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Sample records for activities regulations statutes

  1. 32 CFR 516.29 - Federal statutes and regulations.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 32 National Defense 3 2010-07-01 2010-07-01 true Federal statutes and regulations. 516.29 Section 516.29 National Defense Department of Defense (Continued) DEPARTMENT OF THE ARMY AID OF CIVIL AUTHORITIES AND PUBLIC RELATIONS LITIGATION Individual Liability § 516.29 Federal statutes and regulations....

  2. Vessel Sewage Discharges: Statutes, Regulations, and Related Laws and Treaties

    EPA Pesticide Factsheets

    Vessel sewage discharges can be regulated under multiple statutes, regulations, and laws/treaties, including the Clean Water Act, Title XIV, MARPOL Annex IV and the Vessel General Permit. This page describes how these are applied to vessel sewage.

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

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 15 2012-01-01 2012-01-01 false Applicable Federal statutes and regulations. 2903.21 Section 2903.21 Agriculture Regulations of the Department of Agriculture (Continued) OFFICE OF ENERGY POLICY AND NEW USES, DEPARTMENT OF AGRICULTURE BIODIESEL FUEL EDUCATION PROGRAM Supplementary...

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

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 15 2014-01-01 2014-01-01 false Applicable Federal statutes and regulations. 2903.21 Section 2903.21 Agriculture Regulations of the Department of Agriculture (Continued) OFFICE OF ENERGY POLICY AND NEW USES, DEPARTMENT OF AGRICULTURE BIODIESEL FUEL EDUCATION PROGRAM Supplementary...

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

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 15 2011-01-01 2011-01-01 false Applicable Federal statutes and regulations. 2903.21 Section 2903.21 Agriculture Regulations of the Department of Agriculture (Continued) OFFICE OF ENERGY POLICY AND NEW USES, DEPARTMENT OF AGRICULTURE BIODIESEL FUEL EDUCATION PROGRAM Supplementary...

  6. 7 CFR 2903.21 - Applicable Federal statutes and regulations.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 15 2013-01-01 2013-01-01 false Applicable Federal statutes and regulations. 2903.21 Section 2903.21 Agriculture Regulations of the Department of Agriculture (Continued) OFFICE OF ENERGY POLICY AND NEW USES, DEPARTMENT OF AGRICULTURE BIODIESEL FUEL EDUCATION PROGRAM Supplementary...

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

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 15 2010-01-01 2010-01-01 false Applicable Federal statutes and regulations. 2903.21 Section 2903.21 Agriculture Regulations of the Department of Agriculture (Continued) OFFICE OF ENERGY POLICY AND NEW USES, DEPARTMENT OF AGRICULTURE BIODIESEL FUEL EDUCATION PROGRAM Supplementary...

  8. 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,…

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

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... environmental statutes, regulations and executive orders. (a) Other Federal environmental laws. All projects... 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. 28 CFR 91.68 - Compliance with other Federal environmental statutes, regulations and executive orders.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... environmental statutes, regulations and executive orders. (a) Other Federal environmental laws. All projects... 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...

  11. 28 CFR 91.68 - Compliance with other Federal environmental statutes, regulations and executive orders.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... environmental statutes, regulations and executive orders. (a) Other Federal environmental laws. All projects... 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...

  12. 28 CFR 91.68 - Compliance with other Federal environmental statutes, regulations and executive orders.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... environmental statutes, regulations and executive orders. (a) Other Federal environmental laws. All projects... 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...

  13. 28 CFR 91.68 - Compliance with other Federal environmental statutes, regulations and executive orders.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... environmental statutes, regulations and executive orders. (a) Other Federal environmental laws. All projects... 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...

  14. 1 CFR 2.5 - Publication of statutes, regulations, and related documents.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 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 REGISTER GENERAL GENERAL INFORMATION § 2.5 Publication of statutes, regulations, and related documents. (a)...

  15. 1 CFR 2.5 - Publication of statutes, regulations, and related documents.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 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 REGISTER GENERAL GENERAL INFORMATION § 2.5 Publication of statutes, regulations, and related documents. (a)...

  16. 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)...

  17. 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)...

  18. 14 CFR 223.21 - Free and reduced-rate transportation authorized by statute or regulation.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

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

  19. 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)...

  20. 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)...

  1. 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...

  2. 7 CFR 3415.8 - Other Federal statutes and regulations that apply.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 15 2014-01-01 2014-01-01 false Other Federal statutes and regulations that apply. 3415.8 Section 3415.8 Agriculture Regulations of the Department of Agriculture (Continued) NATIONAL INSTITUTE OF FOOD AND AGRICULTURE BIOTECHNOLOGY RISK ASSESSMENT RESEARCH GRANTS PROGRAM General §...

  3. 7 CFR 3415.8 - 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. 3415.8 Section 3415.8 Agriculture Regulations of the Department of Agriculture (Continued) NATIONAL INSTITUTE OF FOOD AND AGRICULTURE BIOTECHNOLOGY RISK ASSESSMENT RESEARCH GRANTS PROGRAM General §...

  4. 7 CFR 3415.8 - Other Federal statutes and regulations that apply.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 15 2013-01-01 2013-01-01 false Other Federal statutes and regulations that apply. 3415.8 Section 3415.8 Agriculture Regulations of the Department of Agriculture (Continued) NATIONAL INSTITUTE OF FOOD AND AGRICULTURE BIOTECHNOLOGY RISK ASSESSMENT RESEARCH GRANTS PROGRAM General §...

  5. 7 CFR 3415.8 - Other Federal statutes and regulations that apply.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 15 2010-01-01 2010-01-01 false Other Federal statutes and regulations that apply. 3415.8 Section 3415.8 Agriculture Regulations of the Department of Agriculture (Continued) COOPERATIVE STATE RESEARCH, EDUCATION, AND EXTENSION SERVICE, DEPARTMENT OF AGRICULTURE BIOTECHNOLOGY...

  6. 7 CFR 3415.8 - Other Federal statutes and regulations that apply.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 15 2012-01-01 2012-01-01 false Other Federal statutes and regulations that apply. 3415.8 Section 3415.8 Agriculture Regulations of the Department of Agriculture (Continued) NATIONAL INSTITUTE OF FOOD AND AGRICULTURE BIOTECHNOLOGY RISK ASSESSMENT RESEARCH GRANTS PROGRAM General §...

  7. 34 CFR 222.55 - What other statutes and regulations are applicable to this subpart?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 34 Education 1 2010-07-01 2010-07-01 false What other statutes and regulations are applicable to this subpart? 222.55 Section 222.55 Education Regulations of the Offices of the Department of Education OFFICE OF ELEMENTARY AND SECONDARY EDUCATION, DEPARTMENT OF EDUCATION IMPACT AID PROGRAMS Payments...

  8. 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...

  9. 7 CFR 3402.20 - Other Federal statutes and regulations that apply.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 15 2014-01-01 2014-01-01 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...

  10. 7 CFR 3402.20 - Other Federal statutes and regulations that apply.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 15 2013-01-01 2013-01-01 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...

  11. 7 CFR 3402.20 - Other Federal statutes and regulations that apply.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 15 2012-01-01 2012-01-01 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...

  12. 34 CFR 222.92 - What additional statutes and regulations apply to this subpart?

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 34 Education 1 2012-07-01 2012-07-01 false What additional statutes and regulations apply to this subpart? 222.92 Section 222.92 Education Regulations of the Offices of the Department of Education OFFICE... for Local Educational Agencies That Claim Children Residing on Indian Lands General § 222.92...

  13. 34 CFR 222.55 - What other statutes and regulations are applicable to this subpart?

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 34 Education 1 2012-07-01 2012-07-01 false What other statutes and regulations are applicable to this subpart? 222.55 Section 222.55 Education Regulations of the Offices of the Department of Education... Section 8003(d) of the Act for Local Educational Agencies That Serve Children With Disabilities §...

  14. 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...

  15. 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.... 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...

  16. 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.... 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...

  17. 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.... 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...

  18. 47 CFR 19.735-105 - Availability of ethics and other conduct related regulations and statutes.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 47 Telecommunication 1 2012-10-01 2012-10-01 false Availability of ethics and other conduct... ethics and other conduct related regulations and statutes. (a)(1) The Commission shall furnish each new employee, at the time of his or her entrance on duty, with a copy of: (i) The Standards of Ethical...

  19. 47 CFR 19.735-105 - Availability of ethics and other conduct related regulations and statutes.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 47 Telecommunication 1 2013-10-01 2013-10-01 false Availability of ethics and other conduct... ethics and other conduct related regulations and statutes. (a)(1) The Commission shall furnish each new employee, at the time of his or her entrance on duty, with a copy of: (i) The Standards of Ethical...

  20. 47 CFR 19.735-105 - Availability of ethics and other conduct related regulations and statutes.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 47 Telecommunication 1 2014-10-01 2014-10-01 false Availability of ethics and other conduct... ethics and other conduct related regulations and statutes. (a)(1) The Commission shall furnish each new employee, at the time of his or her entrance on duty, with a copy of: (i) The Standards of Ethical...

  1. 47 CFR 19.735-105 - Availability of ethics and other conduct related regulations and statutes.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 47 Telecommunication 1 2010-10-01 2010-10-01 false Availability of ethics and other conduct... ethics and other conduct related regulations and statutes. (a)(1) The Commission shall furnish each new employee, at the time of his or her entrance on duty, with a copy of: (i) The Standards of Ethical...

  2. 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...

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

    Code of Federal Regulations, 2010 CFR

    2010-10-01

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

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

    Code of Federal Regulations, 2011 CFR

    2011-10-01

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

  5. 42 CFR 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...

  6. 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...

  7. 75 FR 17708 - Enforcement of Statutes, Orders, Rules and Regulations; Second Notice of Workshops on Penalty...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-07

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF ENERGY Federal Energy Regulatory Commission Enforcement of Statutes, Orders, Rules and Regulations; Second Notice of... or registration fee to attend. The purpose of this second notice is to provide the times...

  8. 47 CFR 19.735-105 - Availability of ethics and other conduct related regulations and statutes.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 47 Telecommunication 1 2011-10-01 2011-10-01 false Availability of ethics and other conduct... ethics and other conduct related regulations and statutes. (a)(1) The Commission shall furnish each new employee, at the time of his or her entrance on duty, with a copy of: (i) The Standards of Ethical...

  9. 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...

  10. 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...

  11. 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...

  12. 42 CFR 9.13 - Other federal laws, regulations, and statutes that apply to the sanctuary.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 42 Public Health 1 2014-10-01 2014-10-01 false Other federal laws, regulations, and statutes that apply to the sanctuary. 9.13 Section 9.13 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL PROVISIONS STANDARDS OF CARE FOR CHIMPANZEES HELD IN THE FEDERALLY...

  13. 42 CFR 9.13 - Other federal laws, regulations, and statutes that apply to the sanctuary.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 42 Public Health 1 2011-10-01 2011-10-01 false Other federal laws, regulations, and statutes that apply to the sanctuary. 9.13 Section 9.13 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL PROVISIONS STANDARDS OF CARE FOR CHIMPANZEES HELD IN THE FEDERALLY...

  14. 42 CFR 9.13 - Other federal laws, regulations, and statutes that apply to the sanctuary.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 1 2010-10-01 2010-10-01 false Other federal laws, regulations, and statutes that apply to the sanctuary. 9.13 Section 9.13 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL PROVISIONS STANDARDS OF CARE FOR CHIMPANZEES HELD IN THE FEDERALLY...

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

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 42 Public Health 1 2013-10-01 2013-10-01 false Other federal laws, regulations, and statutes that apply to the sanctuary. 9.13 Section 9.13 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL PROVISIONS STANDARDS OF CARE FOR CHIMPANZEES HELD IN THE FEDERALLY...

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

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 42 Public Health 1 2012-10-01 2012-10-01 false Other federal laws, regulations, and statutes that apply to the sanctuary. 9.13 Section 9.13 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL PROVISIONS STANDARDS OF CARE FOR CHIMPANZEES HELD IN THE FEDERALLY...

  17. 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... Governmentwide Requirements for Drug-Free Workplace (Financial Assistance). (j) 7 CFR Part 3052—USDA... regulations are contained in 37 CFR part 401) (n) Title IX of the Education Amendment of 1972 (20 U.S.C....

  18. 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... Governmentwide Requirements for Drug-Free Workplace (Financial Assistance). (j) 7 CFR Part 3052—USDA... regulations are contained in 37 CFR part 401) (n) Title IX of the Education Amendment of 1972 (20 U.S.C....

  19. 7 CFR 2500.003 - Other applicable statutes and regulations.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... Administrative Requirements for Grants and Agreements with Institutions of Higher Education, Hospitals and Other... Governmentwide Requirements for Drug-Free Workplace (Financial Assistance). (j) 7 CFR Part 3052—USDA... regulations are contained in 37 CFR part 401) (n) Title IX of the Education Amendment of 1972 (20 U.S.C....

  20. 7 CFR 3400.8 - Other Federal statutes and regulations that apply.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... and Suspension (Nonprocurement) and Governmentwide Requirements for Drug-Free Workplace (Grants). 7... implementation of statute), prohibiting discrimination based upon physical or mental handicap in...

  1. 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

    ... 10 Energy 4 2010-01-01 2010-01-01 false Applicable Federal Statutes, Executive Orders, and Government-wide Regulations A Appendix A to Part 603 Energy DEPARTMENT OF ENERGY (CONTINUED) ASSISTANCE... sources of drinking water. 4. If the project may impact a historic property, it is subject to the...

  2. 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...

  3. 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.

  4. 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...

  5. 7 CFR 3401.10 - Other Federal statutes and regulations that apply.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... and Suspension (Nonprocurement) and Governmentwide Requirements for Drug-Free Workplace (Grants); 7..., Rehabilitation Act of 1973) and 7 CFR Part 15B (USDA implementation of statute)—prohibiting discrimination...

  6. 49 CFR 228.413 - Compliance date for regulations; exemption from compliance with statute.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... EMPLOYEES Substantive Hours of Service Requirements for Train Employees Engaged in Commuter or Intercity....11(c)(1)-(2) and 228.19(c)(5)-(c)(8) with respect to their train employees who are engaged in commuter or intercity rail passenger transportation. (b) Exemption from compliance with statute. On...

  7. 7 CFR 3406.27 - Other Federal statutes and regulations that apply.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ...—Governmentwide Debarment and Suspension (Nonprocurement); Governmentwide Requirements for Drug-Free Workplace (Grants), implementing Executive Order 12549 on debarment and suspension and the Drug-Free Workplace Act... Part 15b (USDA implementation of statute), prohibiting discrimination based upon physical or...

  8. 40 CFR 1700.6 - Effect on State and local statutes and regulations.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... DEFENSE; UNIFORM NATIONAL DISCHARGE STANDARDS FOR VESSELS OF THE ARMED FORCES UNIFORM NATIONAL DISCHARGE STANDARDS FOR VESSELS OF THE ARMED FORCES Effect on States § 1700.6 Effect on State and local statutes and... the normal operation of an Armed Forces vessel, States or political subdivisions of States may...

  9. 40 CFR 1700.6 - Effect on State and local statutes and regulations.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... DEFENSE; UNIFORM NATIONAL DISCHARGE STANDARDS FOR VESSELS OF THE ARMED FORCES UNIFORM NATIONAL DISCHARGE STANDARDS FOR VESSELS OF THE ARMED FORCES Effect on States § 1700.6 Effect on State and local statutes and... the normal operation of an Armed Forces vessel, States or political subdivisions of States may...

  10. 40 CFR 1700.6 - Effect on State and local statutes and regulations.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... DEFENSE; UNIFORM NATIONAL DISCHARGE STANDARDS FOR VESSELS OF THE ARMED FORCES UNIFORM NATIONAL DISCHARGE STANDARDS FOR VESSELS OF THE ARMED FORCES Effect on States § 1700.6 Effect on State and local statutes and... the normal operation of an Armed Forces vessel, States or political subdivisions of States may...

  11. 40 CFR 1700.6 - Effect on State and local statutes and regulations.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... DEFENSE; UNIFORM NATIONAL DISCHARGE STANDARDS FOR VESSELS OF THE ARMED FORCES UNIFORM NATIONAL DISCHARGE STANDARDS FOR VESSELS OF THE ARMED FORCES Effect on States § 1700.6 Effect on State and local statutes and... the normal operation of an Armed Forces vessel, States or political subdivisions of States may...

  12. 40 CFR 1700.6 - Effect on State and local statutes and regulations.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... DEFENSE; UNIFORM NATIONAL DISCHARGE STANDARDS FOR VESSELS OF THE ARMED FORCES UNIFORM NATIONAL DISCHARGE STANDARDS FOR VESSELS OF THE ARMED FORCES Effect on States § 1700.6 Effect on State and local statutes and... the normal operation of an Armed Forces vessel, States or political subdivisions of States may...

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

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... paragraph (a) of this section, the Office also publishes “The United States Government Manual,” the “Public Papers of the Presidents of the United States,” the “Daily Compilation of Presidential Documents,” the... laws,” the “United States Statutes at Large,” the daily Federal Register and the “Code of...

  14. 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.

  15. 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...

  16. 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...

  17. 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...

  18. 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...

  19. 34 CFR 222.19 - What other statutes and regulations apply to this part?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 1964 (Pub. L. 88-352) (prohibition of discrimination on the basis of race, color or national origin... provisions of title IX of the Education Amendments of 1972 (Pub. L. 92-318) (prohibition of discrimination on... discrimination on the basis of disability), and the implementing regulations (34 CFR part 104). (Authority: 29...

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

    ERIC Educational Resources Information Center

    Dykhouse, Caroline Dow

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

  1. 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…

  2. 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

    ... criminal justice systems for adults and juvenile justice systems, and the entire statute is predicated upon... between criminal justice systems for adults and juvenile justice systems. This law also singles out... justice systems and for purposes related to the prevention of juvenile delinquency. The......

  3. 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

    ... criminal justice systems for adults and juvenile justice systems, and the entire statute is predicated upon... between criminal justice systems for adults and juvenile justice systems. This law also singles out... justice systems and for purposes related to the prevention of juvenile delinquency. The......

  4. 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

    ... criminal justice systems for adults and juvenile justice systems, and the entire statute is predicated upon... between criminal justice systems for adults and juvenile justice systems. This law also singles out... justice systems and for purposes related to the prevention of juvenile delinquency. The......

  5. 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

    ... criminal justice systems for adults and juvenile justice systems, and the entire statute is predicated upon... between criminal justice systems for adults and juvenile justice systems. This law also singles out... justice systems and for purposes related to the prevention of juvenile delinquency. The......

  6. 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

    ... criminal justice systems for adults and juvenile justice systems, and the entire statute is predicated upon... between criminal justice systems for adults and juvenile justice systems. This law also singles out... justice systems and for purposes related to the prevention of juvenile delinquency. The......

  7. 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...

  8. Elder Abuse Reporting: Limitations of Statutes.

    ERIC Educational Resources Information Center

    Salend, Elyse; And Others

    1984-01-01

    Compares 16 state elder abuse reporting statutes and analyzes their implementation. Generally, the statutes have failed to ensure consistent information about elder abuse within or across states. Neglect is more often reported than abuse and little prosecutory activity was noted. Suggestions for improving reporting policies are made. (JAC)

  9. 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

    ... Assurances for SF 424(R&R)” on the DOE Applicant and Recipient page at http://grants.pr.doe.gov includes the... 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....

  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

    ... Assurances for SF 424(R&R)” on the DOE Applicant and Recipient page at http://grants.pr.doe.gov includes the... 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....

  11. 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

    ... Assurances for SF 424(R&R)” on the DOE Applicant and Recipient page at http://grants.pr.doe.gov includes the... Act of 1964 (42 U.S.C. 2000d, et seq.) as implemented by DOE regulations at 10 CFR part 1040. These... Discrimination Act of 1975 (42 U.S.C. 6101, et seq.) as implemented by DOE regulations at 10 CFR part 1040....

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

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... Assurances for SF 424(R&R)” on the DOE Applicant and Recipient page at http://grants.pr.doe.gov includes the... 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....

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

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... Chapter 32 of Title 38, U.S.C. is: “(1) To provide educational asssistance to those men and women who... AFFAIRS-EFFECTUATION OF TITLE VI OF THE CIVIL RIGHTS ACT OF 1964 Nondiscrimination on the Basis of Age Pt... regulations affecting financial assistance administered by the agency. This appendix is VA's list of...

  14. 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...

  15. 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...

  16. 24 CFR 1007.45 - Applicability of civil rights statutes.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

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

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

    Code of Federal Regulations, 2014 CFR

    2014-04-01

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

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

    Code of Federal Regulations, 2012 CFR

    2012-04-01

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

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

    Code of Federal Regulations, 2011 CFR

    2011-04-01

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

  20. 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...

  1. 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...

  2. 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...

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

    PubMed

    Cozort, L A

    2001-03-01

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

  4. Environmental statutes. 1999 edition

    SciTech Connect

    1999-04-01

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

  5. 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

  6. 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...

  7. 45 CFR 5.64 - Exemption three: Records exempted by other statutes.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

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

  8. 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...

  9. 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...

  10. 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 ENFORCEMENT PROGRAM), ADMINISTRATION FOR CHILDREN AND FAMILIES, DEPARTMENT OF HEALTH AND HUMAN SERVICES...

  11. 36 CFR 67.8 - Certifications of statutes.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... regulation, a State or local statute is a law of the State or local government designating, or providing a method for the designation of, a historic district or districts. This includes any by-laws or ordinances... legislation which authorizes local governments to designate, or provides local governments with a method...

  12. 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... the official or officials who were charged with the responsibility for discovery and collection...

  13. 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.

  14. 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.

  15. Adrenocortical Activity and Emotion Regulation.

    ERIC Educational Resources Information Center

    Stansbury, Kathy; Gunnar, Megan R.

    1994-01-01

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

  16. 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.

  17. 48 CFR 53.301-273 - Reinsurance Agreement for a Bonds Statute Performance Bond.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 48 Federal Acquisition Regulations System 2 2014-10-01 2014-10-01 false Reinsurance Agreement for a Bonds Statute Performance Bond. 53.301-273 Section 53.301-273 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION (CONTINUED) CLAUSES AND FORMS FORMS Illustrations of Forms...

  18. 48 CFR 53.301-274 - Reinsurance Agreement for a Bonds Statute Payment Bond.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 48 Federal Acquisition Regulations System 2 2014-10-01 2014-10-01 false Reinsurance Agreement for a Bonds Statute Payment Bond. 53.301-274 Section 53.301-274 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION (CONTINUED) CLAUSES AND FORMS FORMS Illustrations of Forms...

  19. 13 CFR 147.625 - Criminal drug statute.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 13 Business Credit and Assistance 1 2010-01-01 2010-01-01 false Criminal drug statute. 147.625... FOR DRUG-FREE WORKPLACE (NONPROCUREMENT) Definitions § 147.625 Criminal drug statute. Criminal drug statute means a Federal or non-Federal criminal statute involving the manufacture,...

  20. 21 CFR 1405.625 - Criminal drug statute.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 9 2010-04-01 2010-04-01 false Criminal drug statute. 1405.625 Section 1405.625... WORKPLACE (FINANCIAL ASSISTANCE) Definitions § 1405.625 Criminal drug statute. Criminal drug statute means a Federal or non-Federal criminal statute involving the manufacture, distribution, dispensing, use,...

  1. 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...

  2. 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...

  3. 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...

  4. 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...

  5. 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...

  6. 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...

  7. 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...

  8. 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...

  9. 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...

  10. 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...

  11. 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...

  12. 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...

  13. 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...

  14. 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,...

  15. 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...

  16. 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...

  17. 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...

  18. 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...

  19. 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...

  20. 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...

  1. 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...

  2. 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...

  3. 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...

  4. 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...

  5. 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...

  6. 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...

  7. 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.

  8. 48 CFR 806.302-5 - Authorized or required by statute.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 48 Federal Acquisition Regulations System 5 2014-10-01 2014-10-01 false Authorized or required by statute. 806.302-5 Section 806.302-5 Federal Acquisition Regulations System DEPARTMENT OF VETERANS AFFAIRS... to be associated with affiliated institutions), or with blood banks, organ banks, or research...

  9. 48 CFR 222.404 - Construction Wage Rate Requirements statute wage determinations.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 48 Federal Acquisition Regulations System 3 2014-10-01 2014-10-01 false Construction Wage Rate Requirements statute wage determinations. 222.404 Section 222.404 Federal Acquisition Regulations System... LAWS TO GOVERNMENT ACQUISITIONS Labor Standards for Contracts Involving Construction...

  10. [Health culture in the Statute of Lastovo].

    PubMed

    Milovic Karic, Grozdana; Milovic, Dorde

    2013-01-01

    The aim of this article was to define the elements of health culture in the Statute of Lastovo, from its declaration in 1310 to amendments made in the 18th century. The source we used was a recently published translation of the Statute from Latin, in which we identified the lawmaker's stipulations directly or indirectly related to public health of the times. The Statute stipulates several preventive measures to keep plague at bay and to control it if it breaks out. Stipulations on communal slaughterhouses and fish markets, even if not directly intended to address healthcare issues, brought a definite improvement to public hygiene and sanitation. Penal provisions for the perpetrators included death, whipping, branding, cutting fingers off, standing on logs, and pillorying. The article concludes that even though the Statute of Lastovo is quite comprehensive and voluminous, it does not give much space to health culture, in fact, even less space than other Medieval statutes of towns along the east coast of the Adriatic.

  11. Georgia Supreme Court invalidates involuntary sterilization statute.

    PubMed

    Harper, T D

    1983-11-01

    In the US, the concept of eugenics has been limited to restrictions on the reproductive capabilities of criminals and the mentally defective. Moreover, the rights of persons subject to this restriction have been enhanced by recent judicial recognition of procreation as a fundamental right. Constitutional challenges have been mounted on the grounds that sterilization statutes constitute cruel or unusual punishment, a violation of the Equal Protection clause, an unlawful delegation of legislative or judicial powers, a bill of attainder, or a violation of the right to life, liberty, and the pursuit of happiness. These challenges have resulted in a reduction in the number of state-mandated sterilizations. This paper reviews the Georgia Supreme Court's recent invalidation of a 1970 statute authorizing the sterilization of mentally incompetent persons (O.C.G.A. 31-20-3). Motes v. Hall County Department of Family and Children Services, filed on behalf of a 21-year old retarded woman, challenged the statute as a violation of Motes' constitutional rights to due process and equal protection and contended that the state was required to prove the necessity of sterilization by more than a simple preponderance of the evidence. The Georgia Supreme Court negated both the sterilization order and the statute upon which it was based. In its decision, the Court recognized that an intrusion upon so fundamental a right as the ability to bear children requires proof by the state of at least "clear and convincing evidence" of the necessity of such an act.

  12. 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... (FINANCIAL ASSISTANCE) Definitions § 84.625 Criminal drug statute. Criminal drug statute means a Federal or... 3474; and Sec. 2455, Pub. L. 103-355, 108 Stat. 3243 at 3327.)...

  13. 36 CFR 1212.625 - Criminal drug statute.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 36 Parks, Forests, and Public Property 3 2010-07-01 2010-07-01 false Criminal drug statute. 1212.625 Section 1212.625 Parks, Forests, and Public Property NATIONAL ARCHIVES AND RECORDS ADMINISTRATION... § 1212.625 Criminal drug statute. Criminal drug statute means a Federal or non-Federal criminal...

  14. 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...

  15. 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 WORKPLACE (FINANCIAL ASSISTANCE) Definitions § 1509.625 Criminal drug statute. Criminal drug statute means...

  16. 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 (FINANCIAL ASSISTANCE) Definitions § 1509.625 Criminal drug statute. Criminal drug statute means a Federal...

  17. 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) Definitions § 312.625 Criminal drug statute. Criminal drug statute means a Federal or non-Federal...

  18. 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...

  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. 22 CFR 312.625 - Criminal drug statute.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

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

  1. 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...

  2. 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...

  3. 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...

  4. 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...

  5. 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...

  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. 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. 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...

  9. 29 CFR 94.625 - Criminal drug statute.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

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

  10. 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...

  11. 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...

  12. 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...

  13. 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...

  14. 22 CFR 210.625 - Criminal drug statute.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

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

  15. 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...

  16. 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...

  17. 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...

  18. 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...

  19. 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...

  20. 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...

  1. 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...

  2. 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...

  3. 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...

  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. 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...

  6. 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...

  7. 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...

  8. 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...

  9. 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...

  10. 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...

  11. 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...

  12. 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...

  13. 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...

  14. 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...

  15. 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...

  16. 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...

  17. 24 CFR 203.427 - Statute of limitations on payment of distributive shares.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... COMMISSIONER, DEPARTMENT OF HOUSING AND URBAN DEVELOPMENT MORTGAGE AND LOAN INSURANCE PROGRAMS UNDER NATIONAL... 24 Housing and Urban Development 2 2011-04-01 2011-04-01 false Statute of limitations on payment of distributive shares. 203.427 Section 203.427 Housing and Urban Development Regulations Relating...

  18. 24 CFR 203.427 - Statute of limitations on payment of distributive shares.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... COMMISSIONER, DEPARTMENT OF HOUSING AND URBAN DEVELOPMENT MORTGAGE AND LOAN INSURANCE PROGRAMS UNDER NATIONAL... 24 Housing and Urban Development 2 2010-04-01 2010-04-01 false Statute of limitations on payment of distributive shares. 203.427 Section 203.427 Housing and Urban Development Regulations Relating...

  19. 24 CFR 203.427 - Statute of limitations on payment of distributive shares.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... COMMISSIONER, DEPARTMENT OF HOUSING AND URBAN DEVELOPMENT MORTGAGE AND LOAN INSURANCE PROGRAMS UNDER NATIONAL... 24 Housing and Urban Development 2 2013-04-01 2013-04-01 false Statute of limitations on payment of distributive shares. 203.427 Section 203.427 Housing and Urban Development Regulations Relating...

  20. 24 CFR 203.427 - Statute of limitations on payment of distributive shares.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... COMMISSIONER, DEPARTMENT OF HOUSING AND URBAN DEVELOPMENT MORTGAGE AND LOAN INSURANCE PROGRAMS UNDER NATIONAL... 24 Housing and Urban Development 2 2012-04-01 2012-04-01 false Statute of limitations on payment of distributive shares. 203.427 Section 203.427 Housing and Urban Development Regulations Relating...

  1. 10 CFR 1015.104 - Compromise, waiver, or disposition under other statutes not precluded.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 10 Energy 4 2013-01-01 2013-01-01 false Compromise, waiver, or disposition under other statutes not precluded. 1015.104 Section 1015.104 Energy DEPARTMENT OF ENERGY (GENERAL PROVISIONS) COLLECTION... applicable laws and regulations will generally take precedence over this part....

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

    PubMed

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

    2006-11-01

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

  3. Food safety: revising the statute.

    PubMed

    Kessler, D A

    1984-03-09

    There is increasing recognition that federal food safety laws and policies need to be revised. Congressional debate on proposed amendments to the Food, Drug, and Cosmetic Act has generated several different perspectives on how the food safety laws should be changed. Before a consensus can be reached, scientists, regulators, the food industry, and consumers will have to review such complex and controversial issues as the level of acceptable risk, the value of risk-benefit analysis, the proper role of independent scientific review, and the reliability of quantitative risk assessment.

  4. The plasminogen activator system: biology and regulation.

    PubMed

    Irigoyen, J P; Muñoz-Cánoves, P; Montero, L; Koziczak, M; Nagamine, Y

    1999-10-01

    The regulation of plasminogen activation involves genes for two plasminogen activators (tissue type and urokinase type), two specific inhibitors (type 1 and type 2), and a membrane-anchored urokinase-type plasminogen-activator-specific receptor. This system plays an important role in various biological processes involving extracellular proteolysis. Recent studies have revealed that the system, through interplay with integrins and the extracellular matrix protein vitronectin, is also involved in the regulation of cell migration and proliferation in a manner independent of proteolytic activity. The genes are expressed in many different cell types and their expression is under the control of diverse extracellular signals. Gene expression reflects the levels of the corresponding mRNA, which should be the net result of synthesis and degradation. Thus, modulation of mRNA stability is an important factor in overall regulation. This review summarizes current understanding of the biology and regulation of genes involved in plasminogen activation at different levels.

  5. Glycosylation regulates prestin cellular activity.

    PubMed

    Rajagopalan, Lavanya; Organ-Darling, Louise E; Liu, Haiying; Davidson, Amy L; Raphael, Robert M; Brownell, William E; Pereira, Fred A

    2010-03-01

    Glycosylation is a common post-translational modification of proteins and is implicated in a variety of cellular functions including protein folding, degradation, sorting and trafficking, and membrane protein recycling. The membrane protein prestin is an essential component of the membrane-based motor driving electromotility changes (electromotility) in the outer hair cell (OHC), a central process in auditory transduction. Prestin was earlier identified to possess two N-glycosylation sites (N163, N166) that, when mutated, marginally affect prestin nonlinear capacitance (NLC) function in cultured cells. Here, we show that the double mutant prestin(NN163/166AA) is not glycosylated and shows the expected NLC properties in the untreated and cholesterol-depleted HEK 293 cell model. In addition, unlike WT prestin that readily forms oligomers, prestin(NN163/166AA) is enriched as monomers and more mobile in the plasma membrane, suggesting that oligomerization of prestin is dependent on glycosylation but is not essential for the generation of NLC in HEK 293 cells. However, in the presence of increased membrane cholesterol, unlike the hyperpolarizing shift in NLC seen with WT prestin, cells expressing prestin(NN163/166AA) exhibit a linear capacitance function. In an attempt to explain this finding, we discovered that both WT prestin and prestin(NN163/166AA) participate in cholesterol-dependent cellular trafficking. In contrast to WT prestin, prestin(NN163/166AA) shows a significant cholesterol-dependent decrease in cell-surface expression, which may explain the loss of NLC function. Based on our observations, we conclude that glycosylation regulates self-association and cellular trafficking of prestin(NN163/166AA). These observations are the first to implicate a regulatory role for cellular trafficking and sorting in prestin function. We speculate that the cholesterol regulation of prestin occurs through localization to and internalization from membrane microdomains by

  6. 50 CFR 404.7 - Regulated activities.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... Wildlife and Fisheries JOINT REGULATIONS (UNITED STATES FISH AND WILDLIFE SERVICE, DEPARTMENT OF THE INTERIOR AND NATIONAL MARINE FISHERIES SERVICE, NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT... MARINE NATIONAL MONUMENT § 404.7 Regulated activities. Except as provided in §§ 404.8, 404.9 and...

  7. p53 regulates thymic Notch1 activation.

    PubMed

    Laws, Amy M; Osborne, Barbara A

    2004-03-01

    Notch is crucial for multiple stages of T cell development, including the CD4+CD8+ double positive (DP)/CD8+ single positive (SP) transition, but regulation of Notchactivation is not well understood. p53 regulates Presenilin1 (PS1) expression, and PS1 cleaves Notch, releasing its intracellular domain (NIC), leading to the expression of downstream targets, e.g. the HES1 gene. We hypothesize that p53 regulates Notch activity during T cell development. We found that Notch1 expression and activation were negatively regulated by p53in several thymoma lines. Additionally, NIC was elevated in Trp53(-/-) thymocytes as compared to Trp53(+/+) thymocytes. To determine if elevated Notch1 activation in Trp53(-/-) thymocytes had an effect on T cell development, CD4 and CD8 expression were analyzed. The CD4+ SP/CD8+ SP T cell ratio was decreased in Trp53(-/-) splenocytes and thymocytes. This alteration in T cell development correlated with the increased Notch1 activation observed in the absence of p53. These data indicate that p53 negatively regulates Notch1 activation during T cell development. Skewing of T cell development toward CD8+SP T cells in Trp53(-/-) mice is reminiscent of the phenotype of NIC-overexpressing mice. Thus, we suggest that p53 plays a role in T cell development, in part by regulating Notch1 activation.

  8. Regulation of TRPM8 channel activity

    PubMed Central

    Yudin, Yevgen; Rohacs, Tibor

    2011-01-01

    Transient Receptor Potential Melastatin 8 (TRPM8) is a Ca2+ permeable non-selective cation channel directly activated by cold temperatures and chemical agonists such as menthol. It is a well established sensor of environmental cold temperatures, found in peripheral sensory neurons, where its activation evokes depolarization and action potentials. The activity of TRPM8 is regulated by a number of cellular signaling pathways, most notably by phosphoinositides and the activation of phospholipase C. This review will summarize current knowledge on the physiological and pathophysiological roles of TRPM8 and its regulation by various intracellular messenger molecules and signaling pathways. PMID:22061619

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

    PubMed

    Gaddis, Christine A

    2014-01-01

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

  10. 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... § 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...

  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. Art fakes and the statute of limitations

    NASA Astrophysics Data System (ADS)

    Feld, Alan L.

    2000-03-01

    A purchaser of fine art often relies on the vendor's representations as to the authorship and provenance of the work. Occasionally the new owner later makes the unpleasant discovery that the treasured work is a fake. The aggrieved purchaser then may demand that eh vendor make good on its assurances concerning the work. If the vendor declines to do so, the purchaser may seek legal redress against the vendor. At that point, the purchaser may find an unexpected barrier to success in the lawsuit. An otherwise sound claim may fail by reason of the statute of limitations -- the legal rule that a lawsuit must commence in a timely fashion. The rule may operate with dismaying rigor to art purchases, given the difficulty in distinguishing an authentic work from an imitation. This paper reviews the effects of statute of limitations claims in litigation involving artworks that do not live up to their promised authenticity. After a brief general introduction to limitations issues generally, the paper examines their varying application to claims regarding fake art.

  13. 45 CFR 73.735-1003 - Conflicts of interest statutes.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 45 Public Welfare 1 2011-10-01 2011-10-01 false Conflicts of interest statutes. 73.735-1003...-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...

  14. 45 CFR 73.735-1003 - Conflicts of interest statutes.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 45 Public Welfare 1 2014-10-01 2014-10-01 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...

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

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 45 Public Welfare 1 2013-10-01 2013-10-01 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...

  16. 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 590.101 Banks and Banking OFFICE OF THRIFT SUPERVISION, DEPARTMENT OF THE TREASURY PREEMPTION OF STATE... residential first mortgage. It does not matter whether the statute in question imposes criminal or...

  17. 12 CFR 590.101 - State criminal usury statutes.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 12 Banks and Banking 6 2013-01-01 2012-01-01 true State criminal usury statutes. 590.101 Section 590.101 Banks and Banking OFFICE OF THRIFT SUPERVISION, DEPARTMENT OF THE TREASURY PREEMPTION OF STATE... residential first mortgage. It does not matter whether the statute in question imposes criminal or...

  18. 12 CFR 590.101 - State criminal usury statutes.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 12 Banks and Banking 5 2011-01-01 2011-01-01 false State criminal usury statutes. 590.101 Section 590.101 Banks and Banking OFFICE OF THRIFT SUPERVISION, DEPARTMENT OF THE TREASURY PREEMPTION OF STATE... residential first mortgage. It does not matter whether the statute in question imposes criminal or...

  19. 15 CFR 29.625 - Criminal drug statute.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

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

  20. 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...

  1. 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...

  2. 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...

  3. 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...

  4. 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...

  5. 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...

  6. 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,...

  7. 50 CFR 665.904 - 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. 665.904 Section 665.904 Wildlife and Fisheries FISHERY CONSERVATION AND MANAGEMENT, NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE (CONTINUED) FISHERIES IN THE WESTERN PACIFIC Marianas Trench...

  8. 50 CFR 665.904 - 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. 665.904 Section 665.904 Wildlife and Fisheries FISHERY CONSERVATION AND MANAGEMENT, NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE (CONTINUED) FISHERIES IN THE WESTERN PACIFIC Marianas Trench...

  9. 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...

  10. 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...

  11. Criminal DNA databank statutes and medical research.

    PubMed

    Bressler, Davina Dana

    2002-01-01

    Every state and the federal government collects DNA from convicted individuals for certain crimes. Furthermore, most states participate in the Federal Bureau of Investigation's Combined DNA Identification System, which allows states to share criminal DNA records for solving crimes. Some commentators claim that the statues that authorize this practice also would allow the government to use criminal DNA samples or records in medical or behavioral research. A careful reading of the statutes reveals that these assertions are either wrong or exaggerated. Only one state allows for medical research with records, and no state allows medical or behavioral research with DNA samples. This note explains that the DNA samples, not the DNA records, are needed in order to conduct medical or behavioral research. Moreover, this note shows that the statutory phrases "law enforcement purposes," "other humanitarian purposes," and "research" into quality control or protocol probably do not authorize medical or behavioral research.

  12. 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.

  13. Proteolytic Processing Regulates Placental Growth Factor Activities*

    PubMed Central

    Hoffmann, Daniel C.; Willenborg, Sebastian; Koch, Manuel; Zwolanek, Daniela; Müller, Stefan; Becker, Ann-Kathrin A.; Metzger, Stephanie; Ehrbar, Martin; Kurschat, Peter; Hellmich, Martin; Hubbell, Jeffrey A.; Eming, Sabine A.

    2013-01-01

    Placental growth factor (PlGF) is a critical mediator of blood vessel formation, yet mechanisms of its action and regulation are incompletely understood. Here we demonstrate that proteolytic processing regulates the biological activity of PlGF. Specifically, we show that plasmin processing of PlGF-2 yields a protease-resistant core fragment comprising the vascular endothelial growth factor receptor-1 binding site but lacking the carboxyl-terminal domain encoding the heparin-binding domain and an 8-amino acid peptide encoded by exon 7. We have identified plasmin cleavage sites, generated a truncated PlGF118 isoform mimicking plasmin-processed PlGF, and explored its biological function in comparison with that of PlGF-1 and -2. The angiogenic responses induced by the diverse PlGF forms were distinct. Whereas PlGF-2 increased endothelial cell chemotaxis, vascular sprouting, and granulation tissue formation upon skin injury, these activities were abrogated following plasmin digestion. Investigation of PlGF/Neuropilin-1 binding and function suggests a critical role for heparin-binding domain/Neuropilin-1 interaction and its regulation by plasmin processing. Collectively, here we provide new mechanistic insights into the regulation of PlGF-2/Neuropilin-1-mediated tissue vascularization and growth. PMID:23645683

  14. 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...

  15. 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...

  16. 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...

  17. 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...

  18. 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...

  19. 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

  20. 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…

  1. Activities and regulation of peptidoglycan synthases.

    PubMed

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

    2015-10-05

    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.

  2. 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

  3. 49 CFR 1302.42 - Further suspension of statute.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

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

  4. 49 CFR 1302.42 - Further suspension of statute.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

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

  5. 49 CFR 1302.42 - Further suspension of statute.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

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

  6. 49 CFR 1302.42 - Further suspension of statute.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

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

  7. 49 CFR 1302.42 - Further suspension of statute.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

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

  8. Regulation of polymorphonuclear cell activation by thrombopoietin.

    PubMed Central

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

    1997-01-01

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

  9. 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... individual. (b) Federal Employees Liability Reform and Tort Compensation Act of l988 (FELRTCA or the...

  10. 32 CFR 516.29 - Federal statutes and regulations.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... health care provider. (d) 28 CFR 50.15 (Representation of Federal officials and employees by Department... individual. (b) Federal Employees Liability Reform and Tort Compensation Act of l988 (FELRTCA or the...

  11. 32 CFR 516.29 - Federal statutes and regulations.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... health care provider. (d) 28 CFR 50.15 (Representation of Federal officials and employees by Department... individual. (b) Federal Employees Liability Reform and Tort Compensation Act of l988 (FELRTCA or the...

  12. 32 CFR 516.29 - Federal statutes and regulations.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... health care provider. (d) 28 CFR 50.15 (Representation of Federal officials and employees by Department... individual. (b) Federal Employees Liability Reform and Tort Compensation Act of l988 (FELRTCA or the...

  13. Workbook for the Codification of State Statutes and Regulations

    EPA Pesticide Factsheets

    The Codification Workbook package consists of two documents. The first is this document -- the Codification Workbook which contains information and instructions for codification. The second document is the Appendix containing the supporting documents.

  14. 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:...

  15. 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

  16. 78 FR 37819 - Proposed Information Collection Activity; Comment Request

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-06-24

    .... 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 area. Information from the ACF-700 and supplemental narrative report will be included in the Secretary's Report...

  17. 75 FR 30031 - Proposed Information Collection Activity; Comment Request

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-05-28

    .... 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 area. Information from the ACF-700 and supplemental narrative report will be included in the Secretary's Report...

  18. 12 CFR 26.4 - Interlocking relationships permitted by statute.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... MANAGEMENT OFFICIAL INTERLOCKS § 26.4 Interlocking relationships permitted by statute. The prohibitions of... served by a management official of another credit union; (d) A depository organization that does not do... in any part of the United States; (ii) The service would lead to substantial conflicts of interest...

  19. 12 CFR 196.4 - Interlocking relationships permitted by statute.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... MANAGEMENT OFFICIAL INTERLOCKS § 196.4 Interlocking relationships permitted by statute. The prohibitions of... served by a management official of another credit union; (d) A depository organization that does not do... in any part of the United States; (ii) The service would lead to substantial conflicts of interest...

  20. 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 MEDICAL Confidentiality of Healthcare Quality Assurance Review Records § 17.502 Applicability of...

  1. 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 MEDICAL Confidentiality of Healthcare Quality Assurance Review Records § 17.502 Applicability of...

  2. 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 MEDICAL Confidentiality of Healthcare Quality Assurance Review Records § 17.502 Applicability of...

  3. 32 CFR 842.105 - Statute of limitations.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 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.... A claim must be filed in writing within 2 years after it accrues. (a) Federal, not state...

  4. 42 CFR 435.901 - Consistency with objectives and statutes.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... Section 435.901 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN... Methods of Administration § 435.901 Consistency with objectives and statutes. The Medicaid agency's standards and methods for determining eligibility must be consistent with the objectives of the program...

  5. 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 MEDICAL Confidentiality of Healthcare Quality Assurance Review Records § 17.502 Applicability of...

  6. 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 MEDICAL Confidentiality of Healthcare Quality Assurance Review Records § 17.502 Applicability of...

  7. 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 Section 21.625 Housing and Urban Development Office of the Secretary, Department of Housing and Urban Development GOVERNMENTWIDE REQUIREMENTS FOR DRUG-FREE WORKPLACE (GRANTS) Definitions § 21.625 Criminal...

  8. 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)

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

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 12 Banks and Banking 2 2012-01-01 2012-01-01 false Interlocking relationships permitted by statute. 212.4 Section 212.4 Banks and Banking FEDERAL RESERVE SYSTEM BOARD OF GOVERNORS OF THE FEDERAL RESERVE... corporation operating under section 25 or section 25A of the Federal Reserve Act (12 U.S.C. 601 et seq. and...

  10. 12 CFR 212.4 - Interlocking relationships permitted by statute.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 12 Banks and Banking 2 2014-01-01 2014-01-01 false Interlocking relationships permitted by statute. 212.4 Section 212.4 Banks and Banking FEDERAL RESERVE SYSTEM BOARD OF GOVERNORS OF THE FEDERAL RESERVE... corporation operating under section 25 or section 25A of the Federal Reserve Act (12 U.S.C. 601 et seq. and...

  11. 12 CFR 212.4 - Interlocking relationships permitted by statute.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 12 Banks and Banking 2 2010-01-01 2010-01-01 false Interlocking relationships permitted by statute. 212.4 Section 212.4 Banks and Banking FEDERAL RESERVE SYSTEM BOARD OF GOVERNORS OF THE FEDERAL RESERVE... corporation operating under section 25 or section 25A of the Federal Reserve Act (12 U.S.C. 601 et seq. and...

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

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 12 Banks and Banking 2 2011-01-01 2011-01-01 false Interlocking relationships permitted by statute. 212.4 Section 212.4 Banks and Banking FEDERAL RESERVE SYSTEM BOARD OF GOVERNORS OF THE FEDERAL RESERVE... corporation operating under section 25 or section 25A of the Federal Reserve Act (12 U.S.C. 601 et seq. and...

  13. 12 CFR 212.4 - Interlocking relationships permitted by statute.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 12 Banks and Banking 2 2013-01-01 2013-01-01 false Interlocking relationships permitted by statute. 212.4 Section 212.4 Banks and Banking FEDERAL RESERVE SYSTEM BOARD OF GOVERNORS OF THE FEDERAL RESERVE... corporation operating under section 25 or section 25A of the Federal Reserve Act (12 U.S.C. 601 et seq. and...

  14. 7 CFR 1775.8 - Other Federal statutes.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... Workplace (Grants), implementing Executive Order 12549 on debarment and suspension and the Drug-Free Workplace Act of 1988 (41 U.S.C. 701). (i) 7 CFR part 3018—Restrictions on Lobbying, prohibiting the use of... implementation of statute), prohibiting discrimination based upon physical or mental handicap in...

  15. 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…

  16. 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 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...

  17. 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...

  18. 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...

  19. 7 CFR 1774.8 - Other Federal Statutes.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 12 2011-01-01 2011-01-01 false Other Federal Statutes. 1774.8 Section 1774.8... Higher Education, Hospitals, and Other Nonprofit Organizations. (j) 7 CFR part 3021, as amended... Workplace Act of 1988 (41 U.S.C. 701). (k) 7 CFR part 3052—USDA implementation of OMB Circular No....

  20. 7 CFR 1775.8 - Other Federal statutes.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... Higher Education, Hospitals, and Other Nonprofit Organizations. (k) 7 CFR part 3052—USDA implementation of OMB Circular No. A-133 regarding audits of institutions of higher education and other nonprofit... 7 Agriculture 12 2014-01-01 2013-01-01 true Other Federal statutes. 1775.8 Section...

  1. 7 CFR 1774.8 - Other Federal Statutes.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 12 2014-01-01 2013-01-01 true Other Federal Statutes. 1774.8 Section 1774.8... Higher Education, Hospitals, and Other Nonprofit Organizations. (j) 7 CFR part 3021, as amended... Workplace Act of 1988 (41 U.S.C. 701). (k) 7 CFR part 3052—USDA implementation of OMB Circular No....

  2. 7 CFR 1775.8 - Other Federal statutes.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... Higher Education, Hospitals, and Other Nonprofit Organizations. (k) 7 CFR part 3052—USDA implementation of OMB Circular No. A-133 regarding audits of institutions of higher education and other nonprofit... 7 Agriculture 12 2011-01-01 2011-01-01 false Other Federal statutes. 1775.8 Section...

  3. 7 CFR 1774.8 - Other Federal Statutes.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 12 2013-01-01 2013-01-01 false Other Federal Statutes. 1774.8 Section 1774.8... Higher Education, Hospitals, and Other Nonprofit Organizations. (j) 7 CFR part 3021, as amended... Workplace Act of 1988 (41 U.S.C. 701). (k) 7 CFR part 3052—USDA implementation of OMB Circular No....

  4. 7 CFR 1775.8 - Other Federal statutes.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... Higher Education, Hospitals, and Other Nonprofit Organizations. (k) 7 CFR part 3052—USDA implementation of OMB Circular No. A-133 regarding audits of institutions of higher education and other nonprofit... 7 Agriculture 12 2013-01-01 2013-01-01 false Other Federal statutes. 1775.8 Section...

  5. Regulation of Parkin E3 ubiquitin ligase activity.

    PubMed

    Walden, Helen; Martinez-Torres, R Julio

    2012-09-01

    Parkin is an E3 ubiquitin ligase mutated in autosomal recessive juvenile Parkinson's disease. In addition, it is a putative tumour suppressor, and has roles outside its enzymatic activity. It is critical for mitochondrial clearance through mitophagy, and is an essential protein in most eukaryotes. As such, it is a tightly controlled protein, regulated through an array of external interactions with multiple proteins, posttranslational modifications including phosphorylation and S-nitrosylation, and self-regulation through internal associations. In this review, we highlight some of the recent studies into Parkin regulation and discuss future challenges for gaining a full molecular understanding of the regulation of Parkin E3 ligase activity.

  6. Capital Punishment: An Overview of Federal Death Penalty Statutes

    DTIC Science & Technology

    2005-01-05

    Antiterrorism and Effective Death Penalty Act of 1996 made further modifications and additions to the list of federal capital crimes. On June 25, 2002...civilian offenses. Further changes to the list of federal capital punishment statutes resulted from the passage of the Antiterrorism and Effective Death ...offenses. The Antiterrorism and Effective Death Penalty Act of 1996, P.L. 104-132, CRS-4 3The offense is set forth generally in 18 U.S.C. § 32, while the

  7. Cysteine cathepsin activity regulation by glycosaminoglycans.

    PubMed

    Novinec, Marko; Lenarčič, Brigita; Turk, Boris

    2014-01-01

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

  8. Regulation of myostatin activity and muscle growth.

    PubMed

    Lee, S J; McPherron, A C

    2001-07-31

    Myostatin is a transforming growth factor-beta family member that acts as a negative regulator of skeletal muscle mass. To identify possible myostatin inhibitors that may have applications for promoting muscle growth, we investigated the regulation of myostatin signaling. Myostatin protein purified from mammalian cells consisted of a noncovalently held complex of the N-terminal propeptide and a disulfide-linked dimer of C-terminal fragments. The purified C-terminal myostatin dimer was capable of binding the activin type II receptors, Act RIIB and, to a lesser extent, Act RIIA. Binding of myostatin to Act RIIB could be inhibited by the activin-binding protein follistatin and, at higher concentrations, by the myostatin propeptide. To determine the functional significance of these interactions in vivo, we generated transgenic mice expressing high levels of the propeptide, follistatin, or a dominant-negative form of Act RIIB by using a skeletal muscle-specific promoter. Independent transgenic mouse lines for each construct exhibited dramatic increases in muscle mass comparable to those seen in myostatin knockout mice. Our findings suggest that the propeptide, follistatin, or other molecules that block signaling through this pathway may be useful agents for enhancing muscle growth for both human therapeutic and agricultural applications.

  9. 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

  10. 15 CFR 922.102 - Prohibited or otherwise regulated activities.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

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

  11. Regulation of MDM2 Activity by Nucleolin

    DTIC Science & Technology

    2007-06-01

    p53 (1 ml produced in a wheat germ transcription-coupled in vitro translation system (Pro- mega, Madison, WI, USA)), GST-Mdm2 (400 ng) and 10mg...interaction of the p53 Box V region with the acid domain of Hdm2, activating the Hdm2 ubiquitin ligase activity towards p53. Nucleolin contains three...is located in the N-terminal half of nucleolin, adjacent to the 4th acidic domain. While not extensive, we will test these sequences in future

  12. 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

  13. Fragile phagocytes: FMRP positively regulates engulfment activity.

    PubMed

    Logan, Mary A

    2017-03-06

    Defective immune system function is implicated in autism spectrum disorders, including Fragile X syndrome. In this issue, O'Connor et al. (2017. J. Cell Biol. https://doi.org/10.1083/jcb.201607093) demonstrate that phagocytic activity of systemic immune cells is compromised in a Drosophila melanogaster model of Fragile X, highlighting intriguing new mechanistic connections between FMRP, innate immunity, and abnormal development.

  14. Renalase regulates peripheral and central dopaminergic activities.

    PubMed

    Quelhas-Santos, Janete; 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

    2015-01-15

    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.

  15. 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

  16. Regulation of APC/C activators in mitosis and meiosis.

    PubMed

    Pesin, Jillian A; Orr-Weaver, Terry L

    2008-01-01

    The anaphase-promoting complex/cyclosome (APC/C) is a multisubunit E3 ubiquitin ligase that triggers the degradation of multiple substrates during mitosis. Cdc20/Fizzy and Cdh1/Fizzy-related activate the APC/C and confer substrate specificity through complex interactions with both the core APC/C and substrate proteins. The regulation of Cdc20 and Cdh1 is critical for proper APC/C activity and occurs in multiple ways: targeted protein degradation, phosphorylation, and direct binding of inhibitory proteins. During the specialized divisions of meiosis, the activity of the APC/C must be modified to achieve proper chromosome segregation. Recent studies show that one way in which APC/C activity is modified is through the use of meiosis-specific APC/C activators. Furthermore, regulation of the APC/C during meiosis is carried out by both mitotic regulators of the APC/C as well as meiosis-specific regulators. Here, we review the regulation of APC/C activators during mitosis and the role and regulation of the APC/C during female meiosis.

  17. Temperature Regulator for Actively Cooled Structures

    NASA Technical Reports Server (NTRS)

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

    1995-01-01

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

  18. Regulation and activity of a zinc uptake regulator, Zur, in Corynebacterium diphtheriae.

    PubMed

    Smith, Kelsy F; Bibb, Lori A; Schmitt, Michael P; Oram, Diana M

    2009-03-01

    Regulation of metal ion homeostasis is essential to bacterial cell survival, and in most species it is controlled by metal-dependent transcriptional regulators. In this study, we describe a Corynebacterium diphtheriae ferric uptake regulator-family protein, Zur, that controls expression of genes involved in zinc uptake. By measuring promoter activities and mRNA levels, we demonstrate that Zur represses transcription of three genes (zrg, cmrA, and troA) in zinc-replete conditions. All three of these genes have similarity to genes involved in zinc uptake. Transcription of zrg and cmrA was also shown to be regulated in response to iron and manganese, respectively, by mechanisms that are independent of Zur. We demonstrate that the activity of the zur promoter is slightly decreased under low zinc conditions in a process that is dependent on Zur itself. This regulation of zur transcription is distinctive and has not yet been described for any other zur. An adjacent gene, predicted to encode a metal-dependent transcriptional regulator in the ArsR/SmtB family, is transcribed from a separate promoter whose activity is unaffected by Zur. A C. diphtheriae zur mutant was more sensitive to peroxide stress, which suggests that zur has a role in protecting the bacterium from oxidative damage. Our studies provide the first evidence of a zinc specific transcriptional regulator in C. diphtheriae and give new insights into the intricate regulatory network responsible for regulating metal ion concentrations in this toxigenic human pathogen.

  19. 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.

  20. Scaffolds are 'active' regulators of signaling modules.

    PubMed

    Alexa, Anita; Varga, János; Reményi, Attila

    2010-11-01

    Signaling cascades, in addition to proteins with obvious signaling-relevant activities (e.g. protein kinases or receptors), also employ dedicated 'inactive' proteins whose functions appear to be the organization of the former components into higher order complexes through protein-protein interactions. The core function of signaling adaptors, anchors and scaffolds is the recruitment of proteins into one macromolecular complex. Several recent studies have demonstrated that the recruiter and the recruited molecules mutually influence each other in a scaffolded complex. This yields fundamentally novel properties for the signaling complex as a whole. Because these are not merely additive to the properties of the individual components, scaffolded signaling complexes may behave as functionally distinct modules.

  1. Intricate regulation of tyrosine hydroxylase activity and gene expression.

    PubMed

    Kumer, S C; Vrana, K E

    1996-08-01

    Tyrosine hydroxylase catalyzes the rate-limiting step in the biosynthesis of the catecholamines dopamine, norepinephrine, and epinephrine. Therefore, the regulation of tyrosine hydroxylase enzyme number and intrinsic enzyme activity represents the central means for controlling the synthesis of these important biogenic amines. An intricate scheme has evolved whereby tyrosine hydroxylase activity is modulated by nearly every documented form of regulation. Beginning with the genomic DNA, evidence exists for the transcriptional regulation of tyrosine hydroxylase mRNA levels, alternative RNA processing, and the regulation of RNA stability. There is also experimental support for the role of both translational control and enzyme stability in establishing steady-state levels of active tyrosine hydroxylase protein. Finally, mechanisms have been proposed for feedback inhibition of the enzyme by catecholamine products, allosteric modulation of enzyme activity, and phosphorylation-dependent activation of the enzyme by various different kinase systems. Given the growing literature suggesting that different tissues regulate tyrosine hydroxylase mRNA levels and activity in different ways, regulatory mechanisms provide not only redundancy but also diversity in the control of catecholamine biosynthesis.

  2. Astrocyte Ca2+ Influx Negatively Regulates Neuronal Activity

    PubMed Central

    Ormerod, Kiel G.

    2017-01-01

    Abstract Maintenance of neural circuit activity requires appropriate regulation of excitatory and inhibitory synaptic transmission. Recently, glia have emerged as key partners in the modulation of neuronal excitability; however, the mechanisms by which glia regulate neuronal signaling are still being elucidated. Here, we describe an analysis of how Ca2+ signals within Drosophila astrocyte-like glia regulate excitability in the nervous system. We find that Drosophila astrocytes exhibit robust Ca2+ oscillatory activity manifested by fast, recurrent microdomain Ca2+ fluctuations within processes that infiltrate the synaptic neuropil. Unlike the enhanced neuronal activity and behavioral seizures that were previously observed during manipulations that trigger Ca2+ influx into Drosophila cortex glia, we find that acute induction of astrocyte Ca2+ influx leads to a rapid onset of behavioral paralysis and a suppression of neuronal activity. We observe that Ca2+ influx triggers rapid endocytosis of the GABA transporter (GAT) from astrocyte plasma membranes, suggesting that increased synaptic GABA levels contribute to the neuronal silencing and paralysis. We identify Rab11 as a novel regulator of GAT trafficking that is required for this form of activity regulation. Suppression of Rab11 function strongly offsets the reduction of neuronal activity caused by acute astrocyte Ca2+ influx, likely by inhibiting GAT endocytosis. Our data provide new insights into astrocyte Ca2+ signaling and indicate that distinct glial subtypes in the Drosophila brain can mediate opposing effects on neuronal excitability. PMID:28303263

  3. 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

  4. Mitophagy: a balance regulator of NLRP3 inflammasome activation

    PubMed Central

    Kim, Min-Ji; Yoon, Joo-Heon; Ryu, Ji-Hwan

    2016-01-01

    The NLRP3 inflammasome is activated by a variety of external or host-derived stimuli and its activation initiates an inflammatory response through caspase-1 activation, resulting in inflammatory cytokine IL-1β maturation and secretion. The NLRP3 inflammasome activation is a kind of innate immune response, most likely mediated by myeloid cells acting as a host defense mechanism. However, if this activation is not properly regulated, excessive inflammation induced by overactivated NLRP3 inflammasome can be detrimental to the host, causing tissue damage and organ dysfunction, eventually causing several diseases. Previous studies have suggested that mitochondrial damage may be a cause of NLRP3 inflammasome activation and autophagy, which is a conserved self-degradation process that negatively regulates NLRP3 inflammasome activation. Recently, mitochondria-selective autophagy, termed mitophagy, has emerged as a central player for maintaining mitochondrial homeostasis through the elimination of damaged mitochondria, leading to the prevention of hyperinflammation triggered by NLRP3 inflammasome activation. In this review, we will first focus on the molecular mechanisms of NLRP3 inflammasome activation and NLRP3 inflammasome-related diseases. We will then discuss autophagy, especially mitophagy, as a negative regulator of NLPP3 inflammasome activation by examining recent advances in research. [BMB Reports 2016; 49(10): 529-535] PMID:27439607

  5. 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…

  6. 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.

  7. Tbx16 regulates hox gene activation in mesodermal progenitor cells

    PubMed Central

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

    2016-01-01

    The transcription factor T-box 16 (Tbx16/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. The mechanisms by which Tbx16 controls mesoderm patterning have remained enigmatic, and we describe here the application of photoactivatable morpholino oligonucleotides to determine the Tbx16 transcriptome in MPCs. We identify 124 Tbx16-regulated genes that are expressed in zebrafish gastrulae, including several developmental signaling proteins and regulators of gastrulation, myogenesis, and somitogenesis. Unexpectedly, we observe that loss of Tbx16 function precociously activates posterior hox genes in MPCs, and overexpression of a single posterior hox gene is 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. Prolyl isomerase Pin1 regulates the osteogenic activity of Osterix.

    PubMed

    Lee, Sung Ho; Jeong, Hyung Min; Han, Younho; Cheong, Heesun; Kang, Bok Yun; Lee, Kwang Youl

    2015-01-15

    Osterix is an essential transcription factor for osteoblast differentiation and bone formation. The mechanism of regulation of Osterix by post-translational modification remains unknown. Peptidyl-prolyl isomerase 1 (Pin1) catalyzes the isomerization of pSer/Thr-Pro bonds and induces a conformational change in its substrates, subsequently regulating diverse cellular processes. In this study, we demonstrated that Pin1 interacts with Osterix and influences its protein stability and transcriptional activity. This regulation is likely due to the suppression of poly-ubiquitination-mediated proteasomal degradation of Osterix. Collectively, our data demonstrate that Pin1 is a novel regulator of Osterix and may play an essential role in the regulation of osteogenic differentiation.

  9. 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…

  10. Regulation of ligands for the NKG2D activating receptor

    PubMed Central

    Raulet, David H.; Gasser, Stephan; Gowen, Benjamin G.; Deng, Weiwen; Jung, Heiyoun

    2014-01-01

    NKG2D is an activating receptor expressed by all NK cells and subsets of T cells. It serves as a major recognition receptor for detection and elimination of transformed and infected cells and participates in the genesis of several inflammatory diseases. The ligands for NKG2D are self-proteins that are induced by pathways that are active in certain pathophysiological states. NKG2D ligands are regulated transcriptionally, at the level of mRNA and protein stability, and by cleavage from the cell surface. In some cases, ligand induction can be attributed to pathways that are activated specifically in cancer cells or infected cells. We review the numerous pathways that have been implicated in the regulation of NKG2D ligands, discuss the pathologic states in which those pathways are likely to act, and attempt to synthesize the findings into general schemes of NKG2D ligand regulation in NK cell responses to cancer and infection. PMID:23298206

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

    PubMed

    Roby, Jini L; White, Holly

    2010-07-01

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

  12. Sirtuin 4 is a lipoamidase regulating pyruvate dehydrogenase complex activity

    PubMed Central

    Mathias, Rommel A.; Greco, Todd M.; Oberstein, Adam; Budayeva, Hanna G.; Chakrabarti, Rumela; Rowland, Elizabeth A.; Kang, Yibin; Shenk, Thomas; Cristea, Ileana M.

    2014-01-01

    Summary Sirtuins (SIRTs) are critical enzymes that govern genome regulation, metabolism, and aging. Despite conserved deacetylase domains, mitochondrial SIRT4 and SIRT5 have little to no deacetylase activity, and a robust catalytic activity for SIRT4 has been elusive. Here, we establish SIRT4 as a cellular lipoamidase that regulates the pyruvate dehydrogenase complex (PDH). Importantly, SIRT4 catalytic efficiency for lipoyl- and biotinyl-lysine modifications is superior to its deacetylation activity. PDH, which converts pyruvate to acetyl-CoA, has been known to be primarily regulated by phosphorylation of its E1 component. We determine that SIRT4 enzymatically hydrolyzes the lipoamide cofactors from the E2 component dihydrolipoyllysine acetyltransferase (DLAT), diminishing PDH activity. We demonstrate SIRT4-mediated regulation of DLAT lipoyl levels and PDH activity in cells and in vivo, in mouse liver. Furthermore, metabolic flux switching via glutamine stimulation induces SIRT4 lipoamidase activity to inhibit PDH, highlighting SIRT4 as a guardian of cellular metabolism. PMID:25525879

  13. Akt phosphorylates and regulates the osteogenic activity of Osterix.

    PubMed

    Choi, You Hee; Jeong, Hyung Min; Jin, Yun-Hye; Li, Hongyan; Yeo, Chang-Yeol; Lee, Kwang-Youl

    2011-08-05

    Osterix (Osx), a zinc-finger transcription factor is required for osteoblast differentiation and new bone formation during embryonic development. Akt is a member of the serine/threonine-specific protein kinase and plays important roles in osteoblast differentiation. The function of Osterix can be also modulated by post-translational modification. But, the precise molecular signaling mechanisms between Osterix and Akt are not known. In this study, we investigated the potential regulation of Osterix function by Akt in osteoblast differentiation. We found that Akt phosphorylates Osterix and that Akt activation increases protein stability, osteogenic activity and transcriptional activity of Osterix. We also found that BMP-2 increases the protein level of Osterix in an Akt activity-dependent manner. These results suggest that Akt activity enhances the osteogenic function of Osterix, at least in part, through protein stabilization and that BMP-2 regulates the osteogenic function of Osterix, at least in part, through Akt.

  14. Wisconsin statutes regarding HIV testing in primary care: frequent questions and answers.

    PubMed

    Vergeront, J M; Reiser, W J; Druckenmiller, J K; Krchnavek, K A; Davis, J P

    1998-12-01

    The authors review Wisconsin statutes related to human immunodeficiency virus (HIV) testing in primary care, including the areas of written informed consent, documentation of consent, testing without consent, testing of minors, disclosure of test results without the consent of the test subject, reporting requirements, discrimination, access by insurance companies and third-party payors to HIV test results, and civil liabilities and criminal penalties associated with violation of HIV-related state statutes. During the course of the HIV epidemic in Wisconsin, many individuals (service providers, legislators, consumers and advocates) supported the enactment of HIV-related legislation. Today, Wisconsin has some of the nation's most comprehensive HIV legislation. These laws have set a legal framework that balances the rights of individuals with protection of public's health. The relatively low seroprevalence of HIV infection in Wisconsin can be attributed, in part, to the state's HIV-related legislation. While Wisconsin HIV legislation is broadly focused, much of it is concerned with HIV testing. This article examines common questions as they pertain to HIV testing in primary care and to the following areas addressed by state statutes: counseling and referral for health and support services [Wisconsin statute s. 252 14(3)] informed consent for testing or disclosure [Wisconsin statute s. 252.15(2)] written consent to disclose [Wisconsin statute s. 252.15(3) & (4)] testing without consent of the test subject [Wisconsin statute s. 252.15(2)] confidentiality of an HIV test [Wisconsin statute s. 252.15(5)] reporting of positive test results [Wisconsin statute s. 252.15(7)] discrimination [Wisconsin statute s. 252.14(2)] civil and criminal liabilities [Wisconsin statute s. 252.14(4); 252.15(8) & (9)].

  15. Activation of ion transport systems during cell volume regulation

    SciTech Connect

    Eveloff, J.L.; Warnock, D.G.

    1987-01-01

    This review discusses the activation of transport pathways during volume regulation, including their characteristics, the possible biochemical pathways that may mediate the activation of transport pathways, and the relations between volume regulation and transepithelial transport in renal cells. Many cells regulate their volume when exposed to an anisotonic medium. The changes in cell volume are caused by activation of ion transport pathways, plus the accompanying osmotically driven water movement such that cell volume returns toward normal levels. The swelling of hypertonically shrunken cells is termed regulatory volume increase (RVI) and involves an influx of NaCl into the cell via either activation of Na-Cl, Na-K-2Cl cotransport systems, or Na/sup +/-H/sup +/ and Cl/sup -/-HCO/sub 3//sup -/ exchangers. The reshrinking of hypotonically swollen cells is termed regulatory volume decrease (RVD) and involves an efflux of KCl and water from the cell by activation of either separate K/sup +/ and Cl/sup -/ conductances, a K-Cl cotransport system, or parallel K/sup +/-H/sup +/ and Cl/sup -/-HCO/sub 3//sup -/ exchangers. The biochemical mechanisms involved in the activation of transport systems are largely unknown, however, the phosphoinositide pathway may be implicated in RVI; phorbol esters, cGMP, and Ca/sup 2 +/ affect the process of volume regulation. Renal tubular cells, as well as the blood cells that transverse the medulla, are subjected to increasing osmotic gradients from the corticomedullary junction to the papillary tip, as well as changing interstitial and tubule fluid osmolarity, depending on the diuretic state of the animal. Medullary cells from the loop of Henle and the papilla can volume regulate by activating Na-K-2Cl cotransport or Na/sup +/-H/sup +/ and Cl/sup -/-HCO/sub 3//sup -/ exchange systems.

  16. 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.

  17. 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

  18. Differential regulation of neocortical synapses by neuromodulators and activity.

    PubMed

    Gil, Z; Connors, B W; Amitai, Y

    1997-09-01

    Synapses are continually regulated by chemical modulators and by their own activity. We tested the specificity of regulation in two excitatory pathways of the neocortex: thalamocortical (TC) synapses, which mediate specific inputs, and intracortical (IC) synapses, which mediate the recombination of cortical information. Frequency-sensitive depression was much stronger in TC synapses than in IC synapses. The two synapse types were differentially sensitive to presynaptic neuromodulators: only IC synapses were suppressed by activation of GABA(B) receptors, only TC synapses were enhanced by nicotinic acetylcholine receptors, and muscarinic acetylcholine receptors suppressed both synapse types. Modulators also differentially altered the frequency sensitivity of the synapses. Our results suggest a mechanism by which the relative strength and dynamics of input and associational pathways of neocortex are regulated during changes in behavioral state.

  19. Active galactic nuclei activity: self-regulation from backflow

    NASA Astrophysics Data System (ADS)

    Antonuccio-Delogu, V.; Silk, Joseph

    2010-06-01

    We study the internal circulation within the cocoon carved out by the relativistic jet emanating from an active galactic nucleus (AGN) within the interstellar medium (ISM) of its host galaxy. First, we develop a model for the origin of the internal flow, noticing that a significant increase of large-scale velocity circulation within the cocoon arises as significant gradients in the density and entropy are created near the hotspot (a consequence of Crocco's vorticity generation theorem). We find simple and accurate approximate solutions for the large-scale flow, showing that a backflow towards the few inner parsec region develops. We solve the appropriate fluid dynamic equations, and we use these solutions to predict the mass inflow rates towards the central regions. We then perform a series of 2D simulations of the propagation of jets using FLASH 2.5, in order to validate the predictions of our model. In these simulations, we vary the mechanical input power between 1043 and 1045 ergs-1, and assume a Navarro-Frenk-White (NFW) density profile for the dark matter halo, within which an isothermal diffuse ISM is embedded. The backflows which arise supply the central AGN region with very low angular-momentum gas, at average rates of the order of , the exact value seen to be strongly dependent on the central ISM density (for fixed input jet power). The time-scales of these inflows are apparently weakly dependent on the jet/ISM parameters, and are of the order of . We then argue that these backflows could (at least partially) feed the AGN, and provide a self-regulatory mechanism of AGN activity, that is not directly controlled by, but instead controls, the star formation rate within the central circumnuclear disc.

  20. Regulation of p53 and MDM2 activity by MTBP.

    PubMed

    Brady, Mark; Vlatkovic, Nikolina; Boyd, Mark T

    2005-01-01

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

  1. 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

  2. Neuronal Activity Regulates Hippocampal miRNA Expression

    PubMed Central

    Eacker, Stephen M.; Keuss, Matthew J.; Berezikov, Eugene; Dawson, Valina L.; Dawson, Ted M.

    2011-01-01

    Neuronal activity regulates a broad range of processes in the hippocampus, including the precise regulation of translation. Disruptions in proper translational control in the nervous system are associated with a variety of disorders that fall in the autistic spectrum. MicroRNA (miRNA) represent a relatively recently discovered player in the regulation of translation in the nervous system. We have conducted an in depth analysis of how neuronal activity regulates miRNA expression in the hippocampus. Using deep sequencing we exhaustively identify all miRNAs, including 15 novel miRNAs, expressed in hippocampus of the adult mouse. We identified 119 miRNAs documented in miRBase but less than half of these miRNA were expressed at a level greater than 0.1% of total miRNA. Expression profiling following induction of neuronal activity by electroconvulsive shock demonstrates that most miRNA show a biphasic pattern of expression: rapid induction of specific mature miRNA expression followed by a decline in expression. These results have important implications into how miRNAs influence activity-dependent translational control. PMID:21984899

  3. Using Regulation Activities to Improve Undergraduate Collaborative Writing on Wikis

    ERIC Educational Resources Information Center

    Cho, Moon-Heum; Lim, Seongmi

    2017-01-01

    Although wikis have been widely adopted to support collaborative writing in undergraduate classrooms, educators remain concerned about the level of student participation. Using regulation theories to design interventions in the form of activities, we examined their effects on collaborative writing on wikis. Results demonstrate that with the…

  4. 76 FR 28801 - Agency Information Collection Activities: Bonded Warehouse Regulations

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-05-18

    ... 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 proposed..., mechanical, or other technological techniques or other forms of information. Title: Bonded...

  5. Regulation of Sodium Channel Activity by Capping of Actin Filaments

    PubMed Central

    Shumilina, Ekaterina V.; Negulyaev, Yuri A.; Morachevskaya, Elena A.; Hinssen, Horst; Khaitlina, Sofia Yu

    2003-01-01

    Ion transport in various tissues can be regulated by the cortical actin cytoskeleton. Specifically, involvement of actin dynamics in the regulation of nonvoltage-gated sodium channels has been shown. Herein, inside-out patch clamp experiments were performed to study the effect of the heterodimeric actin capping protein CapZ on sodium channel regulation in leukemia K562 cells. The channels were activated by cytochalasin-induced disruption of actin filaments and inactivated by G-actin under ionic conditions promoting rapid actin polymerization. CapZ had no direct effect on channel activity. However, being added together with G-actin, CapZ prevented actin-induced channel inactivation, and this effect occurred at CapZ/actin molar ratios from 1:5 to 1:100. When actin was allowed to polymerize at the plasma membrane to induce partial channel inactivation, subsequent addition of CapZ restored the channel activity. These results can be explained by CapZ-induced inhibition of further assembly of actin filaments at the plasma membrane due to the modification of actin dynamics by CapZ. No effect on the channel activity was observed in response to F-actin, confirming that the mechanism of channel inactivation does not involve interaction of the channel with preformed filaments. Our data show that actin-capping protein can participate in the cytoskeleton-associated regulation of sodium transport in nonexcitable cells. PMID:12686620

  6. [Regulation of myostatin promoter activity by myocyte enhancer factor 2].

    PubMed

    Li, Jia; Deng, Jie; Zhang, Junlin; Cheng, De; Wang, Huayan

    2012-08-01

    Myostatin (Mstn) is a member of the transforming growth factor-beta superfamily that functions as a negative regulator of skeletal muscle growth and differentiation in mammals. The transcriptional regulation of Mstn is controlled by multiple genes including MEF2, which raise the importance of identifying the binding sites of MEF2 on myostatin promoter region and mechanisms underlying. In this study, we investigated the transcriptional regulation of MEF2 on porcine Mstn promoter activity in C2C12 cells. Sequence analysis of the 1 969 bp porcine Mstn promoter region revealed that it contained three potential MEF2 motifs. Using a serial deletion strategy, we tested the activity of several promoter fragments by luciferase assay. Overexpression of MEF2C, but not MEF2A increased Mstn promoter activity in all the promoter fragments with MEF2 motifs by two to six folds, in both C2C12 myoblasts and myotubes. When we transfected exogenous MEF2C, Mstn mRNA level was also upregulated in C2C12 cells, but the protein level was only significantly increased in myotubes. Thus, we propose that MEF2C could modulate and restrain myogenesis by Mstn activation and Mstn-dependent gene processing in porcine. Our research also provided potential targets and an effective molecule to regulate Mstn expression and gave a new way to explore the functional performance of Mstn.

  7. 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...

  8. 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...

  9. 45 CFR 30.4 - Compromise, waiver, or disposition under other statutes not precluded.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 45 Public Welfare 1 2012-10-01 2012-10-01 false Compromise, waiver, or disposition under other statutes not precluded. 30.4 Section 30.4 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL... States Code and the Federal Claims Collection Standards, 31 CFR parts 900 through 904. Any statute...

  10. 45 CFR 30.4 - Compromise, waiver, or disposition under other statutes not precluded.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 45 Public Welfare 1 2010-10-01 2010-10-01 false Compromise, waiver, or disposition under other statutes not precluded. 30.4 Section 30.4 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL... States Code and the Federal Claims Collection Standards, 31 CFR parts 900 through 904. Any statute...

  11. 29 CFR 70.39 - Statutes specifically providing for setting of fees.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 29 Labor 1 2012-07-01 2012-07-01 false Statutes specifically providing for setting of fees. 70.39... Costs for Production of Records § 70.39 Statutes specifically providing for setting of fees. This... an agency to set and collect fees for particular types of records....

  12. 29 CFR 70.39 - Statutes specifically providing for setting of fees.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 29 Labor 1 2011-07-01 2011-07-01 false Statutes specifically providing for setting of fees. 70.39... Costs for Production of Records § 70.39 Statutes specifically providing for setting of fees. This... an agency to set and collect fees for particular types of records....

  13. 38 CFR 1.468 - Relationship to Federal statutes protecting research subjects against compulsory disclosure of...

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2012-07-01 2012-07-01 false Relationship to Federal statutes protecting research subjects against compulsory disclosure of their identity. 1.468 Section 1.468... to Federal statutes protecting research subjects against compulsory disclosure of their identity....

  14. 38 CFR 1.468 - Relationship to Federal statutes protecting research subjects against compulsory disclosure of...

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2014-07-01 2014-07-01 false Relationship to Federal statutes protecting research subjects against compulsory disclosure of their identity. 1.468 Section 1.468... to Federal statutes protecting research subjects against compulsory disclosure of their identity....

  15. 38 CFR 1.468 - Relationship to Federal statutes protecting research subjects against compulsory disclosure of...

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2013-07-01 2013-07-01 false Relationship to Federal statutes protecting research subjects against compulsory disclosure of their identity. 1.468 Section 1.468... to Federal statutes protecting research subjects against compulsory disclosure of their identity....

  16. 40 CFR 35.935-5 - Davis-Bacon and related statutes.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 1 2013-07-01 2013-07-01 false Davis-Bacon and related statutes. 35... § 35.935-5 Davis-Bacon and related statutes. Before soliciting bids or proposals for step 3-type work, the grantee must consult with the Regional Administrator concerning compliance with Davis-Bacon...

  17. 40 CFR 35.935-5 - Davis-Bacon and related statutes.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 1 2011-07-01 2011-07-01 false Davis-Bacon and related statutes. 35... § 35.935-5 Davis-Bacon and related statutes. Before soliciting bids or proposals for step 3-type work, the grantee must consult with the Regional Administrator concerning compliance with Davis-Bacon...

  18. 40 CFR 35.935-5 - Davis-Bacon and related statutes.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 1 2012-07-01 2012-07-01 false Davis-Bacon and related statutes. 35... § 35.935-5 Davis-Bacon and related statutes. Before soliciting bids or proposals for step 3-type work, the grantee must consult with the Regional Administrator concerning compliance with Davis-Bacon...

  19. 40 CFR 35.935-5 - Davis-Bacon and related statutes.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 1 2010-07-01 2010-07-01 false Davis-Bacon and related statutes. 35... § 35.935-5 Davis-Bacon and related statutes. Before soliciting bids or proposals for step 3-type work, the grantee must consult with the Regional Administrator concerning compliance with Davis-Bacon...

  20. 40 CFR 35.935-5 - Davis-Bacon and related statutes.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 1 2014-07-01 2014-07-01 false Davis-Bacon and related statutes. 35... § 35.935-5 Davis-Bacon and related statutes. Before soliciting bids or proposals for step 3-type work, the grantee must consult with the Regional Administrator concerning compliance with Davis-Bacon...

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

    PubMed

    Sheehan, James G; Goldner, Jesse A

    2007-01-01

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

  2. 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.

  3. Self-regulated homoclinic chaos in neural networks activity

    NASA Astrophysics Data System (ADS)

    Volman, Vladislav; Baruchi, Itay; Ben-Jacob, Eshel

    2004-12-01

    We compare the recorded activity of cultured neuronal networks with hybridized model simulations, in which the model neurons are driven by the recorded activity of special neurons. The latter, named `spiker' neurons, that exhibit fast firing with homoclinic chaos like characteristics, are expected to play an important role in the networks' self regulation. The cultured networks are grown from dissociated mixtures of cortical neurons and glia cells. Despite the artificial manner of their construction, the spontaneous activity of these networks exhibits rich dynamical behavior, marked by the formation of temporal sequences of synchronized bursting events (SBEs), and additional features which seemingly reflect the action of underlying regulating mechanism, rather than arbitrary causes and effects. Our model neurons are composed of soma described by the two Morris-Lecar dynamical variables (voltage and fraction of open potassium channels), with dynamical synapses described by the Tsodyks-Markram three variables dynamics. To study the recorded and simulated activities we evaluated the inter-neuron correlation matrices, and analyzed them utilizing the functional holography approach: the correlations are re-normalized by the correlation distances — Euclidean distances between the matrix columns. Then, we project the N-dimensional (for N channels) space spanned by the matrix of re-normalized correlations, or correlation affinities, onto a corresponding 3-D causal manifold (3-D Cartesian space constructed by the 3 leading principal vectors of the N-dimensional space. The neurons are located by their principal eigenvalues and linked by their original (not-normalized) correlations. This reveals hidden causal motifs: the neuron locations and their links form simple structures. Similar causal motifs are exhibited by the model simulations when feeded by the recorded activity of the spiker neurons. We illustrate that the homoclinic chaotic behavior of the spiker neurons can be

  4. 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.

  5. DEC1 negatively regulates AMPK activity via LKB1

    PubMed Central

    Sato, Fuyuki; Muragaki, Yasuteru; Zhang, Yanping

    2016-01-01

    Basic helix-loop-helix (bHLH) transcription factor DEC1 (bHLHE40/Stra13/Sharp2) is one of the clock genes that show a circadian rhythm in various tissues. AMP-activated protein kinase (AMPK) activity plays important roles in the metabolic process and in cell death induced by glucose depletion. Recent reports have shown that AMPK activity exhibited a circadian rhythm. However, little is known regarding the regulatory mechanisms involved in the circadian rhythm of AMPK activity. The aim of this study is to investigate whether there is a direct correlation between DEC1 expression and AMPK activity. DEC1 protein and AMPK activity showed a circadian rhythm in the mouse liver with different peak levels. Knocking down DEC1 expression increased AMPK activity, whereas overexpression of DEC1 decreased it. Overexpressing the DEC1 basic mutants had little effect on the AMPK activity. DEC1 bound to the E-box of the LKB1 promoter, decreased LKB1 activity and total protein levels. There was an inverse relationship between DEC1 expression and AMPK activity. Our results suggest that DEC1 negatively regulates AMPK activity via LKB1. PMID:26498531

  6. Regulation of tissue factor coagulant activity on cell surfaces

    PubMed Central

    RAO, L.V.M.; PENDURTHI, U.R.

    2012-01-01

    Summary Tissue factor (TF) is a transmembrane glycoprotein and an essential component of factor VIIa-TF enzymatic complex that triggers activation of the coagulation cascade. Formation of TF-FVIIa complexes on cell surfaces not only trigger the coagulation cascade but also transduce cell signaling via activation of protease-activated receptors. Tissue factor is expressed constitutively on cell surfaces of a variety of extravascular cell types, including fibroblasts and pericytes in and surrounding blood vessel walls and epithelial cells but generally absent on cells that come in contact with blood directly. However, TF expression could be induced in some blood cells, such as monocytes and endothelial cells, following an injury or pathological stimuli. Tissue factor is essential for hemostasis, but aberrant expression of TF leads to thrombosis. Therefore, a proper regulation of TF activity is critical for the maintenance of hemostatic balance and health in general. TF-FVIIa coagulant activity at the cell surface is influenced not only by TF protein expression levels but also independently by a variety of mechanisms, including alterations in membrane phospholipid composition and cholesterol content, thiol-dependent modifications of TF allosteric disulfide bond, and other post-translational modifications of TF. In this article, we critically review key literature on mechanisms by which TF coagulant activity is regulated at the cell surface in the absence of changes in TF protein levels with specific emphasis on recently published data and provide the authors’ perspective on the subject. PMID:23006890

  7. Activity-Regulated Genes as Mediators of Neural Circuit Plasticity

    PubMed Central

    Leslie, Jennifer H.; Nedivi, Elly

    2011-01-01

    Modifications of neuronal circuits allow the brain to adapt and change with experience. This plasticity manifests during development and throughout life, and can be remarkably long lasting. Many electrophysiological and molecular mechanisms are common to the seemingly diverse types of activity-dependent functional adaptation that take place during developmental critical periods, learning and memory, and alterations to sensory map representations in the adult. Experience-dependent plasticity is triggered when neuronal excitation activates cellular signaling pathways from the synapse to the nucleus that initiate new programs of gene expression. The protein products of activity-regulated genes then work via a diverse array of cellular mechanisms to modify neuronal functional properties. They fine-tune brain circuits by strengthening or weakening synaptic connections or by altering synapse numbers. Their effects are further modulated by posttranscriptional regulatory mechanisms, often also dependent on activity, that control activity-regulated gene transcript and protein function. Thus, the cellular response to neuronal activity integrates multiple tightly coordinated mechanisms to precisely orchestrate long-lasting, functional and structural changes in brain circuits. PMID:21601615

  8. A network model for activity-dependent sleep regulation.

    PubMed

    Roy, Sandip; Krueger, James M; Rector, David M; Wan, Yan

    2008-08-07

    We develop and characterize a dynamical network model for activity-dependent sleep regulation. Specifically, in accordance with the activity-dependent theory for sleep, we view organism sleep as emerging from the local sleep states of functional units known as cortical columns; these local sleep states evolve through integration of local activity inputs, loose couplings with neighboring cortical columns, and global regulation (e.g. by the circadian clock). We model these cortical columns as coupled or networked activity-integrators that transition between sleep and waking states based on thresholds on the total activity. The model dynamics for three canonical experiments (which we have studied both through simulation and system-theoretic analysis) match with experimentally observed characteristics of the cortical-column network. Most notably, assuming connectedness of the network graph, our model predicts the recovery of the columns to a synchronized state upon temporary overstimulation of a single column and/or randomization of the initial sleep and activity-integration states. In analogy with other models for networked oscillators, our model also predicts the possibility for such phenomena as mode-locking.

  9. Regulation of glucokinase activity in the domestic fowl.

    PubMed

    Klandorf, H; Clarke, B L; Scheck, A C; Brown, J

    1986-09-30

    The factors which regulate soluble and particulate glucokinase and hexokinase activity in the liver of domestic chickens has been investigated. Pretreatment with oral administration (via tube feeding) of glucose plus injection of insulin resulted in a significant increase in the activity of soluble (p less than 0.01) and particulate (p less than 0.01) glucokinase activity whereas fasting for 48 hours reduced glucokinase and hexokinase activity (p less than 0.01) in the particulate fraction only. Treatment of fed chickens for 2 weeks with thyroxine (50 micrograms: i.m. daily) plus triiodothyronine (50 micrograms) resulted in a marginal decrease (NS) in soluble glucokinase activity but significantly increased soluble hexokinase (p less than 0.05) activity. Thyroidectomized animals showed a decline in both soluble glucokinase (p less than 0.01) and hexokinase (p less than 0.025) activity. There was no effect of thyroid hormone manipulation on particulate glucokinase activity although there was a significant reduction in particulate hexokinase activity (p less than 0.05) in thyroidectomized birds. These data establish a physiological role for the glucokinase enzyme activity in avian carbohydrate metabolism and suggest that in contrast with the mammal, the particulate fraction is the more physiologically important enzyme.

  10. Neuronal activity-induced regulation of Lingo-1.

    PubMed

    Trifunovski, Alexandra; Josephson, Anna; Ringman, Andreas; Brené, Stefan; Spenger, Christian; Olson, Lars

    2004-10-25

    Axonal regeneration after injury can be limited in the adult CNS by the presence of inhibitory proteins such as Nogo. Nogo binds to a receptor complex that consists of Nogo receptor (NgR), p75NTR, and Lingo-1. Nogo binding activates RhoA, which inhibits axonal outgrowth. Here we assessed Lingo-1 and NgR mRNA levels after delivery of BDNF into the rat hippocampal formation, Lingo-1 mRNA levels in rats subjected to kainic acid (KA) and running in running wheels. Lingo-1 mRNA was not changed by running. However, we found that Lingo-1 mRNA was strongly up-regulated while NgR mRNA was down-regulated in the dentate gyrus in both the BDNF and the KA experiments. Our data demonstrate inverse regulation of NgR and Lingo-1 in these situations, suggesting that Lingo-1 up-regulation is one characteristic of activity-induced neural plasticity responses.

  11. Protein kinase A regulates the osteogenic activity of Osterix.

    PubMed

    He, Siyuan; Choi, You Hee; Choi, Joong-Kook; Yeo, Chang-Yeol; Chun, ChangJu; Lee, Kwang Youl

    2014-10-01

    Osterix belongs to the SP gene family and is a core transcription factor responsible for osteoblast differentiation and bone formation. Activation of protein kinase A (PKA), a serine/threonine kinase, is essential for controlling bone formation and BMP-induced osteoblast differentiation. However, the relationship between Osterix and PKA is still unclear. In this report, we investigated the precise role of the PKA pathway in regulating Osterix during osteoblast differentiation. We found that PKA increased the protein level of Osterix; PKA phosphorylated Osterix, increased protein stability, and enhanced the transcriptional activity of Osterix. These results suggest that Osterix is a novel target of PKA, and PKA modulates osteoblast differentiation partially through the regulation of Osterix.

  12. 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.

  13. PLAP-1/Asporin Positively Regulates FGF-2 Activity.

    PubMed

    Awata, T; Yamada, S; Tsushima, K; Sakashita, H; Yamaba, S; Kajikawa, T; Yamashita, M; Takedachi, M; Yanagita, M; Kitamura, M; Murakami, S

    2015-10-01

    PLAP-1 is an extracellular matrix protein that is predominantly expressed in the periodontal ligament within periodontal tissue. It was previously revealed that PLAP-1 negatively regulates bone morphogenetic protein 2 and transforming growth factor β activity through direct interactions. However, the interaction between PLAP-1 and other growth factors has not been defined. Here, we revealed that PLAP-1 positively regulates the activity of fibroblast growth factor 2 (FGF-2), a critical growth factor in tissue homeostasis and repair. In this study, we isolated mouse embryonic fibroblasts (MEFs) from Plap-1(-/-) mice generated in our laboratory. Interestingly, Plap-1(-/-) MEFs exhibited enhanced responses to bone morphogenetic protein 2 but defective responses to FGF-2, and Plap-1 transfection into Plap-1(-/-) MEFs rescued these defective responses. In addition, binding assays revealed that PLAP-1 promotes FGF-2-FGF receptor 1 (FGFR1) complex formation by direct binding to FGF-2. Immunocytochemistry analyses revealed colocalization of PLAP-1 and FGF-2 in wild-type MEFs and reduced colocalization of FGF-2 and FGFR1 in Plap-1(-/-) MEFs compared with wild-type MEFs. Taken together, PLAP-1 positively regulates FGF-2 activity through a direct interaction. Extracellular matrix-growth factor interactions have considerable effects; thus, this approach may be useful in several regenerative medicine applications.

  14. The regulation of AMP-activated protein kinase by phosphorylation.

    PubMed Central

    Stein, S C; Woods, A; Jones, N A; Davison, M D; Carling, D

    2000-01-01

    The AMP-activated protein kinase (AMPK) cascade is activated by an increase in the AMP/ATP ratio within the cell. AMPK is regulated allosterically by AMP and by reversible phosphorylation. Threonine-172 within the catalytic subunit (alpha) of AMPK (Thr(172)) was identified as the major site phosphorylated by the AMP-activated protein kinase kinase (AMPKK) in vitro. We have used site-directed mutagenesis to study the role of phosphorylation of Thr(172) on AMPK activity. Mutation of Thr(172) to an aspartic acid residue (T172D) in either alpha1 or alpha2 resulted in a kinase complex with approx. 50% the activity of the corresponding wild-type complex. The activity of wild-type AMPK decreased by greater than 90% following treatment with protein phosphatases, whereas the activity of the T172D mutant complex fell by only 10-15%. Mutation of Thr(172) to an alanine residue (T172A) almost completely abolished kinase activity. These results indicate that phosphorylation of Thr(172) accounts for most of the activation by AMPKK, but that other sites are involved. In support of this we have shown that AMPKK phosphorylates at least two other sites on the alpha subunit and one site on the beta subunit. Furthermore, we provide evidence that phosphorylation of Thr(172) may be involved in the sensitivity of the AMPK complex to AMP. PMID:10642499

  15. Regulation of eNOS enzyme activity by posttranslational modification.

    PubMed

    Heiss, Elke H; Dirsch, Verena M

    2014-01-01

    The regulation of endothelial NO synthase (eNOS) employs multiple different cellular control mechanisms impinging on level and activity of the enzyme. This review aims at summarizing the current knowledge on the posttranslational modifications of eNOS, including acylation, nitrosylation, phosphorylation, acetylation, glycosylation and glutathionylation. Sites, mediators and impact on enzyme localization and activity of the single modifications will be discussed. Moreover, interdependence, cooperativity and competition between the different posttranslational modifications will be elaborated with special emphasis on the susceptibility of eNOS to metabolic cues.

  16. Length regulation of active biopolymers by molecular motors.

    PubMed

    Johann, Denis; Erlenkämper, Christoph; Kruse, Karsten

    2012-06-22

    For biopolymers like cytoskeletal actin filaments and microtubules, assembly and disassembly are inherently dissipative processes. Molecular motors can affect the rates of subunit removal at filament ends. We introduce a driven lattice-gas model to study the effects of motor-induced depolymerization on the length of active biopolymers and find that increasing motor activity sharpens unimodal steady-state length distributions. Furthermore, for sufficiently fast moving motors, the relative width of the length distribution is determined only by the attachment rate of motors. Our results show how established molecular processes can be used to robustly regulate the size of cytoskeletal structures like mitotic spindles.

  17. MERTK as negative regulator of human T cell activation

    PubMed Central

    Cabezón, Raquel; Carrera-Silva, E. Antonio; Flórez-Grau, Georgina; Errasti, Andrea E.; Calderón-Gómez, Elisabeth; Lozano, Juan José; España, Carolina; Ricart, Elena; Panés, Julián; Rothlin, Carla Vanina; Benítez-Ribas, Daniel

    2015-01-01

    The aim of this study was to test the hypothesis whether MERTK, which is up-regulated in human DCs treated with immunosuppressive agents, is directly involved in modulating T cell activation. MERTK is a member of the TAM family and contributes to regulating innate immune response to ACs by inhibiting DC activation in animal models. However, whether MERTK interacts directly with T cells has not been addressed. Here, we show that MERTK is highly expressed on dex-induced human tol-DCs and participates in their tolerogenic effect. Neutralization of MERTK in allogenic MLR, as well as autologous DC–T cell cultures, leads to increased T cell proliferation and IFN-γ production. Additionally, we identify a previously unrecognized noncell-autonomous regulatory function of MERTK expressed on DCs. Mer-Fc protein, used to mimic MERTK on DCs, suppresses naïve and antigen-specific memory T cell activation. This mechanism is mediated by the neutralization of the MERTK ligand PROS1. We find that MERTK and PROS1 are expressed in human T cells upon TCR activation and drive an autocrine proproliferative mechanism. Collectively, these results suggest that MERTK on DCs controls T cell activation and expansion through the competition for PROS1 interaction with MERTK in the T cells. In conclusion, this report identified MERTK as a potent suppressor of T cell response. PMID:25624460

  18. ATPase activity of the cystic fibrosis transmembrane conductance regulator.

    PubMed

    Li, C; Ramjeesingh, M; Wang, W; Garami, E; Hewryk, M; Lee, D; Rommens, J M; Galley, K; Bear, C E

    1996-11-08

    The gene mutated in cystic fibrosis codes for the cystic fibrosis transmembrane conductance regulator (CFTR), a cyclic AMP-activated chloride channel thought to be critical for salt and water transport by epithelial cells. Plausible models exist to describe a role for ATP hydrolysis in CFTR channel activity; however, biochemical evidence that CFTR possesses intrinsic ATPase activity is lacking. In this study, we report the first measurements of the rate of ATP hydrolysis by purified, reconstituted CFTR. The mutation CFTRG551D resides within a motif conserved in many nucleotidases and is known to cause severe human disease. Following reconstitution the mutant protein exhibited both defective ATP hydrolysis and channel gating, providing direct evidence that CFTR utilizes ATP to gate its channel activity.

  19. Methamphetamine Regulation of Firing Activity of Dopamine Neurons.

    PubMed

    Lin, Min; Sambo, Danielle; Khoshbouei, Habibeh

    2016-10-05

    Methamphetamine (METH) is a substrate for the dopamine transporter that increases extracellular dopamine levels by competing with dopamine uptake and increasing reverse transport of dopamine via the transporter. METH has also been shown to alter the excitability of dopamine neurons. The mechanism of METH regulation of the intrinsic firing behaviors of dopamine neurons is less understood. Here we identified an unexpected and unique property of METH on the regulation of firing activity of mouse dopamine neurons. METH produced a transient augmentation of spontaneous spike activity of midbrain dopamine neurons that was followed by a progressive reduction of spontaneous spike activity. Inspection of action potential morphology revealed that METH increased the half-width and produced larger coefficients of variation of the interspike interval, suggesting that METH exposure affected the activity of voltage-dependent potassium channels in these neurons. Since METH has been shown to affect Ca(2+) homeostasis, the unexpected findings that METH broadened the action potential and decreased the amplitude of afterhyperpolarization led us to ask whether METH alters the activity of Ca(2+)-activated potassium (BK) channels. First, we identified BK channels in dopamine neurons by their voltage dependence and their response to a BK channel blocker or opener. While METH suppressed the amplitude of BK channel-mediated unitary currents, the BK channel opener NS1619 attenuated the effects of METH on action potential broadening, afterhyperpolarization repression, and spontaneous spike activity reduction. Live-cell total internal reflection fluorescence microscopy, electrophysiology, and biochemical analysis suggest METH exposure decreased the activity of BK channels by decreasing BK-α subunit levels at the plasma membrane.

  20. 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

  1. Regulation of Nox and Duox Enzymatic Activity and Expression

    PubMed Central

    Lambeth, J. David; Kawahara, Tsukasa; Diebold, Becky

    2007-01-01

    Summary In recent years, it has become clear that reactive oxygen species (ROS, which include superoxide, hydrogen peroxide and other metabolites) are produced in biological systems. Rather than being simply a byproduct of aerobic metabolism, it is now recognized that specific enzymes --- the Nox (NADPH-oxidase) and Duox (Dual oxidase) enzymes ---- seem to have the sole function of generating ROS in a carefully regulated manner, and key roles in signal transduction, immune function, hormone biosynthesis and other normal biological functions are being uncovered. The prototypical Nox is the respiratory burst oxidase or phagocyte oxidase, which generates large amounts of superoxide and other reactive species in the phagosomes of neutrophils and macrophages, playing a central role in innate immunity by killing microbes. This enzyme system has been extensively studied over the past two decades, and provides a basis for comparison with the more recently described Nox and Duox enzymes, which generate ROS in a variety of cells and tissues. This review first considers the structure and regulation of the respiratory burst oxidase, and then reviews recent studies relating to the regulation of the activity of the novel Nox/Duox enzymes. The regulation of Nox and Duox expression in tissues and by specific stimuli is also considered here. An accompanying review considers biological and pathological roles of the Nox family of enzymes. PMID:17602947

  2. Macroautophagy regulates energy metabolism during effector T cell activation.

    PubMed

    Hubbard, Vanessa M; Valdor, Rut; Patel, Bindi; Singh, Rajat; Cuervo, Ana Maria; Macian, Fernando

    2010-12-15

    Macroautophagy is a highly conserved mechanism of lysosomal-mediated protein degradation that plays a key role in maintaining cellular homeostasis by recycling amino acids, reducing the amount of damaged proteins, and regulating protein levels in response to extracellular signals. We have found that macroautophagy is induced after effector T cell activation. Engagement of the TCR and CD28 results in enhanced microtubule-associated protein 1 light chain 3 (LC3) processing, increased numbers of LC3-containing vesicles, and increased LC3 flux, indicating active autophagosome formation and clearance. The autophagosomes formed in stimulated T cells actively fuse with lysosomes to degrade their cargo. Using a conditional KO mouse model where Atg7, a critical gene for macroautophagy, is specifically deleted in T cells, we have found that macroautophagy-deficient effector Th cells have defective IL-2 and IFN-γ production and reduced proliferation after stimulation, with no significant increase in apoptosis. We have found that ATP generation is decreased when autophagy is blocked, and defects in activation-induced cytokine production are restored when an exogenous energy source is added to macroautophagy-deficient T cells. Furthermore, we present evidence showing that the nature of the cargo inside autophagic vesicles found in resting T cells differs from the cargo of autophagosomes in activated T cells, where mitochondria and other organelles are selectively excluded. These results suggest that macroautophagy is an actively regulated process in T cells that can be induced in response to TCR engagement to accommodate the bioenergetic requirements of activated T cells.

  3. RGS10 Negatively Regulates Platelet Activation and Thrombogenesis

    PubMed Central

    Druey, Kirk M.; Tansey, Malú G.; Khasawneh, Fadi T.

    2016-01-01

    Regulators of G protein signaling (RGS) proteins act as GTPase activating proteins to negatively regulate G protein-coupled receptor (GPCR) signaling. Although several RGS proteins including RGS2, RGS16, RGS10, and RGS18 are expressed in human and mouse platelets, the respective unique function(s) of each have not been fully delineated. RGS10 is a member of the D/R12 subfamily of RGS proteins and is expressed in microglia, macrophages, megakaryocytes, and platelets. We used a genetic approach to examine the role(s) of RGS10 in platelet activation in vitro and hemostasis and thrombosis in vivo. GPCR-induced aggregation, secretion, and integrin activation was much more pronounced in platelets from Rgs10-/- mice relative to wild type (WT). Accordingly, these mice had markedly reduced bleeding times and were more susceptible to vascular injury-associated thrombus formation than control mice. These findings suggest a unique, non-redundant role of RGS10 in modulating the hemostatic and thrombotic functions of platelets in mice. RGS10 thus represents a potential therapeutic target to control platelet activity and/or hypercoagulable states. PMID:27829061

  4. 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

  5. The Lysosome Rupture-activated TAK1-JNK Pathway Regulates NLRP3 Inflammasome Activation*

    PubMed Central

    Okada, Masahiro; Matsuzawa, Atsushi; Yoshimura, Akihiko; Ichijo, Hidenori

    2014-01-01

    Lysosome rupture triggers NLRP3 inflammasome activation in macrophages. However, the underlying mechanism is not fully understood. Here we showed that the TAK1-JNK pathway, a MAPK signaling pathway, is activated through lysosome rupture and that this activation is necessary for the complete activation of the NLRP3 inflammasome through the oligomerization of an adapter protein, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC). We also revealed that the activation of the TAK1-JNK pathway is sustained through Ca2+ ions and that calcium/calmodulin-dependent protein kinase type II functions upstream of the TAK1-JNK pathway and specifically regulates lysosome rupture-induced NLRP3 inflammasome activation. These data suggest a novel role for the TAK1-JNK pathway as a critical regulator of NLRP3 inflammasome activation. PMID:25288801

  6. Amine oxidase activity regulates the development of pulmonary fibrosis.

    PubMed

    Marttila-Ichihara, Fumiko; Elima, Kati; Auvinen, Kaisa; Veres, Tibor Z; Rantakari, Pia; Weston, Christopher; Miyasaka, Masayuki; Adams, David; Jalkanen, Sirpa; Salmi, Marko

    2017-03-01

    In pulmonary fibrosis, an inflammatory reaction and differentiation of myofibroblasts culminate in pathologic deposition of collagen. Amine oxidase copper containing-3 (AOC3) is a cell-surface expressed oxidase that regulates leukocyte extravasation. Here we analyzed the potential role of AOC3 using gene-modified and inhibitor-treated mice in a bleomycin-induced pulmonary fibrosis model. Inflammation and fibrosis of lungs were assessed by histologic, flow cytometric, and quantitative PCR analysis. AOC3-deficient mice showed a 30-50% reduction in fibrosis, collagen synthesis, numbers of myofibroblasts, and accumulation of CD4(+) lymphocytes, NK T cells, macrophages, and type 2 innate lymphoid cells compared with wild-type control mice. AOC3 knock-in mice, which express a catalytically inactive form of AOC3, were also protected from lung fibrosis. In wild-type mice, a small-molecule AOC3 inhibitor treatment reduced leukocyte infiltration, myofibroblast differentiation, and fibrotic injury both in prophylactic and early therapeutic settings by about 50% but was unable to reverse the established fibrosis. AOC3 was also induced in myofibroblasts in human idiopathic pulmonary fibrosis. Thus, the oxidase activity of AOC3 contributes to the development of lung fibrosis mainly by regulating the accumulation of pathogenic leukocyte subtypes, which drive the fibrotic response.-Marttila-Ichihara, F., Elima, K., Auvinen, K., Veres, T. Z., Rantakari, P., Weston, C., Miyasaka, M., Adams, D., Jalkanen, S., Salmi, M. Amine oxidase activity regulates the development of pulmonary fibrosis.

  7. DUB3 Deubiquitylating Enzymes Regulate Hippo Pathway Activity by Regulating the Stability of ITCH, LATS and AMOT Proteins.

    PubMed

    Nguyen, Hung Thanh; Kugler, Jan-Michael; Cohen, Stephen M

    2017-01-01

    The YAP and TAZ transcriptional coactivators promote oncogenic transformation. Elevated YAP/TAZ activity has been documented in human tumors. YAP and TAZ are negatively regulated by the Hippo tumor suppressor pathway. The activity and stability of several Hippo pathway components, including YAP/TAZ, is regulated by ubiquitin mediated protein turnover and several ubiquitin ligase complexes have been implicated in human cancer. However, little is known about the deubiquitylating enzymes that counteract these ubiquitin ligases in regulation of the Hippo pathway. Here we identify the DUB3 family deubiquitylating enzymes as regulators of Hippo pathway activity. We provide evidence that DUB3 proteins regulate YAP/TAZ activity by controlling the stability of the E3 ligase ITCH, the LATS kinases and the AMOT family proteins. As a novel Hippo pathway regulator, DUB3 has the potential to act a tumor suppressor by limiting YAP activity.

  8. DUB3 Deubiquitylating Enzymes Regulate Hippo Pathway Activity by Regulating the Stability of ITCH, LATS and AMOT Proteins

    PubMed Central

    2017-01-01

    The YAP and TAZ transcriptional coactivators promote oncogenic transformation. Elevated YAP/TAZ activity has been documented in human tumors. YAP and TAZ are negatively regulated by the Hippo tumor suppressor pathway. The activity and stability of several Hippo pathway components, including YAP/TAZ, is regulated by ubiquitin mediated protein turnover and several ubiquitin ligase complexes have been implicated in human cancer. However, little is known about the deubiquitylating enzymes that counteract these ubiquitin ligases in regulation of the Hippo pathway. Here we identify the DUB3 family deubiquitylating enzymes as regulators of Hippo pathway activity. We provide evidence that DUB3 proteins regulate YAP/TAZ activity by controlling the stability of the E3 ligase ITCH, the LATS kinases and the AMOT family proteins. As a novel Hippo pathway regulator, DUB3 has the potential to act a tumor suppressor by limiting YAP activity. PMID:28061504

  9. 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.

  10. Hsp90 regulation of fibroblast activation in pulmonary fibrosis

    PubMed Central

    Sontake, Vishwaraj; Wang, Yunguan; Kasam, Rajesh K.; Sinner, Debora; Reddy, Geereddy B.; Naren, Anjaparavanda P.; McCormack, Francis X.; Jegga, Anil G.; Madala, Satish K.

    2017-01-01

    Idiopathic pulmonary fibrosis (IPF) is a severe fibrotic lung disease associated with fibroblast activation that includes excessive proliferation, tissue invasiveness, myofibroblast transformation, and extracellular matrix (ECM) production. To identify inhibitors that can attenuate fibroblast activation, we queried IPF gene signatures against a library of small-molecule-induced gene-expression profiles and identified Hsp90 inhibitors as potential therapeutic agents that can suppress fibroblast activation in IPF. Although Hsp90 is a molecular chaperone that regulates multiple processes involved in fibroblast activation, it has not been previously proposed as a molecular target in IPF. Here, we found elevated Hsp90 staining in lung biopsies of patients with IPF. Notably, fibroblasts isolated from fibrotic lesions showed heightened Hsp90 ATPase activity compared with normal fibroblasts. 17-N-allylamino-17-demethoxygeldanamycin (17-AAG), a small-molecule inhibitor of Hsp90 ATPase activity, attenuated fibroblast activation and also TGF-β–driven effects on fibroblast to myofibroblast transformation. The loss of the Hsp90AB, but not the Hsp90AA isoform, resulted in reduced fibroblast proliferation, myofibroblast transformation, and ECM production. Finally, in vivo therapy with 17-AAG attenuated progression of established and ongoing fibrosis in a mouse model of pulmonary fibrosis, suggesting that targeting Hsp90 represents an effective strategy for the treatment of fibrotic lung disease. PMID:28239659

  11. 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...

  12. Inhibitory neurotransmission regulates vagal efferent activity and gastric motility

    PubMed Central

    McMenamin, Caitlin A; Travagli, R Alberto

    2016-01-01

    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

  13. 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.

  14. The PI3K-mediated activation of CRAC independently regulates adenylyl cyclase activation and chemotaxis.

    PubMed

    Comer, Frank I; Lippincott, Christopher K; Masbad, Joseph J; Parent, Carole A

    2005-01-26

    The ability of a cell to detect an external chemical signal and initiate a program of directed migration along a gradient comprises the fundamental process called chemotaxis. Investigations in Dictyostelium discoideum and neutrophils have established that pleckstrin homology (PH) domain-containing proteins that bind to the PI3K products PI(3,4)P2 and PI(3,4,5)P3, such as CRAC (cytosolic regulator of adenylyl cyclase) and Akt/PKB, translocate specifically to the leading edge of chemotaxing cells. CRAC is essential for the chemoattractant-mediated activation of the adenylyl cyclase ACA, which converts ATP into cAMP, the primary chemoattractant for D. discoideum. The mechanisms by which CRAC activates ACA remain to be determined. We now show that in addition to its essential role in the activation of ACA, CRAC is involved in regulating chemotaxis. Through mutagenesis, we show that these two functions are independently regulated downstream of PI3K. A CRAC mutant that has lost the capacity to bind PI3K products does not support chemotaxis and shows minimal ACA activation. Finally, overexpression of CRAC and various CRAC mutants show strong effects on ACA activation with little effect on chemotaxis. These findings establish that chemoattractant-mediated activation of PI3K is important for the CRAC-dependent regulation of both chemotaxis and adenylyl cyclase activation.

  15. Myostatin signaling regulates Akt activity via the regulation of miR-486 expression.

    PubMed

    Hitachi, Keisuke; Nakatani, Masashi; Tsuchida, Kunihiro

    2014-02-01

    Myostatin, also known as growth and differentiation factor-8, is a pivotal negative regulator of skeletal muscle mass and reduces muscle protein synthesis by inhibiting the insulin-like growth factor-1 (IGF-1)/Akt/mammalian target of rapamycin (mTOR) pathway. However, the precise mechanism by which myostatin inhibits the IGF-1/Akt/mTOR pathway remains unclear. In this study, we investigated the global microRNA expression profile in myostatin knockout mice and identified miR-486, a positive regulator of the IGF-1/Akt pathway, as a novel target of myostatin signaling. In myostatin knockout mice, the expression level of miR-486 in skeletal muscle was significantly increased. In addition, we observed increased expression of the primary transcript of miR-486 (pri-miR-486) and Ankyrin 1.5 (Ank1.5), the host gene of miR-486, in myostatin knockout mice. In C2C12 cells, myostatin negatively regulated the expression of Ank1.5. Moreover, canonical myostatin signaling repressed the skeletal muscle-specific promoter activity of miR-486/Ank1.5. This repression was partially mediated by the E-box elements in the proximal region of the promoter. We also show that overexpression of miR-486 induced myotube hypertrophy in vitro and that miR-486 was essential to maintain skeletal muscle size both in vitro and in vivo. In addition, inhibition of miR-486 led to a decrease in Akt activity in C2C12 myotubes. Our findings indicate that miR-486 is one of the intermediary molecules connecting myostatin signaling and the IGF-1/Akt/mTOR pathway in the regulation of skeletal muscle size.

  16. Regulation of ligands for the activating receptor NKG2D

    PubMed Central

    Mistry, Anita R; O'Callaghan, Chris A

    2007-01-01

    The outcome of an encounter between a cytotoxic cell and a potential target cell depends on the balance of signals from inhibitory and activating receptors. Natural Killer group 2D (NKG2D) has recently emerged as a major activating receptor on T lymphocytes and natural killer cells. In both humans and mice, multiple different genes encode ligands for NKG2D, and these ligands are non-classical major histocompatibility complex class I molecules. The NKG2D–ligand interaction triggers an activating signal in the cell expressing NKG2D and this promotes cytotoxic lysis of the cell expressing the ligand. Most normal tissues do not express ligands for NKG2D, but ligand expression has been documented in tumour and virus-infected cells, leading to lysis of these cells. Tight regulation of ligand expression is important. If there is inappropriate expression in normal tissues, this will favour autoimmune processes, whilst failure to up-regulate the ligands in pathological conditions would favour cancer development or dissemination of intracellular infection. PMID:17614877

  17. FANCI is a negative regulator of Akt activation.

    PubMed

    Zhang, Xiaoshan; Lu, Xiaoyan; Akhter, Shamima; Georgescu, Maria-Magdalena; Legerski, Randy J

    2016-01-01

    Akt is a critical mediator of the oncogenic PI3K pathway, and its activation is regulated by kinases and phosphatases acting in opposition. We report here the existence of a novel protein complex that is composed minimally of Akt, PHLPP1, PHLPP2, FANCI, FANCD2, USP1 and UAF1. Our studies show that depletion of FANCI, but not FANCD2 or USP1, results in increased phosphorylation and activation of Akt. This activation is due to a reduction in the interaction between PHLPP1 and Akt in the absence of FANCI. In response to DNA damage or growth factor treatment, the interactions between Akt, PHLPP1 and FANCI are reduced consistent with the known phosphorylation of Akt in response to these stimuli. Furthermore, depletion of FANCI results in reduced apoptosis after DNA damage in accord with its role as a negative regular of Akt. Our findings describe an unexpected function for FANCI in the regulation of Akt and define a previously unrecognized intersection between the PI3K-Akt and FA pathways.

  18. 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.

  19. Glutamate regulates the activity of topoisomerase I in mouse cerebellum.

    PubMed

    Zehorai, Eldar; Eitan, Erez; Hershfinkel, Michal; Sekler, Israel; Priel, Esther

    2008-12-01

    Topoisomerase I (topo I) is a nuclear enzyme which participates in most DNA transactions. It was shown to be inhibited in depolarized neurons by poly adenosine diphosphate (ADP)-ribosylation of the enzyme protein. We demonstrated previously an age and sex dependent topo I activity and enzyme protein level in the various regions of mouse brain. A specific distribution pattern of topo I was observed and the inhibitory neurons exhibited the highest enzyme activity and protein level in both the nucleus and the cytoplasm. Here, we show that neurotransmitters (glutamate and gamma-aminobutyric acid (GABA)) regulate the activity of topo I in mouse cerebellum sections. Glutamate exhibited a significant time-dependent inhibition of topo I activity but no effect of the enzyme protein level. GABA in contrary only slightly and transiently inhibited topo I activity. The inhibitory effect of glutamate was mediated by Ca(+2) and by ADP-ribosylation of topo I protein and the glutamate ionotropic receptors were involved. Glutamate also diminished the inhibitory effect of topotecan on topo I. These results point to distinct and highly specific effects of the major neurotransmitters on topo I activity in the cerebellum suggesting that topo I possesses a specific role in the brain which differs from its known biological functions.

  20. 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.

  1. 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

    2016-07-08

    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.

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

    PubMed

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

    2007-12-01

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

  3. SUMOylation of Argonaute-2 regulates RNA interference activity

    PubMed Central

    Josa-Prado, Fernando; Henley, Jeremy M.; Wilkinson, Kevin A.

    2015-01-01

    Post-translational modification of substrate proteins by small ubiquitin-like modifier (SUMO) regulates a vast array of cellular processes. SUMOylation occurs through three sequential enzymatic steps termed E1, E2 and E3. Substrate selection can be determined through interactions between the target protein and the SUMO E2 conjugating enzyme Ubc9 and specificity can be enhanced by substrate interactions with E3 ligase enzymes. We used the putative substrate recognition (PINIT) domain from the SUMO E3 PIAS3 as bait to identify potential SUMO substrates. One protein identified was Argonaute-2 (Ago2), which mediates RNA-induced gene silencing through binding small RNAs and promoting degradation of complimentary target mRNAs. We show that Ago2 can be SUMOylated in mammalian cells by both SUMO1 and SUMO2. SUMOylation occurs primarily at K402, and mutation of the SUMO consensus site surrounding this lysine reduces Ago2-mediated siRNA-induced silencing in a luciferase-based reporter assay. These results identify SUMOylation as a potential regulator of Ago2 activity and open new avenues for research into the mechanisms underlying the regulation of RNA-induced gene silencing. PMID:26188511

  4. Comparative Analysis of Protein Tyrosine Phosphatases Regulating Microglial Activation

    PubMed Central

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

    2016-01-01

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

  5. ROMK1 channel activity is regulated by monoubiquitination.

    PubMed

    Lin, Dao-Hong; Sterling, Hyacinth; Wang, Zhijian; Babilonia, Elisa; Yang, Baofeng; Dong, Ke; Hebert, Steven C; Giebisch, Gerhard; Wang, Wen-Hui

    2005-03-22

    The ubiquitination of proteins can signal their degradation, modify their activity or target them to specific membranes or cellular organelles. Here, we show that monoubiquitination regulates the plasma membrane abundance and function of the potassium channel, ROMK. Immunoprecipitation of proteins obtained from renal cortex and outer medulla with ROMK antibody revealed that this channel was monoubiquitinated. To determine the ubiquitin binding site on ROMK1, all intracellular lysine (Lys) residues of ROMK1 were individually mutated to arginine (Arg), and a two-electrode voltage clamp was used to measure the ROMK1 channel activity in Xenopus oocytes. ROMK1 channel activity increased from 8.1 to 27.2 microA only when Lys-22 was mutated to Arg. Furthermore, Western blotting failed to detect the ubiquitinated ROMK1 in oocytes injected with R1K22R. Patch-clamp experiments showed that biophysical properties of R1K22R were identical to those of wild-type ROMK1. Although total protein expression levels of GFP-ROMK1 and GFP-R1K22R in oocytes were similar, confocal microscopy showed that the surface fluorescence intensity in oocytes injected with GFP-R1K22R was higher than that of GFP-ROMK1. In addition, biotin labeling of ROMK1 and R1K22R proteins expressed in HEK293 cells showed increased surface expression of the Lys-22 mutant channel. Finally, expression of R1K22R in COS7 cells significantly stimulated the surface expression of ROMK1. We conclude that ROMK1 can be monoubiquitinated and that Lys-22 is an ubiquitin-binding site. Thus, monoubiquitination of ROMK1 regulates channel activity by reducing the surface expression of channel protein. This finding implicates the linking of a single ubiquitin molecule to channels as an important posttranslational regulatory signal.

  6. ROMK1 channel activity is regulated by monoubiquitination

    PubMed Central

    Lin, Dao-Hong; Sterling, Hyacinth; Wang, Zhijian; Babilonia, Elisa; Yang, Baofeng; Dong, Ke; Hebert, Steven C.; Giebisch, Gerhard; Wang, Wen-Hui

    2005-01-01

    The ubiquitination of proteins can signal their degradation, modify their activity or target them to specific membranes or cellular organelles. Here, we show that monoubiquitination regulates the plasma membrane abundance and function of the potassium channel, ROMK. Immunoprecipitation of proteins obtained from renal cortex and outer medulla with ROMK antibody revealed that this channel was monoubiquitinated. To determine the ubiquitin binding site on ROMK1, all intracellular lysine (Lys) residues of ROMK1 were individually mutated to arginine (Arg), and a two-electrode voltage clamp was used to measure the ROMK1 channel activity in Xenopus oocytes. ROMK1 channel activity increased from 8.1 to 27.2 μA only when Lys-22 was mutated to Arg. Furthermore, Western blotting failed to detect the ubiquitinated ROMK1 in oocytes injected with R1K22R. Patch-clamp experiments showed that biophysical properties of R1K22R were identical to those of wild-type ROMK1. Although total protein expression levels of GFP-ROMK1 and GFP-R1K22R in oocytes were similar, confocal microscopy showed that the surface fluorescence intensity in oocytes injected with GFP-R1K22R was higher than that of GFP-ROMK1. In addition, biotin labeling of ROMK1 and R1K22R proteins expressed in HEK293 cells showed increased surface expression of the Lys-22 mutant channel. Finally, expression of R1K22R in COS7 cells significantly stimulated the surface expression of ROMK1. We conclude that ROMK1 can be monoubiquitinated and that Lys-22 is an ubiquitin-binding site. Thus, monoubiquitination of ROMK1 regulates channel activity by reducing the surface expression of channel protein. This finding implicates the linking of a single ubiquitin molecule to channels as an important posttranslational regulatory signal. PMID:15767585

  7. The alternative translated MDMXp60 isoform regulates MDM2 activity

    PubMed Central

    Tournillon, Anne-Sophie; López, Ignacio; Malbert-Colas, Laurence; Naski, Nadia; Olivares-Illana, Vanesa; Fåhraeus, Robin

    2015-01-01

    Isoforms derived from alternative splicing, mRNA translation initiation or promoter usage extend the functional repertoire of the p53, p63 and p73 genes family and of their regulators MDM2 and MDMX. Here we show cap-independent translation of an N-terminal truncated isoform of hMDMX, hMDMXp60, which is initiated at the 7th AUG codon downstream of the initiation site for full length hMDMXFL at position +384. hMDMXp60 lacks the p53 binding motif but retains the RING domain and interacts with hMDM2 and hMDMXFL. hMDMXp60 shows higher affinity for hMDM2, as compared to hMDMXFL. In vitro data reveal a positive cooperative interaction between hMDMXp60 and hMDM2 and in cellulo data show that low levels of hMDMXp60 promote degradation of hMDM2 whereas higher levels stabilize hMDM2 and prevent hMDM2-mediated degradation of hMDMXFL. These results describe a novel alternatively translated hMDMX isoform that exhibits unique regulatory activity toward hMDM2 autoubiquitination. The data illustrate how the N-terminus of hMDMX regulates its C-terminal RING domain and the hMDM2 activity. PMID:25659040

  8. Regulated O2 activation in flavin-dependent monooxygenases.

    PubMed

    Frederick, Rosanne E; Mayfield, Jeffery A; DuBois, Jennifer L

    2011-08-17

    Flavin-dependent monooxygenases (FMOs) are involved in important biosynthetic pathways in diverse organisms, including production of the siderophores used for the import and storage of essential iron in serious pathogens. We have shown that the FMO from Aspergillus fumigatus, an ornithine monooxygenase (Af-OMO), is mechanistically similar to its well-studied distant homologues from mammalian liver. The latter are highly promiscuous in their choice of substrates, while Af-OMO is unusually specific. This presents a puzzle: how do Af-OMO and other FMOs of the biosynthetic classes achieve such specificity? We have discovered substantial enhancement in the rate of O(2) activation in Af-OMO in the presence of L-arginine, which acts as a small molecule regulator. Such protein-level regulation could help explain how this and related biosynthetic FMOs manage to couple O(2) activation and substrate hydroxylation to each other and to the appropriate cellular conditions. Given the essentiality of Fe to Af and the avirulence of the Af-OMO gene knock out, inhibitors of Af-OMO are likely to be drug targets against this medically intractable pathogen.

  9. REGgamma modulates p53 activity by regulating its cellular localization.

    PubMed

    Liu, Jian; Yu, Guowu; Zhao, Yanyan; Zhao, Dengpan; Wang, Ying; Wang, Lu; Liu, Jiang; Li, Lei; Zeng, Yu; Dang, Yongyan; Wang, Chuangui; Gao, Guang; Long, Weiwen; Lonard, David M; Qiao, Shanlou; Tsai, Ming-Jer; Zhang, Bianhong; Luo, Honglin; Li, Xiaotao

    2010-12-01

    The proteasome activator REGγ mediates a shortcut for the destruction of intact mammalian proteins. The biological roles of REGγ and the underlying mechanisms are not fully understood. Here we provide evidence that REGγ regulates cellular distribution of p53 by facilitating its multiple monoubiquitylation and subsequent nuclear export and degradation. We also show that inhibition of p53 tetramerization by REGγ might further enhance cytoplasmic relocation of p53 and reduce active p53 in the nucleus. Furthermore, multiple monoubiquitylation of p53 enhances its physical interaction with HDM2 and probably facilitates subsequent polyubiquitylation of p53, suggesting that monoubiquitylation can act as a signal for p53 degradation. Depletion of REGγ sensitizes cells to stress-induced apoptosis, validating its crucial role in the control of apoptosis, probably through regulation of p53 function. Using a mouse xenograft model, we show that REGγ knockdown results in a significant reduction of tumor growth, suggesting an important role for REGγ in tumor development. Our study therefore demonstrates that REGγ-mediated inactivation of p53 is one of the mechanisms involved in cancer progression.

  10. GARP regulates the bioavailability and activation of TGFβ.

    PubMed

    Wang, Rui; Zhu, Jianghai; Dong, Xianchi; Shi, Minlong; Lu, Chafen; Springer, Timothy A

    2012-03-01

    Glycoprotein-A repetitions predominant protein (GARP) associates with latent transforming growth factor-β (proTGFβ) on the surface of T regulatory cells and platelets; however, whether GARP functions in latent TGFβ activation and the structural basis of coassociation remain unknown. We find that Cys-192 and Cys-331 of GARP disulfide link to the TGFβ1 prodomain and that GARP with C192A and C331A mutations can also noncovalently associate with proTGFβ1. Noncovalent association is sufficiently strong for GARP to outcompete latent TGFβ-binding protein for binding to proTGFβ1. Association between GARP and proTGFβ1 prevents the secretion of TGFβ1. Integrin α(V)β(6) and to a lesser extent α(V)β(8) are able to activate TGFβ from the GARP-proTGFβ1 complex. Activation requires the RGD motif of latent TGFβ, disulfide linkage between GARP and latent TGFβ, and membrane association of GARP. Our results show that GARP is a latent TGFβ-binding protein that functions in regulating the bioavailability and activation of TGFβ.

  11. Activation of epithelial STAT3 regulates intestinal homeostasis.

    PubMed

    Neufert, Clemens; Pickert, Geethanjali; Zheng, Yan; Wittkopf, Nadine; Warntjen, Moritz; Nikolaev, Alexei; Ouyang, Wenjun; Neurath, Markus F; Becker, Christoph

    2010-02-15

    The intestinal epithelium that lines the mucosal surface along the GI-tract is a key player for the intestinal homeostasis of the healthy individual. In case of a mucosal damage or a barrier defect as seen in patients with inflammatory bowel disease, the balance is disturbed, and translocation of intestinal microbes to the submucosa is facilitated. We recently demonstrated a pivotal role of STAT3 activation in intestinal epithelial cells (IEC) for the restoration of the balance at the mucosal surface of the gut in an experimental colitis model. STAT3 was rapidly induced in intestinal epithelial cells upon challenge of mice in both experimental colitis and intestinal wound healing models. STAT3 activation was found to be dispensable in the steady-state conditions but was important for efficient regeneration of the epithelium in response to injury. Here, we extend our previous findings by showing epithelial STAT3 activation in human patients suffering from IBD and provide additional insights how the activation of epithelial STAT3 by IL-22 regulates intestinal homeostasis and mucosal wound healing. We also demonstrate that antibody-mediated neutralization of IL-22 has little impact on the development of experimental colitis in mice, but significantly delays recovery from colitis. Thus, our data suggest that targeting the STAT3 signaling pathway in IEC is a promising therapeutic approach in situations when the intestinal homeostasis is disturbed, e.g., as seen in Crohn's disease or Ulcerative colitis.

  12. 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.

  13. LAR, liprin alpha and the regulation of active zone morphogenesis.

    PubMed

    Stryker, Emily; Johnson, Karl G

    2007-11-01

    Active zones are protein-rich regions of neurons that act as sites of synaptic vesicle fusion and neurotransmitter release at the pre-synaptic terminus. Although the discovery that the receptor protein tyrosine phosphatase LAR and its cytoplasmic binding partner liprin alpha are essential for proper active zone formation is nearly a decade old, the underlying mechanisms are still poorly understood. Recent studies have identified a number of binding partners for both LAR and liprin alpha, several of which play key roles in active zone assembly. These include nidogen, dallylike and syndecan--extracellular ligands for LAR that regulate synapse morphogenesis. In addition, liprin-alpha-interacting proteins such as ERC2, RIM and the MALS/Veli-Cask-Mint1 complex cooperate to form a dense molecular scaffold at the active zone that is crucial for proper synaptic function. These studies allow us to propose testable models of LAR and liprin alpha function, and provide insights into the fundamental molecular mechanisms of synapse formation and stabilization.

  14. 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

  15. Stra13 regulates satellite cell activation by antagonizing Notch signaling

    PubMed Central

    Sun, Hong; Li, Li; Vercherat, Cécile; Gulbagci, Neriman Tuba; Acharjee, Sujata; Li, Jiali; Chung, Teng-Kai; Thin, Tin Htwe; Taneja, Reshma

    2007-01-01

    Satellite cells play a critical role in skeletal muscle regeneration in response to injury. Notch signaling is vital for satellite cell activation and myogenic precursor cell expansion but inhibits myogenic differentiation. Thus, precise spatial and temporal regulation of Notch activity is necessary for efficient muscle regeneration. We report that the basic helix-loop-helix transcription factor Stra13 modulates Notch signaling in regenerating muscle. Upon injury, Stra13−/− mice exhibit increased cellular proliferation, elevated Notch signaling, a striking regeneration defect characterized by degenerated myotubes, increased mononuclear cells, and fibrosis. Stra13−/− primary myoblasts also exhibit enhanced Notch activity, increased proliferation, and defective differentiation. Inhibition of Notch signaling ex vivo and in vivo ameliorates the phenotype of Stra13−/− mutants. We demonstrate in vitro that Stra13 antagonizes Notch activity and reverses the Notch-imposed inhibition of myogenesis. Thus, Stra13 plays an important role in postnatal myogenesis by attenuating Notch signaling to reduce myoblast proliferation and promote myogenic differentiation. PMID:17502421

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

    PubMed

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

    2016-09-01

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

  17. Protein kinase C-associated kinase regulates NF-κB activation through inducing IKK activation.

    PubMed

    Kim, Sang-Woo; Schifano, Matthew; Oleksyn, David; Jordan, Craig T; Ryan, Daniel; Insel, Richard; Zhao, Jiyong; Chen, Luojing

    2014-10-01

    Activation of the transcription factor NF-κB induced by extracellular stimuli requires IKKα and IKKβ kinase activity. How IKKα and IKKβ are activated by various upstream signaling molecules is not fully understood. We previously showed that protein kinase C-associated kinase (PKK, also known as DIK/RIP4), which belongs to the receptor-interacting protein (RIP) kinase family, mediates the B cell activating factor of the TNF family (BAFF)-induced NF-κB activation in diffuse large B cell lymphoma (DLBCL) cell lines. Here we have investigated the mechanism underlying NF-κB activation regulated by PKK. Our results suggest that PKK can activate both the classical and the alternative NF-κB activation pathways. PKK associates with IKKα and IKKβ in mammalian cells and induces activation of both IKKα and IKKβ via phosphorylation of their serine residues 176/180 and 177/181, respectively. Unlike other members of the RIP family that activate NF-κB through a kinase-independent pathway, PKK appears to activate IKK and NF-κB mainly in a kinase-dependent manner. Suppression of PKK expression by RNA interference inhibits phosphorylation of IKKα and IKKβ as well as activation of NF-κB in human cancer cell lines. Thus, PKK regulates NF-κB activation by modulating activation of IKKα and IKKβ in mammalian cells. We propose that PKK may provide a critical link between IKK activation and various upstream signaling cascades, and may represent a potential target for inhibiting abnormal NF-κB activation in human cancers.

  18. 44 CFR 7.912 - To what programs or activities does this regulation apply?

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... activities does this regulation apply? 7.912 Section 7.912 Emergency Management and Assistance FEDERAL... Financial Assistance From FEMA General § 7.912 To what programs or activities does this regulation apply? (a) The Act and this regulation apply to each FEMA recipient and to each program or activity operated...

  19. 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

  20. Histidine-regulated activity of M-ficolin.

    PubMed

    Tanio, Michikazu; Kohno, Toshiyuki

    2009-01-15

    Human M-ficolin is a pathogen-associated molecular recognition molecule in the innate immune system, and it binds to some sugars, such as GlcNAc (N-acetylglucosamine), on pathogen surfaces. From previous structural and functional studies of the FD1 (M-ficolin fibrinogen-like domain), we proposed that the ligand-binding region of FD1 exists in a conformational equilibrium between active and non-active states depending on three groups with a pK(a) of 6.2, which are probably histidine residues, and suggested that the 2-state conformational equilibrium as well as the trimer formation contributes to the discrimination mechanism between self and non-self of FD1 [Tanio, M., Kondo, S., Sugio, S. and Kohno, T. (2007) J. Biol. Chem. 282, 3889-3895]. To investigate the origins of the pH dependency, mutational analyses were performed on FD1 expressed by Brevibacillus choshinensis. The GlcNAc binding study of a series of single histidine mutants of FD1 demonstrated that His(251), His(284) and His(297) are required for the activity, and thus we concluded that the three histidines are the origins of the pH dependency of FD1. Monomeric mutants of FD1 show weaker affinity for the ligand than the trimeric wild-type, indicating that trimer formation confers high avidity for the ligand. In addition, analyses of the GlcNAc association and dissociation of FD1 provided evidence that FD1 always exchanges between the active and non-active states with the pH-dependent populations in solution. The biological roles of the histidine-regulated conformational equilibrium of M-ficolin are discussed in terms of the self and non-self discrimination mechanism.

  1. 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

  2. Myosin 3A Kinase Activity Is Regulated by Phosphorylation of the Kinase Domain Activation Loop*

    PubMed Central

    Quintero, Omar A.; Unrath, William C.; Stevens, Stanley M.; Manor, Uri; Kachar, Bechara; Yengo, Christopher M.

    2013-01-01

    Class III myosins are unique members of the myosin superfamily in that they contain both a motor and kinase domain. We have found that motor activity is decreased by autophosphorylation, although little is known about the regulation of the kinase domain. We demonstrate by mass spectrometry that Thr-178 and Thr-184 in the kinase domain activation loop and two threonines in the loop 2 region of the motor domain are autophosphorylated (Thr-908 and Thr-919). The kinase activity of MYO3A 2IQ with the phosphomimic (T184E) or phosphoblock (T184A) mutations demonstrates that kinase activity is reduced 30-fold as a result of the T184A mutation, although the Thr-178 site only had a minor impact on kinase activity. Interestingly, the actin-activated ATPase activity of MYO3A 2IQ is slightly reduced as a result of the T178A and T184A mutations suggesting coupling between motor and kinase domains. Full-length GFP-tagged T184A and T184E MYO3A constructs transfected into COS7 cells do not disrupt the ability of MYO3A to localize to filopodia structures. In addition, we demonstrate that T184E MYO3A reduces filopodia elongation in the presence of espin-1, whereas T184A enhances filopodia elongation in a similar fashion to kinase-dead MYO3A. Our results suggest that as MYO3A accumulates at the tips of actin protrusions, autophosphorylation of Thr-184 enhances kinase activity resulting in phosphorylation of the MYO3A motor and reducing motor activity. The differential regulation of the kinase and motor activities allows for MYO3A to precisely self-regulate its concentration in the actin bundle-based structures of cells. PMID:24214986

  3. 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.

  4. Regulation of neuronal P53 activity by CXCR4

    PubMed Central

    Khan, Muhammad Z.; Shimizu, Saori; Patel, Jeegar P.; Nelson, Autumn; Le, My-Thao; Mullen-Przeworski, Anna; Brandimarti, Renato; Fatatis, Alessandro; Meucci, Olimpia

    2009-01-01

    Abnormal activation of CXCR4 during inflammatory/infectious states may lead to neuronal dysfunction or damage. The major goal of this study was to determine the coupling of CXCR4 to p53-dependent survival pathways in primary neurons. Neurons were stimulated with the HIV envelope protein gp120IIIB or the endogenous CXCR4 agonist, SDF-1α. We found that gp120 stimulates p53 activity and induces expression of the p53 pro-apoptotic target Apaf-1 in cultured neurons. Inhibition of CXCR4 by AMD3100 abrogates the effect of gp120 on both p53 and Apaf-1. Moreover, gp120 neurotoxicity is markedly reduced by the p53-inhibitor, pifithrin-α. The viral protein also regulates p53 phosphorylation and expression of other p53-responsive genes, such as MDM2 and p21. Conversely, SDF-1α, which can promote neuronal survival, increases p53 acetylation and p21 expression in neurons. Thus, the stimulation of different p53 targets could be instrumental in determining the outcome of CXCR4 activation on neuronal survival in neuroinflammatory disorders. PMID:16005638

  5. 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.

  6. Serotonin transporter genotype modulates amygdala activity during mood regulation

    PubMed Central

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

    2010-01-01

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

  7. 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

  8. Regulation of endonuclease activity in human nucleotide excision repair

    PubMed Central

    Fagbemi, Adebanke F.; Orelli, Barbara; Schärer, Orlando D.

    2011-01-01

    Nucleotide excision repair (NER) is a DNA repair pathway that is responsible for removing a variety of lesions caused by harmful UV light, chemical carcinogens, and environmental mutagens from DNA. NER involves the concerted action of over 30 proteins that sequentially recognize a lesion, excise it in the form of an oligonucleotide, and fill in the resulting gap by repair synthesis. ERCC1-XPF and XPG are structure-specific endonucleases responsible for carrying out the incisions 5′ and 3′ to the damage respectively, culminating in the release of the damaged oligonucleotide. This review focuses on the recent work that led to a greater understanding of how the activities of ERCC1-XPF and XPG are regulated in NER to prevent unwanted cuts in DNA or the persistence of gaps after incision that could result in harmful, cytotoxic DNA structures. PMID:21592868

  9. 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

  10. Regulation of pyruvate dehydrogenase kinase activity from pig kidney cortex.

    PubMed Central

    Pawelczyk, T; Olson, M S

    1992-01-01

    The activity of pyruvate dehydrogenase (PDH) kinase in the purified PDH complex from pig kidney is sensitive to changes in ionic strength. The enzyme has optimum activity within a small range of ionic strength (0.03-0.05 M). An increase in ionic strength from 0.04 M to 0.2 M lowers the activity of PDH kinase by 32% and decreases the Km for ATP from 25 microM to 10 microM. At constant ionic strength (0.15 M) the enzyme has optimum activity over a broad pH range (7.2-8.0). The PDH kinase is stimulated 2.2-fold by 20 mM-K+, whereas Na+ even at high concentration (80 mM) has no effect on the enzyme activity. The stimulation of PDH kinase by K+ is not dependent on pH and ionic strength. PDH kinase is inhibited by HPO4(2-) in the presence of K+, whereas HPO4(2-) has no effect on the activity of this enzyme in the absence of K+. HPO4(2-) at concentrations of 2 and 10 mM inhibits PDH kinase by 28% and 55% respectively. The magnitude of this inhibition is not dependent on the ATP/ADP ratio. Inhibition by HPO4(2-) in the concentration range 0-10 mM is non-competitive with respect to ATP, and becomes mixed-type at concentrations over 10 mM. The Ki for HPO4(2-) is 10 mM. When HPO4(2-) is replaced by SO4(2-), the same effects on the activity of PDH kinase are observed. PDH kinase is also inhibited by Cl-. In the presence of 80 mM-Cl- the PDH kinase is inhibited by 40%. The inhibition by Cl- is not dependent on K+. In conclusion, we postulate that changes in phosphate concentrations may play a significant role in the regulation of PDH kinase activity in vivo. PMID:1463442

  11. Regulation of glomerulotubular balance: flow-activated proximal tubule function.

    PubMed

    Wang, Tong; Weinbaum, Sheldon; Weinstein, Alan M

    2017-03-07

    The purpose of this review is to summarize our knowledge and understanding of the physiological importance and the mechanisms underlying flow-activated proximal tubule transport. Since the earliest micropuncture studies of mammalian proximal tubule, it has been recognized that tubular flow is an important regulator of sodium, potassium, and acid-base transport in the kidney. Increased fluid flow stimulates Na(+) and HCO3(-) absorption in the proximal tubule via stimulation of Na/H-exchanger isoform 3 (NHE3) and H(+)-ATPase. In the proximal tubule, brush border microvilli are the major flow sensors, which experience changes in hydrodynamic drag and bending moment as luminal flow velocity changes and which transmit the force of altered flow to cytoskeletal structures within the cell. The signal to NHE3 depends upon the integrity of the actin cytoskeleton; the signal to the H(+)-ATPase depends upon microtubules. We have demonstrated that alterations in fluid drag impact tubule function by modulating ion transporter availability within the brush border membrane of the proximal tubule. Beyond that, there is evidence that transporter activity within the peritubular membrane is also modulated by luminal flow. Secondary messengers that regulate the flow-mediated tubule function have also been delineated. Dopamine blunts the responsiveness of proximal tubule transporters to changes in luminal flow velocity, while a DA1 antagonist increases flow sensitivity of solute reabsorption. IP3 receptor-mediated intracellular Ca(2+) signaling is critical to transduction of microvillus drag. In this review, we summarize our findings of the regulatory mechanism of flow-mediated Na(+) and HCO3(-) transport in the proximal tubule and review available information about flow sensing and regulatory mechanism of glomerulotubular balance.

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

    PubMed

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

    2009-08-01

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

  13. 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.

  14. KIF4 motor regulates activity-dependent neuronal survival by suppressing PARP-1 enzymatic activity.

    PubMed

    Midorikawa, Ryosuke; Takei, Yosuke; Hirokawa, Nobutaka

    2006-04-21

    In brain development, apoptosis is a physiological process that controls the final numbers of neurons. Here, we report that the activity-dependent prevention of apoptosis in juvenile neurons is regulated by kinesin superfamily protein 4 (KIF4), a microtubule-based molecular motor. The C-terminal domain of KIF4 is a module that suppresses the activity of poly (ADP-ribose) polymerase-1 (PARP-1), a nuclear enzyme known to maintain cell homeostasis by repairing DNA and serving as a transcriptional regulator. When neurons are stimulated by membrane depolarization, calcium signaling mediated by CaMKII induces dissociation of KIF4 from PARP-1, resulting in upregulation of PARP-1 activity, which supports neuron survival. After dissociation from PARP-1, KIF4 enters into the cytoplasm from the nucleus and moves to the distal part of neurites in a microtubule-dependent manner. We suggested that KIF4 controls the activity-dependent survival of postmitotic neurons by regulating PARP-1 activity in brain development.

  15. 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.

  16. Carry-over of self-regulation for physical activity to self-regulating eating in women with morbid obesity.

    PubMed

    Annesi, James J; Porter, Kandice J; Johnson, Ping H

    2015-01-01

    Poor outcomes from behavioral treatments of severe obesity have led to a dependence on invasive medical interventions, including surgery for morbidly obese individuals. Improved methods to self-regulate eating will be required to reduce obesity. The use of self-regulation methods for completing physical activity may carry over to increased self-regulation for eating through improved feelings of competence (self-efficacy) and mood. The study recruited women (Meanage = 43 years) with morbid obesity (MeanBMI = 44 kg/m(2)) to participate in 26 weeks of cognitive-behavioral support of physical activity paired with either nutrition education (n = 51) or cognitive-behavioral nutrition (n = 51) methods. Data collected were from 2011 and 2012. Significant improvements in self-regulation for physical activity, self-regulation for eating, overall mood, and self-efficacy for eating, with greater improvement in self-regulation for eating, were observed in the cognitive-behavioral nutrition group. Changes in mood and self-efficacy for eating significantly mediated the relationship between changes in self-regulation for physical activity and self-regulation for eating. When subscales of overall mood and self-efficacy were entered into separate regression equations as mediators, the only significant mediators were vigor, and controlling eating when socially pressured and when increased cues to overeat were present.

  17. ELF5-Mediated AR Activation Regulates Prostate Cancer Progression

    PubMed Central

    Li, Kai; Guo, Yongmin; Yang, Xiong; Zhang, Zhihong; Zhang, Changwen; Xu, Yong

    2017-01-01

    The transcription factor E74-like factor 5 (ELF5) is a potent antioncogene that can prevent epithelial-mesenchymal transition (EMT) and metastasis in prostate cancer (PCa). However, little is known how it suppress the tumor growth and if it can interact with androgen receptor (AR). In this study, we find that the ELF5 is frequently expressed in AR activated PCa cells, where it binds to AR acting as a physiological partner and negatively regulates its transcriptional activity. In addition, the interaction between ELF5 and AR is androgen-dependent. Downregulation of ELF5 by shRNA increases the expression of AR-response genes and the progression of PCa. Moreover, ELF5 is a AR-dependent gene that its expression can be induced by androgen and suppressed by antiandrogen treatment. Notably, forced reduction of ELF5 in LNCaP cells facilitates the binding of AR to ARE in ELF5 gene and enabling its transcription, so that low level ELF5 can turn up its own expression by the negative feedback loop. PMID:28287091

  18. 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.

  19. 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

  20. ELF5-Mediated AR Activation Regulates Prostate Cancer Progression.

    PubMed

    Li, Kai; Guo, Yongmin; Yang, Xiong; Zhang, Zhihong; Zhang, Changwen; Xu, Yong

    2017-03-13

    The transcription factor E74-like factor 5 (ELF5) is a potent antioncogene that can prevent epithelial-mesenchymal transition (EMT) and metastasis in prostate cancer (PCa). However, little is known how it suppress the tumor growth and if it can interact with androgen receptor (AR). In this study, we find that the ELF5 is frequently expressed in AR activated PCa cells, where it binds to AR acting as a physiological partner and negatively regulates its transcriptional activity. In addition, the interaction between ELF5 and AR is androgen-dependent. Downregulation of ELF5 by shRNA increases the expression of AR-response genes and the progression of PCa. Moreover, ELF5 is a AR-dependent gene that its expression can be induced by androgen and suppressed by antiandrogen treatment. Notably, forced reduction of ELF5 in LNCaP cells facilitates the binding of AR to ARE in ELF5 gene and enabling its transcription, so that low level ELF5 can turn up its own expression by the negative feedback loop.

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

    PubMed

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

    2009-06-01

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

  2. Cortical neuronal activity does not regulate sleep homeostasis.

    PubMed

    Qiu, M-H; Chen, M C; Lu, J

    2015-06-25

    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 (100mg/kg) to rats, producing a dissociated state with slow-wave cortical electroencephalogram (EEG) but waking behavior (e.g. locomotion). Atropine injections during the light period produced 6h of slow-wave cortical EEG but also subcortical arousal. Afterward, 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.

  3. 15 CFR 922.82 - Prohibited or otherwise regulated activities.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... the final regulation. (11) Taking any marine mammal, sea turtle, or bird within or above the Sanctuary... mammal, sea turtle, or bird taken, except as authorized by the MMPA, ESA, MBTA, by any regulation,...

  4. 15 CFR 922.82 - Prohibited or otherwise regulated activities.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... the final regulation. (11) Taking any marine mammal, sea turtle, or bird within or above the Sanctuary... mammal, sea turtle, or bird taken, except as authorized by the MMPA, ESA, MBTA, by any regulation,...

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

    PubMed

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

    2005-04-01

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

  6. 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

  7. 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.

  8. 75 FR 5100 - Agency Information Collection Activities: NAFTA Regulations and Certificate of Origin

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-02-01

    ... SECURITY Customs and Border Protection Agency Information Collection Activities: NAFTA Regulations and... collection requirement concerning the NAFTA Regulations and Certificate of Origin. This request for comment... CBP is soliciting comments concerning the following information collection: Title: NAFTA...

  9. Endothelin-converting enzyme 2 differentially regulates opioid receptor activity

    PubMed Central

    Gupta, A; Fujita, W; Gomes, I; Bobeck, E; Devi, L A

    2015-01-01

    BACKGROUND AND PURPOSE Opioid receptor function is modulated by post-activation events such as receptor endocytosis, recycling and/or degradation. While it is generally understood that the peptide ligand gets co-endocytosed with the receptor, relatively few studies have investigated the role of the endocytosed peptide and peptide processing enzymes in regulating receptor function. In this study, we focused on endothelin-converting enzyme 2 (ECE2), a member of the neprilysin family of metallopeptidases that exhibits an acidic pH optimum, localizes to an intracellular compartment and selectively processes neuropeptides including opioid peptides in vitro, and examined its role in modulating μ receptor recycling and resensitization. EXPERIMENTAL APPROACH The effect of ECE2 inhibition on hydrolysis of the endocytosed peptide was examined using thin-layer chromatography and on μ opioid receptor trafficking using either elisa or microscopy. The effect of ECE2 inhibition on receptor signalling was measured using a cAMP assay and, in vivo, on antinociception induced by intrathecally administered opioids by the tail-flick assay. KEY RESULTS The highly selective ECE2 inhibitor, S136492, significantly impaired μ receptor recycling and signalling by only those ligands that are ECE2 substrates and this was seen both in heterologous cells and in cells endogenously co-expressing μ receptors with ECE2. We also found that ECE2 inhibition attenuated antinociception mediated only by opioid peptides that are ECE2 substrates. CONCLUSIONS AND IMPLICATIONS These results suggest that ECE2, by selectively processing endogenous opioid peptides in the endocytic compartment, plays a role in modulating opioid receptor activity. LINKED ARTICLES This article is part of a themed section on Opioids: New Pathways to Functional Selectivity. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2015.172.issue-2 PMID:24990314

  10. V-1 regulates capping protein activity in vivo.

    PubMed

    Jung, Goeh; Alexander, Christopher J; Wu, Xufeng S; Piszczek, Grzegorz; Chen, Bi-Chang; Betzig, Eric; Hammer, John A

    2016-10-25

    Capping Protein (CP) plays a central role in the creation of the Arp2/3-generated branched actin networks comprising lamellipodia and pseudopodia by virtue of its ability to cap the actin filament barbed end, which promotes Arp2/3-dependent filament nucleation and optimal branching. The highly conserved protein V-1/Myotrophin binds CP tightly in vitro to render it incapable of binding the barbed end. Here we addressed the physiological significance of this CP antagonist in Dictyostelium, which expresses a V-1 homolog that we show is very similar biochemically to mouse V-1. Consistent with previous studies of CP knockdown, overexpression of V-1 in Dictyostelium reduced the size of pseudopodia and the cortical content of Arp2/3 and induced the formation of filopodia. Importantly, these effects scaled positively with the degree of V-1 overexpression and were not seen with a V-1 mutant that cannot bind CP. V-1 is present in molar excess over CP, suggesting that it suppresses CP activity in the cytoplasm at steady state. Consistently, cells devoid of V-1, like cells overexpressing CP described previously, exhibited a significant decrease in cellular F-actin content. Moreover, V-1-null cells exhibited pronounced defects in macropinocytosis and chemotactic aggregation that were rescued by V-1, but not by the V-1 mutant. Together, these observations demonstrate that V-1 exerts significant influence in vivo on major actin-based processes via its ability to sequester CP. Finally, we present evidence that V-1's ability to sequester CP is regulated by phosphorylation, suggesting that cells may manipulate the level of active CP to tune their "actin phenotype."

  11. The yeast regulator of transcription protein Rtr1 lacks an active site and phosphatase activity.

    PubMed

    Xiang, Kehui; Manley, James L; Tong, Liang

    2012-07-10

    The activity of RNA polymerase II (Pol II) is controlled in part by the phosphorylation state of the C-terminal domain (CTD) of its largest subunit. Recent reports have suggested that yeast regulator of transcription protein, Rtr1, and its human homologue RPAP2, possess Pol II CTD Ser5 phosphatase activity. Here we report the crystal structure of Kluyveromyces lactis Rtr1, which reveals a new type of zinc finger protein and does not have any close structural homologues. Importantly, the structure does not show evidence of an active site, and extensive experiments to demonstrate its CTD phosphatase activity have been unsuccessful, suggesting that Rtr1 has a non-catalytic role in CTD dephosphorylation.

  12. Manipulation of Rubisco: the amount, activity, function and regulation.

    PubMed

    Parry, M A J; Andralojc, P J; Mitchell, R A C; Madgwick, P J; Keys, A J

    2003-05-01

    Genetic modification to increase the specificity of Rubisco for CO(2) relative to O(2) and to increase the catalytic rate of Rubisco in crop plants would have great agronomic importance. The availability of three-dimensional structures of Rubisco at atomic resolution and the characterization of site-directed mutants have greatly enhanced the understanding of the catalytic mechanism of Rubisco. Considerable progress has been made in identifying natural variation in the catalytic properties of Rubisco from different species and in developing the tools for introducing both novel and foreign Rubisco genes into plants. The additional complexities of assembling copies of the two distinct polypeptide subunits of Rubisco into a functional holoenzyme in vivo (requiring sufficient expression, post-translational modification, interaction with chaperonins, and interaction with Rubisco activase) remain a major challenge. The consequences of changing the amount of Rubisco present in leaves have been investigated by the use of antisense constructs. The manipulation of genes encoding Rubisco activase has provided a means to investigate the regulation of Rubisco activity.

  13. 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.

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

    PubMed Central

    Liu, Xinhuai

    2016-01-01

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

  15. Cytoskeletal Modulation of Lipid Interactions Regulates Lck Kinase Activity*

    PubMed Central

    Chichili, Gurunadh R.; Cail, Robert C.; Rodgers, William

    2012-01-01

    The actin cytoskeleton promotes clustering of proteins associated with cholesterol-dependent rafts, but its effect on lipid interactions that form and maintain rafts is not understood. We addressed this question by determining the effect of disrupting the cytoskeleton on co-clustering of dihexadecyl-(C16)-anchored DiO and DiI, which co-enrich in ordered lipid environments such as rafts. Co-clustering was assayed by fluorescence resonance energy transfer (FRET) in labeled T cells, where rafts function in the phosphoregulation of the Src family kinase Lck. Our results show that probe co-clustering was sensitive to depolymerization of actin filaments with latrunculin B (Lat B), inhibition of myosin II with blebbistatin, and treatment with neomycin to sequester phosphatidylinositol 4,5-bisphosphate. Cytoskeletal effects on lipid interactions were not restricted to order-preferring label because co-clustering of C16-anchored DiO with didodecyl (C12)-anchored DiI, which favors disordered lipids, was also reduced by Lat B and blebbistatin. Furthermore, conditions that disrupted probe co-clustering resulted in activation of Lck. These data show that the cytoskeleton globally modulates lipid interactions in the plasma membrane, and this property maintains rafts that function in Lck regulation. PMID:22613726

  16. HIPK2 catalytic activity and subcellular localization are regulated by activation-loop Y354 autophosphorylation

    PubMed Central

    Siepi, Francesca; Gatti, Veronica; Camerini, Serena; Crescenzi, Marco; Soddu, Silvia

    2013-01-01

    HIPK2 (homeodomain-interacting protein kinase-2) binds to and phosphorylates, at Ser and Thr residues, a large number of targets involved in cell division and cell fate decision in response to different physiological or stress stimuli. Inactivation of HIPK2 has been observed in human and mouse cancers supporting its role as a tumor suppressor. Despite the biological relevance of this kinase, very little is known on how HIPK2 becomes catalytically active. Based on sequence homologies, HIPK2 has been taxonomically classified as a subfamily member of the dual-specificity tyrosine-regulated kinases (DYRKs) and the activation-loop Y354 of HIPK2 has been found phosphorylated in different cells; however, the relevance of this Y phosphorylation is presently unknown. Here, we show that HIPK2, which is extensively phosphorylated at S/T sites throughout its functional domains, becomes catalytically active by autophosphorylation at the activation-loop Y354. In particular, we found that, in analogy to DYRKs, HIPK2-Y354 phosphorylation is an autocatalytic event and its prevention, through Y354 substitution with non-phosphorylatable amino acids or by using the kinase inhibitor purvalanol A, induces a strong reduction of the HIPK2 S/T-kinase activity on different substrates. Interestingly, at variance from DYRKs, inhibition of HIPK2-Y354 phosphorylation induces a strong out-of-target Y-kinase activity in cis and a strong cytoplasmic relocalization of the kinase. Together, these results demonstrate that the catalytic activity, substrate specificity, and subcellular localization of HIPK2 are regulated by autophosphorylation of its activation-loop Y354. PMID:23485397

  17. Chaperone-mediated autophagy regulates T cell responses through targeted degradation of negative regulators of T cell activation.

    PubMed

    Valdor, Rut; Mocholi, Enric; Botbol, Yair; Guerrero-Ros, Ignacio; Chandra, Dinesh; Koga, Hiroshi; Gravekamp, Claudia; Cuervo, Ana Maria; Macian, Fernando

    2014-11-01

    Chaperone-mediated autophagy (CMA) targets soluble proteins for lysosomal degradation. Here we found that CMA was activated in T cells in response to engagement of the T cell antigen receptor (TCR), which induced expression of the CMA-related lysosomal receptor LAMP-2A. In activated T cells, CMA targeted the ubiquitin ligase Itch and the calcineurin inhibitor RCAN1 for degradation to maintain activation-induced responses. Consequently, deletion of the gene encoding LAMP-2A in T cells caused deficient in vivo responses to immunization or infection with Listeria monocytogenes. Impaired CMA activity also occurred in T cells with age, which negatively affected their function. Restoration of LAMP-2A in T cells from old mice resulted in enhancement of activation-induced responses. Our findings define a role for CMA in regulating T cell activation through the targeted degradation of negative regulators of T cell activation.

  18. Statins enhance peroxisome proliferator-activated receptor gamma coactivator-1alpha activity to regulate energy metabolism.

    PubMed

    Wang, Wenxian; Wong, Chi-Wai

    2010-03-01

    Peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC-1alpha) serves as an inducible coactivator for a number of transcription factors to control energy metabolism. Insulin signaling through Akt kinase has been demonstrated to phosphorylate PGC-1alpha at serine 571 and downregulate its activity in the liver. Statins are 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors that reduce cholesterol synthesis in the liver. In this study, we found that statins reduced the active form of Akt and enhanced PGC-1alpha activity. Specifically, statins failed to activate an S571A mutant of PGC-1alpha. The activation of PGC-1alpha by statins selectively enhanced the expression of energy metabolizing enzymes and regulators including peroxisome proliferator-activated receptor alpha, acyl-CoA oxidase, carnitine palmitoyl transferase-1A, and pyruvate dehydrogenase kinase 4. Importantly, a constitutively active form of Akt partially reduced the statin-enhanced gene expression. Our study thus provides a plausible mechanistic explanation for the hypolipidemic effect of statin through elevating the rate of beta-oxidation and mitochondrial Kreb's cycle capacity to enhance fatty acid utilization while reducing the rate of glycolysis.

  19. Human kallikrein 6 activity is regulated via an autoproteolytic mechanism of activation/inactivation.

    PubMed

    Bayés, Alex; Tsetsenis, Theodoros; Ventura, Salvador; Vendrell, Josep; Aviles, Francesc X; Sotiropoulou, Georgia

    2004-06-01

    Human kallikrein 6 (protease M/zyme/neurosin) is a serine protease that has been suggested to be a serum biomarker for ovarian cancer and may also be involved in pathologies of the CNS. The precursor form of human kallikrein 6 (pro-hK6) was overexpressed in Pichia pastoris and found to be autoprocessed to an active but unstable mature enzyme that subsequently yielded the inactive, self-cleavage product, hK6 (D81-K244). Site-directed mutagenesis was used to investigate the basis for the intrinsic catalytic activity and the activation mechanism of pro-hK6. A single substitution R80 --> Q stabilized the activity of the mature enzyme, while substitution of the active site serine (S197 --> A) resulted in complete loss of hK6 proteolytic activity and facilitated protein production. Our data suggest that the enzymatic activity of hK6 is regulated by an autoactivation/autoinactivation mechanism. Mature hK6 displayed a trypsin-like activity against synthetic substrates and human plasminogen was identified as a putative physiological substrate for hK6, as specific cleavage at the plasminogen internal bond S460-V461 resulted in the generation of angiostatin, an endogenous inhibitor of angiogenesis and metastatic growth.

  20. 15 CFR 922.102 - Prohibited or otherwise regulated activities.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ..., coral, bottom formation, or marine plant. (B) Taking, gathering, cutting, damaging, destroying, or... COASTAL RESOURCE MANAGEMENT NATIONAL MARINE SANCTUARY PROGRAM REGULATIONS Fagatele Bay National...

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

    PubMed Central

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

    2012-01-01

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

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

    PubMed Central

    Hahn, Steven; Young, Elton T.

    2011-01-01

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

  3. Arabidopsis TTG2 regulates TRY expression through enhancement of activator complex-triggered activation.

    PubMed

    Pesch, Martina; Dartan, Burcu; Birkenbihl, Rainer; Somssich, Imre E; Hülskamp, Martin

    2014-10-01

    Trichome patterning in Arabidopsis thaliana is regulated by a regulatory feedback loop of the trichome promoting factors TRANSPARENT TESTA GLABRA1 (TTG1), GLABRA3 (GL3)/ENHANCER OF GL3 (EGL3), and GL1 and a group of homologous R3MYB proteins that act as their inhibitors. Together, they regulate the temporal and spatial expression of GL2 and TTG2, which are considered to control trichome cell differentiation. In this work, we show that TTG2 is a specific activator of TRY (but not CPC or GL2). The WRKY protein TTG2 binds to W-boxes in a minimal promoter fragment of TRY, and these W-boxes are essential for rescue of the try mutant phenotype. We further show that TTG2 alone is not able to activate TRY expression, but rather drastically enhances the activation by TTG1 and GL3. As TTG2 physically interacts with TTG1 and because TTG2 can associate with GL3 through its interaction with TTG1, we propose that TTG2 enhances the activity of TTG1 and GL3 by forming a protein complex.

  4. 8 CFR 319.5 - Public international organizations in which the U.S. participates by treaty or statute.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... UNITED STATES CITIZENS § 319.5 Public international organizations in which the U.S. participates by treaty or statute. Organizations designated by the President as international organizations pursuant to... which the United States participates by treaty or statute within the meaning of section 319(b) or...

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

    ERIC Educational Resources Information Center

    Roby, Jini L.; White, Holly

    2010-01-01

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

  6. Detection of Neu1 sialidase activity in regulating Toll-like receptor activation.

    PubMed

    Amith, Schammim R; Jayanth, Preethi; Finlay, Trisha; Franchuk, Susan; Gilmour, Alanna; Abdulkhalek, Samar; Szewczuk, Myron R

    2010-09-07

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

  7. Autonomic regulation of anti-inflammatory activities from salivary glands.

    PubMed

    Mathison, Ronald D; Davison, Joseph S; St Laurent, Chris D; Befus, A Dean

    2012-01-01

    The cervical sympathetic nerves which innervate the medial basal hypothalamus-hypophyseal complex, primary and secondary lymph organs, and numerous glands, such as the pineal, thyroid, parathyroid and salivary glands form a relevant neuroimmunoendocrine structure that is involved in the regulation of systemic homeostasis. The superior cervical ganglia and the submandibular glands form a 'neuroendocrine axis' called the cervical sympathetic trunk submandibular gland (CST-SMG) axis. The identification of this axis usurps the traditional view of salivary glands as accessory digestive structures and reinforces the view that they are important sources of systemically active immunoregulatory and anti-inflammatory factors whose release is intimately controlled by the autonomic nervous system, and in particular the sympathetic branch. An end component of the CST-SMG axis is the synthesis, processing and release of submandibular rat-1 protein (SMR1), a prohormone, that generates several different peptides, one from near its N-terminus called sialorphin and another from its C-terminus called - submandibular gland peptide-T (SGP-T). SGP-T formed the template for tripeptide fragment (FEG) and its metabolically stable D-isomeric peptide feG, which are potent inhibitors of allergy and asthma (IgE-mediated allergic reactions) and several non-IgE-mediated inflammations. The translation from rat genetics and proteomics to humans has yielded structural and functional correlates that hopefully will lead to the development of new medications and therapeutic approaches for difficult to treat disorders. Although the CST-SMG axis has barely been explored in humans recognition of the importance of this axis could facilitate an understanding and improved management of periodontal disease, and other diseases with a more systemic and nervous system basis such as asthma, autoimmunity, graft-versus-host disease and even Parkinson's disease.

  8. Identity, regulation, and activity of inducible diterpenoid phytoalexins in maize.

    PubMed

    Schmelz, Eric A; Kaplan, Fatma; Huffaker, Alisa; Dafoe, Nicole J; Vaughan, Martha M; Ni, Xinzhi; Rocca, James R; Alborn, Hans T; Teal, Peter E

    2011-03-29

    Phytoalexins constitute a broad category of pathogen- and insect-inducible biochemicals that locally protect plant tissues. Because of their agronomic significance, maize and rice have been extensively investigated for their terpenoid-based defenses, which include insect-inducible monoterpene and sesquiterpene volatiles. Rice also produces a complex array of pathogen-inducible diterpenoid phytoalexins. Despite the demonstration of fungal-induced ent-kaur-15-ene production in maize over 30 y ago, the identity of functionally analogous maize diterpenoid phytoalexins has remained elusive. In response to stem attack by the European corn borer (Ostrinia nubilalis) and fungi, we observed the induced accumulation of six ent-kaurane-related diterpenoids, collectively termed kauralexins. Isolation and identification of the predominant Rhizopus microsporus-induced metabolites revealed ent-kaur-19-al-17-oic acid and the unique analog ent-kaur-15-en-19-al-17-oic acid, assigned as kauralexins A3 and B3, respectively. Encoding an ent-copalyl diphosphate synthase, fungal-induced An2 transcript accumulation precedes highly localized kauralexin production, which can eventually exceed 100 μg · g(-1) fresh weight. Pharmacological applications of jasmonic acid and ethylene also synergize the induced accumulation of kauralexins. Occurring at elevated levels in the scutella of all inbred lines examined, kauralexins appear ubiquitous in maize. At concentrations as low as 10 μg · mL(-1), kauralexin B3 significantly inhibited the growth of the opportunistic necrotroph R. microsporus and the causal agent of anthracnose stalk rot, Colletotrichum graminicola. Kauralexins also exhibited significant O. nubilalis antifeedant activity. Our work establishes the presence of diterpenoid defenses in maize and enables a more detailed analysis of their biosynthetic pathways, regulation, and crop defense function.

  9. Vinculin contributes to Cell Invasion by Regulating Contractile Activation

    NASA Astrophysics Data System (ADS)

    Mierke, Claudia Tanja

    2008-07-01

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

  10. Endogenous activation of kainate receptors regulates glutamate release and network activity in the developing hippocampus.

    PubMed

    Lauri, Sari E; Segerstråle, Mikael; Vesikansa, Aino; Maingret, Francois; Mulle, Christophe; Collingridge, Graham L; Isaac, John T R; Taira, Tomi

    2005-05-04

    Kainate receptors (KARs) are highly expressed throughout the neonatal brain, but their function during development is unclear. Here, we show that the maturation of the hippocampus is associated with a switch in the functional role of presynaptic KARs. In a developmental period restricted to the first postnatal week, endogenous L-glutamate tonically activates KARs at CA3 glutamatergic synapses to regulate release in an action potential-independent manner. At synapses onto pyramidal cells, KARs inhibit glutamate release via a G-protein and PKC-dependent mechanism. In contrast, at glutamatergic terminals onto CA3 interneurons, presynaptic KARs can facilitate release in a G-protein-independent mechanism. In both cell types, however, KAR activation strongly upregulates inhibitory transmission. We show that, through the interplay of these novel diverse mechanisms, KARs strongly regulate the characteristic synchronous network activity observed in the neonatal hippocampus. By virtue of this, KARs are likely to play a central role in the development of hippocampal synaptic circuits.

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

    NASA Technical Reports Server (NTRS)

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

    1993-01-01

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

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

    NASA Technical Reports Server (NTRS)

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

    1993-01-01

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

  13. A Summary and Analysis of Warrantless Arrest Statutes for Domestic Violence in the United States

    ERIC Educational Resources Information Center

    Zeoli, April M.; Norris, Alexis; Brenner, Hannah

    2011-01-01

    In the United States, all 50 states and the District of Columbia have enacted statutes that allow police officers to make warrantless arrests for domestic violence given probable cause; however, state laws differ from one another in multiple, important ways. Research on domestic violence warrantless arrest laws rarely describe them as anything…

  14. 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... shipments in transit when statute becomes effective. The following conditions are hereby prescribed as... during the time when export or import shipments are in transit to or from the ports of export or...

  15. 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... shipments in transit when statute becomes effective. The following conditions are hereby prescribed as... during the time when export or import shipments are in transit to or from the ports of export or...

  16. 49 CFR 1302.43 - Applicable rates on shipments in transit when statute becomes effective.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 49 Transportation 9 2012-10-01 2012-10-01 false Applicable rates on shipments in transit when... shipments in transit when statute becomes effective. The following conditions are hereby prescribed as... during the time when export or import shipments are in transit to or from the ports of export or...

  17. 49 CFR 1302.43 - Applicable rates on shipments in transit when statute becomes effective.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 49 Transportation 9 2014-10-01 2014-10-01 false Applicable rates on shipments in transit when... shipments in transit when statute becomes effective. The following conditions are hereby prescribed as... during the time when export or import shipments are in transit to or from the ports of export or...

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

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 9 2013-10-01 2013-10-01 false Applicable rates on shipments in transit when... shipments in transit when statute becomes effective. The following conditions are hereby prescribed as... during the time when export or import shipments are in transit to or from the ports of export or...

  19. 36 CFR 1256.50 - Information exempted from disclosure by statute.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 36 Parks, Forests, and Public Property 3 2014-07-01 2014-07-01 false Information exempted from disclosure by statute. 1256.50 Section 1256.50 Parks, Forests, and Public Property NATIONAL ARCHIVES AND RECORDS ADMINISTRATION PUBLIC AVAILABILITY AND USE ACCESS TO RECORDS AND DONATED HISTORICAL...

  20. 36 CFR 902.53 - Records exempted from disclosure by statute.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 36 Parks, Forests, and Public Property 3 2010-07-01 2010-07-01 false Records exempted from disclosure by statute. 902.53 Section 902.53 Parks, Forests, and Public Property PENNSYLVANIA AVENUE... 1905 of title 18 U.S.C., protecting trade secrets, processes, and certain economic and other...

  1. 36 CFR 902.53 - Records exempted from disclosure by statute.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 36 Parks, Forests, and Public Property 3 2011-07-01 2011-07-01 false Records exempted from disclosure by statute. 902.53 Section 902.53 Parks, Forests, and Public Property PENNSYLVANIA AVENUE... 1905 of title 18 U.S.C., protecting trade secrets, processes, and certain economic and other...

  2. 36 CFR 902.53 - Records exempted from disclosure by statute.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 36 Parks, Forests, and Public Property 3 2014-07-01 2014-07-01 false Records exempted from disclosure by statute. 902.53 Section 902.53 Parks, Forests, and Public Property PENNSYLVANIA AVENUE... 1905 of title 18 U.S.C., protecting trade secrets, processes, and certain economic and other...

  3. An Analysis of Impasse Resolution Provisions of State Teacher-Board Negotiations Statutes.

    ERIC Educational Resources Information Center

    Zirkel, Perry A.

    The purpose of this analysis is to systematically survey the impasse resolution provisions of the 30 state statutes governing teacher-board negotiations and to tentatively explore via statistical techniques whether there is a significant relationship between the degree of compulsion in such provisions and the type and comprehensiveness of such…

  4. 41 CFR Appendix A to Part 102 - 37-Miscellaneous Donation Statutes

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... Property: Obsolete material not needed for naval purposes. Eligible Recipients: Sea scouts of the Boy Scouts of America; Naval Sea Cadet Corps; and the Young Marines of the Marine Corps League. Statute: 10 U... needed for the Coast Guard. Eligible Recipients: Coast Guard Auxiliary; sea scout service of the...

  5. 32 CFR 537.2 - Scope of non-maritime affirmative claims statutes.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... statutes. (a) Recovery for government property loss or damage. The FCCA, originally passed in 1966, gives... medical care recoveries. (b) Recovery for medical expenses and lost military pay. (1) The FMCRA, passed in 1962, authorizes recovery from a third person of the expenses for medical care the United...

  6. 32 CFR 22.310 - Statutes concerning certain research, development, and facilities construction grants.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ...)(i) of this section does not apply to any grant that calls upon the National Academy of Sciences to... 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...

  7. Nitric Oxide Regulates Neuronal Activity via Calcium-Activated Potassium Channels

    PubMed Central

    Zhong, Lei Ray; Estes, Stephen; Artinian, Liana; Rehder, Vincent

    2013-01-01

    Nitric oxide (NO) is an unconventional membrane-permeable messenger molecule that has been shown to play various roles in the nervous system. How NO modulates ion channels to affect neuronal functions is not well understood. In gastropods, NO has been implicated in regulating the feeding motor program. The buccal motoneuron, B19, of the freshwater pond snail Helisoma trivolvis is active during the hyper-retraction phase of the feeding motor program and is located in the vicinity of NO-producing neurons in the buccal ganglion. Here, we asked whether B19 neurons might serve as direct targets of NO signaling. Previous work established NO as a key regulator of growth cone motility and neuronal excitability in another buccal neuron involved in feeding, the B5 neuron. This raised the question whether NO might modulate the electrical activity and neuronal excitability of B19 neurons as well, and if so whether NO acted on the same or a different set of ion channels in both neurons. To study specific responses of NO on B19 neurons and to eliminate indirect effects contributed by other cells, the majority of experiments were performed on single cultured B19 neurons. Addition of NO donors caused a prolonged depolarization of the membrane potential and an increase in neuronal excitability. The effects of NO could mainly be attributed to the inhibition of two types of calcium-activated potassium channels, apamin-sensitive and iberiotoxin-sensitive potassium channels. NO was found to also cause a depolarization in B19 neurons in situ, but only after NO synthase activity in buccal ganglia had been blocked. The results suggest that NO acts as a critical modulator of neuronal excitability in B19 neurons, and that calcium-activated potassium channels may serve as a common target of NO in neurons. PMID:24236040

  8. 15 CFR 922.132 - Prohibited or otherwise regulated activities.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... National Weather Service and is in effect for San Mateo County, and only during December, January, and... Trade (Continued) NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE OCEAN AND COASTAL RESOURCE MANAGEMENT NATIONAL MARINE SANCTUARY PROGRAM REGULATIONS Monterey Bay National...

  9. 15 CFR 922.132 - Prohibited or otherwise regulated activities.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... National Weather Service and is in effect for San Mateo County, and only during December, January, and... Trade (Continued) NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE OCEAN AND COASTAL RESOURCE MANAGEMENT NATIONAL MARINE SANCTUARY PROGRAM REGULATIONS Monterey Bay National...

  10. 15 CFR 922.102 - Prohibited or otherwise regulated activities.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... COASTAL RESOURCE MANAGEMENT NATIONAL MARINE SANCTUARY PROGRAM REGULATIONS Fagatele Bay National Marine..., coral, bottom formation, or marine plant. (B) Taking, gathering, cutting, damaging, destroying, or..., filling, dynamiting, bottom trawling, or otherwise altering the seabed. (6) Removing, damaging,...

  11. Flipped Classroom with Problem Based Activities: Exploring Self-Regulated Learning in a Programming Language Course

    ERIC Educational Resources Information Center

    Çakiroglu, Ünal; Öztürk, Mücahit

    2017-01-01

    This study intended to explore the development of self-regulation in a flipped classroom setting. Problem based learning activities were carried out in flipped classrooms to promote self-regulation. A total of 30 undergraduate students from Mechatronic department participated in the study. Self-regulation skills were discussed through students'…

  12. 32 CFR 757.17 - Statute of limitations.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... treatment. (b) Claims asserted under 10 U.S.C. 1095. Although legal arguments can be made that claims... contract and can be brought within 6 years (28 U.S.C. 2415a), all claims should be asserted within 3 years... REGULATIONS Medical Care Recovery Act (MCRA) Claims and Claims Asserted Pursuant to 10 U.S.C. 1095 §...

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

    PubMed Central

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

    2015-01-01

    It is fast emerging that maintaining mitochondrial function is important for regulating astrocyte function, although the specific mechanisms that govern astrocyte mitochondrial trafficking and positioning remain poorly understood. The mitochondrial Rho-GTPase 1 protein (Miro1) regulates mitochondrial trafficking and detachment from the microtubule transport network to control activity-dependent mitochondrial positioning in neurons. However, whether Miro proteins are important for regulating signaling-dependent mitochondrial dynamics in astrocytic processes remains unclear. Using live-cell confocal microscopy of rat organotypic hippocampal slices, we find that enhancing neuronal activity induces transient mitochondrial remodeling in astrocytes, with a concomitant, transient reduction in mitochondrial trafficking, mediated by elevations in intracellular Ca2+. Stimulating neuronal activity also induced mitochondrial confinement within astrocytic processes in close proximity to synapses. Furthermore, we show that the Ca2+-sensing EF-hand domains of Miro1 are important for regulating mitochondrial trafficking in astrocytes and required for activity-driven mitochondrial confinement near synapses. Additionally, activity-dependent mitochondrial positioning by Miro1 reciprocally regulates the levels of intracellular Ca2+ in astrocytic processes. Thus, the regulation of intracellular Ca2+ signaling, dependent on Miro1-mediated mitochondrial positioning, could have important consequences for astrocyte Ca2+ wave propagation, gliotransmission, and ultimately neuronal function. SIGNIFICANCE STATEMENT Mitochondria are key cellular organelles that play important roles in providing cellular energy and buffering intracellular calcium ions. The mechanisms that control mitochondrial distribution within the processes of glial cells called astrocytes and the impact this may have on calcium signaling remains unclear. We show that activation of glutamate receptors or increased neuronal

  14. Self-Regulated Learning and Perceived Health among University Students Participating in Physical Activity Classes

    ERIC Educational Resources Information Center

    McBride, Ron E.; Altunsöz, Irmak Hürmeriç; Su, Xiaoxia; Xiang, Ping; Demirhan, Giyasettin

    2016-01-01

    The purpose of this study was to explore motivational indicators of self-regulated learning (SRL) and the relationship between self-regulation (SR) and perceived health among university students enrolled in physical activity (PA) classes. One hundred thirty-one Turkish students participating in physical education activity classes at two…

  15. Physical Activity, Self-Regulation, and Early Academic Achievement in Preschool Children

    ERIC Educational Resources Information Center

    Becker, Derek R.; McClelland, Megan M.; Loprinzi, Paul; Trost, Stewart G.

    2014-01-01

    Research Findings: The present study investigated whether active play during recess was associated with self-regulation and academic achievement in a prekindergarten sample. A total of 51 children in classes containing approximately half Head Start children were assessed on self-regulation, active play, and early academic achievement. Path…

  16. 15 CFR 922.132 - Prohibited or otherwise regulated activities.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... Weather Service and is in effect for San Mateo County, and only during December, January, and February. (8... Trade (Continued) NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE OCEAN AND COASTAL RESOURCE MANAGEMENT NATIONAL MARINE SANCTUARY PROGRAM REGULATIONS Monterey Bay National...

  17. 15 CFR 922.132 - Prohibited or otherwise regulated activities.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... (at Pillar Point) exists only when a High Surf Warning has been issued by the National Weather Service... Trade (Continued) NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE OCEAN AND COASTAL RESOURCE MANAGEMENT NATIONAL MARINE SANCTUARY PROGRAM REGULATIONS Monterey Bay National...

  18. 15 CFR 922.132 - Prohibited or otherwise regulated activities.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... Weather Service and is in effect for San Mateo County, and only during December, January, and February. (8... Trade (Continued) NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE OCEAN AND COASTAL RESOURCE MANAGEMENT NATIONAL MARINE SANCTUARY PROGRAM REGULATIONS Monterey Bay National...

  19. Polyphosphate - an ancient energy source and active metabolic regulator

    PubMed Central

    2011-01-01

    There are a several molecules on Earth that effectively store energy within their covalent bonds, and one of these energy-rich molecules is polyphosphate. In microbial cells, polyphosphate granules are synthesised for both energy and phosphate storage and are degraded to produce nucleotide triphosphate or phosphate. Energy released from these energetic carriers is used by the cell for production of all vital molecules such as amino acids, nucleobases, sugars and lipids. Polyphosphate chains directly regulate some processes in the cell and are used as phosphate donors in gene regulation. These two processes, energetic metabolism and regulation, are orchestrated by polyphosphate kinases. Polyphosphate kinases (PPKs) can currently be categorized into three groups (PPK1, PPK2 and PPK3) according their functionality; they can also be divided into three groups according their homology (EcPPK1, PaPPK2 and ScVTC). This review discusses historical information, similarities and differences, biochemical characteristics, roles in stress response regulation and possible applications in the biotechnology industry of these enzymes. At the end of the review, a hypothesis is discussed in view of synthetic biology applications that states polyphosphate and calcium-rich organelles have endosymbiotic origins from ancient protocells that metabolized polyphosphate. PMID:21816086

  20. 15 CFR 922.142 - Prohibited or otherwise regulated activities.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... maximum extent practicable any advance impact on Sanctuary resources and qualities. Civil engineering and... COASTAL RESOURCE MANAGEMENT NATIONAL MARINE SANCTUARY PROGRAM REGULATIONS Stellwagen Bank National Marine... the Sanctuary, any material or other matter except: (A) Fish, fish parts, chumming materials or...

  1. 18.6-year Earth tide regulates geyser activity.

    PubMed

    Rinehart, J S

    1972-07-28

    Over 40 years of records from Yellowstone National Park, Wyoming, show that the 18.6-year tidal component strongly regulates the frequencies of eruption of Grand and Steamboat geysers. The frequency of Grand Geyser increases with increasing tidal force and that of Steamboat Geyser decreases, which suggests that tidal dilatation is one factor affecting heat flow to a geyser.

  2. 15 CFR 922.92 - Prohibited or otherwise regulated activities.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... COASTAL RESOURCE MANAGEMENT NATIONAL MARINE SANCTUARY PROGRAM REGULATIONS Gray's Reef National Marine... marine sanitation devices; and (iii) Vessel cooling water. (4) Operating a watercraft other than in... marine organism, or any part thereof, living or dead, within the Sanctuary by any means except by use...

  3. 15 CFR 922.61 - Prohibited or otherwise regulated activities.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... COASTAL RESOURCE MANAGEMENT NATIONAL MARINE SANCTUARY PROGRAM REGULATIONS Monitor National Marine... explosive or explosive mechanism; (f) Drilling or coring the seabed; (g) Lowering, laying, positioning or raising any type of seabed cable or cable-laying device; (h) Trawling; or (i) Discharging waster...

  4. Membrane lipids regulate ganglioside GM2 catabolism and GM2 activator protein activity[S

    PubMed Central

    Anheuser, Susi; Breiden, Bernadette; Schwarzmann, Günter; Sandhoff, Konrad

    2015-01-01

    Ganglioside GM2 is the major lysosomal storage compound of Tay-Sachs disease. It also accumulates in Niemann-Pick disease types A and B with primary storage of SM and with cholesterol in type C. Reconstitution of GM2 catabolism with β-hexosaminidase A and GM2 activator protein (GM2AP) at uncharged liposomal surfaces carrying GM2 as substrate generated only a physiologically irrelevant catabolic rate, even at pH 4.2. However, incorporation of anionic phospholipids into the GM2 carrying liposomes stimulated GM2 hydrolysis more than 10-fold, while the incorporation of plasma membrane stabilizing lipids (SM and cholesterol) generated a strong inhibition of GM2 hydrolysis, even in the presence of anionic phospholipids. Mobilization of membrane lipids by GM2AP was also inhibited in the presence of cholesterol or SM, as revealed by surface plasmon resonance studies. These lipids also reduced the interliposomal transfer rate of 2-NBD-GM1 by GM2AP, as observed in assays using Förster resonance energy transfer. Our data raise major concerns about the usage of recombinant His-tagged GM2AP compared with untagged protein. The former binds more strongly to anionic GM2-carrying liposomal surfaces, increases GM2 hydrolysis, and accelerates intermembrane transfer of 2-NBD-GM1, but does not mobilize membrane lipids. PMID:26175473

  5. mTORC1-Induced HK1-Dependent Glycolysis Regulates NLRP3 Inflammasome Activation.

    PubMed

    Moon, Jong-Seok; Hisata, Shu; Park, Mi-Ae; DeNicola, Gina M; Ryter, Stefan W; Nakahira, Kiichi; Choi, Augustine M K

    2015-07-07

    The mammalian target of rapamycin complex 1 (mTORC1) regulates activation of immune cells and cellular energy metabolism. Although glycolysis has been linked to immune functions, the mechanisms by which glycolysis regulates NLRP3 inflammasome activation remain unclear. Here, we demonstrate that mTORC1-induced glycolysis provides an essential mechanism for NLRP3 inflammasome activation. Moreover, we demonstrate that hexokinase 1 (HK1)-dependent glycolysis, under the regulation of mTORC1, represents a critical metabolic pathway for NLRP3 inflammasome activation. Downregulation of glycolysis by inhibition of Raptor/mTORC1 or HK1 suppressed both pro-IL-1β maturation and caspase-1 activation in macrophages in response to LPS and ATP. These results suggest that upregulation of HK1-dependent glycolysis by mTORC1 regulates NLRP3 inflammasome activation.

  6. Activation of TRPV4 Regulates Respiration through Indirect Activation of Bronchopulmonary Sensory Neurons

    PubMed Central

    Gu, Qihai (David); Moss, Charles R.; Kettelhut, Kristen L.; Gilbert, Carolyn A.; Hu, Hongzhen

    2016-01-01

    Transient receptor potential vanilloid receptor 4 (TRPV4) is a calcium-permeable non-selective cation channel implicated in numerous physiological and pathological functions. This study aimed to investigate the effect of TRPV4 activation on respiration and to explore the potential involvement of bronchopulmonary sensory neurons. Potent TRPV4 agonist GSK1016790A was injected into right atrium in anesthetized spontaneously breathing rats and the changes in breathing were measured. Patch-clamp recording was performed to investigate the effect of GSK1016790A or another TRPV4 activator 4α-PDD on cultured rat vagal bronchopulmonary sensory neurons. Immunohistochemistry was carried out to determine the TRPV4-expressing cells in lung slices obtained from TRPV4-EGFP mice. Our results showed, that right-atrial injection of GSK1016790A evoked a slow-developing, long-lasting rapid shallow breathing in anesthetized rats. Activation of TRPV4 also significantly potentiated capsaicin-evoked chemoreflex responses. The alteration in ventilation induced by GSK1016790A was abolished by cutting or perineural capsaicin treatment of both vagi, indicating the involvement of bronchopulmonary afferent neurons. The stimulating and sensitizing effects of GSK1016790A were abolished by a selective TRPV4 antagonist GSK2193874 and also by inhibiting cyclooxygenase with indomethacin. Surprising, GSK1016790A or 4α-PDD did not activate isolated bronchopulmonary sensory neurons, nor did they modulate capsaicin-induced inward currents in these neurons. Furthermore, TRPV4 expression was found in alveolar macrophages, alveolar epithelial, and vascular endothelial cells. Collectively, our results suggest that GSK1016790A regulates the respiration through an indirect activation of bronchopulmonary sensory neurons, likely via its stimulation of other TRPV4-expressing cells in the lungs and airways. PMID:26973533

  7. Medicare and State Health Care Programs: Fraud and Abuse; Revisions to the Safe Harbors Under the Anti-Kickback Statute and Civil Monetary Penalty Rules Regarding Beneficiary Inducements. Final rule.

    PubMed

    2016-12-07

    In this final rule, OIG amends the safe harbors to the anti-kickback statute by adding new safe harbors that protect certain payment practices and business arrangements from sanctions under the anti-kickback statute. The OIG also amends the civil monetary penalty (CMP) rules by codifying revisions to the definition of "remuneration," added by the Balanced Budget Act (BBA) of 1997 and the Patient Protection and Affordable Care Act, Public Law 111-148, 124 Stat. 119 (2010), as amended by the Health Care and Education Reconciliation Act of 2010 (ACA). This rule updates the existing safe harbor regulations and enhances flexibility for providers and others to engage in health care business arrangements to improve efficiency and access to quality care while protecting programs and patients from fraud and abuse.

  8. Supreme Court refuses to review clinic access law; Second Appeals Court upholds statute.

    PubMed

    1995-06-30

    On June 19, the US Supreme Court refused to review "Woodall v. Reno," a challenge to the Freedom of Access to Clinic Entrances Act (FACE) filed in Virginia by an anti-choice individual. FACE prohibits the use of force, threat of force, or physical obstruction to intentionally injure, intimidate, or interfere with anyone providing or obtaining reproductive health services. By denying the petition for "certiorari," the High Court let stand the US Court of Appeals for the Fourth Circuit decision in February. In that ruling, the midlevel federal court affirmed a lower court's dismissal of two of the eight anti-choice lawsuits challenging FACE, "Woodall v. Reno" and "American Life League v. Reno," which were consolidated by the appeals panel. Although plaintiffs in the first case filed a request for review by the High Court within days of the appellate court ruling, plaintiffs in the latter case waited until May to do so. The Department of Justice, which is defending the federal statute, and CRLP and the NOW Legal Defense and Education Fund, who are intervening on behalf of women and health care providers, will file their opposition to the review by July 26. The Justices will then decide to hear the case. On June 23, a three-judge panel for the US Court of Appeals for the Eleventh Circuit affirmed a lower court's decision to dismiss "Cheffer v. Reno," a facial challenge by Florida anti-choice activists seeking to invalidate FACE. The appeals court had ruled the law did not infringe on First Amendment rights, and the panel rejected the argument that Congress had exceeded its authority under the Commerce Clause of the US Constitution by finding that the measure "protects and regulates commercial enterprises." The appeals court accepted an "amicus" brief filed by CRLP and NOW Legal Defense and Education Fund on behalf of the National Abortion Federation, the National Organization of Women, physicians, and women's health clinics, but denied their request to intervene in the

  9. Adenosine monophosphate-activated kinase and its key role in catabolism: structure, regulation, biological activity, and pharmacological activation.

    PubMed

    Krishan, Sukriti; Richardson, Des R; Sahni, Sumit

    2015-01-01

    Adenosine monophosphate-activated protein kinase (AMPK) is a cellular energy sensor, which once activated, plays a role in several processes within the cell to restore energy homeostasis. The protein enhances catabolic pathways, such as β-oxidation and autophagy, to generate ATP, and inhibits anabolic processes that require energy, including fatty acid, cholesterol, and protein synthesis. Due to its key role in the regulation of critical cellular pathways, deregulation of AMPK is associated with the pathology of many diseases, including cancer, Wolff-Parkinson-White syndrome, neurodegenerative disorders, diabetes, and metabolic syndrome. In fact, AMPK is a target of some pharmacological agents implemented in the treatment of diabetes (metformin and thiazolidinediones) as well as other naturally derived products, such as berberine, which is used in traditional medicine. Due to its critical role in the cell and the pathology of several disorders, research into developing AMPK as a therapeutic target is becoming a burgeoning and exciting field of pharmacological research. A profound understanding of the regulation and activity of AMPK would enhance its development as a promising therapeutic target.

  10. 29 CFR 790.3 - Provisions of the statute.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... PORTAL-TO-PORTAL ACT OF 1947 ON THE FAIR LABOR STANDARDS ACT OF 1938 Provisions Relating to Certain... the Portal Act, which relates to so-called “portal-to-portal” activities engaged in by employees on...

  11. 29 CFR 790.3 - Provisions of the statute.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... PORTAL-TO-PORTAL ACT OF 1947 ON THE FAIR LABOR STANDARDS ACT OF 1938 Provisions Relating to Certain... the Portal Act, which relates to so-called “portal-to-portal” activities engaged in by employees on...

  12. 29 CFR 790.3 - Provisions of the statute.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... PORTAL-TO-PORTAL ACT OF 1947 ON THE FAIR LABOR STANDARDS ACT OF 1938 Provisions Relating to Certain... the Portal Act, which relates to so-called “portal-to-portal” activities engaged in by employees on...

  13. 29 CFR 790.3 - Provisions of the statute.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... PORTAL-TO-PORTAL ACT OF 1947 ON THE FAIR LABOR STANDARDS ACT OF 1938 Provisions Relating to Certain... the Portal Act, which relates to so-called “portal-to-portal” activities engaged in by employees on...

  14. 29 CFR 790.3 - Provisions of the statute.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... PORTAL-TO-PORTAL ACT OF 1947 ON THE FAIR LABOR STANDARDS ACT OF 1938 Provisions Relating to Certain... the Portal Act, which relates to so-called “portal-to-portal” activities engaged in by employees on...

  15. Examining "Active" Procrastination from a Self-Regulated Learning Perspective

    ERIC Educational Resources Information Center

    Cao, Li

    2012-01-01

    This study examined the notion that active procrastinators are a positive type of procrastinators who possess desirable characteristics similar to non-procrastinators, but different from the traditional passive procrastinators. A two-step procedure was followed to categorise university students (N = 125) as active procrastinators, passive…

  16. Insulin Signaling Regulates Fatty Acid Catabolism at the Level of CoA Activation

    PubMed Central

    Xu, Xiaojun; Gopalacharyulu, Peddinti; Seppänen-Laakso, Tuulikki; Ruskeepää, Anna-Liisa; Aye, Cho Cho; Carson, Brian P.; Mora, Silvia; Orešič, Matej; Teleman, Aurelio A.

    2012-01-01

    The insulin/IGF signaling pathway is a highly conserved regulator of metabolism in flies and mammals, regulating multiple physiological functions including lipid metabolism. Although insulin signaling is known to regulate the activity of a number of enzymes in metabolic pathways, a comprehensive understanding of how the insulin signaling pathway regulates metabolic pathways is still lacking. Accepted knowledge suggests the key regulated step in triglyceride (TAG) catabolism is the release of fatty acids from TAG via the action of lipases. We show here that an additional, important regulated step is the activation of fatty acids for beta-oxidation via Acyl Co-A synthetases (ACS). We identify pudgy as an ACS that is transcriptionally regulated by direct FOXO action in Drosophila. Increasing or reducing pudgy expression in vivo causes a decrease or increase in organismal TAG levels respectively, indicating that pudgy expression levels are important for proper lipid homeostasis. We show that multiple ACSs are also transcriptionally regulated by insulin signaling in mammalian cells. In sum, we identify fatty acid activation onto CoA as an important, regulated step in triglyceride catabolism, and we identify a mechanistic link through which insulin regulates lipid homeostasis. PMID:22275878

  17. Simulated shift work in rats perturbs multiscale regulation of locomotor activity

    PubMed Central

    Hsieh, Wan-Hsin; Escobar, Carolina; Yugay, Tatiana; Lo, Men-Tzung; Pittman-Polletta, Benjamin; Salgado-Delgado, Roberto; Scheer, Frank A. J. L.; Shea, Steven A.; Buijs, Ruud M.; Hu, Kun

    2014-01-01

    Motor activity possesses a multiscale regulation that is characterized by fractal activity fluctuations with similar structure across a wide range of timescales spanning minutes to hours. Fractal activity patterns are disturbed in animals after ablating the master circadian pacemaker (suprachiasmatic nucleus, SCN) and in humans with SCN dysfunction as occurs with aging and in dementia, suggesting the crucial role of the circadian system in the multiscale activity regulation. We hypothesized that the normal synchronization between behavioural cycles and the SCN-generated circadian rhythms is required for multiscale activity regulation. To test the hypothesis, we studied activity fluctuations of rats in a simulated shift work protocol that was designed to force animals to be active during the habitual resting phase of the circadian/daily cycle. We found that these animals had gradually decreased mean activity level and reduced 24-h activity rhythm amplitude, indicating disturbed circadian and behavioural cycles. Moreover, these animals had disrupted fractal activity patterns as characterized by more random activity fluctuations at multiple timescales from 4 to 12 h. Intriguingly, these activity disturbances exacerbated when the shift work schedule lasted longer and persisted even in the normal days (without forced activity) following the shift work. The disrupted circadian and fractal patterns resemble those of SCN-lesioned animals and of human patients with dementia, suggesting a detrimental impact of shift work on multiscale activity regulation. PMID:24829282

  18. Simulated shift work in rats perturbs multiscale regulation of locomotor activity.

    PubMed

    Hsieh, Wan-Hsin; Escobar, Carolina; Yugay, Tatiana; Lo, Men-Tzung; Pittman-Polletta, Benjamin; Salgado-Delgado, Roberto; Scheer, Frank A J L; Shea, Steven A; Buijs, Ruud M; Hu, Kun

    2014-07-06

    Motor activity possesses a multiscale regulation that is characterized by fractal activity fluctuations with similar structure across a wide range of timescales spanning minutes to hours. Fractal activity patterns are disturbed in animals after ablating the master circadian pacemaker (suprachiasmatic nucleus, SCN) and in humans with SCN dysfunction as occurs with aging and in dementia, suggesting the crucial role of the circadian system in the multiscale activity regulation. We hypothesized that the normal synchronization between behavioural cycles and the SCN-generated circadian rhythms is required for multiscale activity regulation. To test the hypothesis, we studied activity fluctuations of rats in a simulated shift work protocol that was designed to force animals to be active during the habitual resting phase of the circadian/daily cycle. We found that these animals had gradually decreased mean activity level and reduced 24-h activity rhythm amplitude, indicating disturbed circadian and behavioural cycles. Moreover, these animals had disrupted fractal activity patterns as characterized by more random activity fluctuations at multiple timescales from 4 to 12 h. Intriguingly, these activity disturbances exacerbated when the shift work schedule lasted longer and persisted even in the normal days (without forced activity) following the shift work. The disrupted circadian and fractal patterns resemble those of SCN-lesioned animals and of human patients with dementia, suggesting a detrimental impact of shift work on multiscale activity regulation.

  19. Substrate Stiffness Regulates Filopodial Activities in Lung Cancer Cells

    PubMed Central

    Liou, Yu-Ren; Torng, Wen; Kao, Yu-Chiu; Sung, Kung-Bin; Lee, Chau-Hwang; Kuo, Po-Ling

    2014-01-01

    Microenvironment stiffening plays a crucial role in tumorigenesis. While filopodia are generally thought to be one of the cellular mechanosensors for probing environmental stiffness, the effects of environmental stiffness on filopodial activities of cancer cells remain unclear. In this work, we investigated the filopodial activities of human lung adenocarcinoma cells CL1-5 cultured on substrates of tunable stiffness using a novel platform. The platform consists of an optical system called structured illumination nano-profilometry, which allows time-lapsed visualization of filopodial activities without fluorescence labeling. The culturing substrates were composed of polyvinyl chloride mixed with an environmentally friendly plasticizer to yield Young's modulus ranging from 20 to 60 kPa. Cell viability studies showed that the viability of cells cultured on the substrates was similar to those cultured on commonly used elastomers such as polydimethylsiloxane. Time-lapsed live cell images were acquired and the filopodial activities in response to substrates with varying degrees of stiffness were analyzed. Statistical analyses revealed that lung cancer cells cultured on softer substrates appeared to have longer filopodia, higher filopodial densities with respect to the cellular perimeter, and slower filopodial retraction rates. Nonetheless, the temporal analysis of filopodial activities revealed that whether a filopodium decides to extend or retract is purely a stochastic process without dependency on substrate stiffness. The discrepancy of the filopodial activities between lung cancer cells cultured on substrates with different degrees of stiffness vanished when the myosin II activities were inhibited by treating the cells with blebbistatin, which suggests that the filopodial activities are closely modulated by the adhesion strength of the cells. Our data quantitatively relate filopodial activities of lung cancer cells with environmental stiffness and should shed light

  20. Successful emotion regulation is predicted by amygdala activity and aspects of personality: A latent variable approach.

    PubMed

    Morawetz, Carmen; Alexandrowicz, Rainer W; Heekeren, Hauke R

    2017-04-01

    The experience of emotions and their cognitive control are based upon neural responses in prefrontal and subcortical regions and could be affected by personality and temperamental traits. Previous studies established an association between activity in reappraisal-related brain regions (e.g., inferior frontal gyrus and amygdala) and emotion regulation success. Given these relationships, we aimed to further elucidate how individual differences in emotion regulation skills relate to brain activity within the emotion regulation network on the one hand, and personality/temperamental traits on the other. We directly examined the relationship between personality and temperamental traits, emotion regulation success and its underlying neuronal network in a large sample (N = 82) using an explicit emotion regulation task and functional MRI (fMRI). We applied a multimethodological analysis approach, combing standard activation-based analyses with structural equation modeling. First, we found that successful downregulation is predicted by activity in key regions related to emotion processing. Second, the individual ability to successfully upregulate emotions is strongly associated with the ability to identify feelings, conscientiousness, and neuroticism. Third, the successful downregulation of emotion is modulated by openness to experience and habitual use of reappraisal. Fourth, the ability to regulate emotions is best predicted by a combination of brain activity and personality as well temperamental traits. Using a multimethodological analysis approach, we provide a first step toward a causal model of individual differences in emotion regulation ability by linking biological systems underlying emotion regulation with descriptive constructs. (PsycINFO Database Record