1 phase of the cell cycle is shortened through a mechanism likely involving reduced Gli3 activity and a resulting increase in expression of cyclin D1 and Fgf15. The defects in Gli3 activity alone are sufficient to accelerate cell cycle kinetics and cause the molecular changes seen in brains that lack cilia. Finally, we show that levels of full-length and repressor Gli3 proteins are tightly regulated during normal development and correlate with changes in expression of two known Shh-target genes, CyclinD1 and Fgf15, and with the normal lengthening of the cell cycle during corticogenesis. These data suggest that Gli3 activity is regulated through the primary cilium to control cell cycle length in the cortex and thus determine cortical size. PMID:21976438

  18. 76 FR 44350 - Agency Information Collection Activities: Drawback Process Regulations

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-07-25

    ... 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, 7552... collection was previously published in the Federal Register (76 FR 19120) on April 6, 2011, allowing for a...

  19. 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...

  20. 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...

  1. 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.

  2. 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

  3. 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.

  4. 29 CFR 790.3 - Provisions of the statute.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... POLICY OR INTERPRETATION NOT DIRECTLY RELATED TO REGULATIONS GENERAL STATEMENT AS TO THE EFFECT OF THE...: (1) An express provision of a written or nonwritten contract in effect, at the time of such activity... custom or practice in effect, at the time of such activity, at the establishment or other place...

  5. 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

  6. 7 CFR 1421.408 - Prohibited activity.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ..., color, national origin, gender, religion, age, disability, political beliefs, sexual orientation, and marital or family status for which they would otherwise be eligible under the statutes regulating the...

  7. Tbx16 regulates hox gene activation in mesodermal progenitor cells.

    PubMed

    Payumo, Alexander Y; McQuade, Lindsey E; Walker, Whitney J; Yamazoe, Sayumi; Chen, James K

    2016-09-01

    The transcription factor T-box 16 (Tbx16, or Spadetail) is an essential regulator of paraxial mesoderm development in zebrafish (Danio rerio). Mesodermal progenitor cells (MPCs) fail to differentiate into trunk somites in tbx16 mutants and instead accumulate within the tailbud in an immature state. However, the mechanisms by which Tbx16 controls mesoderm patterning have remained enigmatic. We describe here the use of photoactivatable morpholino oligonucleotides to determine the Tbx16 transcriptome in MPCs. We identified 124 Tbx16-regulated genes that were expressed in zebrafish gastrulae, including several developmental signaling proteins and regulators of gastrulation, myogenesis and somitogenesis. Unexpectedly, we observed that a loss of Tbx16 function precociously activated posterior hox genes in MPCs, and overexpression of a single posterior hox gene was sufficient to disrupt MPC migration. Our studies support a model in which Tbx16 regulates the timing of collinear hox gene activation to coordinate the anterior-posterior fates and positions of paraxial MPCs. PMID:27376691

  8. Activation and Regulation of DNA-Driven Immune Responses

    PubMed Central

    2015-01-01

    SUMMARY The innate immune system provides early defense against infections and also plays a key role in monitoring alterations of homeostasis in the body. DNA is highly immunostimulatory, and recent advances in this field have led to the identification of the innate immune sensors responsible for the recognition of DNA as well as the downstream pathways that are activated. Moreover, information on how cells regulate DNA-driven immune responses to avoid excessive inflammation is now emerging. Finally, several reports have demonstrated how defects in DNA sensing, signaling, and regulation are associated with susceptibility to infections or inflammatory diseases in humans and model organisms. In this review, the current literature on DNA-stimulated innate immune activation is discussed, and important new questions facing this field are proposed. PMID:25926682

  9. 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

  10. 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

  11. 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

  12. Sphingosine-1-Phosphate Is a Novel Regulator of Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Activity

    PubMed Central

    Semenkov, Illya; Molinski, Steven; Pasyk, Stan; Ahmadi, Saumel; Bui, Hai H.; Bear, Christine E.; Lidington, Darcy; Bolz, Steffen-Sebastian

    2015-01-01

    The cystic fibrosis transmembrane conductance regulator (CFTR) attenuates sphingosine-1-phosphate (S1P) signaling in resistance arteries and has emerged as a prominent regulator of myogenic vasoconstriction. This investigation demonstrates that S1P inhibits CFTR activity via adenosine monophosphate-activated kinase (AMPK), establishing a potential feedback link. In Baby Hamster Kidney (BHK) cells expressing wild-type human CFTR, S1P (1μmol/L) attenuates forskolin-stimulated, CFTR-dependent iodide efflux. S1P’s inhibitory effect is rapid (within 30 seconds), transient and correlates with CFTR serine residue 737 (S737) phosphorylation. Both S1P receptor antagonism (4μmol/L VPC 23019) and AMPK inhibition (80μmol/L Compound C or AMPK siRNA) attenuate S1P-stimluated (i) AMPK phosphorylation, (ii) CFTR S737 phosphorylation and (iii) CFTR activity inhibition. In BHK cells expressing the ΔF508 CFTR mutant (CFTRΔF508), the most common mutation causing cystic fibrosis, both S1P receptor antagonism and AMPK inhibition enhance CFTR activity, without instigating discernable correction. In summary, we demonstrate that S1P/AMPK signaling transiently attenuates CFTR activity. Since our previous work positions CFTR as a negative S1P signaling regulator, this signaling link may positively reinforce S1P signals. This discovery has clinical ramifications for the treatment of disease states associated with enhanced S1P signaling and/or deficient CFTR activity (e.g. cystic fibrosis, heart failure). S1P receptor/AMPK inhibition could synergistically enhance the efficacy of therapeutic strategies aiming to correct aberrant CFTR trafficking. PMID:26079370

  13. Sphingosine-1-Phosphate Is a Novel Regulator of Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Activity.

    PubMed

    Malik, Firhan A; Meissner, Anja; Semenkov, Illya; Molinski, Steven; Pasyk, Stan; Ahmadi, Saumel; Bui, Hai H; Bear, Christine E; Lidington, Darcy; Bolz, Steffen-Sebastian

    2015-01-01

    The cystic fibrosis transmembrane conductance regulator (CFTR) attenuates sphingosine-1-phosphate (S1P) signaling in resistance arteries and has emerged as a prominent regulator of myogenic vasoconstriction. This investigation demonstrates that S1P inhibits CFTR activity via adenosine monophosphate-activated kinase (AMPK), establishing a potential feedback link. In Baby Hamster Kidney (BHK) cells expressing wild-type human CFTR, S1P (1μmol/L) attenuates forskolin-stimulated, CFTR-dependent iodide efflux. S1P's inhibitory effect is rapid (within 30 seconds), transient and correlates with CFTR serine residue 737 (S737) phosphorylation. Both S1P receptor antagonism (4μmol/L VPC 23019) and AMPK inhibition (80μmol/L Compound C or AMPK siRNA) attenuate S1P-stimluated (i) AMPK phosphorylation, (ii) CFTR S737 phosphorylation and (iii) CFTR activity inhibition. In BHK cells expressing the ΔF508 CFTR mutant (CFTRΔF508), the most common mutation causing cystic fibrosis, both S1P receptor antagonism and AMPK inhibition enhance CFTR activity, without instigating discernable correction. In summary, we demonstrate that S1P/AMPK signaling transiently attenuates CFTR activity. Since our previous work positions CFTR as a negative S1P signaling regulator, this signaling link may positively reinforce S1P signals. This discovery has clinical ramifications for the treatment of disease states associated with enhanced S1P signaling and/or deficient CFTR activity (e.g. cystic fibrosis, heart failure). S1P receptor/AMPK inhibition could synergistically enhance the efficacy of therapeutic strategies aiming to correct aberrant CFTR trafficking. PMID:26079370

  14. The immune system as a regulator of thyroid hormone activity.

    PubMed

    Klein, John R

    2006-03-01

    It has been known for decades that the neuroendocrine system can both directly and indirectly influence the developmental and functional activity of the immune system. In contrast, far less is known about the extent to which the immune system collaborates in the regulation of endocrine activity. This is particularly true for immune-endocrine interactions of the hypothalamus-pituitary-thyroid axis. Although thyroid-stimulating hormone (TSH) can be produced by many types of extra-pituitary cells--including T cells, B cells, splenic dendritic cells, bone marrow hematopoietic cells, intestinal epithelial cells, and lymphocytes--the functional significance of those TSH pathways remains elusive and historically has been largely ignored from a research perspective. There is now, however, evidence linking cells of the immune system to the regulation of thyroid hormone activity in normal physiological conditions as well as during times of immunological stress. Although the mechanisms behind this are poorly understood, they appear to reflect a process of local intrathyroidal synthesis of TSH mediated by a population of bone marrow cells that traffic to the thyroid. This hitherto undescribed cell population has the potential to microregulate thyroid hormone secretion leading to critical alterations in metabolic activity independent of pituitary TSH output, and it has expansive implications for understanding mechanisms by which the immune system may act to modulate neuroendocrine function during times of host stress. In this article, the basic underpinnings of the hematopoietic-thyroid connection are described, and a model is presented in which the immune system participates in the regulation of thyroid hormone activity during acute infection. PMID:16514168

  15. Regulation of maternal transcript destabilization during egg activation in Drosophila.

    PubMed Central

    Tadros, Wael; Houston, Simon A; Bashirullah, Arash; Cooperstock, Ramona L; Semotok, Jennifer L; Reed, Bruce H; Lipshitz, Howard D

    2003-01-01

    In animals, the transfer of developmental control from maternal RNAs and proteins to zygotically derived products occurs at the midblastula transition. This is accompanied by the destabilization of a subset of maternal transcripts. In Drosophila, maternal transcript destabilization occurs in the absence of fertilization and requires specific cis-acting instability elements. We show here that egg activation is necessary and sufficient to trigger transcript destabilization. We have identified 13 maternal-effect lethal loci that, when mutated, result in failure of maternal transcript degradation. All mutants identified are defective in one or more additional processes associated with egg activation. These include vitelline membrane reorganization, cortical microtubule depolymerization, translation of maternal mRNA, completion of meiosis, and chromosome condensation (the S-to-M transition) after meiosis. The least pleiotropic class of transcript destabilization mutants consists of three genes: pan gu, plutonium, and giant nuclei. These three genes regulate the S-to-M transition at the end of meiosis and are thought to be required for the maintenance of cyclin-dependent kinase (CDK) activity during this cell cycle transition. Consistent with a possible functional connection between this S-to-M transition and transcript destabilization, we show that in vitro-activated eggs, which exhibit aberrant postmeiotic chromosome condensation, fail to initiate transcript degradation. Several genetic tests exclude the possibility that reduction of CDK/cyclin complex activity per se is responsible for the failure to trigger transcript destabilization in these mutants. We propose that the trigger for transcript destabilization occurs coincidently with the S-to-M transition at the end of meiosis and that pan gu, plutonium, and giant nuclei regulate maternal transcript destabilization independent of their role in cell cycle regulation. PMID:12871909

  16. Antiviral Regulation in Porcine Monocytic Cells at Different Activation States

    PubMed Central

    Rowland, Raymond R. R.

    2014-01-01

    ABSTRACT Monocytic cells, including macrophages and dendritic cells, exist in different activation states that are critical to the regulation of antimicrobial immunity. Many pandemic viruses are monocytotropic, including porcine reproductive and respiratory syndrome virus (PRRSV), which directly infects subsets of monocytic cells and interferes with antiviral responses. To study antiviral responses in PRRSV-infected monocytic cells, we characterized inflammatory cytokine responses and genome-wide profiled signature genes to investigate response pathways in uninfected and PRRSV-infected monocytic cells at different activation states. Our findings showed suppressed interferon (IFN) production in macrophages in non-antiviral states and an arrest of lipid metabolic pathways in macrophages at antiviral states. Importantly, porcine monocytic cells at different activation states were susceptible to PRRSV and responded differently to viral infection. Based on Gene Ontology (GO) analysis, two approaches were used to potentiate antiviral activity: (i) pharmaceutical modulation of cellular lipid metabolism and (ii) in situ PRRSV replication-competent expression of interferon alpha (IFN-α). Both approaches significantly suppressed exogenous viral infection in monocytic cells. In particular, the engineered IFN-expressing PRRSV strain eliminated exogenous virus infection and sustained cell viability at 4 days postinfection in macrophages. These findings suggest an intricate interaction of viral infection with the activation status of porcine monocytic cells. An understanding and integration of antiviral infection with activation status of monocytic cells may provide a means of potentiating antiviral immunity. IMPORTANCE Activation statuses of monocytic cells, including monocytes, macrophages (Mϕs), and dendritic cells (DCs), are critically important for antiviral immunity. Unfortunately, the activation status of porcine monocytic cells or how cell activation status

  17. The molecular regulation of Janus kinase (JAK) activation.

    PubMed

    Babon, Jeffrey J; Lucet, Isabelle S; Murphy, James M; Nicola, Nicos A; Varghese, Leila N

    2014-08-15

    The JAK (Janus kinase) family members serve essential roles as the intracellular signalling effectors of cytokine receptors. This family, comprising JAK1, JAK2, JAK3 and TYK2 (tyrosine kinase 2), was first described more than 20 years ago, but the complexities underlying their activation, regulation and pleiotropic signalling functions are still being explored. Here, we review the current knowledge of their physiological functions and the causative role of activating and inactivating JAK mutations in human diseases, including haemopoietic malignancies, immunodeficiency and inflammatory diseases. At the molecular level, recent studies have greatly advanced our knowledge of the structures and organization of the component FERM (4.1/ezrin/radixin/moesin)-SH2 (Src homology 2), pseudokinase and kinase domains within the JAKs, the mechanism of JAK activation and, in particular, the role of the pseudokinase domain as a suppressor of the adjacent tyrosine kinase domain's catalytic activity. We also review recent advances in our understanding of the mechanisms of negative regulation exerted by the SH2 domain-containing proteins, SOCS (suppressors of cytokine signalling) proteins and LNK. These recent studies highlight the diversity of regulatory mechanisms utilized by the JAK family to maintain signalling fidelity, and suggest alternative therapeutic strategies to complement existing ATP-competitive kinase inhibitors. PMID:25057888

  18. Oxidative Regulation of Large Conductance Calcium-Activated Potassium Channels

    PubMed Central

    Tang, Xiang D.; Daggett, Heather; Hanner, Markus; Garcia, Maria L.; McManus, Owen B.; Brot, Nathan; Weissbach, Herbert; Heinemann, Stefan H.; Hoshi, Toshinori

    2001-01-01

    Reactive oxygen/nitrogen species are readily generated in vivo, playing roles in many physiological and pathological conditions, such as Alzheimer's disease and Parkinson's disease, by oxidatively modifying various proteins. Previous studies indicate that large conductance Ca2+-activated K+ channels (BKCa or Slo) are subject to redox regulation. However, conflicting results exist whether oxidation increases or decreases the channel activity. We used chloramine-T, which preferentially oxidizes methionine, to examine the functional consequences of methionine oxidation in the cloned human Slo (hSlo) channel expressed in mammalian cells. In the virtual absence of Ca2+, the oxidant shifted the steady-state macroscopic conductance to a more negative direction and slowed deactivation. The results obtained suggest that oxidation enhances specific voltage-dependent opening transitions and slows the rate-limiting closing transition. Enhancement of the hSlo activity was partially reversed by the enzyme peptide methionine sulfoxide reductase, suggesting that the upregulation is mediated by methionine oxidation. In contrast, hydrogen peroxide and cysteine-specific reagents, DTNB, MTSEA, and PCMB, decreased the channel activity. Chloramine-T was much less effective when concurrently applied with the K+ channel blocker TEA, which is consistent with the possibility that the target methionine lies within the channel pore. Regulation of the Slo channel by methionine oxidation may represent an important link between cellular electrical excitability and metabolism. PMID:11222629

  19. The molecular regulation of Janus kinase (JAK) activation

    PubMed Central

    2014-01-01

    The Janus Kinase (JAK) family members serve essential roles as the intracellular signalling effectors of cytokine receptors. This family, comprising JAK1, JAK2, JAK3 and TYK2, was first described more than 20 years ago, but the complexities underlying their activation, regulation and pleiotropic signalling functions are still being explored. Here, we review the current knowledge of their physiological functions and the causative role of activating and inactivating JAK mutations in human diseases, including haematopoietic malignancies, immunodeficiency and inflammatory diseases. At the molecular level, recent studies have greatly advanced our knowledge of the structures and organisation of the component FERM-SH2, pseudokinase and kinase domains within the JAKs, the mechanism of JAK activation and, in particular, the role of the pseudokinase domain as a suppressor of the adjacent tyrosine kinase domain's catalytic activity. We also review recent advances in our understanding of the mechanisms of negative regulation exerted by the SH2 domain containing proteins, SOCS (Suppressors of Cytokine Signalling) proteins and Lnk. These recent advances highlight the diversity of regulatory mechanisms utilised by the JAK family to maintain signalling fidelity, and suggest alternative therapeutic strategies to complement existing ATP-competitive kinase inhibitors. PMID:25057888

  20. Synapsins are late activity-induced genes regulated by birdsong

    PubMed Central

    Velho, Tarciso A. F.; Mello, Claudio V.

    2008-01-01

    The consolidation of long-lasting sensory memories requires the activation of gene expression programs in the brain. In spite of considerable knowledge about the early components of this response, little is known about late components (i.e. genes regulated 2-6 hr after stimulation) and the relationship between early and late genes. Birdsong represents one of the best natural behaviors to study sensory-induced gene expression in awake, freely behaving animals. Here we show that the expression of several isoforms of synapsins, a group of phosphoproteins thought to regulate the dynamics of synaptic vesicle storage and release, is induced by auditory stimulation with birdsong in the caudomedial nidopallium (NCM) of the zebra finch (Taeniopygia guttata) brain. This induction occurs mainly in excitatory (non-GABAergic) neurons and is modulated (suppressed) by early song-inducible proteins. We also show that ZENK, an early song-inducible transcription factor, interacts with the syn3 promoter in vivo, consistent with a direct regulatory effect and an emerging novel view of ZENK action. These results demonstrate that synapsins are a late component of the genomic response to neuronal activation and that their expression depends on a complex set of regulatory interactions between early and late regulated genes. PMID:19005052

  1. 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.

  2. 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…

  3. 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...

  4. Regulation of calf renal 25-hydroxyvitamin D-hydroxylase activities by calcium-regulating hormones.

    PubMed

    Engstrom, G W; Goff, J P; Horst, R L; Reinhardt, T A

    1987-11-01

    Parathyroid hormone and 1,25-dihydroxyvitamin D3 had opposite effects on calf renal 25-hydroxyvitamin D3 24-, 23-, and 1 alpha-hydroxylase activities. Parathyroid hormone administration increased renal 25-hydroxyvitamin D3-1 alpha-hydroxylase activity 7-fold while 25-hydroxyvitamin D3-23- and 24-hydroxylase activities were essentially the same as controls. Administration of 1,25-dihydroxyvitamin D3 increased 25-hydroxyvitamin D3-23-hydroxylase and 24-hydroxylase activities 4-fold and decreased 25-hydroxyvitamin D3-1 alpha-hydroxylase activity to undetectable concentrations. Vitamin D deficiency increased 25-hydroxyvitamin D3-1 alpha -hydroxylase activity 13-fold, and 25-hydroxyvitamin D3-23-hydroxylase and 24-hydroxylase activities were undetectable. These results confirm previous reports with regard to control of renal 25-hydroxyvitamin D3-24-hydroxylase and 1 alpha -hydroxylase in other species and represent new findings relative to the control of 25-hydroxyvitamin D3-23-hydroxylase. Plasma P was lower and 1,25-dihydroxyvitamin D3 higher in calves treated with parathyroid hormone, and Ca and 1,25-dihydroxyvitamin D3 were lower in the vitamin D-deficient calves. 1,25-Dihydroxyvitamin D3-treated calves had higher plasma P and lower Mg than controls. Further studies using this calf model should lead to better understanding of Ca-regulating hormones control of vitamin D metabolism. PMID:3693631

  5. 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

  6. [Polymethoxylated flavonoids activate cystic fibrosis transmembrane conductance regulator chloride channel].

    PubMed

    Cao, Huan-Huan; Fang, Fang; Yu, Bo; Luan, Jian; Jiang, Yu; Yang, Hong

    2015-04-25

    Cystic fibrosis transmembrane conductance regulator (CFTR), a cAMP-dependent chloride channel, plays key roles in fluid secretion in serous epithelial cells. Previously, we identified two polymethoxylated flavonoids, 3',4',5,5',6,7-hexamethoxyflavone (HMF) and 5-hydroxy-6,7,3',4'-tetramethoxyflavone (HTF) which could potentiate CFTR chloride channel activities. The present study was aimed to investigate the potentiation effects of HMF and HTF on CFTR Cl(-) channel activities by using a cell-based fluorescence assay and the short circuit Ussing chamber assay. The results of cell-based fluorescence assay showed that both HMF and HTF could dose-dependently potentiate CFTR Cl(-) channel activities in rapid and reversible ways, and the activations could be reversed by the CFTR blocker CFTRinh-172. Notably, HMF showed the highest affinity (EC50 = 2 μmol/L) to CFTR protein among the flavonoid CFTR activators identified so far. The activation of CFTR by HMF or HTF was forskolin (FSK) dependent. Both compounds showed additive effect with FSK and 3-Isobutyl-1-methylx (IBMX) in the activation of CFTR, while had no additive effect with genistein (GEN). In ex vivo studies, HMF and HTF could stimulate transepithelial Cl(-) secretion in rat colonic mucosa and enhance fluid secretion in mouse trachea submucosal glands. These results suggest that HMF and HTF may potentiate CFTR Cl(-) channel activities through both elevation of cAMP level and binding to CFTR protein pathways. The results provide new clues in elucidating structure and activity relationship of flavonoid CFTR activators. HMF might be developed as a new drug in the therapy of CFTR-related diseases such as bronchiectasis and habitual constipation. PMID:25896054

  7. Pupil Nondiscrimination Guidelines. Implementing S.118.13 of the Wisconsin Statutes and PI 9 of the Wisconsin Administrative Code. Bullein No. 8327.

    ERIC Educational Resources Information Center

    Wisconsin State Dept. of Public Instruction, Madison.

    The new S. 118.13, Wisconsin Statutes, bans pupil discrimination in any curricular, extracurricular, pupil services, recreational, or other program or activity in the State of Wisconsin on the basis of sex; race; national origin; ancestry; creed; pregnancy; marital or parental status; sexual orientation; or physical, mental, emotional, or learning…

  8. 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.

  9. Lysyl oxidase activity regulates oncogenic stress response and tumorigenesis.

    PubMed

    Wiel, C; Augert, A; Vincent, D F; Gitenay, D; Vindrieux, D; Le Calvé, B; Arfi, V; Lallet-Daher, H; Reynaud, C; Treilleux, I; Bartholin, L; Lelievre, E; Bernard, D

    2013-01-01

    Cellular senescence, a stable proliferation arrest, is induced in response to various stresses. Oncogenic stress-induced senescence (OIS) results in blocked proliferation and constitutes a fail-safe program counteracting tumorigenesis. The events that enable a tumor in a benign senescent state to escape from OIS and become malignant are largely unknown. We show that lysyl oxidase activity contributes to the decision to maintain senescence. Indeed, in human epithelial cell the constitutive expression of the LOX or LOXL2 protein favored OIS escape, whereas inhibition of lysyl oxidase activity was found to stabilize OIS. The relevance of these in vitro observations is supported by in vivo findings: in a transgenic mouse model of aggressive pancreatic ductal adenocarcinoma (PDAC), increasing lysyl oxidase activity accelerates senescence escape, whereas inhibition of lysyl oxidase activity was found to stabilize senescence, delay tumorigenesis, and increase survival. Mechanistically, we show that lysyl oxidase activity favors the escape of senescence by regulating the focal-adhesion kinase. Altogether, our results demonstrate that lysyl oxidase activity participates in primary tumor growth by directly impacting the senescence stability. PMID:24113189

  10. IKKα negatively regulates ASC-dependent inflammasome activation.

    PubMed

    Martin, Bradley N; Wang, Chenhui; Willette-Brown, Jami; Herjan, Tomasz; Gulen, Muhammet F; Zhou, Hao; Bulek, Katarzyna; Franchi, Luigi; Sato, Takashi; Alnemri, Emad S; Narla, Goutham; Zhong, Xiao-Ping; Thomas, James; Klinman, Dennis; Fitzgerald, Katherine A; Karin, Michael; Nuñez, Gabriel; Dubyak, George; Hu, Yinling; Li, Xiaoxia

    2014-01-01

    The inflammasomes are multiprotein complexes that activate caspase-1 in response to infections and stress, resulting in the secretion of pro-inflammatory cytokines. Here we report that IκB kinase α (IKKα) is a critical negative regulator of apoptosis-associated specklike protein containing a C-terminal caspase-activation-andrecruitment (CARD) domain (ASC)-dependent inflammasomes. IKKα controls the inflammasome at the level of the adaptor ASC, which interacts with IKKα in the nucleus of resting macrophages in an IKKα kinase-dependent manner. Loss of IKKα kinase activity results in inflammasome hyperactivation. Mechanistically, the downstream nuclear effector IKK-related kinase (IKKi) facilitates translocation of ASC from the nucleus to the perinuclear area during inflammasome activation. ASC remains under the control of IKKα in the perinuclear area following translocation of the ASC/IKKα complex. Signal 2 of NLRP3 activation leads to inhibition of IKKα kinase activity through the recruitment of PP2A, allowing ASC to participate in NLRP3 inflammasome assembly. Taken together, these findings reveal a IKKi-IKKα-ASC axis that serves as a common regulatory mechanism for ASC-dependent inflammasomes. PMID:25266676

  11. 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. Stem Cells 2016;34:948-959. PMID:26727165

  12. B4GALT6 regulates astrocyte activation during CNS inflammation

    PubMed Central

    Mayo, Lior; Trauger, Sunia A.; Blain, Manon; Nadeau, Meghan; Patel, Bonny; Alvarez, Jorge I.; Mascanfroni, Ivan D.; Yeste, Ada; Kivisäkk, Pia; Kallas, Keith; Ellezam, Benjamin; Bakshi, Rohit; Prat, Alexandre; Antel, Jack P.; Weiner, Howard L.; Quintana, Francisco J.

    2014-01-01

    Astrocytes play complex roles in the response to trauma, infection or inflammation in the central nervous system (CNS). Thus, it is important to characterize the mechanisms regulating astrocyte function, as well as potential targets for the therapeutic modulation of astrocyte activity. Here we report that lactosylceramide (LacCer) levels are up-regulated in the CNS during chronic experimental autoimmune encephalomyelitis (EAE), an experimental model of multiple sclerosis (MS). We found that LacCer synthesized by β-1,4-galactosyltransferase 6 (B4GALT6) in astrocytes acts in an autocrine manner to trigger transcriptional programs that promote the recruitment and activation of CNS-infiltrating monocytes and microglia, and neurodegeneration. We also detected increased B4GALT6 expression and LacCer levels in CNS MS lesions. Finally, the inhibition of LacCer synthesis suppressed local CNS innate immunity and neurodegeneration in EAE, and interfered with the activation of human astrocytes in vitro. Thus, B4GALT6 is a potential therapeutic target for MS and other neuroinflammatory disorders. PMID:25216636

  13. 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

  14. 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

  15. Diversity in Overall Activity Regulation of Ribonucleotide Reductase*

    PubMed Central

    Jonna, Venkateswara Rao; Crona, Mikael; Rofougaran, Reza; Lundin, Daniel; Johansson, Samuel; Brännström, Kristoffer; Sjöberg, Britt-Marie; Hofer, Anders

    2015-01-01

    Ribonucleotide reductase (RNR) catalyzes the reduction of ribonucleotides to the corresponding deoxyribonucleotides, which are used as building blocks for DNA replication and repair. This process is tightly regulated via two allosteric sites, the specificity site (s-site) and the overall activity site (a-site). The a-site resides in an N-terminal ATP cone domain that binds dATP or ATP and functions as an on/off switch, whereas the composite s-site binds ATP, dATP, dTTP, or dGTP and determines which substrate to reduce. There are three classes of RNRs, and class I RNRs consist of different combinations of α and β subunits. In eukaryotic and Escherichia coli class I RNRs, dATP inhibits enzyme activity through the formation of inactive α6 and α4β4 complexes, respectively. Here we show that the Pseudomonas aeruginosa class I RNR has a duplicated ATP cone domain and represents a third mechanism of overall activity regulation. Each α polypeptide binds three dATP molecules, and the N-terminal ATP cone is critical for binding two of the dATPs because a truncated protein lacking this cone could only bind dATP to its s-site. ATP activates the enzyme solely by preventing dATP from binding. The dATP-induced inactive form is an α4 complex, which can interact with β2 to form a non-productive α4β2 complex. Other allosteric effectors induce a mixture of α2 and α4 forms, with the former being able to interact with β2 to form active α2β2 complexes. The unique features of the P. aeruginosa RNR are interesting both from evolutionary and drug discovery perspectives. PMID:25971975

  16. 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

  17. The passage of Florida's Statute on Assisted Reproductive Technology.

    PubMed

    Maun, A R; Williams, R S; Graber, B; Myers, W G

    1994-11-01

    Until 1993, there were no statutes in the United States covering gestational surrogacy contracts, disposition of stored embryos and gametes, parentage of children born from donated gametes and embryos, and the inheritance rights of cryopreserved embryos of deceased donors. In March 1993, the Florida Assisted Reproductive Technology Act was passed to address some of these issues and to minimize the expense and emotional cost of related courtroom proceedings. Authors of the bill believed that motherhood of a newborn in the eyes of the law should be determined by two factors: genetic inheritance and the original intent of the woman to become the parent of record. The bill included the assumption that, in the cases of children born of gestational surrogacy, the commissioning genetic parents would be the "natural parents" of the child. Some of the reasons for legislative success of the statute include: 1) clear need for statutory guidance in cases involving reproductive technology, 2) relevance of the issue to cost containment (ie, judicial costs) in an era of health care reform, 3) careful use of scientific terminology and the support of the medical community, 4) involvement of a skilled legislative team, 5) participation of physician specialists in the development of the bill (ie, practicing gynecologists in assisted reproductive technology programs), 6) participation of the State of Florida legislative staff, and 7) consultation with appropriate lobbying groups (eg, Florida Catholic Conference). The successful legislative process that was followed to achieve passage of this bill can serve as an example for other states to emulate. PMID:7936533

  18. 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

  19. Regulation of contractile vacuole formation and activity in Dictyostelium.

    PubMed

    Du, Fei; Edwards, Kimberly; Shen, Zhouxin; Sun, Binggang; De Lozanne, Arturo; Briggs, Steven; Firtel, Richard A

    2008-08-01

    The contractile vacuole (CV) system is the osmoregulatory organelle required for survival for many free-living cells under hypotonic conditions. We identified a new CV regulator, Disgorgin, a TBC-domain-containing protein, which translocates to the CV membrane at the late stage of CV charging and regulates CV-plasma membrane fusion and discharging. disgorgin(-) cells produce large CVs due to impaired CV-plasma membrane fusion. Disgorgin is a specific GAP for Rab8A-GTP, which also localizes to the CV and whose hydrolysis is required for discharging. We demonstrate that Drainin, a previously identified TBC-domain-containing protein, lies upstream from Disgorgin in this pathway. Unlike Disgorgin, Drainin lacks GAP activity but functions as a Rab11A effector. The BEACH family proteins LvsA and LvsD were identified in a suppressor/enhancer screen of the disgorgin(-) large CV phenotype and demonstrated to have distinct functions in regulating CV formation. Our studies help define the pathways controlling CV function. PMID:18636095

  20. Activity and regulation of the centrosome-associated proteasome.

    PubMed

    Fabunmi, R P; Wigley, W C; Thomas, P J; DeMartino, G N

    2000-01-01

    Regulated proteolysis is important for maintaining appropriate cellular levels of many proteins. The bulk of intracellular protein degradation is catalyzed by the proteasome. Recently, the centrosome was identified as a novel site for concentration of the proteasome and associated regulatory proteins (Wigley, W. C., Fabunmi, R. P., Lee, M. G., Marino, C. R., Muallem, S., DeMartino, G. N., and Thomas, P. J. (1999) J. Cell Biol. 145, 481-490). Here we provide evidence that centrosomes contain the active 26 S proteasome that degrades ubiquitinated-protein and proteasome-specific peptide substrates. Moreover, the centrosomes contain an ubiquitin isopeptidase activity. The proteolytic activity is ATP-dependent and is inhibited by proteasome inhibitors. Notably, treatment of cells with inhibitors of proteasome activity promotes redistribution of the proteasome and associated regulatory proteins to the centrosome independent of an intact microtubule system. These data provide biochemical evidence for active proteasomal complexes at the centrosome, highlighting a novel function for this organizing structure. PMID:10617632

  1. PKC phosphorylates HEXIM1 and regulates P-TEFb activity

    PubMed Central

    Fujinaga, Koh; Barboric, Matjaz; Li, Qintong; Luo, Zeping; Price, David H.; Peterlin, B. Matija

    2012-01-01

    The positive transcription elongation factor b (P-TEFb) regulates RNA polymerase II elongation. In cells, P-TEFb partitions between small active and larger inactive states. In the latter, HEXIM1 binds to 7SK snRNA and recruits as well as inactivates P-TEFb in the 7SK snRNP. Several stimuli can affect this P-TEFb equilibrium. In this study, we demonstrate that protein kinase C (PKC) phosphorylates the serine at position158 (S158) in HEXIM1. This phosphorylated HEXIM1 protein neither binds to 7SK snRNA nor inhibits P-TEFb. Phorbol esters or the engagement of the T cell antigen receptor, which activate PKC and the expression of the constitutively active (CA) PKCθ protein, which is found in T cells, inhibit the formation of the 7SK snRNP. All these stimuli increase P-TEFb-dependent transcription. In contrast, the kinase-negative PKCθ and the mutant HEXIM1 (S158A) proteins block effects of these PKC-activating stimuli. These results indicate that the phosphorylation of HEXIM1 by PKC represents a major regulatory step of P-TEFb activity in cells. PMID:22821562

  2. IKKα negatively regulates ASC-dependent inflammasome activation

    PubMed Central

    Martin, Bradley N.; Wang, Chenhui; Willette-Brown, Jami; Herjan, Tomasz; Gulen, Muhammet F.; Zhou, Hao; Bulek, Katarzyna; Franchi, Luigi; Sato, Takashi; Narla, Goutham; Zhong, Xiao-Ping; Thomas, James; Klinman, Dennis; Fitzgerald, Katherine A.; Karin, Michael; Nuñez, Gabriel; Dubyak, George; Hu, Yinling; Li, Xiaoxia

    2014-01-01

    The inflammasomes are multiprotein complexes that activate caspase-1 in response to infections and stress, resulting in the secretion of pro-inflammatory cytokines. Here we report that IKKα is a critical negative regulator of ASC-dependent inflammasomes. IKKα controls the inflammasome at the level of the adaptor ASC, which interacts with IKKα in the nucleus of resting macrophages in an IKKα kinase-dependent manner. Loss of IKKα kinase activity results in inflammasome hyperactivation. Mechanistically, the downstream nuclear effector IKKi facilitates translocation of ASC from the nucleus to the perinuclear area during inflammasome activation. ASC remains under the control of IKKα in the perinuclear area following translocation of the ASC/IKKα complex. Signal 2 of NLRP3 activation leads to inhibition of IKKα kinase activity through the recruitment of PP2A, allowing ASC to participate in NLRP3 inflammasome assembly. Taken together, these findings reveal a IKKi-IKKα-ASC axis that serves as a common regulatory mechanism for ASC-dependent inflammasomes. PMID:25266676

  3. Systematic identification of signal-activated stochastic gene regulation.

    PubMed

    Neuert, Gregor; Munsky, Brian; Tan, Rui Zhen; Teytelman, Leonid; Khammash, Mustafa; van Oudenaarden, Alexander

    2013-02-01

    Although much has been done to elucidate the biochemistry of signal transduction and gene regulatory pathways, it remains difficult to understand or predict quantitative responses. We integrate single-cell experiments with stochastic analyses, to identify predictive models of transcriptional dynamics for the osmotic stress response pathway in Saccharomyces cerevisiae. We generate models with varying complexity and use parameter estimation and cross-validation analyses to select the most predictive model. This model yields insight into several dynamical features, including multistep regulation and switchlike activation for several osmosensitive genes. Furthermore, the model correctly predicts the transcriptional dynamics of cells in response to different environmental and genetic perturbations. Because our approach is general, it should facilitate a predictive understanding for signal-activated transcription of other genes in other pathways or organisms. PMID:23372015

  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. Phosphatidylinositol-3-kinase regulates mast cell ion channel activity.

    PubMed

    Lam, Rebecca S; Shumilina, Ekaterina; Matzner, Nicole; Zemtsova, Irina M; Sobiesiak, Malgorzata; Lang, Camelia; Felder, Edward; Dietl, Paul; Huber, Stephan M; Lang, Florian

    2008-01-01

    Stimulation of the mast cell IgE-receptor (FcepsilonRI) by antigen leads to stimulation of Ca(2+) entry with subsequent mast cell degranulation and release of inflammatory mediators. Ca(2+) further activates Ca(2+)-activated K(+) channels, which in turn provide the electrical driving force for Ca(2+) entry. Since phosphatidylinositol (PI)-3-kinase has previously been shown to be required for mast cell activation and degranulation, we explored, whether mast cell Ca(2+) and Ca(2+)-activated K(+) channels may be sensitive to PI3-kinase activity. Whole-cell patch clamp experiments and Fura-2 fluorescence measurements for determination of cytosolic Ca(2+) concentration were performed in mouse bone marrow-derived mast cells either treated or untreated with the PI3-kinase inhibitors LY-294002 (10 muM) and wortmannin (100 nM). Antigen-stimulated Ca(2+) entry but not Ca(2+) release from the intracellular stores was dramatically reduced upon PI3-kinase inhibition. Ca(2+) entry was further inhibited by TRPV blocker ruthenium red (10 muM). Ca(2+) entry following readdition after Ca(+)-store depletion with thapsigargin was again decreased by LY-294002, pointing to inhibition of store-operated channels (SOCs). Moreover, inhibition of PI3-kinase abrogated IgE-stimulated, but not ionomycin-induced stimulation of Ca(2+)-activated K(+) channels. These observations disclose PI3-kinase-dependent regulation of Ca(2+) entry and Ca(2+)-activated K(+)-channels, which in turn participate in triggering mast cell degranulation. PMID:18769043

  6. Osteoblast differentiation and migration are regulated by dynamin GTPase activity.

    PubMed

    Eleniste, Pierre P; Huang, Su; Wayakanon, Kornchanok; Largura, Heather W; Bruzzaniti, Angela

    2014-01-01

    Bone formation is controlled by osteoblasts, but the signaling proteins that control osteoblast differentiation and function are still unclear. We examined if the dynamin GTPase, which is associated with actin remodeling and migration in other cells, plays a role in osteoblast differentiation and migration. Dynamin mRNA was expressed in primary osteoblasts throughout differentiation (0-21 days). However, alkaline phosphatase (ALP) activity, a marker of osteoblast differentiation, was decreased in osteoblasts over-expressing dynamin. Conversely, ALP activity was increased following shRNA-mediated knockdown of dynamin and in osteoblasts treated with the dynamin inhibitor, dynasore. Dynasore also reduced c-fos and osterix expression, markers of early osteoblasts, suggesting a role for dynamin in pre-osteoblast to osteoblast differentiation. Since dynamin GTPase activity is regulated by tyrosine phosphorylation, we examined the mechanism of dynamin dephosphorylation in osteoblasts. Dynamin formed a protein complex with the tyrosine phosphatase PTP-PEST and inhibition of phosphatase activity increased the level of phosphorylated dynamin. Further, PTP-PEST blocked the Src-mediated increase in the phosphorylation and GTPase activity of wild-type dynamin but not the phosphorylation mutant dynY231F/Y597F. Although ALP activity was increased in osteoblasts expressing GTPase-defective dynK44A, and to a lesser extent dynY231F/Y597F, osteoblast migration was significantly inhibited by dynK44A and dynY231F/Y597F. These studies demonstrate a novel role for dynamin GTPase activity and phosphorylation in osteoblast differentiation and migration, which may be important for bone formation. PMID:24387844

  7. Osteoblast differentiation and migration are regulated by Dynamin GTPase activity

    PubMed Central

    Eleniste, Pierre P.; Huang, Su; Wayakanon, Kornchanok; Largura, Heather W.; Bruzzaniti, Angela

    2013-01-01

    Bone formation is controlled by osteoblasts but the signaling proteins that control osteoblast differentiation and function are still unclear. We examined if the dynamin GTPase, which is associated with actin remodeling and migration in other cells, plays a role in osteoblast differentiation and migration. Dynamin mRNA was expressed in primary osteoblasts throughout differentiation (0–21 days). However, alkaline phosphatase (ALP) activity, a marker of osteoblast differentiation, was decreased in osteoblasts over-expressing dynamin. Conversely, ALP activity was increased following shRNA-mediated knockdown of dynamin and in osteoblasts treated with the dynamin inhibitor, dynasore. Dynasore also reduced c-fos and osterix expression, markers of early osteoblasts, suggesting a role for dynamin in pre-osteoblast to osteoblast differentiation. Since dynamin GTPase activity is regulated by tyrosine phosphorylation, we examined the mechanism of dynamin dephosphorylation in osteoblasts. Dynamin formed a protein complex with the tyrosine phosphatase PTP-PEST and inhibition of phosphatase activity increased the level of phosphorylated dynamin. Further, PTP-PEST blocked the Src-mediated increase in the phosphorylation and GTPase activity of wild-type dynamin but not the phosphorylation mutant dynY231F/Y597F. Although ALP activity was increased in osteoblasts expressing GTPase-defective dynK44A, and to a lesser extent dynY231F/Y597F, osteoblast migration was significantly inhibited by dynK44A and dynY231F/Y597F. These studies demonstrate a novel role for dynamin GTPase activity and phosphorylation in osteoblast differentiation and migration, which may be important for bone formation. PMID:24387844

  8. 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

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

    PubMed

    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

    2013-06-11

    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

  10. 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

  11. 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.

  12. Regulation of α-Amylase Activity in Bean Stem Tissues

    PubMed Central

    Davis, Bill D.

    1984-01-01

    α-Amylase activity was assayed in 1-centimeter sections taken from bean (Phaseolus vulgaris var. Kentucky Wonder) hypocotyls and epicotyls at measured distances from the cotyledons. The activity was low throughout the hypocotyl for the first 7 days. An increase was first observed with etiolated hypocotyls in the basal region, becoming higher in the more central regions by 14 to 17 days. By 21 days the activity was highest in the upper region, but had decreased in the lower regions. A comparable pattern was observed for the epicotyl from etiolated seedlings, the activity increasing first in the region closest to the cotyledons. These increases were associated with loss of cells from the pith in the hypocotyl and epicotyl of both dark- and light-grown plants. Since the changes were observed in tissues virtually devoid of starch, it is hypothesized that the control mechanism is related to the cellular disassembly associated with the mobilization of materials released during senescence rather than to a regulation by the enzyme's substrate or products. PMID:16663519

  13. NEURONAL ACTIVITY REGULATES GLUTAMATE TRANSPORTER DYNAMICS IN DEVELOPING ASTROCYTES

    PubMed Central

    Benediktsson, A.M.; Marrs, G.S.; Tu, J.C.; Worley, P.F.; Rothstein, J.D.; Bergles, D.E.; Dailey, M.E.

    2011-01-01

    Glutamate transporters maintain a low ambient level of glutamate in the CNS and shape the activation of glutamate receptors at synapses. Nevertheless, the mechanisms that regulate the trafficking and localization of transporters near sites of glutamate release are poorly understood. Here we examined the subcellular distribution and dynamic remodeling of the predominant glutamate transporter GLT-1 (EAAT2) in developing hippocampal astrocytes. Immunolabeling revealed that endogenous GLT-1 is concentrated into discrete clusters along branches of developing astrocytes that were apposed preferentially to synapsin-1 positive synapses. GFP-GLT-1 fusion proteins expressed in astrocytes also formed distinct clusters that lined the edges of astrocyte processes, as well as the tips of filopodia and spine-like structures. Time-lapse 3D confocal imaging in tissue slices revealed that GFP-GLT-1 clusters were dynamically remodeled on a timescale of minutes. Some transporter clusters moved within developing astrocyte branches as filopodia extended and retracted, while others maintained stable positions at the tips of spine-like structures. Blockade of neuronal activity with tetrodotoxin reduced both the density and perisynaptic localization of GLT-1 clusters. Conversely, enhancement of neuronal activity increased the size of GLT-1 clusters and their proximity to synapses. Together, these findings indicate that neuronal activity influences both the organization of glutamate transporters in developing astrocyte membranes and their position relative to synapses. PMID:22052455

  14. Activation Tagging Identifies a Conserved MYB Regulator of Phenylpropanoid Biosynthesis

    PubMed Central

    Borevitz, Justin O.; Xia, Yiji; Blount, Jack; Dixon, Richard A.; Lamb, Chris

    2000-01-01

    Plants produce a wide array of natural products, many of which are likely to be useful bioactive structures. Unfortunately, these complex natural products usually occur at very low abundance and with restricted tissue distribution, thereby hindering their evaluation. Here, we report a novel approach for enhancing the accumulation of natural products based on activation tagging by Agrobacterium-mediated transformation with a T-DNA that carries cauliflower mosaic virus 35S enhancer sequences at its right border. Among ∼5000 Arabidopsis activation-tagged lines, we found a plant that exhibited intense purple pigmentation in many vegetative organs throughout development. This upregulation of pigmentation reflected a dominant mutation that resulted in massive activation of phenylpropanoid biosynthetic genes and enhanced accumulation of lignin, hydroxycinnamic acid esters, and flavonoids, including various anthocyanins that were responsible for the purple color. These phenotypes, caused by insertion of the viral enhancer sequences adjacent to an MYB transcription factor gene, indicate that activation tagging can overcome the stringent genetic controls regulating the accumulation of specific natural products during plant development. Our findings suggest a functional genomics approach to the biotechnological evaluation of phytochemical biodiversity through the generation of massively enriched tissue sources for drug screening and for isolating underlying regulatory and biosynthetic genes. PMID:11148285

  15. 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

  16. 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

  17. 22 CFR 1421.1 - Foreign Service Labor-Management Relations Statute.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 22 Foreign Relations 2 2011-04-01 2009-04-01 true Foreign Service Labor-Management Relations... RELATIONS AUTHORITY MEANING OF TERMS AS USED IN THIS SUBCHAPTER § 1421.1 Foreign Service Labor-Management Relations Statute. The term Foreign Service Labor-Management Relations Statute means chapter 10 of title...

  18. 22 CFR 1421.1 - Foreign Service Labor-Management Relations Statute.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 22 Foreign Relations 2 2010-04-01 2010-04-01 true Foreign Service Labor-Management Relations... RELATIONS AUTHORITY MEANING OF TERMS AS USED IN THIS SUBCHAPTER § 1421.1 Foreign Service Labor-Management Relations Statute. The term Foreign Service Labor-Management Relations Statute means chapter 10 of title...

  19. 32 CFR 22.310 - Statutes concerning certain research, development, and facilities construction grants.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 32 National Defense 1 2010-07-01 2010-07-01 false Statutes concerning certain research... AND ADMINISTRATION Competition § 22.310 Statutes concerning certain research, development, and... grant. A grant that provides for continuation of research and development performed by a recipient...

  20. 32 CFR 22.310 - Statutes concerning certain research, development, and facilities construction grants.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 32 National Defense 1 2011-07-01 2011-07-01 false Statutes concerning certain research... AND ADMINISTRATION Competition § 22.310 Statutes concerning certain research, development, and... grant. A grant that provides for continuation of research and development performed by a recipient...

  1. 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,…

  2. 15 CFR Appendix A to Part 0 - Statutes Governing Conduct of Federal Employees

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 15 Commerce and Foreign Trade 1 2014-01-01 2014-01-01 false Statutes Governing Conduct of Federal Employees A Appendix A to Part 0 Commerce and Foreign Trade Office of the Secretary of Commerce EMPLOYEE RESPONSIBILITIES AND CONDUCT Pt. 0, App. A Appendix A to Part 0—Statutes Governing Conduct of Federal Employees There are numerous...

  3. 15 CFR Appendix A to Part 0 - Statutes Governing Conduct of Federal Employees

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 15 Commerce and Foreign Trade 1 2012-01-01 2012-01-01 false Statutes Governing Conduct of Federal Employees A Appendix A to Part 0 Commerce and Foreign Trade Office of the Secretary of Commerce EMPLOYEE RESPONSIBILITIES AND CONDUCT Pt. 0, App. A Appendix A to Part 0—Statutes Governing Conduct of Federal Employees There are numerous...

  4. 15 CFR Appendix A to Part 0 - Statutes Governing Conduct of Federal Employees

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 15 Commerce and Foreign Trade 1 2013-01-01 2013-01-01 false Statutes Governing Conduct of Federal Employees A Appendix A to Part 0 Commerce and Foreign Trade Office of the Secretary of Commerce EMPLOYEE RESPONSIBILITIES AND CONDUCT Pt. 0, App. A Appendix A to Part 0—Statutes Governing Conduct of Federal Employees There are numerous...

  5. 15 CFR Appendix A to Part 0 - Statutes Governing Conduct of Federal Employees

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 15 Commerce and Foreign Trade 1 2011-01-01 2011-01-01 false Statutes Governing Conduct of Federal Employees A Appendix A to Part 0 Commerce and Foreign Trade Office of the Secretary of Commerce EMPLOYEE RESPONSIBILITIES AND CONDUCT Pt. 0, App. A Appendix A to Part 0—Statutes Governing Conduct of Federal Employees There are numerous...

  6. Ligand-dependent Enhancer Activation Regulated by Topoisomerase-I Activity

    PubMed Central

    Puc, Janusz; Kozbial, Piotr; Li, Wenbo; Tan, Yuliang; Liu, Zhijie; Suter, Tom; Ohgi, Kenneth A.; Zhang, Jie; Aggarwal, Aneel K.; Rosenfeld, Michael G.

    2014-01-01

    SUMMARY The discovery that enhancers are regulated transcription units, encoding eRNAs, has raised new questions about the mechanisms of their activation. Here, we report an unexpected molecular mechanism that underlies ligand-dependent enhancer activation, based on DNA nicking to relieve torsional stress from eRNA synthesis. Using dihydrotestosterone (DHT)-induced binding of androgen receptor (AR) to prostate cancer cell enhancers as a model, we show rapid recruitment, within minutes, of DNA topoisomerase I (TOP1) to a large cohort of AR-regulated enhancers. Furthermore, we show that the DNA nicking activity of TOP1 is a prerequisite for robust eRNA synthesis and enhancer activation, and is kinetically accompanied by the recruitment of ATR and the MRN complex, followed by additional components of DNA damage repair machinery to the AR-regulated enhancers. Together, our studies reveal a linkage between eRNA synthesis and ligand-dependent TOP1-mediated nicking a strategy exerting quantitative effects on eRNA expression in regulating AR-bound enhancer-dependent transcriptional programs. PMID:25619691

  7. 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

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

    PubMed

    Zawahir, Sharmila; Li, Guanghui; Banerjee, Aditi; Shiu, Jessica; Blanchard, Thomas G; Okogbule-Wonodi, Adora C

    2015-08-01

    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

  9. 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

  10. Spatial Regulation and the Rate of Signal Transduction Activation

    PubMed Central

    Batada, Nizar N; Shepp, Larry A; Siegmund, David O; Levitt, Michael

    2006-01-01

    Of the many important signaling events that take place on the surface of a mammalian cell, activation of signal transduction pathways via interactions of cell surface receptors is one of the most important. Evidence suggests that cell surface proteins are not as freely diffusible as implied by the classic fluid mosaic model and that their confinement to membrane domains is regulated. It is unknown whether these dynamic localization mechanisms function to enhance signal transduction activation rate or to minimize cross talk among pathways that share common intermediates. To determine which of these two possibilities is more likely, we derive an explicit equation for the rate at which cell surface membrane proteins interact based on a Brownian motion model in the presence of endocytosis and exocytosis. We find that in the absence of any diffusion constraints, cell surface protein interaction rate is extremely high relative to cytoplasmic protein interaction rate even in a large mammalian cell with a receptor abundance of a mere two hundred molecules. Since a larger number of downstream signaling events needs to take place, each occurring at a much slower rate than the initial activation via association of cell surface proteins, we conclude that the role of co-localization is most likely that of cross-talk reduction rather than coupling efficiency enhancement. PMID:16699596

  11. 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.

  12. Ribosomal protein S14 negatively regulates c-Myc activity.

    PubMed

    Zhou, Xiang; Hao, Qian; Liao, Jun-Ming; Liao, Peng; Lu, Hua

    2013-07-26

    The ribosomal gene RPS14 is associated with the cancer-prone 5q-syndrome, which is caused by an interstitial deletion of the long arm of human chromosome 5. Previously, we found that ribosomal protein S14 (RPS14) binds to and inactivates MDM2, consequently leading to p53-dependent cell-cycle arrest and growth inhibition. However, it remains elusive whether RPS14 regulates cell proliferation in a p53-independent manner. Here, we show that RPS14 interacts with the Myc homology box II (MBII) and the C-terminal basic helix-loop-helix leucine zipper (bHLH-LZ) domains of the oncoprotein c-Myc. Further, RPS14 inhibited c-Myc transcriptional activity by preventing the recruitment of c-Myc and its cofactor, TRRAP, to the target gene promoters, as thus suppressing c-Myc-induced cell proliferation. Also, siRNA-mediated RPS14 depletion elevated c-Myc transcriptional activity determined by its target gene, Nucleolin, expression. Interestingly, RPS14 depletion also resulted in the induction of c-Myc mRNA and subsequent protein levels. Consistent with this, RPS14 promoted c-Myc mRNA turnover through an Argonaute 2 (Ago2)- and microRNA-mediated pathway. Taken together, our study demonstrates that RPS14 negates c-Myc functions by directly inhibiting its transcriptional activity and mediating its mRNA degradation via miRNA. PMID:23775087

  13. 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

  14. Activity, regulation, copy number and function in the glyoxalase system.

    PubMed

    Rabbani, Naila; Xue, Mingzhan; Thornalley, Paul J

    2014-04-01

    Molecular, catalytic and structural properties of glyoxalase pathway enzymes of many species are now known. Current research has focused on the regulation of activity and expression of Glo1 (glyoxalase I) and Glo2 (glyoxalase II) and their role in health and disease. Human GLO1 has MRE (metal-response element), IRE (insulin-response element), E2F4 (early gene 2 factor isoform 4), AP-2α (activating enhancer-binding protein 2α) and ARE (antioxidant response-element) regulatory elements and is a hotspot for copy number variation. The human Glo2 gene, HAGH (hydroxyacylglutathione hydrolase), has a regulatory p53-response element. Glo1 is linked to healthy aging, obesity, diabetes and diabetic complications, chronic renal disease, cardiovascular disease, other disorders and multidrug resistance in cancer chemotherapy. Mathematical modelling of the glyoxalase pathway predicts that pharmacological levels of increased Glo1 activity markedly decrease cellular methylglyoxal and related glycation, and pharmacological Glo1 inhibition markedly increases cellular methylglyoxal and related glycation. Glo1 inducers are in development to sustain healthy aging and for treatment of vascular complications of diabetes and other disorders, and cell-permeant Glo1 inhibitors are in development for treatment of multidrug-resistant tumours, malaria and potentially pathogenic bacteria and fungi. PMID:24646254

  15. 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

  16. Substrate regulation of ascorbate transport activity in astrocytes

    SciTech Connect

    Wilson, J.X.; Jaworski, E.M.; Kulaga, A.; Dixon, S.J. )

    1990-10-01

    Astrocytes possess a concentrative L-ascorbate (vitamin C) uptake mechanism involving a Na(+)-dependent L-ascorbate transporter located in the plasma membrane. The present experiments examined the effects of deprivation and supplementation of extracellular L-ascorbate on the activity of this transport system. Initial rates of L-ascorbate uptake were measured by incubating primary cultures of rat astrocytes with L-(14C)ascorbate for 1 min at 37 degrees C. We observed that the apparent maximal rate of uptake (Vmax) increased rapidly (less than 1 h) when cultured cells were deprived of L-ascorbate. In contrast, there was no change in the apparent affinity of the transport system for L-(14C)ascorbate. The increase in Vmax was reversed by addition of L-ascorbate, but not D-isoascorbate, to the medium. The effects of external ascorbate on ascorbate transport activity were specific in that preincubation of cultures with L-ascorbate did not affect uptake of 2-deoxy-D-(3H(G))glucose. We conclude that the astroglial ascorbate transport system is modulated by changes in substrate availability. Regulation of transport activity may play a role in intracellular ascorbate homeostasis by compensating for regional differences and temporal fluctuations in external ascorbate levels.

  17. Pharmacological activation of lysophosphatidic acid receptors regulates erythropoiesis.

    PubMed

    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

  18. Ultrasensitive regulation of anapleurosis via allosteric activation of PEP carboxylase

    PubMed Central

    Xu, Yi-Fan; Amador-Noguez, Daniel; Reaves, Marshall Louis; Feng, Xiao-Jiang; Rabinowitz, Joshua D.

    2012-01-01

    Anapleurosis is the filling of the TCA cycle with four-carbon units. The common substrate for both anapleurosis and glucose phosphorylation in bacteria is the terminal glycolytic metabolite, phosphoenolpyruvate (PEP). Here we show that E. coli quickly and almost completely turns off PEP consumption upon glucose removal. The resulting build-up of PEP is used to quickly import glucose if it becomes re-available. The switch-like termination of anapleurosis results from depletion of fructose-1,6-bisphosphate (FBP), an ultrasensitive allosteric activator of PEP carboxylase. E. coli expressing an FBP-insensitive point mutant of PEP carboxylase grow normally on steady glucose. However, they fail to build-up PEP upon glucose removal, grow poorly on oscillating glucose, and suffer from futile cycling at the PEP node on gluconeogenic substrates. Thus, bacterial central carbon metabolism is intrinsically programmed with ultrasensitive allosteric regulation to enable rapid adaptation to changing environmental conditions. PMID:22522319

  19. 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

  20. Parkin Regulates the Activity of Pyruvate Kinase M2.

    PubMed

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

    2016-05-01

    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

  1. Tissue plasminogen activator regulates Purkinje neuron development and survival

    PubMed Central

    Li, Jianxue; Yu, Lili; Gu, Xuesong; Ma, Yinghua; Pasqualini, Renata; Arap, Wadih; Snyder, Evan Y.; Sidman, Richard L.

    2013-01-01

    The cerebellar cortex is centrally involved in motor coordination and learning, and its sole output is provided by Purkinje neurons (PNs). Growth of PN dendrites and their major synaptic input from granule cell parallel fiber axons takes place almost entirely in the first several postnatal weeks. PNs are more vulnerable to cell death than most other neurons, but the mechanisms remain unclear. We find that the homozygous nervous (nr) mutant mouse’s 10-fold–increased cerebellar tissue plasminogen activator (tPA), a part of the tPA/plasmin proteolytic system, influences several different molecular mechanisms, each regulating a key aspect of postnatal PN development, followed by selective PN necrosis, as follows. (i) Excess endogenous or exogenous tPA inhibits dendritic growth in vivo and in vitro by activating protein kinase Cγ and phosphorylation of microtubule-associated protein 2. (ii) tPA/plasmin proteolysis impairs parallel fiber-PN synaptogenesis by blocking brain-derived neurotrophic factor/tyrosine kinase receptor B signaling. (iii) Voltage-dependent anion channel 1 (a mitochondrial and plasma membrane protein) bound with kringle 5 (a peptide derived from the excess plasminogen) promotes pathological enlargement and rounding of PN mitochondria, reduces mitochondrial membrane potential, and damages plasma membranes. These abnormalities culminate in young nr PN necrosis that can be mimicked in wild-type PNs by exogenous tPA injection into cerebellum or prevented by endogenous tPA deletion in nr:tPA-knockout double mutants. In sum, excess tPA/plasmin, through separate downstream molecular mechanisms, regulates postnatal PN dendritogenesis, synaptogenesis, mitochondrial structure and function, and selective PN viability. PMID:23674688

  2. 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. PMID:26132887

  3. 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.

  4. Redox regulation of muscle adaptations to contractile activity and aging

    PubMed Central

    2015-01-01

    Superoxide and nitric oxide are generated by skeletal muscle, and these species are increased by contractile activity. Mitochondria have long been assumed to play the primary role in generation of superoxide in muscle, but recent studies indicate that, during contractile activity, membrane-localized NADPH oxidase(s) rapidly generate(s) superoxide that plays a role in redox signaling. This process is important in upregulation of rapid and specific cytoprotective responses that aid maintenance of cell viability following contractile activity, but the overall extent to which redox signaling contributes to regulation of muscle metabolism and homeostasis following contractile activity is currently unclear, as is identification of key redox-sensitive protein targets involved in these processes. Reactive oxygen and nitrogen species have also been implicated in the loss of muscle mass and function that occurs with aging, although recent work has questioned whether oxidative damage plays a key role in these processes. A failure of redox signaling occurs in muscle during aging and may contribute to the age-related loss of muscle fibers. Whether such changes in redox signaling reflect primary age-related changes or are secondary to the fundamental mechanisms is unclear. For instance, denervated muscle fibers within muscles from aged rodents or humans appear to generate large amounts of mitochondrial hydrogen peroxide that could influence adjacent innervated fibers. Thus, in this instance, a “secondary” source of reactive oxygen species may be potentially generated as a result of a primary age-related pathology (loss of neurons), but, nevertheless, may contribute to loss of muscle mass and function during aging. PMID:25792715

  5. 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.

  6. 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

  7. Cortical neuronal activity does not regulate sleep homeostasis

    PubMed Central

    Qiu, Mei-Hong; Chen, Michael C.; Lu, Jun

    2015-01-01

    The neural substrate of sleep homeostasis is unclear, but both cortical and subcortical structures are thought to be involved in sleep regulation. To test whether prior neuronal activity in the cortex or in subcortical regions drives sleep rebound, we systemically administered atropine (100 mg/kg) to rats, producing a dissociated state with slow-wave cortical EEG but waking behavior (eg. locomotion). Atropine injections during the light period produced six hours of slow-wave cortical EEG but also subcortical arousal. Afterwards, rats showed a significant increase in non-rapid eye movement (NREM) sleep, compared to the same period on a baseline day. Consistent with the behavioral and cortical EEG state produced by systemic atropine, c-Fos expression was low in the cortex but high in multiple subcortical arousal systems. These data suggest that subcortical arousal and behavior are sufficient to drive sleep homeostasis, while a sleep-like pattern of cortical activity is not sufficient to satisfy sleep homeostasis. PMID:25864961

  8. Activated Type 2 Innate Lymphoid Cells regulate Beige Fat Biogenesis

    PubMed Central

    Lee, Min-Woo; Odegaard, Justin I.; Mukundan, Lata; Qiu, Yifu; Molofsky, Ari B.; Nussbaum, Jesse C.; Yun, Karen; Locksley, Richard M.; Chawla, Ajay

    2014-01-01

    SUMMARY Type 2 innate lymphoid cells (ILC2s), an innate source of the type 2 cytokines interleukin (IL)-5 and -13, participate in the maintenance of tissue homeostasis. Although type 2 immunity is critically important for mediating metabolic adaptations to environmental cold, the functions of ILC2s in beige or brown fat development are poorly defined. We report here that activation of ILC2s by IL-33 is sufficient to promote the growth of functional beige fat in thermoneutral mice. Mechanistically, ILC2 activation results in the proliferation of bipotential adipocyte precursors (APs) and their subsequent commitment to the beige fat lineage. Loss- and gain-of-function studies reveal that ILC2-and eosinophil-derived type 2 cytokines stimulate signaling via the IL-4Rα in PDGFRα+ APs to promote beige fat biogenesis. Together, our results highlight a critical role for ILC2s and type 2 cytokines in the regulation of adipocyte precursor numbers and fate, and as a consequence, adipose tissue homeostasis. PMID:25543153

  9. Curcumin stimulates cystic fibrosis transmembrane conductance regulator Cl- channel activity.

    PubMed

    Berger, Allan L; Randak, Christoph O; Ostedgaard, Lynda S; Karp, Philip H; Vermeer, Daniel W; Welsh, Michael J

    2005-02-18

    Compounds that enhance either the function or biosynthetic processing of the cystic fibrosis transmembrane conductance regulator (CFTR) Cl(-) channel may be of value in developing new treatments for cystic fibrosis (CF). Previous studies suggested that the herbal extract curcumin might affect the processing of a common CF mutant, CFTR-DeltaF508. Here, we tested the hypothesis that curcumin influences channel function. Curcumin increased CFTR channel activity in excised, inside-out membrane patches by reducing channel closed time and prolonging the time channels remained open. Stimulation was dose-dependent, reversible, and greater than that observed with genistein, another compound that stimulates CFTR. Curcumin-dependent stimulation required phosphorylated channels and the presence of ATP. We found that curcumin increased the activity of both wild-type and DeltaF508 channels. Adding curcumin also increased Cl(-) transport in differentiated non-CF airway epithelia but not in CF epithelia. These results suggest that curcumin may directly stimulate CFTR Cl(-) channels. PMID:15582996

  10. 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

  11. Resolvin E1 Regulates ADP Activation of Human Platelets

    PubMed Central

    Fredman, Gabrielle; Van Dyke, Thomas E.; Serhan, Charles N.

    2010-01-01

    Objective Resolvin E1 (RvE1) is an eicosapentaenoic acid (EPA)-derived specialized pro-resolving mediator generated during resolution of acute inflammation. RvE1 exhibits potent organ-protective actions in vivo and acts on specific cell types including platelets. Here, we investigated the ability of RvE1 to regulate adenosine diphosphate (ADP) activation of platelets via specific receptors because RvE1 reduces platelet aggregation with certain agonists including ADP. Methods and Results RvE1 (0.1nM–100nM) incubated with platelets gave reduced ADP-stimulated P-selectin mobilization (IC50 ~1.6×10−12 M) and polymerized actin content compared to control platelets. RvE1 (1–100nM) did not stimulate or block intracellular calcium mobilization. Using a new P2Y12-β-arrestin-coupled cell system, ADP-activated P2Y12 with an EC50 of 5×10−6 M and RvE1 did not directly stimulate P2Y12 or block ADP-P2Y12 signals. In this system, another eicosanoid LTE4 (EC50 1.3×10−11 M) dose dependently activated P2Y12. When recombinant P2Y12-expressing cells were transiently transfected with an RvE1 receptor, human ChemR23 (present on human platelets), addition of RvE1 (0.1nM-10.0nM) blocked ADP signals (IC50 ~1.6×10−11 M) in P2Y12-ChemR23-expressing cells compared to mock transfections. Conclusions These results demonstrate that RvE1’s regulatory actions (i.e reducing ADP-stimulated P-selectin mobilization and actin polymerization) are hChemR23-dependent. Moreover, they document specific platelet actions of RvE1 selectively engaged with ADP-activated platelets that illuminate a new cellular mechanism and impact of omega-3 EPA that may contribute to both resolution of vascular inflammation and ADP-dependent platelet activation relevant in pathologic cardiovascular events. PMID:20702811

  12. Circadian Regulation of Sucrose Phosphate Synthase Activity in Tomato by Protein Phosphatase Activity.

    PubMed Central

    Jones, T. L.; Ort, D. R.

    1997-01-01

    Sucrose phosphate synthase (SPS), a key enzyme in sucrose biosynthesis, is regulated by protein phosphorylation and shows a circadian pattern of activity in tomato. SPS is most active in its dephosphorylated state, which normally coincides with daytime. Applying okadaic acid, a potent protein phosphatase inhibitor, prevents SPS activation. More interesting is that a brief treatment with cycloheximide, a cytoplasmic translation inhibitor, also prevents the light activation of SPS without any effect on the amount of SPS protein. Cordycepin, an inhibitor of transcript synthesis and processing, has the same effect. Both of these inhibitors also prevent the activation phase of the circadian rhythm in SPS activity. Conversely, cycloheximide and cordycepin do not prevent the decline in circadian SPS activity that normally occurs at night. These observations indicate that SPS phosphatase activity but not SPS kinase activity is controlled, directly or indirectly, at the level of gene expression. Taken together, these data imply that there is a circadian rhythm controlling the transcription of a protein phosphatase that subsequently dictates the circadian rhythm in SPS activity via effects on this enzyme's phosphorylation state. PMID:12223667

  13. 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

  14. 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

  15. AMP-activated protein kinase phosphorylates CtBP1 and down-regulates its activity

    SciTech Connect

    Kim, Jae-Hwan; Choi, Soo-Youn; Kang, Byung-Hee; Lee, Soon-Min; Cho, Eun-Jung; Youn, Hong-Duk

    2013-02-01

    Highlights: ► AMPK phosphorylates CtBP1 on serine 158. ► AMPK-mediated phosphorylation of CtBP1 causes the ubiquitination and nuclear export of CtBP1. ► AMPK downregulates the CtBP1-mediated repression of Bax transcription. -- Abstract: CtBP is a transcriptional repressor which plays a significant role in the regulation of cell proliferation and tumor progression. It was reported that glucose withdrawal causes induction of Bax due to the dissociation of CtBP from the Bax promoter. However, the precise mechanism involved in the regulation of CtBP still remains unclear. In this study, we found that an activated AMP-activated protein kinase (AMPK) phosphorylates CtBP1 on Ser-158 upon metabolic stresses. Moreover, AMPK-mediated phosphorylation of CtBP1 (S158) attenuates the repressive function of CtBP1. We also confirmed that triggering activation of AMPK by various factors resulted in an increase of Bax gene expression. These findings provide connections of AMPK with CtBP1-mediated regulation of Bax expression for cell death under metabolic stresses.

  16. 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).

  17. Distinct Mechanisms Regulate Lck Spatial Organization in Activated T Cells

    PubMed Central

    Kapoor-Kaushik, Natasha; Hinde, Elizabeth; Compeer, Ewoud B.; Yamamoto, Yui; Kraus, Felix; Yang, Zhengmin; Lou, Jieqiong; Pageon, Sophie V.; Tabarin, Thibault; Gaus, Katharina; Rossy, Jérémie

    2016-01-01

    Phosphorylation of the T cell receptor (TCR) by the kinase Lck is the first detectable signaling event upon antigen engagement. The distribution of Lck within the plasma membrane, its conformational state, kinase activity, and protein–protein interactions all contribute to determine how efficiently Lck phosphorylates the engaged TCR. Here, we used cross-correlation raster image correlation spectroscopy and photoactivated localization microscopy to identify two mechanisms of Lck clustering: an intrinsic mechanism of Lck clustering induced by locking Lck in its open conformation and an extrinsic mechanism of clustering controlled by the phosphorylation of tyrosine 192, which regulates the affinity of Lck SH2 domain. Both mechanisms of clustering were differently affected by the absence of the kinase Zap70 or the adaptor Lat. We further observed that the adaptor TSAd bound to and promoted the diffusion of Lck when it is phosphorylated on tyrosine 192. Our data suggest that while Lck open conformation drives aggregation and clustering, the spatial organization of Lck is further controlled by signaling events downstream of TCR phosphorylation. PMID:27014263

  18. Synaptic activity regulates AMPA receptor trafficking through different recycling pathways.

    PubMed

    Zheng, Ning; Jeyifous, Okunola; Munro, Charlotte; Montgomery, Johanna M; Green, William N

    2015-01-01

    Changes in glutamatergic synaptic strength in brain are dependent on AMPA-type glutamate receptor (AMPAR) recycling, which is assumed to occur through a single local pathway. In this study, we present evidence that AMPAR recycling occurs through different pathways regulated by synaptic activity. Without synaptic stimulation, most AMPARs recycled in dynamin-independent endosomes containing the GTPase, Arf6. Few AMPARs recycled in dynamin-dependent endosomes labeled by transferrin receptors (TfRs). AMPAR recycling was blocked by alterations in the GTPase, TC10, which co-localized with Arf6 endosomes. TC10 mutants that reduced AMPAR recycling had no effect on increased AMPAR levels with long-term potentiation (LTP) and little effect on decreased AMPAR levels with long-term depression. However, internalized AMPAR levels in TfR-containing recycling endosomes increased after LTP, indicating increased AMPAR recycling through the dynamin-dependent pathway with synaptic plasticity. LTP-induced AMPAR endocytosis is inconsistent with local recycling as a source of increased surface receptors, suggesting AMPARs are trafficked from other sites. PMID:25970033

  19. 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.

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

    PubMed

    Liu, Xinhuai; Herbison, Allan E

    2016-06-01

    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