Science.gov

Sample records for administrative regulations conditions

  1. 7 CFR 51.1 - Administration of regulations.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 2 2011-01-01 2011-01-01 false Administration of regulations. 51.1 Section 51.1... MARKETING ACT OF 1946 FRESH FRUITS, VEGETABLES AND OTHER PRODUCTS 1,2 (INSPECTION, CERTIFICATION, AND STANDARDS) Regulations 1 Administrative § 51.1 Administration of regulations. (a) The...

  2. 7 CFR 51.1 - Administration of regulations.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 2 2012-01-01 2012-01-01 false Administration of regulations. 51.1 Section 51.1... MARKETING ACT OF 1946 FRESH FRUITS, VEGETABLES AND OTHER PRODUCTS 1,2 (INSPECTION, CERTIFICATION, AND STANDARDS) Regulations 1 Administrative § 51.1 Administration of regulations. (a) The...

  3. 7 CFR 51.1 - Administration of regulations.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 2 2010-01-01 2010-01-01 false Administration of regulations. 51.1 Section 51.1... MARKETING ACT OF 1946 FRESH FRUITS, VEGETABLES AND OTHER PRODUCTS 1,2 (INSPECTION, CERTIFICATION, AND STANDARDS) Regulations 1 Administrative § 51.1 Administration of regulations. (a) The...

  4. 45 CFR 63.8 - Supplemental regulations and grant conditions.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 45 Public Welfare 1 2010-10-01 2010-10-01 false Supplemental regulations and grant conditions. 63.8 Section 63.8 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION GRANT... Supplemental regulations and grant conditions. (a) Grants under section 232 of the Community Services Act....

  5. 7 CFR 52.1 - Administration of regulations.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... Agriculture Regulations of the Department of Agriculture AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing Practices), DEPARTMENT OF AGRICULTURE REGULATIONS AND STANDARDS UNDER THE AGRICULTURAL... regulations. (a) The Administrator, Agricultural Marketing Service, United States Department of Agriculture...

  6. 7 CFR 51.1 - Administration of regulations.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 2 2014-01-01 2014-01-01 false Administration of regulations. 51.1 Section 51.1... MARKETING ACT OF 1946 AND THE EGG PRODUCTS INSPECTION ACT FRESH FRUITS, VEGETABLES AND OTHER PRODUCTS 1 2 (INSPECTION, CERTIFICATION, AND STANDARDS) Regulations 1 Administrative § 51.1 Administration of...

  7. 7 CFR 51.1 - Administration of regulations.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 2 2013-01-01 2013-01-01 false Administration of regulations. 51.1 Section 51.1... MARKETING ACT OF 1946 AND THE EGG PRODUCTS INSPECTION ACT FRESH FRUITS, VEGETABLES AND OTHER PRODUCTS 1,2 (INSPECTION, CERTIFICATION, AND STANDARDS) Regulations 1 Administrative § 51.1 Administration of...

  8. 15 CFR 30.16 - Export Administration Regulations.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 15 Commerce and Foreign Trade 1 2010-01-01 2010-01-01 false Export Administration Regulations. 30... OF THE CENSUS, DEPARTMENT OF COMMERCE FOREIGN TRADE REGULATIONS Export Control and Licensing Requirements § 30.16 Export Administration Regulations. The EAR issued by the U.S. Department of Commerce,...

  9. 42 CFR 417.412 - Qualifying condition: Administration and management.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 3 2010-10-01 2010-10-01 false Qualifying condition: Administration and management... Qualifying condition: Administration and management. The HMO or CMP must demonstrate that it— (a) Has... agents or management staff or persons with ownership or control interests who have been convicted...

  10. 42 CFR 486.324 - Condition: Administration and governing body.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 42 Public Health 5 2013-10-01 2013-10-01 false Condition: Administration and governing body. 486... HUMAN SERVICES (CONTINUED) STANDARDS AND CERTIFICATION CONDITIONS FOR COVERAGE OF SPECIALIZED SERVICES...: Administration and governing body. (a) While an OPO may have more than one board, the OPO must have an...

  11. 75 FR 33682 - Export Administration Regulations; Technical Amendments

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-15

    ... Bureau of Industry and Security 15 CFR Part 766 RIN 0694-AE93 Export Administration Regulations... amendment to the Export Administration Regulations (EAR). Specifically, BIS deletes references concerning Federal court jurisdiction for judicial review of final decisions and orders issued in BIS export...

  12. 77 FR 40493 - Export Administration Regulations

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-07-10

    ... Bureau of Industry and Security 15 CFR Parts 740, 742, 748, 750, 752, and 760 Export Administration... heading of paragraph (d) to read ``Shippers Export Declaration or Automated Export System Record''. 0 2...): Once a mass market classification request is accepted in SNAP-R, you may export and reexport...

  13. 15 CFR 30.16 - Export Administration Regulations.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 15 Commerce and Foreign Trade 1 2014-01-01 2014-01-01 false Export Administration Regulations. 30.16 Section 30.16 Commerce and Foreign Trade Regulations Relating to Commerce and Foreign Trade BUREAU OF THE CENSUS, DEPARTMENT OF COMMERCE FOREIGN TRADE REGULATIONS Export Control and...

  14. 15 CFR 30.16 - Export Administration Regulations.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 15 Commerce and Foreign Trade 1 2012-01-01 2012-01-01 false Export Administration Regulations. 30.16 Section 30.16 Commerce and Foreign Trade Regulations Relating to Commerce and Foreign Trade BUREAU OF THE CENSUS, DEPARTMENT OF COMMERCE FOREIGN TRADE REGULATIONS Export Control and...

  15. The Infralimbic Cortex Regulates the Consolidation of Extinction after Cocaine Self-Administration

    ERIC Educational Resources Information Center

    LaLumiere, Ryan T.; Niehoff, Kate E.; Kalivas, Peter W.

    2010-01-01

    The infralimbic cortex (IL) regulates the consolidation of extinction learning for fear conditioning. Whether the IL influences the consolidation of extinction learning for cocaine self-administration is unknown. To address this issue, male Sprague-Dawley rats underwent 2 wk of cocaine self-administration followed by extinction training. On the…

  16. 42 CFR 403.738 - Condition of participation: Administration.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 2 2010-10-01 2010-10-01 false Condition of participation: Administration. 403.738 Section 403.738 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL PROVISIONS SPECIAL PROGRAMS AND PROJECTS Religious Nonmedical Health Care...

  17. 42 CFR 403.738 - Condition of participation: Administration.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 42 Public Health 2 2014-10-01 2014-10-01 false Condition of participation: Administration. 403.738 Section 403.738 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL PROVISIONS SPECIAL PROGRAMS AND PROJECTS Religious Nonmedical Health Care...

  18. 42 CFR 403.738 - Condition of participation: Administration.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 42 Public Health 2 2012-10-01 2012-10-01 false Condition of participation: Administration. 403.738 Section 403.738 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL PROVISIONS SPECIAL PROGRAMS AND PROJECTS Religious Nonmedical Health Care...

  19. 42 CFR 403.738 - Condition of participation: Administration.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 42 Public Health 2 2011-10-01 2011-10-01 false Condition of participation: Administration. 403.738 Section 403.738 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL PROVISIONS SPECIAL PROGRAMS AND PROJECTS Religious Nonmedical Health Care...

  20. 42 CFR 403.738 - Condition of participation: Administration.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 42 Public Health 2 2013-10-01 2013-10-01 false Condition of participation: Administration. 403.738 Section 403.738 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL PROVISIONS SPECIAL PROGRAMS AND PROJECTS Religious Nonmedical Health Care...

  1. 42 CFR 417.412 - Qualifying condition: Administration and management.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ..., COMPETITIVE MEDICAL PLANS, AND HEALTH CARE PREPAYMENT PLANS Qualifying Conditions for Medicare Contracts § 417...) Has sufficient administrative capability to carry out the requirements of the contract; and (b) Does... convicted of criminal offenses related to their involvement in Medicaid, Medicare, or social...

  2. Food and Drug Administration regulation and evaluation of vaccines.

    PubMed

    Marshall, Valerie; Baylor, Norman W

    2011-05-01

    The vaccine-approval process in the United States is regulated by the Center for Biologics Evaluation and Research of the US Food and Drug Administration. Throughout the life cycle of development, from preclinical studies to after licensure, vaccines are subject to rigorous testing and oversight. Manufacturers must adhere to good manufacturing practices and control procedures to ensure the quality of vaccines. As mandated by Title 21 of the Code of Regulations, licensed vaccines must meet stringent criteria for safety, efficacy, and potency.

  3. 15 CFR 30.16 - Export Administration Regulations.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... Requirements § 30.16 Export Administration Regulations. The EAR issued by the U.S. Department of Commerce, BIS, also contain some additional reporting requirements pertaining to EEI (see 15 CFR 730-774). (a) The EAR... export control information in the EEI are found in the EAR....

  4. 15 CFR 30.16 - Export Administration Regulations.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... Requirements § 30.16 Export Administration Regulations. The EAR issued by the U.S. Department of Commerce, BIS, also contain some additional reporting requirements pertaining to EEI (see 15 CFR 730-774). (a) The EAR... export control information in the EEI are found in the EAR....

  5. 75 FR 33989 - Export Administration Regulations: Technical Corrections

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-16

    ... Security 15 CFR Part 774 RIN 0694-AE69 Export Administration Regulations: Technical Corrections AGENCY... License Requirements section of Export Control Classification Number 2B001 and the other is in the..., clarified language regarding certain performance criteria of turning machines covered by Export...

  6. 75 FR 31678 - Export Administration Regulations: Technical Corrections

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-04

    ... Bureau of Industry and Security 15 CFR Parts 734, 740, 744, 748, 750, 766 and 774 RIN 0694-AE69 Export...: Final Rule. SUMMARY: This rule clarifies language concerning the de minimis provisions of the Export... Foreign Made Items The Export Administration Regulations (EAR) generally do not apply to items that...

  7. 75 FR 14448 - Food and Drug Administration Clinical Trial Requirements, Regulations, Compliance, and Good...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-25

    ... HUMAN SERVICES Food and Drug Administration Food and Drug Administration Clinical Trial Requirements, Regulations, Compliance, and Good Clinical Practices; Public Workshop AGENCY: Food and Drug Administration, HHS. ACTION: Notice of public workshop. SUMMARY: The Food and Drug Administration (FDA) Los...

  8. 75 FR 13763 - General Services Administration Acquisition Regulation; Submission for OMB Review; GSA Form 1217...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-23

    ... ADMINISTRATION DEPARTMENT OF DEFENSE NATIONAL AERONAUTICS AND SPACE ADMINISTRATION General Services Administration Acquisition Regulation; Submission for OMB Review; GSA Form 1217, Lessor's Annual Cost Statement AGENCY: Department of Defense (DOD), General Services Administration (GSA), and National Aeronautics...

  9. 75 FR 59102 - Defense Federal Acquisition Regulation Supplement; Part 204, Administrative Matters

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-27

    ...; Part 204, Administrative Matters AGENCY: Defense Acquisition Regulations System, Department of Defense.... 0 Therefore 48 CFR part 204 is amended as follows: PART 204--ADMINISTRATIVE MATTERS 0 1....

  10. 18 CFR 410.1 - Basin regulations-Water Code and Administrative Manual-Part III Water Quality Regulations.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... Code and Administrative Manual-Part III Water Quality Regulations. 410.1 Section 410.1 Conservation of... CODE AND ADMINISTRATIVE MANUAL-PART III WATER QUALITY REGULATIONS § 410.1 Basin regulations—Water Code and Administrative Manual—Part III Water Quality Regulations. (a) The Water Code of the Delaware...

  11. 18 CFR 410.1 - Basin regulations-Water Code and Administrative Manual-Part III Water Quality Regulations.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... Code and Administrative Manual-Part III Water Quality Regulations. 410.1 Section 410.1 Conservation of... CODE AND ADMINISTRATIVE MANUAL-PART III WATER QUALITY REGULATIONS § 410.1 Basin regulations—Water Code and Administrative Manual—Part III Water Quality Regulations. (a) The Water Code of the Delaware...

  12. 18 CFR 410.1 - Basin regulations-Water Code and Administrative Manual-Part III Water Quality Regulations.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... Code and Administrative Manual-Part III Water Quality Regulations. 410.1 Section 410.1 Conservation of... CODE AND ADMINISTRATIVE MANUAL-PART III WATER QUALITY REGULATIONS § 410.1 Basin regulations—Water Code and Administrative Manual—Part III Water Quality Regulations. (a) The Water Code of the Delaware...

  13. 18 CFR 410.1 - Basin regulations-Water Code and Administrative Manual-Part III Water Quality Regulations.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... Code and Administrative Manual-Part III Water Quality Regulations. 410.1 Section 410.1 Conservation of... CODE AND ADMINISTRATIVE MANUAL-PART III WATER QUALITY REGULATIONS § 410.1 Basin regulations—Water Code and Administrative Manual—Part III Water Quality Regulations. (a) The Water Code of the Delaware...

  14. 18 CFR 410.1 - Basin regulations-Water Code and Administrative Manual-Part III Water Quality Regulations.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... Code and Administrative Manual-Part III Water Quality Regulations. 410.1 Section 410.1 Conservation of... CODE AND ADMINISTRATIVE MANUAL-PART III WATER QUALITY REGULATIONS § 410.1 Basin regulations—Water Code and Administrative Manual—Part III Water Quality Regulations. (a) The Water Code of the Delaware...

  15. 15 CFR 710.6 - Relationship between the Chemical Weapons Convention Regulations and the Export Administration...

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... Weapons Convention Regulations and the Export Administration Regulations, the International Traffic in... INDUSTRY AND SECURITY, DEPARTMENT OF COMMERCE CHEMICAL WEAPONS CONVENTION REGULATIONS GENERAL INFORMATION AND OVERVIEW OF THE CHEMICAL WEAPONS CONVENTION REGULATIONS (CWCR) § 710.6 Relationship between...

  16. 15 CFR 710.6 - Relationship between the Chemical Weapons Convention Regulations and the Export Administration...

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... Weapons Convention Regulations and the Export Administration Regulations, the International Traffic in... INDUSTRY AND SECURITY, DEPARTMENT OF COMMERCE CHEMICAL WEAPONS CONVENTION REGULATIONS GENERAL INFORMATION AND OVERVIEW OF THE CHEMICAL WEAPONS CONVENTION REGULATIONS (CWCR) § 710.6 Relationship between...

  17. 15 CFR 710.6 - Relationship between the Chemical Weapons Convention Regulations and the Export Administration...

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... Weapons Convention Regulations and the Export Administration Regulations, the International Traffic in... INDUSTRY AND SECURITY, DEPARTMENT OF COMMERCE CHEMICAL WEAPONS CONVENTION REGULATIONS GENERAL INFORMATION AND OVERVIEW OF THE CHEMICAL WEAPONS CONVENTION REGULATIONS (CWCR) § 710.6 Relationship between...

  18. 15 CFR 710.6 - Relationship between the Chemical Weapons Convention Regulations and the Export Administration...

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... Weapons Convention Regulations and the Export Administration Regulations, the International Traffic in... INDUSTRY AND SECURITY, DEPARTMENT OF COMMERCE CHEMICAL WEAPONS CONVENTION REGULATIONS GENERAL INFORMATION AND OVERVIEW OF THE CHEMICAL WEAPONS CONVENTION REGULATIONS (CWCR) § 710.6 Relationship between...

  19. 15 CFR 710.6 - Relationship between the Chemical Weapons Convention Regulations and the Export Administration...

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... Weapons Convention Regulations and the Export Administration Regulations, the International Traffic in... INDUSTRY AND SECURITY, DEPARTMENT OF COMMERCE CHEMICAL WEAPONS CONVENTION REGULATIONS GENERAL INFORMATION AND OVERVIEW OF THE CHEMICAL WEAPONS CONVENTION REGULATIONS (CWCR) § 710.6 Relationship between...

  20. 77 FR 66466 - General Services Administration Regulation; Information Collection; Packing List Clause

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-11-05

    ... ADMINISTRATION General Services Administration Regulation; Information Collection; Packing List Clause AGENCY... packing list clause. Public comments are particularly invited on: Whether this collection of information..., Packing List Clause, by any of the following methods: Regulations.gov :...

  1. Human Temperature Regulation during Exercise after Oral Pyridostigmine Administration

    DTIC Science & Technology

    1990-03-01

    or vasomotor elements) which may or during exercise . Tsk was different in the three conditions by result from increased cholinergic activity after...of cholines- oration during steady-state exercise in control experi- terase enzyme activity units by the manual delta pH method ments. Thus, the small...Reprint & Copyright © by Aerospace Medical Association, Washington. DC D T IC ELECTF 0 Human Temperature Regulation * ~During Exercise After N Oral

  2. 41 CFR 105-1.101 - General Services Administration Property Management Regulations.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... Administration Property Management Regulations. 105-1.101 Section 105-1.101 Public Contracts and Property Management Federal Property Management Regulations System (Continued) GENERAL SERVICES ADMINISTRATION 1-INTRODUCTION 1.1-Regulations System § 105-1.101 General Services Administration Property Management...

  3. Conditional gene vectors regulated in cis.

    PubMed

    Pich, Dagmar; Humme, Sibille; Spindler, Mark-Peter; Schepers, Aloys; Hammerschmidt, Wolfgang

    2008-08-01

    Non-integrating gene vectors, which are stably and extrachromosomally maintained in transduced cells would be perfect tools to support long-term expression of therapeutic genes but preserve the genomic integrity of the cellular host. Small extrachromosomal plasmids share some of these ideal characteristics but are primarily based on virus blueprints. These plasmids are dependent on viral trans-acting factors but they can replicate their DNA molecules in synchrony with the chromosome of the cellular host and segregate to daughter cells in an autonomous fashion. On the basis of the concept of the latent origin of DNA replication of Epstein-Barr virus, oriP, we devised novel derivatives, which exclusively rely on an artificial replication factor for both nuclear retention and replication of plasmid DNA. In addition, an allosteric switch regulates the fate of the plasmid molecules, which are rapidly lost upon addition of doxycycline. Conditional maintenance of these novel plasmid vectors allows the reversible transfer of genetic information into target cells for the first time.

  4. 21 CFR 10.90 - Food and Drug Administration regulations, recommendations, and agreements.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 1 2012-04-01 2012-04-01 false Food and Drug Administration regulations, recommendations, and agreements. 10.90 Section 10.90 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF... Procedures § 10.90 Food and Drug Administration regulations, recommendations, and agreements. (a)...

  5. 21 CFR 10.90 - Food and Drug Administration regulations, recommendations, and agreements.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 1 2013-04-01 2013-04-01 false Food and Drug Administration regulations, recommendations, and agreements. 10.90 Section 10.90 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF... Procedures § 10.90 Food and Drug Administration regulations, recommendations, and agreements. (a)...

  6. 75 FR 73951 - Amendments to General Regulations of the Food and Drug Administration

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-11-30

    ... HUMAN SERVICES Food and Drug Administration 21 CFR Parts 1, 14, and 17 RIN 0910-AG55 Amendments to General Regulations of the Food and Drug Administration AGENCY: Food and Drug Administration, HHS. ACTION: Direct final rule. SUMMARY: The Food and Drug Administration (FDA) is amending certain of its...

  7. 75 FR 73984 - Amendments to General Regulations of the Food and Drug Administration

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-11-30

    ... HUMAN SERVICES Food and Drug Administration 21 CFR Parts 1, 14, and 17 RIN 0910-AG55 Amendments to General Regulations of the Food and Drug Administration AGENCY: Food and Drug Administration, HHS. ACTION: Proposed rule. SUMMARY: The Food and Drug Administration (FDA) is proposing to amend certain of its...

  8. 75 FR 1788 - General Services Administration Regulation; Submission for OMB Review; Packing List Clause

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-01-13

    ... ADMINISTRATION General Services Administration Regulation; Submission for OMB Review; Packing List Clause AGENCY... approved information collection requirement regarding the packing list clause. A request for public..., Packing List Clause, in all correspondence. FOR FURTHER INFORMATION CONTACT: Michael O....

  9. 77 FR 69441 - Federal Acquisition Regulation; Information Collection; Cost Accounting Standards Administration

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-11-19

    ... Regulation; Information Collection; Cost Accounting Standards Administration AGENCY: Department of Defense...: Under the provisions of the Paperwork Reduction Act, the Regulatory Secretariat will be submitting to... approved information collection requirement concerning cost accounting standards administration....

  10. [Working conditions, living conditions and physical health problems declared among penitentiary administration personnel in France].

    PubMed

    Goldberg, P; Landre, M F; David, S; Goldberg, M; Dassa, S; Marne, M J

    1996-06-01

    A cross-sectional epidemiological survey was conducted among prison staff in France to investigate the relationships between working conditions and health. The sample included men and women 20 to 64 years old belonging to all categories of prison personnel: prison guards, administrative staff, socioeducational workers, technicians, health care workers, and managers (n = 4587, response rate 45.7%). A mailed self-administered questionnaire was used to assess sociodemographic characteristics, working conditions, and physical and mental disorders. Multiple logistic regression analyses were conducted to determine the effects of working conditions and social relationships on health of prison staff. However, the results reported here only concern 17 health disorders: body mass index, sick leave, medication use, accidents, digestive disorders, lower extremities and back disorders, hypertension, hemorrhoids, arthritis, skin disorders, urinary infections, chronic bronchitis, cholesterol, gastric ulcer, respiratory infections, ocular disorders. The living non professional conditions mostly associated with health disorders were financial difficulties (OR: 1.9 for digestive disorders, 1.8 for gastric ulcer, 1.7 for medication use) and irregularity of meals (OR = 1.5 for digestive disorders, and hypertension). In the occupational environment, the factors most associated with health disorders are seniority (OR = 4.2 for arthritis, 2.3 for cholesterol) and constraints (OR = 1.7 for lower extremities disorders). In spite of some limits associated to this kind of study, relationships between occupational and non occupational factors and physical health conditions were observed; the results also pointed out the protective role of the social relationships for health conditions.

  11. 77 FR 14016 - General Services Administration Acquisition Regulation; Preparation, Submission, and Negotiation...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-03-08

    ...] General Services Administration Acquisition Regulation; Preparation, Submission, and Negotiation of... Negotiation of Subcontracting Plans; Correction. Correction In the information collection document...

  12. 7 CFR 1260.520 - Responsibility for administration of regulations.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... AGRICULTURE BEEF PROMOTION AND RESEARCH Beef Promotion and Research: Certification and Nomination Procedures for the Cattlemen's Beef Promotion and Research Board § 1260.520 Responsibility for administration...

  13. 77 FR 74631 - General Services Administration Acquisition Regulation: Modifications (Multiple Award Schedules...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-12-17

    ... collection requirement regarding General Services Administration Acquisition Regulation (GSAR) clause... Acquisition Regulation (GSAR) to add clause 552.243-72; Modifications (Multiple Award Schedules). Under the modifications clause, vendors may request a contract modification by submitting a request to the...

  14. 7 CFR 52.1 - Administration of regulations.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... Agriculture Regulations of the Department of Agriculture AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing Practices), DEPARTMENT OF AGRICULTURE REGULATIONS AND STANDARDS UNDER THE AGRICULTURAL MARKETING ACT OF 1946 PROCESSED FRUITS AND VEGETABLES, PROCESSED PRODUCTS THEREOF, AND CERTAIN...

  15. 42 CFR 486.324 - Condition: Administration and governing body.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... of this part. (7) Transportation of organs to transplant hospitals. (8) Coordination of activities... FURNISHED BY SUPPLIERS Requirements for Certification and Designation and Conditions for Coverage: Organ Procurement Organizations Organ Procurement Organization Process Performance Measures § 486.324...

  16. The infralimbic cortex regulates the consolidation of extinction after cocaine self-administration.

    PubMed

    LaLumiere, Ryan T; Niehoff, Kate E; Kalivas, Peter W

    2010-04-01

    The infralimbic cortex (IL) regulates the consolidation of extinction learning for fear conditioning. Whether the IL influences the consolidation of extinction learning for cocaine self-administration is unknown. To address this issue, male Sprague-Dawley rats underwent 2 wk of cocaine self-administration followed by extinction training. On the first 5 d of extinction, rats underwent brief (15- or 30-min) extinction sessions and received intra-IL microinjections immediately after each extinction session. On days 6-12 of extinction, rats underwent full-length (2-h) extinction sessions that were used to assess the retention of the extinction learning from the short sessions. IL inactivation via microinjections of the GABA agonists baclofen and muscimol (BM) immediately after the extinction sessions (days 1-5) impaired the retention of extinction learning. Control experiments demonstrated that this effect was not due to inactivation of the prelimbic cortex or due to effects of the drugs on the subsequent day's behavior. In contrast, post-training intra-IL microinjections of the allosteric AMPA receptor potentiator 4-[2-(phenylsulfonylamino)ethylthio]-2,6-difluorophenoxyacetamide (PEPA) enhanced retention of the extinction learning. As evidence suggests a role for the beta-adrenergic receptors in memory consolidation, other rats received microinjections of the beta(2)-adrenergic receptor agonist clenbuterol or antagonist ICI-118,551 (ICI). Post-training intra-IL administration of clenbuterol or pre-training administration of ICI enhanced or impaired, respectively, the retention of extinction learning. These data indicate that the IL, and specifically the glutamatergic and beta-adrenergic systems in the IL, regulates the consolidation of extinction of cocaine self-administration and that the IL can be manipulated to influence the retention of extinction.

  17. 42 CFR 485.56 - Condition of participation: Governing body and administration.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... administration, management, and operation must be retained by the facility itself and not delegated to others. (1... administration. 485.56 Section 485.56 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF... Condition of participation: Governing body and administration. The facility must have a governing body...

  18. 42 CFR 486.324 - Condition: Administration and governing body.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... syndrome (AIDS). (5) Appropriate tissue typing of organs. (6) A system for allocation of organs among... FURNISHED BY SUPPLIERS Requirements for Certification and Designation and Conditions for Coverage: Organ Procurement Organizations Organ Procurement Organization Process Performance Measures § 486.324...

  19. 42 CFR 486.324 - Condition: Administration and governing body.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... syndrome (AIDS). (5) Appropriate tissue typing of organs. (6) A system for allocation of organs among... FURNISHED BY SUPPLIERS Requirements for Certification and Designation and Conditions for Coverage: Organ Procurement Organizations Organ Procurement Organization Process Performance Measures § 486.324...

  20. 42 CFR 486.324 - Condition: Administration and governing body.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... syndrome (AIDS). (5) Appropriate tissue typing of organs. (6) A system for allocation of organs among... FURNISHED BY SUPPLIERS Requirements for Certification and Designation and Conditions for Coverage: Organ Procurement Organizations Organ Procurement Organization Process Performance Measures § 486.324...

  1. 77 FR 22191 - Revisions to the Export Administration Regulations (EAR): Export Control Classification Number...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-04-13

    ... the Export Administration Regulations (EAR): Export Control Classification Number 0Y521 Series, Items..., which amends the Export Administration Regulations (EAR) by establishing a new Export Control... the EAR. The ECCN 0Y521 series will be used for items that warrant control on the CCL but are not...

  2. 42 CFR 485.56 - Condition of participation: Governing body and administration.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 42 Public Health 5 2013-10-01 2013-10-01 false Condition of participation: Governing body and... Condition of participation: Governing body and administration. The facility must have a governing body that... disclose certain information about ownership and control. (b) Standard: Administrator. The governing...

  3. 42 CFR 485.56 - Condition of participation: Governing body and administration.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 42 Public Health 5 2014-10-01 2014-10-01 false Condition of participation: Governing body and... Condition of participation: Governing body and administration. The facility must have a governing body that... disclose certain information about ownership and control. (b) Standard: Administrator. The governing...

  4. 42 CFR 88.13 - WTC Program Administrator's certification of health conditions.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 42 Public Health 1 2014-10-01 2014-10-01 false WTC Program Administrator's certification of health... OCCUPATIONAL SAFETY AND HEALTH RESEARCH AND RELATED ACTIVITIES WORLD TRADE CENTER HEALTH PROGRAM § 88.13 WTC Program Administrator's certification of health conditions. (a) WTC-related health condition. (1) The...

  5. 42 CFR 88.13 - WTC Program Administrator's certification of health conditions.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 42 Public Health 1 2011-10-01 2011-10-01 false WTC Program Administrator's certification of health... OCCUPATIONAL SAFETY AND HEALTH RESEARCH AND RELATED ACTIVITIES WORLD TRADE CENTER HEALTH PROGRAM § 88.13 WTC Program Administrator's certification of health conditions. (a) WTC-related health condition. (1) The...

  6. 42 CFR 88.13 - WTC Program Administrator's certification of health conditions.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 42 Public Health 1 2012-10-01 2012-10-01 false WTC Program Administrator's certification of health... OCCUPATIONAL SAFETY AND HEALTH RESEARCH AND RELATED ACTIVITIES WORLD TRADE CENTER HEALTH PROGRAM § 88.13 WTC Program Administrator's certification of health conditions. (a) WTC-related health condition. (1) The...

  7. 42 CFR 88.13 - WTC Program Administrator's certification of health conditions.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 42 Public Health 1 2013-10-01 2013-10-01 false WTC Program Administrator's certification of health... OCCUPATIONAL SAFETY AND HEALTH RESEARCH AND RELATED ACTIVITIES WORLD TRADE CENTER HEALTH PROGRAM § 88.13 WTC Program Administrator's certification of health conditions. (a) WTC-related health condition. (1) The...

  8. 22 CFR 120.42 - Subject to the Export Administration Regulations (EAR).

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... Regulations (EAR). 120.42 Section 120.42 Foreign Relations DEPARTMENT OF STATE INTERNATIONAL TRAFFIC IN ARMS REGULATIONS PURPOSE AND DEFINITIONS § 120.42 Subject to the Export Administration Regulations (EAR). Items “subject to the EAR” are those items listed on the Commerce Control List in part 774 of the EAR and...

  9. 78 FR 18285 - General Services Administration Acquisition Regulation; Submission for OMB Review; Modifications...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-03-26

    ... OMB Review; Modifications 552.243-72 (Multiple Award Schedules) AGENCY: Office of Acquisition Policy... to review and approve an information collection requirement regarding the Modifications (Multiple... Services Administration Acquisition Regulation (GSAR) to add clause 552.243-72 Modifications...

  10. 77 FR 11355 - Defense Federal Acquisition Regulation Supplement; Business Systems-Definition and Administration...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-02-24

    ... imminent cost savings that will result. Contractor business systems and internal controls are the first... Defense Federal Acquisition Regulation Supplement; Business Systems--Definition and Administration (DFARS... contractor business systems. DATES: Effective date: February 24, 2012. FOR FURTHER INFORMATION CONTACT:...

  11. 77 FR 31026 - Requirements for Importing Food and Drug Administration Regulated Products Into the United States

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-05-24

    ... respect to importing pharmaceutical products, medical devices, food products, as well as technology which... No: 2012-12592] DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2012-N-0001] Requirements for Importing Food and Drug Administration Regulated Products Into the...

  12. 78 FR 11188 - General Services Administration Regulation; Submission for OMB Review; Packing List Clause

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-15

    ... ADMINISTRATION General Services Administration Regulation; Submission for OMB Review; Packing List Clause AGENCY... packing list clause. A notice was published in the Federal Register at 77 FR 66466, on November 5, 2012...: Submit comments identified by Information Collection 3090- 0246, Packing List Clause, by any of...

  13. 21 CFR 10.90 - Food and Drug Administration regulations, recommendations, and agreements.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATIVE PRACTICES AND PROCEDURES General Administrative.... FDA regulations are issued in the Federal Register under § 10.40 or § 10.50 and codified in the Code... included in a separate public file of recommendations established by the Division of Dockets Management...

  14. 75 FR 82029 - General Services Administration Acquisition Regulation; Submission for OMB Review; GSA Form 1217...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-12-29

    ... Doc No: 2010-32775] GENERAL SERVICES ADMINISTRATION [OMB Control No. 3090-00XX; Docket 2010-0002; Sequence 15] General Services Administration Acquisition Regulation; Submission for OMB Review; GSA Form 1217, Lessor's Annual Cost Statement AGENCY: Department of Defense (DOD), General...

  15. 75 FR 2457 - Defense Federal Acquisition Regulation Supplement; Business Systems-Definition and Administration...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-01-15

    ... Federal Acquisition Regulation Supplement; Business Systems--Definition and Administration (DFARS Case... the definition and administration of contractor business systems as follows: 1. DoD is proposing to... analysis is summarized as follows: The objective of the rule is to establish a definition for...

  16. 78 FR 60695 - Regulatory Reorganization; Administrative Changes to Regulations Due to the Consolidation of the...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-10-02

    ... Reorganization; Administrative Changes to Regulations Due to the Consolidation of the Financial Management... consolidated the bureaus formerly known as the Financial Management Service (``FMS'') and the Bureau of the... consolidation requires reorganization of, and administrative changes to, title 31 of the Code of...

  17. 75 FR 13131 - General Services Administration Acquisition Regulation; Submission for OMB Review; GSA Advantage...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-18

    ...) contractors must participate in the GSA Advantage! system at 552.238-55. It is an online shopping service... From the Federal Register Online via the Government Publishing Office GENERAL SERVICES ADMINISTRATION General Services Administration Acquisition Regulation; Submission for OMB Review; GSA...

  18. 77 FR 15370 - General Services Administration Acquisition Regulation; Information Collection; Price Reductions...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-03-15

    ... Clause; Extension of Comment Period AGENCY: Office of Acquisition Policy; General Services Administration... date of the notice of request for comments regarding OMB Control No. 3090-0235, Price Reductions Clause... Reductions Clause, by any of the following methods: Regulations.gov : http://www.regulations.gov ....

  19. 78 FR 76738 - Updated Statements of Legal Authority for the Export Administration Regulations

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-12-19

    ...This rule updates the Code of Federal Regulations (CFR) legal authority paragraphs in the Export Administration Regulations (EAR) to include the citations to five Presidential notices extending emergencies declared pursuant to the International Emergency Economic Powers Act. This is a procedural rule that only updates authority paragraphs of the EAR. It does not alter any right, obligation or......

  20. 14 CFR 294.33 - Compliance with the regulations of the Federal Aviation Administration.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... Federal Aviation Administration. 294.33 Section 294.33 Aeronautics and Space OFFICE OF THE SECRETARY, DEPARTMENT OF TRANSPORTATION (AVIATION PROCEEDINGS) ECONOMIC REGULATIONS CANADIAN CHARTER AIR TAXI OPERATORS General Rules for Registrants § 294.33 Compliance with the regulations of the Federal...

  1. 14 CFR 294.33 - Compliance with the regulations of the Federal Aviation Administration.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... Federal Aviation Administration. 294.33 Section 294.33 Aeronautics and Space OFFICE OF THE SECRETARY, DEPARTMENT OF TRANSPORTATION (AVIATION PROCEEDINGS) ECONOMIC REGULATIONS CANADIAN CHARTER AIR TAXI OPERATORS General Rules for Registrants § 294.33 Compliance with the regulations of the Federal...

  2. 14 CFR 294.33 - Compliance with the regulations of the Federal Aviation Administration.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... Federal Aviation Administration. 294.33 Section 294.33 Aeronautics and Space OFFICE OF THE SECRETARY, DEPARTMENT OF TRANSPORTATION (AVIATION PROCEEDINGS) ECONOMIC REGULATIONS CANADIAN CHARTER AIR TAXI OPERATORS General Rules for Registrants § 294.33 Compliance with the regulations of the Federal...

  3. 14 CFR 294.33 - Compliance with the regulations of the Federal Aviation Administration.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... Federal Aviation Administration. 294.33 Section 294.33 Aeronautics and Space OFFICE OF THE SECRETARY, DEPARTMENT OF TRANSPORTATION (AVIATION PROCEEDINGS) ECONOMIC REGULATIONS CANADIAN CHARTER AIR TAXI OPERATORS General Rules for Registrants § 294.33 Compliance with the regulations of the Federal...

  4. 14 CFR 294.33 - Compliance with the regulations of the Federal Aviation Administration.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... Federal Aviation Administration. 294.33 Section 294.33 Aeronautics and Space OFFICE OF THE SECRETARY, DEPARTMENT OF TRANSPORTATION (AVIATION PROCEEDINGS) ECONOMIC REGULATIONS CANADIAN CHARTER AIR TAXI OPERATORS General Rules for Registrants § 294.33 Compliance with the regulations of the Federal...

  5. 76 FR 12563 - Amendments to General Regulations of the Food and Drug Administration; Confirmation of Effective...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-03-08

    ... HUMAN SERVICES Food and Drug Administration 21 CFR Parts 1, 14, and 17 RIN 0910-AG55 Amendments to... certain general regulations of FDA to include tobacco products, where appropriate, in light of FDA's authority to regulate these products under the Family Smoking Prevention and Tobacco Control Act,...

  6. 32 CFR 250.7 - Pertinent portions of Export Administration Regulations (EAR).

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... Regulations (EAR). 250.7 Section 250.7 National Defense Department of Defense (Continued) OFFICE OF THE... DISCLOSURE § 250.7 Pertinent portions of Export Administration Regulations (EAR). The following pertinent section of the EAR is provided for the guidance of DoD personnel in determining the...

  7. 32 CFR 250.7 - Pertinent portions of Export Administration Regulations (EAR).

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... Regulations (EAR). 250.7 Section 250.7 National Defense Department of Defense (Continued) OFFICE OF THE... DISCLOSURE § 250.7 Pertinent portions of Export Administration Regulations (EAR). The following pertinent section of the EAR is provided for the guidance of DoD personnel in determining the...

  8. 32 CFR 250.7 - Pertinent portions of Export Administration Regulations (EAR).

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... Regulations (EAR). 250.7 Section 250.7 National Defense Department of Defense (Continued) OFFICE OF THE... DISCLOSURE § 250.7 Pertinent portions of Export Administration Regulations (EAR). The following pertinent section of the EAR is provided for the guidance of DoD personnel in determining the...

  9. 32 CFR 250.7 - Pertinent portions of Export Administration Regulations (EAR).

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... Regulations (EAR). 250.7 Section 250.7 National Defense Department of Defense (Continued) OFFICE OF THE... DISCLOSURE § 250.7 Pertinent portions of Export Administration Regulations (EAR). The following pertinent section of the EAR is provided for the guidance of DoD personnel in determining the...

  10. 32 CFR 250.7 - Pertinent portions of Export Administration Regulations (EAR).

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... Regulations (EAR). 250.7 Section 250.7 National Defense Department of Defense (Continued) OFFICE OF THE... DISCLOSURE § 250.7 Pertinent portions of Export Administration Regulations (EAR). The following pertinent section of the EAR is provided for the guidance of DoD personnel in determining the...

  11. 75 FR 3236 - Federal Acquisition Regulation; Submission for OMB Review; Cost Accounting Standards Administration

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-01-20

    ... and the provision at 52.230-5 include pertinent rules and regulations related to the Cost Accounting... Regulation; Submission for OMB Review; Cost Accounting Standards Administration AGENCIES: Department of...-0129). SUMMARY: Under the provisions of the Paperwork Reduction Act of 1995 (44 U.S.C. Chapter 35),...

  12. 75 FR 76692 - Defense Federal Acquisition Regulation Supplement; Business Systems-Definition and Administration...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-12-09

    ... Defense Acquisition Regulations System 48 CFR Parts 215, 234, 242, 244, 245, and 252 RIN 0750-AG58 Defense Federal Acquisition Regulation Supplement; Business Systems--Definition and Administration (DFARS Case... INFORMATION: I. Background DoD published a proposed rule for Business Systems--Definition and...

  13. Restoring Equal Opportunity in Education: An Analysis of Arguments for and against the Bush Administration Single-Sex Education Regulations. Briefing Paper #C368

    ERIC Educational Resources Information Center

    English, Ashley

    2009-01-01

    In 2006, the George W. Bush Administration issued new Title IX regulations that allow for sex-segregated classrooms and schools in public, non-vocational elementary and secondary schools. These regulations provide schools with another condition that allows them to provide sex-segregated programs as long as they meet an "important governmental…

  14. 7 CFR 301.74-4 - Conditions governing the interstate movement of regulated articles from quarantined areas.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... DOMESTIC QUARANTINE NOTICES Plum Pox § 301.74-4 Conditions governing the interstate movement of regulated... Departmental permit and found by the Administrator to be adequate to prevent the spread of plum pox; and (4... plum pox while in the quarantined area; (2) The regulated article's point of origin is indicated on...

  15. 7 CFR 301.74-4 - Conditions governing the interstate movement of regulated articles from quarantined areas.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... DOMESTIC QUARANTINE NOTICES Plum Pox § 301.74-4 Conditions governing the interstate movement of regulated... Departmental permit and found by the Administrator to be adequate to prevent the spread of plum pox; and (4... plum pox while in the quarantined area; (2) The regulated article's point of origin is indicated on...

  16. 7 CFR 301.74-4 - Conditions governing the interstate movement of regulated articles from quarantined areas.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... DOMESTIC QUARANTINE NOTICES Plum Pox § 301.74-4 Conditions governing the interstate movement of regulated... Departmental permit and found by the Administrator to be adequate to prevent the spread of plum pox; and (4... plum pox while in the quarantined area; (2) The regulated article's point of origin is indicated on...

  17. 7 CFR 301.74-4 - Conditions governing the interstate movement of regulated articles from quarantined areas.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... DOMESTIC QUARANTINE NOTICES Plum Pox § 301.74-4 Conditions governing the interstate movement of regulated... Departmental permit and found by the Administrator to be adequate to prevent the spread of plum pox; and (4... plum pox while in the quarantined area; (2) The regulated article's point of origin is indicated on...

  18. 7 CFR 301.74-4 - Conditions governing the interstate movement of regulated articles from quarantined areas.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... DOMESTIC QUARANTINE NOTICES Plum Pox § 301.74-4 Conditions governing the interstate movement of regulated... Departmental permit and found by the Administrator to be adequate to prevent the spread of plum pox; and (4... plum pox while in the quarantined area; (2) The regulated article's point of origin is indicated on...

  19. 42 CFR 418.100 - Condition of Participation: Organization and administration of services.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 42 Public Health 3 2013-10-01 2013-10-01 false Condition of Participation: Organization and administration of services. 418.100 Section 418.100 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICARE PROGRAM (CONTINUED) HOSPICE CARE Conditions...

  20. 42 CFR 418.100 - Condition of Participation: Organization and administration of services.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 42 Public Health 3 2011-10-01 2011-10-01 false Condition of Participation: Organization and administration of services. 418.100 Section 418.100 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICARE PROGRAM HOSPICE CARE Conditions of...

  1. 42 CFR 418.100 - Condition of Participation: Organization and administration of services.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 42 Public Health 3 2012-10-01 2012-10-01 false Condition of Participation: Organization and administration of services. 418.100 Section 418.100 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICARE PROGRAM (CONTINUED) HOSPICE CARE Conditions...

  2. 42 CFR 418.100 - Condition of Participation: Organization and administration of services.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 42 Public Health 3 2014-10-01 2014-10-01 false Condition of Participation: Organization and... participation: Organizational Environment § 418.100 Condition of Participation: Organization and administration... accepted standards of practice: (i) Nursing services. (ii) Medical social services. (iii)...

  3. MTBreg: The Database of Conditionally Regulated Proteins in Mycobacterium Tuberculosis

    DOE Data Explorer

    Kaufman, Markus; Pal, Debnath; Eisenberg, David

    Proteins up- and down- regulated in Mycobacterium tuberculosis grown under conditions mimicking infection are included in this database. It also includes information on proteins that are regulated by selected transcription factors or other regulatory proteins. The literature data provided here is complimentary to the databases provided by Michael Strong that include recent TB computational functional linkages and the Prolinks Database by Peter Bowers. The experimental condition, the experimental dataset and a literature reference will be displayed, including links to the computationally linked proteins in the Prolinks Database and the entry in the Mycobacterium tuberculosis Structural Genomics Database.[Copied from information at http://www.doe-mbi.ucla.edu/Services/MTBreg/

  4. Employee Retirement Income Security Act of 1974: rules and regulations for administration and enforcement; claims procedure. Pension and Welfare Benefits Administration, Labor. Final regulation.

    PubMed

    2000-11-21

    This document contains a final regulation revising the minimum requirements for benefit claims procedures of employee benefit plans covered by Title I of the Employee Retirement Income Security Act of 1974 (ERISA or the Act). The regulation establishes new standards for the processing of claims under group health plans and plans providing disability benefits and further clarifies existing standards for all other employee benefit plans. The new standards are intended to ensure more timely benefit determinations, to improve access to information on which a benefit determination is made, and to assure that participants and beneficiaries will be afforded a full and fair review of denied claims. When effective, the regulation will affect participants and beneficiaries of employee benefit plans, employers who sponsor employee benefit plans, plan fiduciaries, and others who assist in the provision of plan benefits, such as third-party benefits administrators and health service providers or health maintenance organizations that provide benefits to participants and beneficiaries of employee benefit plans.

  5. Health Care Financing Administration--Fiscal year 1980 regulation plan. Notice of regulation plan.

    PubMed

    1980-06-12

    HCFA has adopted a new regulation management system which includes a process for developing a regulation plan at the beginning of each fiscal year. Each initiative in the plan is designed to achieve specific programmatic goals and objectives in accordance with priorities. The plan includes a projected schedule for publishing each regulatory initiative in priority order. The annual HCFA plan supplements the Semi-Annual Agenda of Regulations published by HHS in June and December of each year in accordance with Executive Order 12044 "Improving Federal Government Regulations" (See 43 FR 12661 published March 23, 1978), and the Department's procedures which implement the Executive Order (See 43 FR 23119 published May 30, 1978, and 44 FR 59662 published October 16, 1979). The HCFA plan includes: [1] initiatives which appear in the Semi-Annual Agenda of Regulations because HCFA and the Secretary of HHS have concluded that specific regulation changes are needed; [2] new initiatives at an early stage of consideration where HCFA and the Secretary have not yet concluded that specific regulation changes are needed; and [3] routine initiatives that provide guidelines for existing regulations. HCFA is publishing the plan to provide the public with advance notice as early as possible of regulation initiatives that are planned or under active consideration. HCFA welcomes comments on the content of the plan, the priority set for each initiative, and projected publications targets.

  6. FHL2 regulates hematopoietic stem cell functions under stress conditions

    PubMed Central

    Hou, Yu; Wang, Xiaoqin; Li, LiPing; Fan, Rong; Chen, Ju; Zhu, Tongyu; Li, Wen; Jiang, Yanwen; Mittal, Nupur; Wu, Wenshu; Peace, David; Qian, Zhijian

    2014-01-01

    FHL2, a member of the four and one half LIM domain protein family, is a critical transcriptional modulator. Here, we identify FHL2 as a critical regulator of hematopoietic stem cells (HSCs) that is essential for maintaining HSC self-renewal under regenerative stress. We find that Fhl2 loss has limited effects on hematopoiesis under homeostatic conditions. In contrast, Fhl2-null chimeric mice reconstituted with Fhl2-null bone marrow cells developed abnormal hematopoiesis with significantly reduced numbers of HSCs, hematopoietic progenitor cells (HPCs), red blood cells and platelets as well as hemoglobin levels. In addition, HSCs displayed a significantly reduced self-renewal capacity and were skewed toward myeloid lineage differentiation. We find that Fhl2 loss reduces both HSC quiescence and survival in response to regenerative stress, probably as a consequence of Fhl2-loss-mediated down-regulation of cyclin dependent kinase (CDK)-inhibitors, including p21(Cip) and p27(Kip1). Interestingly, FHL2 is regulated under control of a tissue specific promoter in hematopoietic cells and it is down-regulated by DNA hypermethylation in the leukemia cell line and primary leukemia cells. Furthermore, we find that down-regulation of FHL2 frequently occurs in myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) patients, raising a possibility that FHL2 down-regulation plays a role in the pathogenesis of myeloid malignancies. PMID:25179730

  7. Mesolimbic leptin signaling negatively regulates cocaine-conditioned reward.

    PubMed

    Shen, M; Jiang, C; Liu, P; Wang, F; Ma, L

    2016-12-06

    The regulatory mechanisms underlying the response to addictive drugs are complex, and increasing evidence indicates that there is a role for appetite-regulating pathways in substance abuse. Leptin, an important adipose hormone that regulates energy balance and appetite, exerts its physiological functions via leptin receptors. However, the role of leptin signaling in regulating the response to cocaine remains unclear. Here we examined the potential role of leptin signaling in cocaine reward using a conditioned place preference (CPP) procedure. Our results showed that inhibition of leptin signaling by intracerebroventricular infusion of the leptin receptor (LepR) antagonist SMLA during cocaine conditioning increased the cocaine-CPP and upregulated the level of dopamine and its metabolites in the nucleus accumbens (NAc). We then selectively knocked down the LepR in the mesolimbic ventral tegmental area (VTA), NAc core and central amygdala (CeA) by injecting AAV-Cre into Lepr(flox/flox) mice. LepR deletion in the VTA increased the dopamine levels in the NAc and enhanced the cocaine-conditioned reward. LepR deletion in the NAc core enhanced the cocaine-conditioned reward and impaired the effect of the D2-dopamine receptor on cocaine-CPP, whereas LepR deletion in the CeA had no effect on cocaine-CPP but increased the anxiety level of mice. In addition, prior exposure to saccharin increased LepR mRNA and STAT3 phosphorylation in the NAc and VTA and impaired cocaine-CPP. These results indicate that leptin signaling is critically involved in cocaine-conditioned reward and the regulation of drug reward by a natural reward and that these effects are dependent on mesolimbic LepR.

  8. Mesolimbic leptin signaling negatively regulates cocaine-conditioned reward

    PubMed Central

    Shen, M; Jiang, C; Liu, P; Wang, F; Ma, L

    2016-01-01

    The regulatory mechanisms underlying the response to addictive drugs are complex, and increasing evidence indicates that there is a role for appetite-regulating pathways in substance abuse. Leptin, an important adipose hormone that regulates energy balance and appetite, exerts its physiological functions via leptin receptors. However, the role of leptin signaling in regulating the response to cocaine remains unclear. Here we examined the potential role of leptin signaling in cocaine reward using a conditioned place preference (CPP) procedure. Our results showed that inhibition of leptin signaling by intracerebroventricular infusion of the leptin receptor (LepR) antagonist SMLA during cocaine conditioning increased the cocaine-CPP and upregulated the level of dopamine and its metabolites in the nucleus accumbens (NAc). We then selectively knocked down the LepR in the mesolimbic ventral tegmental area (VTA), NAc core and central amygdala (CeA) by injecting AAV-Cre into Leprflox/flox mice. LepR deletion in the VTA increased the dopamine levels in the NAc and enhanced the cocaine-conditioned reward. LepR deletion in the NAc core enhanced the cocaine-conditioned reward and impaired the effect of the D2-dopamine receptor on cocaine-CPP, whereas LepR deletion in the CeA had no effect on cocaine-CPP but increased the anxiety level of mice. In addition, prior exposure to saccharin increased LepR mRNA and STAT3 phosphorylation in the NAc and VTA and impaired cocaine-CPP. These results indicate that leptin signaling is critically involved in cocaine-conditioned reward and the regulation of drug reward by a natural reward and that these effects are dependent on mesolimbic LepR. PMID:27922639

  9. 78 FR 40891 - Revisions to the Export Administration Regulations: Military Vehicles; Vessels of War...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-07-08

    ...This rule adds to the Export Administration Regulations (EAR) controls on military vehicles and related items; vessels of war and related items; submersible vessels, oceanographic equipment and related items; and auxiliary and miscellaneous items that the President has determined no longer warrant control on the United States Munitions List (USML). This rule also adds to the EAR controls on......

  10. 76 FR 75799 - General Administrative Regulations; Mutual Consent Cancellation; Food Security Act of 1985...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-05

    ... Consent Cancellation; Food Security Act of 1985, Implementation; Denial of Benefits; and Ineligibility for... remove Subpart C--General Administrative Regulations; Mutual Consent Cancellation and Subpart F--Food... quality of the human environment, health, or safety. Therefore, neither an Environmental Assessment nor...

  11. School Administrators' Opinions on Frequently Changing Regulations Related to Appointments and Relocation: A New Model Proposal

    ERIC Educational Resources Information Center

    Sezer, Senol

    2016-01-01

    The purpose of this study is to reveal school administrators' opinions on frequently changing regulations related to appointments and relocation and to offer a new model. A qualitative research design was employed. The study participants were 20 school principals and 20 vice principals working in the Ordu, Giresun and Trabzon city centres during…

  12. 78 FR 76741 - Revisions to the Export Administration Regulations (EAR): Unverified List (UVL)

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-12-19

    ...The Bureau of Industry and Security (BIS) is amending the Export Administration Regulations (EAR) by: Requiring exporters to file an Automated Export System (AES) record for all exports subject to the EAR involving a party or parties to the transaction who are listed on the Unverified List (the ``Unverified List'' or UVL); suspending the availability of license exceptions for exports,......

  13. 76 FR 58393 - Updated Statements of Legal Authority for the Export Administration Regulations

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-09-21

    ... Bureau of Industry and Security 15 CFR Parts 730, 732, 734, 736, 738, 740, 742, 743, 744, 746, 747, 748... of Legal Authority for the Export Administration Regulations AGENCY: Bureau of Industry and Security... Policy Division, Bureau of Industry and Security, Room H2899B, U.S. Department of Commerce,...

  14. 40 CFR 29.13 - May the Administrator waive any provision of these regulations?

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 1 2014-07-01 2014-07-01 false May the Administrator waive any provision of these regulations? 29.13 Section 29.13 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY GENERAL INTERGOVERNMENTAL REVIEW OF ENVIRONMENTAL PROTECTION AGENCY PROGRAMS AND ACTIVITIES §...

  15. 40 CFR 29.13 - May the Administrator waive any provision of these regulations?

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 1 2012-07-01 2012-07-01 false May the Administrator waive any provision of these regulations? 29.13 Section 29.13 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY GENERAL INTERGOVERNMENTAL REVIEW OF ENVIRONMENTAL PROTECTION AGENCY PROGRAMS AND ACTIVITIES §...

  16. 40 CFR 29.13 - May the Administrator waive any provision of these regulations?

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 1 2011-07-01 2011-07-01 false May the Administrator waive any provision of these regulations? 29.13 Section 29.13 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY GENERAL INTERGOVERNMENTAL REVIEW OF ENVIRONMENTAL PROTECTION AGENCY PROGRAMS AND ACTIVITIES §...

  17. 40 CFR 29.13 - May the Administrator waive any provision of these regulations?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 1 2010-07-01 2010-07-01 false May the Administrator waive any provision of these regulations? 29.13 Section 29.13 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY GENERAL INTERGOVERNMENTAL REVIEW OF ENVIRONMENTAL PROTECTION AGENCY PROGRAMS AND ACTIVITIES §...

  18. 40 CFR 29.13 - May the Administrator waive any provision of these regulations?

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 1 2013-07-01 2013-07-01 false May the Administrator waive any provision of these regulations? 29.13 Section 29.13 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY GENERAL INTERGOVERNMENTAL REVIEW OF ENVIRONMENTAL PROTECTION AGENCY PROGRAMS AND ACTIVITIES §...

  19. 78 FR 31431 - Export Administration Regulations (EAR): Control of Spacecraft Systems and Related Items the...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-05-24

    ... Administration Regulations (EAR): Control of Spacecraft Systems and Related Items the President Determines No Longer Warrant Control Under the United States Munitions List (USML) AGENCY: Bureau of Industry and... articles the President determines no longer warrant control under United States Munitions List...

  20. 76 FR 12279 - Amendment to the Export Administration Regulations: Application Processing, Issuance, and Denial

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-03-07

    ... Export Administration Regulations (EAR) by clarifying the Application Processing, Issuance, and Denial..., and Denial Part 750 of the EAR provides for the revision, suspension or revocation of licenses whenever it is known that the EAR have been violated or that a violation is about to occur. In this...

  1. 78 FR 13675 - Federal Acquisition Regulation; Submission for OMB Review; Cost Accounting Standards Administration

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-28

    ... accounting practice change, the total potential impact of the change on contracts containing a CAS provision... Regulation; Submission for OMB Review; Cost Accounting Standards Administration AGENCY: Department of Defense...: Under the provisions of the Paperwork Reduction Act, the Regulatory Secretariat will be submitting...

  2. Complying with Occupational Safety and Health Administration regulations: a guide for compounding pharmacists.

    PubMed

    Mixon, Bill; Nain, John

    2013-01-01

    In the compounding pharmacy, compliance with Occupational Safety and Health Administration regulations is essential to protect employees and customers from exposure to hazardous substances and a dangerous environment, to avert heavy fines and penalties levied for noncompliance, and to fulfill the moral obligation of pharmacists to do no harm. Without adequate vigilance, compounders are vulnerable to lapses in adherence to Occupational Safety and Health Administration requirements, the results of which can be dire in a climate of increased scrutiny about the safety and integrity of pharmaceutical compounding. Proactively addressing necessary compliance with essential safety regulations can only benefit compounders and their staff and clients, and guidance from an expert in Occupational Safety and Health Administration requirements can be a key factor in accomplishing that goal.

  3. Prohibited or regulated? LSD psychotherapy and the United States Food and Drug Administration.

    PubMed

    Oram, Matthew

    2016-09-01

    Over the 1950s and early 1960s, the use of the hallucinogenic drug lysergic acid diethylamide (LSD) to facilitate psychotherapy was a promising field of psychiatric research in the USA. However, during the 1960s, research began to decline, before coming to a complete halt in the mid-1970s. This has commonly been explained through the increase in prohibitive federal regulations during the 1960s that aimed to curb the growing recreational use of the drug. However, closely examining the Food and Drug Administration's regulation of LSD research in the 1960s will reveal that not only was LSD research never prohibited, but that the administration supported research to a greater degree than has been recognized. Instead, the decline in research reflected more complex changes in the regulation of pharmaceutical research and development.

  4. Compliance with the new Food and Drug Administration regulations: an approach by industry.

    PubMed

    Ward, J W

    1981-09-01

    Good Laboratory Practice regulations became effective on June 20, 1979. The regulations provide guidance for the proper conduct and reporting of nonclinical laboratory studies on articles regulated by the United States Food and Drug Administration. A fundamental requirement of the regulations is the establishment of a quality assurance unit within each research facility to ensure the utilization and maintenance of good laboratory practices. A second significant feature is the requirement for an archival unit responsible for maintaining all raw data, documentation, protocols, specimens, and final reports. Experience with the regulations has been mixed. The quality of reports has been upgraded dramatically. Protocols contain more information than ever, data recording is more extensive and more carefully executed, and reports are prepared more carefully and edited more thoroughly. Conversely, there is no real evidence that quality of science has been improved, and costs have increased markedly.

  5. Thermal conditions influence changes in body temperature induced by intragastric administration of capsaicin in mice.

    PubMed

    Mori, Noriyuki; Urata, Tomomi; Fukuwatari, Tsutomu

    2016-08-01

    Capsaicin has been reported to have unique thermoregulatory actions. However, changes in core temperature after the administration of capsaicin are a controversial point. Therefore, we investigated the effects of environmental thermal conditions on changes in body temperature caused by capsaicin in mice. We showed that intragastric administration of 10 and 15 mg/kg capsaicin increased tail temperature and decreased colonic temperatures in the core temperature (CT)-constant and CT-decreasing conditions. In the CT-increasing condition, 15 mg/kg capsaicin increased tail temperature and decreased colonic temperature. However, 10 mg/kg capsaicin increased colonic temperature. Furthermore, the amount of increase in tail temperature was greater in the CT-decreasing condition and lower in the CT-increasing condition, compared with that of the CT-constant condition. These findings suggest that the changes in core temperature were affected by the environmental thermal conditions and that preliminary thermoregulation state might be more important than the constancy of temperature to evaluate the effects of heat diffusion and thermogensis.

  6. [Mechanisms for regulation of fear conditioning and memory].

    PubMed

    Kida, Satoshi

    2014-11-01

    Pavlovian fear conditioning is a model of fear learning and memory. The mechanisms regulating fear conditioning and memory have been investigated in humans and rodents. In this paradigm, animals learn and memorize an association between a conditioned stimulus (CS), such as context, and an unconditioned stimulus (US), such as an electrical footshock that induces fear. Fear memory generated though fear conditioning is stabilized via a memory consolidation process. Moreover, recent studies have shown the existence of memory processes that control fear memory following the retrieval of consolidated memory. Indeed, when fear memory is retrieved by re-exposure to the CS, the retrieved memory is re-stabilized via the reconsolidation process. On the other hand, the retrieval of fear memory by prolonged re-exposure to the CS also leads to fear memory extinction, new inhibitory learning against the fear memory, in which animals learn that they do not need to respond to the CS. Importantly, the reinforcement of fear memory after retrieval (i.e., re-experience such as flashbacks or nightmares) has been thought to be associated with the development of emotional disorders such as post-traumatic stress disorder (PTSD). In this review, I summarize recent progress in studies on the mechanism of fear conditioning and memory consolidation, reconsolidation and extinction, and furthermore, introduce our recent establishment of a mouse PTSD model that shows enhancement of fear memory after retrieval.

  7. 32 CFR Appendix C to Part 22 - Administrative Requirements and Issues To Be Addressed in Award Terms and Conditions

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 32 National Defense 1 2010-07-01 2010-07-01 false Administrative Requirements and Issues To Be Addressed in Award Terms and Conditions C Appendix C to Part 22 National Defense Department of Defense... AND ADMINISTRATION Pt. 22, App. C Appendix C to Part 22—Administrative Requirements and Issues To...

  8. 32 CFR Appendix C to Part 22 - Administrative Requirements and Issues To Be Addressed in Award Terms and Conditions

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 32 National Defense 1 2013-07-01 2013-07-01 false Administrative Requirements and Issues To Be Addressed in Award Terms and Conditions C Appendix C to Part 22 National Defense Department of Defense... AND ADMINISTRATION Pt. 22, App. C Appendix C to Part 22—Administrative Requirements and Issues To...

  9. 32 CFR Appendix C to Part 22 - Administrative Requirements and Issues To Be Addressed in Award Terms and Conditions

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 32 National Defense 1 2011-07-01 2011-07-01 false Administrative Requirements and Issues To Be Addressed in Award Terms and Conditions C Appendix C to Part 22 National Defense Department of Defense... AND ADMINISTRATION Pt. 22, App. C Appendix C to Part 22—Administrative Requirements and Issues To...

  10. 15 CFR § 772.1 - Definitions of terms as used in the Export Administration Regulations (EAR).

    Code of Federal Regulations, 2010 CFR

    2015-01-01

    ... 15 Commerce and Foreign Trade 2 2015-01-01 2015-01-01 false Definitions of terms as used in the Export Administration Regulations (EAR). § 772.1 Section § 772.1 Commerce and Foreign Trade Regulations Relating to Commerce and Foreign Trade (Continued) BUREAU OF INDUSTRY AND SECURITY, DEPARTMENT OF COMMERCE EXPORT ADMINISTRATION...

  11. 15 CFR § 772.1 - Definitions of terms as used in the Export Administration Regulations (EAR).

    Code of Federal Regulations, 2010 CFR

    2016-01-01

    ... 15 Commerce and Foreign Trade 2 2016-01-01 2016-01-01 false Definitions of terms as used in the Export Administration Regulations (EAR). § 772.1 Section § 772.1 Commerce and Foreign Trade Regulations Relating to Commerce and Foreign Trade (Continued) BUREAU OF INDUSTRY AND SECURITY, DEPARTMENT OF COMMERCE EXPORT ADMINISTRATION...

  12. 49 CFR 171.22 - Authorization and conditions for the use of international standards and regulations.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... Transportation PIPELINE AND HAZARDOUS MATERIALS SAFETY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION HAZARDOUS MATERIALS REGULATIONS GENERAL INFORMATION, REGULATIONS, AND DEFINITIONS Authorization and Requirements for... and the transportation in commerce of hazardous materials in accordance with the International...

  13. Legal Regulation of Sodium Consumption to Reduce Chronic Conditions

    PubMed Central

    Barraza, Leila F.

    2016-01-01

    In the United States, tens of thousands of Americans die each year of heart disease, stroke, or other chronic conditions tied to hypertension from long-term overconsumption of sodium compounds. Major strides to lower dietary sodium have been made over decades, but the goal of reducing Americans’ daily consumption is elusive. The Food and Drug Administration (FDA) has been urged to consider stronger regulatory limits on sodium, especially in processed and prepared foods. Still, FDA categorizes salt (and many other sodium compounds) as “generally recognized as safe,” meaning they can be added to foods when ingested in reasonable amounts. Legal reforms or actions at each level of government offer traditional and new routes to improving chronic disease outcomes. However, using law as a public health tool must be assessed carefully, given potential trade-offs and unproven efficacy. PMID:26890409

  14. Legal Regulation of Sodium Consumption to Reduce Chronic Conditions.

    PubMed

    Hodge, James G; Barraza, Leila F

    2016-02-18

    In the United States, tens of thousands of Americans die each year of heart disease, stroke, or other chronic conditions tied to hypertension from long-term overconsumption of sodium compounds. Major strides to lower dietary sodium have been made over decades, but the goal of reducing Americans' daily consumption is elusive. The Food and Drug Administration (FDA) has been urged to consider stronger regulatory limits on sodium, especially in processed and prepared foods. Still, FDA categorizes salt (and many other sodium compounds) as "generally recognized as safe," meaning they can be added to foods when ingested in reasonable amounts. Legal reforms or actions at each level of government offer traditional and new routes to improving chronic disease outcomes. However, using law as a public health tool must be assessed carefully, given potential trade-offs and unproven efficacy.

  15. Implementing International Health Regulation (2005) in the Brazilian legal-administrative system.

    PubMed

    Lima, Yara Oyram Ramos; Costa, Ediná Alves

    2015-06-01

    The scope of this study was to analyze how the International Sanitary Regulation (ISR 2005)has been incorporated into the Brazilian legal-administrative system, in relation to sanitary control measures involving freight, means of transportation and travelers and possible alterations to health surveillance activities, competencies and procedures. This case study has been undertaken using a qualitative approach, of a descriptive and exploratory nature, using institutional data sources and interviews with key-informants involved in implementing ISR (2005). Alterations to the Brazilian legal-administrative system resulting from ISR (2005) were identified, in relation to standards, special competencies and procedures relating to sanitary controls for freight, modes of transportation and travelers. In its present form, the International Sanitary Regulation is an instrument that, in addition to introducing new international and national sanitary control concepts and elements, also helps to clarify questions that are helpful on a national level, relating to the specific competencies and procedures which will, to a certain extent, put pressure on administrative structures in the areas of sanitary control and surveillance.

  16. Conditioned place aversion induced by intragastric administration of ethanol in rats.

    PubMed

    Fidler, Tara L; Bakner, Lee; Cunningham, Christopher L

    2004-04-01

    Most experiments investigating ethanol-induced place conditioning in rats have produced conditioned place aversion (CPA). In one of the few reports of ethanol-induced conditioned place preference (CPP) in rats, selectively bred alcohol-preferring (msP) rats showed CPP in a biased procedure when ethanol was administered via intragastric (IG) catheter but not when ethanol was administered via intraperitoneal injection or by gavage. This finding suggests the importance of both route of administration and genetic variables to the outcome of place conditioning studies. We conducted three experiments examining place conditioning induced by IG ethanol in genetically heterogeneous rats to test the generality of the earlier finding. We employed an unbiased procedure that is more sensitive to detecting preference changes in either direction (preference or aversion). Ethanol-naive (Experiment 1) and ethanol-experienced Sprague-Dawley rats (Experiment 2) showed robust CPA. In Experiment 3, infusion rate was varied to see if the CPA observed in Experiments 1 and 2 was a result of the rapidity of the transition from the sober to the intoxicated states. Both groups showed strong CPA. Overall, the present findings are consistent with previous findings of CPA in heterogeneous rats, suggesting that the aversive postabsorptive effects of ethanol produce CPA.

  17. Further amendments to general regulations of the Food and Drug Administration to incorporate tobacco products. Final rule.

    PubMed

    2012-02-02

    The Food and Drug Administration (FDA) is amending certain of its general regulations to include tobacco products, where appropriate, in light of FDA's authority to regulate these products under the Family Smoking Prevention and Tobacco Control Act (Tobacco Control Act). With these amendments, tobacco products are subject to the same general requirements that apply to other FDA-regulated products.

  18. Opioid receptors regulate the extinction of Pavlovian fear conditioning.

    PubMed

    McNally, Gavan P; Westbrook, R Frederick

    2003-12-01

    Rats received a single pairing of an auditory conditioned stimulus (CS) with a footshock unconditioned stimulus (US). The fear (freezing) that had accrued to the CS was then extinguished. Injection of naloxone prior to this extinction significantly impaired the development of extinction. This impairment was mediated by opioid receptors in the brain and was not observed when naloxone was injected after extinction training. Finally, an injection of naloxone on test failed to reinstate extinguished responding that had already accrued to the CS. These experiments show that opioid receptors regulate the development, but not the expression, of fear extinction and are discussed with reference to the roles of opioid receptors in US processing, memory, and appetitive motivation.

  19. Impact of new Food and Drug Administration regulations on college, university, and experiment station researchers.

    PubMed

    Willett, L B

    1981-09-01

    The Good Laboratory Practice regulations adopted by the Food and Drug Administration describe specific procedures to assure the integrity of the research results. Those studies conducted with the intent to provide data on the safety of drugs and chemicals will be required to comply with the published relations. The process of bringing research laboratories into compliance with the regulations may be either arduous or fairly routine depending on the organization, goals, and type of research. Typically, the Good Laboratory Practice regulations will increase sharply the cost of health safety information. Hiring more and better trained technical and professional personnel will be much of this expense. If university and experiment station researchers choose to avoid compliance with these regulations, then agricultural research science may not continue to be recognized as an authority on the safety of products used for production of human food. Irrespective of whether universities choose to conduct regulated research or delegate this role to other segments of society, academic institutions must assume the role of training those individuals needed to conduct toxicity research.

  20. Melatonin administration in diabetes: regulation of plasma Cr, V, and Mg in young male Zucker diabetic fatty rats.

    PubMed

    Navarro-Alarcon, Miguel; Ruiz-Ojeda, Francisco J; Blanca-Herrera, Rosa M; Kaki, Abdullah; Adem, Abdu; Agil, Ahmad

    2014-03-01

    The use of melatonin, a neurohormone present in plants, represents an exciting approach for the maintenance of optimum health conditions. Melatonin administration ameliorates glucose homeostasis in Zucker diabetic fatty (ZDF) rats. The objective of this study was to investigate the effects of melatonin in diabetes in relation to the levels and regulation of plasma chromium (Cr), vanadium (V), and magnesium (Mg) in Zucker diabetic fatty (ZDF) and Zucker lean (ZL) rats. At the age of 6 weeks, ZDF (n = 30) and ZL (n = 30) groups were each subdivided into three groups: control (C) (n = 10), vehicle-treated (V') (n = 10) and melatonin-treated (M) (10 mg kg(-1) per day; n = 10) groups for a 6 week period. After treatment, plasma mineral concentrations were measured by flame (Mg) and electrothermal (Cr and V) atomic absorption spectrometry. No significant differences were found between the C and V' groups (p > 0.05). Plasma Mg levels were significantly lower in C-ZDF vs. C-ZL rats, demonstrating the presence of hypomagnesemia in this diabetes mellitus model. Plasma V and Cr levels were significantly higher in M-ZDF vs. C-ZDF rats. Plasma Mg levels in ZDF rats were not affected by melatonin treatment (p > 0.05). Melatonin administration ameliorates the diabetic status of ZDF rats by enhancing plasma Cr and V concentrations. This appears to be the first report of a beneficial effect of melatonin treatment on plasma Cr and V regulation in ZDF rats.

  1. Systemic regulation of soybean nodulation by acidic growth conditions.

    PubMed

    Lin, Meng-Han; Gresshoff, Peter M; Ferguson, Brett J

    2012-12-01

    Mechanisms inhibiting legume nodulation by low soil pH, although highly prevalent and economically significant, are poorly understood. We addressed this in soybean (Glycine max) using a combination of physiological and genetic approaches. Split-root and grafting studies using an autoregulation-of-nodulation-deficient mutant line, altered in the autoregulation-of-nodulation receptor kinase GmNARK, determined that a systemic, shoot-controlled, and GmNARK-dependent mechanism was critical for facilitating the inhibitory effect. Acid inhibition was independent of aluminum ion concentration and occurred early in nodule development, between 12 and 96 h post inoculation with Bradyrhizobium japonicum. Biological effects were confirmed by measuring transcript numbers of known early nodulation genes. Transcripts decreased on both sides of split-root systems, where only one side was subjected to low-pH conditions. Our findings enhance the present understanding of the innate mechanisms regulating legume nodulation control under acidic conditions, which could benefit future attempts in agriculture to improve nodule development and biological nitrogen fixation in acid-stressed soils.

  2. US Food and Drug Administration international collaborations for cellular therapy product regulation

    PubMed Central

    2012-01-01

    Cellular therapy products are an emerging medical product class undergoing rapid scientific and clinical innovation worldwide. These products pose unique regulatory challenges both for countries with existing regulatory frameworks and for countries where regulatory frameworks for cellular therapy products are under development. The United States Food and Drug Administration (US FDA) has a history of productive working relationships with international regulatory authorities, and seeks to extend this to the cellular therapy field. The US FDA and its global regulatory counterparts are engaged in collaborations focused on the convergence of scientific and regulatory approaches, and the education of scientists, clinicians, regulators, and the public at large on the development of cellular therapies. PMID:23021082

  3. United States Food and Drug Administration Regulation of Gene and Cell Therapies.

    PubMed

    Bailey, Alexander M; Arcidiacono, Judith; Benton, Kimberly A; Taraporewala, Zenobia; Winitsky, Steve

    2015-01-01

    The United States (US) Food and Drug Administration (FDA) is a regulatory agency that has oversight for a wide range of products entering the US market, including gene and cell therapies. The regulatory approach for these products is similar to other medical products within the United States and consists of a multitiered framework of statutes, regulations, and guidance documents. Within this framework, there is considerable flexibility which is necessary due to the biological and technical complexity of these products in general. This chapter provides an overview of the US FDA regulatory oversight of gene and cell therapy products.

  4. Grants for graduate programs in health administration and grants for traineeships in health administration--PHS. Amendments to final regulations.

    PubMed

    1984-05-22

    These amendments conform provisions in 42 CFR Part 58, Subpart A, "Grants for Graduate Programs in Health Administration," and Subpart D, entitled "Grants for Traineeships in Health Administration, Hospital Administration, or Health Policy Analysis and Planning at Public or Nonprofit Private Educational Institutions Other Than Schools of Public Health" to statutory amendments made by the Orphan Drug Act, Pub . L. 97-414: the Omnibus Budget Reconciliation Act of 1981, Pub . L. 97-35; and Pub . L. 94-241, the Commonwealth-- Covenant to Establish--Northern Mariana Islands.

  5. Incidence and Variation of Discrepancies in Recording Chronic Conditions in Australian Hospital Administrative Data

    PubMed Central

    Assareh, Hassan; Achat, Helen M.; Stubbs, Joanne M.; Guevarra, Veth M.; Hill, Kim

    2016-01-01

    Diagnostic data routinely collected for hospital admitted patients and used for case-mix adjustment in care provider comparisons and reimbursement are prone to biases. We aim to measure discrepancies, variations and associated factors in recorded chronic morbidities for hospital admitted patients in New South Wales (NSW), Australia. Of all admissions between July 2010 and June 2014 in all NSW public and private acute hospitals, admissions with over 24 hours stay and one or more of the chronic conditions of diabetes, smoking, hepatitis, HIV, and hypertension were included. The incidence of a non-recorded chronic condition in an admission occurring after the first admission with a recorded chronic condition (index admission) was considered as a discrepancy. Poisson models were employed to (i) derive adjusted discrepancy incidence rates (IR) and rate ratios (IRR) accounting for patient, admission, comorbidity and hospital characteristics and (ii) quantify variation in rates among hospitals. The discrepancy incidence rate was highest for hypertension (51% of 262,664 admissions), followed by hepatitis (37% of 12,107), smoking (33% of 548,965), HIV (27% of 1500) and diabetes (19% of 228,687). Adjusted rates for all conditions declined over the four-year period; with the sharpest drop of over 80% for diabetes (47.7% in 2010 vs. 7.3% in 2014), and 20% to 55% for the other conditions. Discrepancies were more common in private hospitals and smaller public hospitals. Inter-hospital differences were responsible for 1% (HIV) to 9.4% (smoking) of variation in adjusted discrepancy incidences, with an increasing trend for diabetes and HIV. Chronic conditions are recorded inconsistently in hospital administrative datasets, and hospitals contribute to the discrepancies. Adjustment for patterns and stratification in risk adjustments; and furthermore longitudinal accumulation of clinical data at patient level, refinement of clinical coding systems and standardisation of comorbidity

  6. Neural circuitry of emotion regulation: Effects of appraisal, attention, and cortisol administration.

    PubMed

    Ma, Sean T; Abelson, James L; Okada, Go; Taylor, Stephan F; Liberzon, Israel

    2017-04-01

    Psychosocial well-being requires effective regulation of emotional responding in context of threat or stress. Neuroimaging studies have focused on instructed, volitional regulation (e.g., reappraisal or distancing), largely ignoring implicit regulation that does not involve purposeful effort to alter emotional experience. These implicit processes may or may not involve the same neural pathways as explicit regulatory strategies. We examined the neurobiology of implicit emotional regulation processes and the impact of the stress hormone cortisol on these processes. Our study task employed composite pictures of faces and places to examine neural activity during implicit emotional processing (of emotional faces), while these responses were implicitly regulated by attention shift away from the emotionally evocative stimuli, and while subjects reflectively appraised their own emotional response to them. Subjects completed the task in an fMRI scanner after random assignment to receive placebo or hydrocortisone (HCT), an orally administered version of cortisol. Implicit emotional processing activated insula/IFG, dACC/dMPFC, midbrain and amygdala. With attention shifting, we saw diminished signal in emotion generating/response regions (e.g., amygdala) and increased activations in task specific attention regions like parahippocampus. With appraisal of emotions, we observed robust activations in medial prefrontal areas, where activation is also seen in instructed reappraisal studies. We observed no main effects of HCT administration on brain, but males and females showed opposing neural effects in prefrontal areas. The data suggest that different types of emotion regulation utilize overlapping circuits, but with some strategy specific activation. Further study of the dimorphic sex response to cortisol is needed.

  7. Conditioned taste aversion dependent regulation of amygdala gene expression.

    PubMed

    Panguluri, Siva K; Kuwabara, Nobuyuki; Kang, Yi; Cooper, Nigel; Lundy, Robert F

    2012-02-28

    The present experiments investigated gene expression in the amygdala following contingent taste/LiCl treatment that supports development of conditioned taste aversion (CTA). The use of whole genome chips and stringent data set filtering led to the identification of 168 genes regulated by CTA compared to non-contingent LiCl treatment that does not support CTA learning. Seventy-six of these genes were eligible for network analysis. Such analysis identified "behavior" as the top biological function, which was represented by 15 of the 76 genes. These genes included several neuropeptides, G protein-coupled receptors, ion channels, kinases, and phosphatases. Subsequent qRT-PCR analyses confirmed changes in mRNA expression for 5 of 7 selected genes. We were able to demonstrate directionally consistent changes in protein level for 3 of these genes; insulin 1, oxytocin, and major histocompatibility complex class I-C. Behavioral analyses demonstrated that blockade of central insulin receptors produced a weaker CTA that was less resistant to extinction. Together, these results support the notion that we have identified downstream genes in the amygdala that contribute to CTA learning.

  8. Tobacco advertising and sales practices in licensed retail outlets after the Food and Drug Administration regulations.

    PubMed

    Frick, Ryan G; Klein, Elizabeth G; Ferketich, Amy K; Wewers, Mary Ellen

    2012-10-01

    To assess retailer compliance with Food and Drug Administration (FDA) regulations on tobacco sales and advertising practices, including point-of-sale advertisements, in two distinct Columbus, Ohio neighborhood groups by income. Data were gathered from a random sample of 129 licensed tobacco retailers, which included data on both exterior and interior advertisements as well as sales practices. Descriptive analyses compared retail outlets by high and low income neighborhood locations. Compliance with FDA regulations was high in the random sample of urban tobacco retail outlets. None of the retail outlets sold loose cigarettes or offered free items with purchase. Less than 10% of the outlets surveyed offered self-service access to cigarettes or smokeless tobacco products. From all surveyed retail outlets 95% had cigarette, 57% had smokeless, and 57% had cigar advertisements at the point-of-sale. There were no significant differences in compliance by income, but the mean number of advertisements on the building and self-service access to cigars was significantly different by neighborhood income. There was a high degree of compliance with the new FDA regulation on tobacco marketing and sales practices in urban retail tobacco outlets in Columbus, Ohio. Tobacco advertising and marketing remain highly prevalent in retail outlets, with some significant differences between high and low income neighborhoods.

  9. Rational Design and Characterization of a Nanosuspension for Intraoral Administration Considering Physiological Conditions.

    PubMed

    Baumgartner, Ramona; Teubl, Birgit J; Tetyczka, Carolin; Roblegg, Eva

    2016-01-01

    The oral cavity displays an attractive route in drug administration that is not associated with gastric transit and hepatic first-pass metabolism. However, limiting factors for an efficient transit of drugs through the oral mucosa are poor water solubility and permeability. Hence, various strategies exist to enhance solubility. Specifically, nanotechnology has attracted much research interest in the past decade. This study aimed at developing a stable nanosuspension of the model compound phenytoin via wet media milling. The nanosuspensions were carefully characterized regarding hydrodynamic particle sizes, crystallinity, and dissolution characteristics under nonphysiological or physiological (salivary) conditions. The permeability of bulk phenytoin and nanophenytoin through a buccal in vitro and ex vivo model was investigated, and the apparent permeability coefficients were determined. Moreover, cytotoxicity studies were conducted. The addition of Tween 80 as stabilizer resulted in a stable crystalline nanosuspension (330 nm). The solubility characteristics significantly increased under salivary conditions, which further impacted the permeability, as the steady state appearance rate of nanosized phenytoin was 1.4-fold higher. Cytotoxicity studies demonstrated that bulk-/nano-phenytoin exhibited no harmful effects. It can be concluded that the salivary environment (i.e., ionic strength, pH) strongly impacts the solubility and consequently the permeability of crystalline nanosuspensions across the buccal mucosa.

  10. Melatonin administration modifies circadian motor activity under constant light depending on the lighting conditions during suckling.

    PubMed

    Carpentieri, Agata R; Oliva, Clara; Díez-Noguera, Antoni; Cambras, Trinitat

    2015-01-01

    Early lighting conditions have been described to produce long-term effects on circadian behavior, which may also influence the response to agents acting on the circadian system. It has been suggested that melatonin (MEL) may act on the circadian pacemaker and as a scavenger of reactive oxygen and nitrogen species. Here, we studied the oxidative and behavioral changes caused by prolonged exposure to constant light (LL) in groups of rats that differed in MEL administration and in lighting conditions during suckling. The rats were exposed to either a light-dark cycle (LD) or LL. At 40 days old, rats were treated for 2 weeks with a daily subcutaneous injection of MEL (10 mg/kg body weight) or a vehicle at activity onset. Blood samples were taken before and after treatment, to determine catalase (CAT) activity and nitrite level in plasma. As expected, LL-reared rats showed a more stable motor activity circadian rhythm than LD rats. MEL treatment produced more reactivity in LD- than in LL rats, and was also able to alter the phase of the rhythm in LD rats. There were no significant differences in nitrite levels or CAT activity between the groups, although both variables increased with time. Finally, we also tested depressive signs by means of sucrose consumption, and anhedonia was found in LD males treated with MEL. The results suggest that the lighting conditions in early infancy are important for the long-term functionality of the circadian system, including rhythm manifestation, responses to MEL and mood alterations.

  11. Regulation of hypnosis in Propofol anesthesia administration based on non-linear control strategy.

    PubMed

    Ilyas, Muhammad; Khaqan, Ali; Iqbal, Jamshed; Riaz, Raja Ali

    Continuous adjustment of Propofol in manual delivery of anesthesia for conducting a surgical procedure overburdens the workload of an anesthetist who is working in a multi-tasking scenario. Going beyond manual administration and Target Controlled Infusion, closed-loop control of Propofol infusion has the potential to offer several benefits in terms of handling perturbations and reducing the effect of inter-patient variability. This paper proposes a closed-loop automated drug administration approach to control Depth Of Hypnosis in anesthesia. In contrast with most of the existing research on anesthesia control which makes use of linear control strategies or their improved variants, the novelty of the present research lies in applying robust control strategy i.e. Sliding Mode Control to accurately control drug infusion. Based on the derived patient's model, the designed controller uses measurements from EEG to regulate DOH on Bispectral Index by controlling infusion rate of Propofol. The performance of the controller is investigated and characterized with real dataset of 8 patients undergoing surgery. Results of this in silico study indicate that for all the patients, with 0% overshoot observed, the steady state error lies in between ±5. Clinically, this implies that in all the cases, without any overdose, the controller maintains the desired DOH level for smooth conduction of surgical procedures.

  12. [Regulation of hypnosis in Propofol anesthesia administration based on non-linear control strategy].

    PubMed

    Ilyas, Muhammad; Khaqan, Ali; Iqbal, Jamshed; Riaz, Raja Ali

    Continuous adjustment of Propofol in manual delivery of anesthesia for conducting a surgical procedure overburdens the workload of an anesthetist who is working in a multi-tasking scenario. Going beyond manual administration and Target Controlled Infusion, closed-loop control of Propofol infusion has the potential to offer several benefits in terms of handling perturbations and reducing the effect of inter-patient variability. This paper proposes a closed-loop automated drug administration approach to control Depth Of Hypnosis in anesthesia. In contrast with most of the existing research on anesthesia control which makes use of linear control strategies or their improved variants, the novelty of the present research lies in applying robust control strategy i.e. Sliding Mode Control to accurately control drug infusion. Based on the derived patient's model, the designed controller uses measurements from EEG to regulate DOH on Bispectral Index by controlling infusion rate of Propofol. The performance of the controller is investigated and characterized with real dataset of 8 patients undergoing surgery. Results of this in silico study indicate that for all the patients, with 0% overshoot observed, the steady state error lies in between ±5. Clinically, this implies that in all the cases, without any overdose, the controller maintains the desired DOH level for smooth conduction of surgical procedures.

  13. SELF-ADMINISTRATION OF COCAINE AND REMIFENTANIL BY MONKEYS UNDER CONCURRENT-ACCESS CONDITIONS

    PubMed Central

    Huskinson, Sally L.; Freeman, Kevin B.; Woolverton, William L.

    2014-01-01

    Rationale Cocaine and opioids are often co-abused. Laboratory research has focused largely on the reinforcing effects of mixtures of drugs relative to the drugs alone. Less research has examined drug mixing by the subject under concurrent-access conditions. Objective Self-administration of various doses of cocaine and remifentanil was examined under concurrent-access conditions. It was hypothesized that if cocaine and opioid combinations were more effective reinforcers than the single drugs, subjects would mix the two drugs by adjusting their responding to cocaine and opioid alternatives to maintain an optimal ratio of cocaine:remifentanil intake. Method Three male rhesus monkeys were allowed to self-administer cocaine (0.05–0.2 mg/kg/inj) or saline on one lever and remifentanil (0.05–0.4 µg/kg/inj) or saline on the other lever under concurrent FR 10 schedules. Daily sessions lasted 2-h, and there was a 1-s timeout after every 10-s injection. Results When saline and drug were concurrently available, responding on the saline-associated lever was low relative to the drug alternative. When cocaine and remifentanil were concurrently available, both drugs were self-administered above saline levels. Cocaine intake decreased and remifentanil intake increased as a function of the remifentanil dose that was available. Conversely, cocaine intake and remifentanil intake did not change systematically as a function of the cocaine dose that was available. Conclusion Monkeys will mix cocaine and an opioid when the two drugs are available concurrently. However, there was no indication that monkeys titrated drug-intake to maintain an optimal ratio of intake of the two compounds. PMID:24961564

  14. CRF-Amplified Neuronal TLR4/MCP-1 Signaling Regulates Alcohol Self-Administration

    PubMed Central

    June, Harry L; Liu, Juan; Warnock, Kaitlin T; Bell, Kimberly A; Balan, Irina; Bollino, Dominique; Puche, Adam; Aurelian, Laure

    2015-01-01

    Alcohol dependence is a complex disorder that initiates with episodes of excessive alcohol drinking known as binge drinking. It has a 50–60% risk contribution from inherited susceptibility genes; however, their exact identity and function are still poorly understood. We report that alcohol-preferring P rats have innately elevated levels of Toll-like receptor 4 (TLR4) and monocyte chemotactic protein-1 (MCP-1) that colocalize in neurons from the central nucleus of the amygdala (CeA) and ventral tegmental area (VTA). To examine the potential role of a TLR4/MCP-1 signal, we used Herpes Simplex Virus (HSV) vectors (amplicons) that retain in vivo neurotropism. Infusion of amplicons for TLR4 or MCP-1 siRNA into the CeA or VTA from the P rats inhibited target gene expression and blunted binge drinking. A similarly delivered amplicon for scrambled siRNA did not inhibit TLR4 or MCP-1 expression nor reduce binge drinking, identifying a neuronal TLR4/MCP-1 signal that regulates the initiation of voluntary alcohol self-administration. The signal was sustained during alcohol drinking by increased expression of corticotropin-releasing factor and its feedback regulation of TLR4 expression, likely contributing to the transition to alcohol dependence. PMID:25567426

  15. 7 CFR 318.13-16 - Regulated articles allowed interstate movement subject to specified conditions.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 5 2014-01-01 2014-01-01 false Regulated articles allowed interstate movement subject... Regulated articles allowed interstate movement subject to specified conditions. (a) The following regulated... applicable regulated articles as specified in paragraph (a) of this section. (1) Restricted movement...

  16. 7 CFR 318.13-16 - Regulated articles allowed interstate movement subject to specified conditions.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 5 2011-01-01 2011-01-01 false Regulated articles allowed interstate movement subject... Regulated articles allowed interstate movement subject to specified conditions. (a) The following regulated... applicable regulated articles as specified in paragraph (a) of this section. (1) Restricted movement...

  17. 7 CFR 318.13-16 - Regulated articles allowed interstate movement subject to specified conditions.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 5 2012-01-01 2012-01-01 false Regulated articles allowed interstate movement subject... Regulated articles allowed interstate movement subject to specified conditions. (a) The following regulated... applicable regulated articles as specified in paragraph (a) of this section. (1) Restricted movement...

  18. 7 CFR 318.13-16 - Regulated articles allowed interstate movement subject to specified conditions.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 5 2013-01-01 2013-01-01 false Regulated articles allowed interstate movement subject... Regulated articles allowed interstate movement subject to specified conditions. (a) The following regulated... applicable regulated articles as specified in paragraph (a) of this section. (1) Restricted movement...

  19. 49 CFR 171.22 - Authorization and conditions for the use of international standards and regulations.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... international standards and regulations. 171.22 Section 171.22 Transportation Other Regulations Relating to... the Use of International Transport Standards and Regulations § 171.22 Authorization and conditions for the use of international standards and regulations. (a) Authorized international standards...

  20. 49 CFR 171.22 - Authorization and conditions for the use of international standards and regulations.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... international standards and regulations. 171.22 Section 171.22 Transportation Other Regulations Relating to... the Use of International Transport Standards and Regulations § 171.22 Authorization and conditions for the use of international standards and regulations. (a) Authorized international standards...

  1. 42 CFR 418.100 - Condition of Participation: Organization and administration of services.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ..., and homemaker services. (vi) Physical therapy, occupational therapy, and speech-language pathology... administration, supervision, and services with the hospice issued the certification number. (iii) The lines...

  2. Differential regulation of MeCP2 and PP1 in passive or voluntary administration of cocaine or food.

    PubMed

    Bodetto, Sarah Pol; Romieu, Pascal; Sartori, Maxime; Tesone-Coelho, Carolina; Majchrzak, Monique; Barbelivien, Alexandra; Zwiller, Jean; Anglard, Patrick

    2014-12-01

    Cocaine exposure induces changes in the expression of numerous genes, in part through epigenetic modifications. We have initially shown that cocaine increases the expression of the chromatin remodeling protein methyl-CpG binding protein 2 (MeCP2) and characterized the protein phosphatase-1Cβ (PP1Cβ) gene, as repressed by passive i.p. cocaine injections through a Mecp2-mediated mechanism involving de novo DNA methylation. Both proteins being involved in learning and memory processes, we investigated whether voluntary cocaine administration would similarly affect their expression using an operant self-administration paradigm. Passive and voluntary i.v. cocaine intake was found to induce Mecp2 and to repress PP1Cβ in the prefrontal cortex and the caudate putamen. This observation is consistent with the role of Mecp2 acting as a transcriptional repressor of PP1Cβ and shows that passive intake was sufficient to alter their expression. Surprisingly, striking differences were observed under the same conditions in food-restricted rats tested for food pellet delivery. In the prefrontal cortex and throughout the striatum, both proteins were induced by food operant conditioning, but remained unaffected by passive food delivery. Although cocaine and food activate a common reward circuit, changes observed in the expression of other genes such as reelin and GAD67 provide new insights into molecular mechanisms differentiating neuroadaptations triggered by each reinforcer. The identification of hitherto unknown genes differentially regulated by drugs of abuse and a natural reinforcer should improve our understanding of how two rewarding stimuli differ in their ability to drive behavior.

  3. Sonoporation of adherent cells under regulated ultrasound cavitation conditions.

    PubMed

    Muleki Seya, Pauline; Fouqueray, Manuela; Ngo, Jacqueline; Poizat, Adrien; Inserra, Claude; Béra, Jean-Christophe

    2015-04-01

    A sonoporation device dedicated to the adherent cell monolayer has been implemented with a regulation process allowing the real-time monitoring and control of inertial cavitation activity. Use of the cavitation-regulated device revealed first that adherent cell sonoporation efficiency is related to inertial cavitation activity, without inducing additional cell mortality. Reproducibility is enhanced for the highest sonoporation rates (up to 17%); sonoporation efficiency can reach 26% when advantage is taken of the standing wave acoustic configuration by applying a frequency sweep with ultrasound frequency tuned to the modal acoustic modes of the cavity. This device allows sonoporation of adherent and suspended cells, and the use of regulation allows some environmental parameters such as the temperature of the medium to be overcome, resulting in the possibility of cell sonoporation even at ambient temperature.

  4. Food and drug administration regulation of drugs that raise blood pressure.

    PubMed

    Blankfield, Robert P; Iftikhar, Imran H

    2015-01-01

    Although it is recognized that a systolic blood pressure (SBP) increase ≥ 2 mm Hg or a diastolic blood pressure (DBP) increase ≥ 1 mm Hg increases the risk of heart attacks and strokes in middle-aged adults, the Food and Drug Administration (FDA) lacks an adequate policy for regulating medications that increase blood pressure (BP). Some FDA reviewers consider a clinically significant increase in BP to occur only if a drug raises SBP ≥ 20 mm Hg or if a drug raises DBP ≥ 10 to 15 mm Hg. In recent years, numerous drugs have been regulated or taken off the market due to cardiovascular safety concerns. The list includes rofecoxib (Vioxx), valdecoxib (Bextra), nonselective nonsteroidal anti-inflammatory drugs, sibutramine (Meridia), and phenylpropanolamine. It is probable that the hypertensive effect of these drugs explains why they increase the risk of adverse cardiovascular events. Other drugs, notably serotonin-norepinephrine reuptake inhibitors and drugs used to treat attention deficit hyperactivity disorder, were approved without cardiovascular safety data despite the fact that they raise BP comparable to valdecoxib and sibutramine. It is the responsibility of the FDA to ensure that drugs are properly labeled regarding risk. Even if a drug raises BP only modestly, FDA guidelines for new drug approvals should include a requirement for cardiovascular safety data. However, such guidelines will not address the problem of how to obtain cardiovascular safety data for the many already approved drugs that increase BP. The FDA should play a role in obtaining cardiovascular safety data for such drugs.

  5. Evaluation of current regulations and real accident conditions

    SciTech Connect

    Fischer, L.E.; Kimura, C.Y.; Witte, M.C.

    1985-04-05

    In order to improve estimates of the effectiveness of current regulatory standards, a program was initiated by the US Nuclear Regulatory Commission (NRC) to have the Lawrence Livermore Laboratory (LLNL) evaluate regulatory standards against real world accident conditions. This paper presents the results of the evaluation performed for the hypothetical 30-foot drop onto an unyielding surface and real world impact conditions which might be experienced by a spent fuel cask being transported by a truck. The results of the evaluations performed for other pertinent accident conditions for truck and train transport will be documented at the conclusion of the program. 10 refs., 8 figs., 3 tabs.

  6. Serotonin-3 receptors in the posterior ventral tegmental area regulate ethanol self-administration of alcohol-preferring (P) rats.

    PubMed

    Rodd, Zachary A; Bell, Richard L; Oster, Scott M; Toalston, Jamie E; Pommer, Tylene J; McBride, William J; Murphy, James M

    2010-05-01

    Several studies indicated the involvement of serotonin-3 ([5-hydroxy tryptamine] 5-HT(3)) receptors in regulating alcohol-drinking behavior. The objective of this study was to determine the involvement of 5-HT(3) receptors within the ventral tegmental area (VTA) in regulating ethanol self-administration by alcohol-preferring (P) rats. Standard two-lever operant chambers (Coulbourn Instruments, Allentown, PA) were used to examine the effects of seven consecutive bilateral microinfusions of ICS 205-930 (ICS), a 5-HT(3) receptor antagonist, directly into the posterior VTA on the acquisition and maintenance of 15% (vol/vol) ethanol self-administration. P rats readily acquired ethanol self-administration by the fourth session. The three highest doses (0.125, 0.25, and 1.25 microg) of ICS prevented acquisition of ethanol self-administration. During the acquisition postinjection period, all rats treated with ICS demonstrated higher responding on the ethanol lever, with the highest dose producing the greatest effect. In contrast, during the maintenance phase, the three highest doses (0.75, 1.0, and 1.25 microg) of ICS significantly increased responding on the ethanol lever; after the 7-day dosing regimen, responding on the ethanol lever returned to control levels. Microinfusion of ICS into the posterior VTA did not alter the low responding on the water lever and did not alter saccharin (0.0125% wt/v) self-administration. Microinfusion of ICS into the anterior VTA did not alter ethanol self-administration. Overall, the results of this study suggest that 5-HT(3) receptors in the posterior VTA of the P rat may be involved in regulating ethanol self-administration. In addition, chronic operant ethanol self-administration and/or repeated treatments with a 5-HT(3) receptor antagonist may alter neuronal circuitry within the posterior VTA.

  7. Homeostatic regulation and Pavlovian conditioning in tolerance to amphetamine-induced anorexia.

    PubMed

    Poulos, C X; Wilkinson, D A; Cappell, H

    1981-10-01

    A series of experiments on the role of Pavlovian processes in tolerance to amphetamine-induced anorexia in rats was conducted. In Experiment 1A, tolerance to the suppressant effect of d-amphetamine (4.0 mg/kg) on milk consumption was substantially diminished in an environment not previously associated with drug administration. Experiment 1B supported the interpretation that Pavlovian compensatory conditioning rather than a nonassociative mechanism mediated this phenomenon. Experiment 2 examined the hypothesis that "contingent tolerance" results from an inadvertent manipulation of Pavlovian cues. As in previous research, tolerance was contingent in that it did not develop if the rats were not exposed to food under the influence of the drug. Tolerance developed only if access to food occurred under the influence of amphetamine, but as in Experiment 1A, it was substantially diminished in an environment not previously associated with drug administration. Thus, tolerance to amphetamine-induced anorexia was shown to be both contingent on previous experience with food in the drugged state and subject to Pavlovian control. No current explanation for the occurrence of contingent tolerance or for the control of tolerance by Pavlovian processes can at once account for both of these findings. Experiment 3 confirmed the hypothesis that interaction with the food stimulus would be necessary to extinguish tolerance. This finding is also problematic for any current behavioral theory of tolerance. It is proposed that interaction with food is necessary for the homeostatic regulation of disturbances in eating caused by amphetamine. When activated, this regulatory process operates by means of Pavlovian conditional compensatory processes.

  8. 77 FR 69768 - General Services Administration Acquisition Regulation (GSAR); Rewrite of Part 504...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-11-21

    ...); Rewrite of Part 504, Administrative Matters; Correction AGENCY: Office of Acquisition Policy, General... Administrative Matters. The final rule contained a typographical error which needs to be corrected. DATES... amendment: PART 504--ADMINISTRATIVE MATTERS 0 1. The authority citation for 48 CFR part 504 continues...

  9. Fragile X mental retardation protein regulates synaptic and behavioral plasticity to repeated cocaine administration.

    PubMed

    Smith, Laura N; Jedynak, Jakub P; Fontenot, Miles R; Hale, Carly F; Dietz, Karen C; Taniguchi, Makoto; Thomas, Feba S; Zirlin, Benjamin C; Birnbaum, Shari G; Huber, Kimberly M; Thomas, Mark J; Cowan, Christopher W

    2014-05-07

    Repeated cocaine exposure causes persistent, maladaptive alterations in brain and behavior, and hope for effective therapeutics lies in understanding these processes. We describe here an essential role for fragile X mental retardation protein (FMRP), an RNA-binding protein and regulator of dendritic protein synthesis, in cocaine conditioned place preference, behavioral sensitization, and motor stereotypy. Cocaine reward deficits in FMRP-deficient mice stem from elevated mGluR5 (or GRM5) function, similar to a subset of fragile X symptoms, and do not extend to natural reward. We find that FMRP functions in the adult nucleus accumbens (NAc), a critical addiction-related brain region, to mediate behavioral sensitization but not cocaine reward. FMRP-deficient mice also exhibit several abnormalities in NAc medium spiny neurons, including reduced presynaptic function and premature changes in dendritic morphology and glutamatergic neurotransmission following repeated cocaine treatment. Together, our findings reveal FMRP as a critical mediator of cocaine-induced behavioral and synaptic plasticity.

  10. 24 CFR 200.857 - Administrative process for scoring and ranking the physical condition of multifamily housing...

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 24 Housing and Urban Development 2 2010-04-01 2010-04-01 false Administrative process for scoring... process for scoring and ranking the physical condition of multifamily housing properties. (a) Scoring and..., standard 2 performing and standard 3 performing—in accordance with the ranking process described...

  11. 24 CFR 200.857 - Administrative process for scoring and ranking the physical condition of multifamily housing...

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 24 Housing and Urban Development 2 2014-04-01 2014-04-01 false Administrative process for scoring... process for scoring and ranking the physical condition of multifamily housing properties. (a) Scoring and..., standard 2 performing and standard 3 performing—in accordance with the ranking process described...

  12. 24 CFR 200.857 - Administrative process for scoring and ranking the physical condition of multifamily housing...

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 24 Housing and Urban Development 2 2011-04-01 2011-04-01 false Administrative process for scoring... process for scoring and ranking the physical condition of multifamily housing properties. (a) Scoring and..., standard 2 performing and standard 3 performing—in accordance with the ranking process described...

  13. 24 CFR 200.857 - Administrative process for scoring and ranking the physical condition of multifamily housing...

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 24 Housing and Urban Development 2 2013-04-01 2013-04-01 false Administrative process for scoring... process for scoring and ranking the physical condition of multifamily housing properties. (a) Scoring and..., standard 2 performing and standard 3 performing—in accordance with the ranking process described...

  14. 24 CFR 200.857 - Administrative process for scoring and ranking the physical condition of multifamily housing...

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 24 Housing and Urban Development 2 2012-04-01 2012-04-01 false Administrative process for scoring... process for scoring and ranking the physical condition of multifamily housing properties. (a) Scoring and..., standard 2 performing and standard 3 performing—in accordance with the ranking process described...

  15. Prevalence of contraindications and conditions for precaution for prasugrel administration in a real world acute coronary syndrome population.

    PubMed

    Alexopoulos, Dimitrios; Xanthopoulou, Ioanna; Mylona, Panagiota; Perperis, Angelos; Panagiotou, Aggeliki; Dimitropoulos, Gerasimos; Tsigkas, Grigorios; Hahalis, George; Davlouros, Periklis

    2011-10-01

    The prevalence of prasugrel contraindications and specific conditions requiring precaution for its use in a real world acute coronary syndrome (ACS) population is not known. We performed a prospective descriptive study in 1016 consecutive moderate to high risk ACS patients. In 646 patients (63.6%) subjected to percutaneous coronary intervention, analysis of absolute contraindications (history of stroke/transient ischemic attack or active bleeding), relative contraindications and specific conditions (age ≥ 75 years and/or weight < 60 kg) for prasugrel theoretical administration was performed. In 242 (37.5%) patients there was at least one absolute or relative contraindication or specific condition requiring attention for its use. Overall, 23.1% of patients in our cohort had a prior stroke/transient ischemic attack and/or specific condition to be considered for prasugrel administration. Specifically, the prevalence of stroke/TIA was 3.6%, the prevalence of patients ≥75 years 20% and the prevalence of patients weighing <60 kg 2.2%. Among patients ≥75 years old, 63 (9.8%) had diabetes mellitus or previous myocardial infarction, consisting a high risk subgroup that might benefit from prasugrel administration. In a real world ACS population a relatively high proportion of patients have a potential contraindication for prasugrel administration or necessitate special attention for its use.

  16. 76 FR 54928 - Export Administration Regulations: Netherlands Antilles, Curaçao, Sint Maarten and Timor-Leste

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-09-06

    ... Administration Regulations (EAR), e.g., the Commerce Country Chart, the Country Groups, and License Exception APP... Services, Bureau of Industry and Security, U.S. Department of Commerce at 202-482-2440 or by e-mail... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF...

  17. Chronic Uridine Administration Induces Fatty Liver and Pre-Diabetic Conditions in Mice

    PubMed Central

    Urasaki, Yasuyo; Pizzorno, Giuseppe; Le, Thuc T.

    2016-01-01

    Uridine is a pyrimidine nucleoside that exerts restorative functions in tissues under stress. Short-term co-administration of uridine with multiple unrelated drugs prevents drug-induced liver lipid accumulation. Uridine has the ability to modulate liver metabolism; however, the precise mechanism has not been delineated. In this study, long-term effects of uridine on liver metabolism were examined in both HepG2 cell cultures and C57BL/6J mice. We report that uridine administration was associated with O-GlcNAc modification of FOXO1, increased gluconeogenesis, reduced insulin signaling activity, and reduced expression of a liver-specific fatty acid binding protein FABP1. Long-term uridine feeding induced systemic glucose intolerance and severe liver lipid accumulation in mice. Our findings suggest that the therapeutic potentials of uridine should be designed for short-term acute administration. PMID:26789264

  18. Effects of simultaneous administration of ethanol on styrene metabolism under fed and fasted conditions in the perfused rat liver.

    PubMed

    Sripaung, N; Motohashi, Y; Nakata, K; Nakamura, K; Takano, T

    1995-08-01

    The purpose of this study was to clarify the simultaneous administration of ethanol on styrene metabolism in the perfused rat liver under fed and fasted conditions. Styrene uptake rate, production rate of styrene glycol, oxygen consumption rate, and changes in reduced pyridine nucleotide fluorescence were monitored in the perfused rat liver. The effects of ethanol on parameters of styrene metabolism were observed in rat livers under fed and fasted conditions: fed (group I), fasted (group II), and fasted with xylitol in the perfusate (group III). The simultaneous administration of ethanol and styrene significantly decreased styrene uptake rate, production rate of styrene glycol, and oxygen consumption rate, and produced significant reduction of pyridine nucleotide fluorescence as compared with the single administration of styrene in groups I and III. In contrast, the simultaneous administration of ethanol and styrene significantly increased the production of styrene glycol and oxygen consumption as compared with the single administration of styrene in group II. Significant effects on the styrene uptake rate and the reduced pyridine nucleotide fluorescence were observed with regard to factors of both nutritional status and the interaction between ethanol and nutritional status by two-way analysis of variance. These findings showed that the effects of ethanol on styrene metabolism in the liver were dependent upon the nutritional status of the animal. The fed and fasted conditions affected the effect of ethanol on styrene metabolism by changing the supply of NADPH to the mixed-function oxidase system. In conclusion, ethanol suppressed styrene metabolism in the fed condition, but enhanced it in the fasted condition. This phenomenon should be considered in the prevention of occupational hazard of styrene exposure in industrial workers with alcohol drinking habits and nutritional problems.

  19. Nurse overtime, working conditions, and the presence of mandatory nurse overtime regulations.

    PubMed

    Bae, Sung-Heui

    2012-05-01

    Although more states have regulated mandatory nurse overtime, limited research has examined the impact of these regulations on the actual time nurses work and their working conditions. The purpose of this study was to compare nurse overtime and working conditions between states with and states without regulations limiting mandatory nurse overtime. Data were collected from registered nurses working in hospitals located in states with and without mandatory nurse overtime regulations; the final sample consisted of 219 nurses. No difference was found in overtime worked between nurses who worked in states with regulations or without. Those nurses working in states with regulations cared for more patients per shift and experienced more chronic nursing shortages on their nursing units than those working in states without regulation. Continuous efforts are needed to improve the implementation of regulations to reduce nurse mandatory overtime and long work hours.

  20. 42 CFR 484.14 - Condition of participation: Organization, services, and administration.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... physician or registered nurse required under paragraph (d) of this section, organizes and directs the agency... administrator. (d) Standard: Supervising physician or registered nurse. The skilled nursing and other therapeutic services furnished are under the supervision and direction of a physician or a registered...

  1. 42 CFR 484.14 - Condition of participation: Organization, services, and administration.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... physician or registered nurse required under paragraph (d) of this section, organizes and directs the agency... administrator. (d) Standard: Supervising physician or registered nurse. The skilled nursing and other therapeutic services furnished are under the supervision and direction of a physician or a registered...

  2. 42 CFR 484.14 - Condition of participation: Organization, services, and administration.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... physician or registered nurse required under paragraph (d) of this section, organizes and directs the agency... administrator. (d) Standard: Supervising physician or registered nurse. The skilled nursing and other therapeutic services furnished are under the supervision and direction of a physician or a registered...

  3. 42 CFR 484.14 - Condition of participation: Organization, services, and administration.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... physician or registered nurse required under paragraph (d) of this section, organizes and directs the agency... administrator. (d) Standard: Supervising physician or registered nurse. The skilled nursing and other therapeutic services furnished are under the supervision and direction of a physician or a registered...

  4. Limitations on Change: Current Conditions Influencing Academic Intransigence in Educational Administration Programs.

    ERIC Educational Resources Information Center

    Logan, Connie Stokes; Pounder, Diana G.

    An analysis of academic intransigence (resistance to change) in educational administrative preparation programs is presented in this paper. Drawing upon two conceptual frameworks, the stakeholder perspective and Porter's (1980) five-force model of industry structure and competitive influence, two factors contributing to academic intransigence are…

  5. American Recovery and Reinvestment Act (ARRA) EPA Administrative Terms and Conditions

    EPA Pesticide Factsheets

    In accordance with EPA regulations,the recipient is authorized to receive advance paymentsunder this agreement,provided that the recipient takes action to minimize the time elapsingbetween the transfer of funds from EPA&the disbursement of those funds.

  6. Effect of peripheral kisspeptin administration on adiponectin, leptin, and resistin secretion under fed and fasting conditions in the adult male rhesus monkey (Macaca mulatta).

    PubMed

    Wahab, F; Bano, R; Jabeen, S; Irfan, S; Shahab, M

    2010-07-01

    In the last few years, kisspeptin-KISS1R signaling has appeared as a major regulator of the reproductive function in several vertebrate species. However, KISS1(encoding kisspeptin) and its putative receptor, KISS1R, are expressed in several other tissues. Adipose tissue, which secretes many peptides with diverse functions in normal physiology, expresses KISS1, which is modulated by gonadal steroids as well as by body nutritional status. Similarly, KISS1Rexpression is also found in adipose tissue, but the local role of kisspeptin in adipocyte function is currently unknown. Therefore, in the present study the effects of exogenous human kisspeptin-10 (KP10) were studied on three important adipokines, namely, adiponectin, leptin, and resistin in a set of four chair-restraint habituated intact adult male rhesus monkeys under; 1) normal fed conditions, 2) 24-h fasting conditions, and 3) 48-h fasting conditions. Plasma resistin and leptin levels decreased (p<0.01), whereas adiponectin levels increased (p<0.05) in fasted monkeys. Kisspeptin administration significantly increased (p<0.05) mean plasma adiponectin levels under fed and 24-h fasting conditions as compared to pretreatment or vehicle-treatment levels. A stimulatory effect was also observed on the 48-h fasting stimulated plasma adiponectin levels, but it lacked statistical significance. In contrast, no effect of kisspeptin was observed on mean plasma leptin and resistin levels. Thus, the present study demonstrated a stimulatory effect of peripheral kisspeptin administration on the plasma adiponectin levels under fed and 24-h fasting conditions in the adult male rhesus monkey. These findings, therefore, assign a novel role to kisspeptin, a regulator of adipocyte function in higher primate.

  7. Additional safeguards for children in clinical investigations of food and drug administration-regulated products. Final rule.

    PubMed

    2013-02-26

    The Food and Drug Administration (FDA) is amending its regulations to provide additional safeguards for children enrolled in clinical investigations of FDA-regulated products. This rule finalizes the interim rule published in 2001 to bring FDA regulations into compliance with provisions of the Children's Health Act of 2000 (the Children's Health Act). The Children's Health Act requires that all research involving children that is conducted, supported, or regulated by the Department of Health and Human Services (HHS) be in compliance with HHS regulations providing additional protections for children involved as subjects in research. FDA is taking this action both to comply with the congressional mandate and because of increases in the enrollment of children in clinical investigations as a result of ongoing pediatric initiatives.

  8. 5-HT7 receptor-mediated fear conditioning and possible involvement of extracellular signal-regulated kinase.

    PubMed

    Takeda, Kotaro; Tsuji, Minoru; Miyagawa, Kazuya; Takeda, Hiroshi

    2017-01-18

    Fear conditioning is a valuable behavioral paradigm for studying the neural basis of emotional learning and memory. The present study examined the involvement of extracellular signal-regulated kinase 1/2 (ERK) signaling on the serotonin (5-HT)7 receptor-mediated fear conditioning. Conditioning was performed in a trial in which a tone was followed by an electrical foot-shock. Context- and tone-dependent fear were examined in tests conducted 24 and 48h after conditioning, respectively. The selective 5-HT7 receptor antagonist 2a-[4-(4-phenyl-1,2,3,6-tetrahydropyridyl)butyl]-2a,3,4,-tetrahydrobenzo(c,d)indol-2-(1H)-one (DR4004) (5mg/kg), when administered intraperitoneally (i.p.) immediately after conditioning, caused a significant decrease in both context- and tone-dependent fear responses (freezing behavior). A significant increase in ERK activity was observed in the amygdala of mice that displayed context- or tone-dependent fear responses, and these changes were also inhibited by the administration of DR4004 (5mg/kg, i.p.) immediately after conditioning. In contrast, the increase in hippocampal ERK activity in mice that displayed context-dependent fear responses was further enhanced by the administration of DR4004 (5mg/kg, i.p.). These results suggest that 5-HT7 receptor-mediated ERK signaling may play a significant role in the processes of emotional learning and memory.

  9. Ketamine administration diminishes operant responding but does not impair conditioned fear.

    PubMed

    Groeber Travis, Caitlin M; Altman, Daniel E; Genovese, Raymond F

    2015-12-01

    While not well understood, the NMDA (N-methyl-D-aspartate) antagonist ketamine, a dissociative anesthetic, has been reported to be efficacious in depression and related psychological disorders. Conditioned fear is a normal emotional conditioning process that is known to become dysfunctional in individuals suffering from Post-Traumatic Stress Disorder (PTSD) and related stress disorders. We examined the effects of ketamine to determine the potential modulation of the acquisition and extinction of a conditioned fear using a conditioned suppression procedure. Rats were trained on a variable interval (VI), food maintained, operant conditioning task to establish a general measure of performance. Rats were exposed to inescapable shock (IES, unconditioned stimulus) paired (×20) with an audio/visual conditioned stimulus (CS) to establish conditioning. Conditioning was quantified by measuring response suppression following CS presentation during subsequent extinction trials where the CS alone was presented. Ketamine or vehicle was administered either after initial conditioning or after each of the subsequent extinction trials. For each regimen, a series of four injections were administered 60 min apart (100, 50, 50, 50 mg/kg, respectively) in order to sustain a ketamine effect for a minimum of 4 h. Ketamine produced a general decrease in responding on the VI, relative to baseline, as response rates were slower on the operant task when tested 24 h later and longer. Ketamine did not affect the acquisition of the conditioned fear when the regimen was administered shortly after the initial pairings of IES and CS. Ketamine did not alter extinction to the conditioned fear when the regimen was administered following each CS only presentation following initial conditioning. Our conclusion from these findings is that while ketamine alters behavior on an appetitively motivated operant task it does not, however, appear to directly modulate learning and memory processes associated

  10. 21 CFR Appendix A to Subpart A of... - List of Applicable Laws, Regulations, and Administrative Provisions

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... Administrative Provisions A Appendix A to Subpart A of Part 26 Food and Drugs FOOD AND DRUG ADMINISTRATION... Good Manufacturing Practices Pt. 26, Subpt. A, App. A Appendix A to Subpart A of Part 26—List of... and veterinary use and establishing a European Agency for the Evaluation of Medicinal...

  11. 21 CFR Appendix A to Subpart A of... - List of Applicable Laws, Regulations, and Administrative Provisions

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... Administrative Provisions A Appendix A to Subpart A of Part 26 Food and Drugs FOOD AND DRUG ADMINISTRATION... Good Manufacturing Practices Pt. 26, Subpt. A, App. A Appendix A to Subpart A of Part 26—List of... and veterinary use and establishing a European Agency for the Evaluation of Medicinal...

  12. 21 CFR Appendix A to Subpart A of... - List of Applicable Laws, Regulations, and Administrative Provisions

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... Administrative Provisions A Appendix A to Subpart A of Part 26 Food and Drugs FOOD AND DRUG ADMINISTRATION... Good Manufacturing Practices Pt. 26, Subpt. A, App. A Appendix A to Subpart A of Part 26—List of... and veterinary use and establishing a European Agency for the Evaluation of Medicinal...

  13. 21 CFR Appendix A to Subpart A of... - List of Applicable Laws, Regulations, and Administrative Provisions

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... Administrative Provisions A Appendix A to Subpart A of Part 26 Food and Drugs FOOD AND DRUG ADMINISTRATION... Good Manufacturing Practices Pt. 26, Subpt. A, App. A Appendix A to Subpart A of Part 26—List of... and veterinary use and establishing a European Agency for the Evaluation of Medicinal...

  14. 21 CFR Appendix A to Subpart A of... - List of Applicable Laws, Regulations, and Administrative Provisions

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... Administrative Provisions A Appendix A to Subpart A of Part 26 Food and Drugs FOOD AND DRUG ADMINISTRATION... Good Manufacturing Practices Pt. 26, Subpt. A, App. A Appendix A to Subpart A of Part 26—List of... and veterinary use and establishing a European Agency for the Evaluation of Medicinal...

  15. 76 FR 78010 - General Services Administration Acquisition Regulation; Information Collection; Contract...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-15

    ... Administration, Quality Assurance (GSAR Parts 542 and 546; GSA Form 1678 and GSA Form 308) AGENCY: Office of the... quality assurance. Public comments are particularly invited on: Whether this collection of information is... comments identified by Information Collection 3090- 0027, Contract Administration and Quality...

  16. 77 FR 18818 - General Services Administration Acquisition Regulation; Submission for OMB Review; Contract...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-03-28

    ... Administration, Quality Assurance (GSAR Parts 542 and 546; GSA Form 1678 and GSA Form 308) AGENCY: Office of the... quality assurance. A notice was published in the Federal Register at 76 FR 78010, on December 15, 2011. No... ``Information Collection 3090-0027, Contract Administration and Quality Assurance (GSAM Part 542 and Part...

  17. 39 CFR 233.9 - Regulations governing remission or mitigation of administrative, civil, and criminal forfeitures.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... administrative, civil, and criminal forfeitures. 233.9 Section 233.9 Postal Service UNITED STATES POSTAL SERVICE... mitigation of administrative, civil, and criminal forfeitures. (a) Purpose, authority, and scope—(1) Purpose... under the supervision of the Chief Counsel. (3) Scope. This section governs any petition for...

  18. p300/CBP-associated factor selectively regulates the extinction of conditioned fear

    PubMed Central

    Wei, Wei; Coelho, Carlos M.; Li, Xiang; Marek, Roger; Yan, Shanzhi; Anderson, Shawn; Meyers, David; Mukherjee, Chandrani; Sbardella, Gianluca; Castellano, Sabrina; Milite, Ciro; Rotili, Dante; Mai, Antonello; Cole, Philip A.; Sah, Pankaj; Kobor, Michael S.; Bredy, Timothy W.

    2012-01-01

    It is well established that the activity of chromatin-modifying enzymes is crucial for regulating gene expression associated with hippocampal-dependent memories. However, very little is known about how these epigenetic mechanisms influence the formation of cortically-dependent memory, particularly when there is competition between opposing memory traces such as that which occurs during the acquisition and extinction of conditioned fear. Here we demonstrate, in C57/Bl6 mice, that the activity of p300/CBP-associated factor (PCAF) within the infralimbic prefrontal cortex is required for long-term potentiation and is necessary for the formation of memory associated with fear extinction, but not for fear acquisition. Further, systemic administration of the PCAF activator SPV106 enhances memory for fear extinction and prevents fear renewal. The selective influence of PCAF on fear extinction is mediated, in part, by a transient recruitment of the repressive transcription factor ATF4 to the promoter of the immediate early gene zif268, which competitively inhibits its expression. Thus, within the context of fear extinction, PCAF functions as a transcriptional co-activator, which may facilitate the formation of memory for fear extinction by interfering with reconsolidation of the original memory trace. PMID:22933779

  19. The relation between cerebral serotonin levels and conditioned behaviour in the rat following the administration of LSD-25 and UML.

    PubMed

    Torre, M; Torre, E; Bogetto, F

    1975-01-01

    Successive daily injections of LSD-25 and UML (1-methyl-d-lysergic acid butanolamide) caused progressive depression of brain 5-HT levels in the rat. On the fourth day, the decrease was significant with respect to the highly significant fall observed after a single administration, whereas it had been shown earlier that conditioned behaviour is no longer affected by LSD-25 after 3 days and that simultaneous administration of a single dose of LSD-25 and UML is equally ineffective in this respect. Its depression of 5-HT levels, however, has now been shown to be equal to that of LSD-25 alone at doses that influence conditioned behaviour. The findings indicate that changes in such behaviour are not dependent on brain 5-HT levels and that no link exists between such levels and the psychotomimetic effect of LSD-25 in man.

  20. To Set Up Norms for Drug Safety and Inspection: To Guarantee Administrative Sufficiency and Avoid Regulators from Being Wrongly Punished.

    PubMed

    Xuan, Qingsheng; Dong, Zuojun; Shao, Mingli

    2015-09-01

    Currently, as there is no systematic norm or standard for drug safety and inspection, it cannot be judged whether the regulatory authority or regulators have fulfilled their administrative responsibilities entirely or not, when a drug safety-related incident occurs. And there is a probability that some may even be wrongly punished. In this study, we have analyzed the risk of not having appropriate norms in place and also put forward recommendations for the government or the regulatory authorities to set up norms to be fulfilled for drug safety and inspection issues. This, on one hand, could provide a basic guideline for the regulatory authorities and regulators to improve their professional levels and administrative acumen and on the other hand, it could also provide a baseline for society to judge whether the regulatory authorities and regulators have fulfilled their responsibilities correctly and thereby also help prevent regulators from being mistakenly punished. This study proposes that a systematic and functional norm for drug safety and inspection could be set up relating to the determination of the responsibilities of regulatory authorities and scope of various inspections, number and frequency of inspections, number and qualifications of regulators, handling of inspection results, inspection records, and disciplinary codes for inspectors. This study also puts forward suggestions on who should be responsible for drafting the norms and what are the factors that need to be considered while formulating the norms.

  1. Impact of implementing an Internal Bed Regulation Committee on administrative and care indicators at a teaching hospital

    PubMed Central

    Rodrigues, Luciane Cristine Ribeiro; Juliani, Carmen Maria Casquel Monti

    2015-01-01

    Objective To compare hospital indicators before and after implementing an Internal Bed Regulation Committee at a reference hospital. Methods It is an quantitative, evaluation, exploratory, descriptive and cross-sectional research. The data was gathered from the hospital administrative reports for the period 2008-2013, provided by the Information Technology Center of the Complexo FAMEMA. Results The indicators improved after implementation of the Internal Bed Regulation Committee. Conclusion The individuals involved in the process acknowledged the improvement. It is necessary to carry on the regulatory actions, especially in a comprehensive and complex healthcare system, such as the brazilian Sistema Único de Saúde. PMID:25993075

  2. Implicit conditioning of faces via the social regulation of emotion: ERP evidence of early attentional biases for security conditioned faces.

    PubMed

    Beckes, Lane; Coan, James A; Morris, James P

    2013-08-01

    Not much is known about the neural and psychological processes that promote the initial conditions necessary for positive social bonding. This study explores one method of conditioned bonding utilizing dynamics related to the social regulation of emotion and attachment theory. This form of conditioning involves repeated presentations of negative stimuli followed by images of warm, smiling faces. L. Beckes, J. Simpson, and A. Erickson (2010) found that this conditioning procedure results in positive associations with the faces measured via a lexical decision task, suggesting they are perceived as comforting. This study found that the P1 ERP was similarly modified by this conditioning procedure and the P1 amplitude predicted lexical decision times to insecure words primed by the faces. The findings have implications for understanding how the brain detects supportive people, the flexibility and modifiability of early ERP components, and social bonding more broadly.

  3. Early methylphenidate exposure enhances cocaine self-administration but not cocaine-induced conditioned place preference in young adult rats

    PubMed Central

    Crawford, Cynthia A.; Baella, Shelley A.; Farley, Cristal M.; Herbert, Matthew S.; Horn, Leslie R.; Campbell, Rachel H.; Zavala, Arturo R.

    2010-01-01

    Rationale Previous studies in rodents show that early exposure to methylphenidate alters later responsiveness to drugs of abuse. An interesting feature of these studies is that early methylphenidate treatment decreases the rewarding value of cocaine when measured by conditioned place preference (CPP), but the same treatment increases cocaine self-administration. Objective The goal of the present study was to examine the effects of early methylphenidate exposure on cocaine-induced responding using both reward paradigms. Methods Rats were treated with methylphenidate (0, 2, or 5 mg/kg) from postnatal day (PD) 11 to PD 20 and then cocaine-induced CPP or cocaine self-administration was measured in separate groups of rats in adulthood. The CPP procedure included eight days of acquisition training, eight days of extinction training, and a reinstatement test. Rats were conditioned with 0, 10 or 20 mg/kg cocaine. Reinstatement was assessed after a priming dose of cocaine (10 mg/kg). For the self-administration experiment, a jugular catheter was implanted and rats were trained to press a lever reinforced with cocaine (0.25 or 0.75 mg/kg/infusion) on a fixed ratio (FR) 1 schedule. Rats were gradually moved from an FR1 to an FR10 schedule and, after criterion was reached, rats were placed on a progressive ratio schedule for five days. Results Cocaine produced robust rewarding effects as determined by both the CPP and self-administration experiments; however, early methylphenidate exposure only enhanced the reinforcing effects of cocaine on the self-administration paradigm. Interestingly, this methylphenidate enhancement was only seen in male rats. Conclusions These data suggest that in males methylphenidate enhances the reinforcing value of cocaine, but not cocaine-associated cues. PMID:20848087

  4. Timing of SCH 23390 administration influences extinction of conditioned hyperactivity in mice.

    PubMed

    Rauhut, Anthony S

    2016-02-01

    The precise role of the dopamine subtype-1 (D1) receptor in differentially mediating extinction-related processes (memory retrieval vs. memory reconsolidation) in the conditioned hyperactivity paradigm is unknown. Thus, the present experiments determined the effect of a selective D1 receptor antagonist, SCH 23390, on extinction of conditioned hyperactivity when SCH 23390 was administered immediately after (memory reconsolidation; experiment 1) or before (memory retrieval; experiment 2) extinction sessions. Male, Swiss-Webster mice received subcutaneous injections of methamphetamine (1.0 mg/kg) associated with locomotor activity chambers (paired) or in their home cages (unpaired) during the acquisition phase. Following acquisition, paired and unpaired mice received an intraperitoneal injection of either vehicle (physiological saline) or SCH 23390 (0.0125, 0.025, 0.05 mg/kg) immediately after (experiment 1) or received vehicle or SCH 23390 (0.05 mg/kg) 30 min before (experiment 2), daily extinction sessions. Methamphetamine produced robust conditioned hyperactivity, followed by extinction. Furthermore, SCH 23390 (0.05 mg/kg) blocked expression of conditioned hyperactivity, without nonspecifically impairing locomotor activity, when administered before the extinction session, but did not alter the rate of extinction when administered immediately following the sessions. Taken together, these results suggest that the D1 receptor is involved in memory retrieval, but not memory reconsolidation, processes during extinction of conditioned hyperactivity.

  5. Effects of intragastric L-arginine administration on proximal stomach tone under basal conditions and after an intragastric diet.

    PubMed

    Savoye, Guillaume; Jemaa, Yassine; Mosni, Grégory; Savoye-Collet, Céline; Morcamp, Paola; Déchelotte, Pierre; Bouin, Mickael; Denis, Philippe; Ducrotté, Philippe

    2006-12-01

    Nitric oxide (NO) plays an important role as a nonadrenergic, noncholinergic inhibitory neurotransmitter in the GI tract. Our study aims were to investigate the effect of a single intragastric L-arginine (L-Arg) administration, as a source of NO, on proximal stomach tone in basal and postintragastric administration of a polymeric diet in humans and to evaluate concomitantly the effect on antral area as an indirect assessment of gastric emptying. Eight healthy volunteers were studied in a randomized double-blind crossover study after, respectively, 15 g L-Arg, 30 g L-Arg, or placebo administered in the stomach through a gastric tube. The drug administration was followed by a polymeric diet infusion (500 ml/500 kcal) at a rate of 250 ml/hr. Gastric tone variations were recorded with an electronic barostat, gastric emptying was concomitantly estimated by repeated ultrasound measurements of antral area, and symptoms were recorded throughout the experiment.L-Arg administration was associated with significantly higher increases in barostat bag volumes at both dosages, 30 g (117+/-16 ml) and 15 g (67+/-15 ml), compared to placebo (46+/-11 ml; P < 0.05). In response to the polymeric diet the 30-g L-Arg challenge was associated with a smaller increase in intrabag volume, whereas postinfusion final volumes did not differ in the three treatment conditions. Antral areas were not different at any time of measurement among the three challenges. Bloating and diarrhea were observed after 30-g L-Arg administration in five subjects of eight. Short-term L-Arg administration was able to induce proximal stomach relaxation that allowed a secondary response to enteral feeding only at the 15-g dosage. This 15-g dosage was as well tolerated as the placebo and was associated with no significant changes in gastric emptying patterns.

  6. Previous Employment and Job Satisfaction Conditions: The Case of Regional Administration

    NASA Astrophysics Data System (ADS)

    Amalia, Myronaki; Nikolaos, Antonakas

    2009-08-01

    In the present work we study the different dimensions of satisfaction and the way of constitution of satisfaction of an important sample of the employees in the Regional administration of Crete and in their connection with the variable of the previous employment. We found statistically important differences for the components of satisfaction from the life, collaboration in and outside from the department, in the social satisfaction and the variable of the years in the service (labour group with <5 years in the service, group with 5-9 years in the service and labour group with 10-15 years in the service). The group with total few years in the work <5, presented smaller social and labour satisfaction than the other previous employment groups. In the other hand the group with many years in the service presents bigger satisfaction than the other groups. Finally, is important to note that the sample present some interesting characteristics.

  7. Comparison study of judged clinical skills competence from standard setting ratings generated under different administration conditions.

    PubMed

    Roberts, William L; Boulet, John; Sandella, Jeanne

    2017-02-21

    When the safety of the public is at stake, it is particularly relevant for licensing and credentialing exam agencies to use defensible standard setting methods to categorize candidates into competence categories (e.g., pass/fail). The aim of this study was to gather evidence to support change to the Comprehensive Osteopathic Medical Licensing-USA Level 2-Performance Evaluation standard setting design and administrative process. Twenty-two video recordings of candidates assessed for clinical competence were randomly selected from the 2014-2015 Humanistic domain test score distribution ranging from the highest to lowest quintile of performance. Nineteen panelists convened at the same site to receive training and practice prior to generating judgments of qualified or not qualified performance to each of the twenty videos. At the end of training, one panel remained onsite to complete their judgments and the second panel was released and given 1 week to observe the same twenty videos and complete their judgments offsite. The two one-sided test procedure established equivalence between panel group means at the 0.05 confidence level, controlling for rater errors within each panel group. From a practical cost-effective and administrative resource perspective, results from this study suggest it is possible to diverge from typical panel groups, who are sequestered the entire time onsite, to larger numbers of panelists who can make their judgments offsite with little impact on judged samples of qualified performance. Standard setting designs having panelists train together and then allowing those to provide judgments yields equivalent ratings and, ultimately, similar cut scores.

  8. 76 FR 8892 - Removal of Expired Federal Aviation Administration Regulations and References

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-02-16

    ... and are not currently in effect. This technical amendment is necessary to update our regulations. The... passed. To maintain an accurate body of regulations, we are removing and/or amending SFAR Nos. 36, 80, 92... recordkeeping requirements. 14 CFR Part 61 Aircraft, Airmen, Alcohol abuse, Aviation safety, Drug...

  9. Conditioning Factors in the Relationship between Stress and Opioid Self-Administration in Rats

    DTIC Science & Technology

    1992-08-03

    correlation between swim -stress induced antinociception and [3Hlleu-enkephalin binding to brain homogenates in mice . Pharmacology Biochemistry and Beha vior...APPROVAL SHEET GRAOIJA TE EDUCATION TEACHING HOSPITALS WALTER REED ARMY MEDICAL CENTER NAVAL HOSPITAL. BETHESDA MALCOLM GROW AIR FORCE MEDICAL...CENTER WILFORD HALL AIR FORCE MEDICAL CENTER Title of Dissertation: "Conditioning Factors in the Relationship between Stress and Opioid Self

  10. Context-Dependent Effects of a Single Administration of Mirtazapine on the Expression of Methamphetamine-Induced Conditioned Place Preference

    PubMed Central

    Voigt, Robin M.; Napier, T. Celeste

    2012-01-01

    Re-exposure to cues repeatedly associated with methamphetamine (Meth) can trigger Meth-seeking and relapse in the abstinent abuser. Weakening the conditioned Meth-associated memory during cue re-exposure may provide a means for relapse-reduction pharmacotherapy. Accordingly, we sought to determine if the atypical antidepressant mirtazapine disrupted the persistence of Meth-induced conditioned place preference (CPP) when administered in conjunction with re-exposure to contextual conditioning cues, and if this effect was altered by Meth being present during cue re-exposure. First, we evaluated the effect of mirtazapine on the maintenance of Meth-induced CPP during re-exposure to either the saline- or Meth-paired chamber 12 days after conditioning. Meth-conditioned rats subsequently administered mirtazapine expressed CPP independent of re-exposure to the saline- or Meth-paired chamber; but the magnitude of CPP was significantly less for mirtazapine-treated rats re-exposed to the Meth-paired chamber. Next, we evaluated the effect of mirtazapine on a “reinforced re-exposure” to the Meth-paired context. Administration of mirtazapine vehicle and Meth, prior to re-exposure to the Meth-paired chamber did not disrupt the ability of rats to demonstrate CPP 15 days after conditioning; however, CPP was disrupted when rats were administered mirtazapine and Meth prior to re-exposure to the Meth-paired chamber. These results indicate that the capacity of mirtazapine to diminish Meth-induced CPP is promoted if mirtazapine treatment is coupled with Meth administration in the Meth-associated context and thus appears to be the consequence of disrupting processes necessary to reconsolidate CPP following activation of drug-associated memories. PMID:22347852

  11. The institutionalization of pharmaceutical administration after the korean liberation: focusing on regulating the pharmaceutical affairs law(yaksabeop) in 1953.

    PubMed

    Sihn, Kyu-Hwan

    2013-12-01

    The pharmaceutical administration under U.S Military Government in Korea and government of the Republic of Korea aimed at cleaning up the vestiges of Japanese imperialism which the pharmaceutical administration attached police administration and preparing with legal and systemic basis after the Korean liberation. The pharmaceutical bureau under U.S Military Government in Korea was reorganized as the independent division. The pharmaceutical bureau focused on preserving order, narcotics control and the distribution of relief drug. U.S Military Government proceeded supply side pharmaceutical policy for the distribution of relief drug without constructing human and material infrastructure. After the Korean War, Korean society asked the construction of system for nation building. Korean national assembly regulated National Medical Law(Gukmin uiryobeop) for promotion of public health in 1951. The Pharmaceutical Affairs Law(Yaksabeop) was regulated in 1953, and it prescribed the job requirement of pharmacist, apothecary, and drug maker and seller, and presented the frame of managing medical supplies. The Pharmaceutical Law originally planned the ideal pharmaceutical administration, but it rather secured the status of traditional apothecary, and drug maker and seller. On the contrary, though the Pharmaceutical Law guaranteed the traditional druggists, it did not materialize reproduction system such as educational and license system. It means that the traditional druggists would be degenerated in the near future. After the armistice agreement in 1953, Korean was in medical difficulties. Korean government was suffered from the deficiency of medical resources. Because of destruction of pharmaceutical facilities, Korean had to depend on United States and international aid. The Pharmaceutical Affairs Law did not cleaned up the vestiges of Japanese imperialism, and compromised with reality lacked human and material infrastructure. As a result, the law became the origin of

  12. 77 FR 58380 - General Services Administration Acquisition Regulation; Submission for OMB Review; Price...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-09-20

    ... Reductions Clause AGENCY: Office of Acquisition Policy, General Services Administration (GSA). ACTION: Notice... collection requirement regarding the GSAR Price Reductions Clause. A notice was published in the Federal... identified by Information Collection 3090- 0235, Price Reduction Clause, by any of the following...

  13. 77 FR 8886 - Food and Drug Administration Clinical Trial Requirements, Regulations, Compliance, and Good...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-02-15

    ... of public workshop. SUMMARY: The Food and Drug Administration (FDA) Detroit District Office, in co... District Office, 300 River Pl., Suite 5900, Detroit, MI 48207, 313-393-8143, Fax: 313- 393-8139, email... 13.3 Continuing Education Credits for SoCRA CE and Nurse CNE. SoCRA designates this live activity...

  14. 76 FR 78933 - Food and Drug Administration Clinical Trial Requirements, Regulations, Compliance, and Good...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-20

    .... ACTION: Notice of public workshop. The Food and Drug Administration (FDA), Los Angeles District Office... continuing nurse education (CNE). SOCRA designates this educational activity for a maximum of 13.3 American.... SoCRA is an approved provider of CNE by the Pennsylvania State Nurses Association (PSNA),...

  15. 76 FR 51040 - Food and Drug Administration Clinical Trial Requirements, Regulations, Compliance, and Good...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-08-17

    .... ACTION: Notice of public workshop. The Food and Drug Administration (FDA) Philadelphia District Office..., Philadelphia District, 900 U.S. Customhouse, Second & Chestnut Streets, Philadelphia, PA 19106, 215-597-4390... Continuing Education Credits for SoCRA CE and Nurse CNE. SOCRA designates this live activity for a maximum...

  16. 76 FR 17138 - Food and Drug Administration Clinical Trial Requirements, Regulations, Compliance, and Good...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-03-28

    .... ACTION: Notice of public workshop. The Food and Drug Administration (FDA) Denver District Office, in co... activity for a maximum of 13.3 Continuing Education (CE) Credits for SoCRA CE and Nurse CNE. SoCRA... nursing education by the Pennsylvania State Nurses Association (PSNA), an accredited approver by...

  17. Extinction Training Regulates Neuroadaptive Responses to Withdrawal from Chronic Cocaine Self-Administration

    ERIC Educational Resources Information Center

    Smagula, Cynthia S.; Self, David W.; Choi, Kwang-Ho; Simmons, Diana; Walker, John R.

    2004-01-01

    Cocaine produces multiple neuroadaptations with chronic repeated use. Many of these neuroadaptations can be reversed or normalized by extinction training during withdrawal from chronic cocaine self-administration in rats. This article reviews our past and present studies on extinction-induced modulation of the neuroadaptive response to chronic…

  18. 76 FR 30842 - General Services Administration Acquisition Regulation; Rewrite of Part 570; Acquiring Leasehold...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-05-27

    ... reference the size standard established by the Small Business Administration. Further revisions were made to include where the size standards may be found on the web. The definition of ``rent and related services...; 52.203-14, Display of Hotline Poster(s). GSAR 570.602 and 570.603 are renumbered as 570.702 and...

  19. A Developmental Psychopathology Perspective on ADHD and Comorbid Conditions: The Role of Emotion Regulation.

    PubMed

    Steinberg, Elizabeth A; Drabick, Deborah A G

    2015-12-01

    Research investigating attention-deficit/hyperactivity disorder (ADHD) and co-occurring disorders such as oppositional defiant disorder, conduct disorder, anxiety, and depression has surged in popularity; however, the developmental relations between ADHD and these comorbid conditions remain poorly understood. The current paper uses a developmental psychopathology perspective to examine conditions commonly comorbid with ADHD during late childhood through adolescence. First, we present evidence for ADHD and comorbid disorders. Next, we discuss emotion regulation and its associations with ADHD. The role of parenting behaviors in the development and maintenance of emotion regulation difficulties and comorbid disorders among children with ADHD is explored. An illustrative example of emotion regulation and parenting over the course of development is provided to demonstrate bidirectional relations among these constructs. We then present an integrated conceptual model of emotion regulation as a shared risk process that may lead to different comorbid conditions among children with ADHD. Implications and directions for future research are presented.

  20. 78 FR 31879 - General Services Administration Acquisition Regulation (GSAR); Electronic Contracting Initiative...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-05-28

    ... From the Federal Register Online via the Government Publishing Office GENERAL SERVICES... Regulation (GSAR); Electronic Contracting Initiative (ECI) AGENCY: Office of Acquisition Policy, General... (Federal Supply Schedule) clause, and an Alternate I version of the clause that will require...

  1. 77 FR 25481 - General Services Administration Acquisition Regulation; Submission for OMB Review; Solicitation...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-04-30

    ... without change to http://www.regulations.gov , including any personal and/or business confidential... measure success in meeting program objectives. As such, GSAR 516.506, Solicitation provision and...

  2. 77 FR 5020 - General Services Administration Acquisition Regulation; Information Collection; GSA Form 527...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-02-01

    ... to http://www.regulations.gov , including any personal and/or business confidential information..., Contractor's Qualifications and Financial Information AGENCY: Office of the Chief Finance Officer, GSA... Financial Information. Public comments are particularly invited on: Whether this collection of...

  3. 42 CFR 494.20 - Condition: Compliance with Federal, State, and local laws and regulations.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 42 Public Health 5 2013-10-01 2013-10-01 false Condition: Compliance with Federal, State, and local laws and regulations. 494.20 Section 494.20 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) STANDARDS AND CERTIFICATION CONDITIONS FOR COVERAGE...

  4. 42 CFR 494.20 - Condition: Compliance with Federal, State, and local laws and regulations.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 42 Public Health 5 2014-10-01 2014-10-01 false Condition: Compliance with Federal, State, and local laws and regulations. 494.20 Section 494.20 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) STANDARDS AND CERTIFICATION CONDITIONS FOR COVERAGE...

  5. 17 CFR 230.508 - Insignificant deviations from a term, condition or requirement of Regulation D.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 17 Commodity and Securities Exchanges 2 2013-04-01 2013-04-01 false Insignificant deviations from a term, condition or requirement of Regulation D. 230.508 Section 230.508 Commodity and Securities... Securities Act of 1933 § 230.508 Insignificant deviations from a term, condition or requirement of...

  6. Administration of the Glial Condition Medium in the Nucleus Accumbens Prolong Maintenance and Intensify Reinstatement of Morphine-Seeking Behavior.

    PubMed

    Arezoomandan, Reza; Khodagholi, Fariba; Haghparast, Abbas

    2016-04-01

    Accumulating evidence suggested that glial cells are involved in synaptic plasticity and behavioral changes induced by drugs abuse. The role of these cells in maintenance and reinstatement of morphine (MRP) conditioned place preference (CPP) remains poorly characterized. The aim of present study was to investigate the direct role of glial cells in nucleus accumbens (NAc) in the maintenance and reinstatement of MRP-seeking behavior. CPP induced with injection of MRP (5 mg/kg, s.c. for 3 days), lasted for 7 days after cessation of MRP treatment and priming dose of MRP (1 mg/kg, s.c.) reinstated the extinguished MRP-induced CPP. The astrocyte-conditioned medium (ACM) and neuroglia conditioned medium (NCM) exposed to MRP (10 and 100 µM) have been microinjected into the NAc. Intra-NAc administration of ACM during extinction period failed to change the maintenance of MRP-CPP, but MRP 100-treated ACM could slightly increase the magnitude of reinstatement. In contrast to ACM, intra-NAc administration of MRP 100-treated NCM caused slower extinction by 3 days and significantly increased the magnitude of reinstatement. Our findings suggest the involvement of glial cells activation in the maintenance and reinstatement of MRP-seeking behaviors, and provides new evidence that these cells might be a potential target for the treatment of MRP addiction.

  7. 77 FR 37523 - Proposed Revisions to the Export Administration Regulations: Implementation of Export Control...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-06-21

    ...President Obama directed the Administration in August 2009 to conduct a broad-based review of the U.S. export control system in order to identify additional ways to enhance national security. Then- Secretary of Defense Gates described in April 2010 the initial results of that effort and why fundamental reform of the U.S. export control system is necessary to enhance national security. Since......

  8. Ghrelin levels are not regulated by recombinant leptin administration and/or three days of fasting in healthy subjects.

    PubMed

    Chan, Jean L; Bullen, John; Lee, Jennifer H; Yiannakouris, Nikos; Mantzoros, Christos S

    2004-01-01

    Ghrelin, a stomach-derived orexigenic peptide, and leptin, a fat-derived anorexigenic hormone, act primarily in the hypothalamus to regulate energy homeostasis and have been reported to be regulated in opposite directions by acute and chronic changes in nutritional state. Nutritional, anthropometric, and hormonal predictors of circulating ghrelin have not yet been fully elucidated, and whether ghrelin is regulated by leptin in humans remains unknown. To address these questions, we performed cross-sectional and interventional studies. In 120 healthy men and women, ghrelin was negatively associated with leptin as well as overall and central adiposity, but not with total energy or specific macronutrient intake. The sexual dimorphism in ghrelin levels (higher levels in women than in men) and the negative correlation between ghrelin and insulin are largely mediated by central adiposity. In six lean men, complete fasting for 3 d resulted in a low leptin state without a major change in fat mass and abolished the meal-related secretory pattern of ghrelin without increasing 24-h ghrelin levels. In addition, recombinant human leptin administration in physiological and pharmacological doses did not regulate ghrelin over several hours to a few days. These data do not support a role for regulation of circulating ghrelin by leptin levels independently of changes in adiposity and suggest that the leptin and ghrelin systems for energy homeostasis function independently of each other in healthy humans.

  9. Effects of single cortisol administrations on human affect reviewed: Coping with stress through adaptive regulation of automatic cognitive processing.

    PubMed

    Putman, Peter; Roelofs, Karin

    2011-05-01

    The human stress hormone cortisol may facilitate effective coping after psychological stress. In apparent agreement, administration of cortisol has been demonstrated to reduce fear in response to stressors. For anxious patients with phobias or posttraumatic stress disorder this has been ascribed to hypothetical inhibition of retrieval of traumatic memories. However, such stress-protective effects may also work via adaptive regulation of early cognitive processing of threatening information from the environment. This paper selectively reviews the available literature on effects of single cortisol administrations on affect and early cognitive processing of affectively significant information. The concluded working hypothesis is that immediate effects of high concentration of cortisol may facilitate stress-coping via inhibition of automatic processing of goal-irrelevant threatening information and through increased automatic approach-avoidance responses in early emotional processing. Limitations in the existing literature and suggestions for future directions are briefly discussed.

  10. 77 FR 71099 - Federal Housing Administration (FHA): Temporary Waiver of FHA's Regulation on Property Flipping...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-11-29

    ...-8000; telephone number 202-708-2121 (this is not a toll-free number). Persons with hearing or speech impairments may access this number through TTY by calling the toll-free Federal Relay Service at 800-877-8339.... Additionally, the waiver is subject to certain conditions, and mortgages must meet these conditions to...

  11. 75 FR 28632 - Federal Housing Administration (FHA)-Temporary Exemption From Compliance With FHA's Regulation on...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-05-21

    ...-3055 (this is not a toll-free number). Individuals with speech or hearing ] impairments may access this...; telephone number 202-708-2121 (this is not a toll-free number). Persons with hearing or speech impairments... properties. The waiver, however, has conditions, and eligible mortgages must meet the conditions specified...

  12. Enhancement of conditioned place preference response to cocaine in rats following subchronic administration of 3, 4-methylenedioxymethamphetamine (MDMA).

    PubMed

    Horan, B; Gardner, E L; Ashby, C R

    2000-02-01

    In this study, we measured conditioned place preference (CPP) responses to cocaine following subchronic administration of the recreationally abused drug (+/-)-3,4-methylenedioxymethamphetamine (MDMA, "ecstasy") in male Sprague-Dawley rats. Animals were given either vehicle (1 ml/kg of distilled water, s.c.) or MDMA (20 mg/kg, s.c.) twice a day for 4 consecutive days. Two weeks later, CPP responses to cocaine (5, 10, or 20 mg/kg, i.p.) were measured. The MDMA-treated animals showed a significantly greater CPP response to cocaine than the vehicle-treated animals. Since conditioned place preference is believed to be a measure of appetitive behavior, these results suggest that MDMA abuse could lead to an increased vulnerability to the rewarding actions of cocaine and, hence, to increased vulnerability to cocaine addiction and dependence.

  13. 77 FR 10665 - General Services Administration Acquisition Regulation; Acquisition-Related Thresholds

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-02-23

    ... Acquisition Regulation (GSAR) to update the acquisition- related thresholds in two GSAR clauses. DATES...-related thresholds, the GSAR clause at 552.219-71, Notice to Offerors of Subcontracting Plan Requirements...'' and ``$1,500,000'', respectively. The GSAR clause at 552.219-72, Preparation, Submission,...

  14. Administrative Action to End Discrimination Based on Handicap: HEW's Section 504 Regulation.

    ERIC Educational Resources Information Center

    Engebretson, Mark F.

    1979-01-01

    Examines the drafting of regulations under Section 504 of the Rehabilitation Act of 1973, which prohibits discrimination against handicapped persons by recipients of federal funds. Available from Harvard Legislative Research Bureau, Langdell Hall, Harvard Law School, Cambridge, MA 02138; single copy $4.00. (Author/IRT)

  15. 77 FR 2726 - General Services Administration Acquisition Regulation; Information Collection; Contract...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-01-19

    ... Final Payment (GSAR Part 532 and 552.232-72; GSA Form 1142 Release of Claims) AGENCY: Office of the... extension of a previously approved information collection requirement and the reinstatement of GSA Form 1142... 1142 was inadvertently deleted as part of the rewrite of GSAR regulations on Contract Financing....

  16. 77 FR 26763 - General Services Administration Acquisition Regulation; Submission for OMB Review; Contract...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-05-07

    ... Financing Final Payment (GSAR Parts 532 and 552.232-72; GSA Form 1142 Release of Claims) AGENCY: Office of... reinstatement of GSA Form 1142, Release of Claims, regarding final payment under construction and building services contract. GSA Form 1142 was inadvertently deleted as part of the rewrite of GSAR regulations...

  17. 76 FR 28855 - Defense Federal Acquisition Regulation Supplement; Business Systems-Definition and Administration

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-05-18

    .... Contractor business systems and internal controls are the first line of defense against waste, fraud, and... business systems are material terms, performance of which is required to ensure contracts will be performed..., 234, 242 et al. Defense Federal Acquisition Regulation Supplement; Business Systems-- Definition...

  18. 76 FR 20901 - Further Amendments to General Regulations of the Food and Drug Administration To Incorporate...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-04-14

    ..., Drug, and Cosmetic Act (the FD&C Act) and providing FDA with the authority to regulate tobacco products... 21 CFR Part 1 Cosmetics, Drugs, Exports, Food labeling, Imports, Labeling, Reporting and... the Federal Food, Drug, and Cosmetic Act and under authority delegated to the Commissioner of Food...

  19. Nutritional conditions regulate transcriptional activity of SF-1 by controlling sumoylation and ubiquitination

    PubMed Central

    Lee, Jiwon; Yang, Dong Joo; Lee, Syann; Hammer, Gary D.; Kim, Ki Woo; Elmquist, Joel K.

    2016-01-01

    Steroidogenic factor 1 (SF-1) is a transcription factor expressed in the ventral medial nucleus of the hypothalamus that regulates energy homeostasis. However, the molecular mechanisms of SF-1 in the control of energy balance are largely unknown. Here, we show that nutritional conditions, such as the presence or absence of serum, affect SF-1 action. Serum starvation significantly decreased hypothalamic SF-1 levels by promoting ubiquitin-dependent degradation, and sumoylation was required for this process. SF-1 transcriptional activity was also differentially regulated by nutritional status. Under normal conditions, the transcriptional activity of hypothalamic SF-1 was activated by SUMO, but this was attenuated during starvation. Taken together, these results indicate that sumoylation and ubiquitination play crucial roles in the regulation of SF-1 function and that these effects are dependent on nutritional conditions, further supporting the importance of SF-1 in the control of energy homeostasis. PMID:26750456

  20. An example of US Food and Drug Administration device regulation: medical devices indicated for use in acute ischemic stroke.

    PubMed

    Peña, Carlos; Li, Khan; Felten, Richard; Ogden, Neil; Melkerson, Mark

    2007-06-01

    The Food and Drug Administration has established requirements for protecting the public health by assuring the safety and effectiveness of a variety of medical products including drugs, devices, and biological products, and for promoting public health by expediting the approval of treatments that are safe and effective. The Center for Devices and Radiological Health is the center within the agency that is responsible for pre- and postmarket regulation of medical devices. In this article, we review current regulation of medical devices, research and development programs, pre- and postmarket perspectives, and future considerations of medical devices, particularly as they relate to devices targeting acute ischemic stroke as an example of the process. We also review the Center for Devices and Radiological Health's historical perspective of acute ischemic stroke trials and clinical trial design considerations used in prior studies that have led to US market clearance as they are related to currently marketed devices indicated for acute ischemic stroke.

  1. Operant ethanol self-administration increases extracellular-signal regulated protein kinase (ERK) phosphorylation in reward-related brain regions: selective regulation of positive reinforcement in the prefrontal cortex of C57BL/6J mice

    PubMed Central

    Faccidomo, Sara; Salling, Michael C; Galunas, Christina; Hodge, Clyde W

    2015-01-01

    Rationale Extracellular-signal regulated protein kinase (ERK1/2) is activated by ethanol in reward-related brain regions. Accordingly, systemic inhibition of ERK1/2 potentiates ethanol reinforcement. However, the brain region(s) that mediate this effect are unknown. Objective To pharmacologically inhibit ERK1/2 in the medial prefrontal cortex (PFC), nucleus accumbens (NAC) and amygdala (AMY) prior to ethanol or sucrose self-administration, and evaluate effects of operant ethanol self-administration on ERK1/2 phosphorylation (pERK1/2). Methods Male C57BL/6J mice were trained to lever press on a fixed-ratio-4 schedule of 9% ethanol+2% sucrose (ethanol) or 2% sucrose (sucrose) reinforcement. Mice were sacrificed immediately after the 30th self-administration session and pERK1/2 immunoreactivity was quantified in targeted brain regions. Additional groups of mice were injected with SL 327 (0–1.7 μg/side) in PFC, NAC or AMY prior to self-administration. Results pERK1/2 immunoreactivity was significantly increased by operant ethanol (g/kg=1.21 g/kg; BAC=54.9 mg/dl) in the PFC, NAC (core and shell), and AMY (central nucleus) as compared to sucrose. Microinjection of SL 327 (1.7 μg) into the PFC selectively increased ethanol self-administration. Intra-NAC injection of SL 327 had no effect on ethanol- but suppressed sucrose-reinforced responding. Intra-AMY microinjection of SL 327 had no effect on either ethanol- or sucrose-reinforced responding. Locomotor activity was unaffected under all conditions. Conclusions Operant ethanol self-administration increases pERK1/2 activation in the PFC, NAC and AMY. However, ERK1/2 activity only in the PFC mechanistically regulates ethanol self-administration. These data suggest that ethanol-induced activation of ERK1/2 in the PFC is a critical pharmacological effect that mediates the reinforcing properties of the drug. PMID:26123321

  2. Increase in cocaine- and amphetamine-regulated transcript (CART) in specific areas of the mouse brain by acute caffeine administration.

    PubMed

    Cho, Jin Hee; Cho, Yun Ha; Kim, Hyo Young; Cha, Seung Ha; Ryu, Hyun; Jang, Wooyoung; Shin, Kyung Ho

    2015-04-01

    Caffeine produces a variety of behavioral effects including increased alertness, reduced food intake, anxiogenic effects, and dependence upon repeated exposure. Although many of the effects of caffeine are mediated by its ability to block adenosine receptors, it is possible that other neural substrates, such as cocaine- and amphetamine-regulated transcript (CART), may be involved in the effects of caffeine. Indeed, a recent study demonstrated that repeated caffeine administration increases CART in the mouse striatum. However, it is not clear whether acute caffeine administration alters CART in other areas of the brain. To explore this possibility, we investigated the dose- and time-dependent changes in CART immunoreactivity (CART-IR) after a single dose of caffeine in mice. We found that a high dose of caffeine (100 mg/kg) significantly increased CART-IR 2 h after administration in the nucleus accumbens shell (AcbSh), dorsal bed nucleus of the stria terminalis (dBNST), central nucleus of the amygdala (CeA), paraventricular hypothalamic nucleus (PVN), arcuate hypothalamic nucleus (Arc), and locus coeruleus (LC), and returned to control levels after 8 h. But this increase was not observed in other brain areas. In addition, caffeine administration at doses of 25 and 50 mg/kg appears to produce dose-dependent increases in CART-IR in these brain areas; however, the magnitude of increase in CART-IR observed at a dose of 50 mg/kg was similar or greater than that observed at a dose of 100 mg/kg. This result suggests that CART-IR in AcbSh, dBNST, CeA, PVN, Arc, and LC is selectively affected by caffeine administration.

  3. The influence of acute stress on the regulation of conditioned fear

    PubMed Central

    Raio, Candace M.; Phelps, Elizabeth A.

    2014-01-01

    Fear learning and regulation is a prominent model for describing the pathogenesis of anxiety disorders and stress-related psychopathology. Fear expression can be modulated using a number of regulatory strategies, including extinction, cognitive emotion regulation, avoidance strategies and reconsolidation. In this review, we examine research investigating the effects of acute stress and stress hormones on these regulatory techniques. We focus on what is known about the impact of stress on the ability to flexibly regulate fear responses that are acquired through Pavlovian fear conditioning. Our primary aim is to explore the impact of stress on fear regulation in humans. Given this, we focus on techniques where stress has been linked to alterations of fear regulation in humans (extinction and emotion regulation), and briefly discuss other techniques (avoidance and reconsolidation) where the impact of stress or stress hormones have been mainly explored in animal models. These investigations reveal that acute stress may impair the persistent inhibition of fear, presumably by altering prefrontal cortex function. Characterizing the effects of stress on fear regulation is critical for understanding the boundaries within which existing regulation strategies are viable in everyday life and can better inform treatment options for those who suffer from anxiety and stress-related psychopathology. PMID:25530986

  4. 15 CFR 772.1 - Definitions of terms as used in the Export Administration Regulations (EAR).

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... flight control systems. (Cat 7)—Function to prevent undesirable “aircraft” and “missile” motions or... (electromagnetic) radiation. Adaptive control. (Cat 2)—A control system that adjusts the response from conditions... departments are under consideration. Decisions are made by majority vote. AES. See “Automated Export...

  5. 15 CFR 772.1 - Definitions of terms as used in the Export Administration Regulations (EAR).

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... flight control systems. (Cat 7)—Function to prevent undesirable “aircraft” and “missile” motions or... (electromagnetic) radiation. Adaptive control. (Cat 2)—A control system that adjusts the response from conditions... departments are under consideration. Decisions are made by majority vote. AES. See “Automated Export...

  6. 15 CFR 772.1 - Definitions of terms as used in the Export Administration Regulations (EAR).

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... flight control systems. (Cat 7)—Function to prevent undesirable “aircraft” and “missile” motions or... (electromagnetic) radiation. Adaptive control. (Cat 2)—A control system that adjusts the response from conditions... departments are under consideration. Decisions are made by majority vote. AES. See “Automated Export...

  7. 15 CFR 772.1 - Definitions of terms as used in the Export Administration Regulations (EAR).

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... flight control systems. (Cat 7)—Function to prevent undesirable “aircraft” and “missile” motions or... (electromagnetic) radiation. Adaptive control. (Cat 2)—A control system that adjusts the response from conditions... departments are under consideration. Decisions are made by majority vote. AES. See “Automated Export...

  8. Central Regulation of Hypothalamic-Pituitary-Thyroid Axis Under Physiological and Pathophysiological Conditions

    PubMed Central

    Lechan, Ronald M.

    2014-01-01

    TRH is a tripeptide amide that functions as a neurotransmitter but also serves as a neurohormone that has a critical role in the central regulation of the hypothalamic-pituitary-thyroid axis. Hypophysiotropic TRH neurons involved in this neuroendocrine process are located in the hypothalamic paraventricular nucleus and secrete TRH into the pericapillary space of the external zone of the median eminence for conveyance to anterior pituitary thyrotrophs. Under basal conditions, the activity of hypophysiotropic TRH neurons is regulated by the negative feedback effects of thyroid hormone to ensure stable, circulating, thyroid hormone concentrations, a mechanism that involves complex interactions between hypophysiotropic TRH neurons and the vascular system, cerebrospinal fluid, and specialized glial cells called tanycytes. Hypophysiotropic TRH neurons also integrate other humoral and neuronal inputs that can alter the setpoint for negative feedback regulation by thyroid hormone. This mechanism facilitates adaptation of the organism to changing environmental conditions, including the shortage of food and a cold environment. The thyroid axis is also affected by other adverse conditions such as infection, but the central mechanisms mediating suppression of hypophysiotropic TRH may be pathophysiological. In this review, we discuss current knowledge about the mechanisms that contribute to the regulation of hypophysiotropic TRH neurons under physiological and pathophysiological conditions. PMID:24423980

  9. Factors Regulating the Effects of Hippocampal Inactivation on Renewal of Conditional Fear after Extinction

    ERIC Educational Resources Information Center

    Corcoran, Kevin A.; Maren, Stephen

    2004-01-01

    After extinction of fear to a Pavlovian conditional stimulus (CS), contextual stimuli come to regulate the expression of fear to that CS. There is growing evidence that the context dependence of memory retrieval after extinction involves the hippocampus. In the present experiment, we examine whether hippocampal involvement in memory retrieval…

  10. CREB phosphorylation regulates striatal transcriptional responses in the self-administration model of methamphetamine addiction in the rat.

    PubMed

    Krasnova, Irina N; Chiflikyan, Margarit; Justinova, Zuzana; McCoy, Michael T; Ladenheim, Bruce; Jayanthi, Subramaniam; Quintero, Cynthia; Brannock, Christie; Barnes, Chanel; Adair, Jordan E; Lehrmann, Elin; Kobeissy, Firas H; Gold, Mark S; Becker, Kevin G; Goldberg, Steven R; Cadet, Jean Lud

    2013-10-01

    Neuroplastic changes in the dorsal striatum participate in the transition from casual to habitual drug use and might play a critical role in the development of methamphetamine (METH) addiction. We examined the influence of METH self-administration on gene and protein expression that may form substrates for METH-induced neuronal plasticity in the dorsal striatum. Male Sprague-Dawley rats self-administered METH (0.1mg/kg/injection, i.v.) or received yoked saline infusions during eight 15-h sessions and were euthanized 2h, 24h, or 1month after cessation of METH exposure. Changes in gene and protein expression were assessed using microarray analysis, RT-PCR and Western blots. Chromatin immunoprecipitation (ChIP) followed by PCR was used to examine epigenetic regulation of METH-induced transcription. METH self-administration caused increases in mRNA expression of the transcription factors, c-fos and fosb, the neurotrophic factor, Bdnf, and the synaptic protein, synaptophysin (Syp) in the dorsal striatum. METH also caused changes in ΔFosB, BDNF and TrkB protein levels, with increases after 2 and 24h, but decreases after 1month of drug abstinence. Importantly, ChIP-PCR showed that METH self-administration caused enrichment of phosphorylated CREB (pCREB), but not of histone H3 trimethylated at lysine 4 (H3K4me3), on promoters of c-fos, fosb, Bdnf and Syp at 2h after cessation of drug intake. These findings show that METH-induced changes in gene expression are mediated, in part, by pCREB-dependent epigenetic phenomena. Thus, METH self-administration might trigger epigenetic changes that mediate alterations in expression of genes and proteins serving as substrates for addiction-related synaptic plasticity.

  11. Voglibose administration regulates body weight and energy intake in high fat-induced obese mice.

    PubMed

    Do, Hyun Ju; Jin, Taeon; Chung, Ji Hyung; Hwang, Ji Won; Shin, Min-Jeong

    2014-01-17

    We tested whether long-term administration of voglibose (VO) prevents diet induced obesity in addition to hypoglycemic effects in high fat fed mice and further investigated the underlying mechanisms by which voglibose exerts its weight lowering effect. Male C57BL/6 mice were fed ad libitum for 12 weeks with the control diet (CTL), high-fat diet (HFD) or the HFD with VO supplementations. Blood lipid profile, plasma leptin levels and hepatic triglyceride content, as well as expressions of genes involved in appetite and mitochondrial function were examined. The results showed that VO significantly reduced body weight, fat mass and energy intakes in high fat fed mice. VO showed improved metabolic profiles including blood glucose, triglyceride and free fatty acid. Elevated levels of plasma leptin in HFD were significantly reduced with the VO, furthermore, VO modulated the hypothalamic expressions of leptin receptors and appetite related genes. VO showed the upregulated expressions of PGC-1 in the liver and epididymal adipose tissue. In conclusion, VO may exert antiobesity properties through reductions in energy intake and improvement in mitochondrial function, indicating that VO has potential therapeutic use in patients with obesity, type 2 diabetes, and related complications.

  12. Employee Retirement Income Security Act of 1974; rules and regulations for administration and enforcement; claims procedure. Final regulation; delay of applicability date.

    PubMed

    2001-07-09

    This action delays for at least six months and not more than one year the applicability date for the regulation governing minimum requirements for benefit claims procedures of group health plans covered by Title I of the Employee Retirement Income Security Act. As published on November 21, 2000, the benefit claims procedure would be applicable to claims filed on or after January 1, 2002. The current action amends the regulation so that it will apply to group health claims filed on or after the first day of the first plan year beginning on or after July 1, 2002, but in no event later than January 1, 2003. This action provides a limited additional period within which group health plan sponsors, administrators, and service providers can bring their claims processing systems into compliance with the new requirements. A postponement of the applicability date with respect to group health claims will allow a more orderly transition to the new standards and will avoid the confusion and additional expense that would be caused if certain pending Congressional bills are enacted before or soon after the original applicability date. This action does not apply to pension plans or plans providing disability or welfare benefits (other than group health). For these plans, the regulation will continue to be applicable to claims filed on or after January 1, 2002.

  13. [The role of beta-endorphin in regulating the conditioned reflex activity of cats].

    PubMed

    Karamian, A I; Pankov, Iu A; Protsenko, A L; Sollertinskaia, T N; Kofman, I L

    1990-08-01

    The role of beta-endorphin in regulation of instrumental food conditioning and in more complicated forms of nervous activity in cats was found to involve a facilitating unspecific effect both on positive and negative food conditioning, the latter having a general adaptive character. The influence of the same small doses of beta-endorphin (10 mkg/kg - 15 x 10(-6) mkg/kg) on the choice responses was more complicated and depended on the basic level of conditioning and the typology of animals. Possible mechanism of the beta-endorphin effect on higher nervous activity, is discussed.

  14. Deciphering Cis-Regulatory Element Mediated Combinatorial Regulation in Rice under Blast Infected Condition

    PubMed Central

    Deb, Arindam; Kundu, Sudip

    2015-01-01

    Combinations of cis-regulatory elements (CREs) present at the promoters facilitate the binding of several transcription factors (TFs), thereby altering the consequent gene expressions. Due to the eminent complexity of the regulatory mechanism, the combinatorics of CRE-mediated transcriptional regulation has been elusive. In this work, we have developed a new methodology that quantifies the co-occurrence tendencies of CREs present in a set of promoter sequences; these co-occurrence scores are filtered in three consecutive steps to test their statistical significance; and the significantly co-occurring CRE pairs are presented as networks. These networks of co-occurring CREs are further transformed to derive higher order of regulatory combinatorics. We have further applied this methodology on the differentially up-regulated gene-sets of rice tissues under fungal (Magnaporthe) infected conditions to demonstrate how it helps to understand the CRE-mediated combinatorial gene regulation. Our analysis includes a wide spectrum of biologically important results. The CRE pairs having a strong tendency to co-occur often exhibit very similar joint distribution patterns at the promoters of rice. We couple the network approach with experimental results of plant gene regulation and defense mechanisms and find evidences of auto and cross regulation among TF families, cross-talk among multiple hormone signaling pathways, similarities and dissimilarities in regulatory combinatorics between different tissues, etc. Our analyses have pointed a highly distributed nature of the combinatorial gene regulation facilitating an efficient alteration in response to fungal attack. All together, our proposed methodology could be an important approach in understanding the combinatorial gene regulation. It can be further applied to unravel the tissue and/or condition specific combinatorial gene regulation in other eukaryotic systems with the availability of annotated genomic sequences and suitable

  15. 7 CFR 301.51-4 - Conditions governing the interstate movement of regulated articles from quarantined areas.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... regulated articles from quarantined areas. 301.51-4 Section 301.51-4 Agriculture Regulations of the... DOMESTIC QUARANTINE NOTICES Asian Longhorned Beetle § 301.51-4 Conditions governing the interstate movement of regulated articles from quarantined areas. (a) Any regulated article may be moved interstate...

  16. Conditioned place preference and locomotor sensitization after repeated administration of cocaine or methamphetamine in rats treated with epidermal growth factor during the neonatal period.

    PubMed

    Mizuno, Makoto; Malta, Romulo S; Nagano, Tadasato; Nawa, Hiroyuki

    2004-10-01

    Epidermal growth factor (EGF) and its structurally related proteins are involved in the developmental regulation of various brain neurons, including midbrain dopaminergic neurons. We recently reported EGF and EGF-receptor abnormalities in both the brain tissues and blood of schizophrenic patients. Administration of EGF to neonatal rats transiently increases tyrosine hydroxylase expression and subsequently results in behavioral abnormalities in prepulse inhibition of acoustic startle, locomotor activity, and social interaction after development. The enhanced locomotor and stereotypic responses of the neonatally EGF-treated rats are considered to be an animal model for positive schizophrenia symptoms. In the present study, we investigated psychostimulant sensitivity of neonatally EGF-treated rats. At the adult stage, EGF-treated rats were challenged with cocaine (15 mg/kg) or methamphetamine (1 mg/kg), and conditioned place preference and locomotor activity were examined. The rats that received EGF during the neonatal period had significantly higher conditioned place preference for where cocaine or methamphetamine was administered than controls. The neonatal EGF treatment enhanced behavioral response to methamphetamine and behavioral sensitization to cocaine at the adult stage. Drug-naive controls gradually increased locomotor responses to cocaine during their daily injections, whereas EGF-treated rats exhibited a larger increase in cocaine responses. These results indicate that overactivation of the EGF receptors (ErbB1) during the neonatal period influences future sensitivity to psychostimulants. Our findings indicate a potential link between EGF-receptor activation and drug addiction.

  17. Regulation of osteogenic differentiation of human adipose-derived stem cells by controlling electromagnetic field conditions

    PubMed Central

    Kang, Kyung Shin; Hong, Jung Min; Kang, Jo A; Rhie, Jong-Won; Jeong, Young Hun; Cho, Dong-Woo

    2013-01-01

    Many studies have reported that an electromagnetic field can promote osteogenic differentiation of mesenchymal stem cells. However, experimental results have differed depending on the experimental and environmental conditions. Optimization of electromagnetic field conditions in a single, identified system can compensate for these differences. Here we demonstrated that specific electromagnetic field conditions (that is, frequency and magnetic flux density) significantly regulate osteogenic differentiation of adipose-derived stem cells (ASCs) in vitro. Before inducing osteogenic differentiation, we determined ASC stemness and confirmed that the electromagnetic field was uniform at the solenoid coil center. Then, we selected positive (30/45 Hz, 1 mT) and negative (7.5 Hz, 1 mT) osteogenic differentiation conditions by quantifying alkaline phosphate (ALP) mRNA expression. Osteogenic marker (for example, runt-related transcription factor 2) expression was higher in the 30/45 Hz condition and lower in the 7.5 Hz condition as compared with the nonstimulated group. Both positive and negative regulation of ALP activity and mineralized nodule formation supported these responses. Our data indicate that the effects of the electromagnetic fields on osteogenic differentiation differ depending on the electromagnetic field conditions. This study provides a framework for future work on controlling stem cell differentiation. PMID:23306704

  18. Systemic Administration of Induced Neural Stem Cells Regulates Complement Activation in Mouse Closed Head Injury Models

    PubMed Central

    Gao, Mou; Dong, Qin; Yao, Hui; Lu, Yingzhou; Ji, Xinchao; Zou, Mingming; Yang, Zhijun; Xu, Minhui; Xu, Ruxiang

    2017-01-01

    Complement activation plays important roles in the pathogenesis of central nervous system (CNS) diseases. Patients face neurological disorders due to the development of complement activation, which contributes to cell apoptosis, brain edema, blood-brain barrier dysfunction and inflammatory infiltration. We previously reported that induced neural stem cells (iNSCs) can promote neurological functional recovery in closed head injury (CHI) animals. Remarkably, we discovered that local iNSC grafts have the potential to modulate CNS inflammation post-CHI. In this study, we aimed to explore the role of systemically delivered iNSCs in complement activation following CNS injury. Our data showed that iNSC grafts decreased the levels of sera C3a and C5a and down-regulated the expression of C3d, C9, active Caspase-3 and Bax in the brain, kidney and lung tissues of CHI mice. Furthermore, iNSC grafts decreased the levels of C3d+/NeuN+, C5b-9+/NeuN+, C3d+/Map2+ and C5b-9+/Map2+ neurons in the injured cortices of CHI mice. Subsequently, we explored the mechanisms underlying these effects. With flow cytometry analysis, we observed a dramatic increase in complement receptor type 1-related protein y (Crry) expression in iNSCs after CHI mouse serum treatment. Moreover, both in vitro and in vivo loss-of-function studies revealed that iNSCs could modulate complement activation via Crry expression. PMID:28383046

  19. Complying with the Drug-Free Schools and Campuses Regulations: [EDGAR Part 86]. A Guide for University and College Administrators. Revised

    ERIC Educational Resources Information Center

    DeRicco, Beth

    2006-01-01

    This guide describes the requirements of the 1989 amendments to the "Drug-Free Schools and Communities Act" (DFSCA), as articulated in the "Education Department General Administrative Regulations" (EDGAR) Part 86,--the Drug-Free Schools and Campuses Regulations--and ways in which institutions of higher education (IHEs) have met…

  20. New tuning conditions for a class of nonlinear PID global regulators of robot manipulators

    NASA Astrophysics Data System (ADS)

    Orrante-Sakanassi, Jorge; Santibánez, Victor; Hernández-Guzmán, Victor M.

    2014-04-01

    Several nonlinear proportional-integral-derivative (PID) controllers for robot manipulators that ensure global asymptotic stability have been proposed in the literature. However, the tuning criteria obtained are expressed in terms of conditions so restrictive that they have avoided, until now, carrying out experimental tests with such controllers. Tuning criteria of some PID controllers for robot manipulators with conditions more relaxed than those presented previously in the literature have been proposed in two recent works by the authors. This was achieved by setting the tuning conditions individually for each joint instead of general conditions for the whole robot. In this paper we extend these results to a class of nonlinear PID global regulators for robot manipulators. The obtained tuning criteria are given in terms of conditions so relaxed that they have allowed to carry out, for the first time, experimental essays with these controllers. Such experiments are presented in this paper using a two-degrees-of-freedom robot manipulator.

  1. Mapping condition-dependent regulation of lipid metabolism in Saccharomyces cerevisiae.

    PubMed

    Jewett, Michael C; Workman, Christopher T; Nookaew, Intawat; Pizarro, Francisco A; Agosin, Eduardo; Hellgren, Lars I; Nielsen, Jens

    2013-11-06

    Lipids play a central role in cellular function as constituents of membranes, as signaling molecules, and as storage materials. Although much is known about the role of lipids in regulating specific steps of metabolism, comprehensive studies integrating genome-wide expression data, metabolite levels, and lipid levels are currently lacking. Here, we map condition-dependent regulation controlling lipid metabolism in Saccharomyces cerevisiae by measuring 5636 mRNAs, 50 metabolites, 97 lipids, and 57 (13)C-reaction fluxes in yeast using a three-factor full-factorial design. Correlation analysis across eight environmental conditions revealed 2279 gene expression level-metabolite/lipid relationships that characterize the extent of transcriptional regulation in lipid metabolism relative to major metabolic hubs within the cell. To query this network, we developed integrative methods for correlation of multi-omics datasets that elucidate global regulatory signatures. Our data highlight many characterized regulators of lipid metabolism and reveal that sterols are regulated more at the transcriptional level than are amino acids. Beyond providing insights into the systems-level organization of lipid metabolism, we anticipate that our dataset and approach can join an emerging number of studies to be widely used for interrogating cellular systems through the combination of mathematical modeling and experimental biology.

  2. Mapping Condition-Dependent Regulation of Lipid Metabolism in Saccharomyces cerevisiae

    PubMed Central

    Jewett, Michael C.; Workman, Christopher T.; Nookaew, Intawat; Pizarro, Francisco A.; Agosin, Eduardo; Hellgren, Lars I.; Nielsen, Jens

    2013-01-01

    Lipids play a central role in cellular function as constituents of membranes, as signaling molecules, and as storage materials. Although much is known about the role of lipids in regulating specific steps of metabolism, comprehensive studies integrating genome-wide expression data, metabolite levels, and lipid levels are currently lacking. Here, we map condition-dependent regulation controlling lipid metabolism in Saccharomyces cerevisiae by measuring 5636 mRNAs, 50 metabolites, 97 lipids, and 57 13C-reaction fluxes in yeast using a three-factor full-factorial design. Correlation analysis across eight environmental conditions revealed 2279 gene expression level-metabolite/lipid relationships that characterize the extent of transcriptional regulation in lipid metabolism relative to major metabolic hubs within the cell. To query this network, we developed integrative methods for correlation of multi-omics datasets that elucidate global regulatory signatures. Our data highlight many characterized regulators of lipid metabolism and reveal that sterols are regulated more at the transcriptional level than are amino acids. Beyond providing insights into the systems-level organization of lipid metabolism, we anticipate that our dataset and approach can join an emerging number of studies to be widely used for interrogating cellular systems through the combination of mathematical modeling and experimental biology. PMID:24062529

  3. [Researches of autonomic regulation of blood circulation in the condition of long-term space flight].

    PubMed

    Baevskiĭ, R M; Luchitskaia, E S; Funtova, I I; Chernikova, A G

    2013-01-01

    In the article is presented five-year experience of experimentation in autonomic regulation of blood circulation onboard the International space station. The heart rate variability (HRV) analysis was the basic methodical approach in the researches. We described probabilistic approach created on the basis of HRV analysis to an estimation of risk of pathology development in the conditions of long space flight. The individual type of autonomic regulation had essential value during the analysis of results. It is shown that the type of regulation, which is inherent in every cosmonaut in the conditions of weightlessness, remains even during following flights. We obtained the new scientific data on connection of character of adaptable reaction of an organism to the space flight factors with individual type of autonomic regulation. It is shown that staying in weightlessness is connected with changeover of regulatory systems and with transition in a zone of prenosological states. Adaptable reactions in weightlessness are characterized by tension growth of regulatory systems at preservation of sufficient functional reserves. The mobilization of additional resources after returning to the Earth is required and consequently functional reserve of mechanisms of regulation decreases. Cosmonauts with vagotonic and normo-sympatotonic types of autonomic regulation appear to be the most resistant. Knowing the type of autonomic regulation we will be able to foresee possible reaction of the cosmonaut to the factors of space flight. As a result of HRV analysis during the flight of the past few months likelihood estimations were calculated and risk categories were defined. Consequently, 3 groups of risk of pathology development were distinguished. In conclusion, theoretical and applied relevance of the conducted experiments were considered.

  4. Up-regulation of hepatic receptor for growth hormone in the flounder ( Paralichthys olivaceus) after oral administration with exogenous GH

    NASA Astrophysics Data System (ADS)

    Liu, Zong-Zhu; Wang, Jin-Bao; Xu, Yong-Li; Wang, Yong; Zhang, Pei-Jun

    2001-06-01

    The iodination efficiency of salmon GH(sGH) was 38.82%, using a modification of the chloramine-T method. The specific activity of the125I-sGH was about 40 μCi/μg protein. The results of binding assay showed a single class of high affinity and low-capacity binding site in flounder liver. Long-term administration with exogenous GH can induce the up-regulation of hepatic GH receptor in total binding capacity though there was no significant difference in capacity of free binding sites of livers from control and experimental fish, this result also indicated that the liver from experimental fish, compared to that from control fish, had more occupied binding sites.

  5. Calciotropic hormones and lipolysis of human adipose tissue: role of extracellular calcium as conditioning but not regulating factor.

    PubMed

    Ziegler, R; Jobst, W; Minne, H; Faulhaber, J D

    1980-01-01

    The influences of different calcium concentrations (0, 0.924 and 2.772 mMol/l) on lipolysis of in vitro incubated human adipose tissue slices or adipocytes were studied under the conditions of stimulation with isoproterenol and parathyroid hormone preparations or inhibition by insulin. Extractive bovine PTH (as well as synthetic PTH 1--34) stimulated glycerol release in a biphasic pattern similarly to isoproterenol; PTH was about half as potent as isoproterenol. The optimal conditions for lipolysis were observed using a calcium concentration of 0.924 mMol/l, whereas lipolysis was distinctly impaired at concentrations of 0 or 2.772 mMol/l; this was true for basal as well as isoproterenol- and PTH stimulated lipolysis or the inhibitory effect of insulin. In contrast to partially purified extractive calcitonin, pure synthetic calcitonin did not inhibit lipolysis. Isoproterenol- and PTH-administrations led to cAMP accumulation in the adipose tissue, this process was also diminished at the non-optimal calcium concentrations. The results suggest a conditioning, but not a regulating significance of extracellular calcium for lipolysis, whereas the importance of the lipolytic potency of PTH remains to be elucidated.

  6. Reducing Conservatism in Aircraft Engine Response Using Conditionally Active Min-Max Limit Regulators

    NASA Technical Reports Server (NTRS)

    May, Ryan D.; Garg, Sanjay

    2012-01-01

    Current aircraft engine control logic uses a Min-Max control selection structure to prevent the engine from exceeding any safety or operational limits during transients due to throttle commands. This structure is inherently conservative and produces transient responses that are slower than necessary. In order to utilize the existing safety margins more effectively, a modification to this architecture is proposed, referred to as a Conditionally Active (CA) limit regulator. This concept uses the existing Min-Max architecture with the modification that limit regulators are active only when the operating point is close to a particular limit. This paper explores the use of CA limit regulators using a publicly available commercial aircraft engine simulation. The improvement in thrust response while maintaining all necessary safety limits is demonstrated in a number of cases.

  7. KNOX1 is expressed and epigenetically regulated during in vitro conditions in Agave spp

    PubMed Central

    2012-01-01

    Background The micropropagation is a powerful tool to scale up plants of economical and agronomical importance, enhancing crop productivity. However, a small but growing body of evidence suggests that epigenetic mechanisms, such as DNA methylation and histone modifications, can be affected under the in vitro conditions characteristic of micropropagation. Here, we tested whether the adaptation to different in vitro systems (Magenta boxes and Bioreactors) modified epigenetically different clones of Agave fourcroydes and A. angustifolia. Furthermore, we assessed whether these epigenetic changes affect the regulatory expression of KNOTTED1-like HOMEOBOX (KNOX) transcription factors. Results To gain a better understanding of epigenetic changes during in vitro and ex vitro conditions in Agave fourcroydes and A. angustifolia, we analyzed global DNA methylation, as well as different histone modification marks, in two different systems: semisolid in Magenta boxes (M) and temporary immersion in modular Bioreactors (B). No significant difference was found in DNA methylation in A. fourcroydes grown in either M or B. However, when A. fourcroydes was compared with A. angustifolia, there was a two-fold difference in DNA methylation between the species, independent of the in vitro system used. Furthermore, we detected an absence or a low amount of the repressive mark H3K9me2 in ex vitro conditions in plants that were cultured earlier either in M or B. Moreover, the expression of AtqKNOX1 and AtqKNOX2, on A. fourcroydes and A. angustifolia clones, is affected during in vitro conditions. Therefore, we used Chromatin ImmunoPrecipitation (ChIP) to know whether these genes were epigenetically regulated. In the case of AtqKNOX1, the H3K4me3 and H3K9me2 were affected during in vitro conditions in comparison with AtqKNOX2. Conclusions Agave clones plants with higher DNA methylation during in vitro conditions were better adapted to ex vitro conditions. In addition, A. fourcroydes and A

  8. 48 CFR 52.241-7 - Change in Rates or Terms and Conditions of Service for Regulated Services.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 48 Federal Acquisition Regulations System 2 2014-10-01 2014-10-01 false Change in Rates or Terms... CONTRACT CLAUSES Text of Provisions and Clauses 52.241-7 Change in Rates or Terms and Conditions of Service... following: Change in Rates or Terms and Conditions of Service for Regulated Services (FEB 1995) (a)...

  9. 48 CFR 52.241-7 - Change in Rates or Terms and Conditions of Service for Regulated Services.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... CONTRACT CLAUSES Text of Provisions and Clauses 52.241-7 Change in Rates or Terms and Conditions of Service... following: Change in Rates or Terms and Conditions of Service for Regulated Services (FEB 1995) (a) This... 48 Federal Acquisition Regulations System 2 2010-10-01 2010-10-01 false Change in Rates or...

  10. Monitoring of transcriptional regulation in Pichia pastoris under protein production conditions

    PubMed Central

    Gasser, Brigitte; Maurer, Michael; Rautio, Jari; Sauer, Michael; Bhattacharyya, Anamitra; Saloheimo, Markku; Penttilä, Merja; Mattanovich, Diethard

    2007-01-01

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

  11. `Up-regulation of histone acetylation induced by social defeat mediates the conditioned rewarding effects of cocaine.

    PubMed

    Montagud-Romero, S; Montesinos, J; Pascual, M; Aguilar, M A; Roger-Sanchez, C; Guerri, C; Miñarro, J; Rodríguez-Arias, M

    2016-10-03

    Social defeat (SD) induces a long-lasting increase in the rewarding effects of psychostimulants measured using the self-administration and conditioned place procedures (CPP). However, little is known about the epigenetic changes induced by social stress and about their role in the increased response to the rewarding effects of psychostimulants. Considering that histone acetylation regulates transcriptional activity and contributes to drug-induced behavioral changes, we addressed the hypothesis that SD induces transcriptional changes by histone modifications associated with the acquisition of place conditioning. After a fourth defeat, H3(K9) acetylation was decreased in the hippocampus, while there was an increase of HAT and a decrease of HDAC levels in the cortex. Three weeks after the last defeat, mice displayed an increase in histone H4(K12) acetylation and an upregulation of histone acetyl transferase (HAT) activity in the hippocampus. In addition, H3(K4)me3, which is closely associated with transcriptional initiation, was also augmented in the hippocampus three weeks after the last defeat. Inhibition of HAT by curcumin (100mg/kg) before each SD blocked the increase in the conditioned reinforcing effects of 1mg/kg of cocaine, while inhibition of HDAC by valproic acid (500mg/kg) before social stress potentiated cocaine-induced CPP. Preference was reinstated when animals received a priming dose of 0.5mg/kg of cocaine, an effect that was absent in untreated defeated mice. These results suggest that the experience of SD induces chromatin remodeling, alters histone acetylation and methylation, and modifies the effects of cocaine on place conditioning. They also point to epigenetic mechanisms as potential avenues leading to new treatments for the long-term effects of social stress on drug addiction.

  12. Grassland species differentially regulate proline concentrations under future climate conditions: an integrated biochemical and modelling approach.

    PubMed

    AbdElgawad, Hamada; De Vos, Dirk; Zinta, Gaurav; Domagalska, Malgorzata A; Beemster, Gerrit T S; Asard, Han

    2015-10-01

    Proline (Pro) is a versatile metabolite playing a role in the protection of plants against environmental stresses. To gain a deeper understanding of the regulation of Pro metabolism under predicted future climate conditions, including drought stress, elevated temperature and CO2 , we combined measurements in contrasting grassland species (two grasses and two legumes) at multiple organisational levels, that is, metabolite concentrations, enzyme activities and gene expression. Drought stress (D) activates Pro biosynthesis and represses its catabolism, and elevated temperature (DT) further elevated its content. Elevated CO2 attenuated the DT effect on Pro accumulation. Computational pathway control analysis allowed a mechanistic understanding of the regulatory changes in Pro metabolism. This analysis indicates that the experimentally observed coregulation of multiple enzymes is more effective in modulating Pro concentrations than regulation of a single step. Pyrroline-5-carboxylate synthetase (P5CS) and pyrroline-5-carboxylate reductase (P5CR) play a central role in grasses (Lolium perenne, Poa pratensis), and arginase (ARG), ornithine aminotransferase (OAT) and P5CR play a central role in legumes (Medicago lupulina, Lotus corniculatus). Different strategies in the regulation of Pro concentrations under stress conditions were observed. In grasses the glutamate pathway is activated predominantly, and in the legumes the ornithine pathway, possibly related to differences in N-nutritional status.

  13. The Conditional Process Model of Mindfulness and Emotion Regulation: An Empirical Test

    PubMed Central

    Curtiss, Joshua; Klemanski, David H.; Andrews, Leigh; Ito, Masaya; Hofmann, Stefan G.

    2017-01-01

    Background The conditional process model (CPM) of mindfulness and emotion regulation posits that specific mediators and moderators link these constructs to mental health outcomes. The current study empirically examined the central tenets of the CPM, which posit that nonreactivity moderates the indirect effect of observation on symptoms of emotional disorders through cognitive emotion regulation strategies. Methods A clinical sample (n=1667) of individuals from Japan completed a battery of self-report instruments. Several path analyses were conducted to determine whether cognitive emotion regulation strategies mediate the relationship between observation and symptoms of individual emotional disorders, and to determine whether nonreactivity moderated these indirect effects. Results Results provided support the CPM. Specifically, nonreactivity moderated the indirect effect of observation on symptoms through reappraisal, but it did not moderate the indirect effect of observation on symptoms through suppression. Limitations Causal interpretations are limited, and cultural considerations must be acknowledged given the Japanese sample Conclusions These results underscore the potential importance of nonreactivity and emotion regulation as targets for interventions. PMID:28157552

  14. Regulations implementing the Federal Coal Mine Health and Safety Act of 1969, as amended. Employment Standards Administration, Labor. Final rule.

    PubMed

    2000-12-20

    On January 22, 1997, the Department issued a proposed rule to amend the regulations implementing the Black Lung Benefits Act. 62 FR 3338-3435 (Jan. 22, 1997). When the comment period closed on August 21, 1997, the Department had received written submissions from almost 200 interested persons, including coal miners, coal mine operators, insurers, physicians, and attorneys. The Department also held hearings in Charleston, West Virginia, and Washington, D.C. at which over 50 people testified. The Department carefully reviewed the testimony and the comments and, on October 8, 1999, issued a second notice of proposed rulemaking. 64 FR 54966-55072 (Oct. 8, 1999). In its second notice, the Department proposed changing several of the most important provisions in its initial proposal. The Department also explained its decision not to alter the original proposal with respect to other key regulations based on the comments received to date. Finally, the Department prepared an initial regulatory flexibility analysis. In order to ensure that small businesses that could be affected by the Department's proposal received appropriate notice of the Department's proposed changes, the Department mailed a copy of the second notice of proposed rulemaking to all coal mine operators contained in the databases maintained by the Mine Safety and Health Administration. The Department initially allowed interested parties until December 7, 1999 to file comments to its second proposal, but extended that period until January 6, 2000. The Department received 37 written submissions before the close of the comment period, from groups representing both coal miners and coal mine operators. The Department also received comments from individual miners, various coal mining and insurance companies, as well as from claims processing organizations, attorneys, and various professional organizations. The Department has carefully reviewed all of the comments, and is issuing its final rule. The rule contains a

  15. Sexual behavior regulated (paced) by the female induces conditioned place preference.

    PubMed

    Paredes, R G; Alonso, A

    1997-02-01

    The possibility that female-paced coital behavior induces a reward state of sufficient intensity and duration to induce conditioning was evaluated by the conditioned-place-preference paradigm. Ovariectomized female rats, treated with estradiol benzoate and progesterone, regulated (paced) their coital interactions with a stud male through a 2-compartment chamber in which only the female could freely move from one compartment to the other. The females that paced their coital interactions showed a clear place preference. In contrast, no change in preference was observed in the females that could not pace their coital contacts. The change in preference in the females that paced their coital interactions was similar to that produced by an injection of morphine (1 mg/kg). These results suggest that coital interactions in females can induce a reward state when the females can control the pace of the sexual interaction.

  16. RSS1 regulates the cell cycle and maintains meristematic activity under stress conditions in rice

    PubMed Central

    Ogawa, Daisuke; Abe, Kiyomi; Miyao, Akio; Kojima, Mikiko; Sakakibara, Hitoshi; Mizutani, Megumi; Morita, Haruka; Toda, Yosuke; Hobo, Tokunori; Sato, Yutaka; Hattori, Tsukaho; Hirochika, Hirohiko; Takeda, Shin

    2011-01-01

    Plant growth and development are sustained by continuous cell division in the meristems, which is perturbed by various environmental stresses. For the maintenance of meristematic functions, it is essential that cell division be coordinated with cell differentiation. However, it is unknown how the proliferative activities of the meristems and the coordination between cell division and differentiation are maintained under stressful conditions. Here we show that a rice protein, RSS1, whose stability is controlled by cell cycle phases, contributes to the vigour of meristematic cells and viability under salinity conditions. These effects of RSS1 are exerted by regulating the G1–S transition, possibly through an interaction of RSS1 with protein phosphatase 1, and are mediated by the phytohormone, cytokinin. RSS1 is conserved widely in plant lineages, except eudicots, suggesting that RSS1-dependent mechanisms might have been adopted in specific lineages during the evolutionary radiation of angiosperms. PMID:21505434

  17. Microcystin production and regulation under nutrient stress conditions in toxic microcystis strains.

    PubMed

    Pimentel, Juliana S M; Giani, Alessandra

    2014-09-01

    Microcystin is a common and well-known cyanobacterial toxin whose intracellular role is still under investigation. Increasing knowledge on microcystin gene expression and regulation can contribute to the understanding of its putative cellular function. In this work, reverse transcription-quantitative PCR (RT-qPCR) was used to investigate the transcriptional response of the mcyD gene to nitrogen (nitrate and ammonium) and phosphorus limitation in two toxic Microcystis strains. The existence of a direct correlation between transcripts of mcyD and ntcA genes was also identified. In previous studies, NtcA (global nitrogen regulator) has been described as a potential component in the control of microcystin biosynthesis. This research showed that stress agents linked to nutrient deprivation could lead to a significant increase of microcystin production in both strains studied. The more toxic strain proved to be more resistant to nutrient limitation. The similar outcomes of mcyD regulation observed for all nutrients suggest that this response can be linked to oxidative stress of cells undergoing adverse growth conditions.

  18. Administrator's Handbook for Elementary, Middle, Junior High and High Schools. Regulations and Criteria for Accrediting and Improving the Schools of Oklahoma. Bulletin No. 113-Y.

    ERIC Educational Resources Information Center

    Oklahoma State Dept. of Education, Oklahoma City. Div. of Instruction.

    This administrator handbook begins with statements summarizing Oklahoma's Division of Instruction and the guiding principles of education at the state's elementary and secondary levels. Following an outline of State Board of Education policies, the handbook lists various general regulations and progress criteria for the state as a whole.…

  19. Differential regulation of two sucrose transporters by defoliation and light conditions in perennial ryegrass.

    PubMed

    Furet, Pierre-Maxime; Berthier, Alexandre; Decau, Marie-Laure; Morvan-Bertrand, Annette; Prud'homme, Marie-Pascale; Noiraud-Romy, Nathalie; Meuriot, Frédéric

    2012-12-01

    Sucrose transport between source and sink tissues is supposed to be a key-step for an efficient regrowth of perennial rye-grass after defoliation and might be altered by light conditions. We assessed the effect of different light regimes (high vs low light applied before or after defoliation) on growth, fructans and sucrose mobilization, as well as on sucrose transporter expression during 14 days of regrowth. Our results reported that defoliation led to a mobilization of C reserves (first sucrose and then fructans), which was parallel to an induction of LpSUT1 sucrose transporter expression in source and sink tissues (i.e. leaf sheaths and elongating leaf bases, respectively) irrespective to light conditions. Light regime (high or low light) had little effects on regrowth and on C reserves mobilization during the first 48 h of regrowth after defoliation. Thereafter, low light conditions, delaying the recovery of photosynthetic capacities, had a negative effect on C reserves re-accumulation (especially sucrose). Surprisingly, high light did not enhance sucrose transporter expression. Indeed, while light conditions had no effect on LpSUT1 expression, LpSUT2 transcripts levels were enhanced for low light grown plants. These results indicate that two sucrose transporter currently identified in Lolium perenne L. are differentially regulated by light and sucrose.

  20. Distinct 5′ UTRs regulate XIAP expression under normal growth conditions and during cellular stress

    PubMed Central

    Riley, Alura; Jordan, Lindsay E.; Holcik, Martin

    2010-01-01

    X-chromosome linked inhibitor of apoptosis, XIAP, is cellular caspase inhibitor and a key regulator of apoptosis. We and others have previously shown that XIAP expression is regulated primarily at the level of protein synthesis; the 5′ untranslated region (UTR) of XIAP mRNA contains an Internal Ribosome Entry Site (IRES) that supports cap-independent expression of XIAP protein during conditions of pathophysiological stress, such as serum deprivation or gamma irradiation. Here, we show that XIAP is encoded by two distinct mRNAs that differ in their 5′ UTRs. We further show that the dominant, shorter, 5′ UTR promotes a basal level of XIAP expression under normal growth conditions. In contrast, the less abundant longer 5′ UTR contains an IRES and supports cap-independent translation during stress. Our data suggest that the combination of alternate regulatory regions and distinct translational initiation modes is critical in maintaining XIAP levels in response to cellular stress and may represent a general mechanism of cellular adaptation. PMID:20385593

  1. Regulation of water permeability in rabbit conjunctival epithelium by anisotonic conditions.

    PubMed

    Candia, Oscar A; Alvarez, Lawrence J; Zamudio, Aldo C

    2006-04-01

    Effects of unilateral exposure to anisotonic conditions on diffusional water permeability of the isolated rabbit conjunctiva were determined. A segment of the bulbar-palpebral conjunctiva was mounted between Ussing-type hemichambers under short-circuit conditions. Unidirectional water fluxes (J(dw)) were measured in either direction by adding (3)H(2)O to one hemichamber and sampling from the other. Electrical parameters were measured simultaneously. J(dw) were determined under control isosmotic conditions and after introduction of either hyper- or hypotonic solutions against the tear or stromal sides of the preparations. In each of these four separate conditions, the anisotonic medium produced an approximately 20-30% reduction in J(dw) across the tissue, with the exception that to obtain such reduction with increased tonicity from the stromal side (medium osmolality increased by adding sucrose), conditions presumptively inhibiting regulatory volume increase mechanisms (e.g., pretreatment with amiloride and bumetanide) were also required. All reductions in J(dw) elicited by the various anisotonic conditions were reversible on restoration of control tonicity. In experiments in which preparations were pretreated with the protein cross-linking agent glutaraldehyde, anisotonicity-elicited reductions in J(dw) were not observed. Such reductions were also not observed in the presence of HgCl(2), implying the involvement of aquaporins. However, it is possible that the mercurial may be toxic to the epithelium, preventing the tonicity response. Nevertheless, from concomitant changes in transepithelial electrical resistance, as well as [(14)C]mannitol fluxes, [(14)C]butanol fluxes, and Arrhenius plots, arguments are presented that the above effects are best explained as a cell-regulated reduction in membrane water permeability that occurs at the level of water-transporting channels. Presumably both apical and basolateral membranes can downregulate their water permeabilities as

  2. 7 CFR 755.1 - Administration.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 7 2011-01-01 2011-01-01 false Administration. 755.1 Section 755.1 Agriculture Regulations of the Department of Agriculture (Continued) FARM SERVICE AGENCY, DEPARTMENT OF AGRICULTURE... FARMERS AND RANCHERS § 755.1 Administration. (a) This part establishes the terms and conditions...

  3. Cellular bioenergetics is regulated by PARP1 under resting conditions and during oxidative stress

    PubMed Central

    Módis, Katalin; Gerő, Domokos; Erdélyi, Katalin; Szoleczky, Petra; DeWitt, Douglas; Szabo, Csaba

    2012-01-01

    Purpose The goal of the current studies was to elucidate the role of the principal poly(ADP-ribose)polymerase isoform, PARP1 in the regulation of cellular energetics in endothelial cells under resting conditions and during oxidative stress. Methods We utilized bEnd.3 endothelial cells and A549 human transformed epithelial cells. PARP1 was inhibited either by pharmacological inhibitors or by siRNA silencing. The Seahorse XF24 Extracellular Flux Analyzer was used to measure indices of mitochondrial respiration (oxygen consumption rate) and of glycolysis (extracellular acidification rate). Cell viability, cellular and mitochondrial NAD+ levels and mitochondrial biogenesis were also measured. Results Silencing of PARP1 increased basal cellular parameters of oxidative phosphorylation, providing direct evidence that PARP1 is a regulator of mitochondrial function in resting cells. Pharmacological inhibitors of PARP1 and siRNA silencing of PARP1 protected against the development of mitochondrial dysfunction and elevated the respiratory reserve capacity in endothelial cells exposed to oxidative stress. The observed effects were unrelated to an effect on mitochondrial biogenesis. Isolated mitochondria of A549 human transformed epithelial cells exhibited an improved resting bioenergetic status after stable lentiviral silencing of PARP1; these effects were associated with elevated resting mitochondrial NAD+ levels in PARP1 silenced cells. Conclusions PARP1 is a regulator of basal cellular energetics in resting endothelial and epithelial cells. Furthermore, endothelial cells respond with a decrease in their mitochondrial reserve capacity during low-level oxidative stress, an effect, which is attenuated by PARP1 inhibition. While PARP1 is a regulator of oxidative phosphorylation in resting and oxidatively stressed cells, it only exerts a minor effect on glycolysis. PMID:22198485

  4. Structural and molecular regulation of lung maturation by intratracheal vascular endothelial growth factor administration in the normally grown and placentally restricted fetus.

    PubMed

    McGillick, Erin V; Orgeig, Sandra; Morrison, Janna L

    2016-03-01

    Inhibition of hypoxia signalling leads to respiratory distress syndrome (RDS), whereas administration of vascular endothelial growth factor (VEGF), the most widely characterized hypoxia responsive factor, protects from RDS. In the lung of the chronically hypoxaemic placentally restricted (PR) fetus, there is altered regulation of hypoxia signalling. This leads to reduced surfactant maturation in late gestation and provides evidence for the increased risk of RDS in growth restricted neonates at birth. We evaluated the effect of recombinant human VEGF administration with respect to bypassing the endogenous regulation of hypoxia signalling in the lung of the normally grown and PR sheep fetus. There was no effect of VEGF administration on fetal blood pressure or fetal breathing movements. We examined the effect on the expression of genes regulating VEGF signalling (FLT1 and KDR), angiogenesis (ANGPT1, AQP1, ADM), alveolarization (MMP2, MMP9, TIMP1, COL1A1, ELN), proliferation (IGF1, IGF2, IGF1R, MKI67, PCNA), inflammation (CCL2, CCL4, IL1B, TNFA, TGFB1, IL10) and surfactant maturation (SFTP-A, SFTP-B, SFTP-C, SFTP-D, PCYT1A, LPCAT, LAMP3, ABCA3). Despite the effects of PR on the expression of genes regulating airway remodelling, inflammatory signalling and surfactant maturation, there were very few effects of VEGF administration on gene expression in the lung of both the normally grown and PR fetus. There were, however, positive effects of VEGF administration on percentage tissue, air space and numerical density of SFTP-B positive alveolar epithelial cells in fetal lung tissue. These results provide evidence for the stimulatory effects of VEGF administration on structural maturation in the lung of both the normally grown and PR fetus.

  5. Effects of cocaine self-administration history under limited and extended access conditions on in vivo striatal dopamine neurochemistry and acoustic startle in rhesus monkeys

    PubMed Central

    Henry, Porche’ Kirkland; Davis, Michael

    2009-01-01

    Rationale The transition from infrequent and controlled cocaine use to dependence may involve enduring changes in neurobiology as a consequence of persistent drug use. Objective The present study utilized an intravenous drug self-administration protocol of increasing cocaine access to evaluate potential changes in dopamine function in vivo, including changes in sensitivity to psychostimulants. Materials and methods Drug-naïve rhesus monkeys were provided limited access (1 h) to cocaine self-administration for 60 days followed by 60 days under an extended access condition (4 h). Basal levels of striatal extracellular dopamine and its metabolites, as well as the effectiveness of cocaine and amphetamine to elevate dopamine, were determined with in vivo microdialysis before the initiation of cocaine self-administration and during limited and extended access. The effect of cocaine and amphetamine on the acoustic startle response was also examined to assess complementary behavioral changes as a function of drug history. Results Extended access to cocaine self-administration lead to increased daily intake compared to limited access conditions but did not result in escalated intake over time. However, cocaine- and amphetamine-induced increases in striatal dopamine were diminished as a function of cocaine self-administration history. Surprisingly, there was no effect of drug-taking history on sensitivity to psychostimulant-induced enhancement of startle amplitude. Conclusions The present experiments provide evidence of a hypofunctional dopamine system that is not associated with an escalation in drug intake or reflected in measures of acoustic startle. PMID:19365621

  6. Development of a multipurpose GATEWAY-based lentiviral tetracycline-regulated conditional RNAi system (GLTR).

    PubMed

    Sigl, Reinhard; Ploner, Christian; Shivalingaiah, Giridhar; Kofler, Reinhard; Geley, Stephan

    2014-01-01

    RNA interference (RNAi) has become an essential technology for functional gene analysis. Its success, however, depends on the effective expression of RNAi-inducing small double-stranded interfering RNA molecules (siRNAs) in target cells. In many cell types, RNAi can be achieved by transfection of chemically synthesised siRNAs, which results in transient knockdown of protein expression. Expression of double-stranded short hairpin RNA (shRNA) provides another means to induce RNAi in cells that are hard to transfect. To facilitate the generation of stable, conditional RNAi cell lines, we have developed novel one- and two-component vector GATEWAY-compatible lentiviral tetracycline-regulated RNAi (GLTR) systems. The combination of a modified RNA-polymerase-III-dependent H1 RNA promoter (designated 'THT') for conditional shRNA expression with different lentiviral delivery vectors allows (1) the use of fluorescent proteins for colour-coded combinatorial RNAi or for monitoring RNAi induction (pGLTR-FP), (2) selection of transduced cells (pGLTR-S), and (3) the generation of conditional cell lines using a one vector system (pGLTR-X). All three systems were found to be suitable for the analysis of essential genes, such as CDC27, a component of the mitotic ubiquitin ligase APC/C, in cell lines and primary human cells.

  7. Increased synthesis of folate transporters regulates folate transport in conditions of ethanol exposure and folate deficiency.

    PubMed

    Thakur, Shilpa; More, Deepti; Rahat, Beenish; Khanduja, Krishan Lal; Kaur, Jyotdeep

    2016-01-01

    Excessive alcohol consumption and dietary folate inadequacy are the main contributors leading to folate deficiency (FD). The present study was planned to study regulation of folate transport in conditions of FD and ethanol exposure in human embryonic kidney cell line. Also, the reversible nature of effects mediated by ethanol exposure and FD was determined by folate repletion and ethanol removal. For ethanol treatment, HEK293 cells were grown in medium containing 100 mM ethanol, and after treatment, one group of cells was shifted on medium that was free from ethanol. For FD treatment, cells were grown in folate-deficient medium followed by shifting of one group of cells on folate containing medium. FD as well as ethanol exposure resulted in an increase in folate uptake which was due to an increase in expression of folate transporters, i.e., reduced folate carrier, proton-coupled folate transporter, and folate receptor, both at the mRNA and protein level. The effects mediated by ethanol exposure and FD were reversible on removal of treatment. Promoter region methylation of folate transporters remained unaffected after FD and ethanol exposure. As far as transcription rate of folate transporters is concerned, an increase in rate of synthesis was observed in both ethanol exposure and FD conditions. Additionally, mRNA life of folate transporters was observed to be reduced by FD. An increased expression of folate transporters under ethanol exposure and FD conditions can be attributed to enhanced rate of synthesis of folate transporters.

  8. 36 CFR 251.15 - Conditions, rules and regulations to govern exercise of mineral rights reserved in conveyances to...

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... regulations to govern exercise of mineral rights reserved in conveyances to the United States. 251.15 Section... Miscellaneous Land Uses Natural Resources Control § 251.15 Conditions, rules and regulations to govern exercise... obedience thereto: (1) Whoever undertakes to exercise the reserved rights shall give prior written notice...

  9. 42 CFR 485.608 - Condition of participation: Compliance with Federal, State, and local laws and regulations.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 42 Public Health 5 2013-10-01 2013-10-01 false Condition of participation: Compliance with Federal, State, and local laws and regulations. 485.608 Section 485.608 Public Health CENTERS FOR MEDICARE... applicable Federal laws and regulations related to the health and safety of patients. (b)...

  10. 42 CFR 485.608 - Condition of participation: Compliance with Federal, State, and local laws and regulations.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 42 Public Health 5 2014-10-01 2014-10-01 false Condition of participation: Compliance with Federal, State, and local laws and regulations. 485.608 Section 485.608 Public Health CENTERS FOR MEDICARE... applicable Federal laws and regulations related to the health and safety of patients. (b)...

  11. 36 CFR 251.15 - Conditions, rules and regulations to govern exercise of mineral rights reserved in conveyances to...

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... regulations to govern exercise of mineral rights reserved in conveyances to the United States. 251.15 Section... Miscellaneous Land Uses Natural Resources Control § 251.15 Conditions, rules and regulations to govern exercise... obedience thereto: (1) Whoever undertakes to exercise the reserved rights shall give prior written notice...

  12. 36 CFR 251.14 - Conditions, rules and regulations to govern exercise of timber rights reserved in conveyance to...

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... regulations to govern exercise of timber rights reserved in conveyance to the United States. 251.14 Section... Miscellaneous Land Uses Natural Resources Control § 251.14 Conditions, rules and regulations to govern exercise... undertakes to exercise the reserved rights, hereinafter called operator, shall give prior written notice...

  13. 36 CFR 251.15 - Conditions, rules and regulations to govern exercise of mineral rights reserved in conveyances to...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... regulations to govern exercise of mineral rights reserved in conveyances to the United States. 251.15 Section... Miscellaneous Land Uses Natural Resources Control § 251.15 Conditions, rules and regulations to govern exercise... obedience thereto: (1) Whoever undertakes to exercise the reserved rights shall give prior written notice...

  14. Regulation of the Function of Eukaryotic DNA Topoisomerase I: Topological Conditions for Inactivity

    NASA Astrophysics Data System (ADS)

    Camilloni, Giorgio; di Martino, Elisabetta; di Mauro, Ernesto; Caserta, Micaela

    1989-05-01

    The effects of supercoiling on the cleavage reaction by eukaryotic DNA topoisomerases I (wheat germ, chicken erythrocyte, and calf thymus) have been analyzed on DNA fragments (0.96 and 2.3 kilobases) encompassing an immunoglobulin kappa light-chain promoter. In one topological condition of the substrate, the absolutely relaxed state, cleavage was found to be impeded. This finding defines the topology-dependent step of the eukaryotic DNA topoisomerase I reaction and shows that for the cleavage reaction topology is more critical than sequence effects. These findings suggest a simple model for the regulation of the DNA topoisomerase I reaction based on topological factors, which may explain the regulatory function of the enzyme in in vivo eukaryotic transcription.

  15. Factors regulating the effects of hippocampal inactivation on renewal of conditional fear after extinction.

    PubMed

    Corcoran, Kevin A; Maren, Stephen

    2004-01-01

    After extinction of fear to a Pavlovian conditional stimulus (CS), contextual stimuli come to regulate the expression of fear to that CS. There is growing evidence that the context dependence of memory retrieval after extinction involves the hippocampus. In the present experiment, we examine whether hippocampal involvement in memory retrieval after extinction is related to the history of CS presentations in the context used for retrieval testing. We used infusions of muscimol to inactivate the dorsal hippocampus (DH) during postextinction retrieval tests that were conducted in contexts that differed in their history of CS presentations in that context. We found that DH inactivation affected the context-dependent retrieval of extinction (i.e., renewal) when testing occurred in a context that had no history of CS exposure, but not in a context that reliably predicted the CS. These results are discussed in terms of theories regarding the role of the hippocampus in contextual memory retrieval.

  16. [Characteristics of autonomic regulations in miners working in hard conditions of coal mines].

    PubMed

    Perederiĭ, H S; Ivanov, V V

    2004-01-01

    72 miners aged from 30 till 40 years have been surveyed. It was established that to achieve socially acceptable results the miners use corresponding strategy doing their job. Under the influence of the work the functional states mediated not only by conditions of working environment but also by resistivity of the organism are developed. It is shown that highly productive, reliable and effective work is possible under adequate interactions of central and autonomic mechanisms of regulation. Alteration in these interactions, particularly, non-adequate centralization of management processes decreases physical capacity for work. Enhancement of sympathetic effects on periphery that leads to development of hypertensive reactions has been observed. Such alterations are accompanied by an increase in physiological cost of work and decreased productivity of labor.

  17. 7 CFR 301.87-4 - Conditions governing the interstate movement of regulated articles from regulated areas in...

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ..., DEPARTMENT OF AGRICULTURE DOMESTIC QUARANTINE NOTICES Sugarcane Diseases Quarantine and Regulations § 301.87... identity has been maintained, and it has not been used for the production of sugarcane while in...

  18. 7 CFR 301.87-4 - Conditions governing the interstate movement of regulated articles from regulated areas in...

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ..., DEPARTMENT OF AGRICULTURE DOMESTIC QUARANTINE NOTICES Sugarcane Diseases Quarantine and Regulations § 301.87... identity has been maintained, and it has not been used for the production of sugarcane while in...

  19. 7 CFR 301.87-4 - Conditions governing the interstate movement of regulated articles from regulated areas in...

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ..., DEPARTMENT OF AGRICULTURE DOMESTIC QUARANTINE NOTICES Sugarcane Diseases Quarantine and Regulations § 301.87... identity has been maintained, and it has not been used for the production of sugarcane while in...

  20. 7 CFR 301.87-4 - Conditions governing the interstate movement of regulated articles from regulated areas in...

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ..., DEPARTMENT OF AGRICULTURE DOMESTIC QUARANTINE NOTICES Sugarcane Diseases Quarantine and Regulations § 301.87... identity has been maintained, and it has not been used for the production of sugarcane while in...

  1. 7 CFR 301.87-4 - Conditions governing the interstate movement of regulated articles from regulated areas in...

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ..., DEPARTMENT OF AGRICULTURE DOMESTIC QUARANTINE NOTICES Sugarcane Diseases Quarantine and Regulations § 301.87... identity has been maintained, and it has not been used for the production of sugarcane while in...

  2. The Regulation of Peace River: a Large-scale Experiment on Fluvial Governing Conditions

    NASA Astrophysics Data System (ADS)

    Church, M.

    2004-12-01

    In 1967, British Columbia Hydro and Power Authority closed W.A.C.Bennett Dam, creating what was then the sixth largest hydropower project in the world. The dam is located in the Rocky Mountain front range so that, although it controls about half the runoff of the 293 000 sq.km basin, almost all of the sediment load originates downstream from the dam in the Alberta Plateau. Hence, the effects of these two principal governing conditions of fluvial systems can be separated. The 378 km immediately downstream to the Smoky River confluence are a wandering, cobble-gravel reach It has effectively ceased to be alluvial and the channel pattern has been simplified. Aggradation is occurring at major tributary junctions, whilst the tributaries themselves have degraded in their lowermost reaches. Smoky River, the principal tributary, delivers a large sand load. The 250 km reach to Carcajou is sandy gravel and the final 600 km to the Peace-Athabasca delta is sand-bed. Aggradation, with a change in fluvial style toward low-order braiding, appears to be underway in the proximal sand-bed reach. More generally, channel shrinkage in response to the regulated flow regime is controlled by the rate of progradation of riparian vegetation onto former bar surfaces In 1996, after 29 years of regulated flow, reservoir drawdown for dam repairs led to full spillway flows for 8 consecutive weeks, creating an effectively bankfull condition in the proximal post-regulation channel. Significant degradation was observed for the first time in many cross-sections but overall changes were surprisingly modest, reflecting the refractory bed and the degree to which riparian vegetation has become firmly established in former channel areas. Overall, sediment supply and flow competence are the principal controls of fluvial response in the system. The experimental aspect of this study of a large, northward flowing, boreal river can be controlled by before-after comparison. However, this strategy must take into

  3. Drug intake is sufficient, but conditioning is not necessary for the emergence of compulsive cocaine seeking after extended self-administration.

    PubMed

    Jonkman, Sietse; Pelloux, Yann; Everitt, Barry J

    2012-06-01

    Compulsive drug seeking, which is characterized by continued instrumental effort despite contingent punishment, has been shown to emerge after extended drug self-administration. Exactly what aspect of drug self-administration drives the appearance of addictive behavior is unclear, but the mechanistic explanations that have been offered differ in one key respect. On one hand, it has been suggested that dysfunctional conditioning during self-administration drives unrealistic reward expectations, ultimately producing resistance to punishment. If this is indeed the pathological process that drives compulsive behavior, then compulsivity should be apparent only in the presence of the pavlovian and instrumental stimuli that underwent frequent pairing with the drug reward. On the other hand, it has also been suggested that extended drug intake produces general changes to reward and decision-making circuits that manifest as compulsive drug seeking. Unfortunately, conditioning history and drug intake are generally intrinsically intertwined. However, here we used an animal model of compulsive cocaine seeking to selectively manipulate drug intake and the degree of conditioning in the test context, to investigate which of the two is more important for the emergence of compulsive cocaine seeking. The results show that extended drug intake alone is sufficient, but extended conditioning in the test context is not necessary for the emergence of compulsive cocaine seeking, resolving a fundamental question in addiction research.

  4. 42 CFR 418.116 - Condition of participation: Compliance with Federal, State, and local laws and regulations...

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ..., State, and local laws and regulations related to the health and safety of patients. 418.116 Section 418... (CONTINUED) MEDICARE PROGRAM (CONTINUED) HOSPICE CARE Conditions of participation: Organizational Environment § 418.116 Condition of participation: Compliance with Federal, State, and local laws and...

  5. 7 CFR 301.45-4 - Conditions governing the interstate movement of regulated articles and outdoor household articles...

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... SERVICE, DEPARTMENT OF AGRICULTURE DOMESTIC QUARANTINE NOTICES Gypsy Moth § 301.45-4 Conditions governing... gypsy moth life stages. (c) A regulated article originating in a generally infested area may be moved... adequate to prevent the dissemination of the gypsy moth, i.e., conditions of treatment,...

  6. 7 CFR 301.45-4 - Conditions governing the interstate movement of regulated articles and outdoor household articles...

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... SERVICE, DEPARTMENT OF AGRICULTURE DOMESTIC QUARANTINE NOTICES Gypsy Moth § 301.45-4 Conditions governing... gypsy moth life stages. (c) A regulated article originating in a generally infested area may be moved... adequate to prevent the dissemination of the gypsy moth, i.e., conditions of treatment,...

  7. 7 CFR 301.45-4 - Conditions governing the interstate movement of regulated articles and outdoor household articles...

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... SERVICE, DEPARTMENT OF AGRICULTURE DOMESTIC QUARANTINE NOTICES Gypsy Moth § 301.45-4 Conditions governing... gypsy moth life stages. (c) A regulated article originating in a generally infested area may be moved... adequate to prevent the dissemination of the gypsy moth, i.e., conditions of treatment,...

  8. 7 CFR 301.45-4 - Conditions governing the interstate movement of regulated articles and outdoor household articles...

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... SERVICE, DEPARTMENT OF AGRICULTURE DOMESTIC QUARANTINE NOTICES Gypsy Moth § 301.45-4 Conditions governing... gypsy moth life stages. (c) A regulated article originating in a generally infested area may be moved... adequate to prevent the dissemination of the gypsy moth, i.e., conditions of treatment,...

  9. 7 CFR 301.45-4 - Conditions governing the interstate movement of regulated articles and outdoor household articles...

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... SERVICE, DEPARTMENT OF AGRICULTURE DOMESTIC QUARANTINE NOTICES Gypsy Moth § 301.45-4 Conditions governing... gypsy moth life stages. (c) A regulated article originating in a generally infested area may be moved... adequate to prevent the dissemination of the gypsy moth, i.e., conditions of treatment,...

  10. 75 FR 9142 - Regulations Under I.R.C. Section 7430 Relating to Awards of Administrative Costs and Attorneys...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-01

    ... Awards of Administrative Costs and Attorneys Fees; Hearing Cancellation AGENCY: Internal Revenue Service... attorneys fees under section 7430 to conform to amendments made in the Taxpayer Relief Act of 1997 and...

  11. Soil-plant-atmosphere conditions regulating convective cloud formation above southeastern US pine plantations.

    PubMed

    Manoli, Gabriele; Domec, Jean-Christophe; Novick, Kimberly; Oishi, Andrew Christopher; Noormets, Asko; Marani, Marco; Katul, Gabriel

    2016-06-01

    Loblolly pine trees (Pinus taeda L.) occupy more than 20% of the forested area in the southern United States, represent more than 50% of the standing pine volume in this region, and remove from the atmosphere about 500 g C m-2 per year through net ecosystem exchange. Hence, their significance as a major regional carbon sink can hardly be disputed. What is disputed is whether the proliferation of young plantations replacing old forest in the southern United States will alter key aspects of the hydrologic cycle, including convective rainfall, which is the focus of the present work. Ecosystem fluxes of sensible (Hs) and latent heat (LE) and large-scale, slowly evolving free atmospheric temperature and water vapor content are known to be first-order controls on the formation of convective clouds in the atmospheric boundary layer. These controlling processes are here described by a zero-order analytical model aimed at assessing how plantations of different ages may regulate the persistence and transition of the atmospheric system between cloudy and cloudless conditions. Using the analytical model together with field observations, the roles of ecosystem Hs and LE on convective cloud formation are explored relative to the entrainment of heat and moisture from the free atmosphere. Our results demonstrate that cloudy-cloudless regimes at the land surface are regulated by a nonlinear relation between the Bowen ratio Bo=Hs/LE and root-zone soil water content, suggesting that young/mature pines ecosystems have the ability to recirculate available water (through rainfall predisposition mechanisms). Such nonlinearity was not detected in a much older pine stand, suggesting a higher tolerance to drought but a limited control on boundary layer dynamics. These results enable the generation of hypotheses about the impacts on convective cloud formation driven by afforestation/deforestation and groundwater depletion projected to increase following increased human population in the

  12. Protein kinase C -dependent regulation of synaptosomal glutamate uptake under conditions of hypergravity

    NASA Astrophysics Data System (ADS)

    Borisova, Tatiana; Krisanova, Natalia; Borisov, Arseniy; Sivko, Roman

    Glutamate is not only the main excitatory neurotransmitter in the mammalian CNS, but also a potent neurotoxin. Excessive concentration of ambient glutamate over activates glutamate receptors and causes neurotoxicity. Uptake of glutamate from the extracellular space into nerve cells was mediated by sodium-dependent glutamate transporters located in the plasma membrane. It was shown that the activity of glutamate transporters in rat brain nerve terminals was decreased after hypergravity (centrifugation of rats in special containers at 10 G for 1 hour). This decrease may result from the reduction in the number of glutamate transporters expressed in the plasma membrane of nerve terminals after hypergravity that was regulated by protein kinase C. The possibility of the involvement of protein kinase C in the regulation of the activity of glutamate transporters was assessed under conditions of hypergravity. The effect of protein kinase C inhibitor GF 109 203X on synaptosomal L-[14C]glutamate uptake was analysed. It was shown that the inhibitor decreased L-[14C]glutamate uptake by 15 % in control but did not influence it after hypergravity. In control, the initial velocity of L-[14C]glutamate uptake in the presence of the inhibitor decreased from 2.5 ± 0.2 nmol x min-1 x mg-1 of proteins to 2.17 ± 0.1 nmol x min-1 x mg-1 of proteins, whereas after hypergravity this value lowered from 2.05 ± 0.1 nmol x min-1 x mg-1 of proteins to 2.04 ± 0.1 nmol x min-1 x mg-1 of proteins. Thus, protein kinase C -dependent alteration in the cell surface expression of glutamate transporters may be one of the causes of a decrease in the activity of glutamate transporters after hypergravity.

  13. Public Services (Conditions of Service for Employees) (Amendment) Regulations, 1989 (No. 26 of 1989). [Selected provisions].

    PubMed

    1989-01-01

    The Zimbabwe Public Service Regulations of 1989 specify the conditions of service for employees. Leave for maternity purposes mandates that the department head grant 90 days leave to a pregnant woman who has served as an employee for more than 1 year beginning no earlier than 45 days and no later than 21 days prior to the estimated date of confinement, provided that, if the baby arrives later than scheduled, the woman may be granted her accrued vacation leave or leave with pay. Before the start of the leave, or before the lapse of 21 days if the period of leave had commenced, the woman shall, following the birth, be permitted to take the full period of the leave for maternity purposes that she applied for it if she provides the Commission with a medical certificate to the effect that the birth was premature, and the Commission is satisfied that she is acting in good faith. The above leave period shall, at the woman's option, consist of 90 days' maternity leave without deduction from her annual or vacation leave, at 75% of her salary, not including allowances; or 60 days maternity leave without deduction from her annual or vacation leave and 30 days' accrued vacation leave or vacation leave in advance, on full pay. The woman shall be paid her normal pensionable and non-pensionable allowances and accrue vacation leave as part of her qualifying service. A department head, with the head of Ministry's approval, may require a pregnant women to cease work earlier if he considers this in the best interest of his office, and may request medical certificate on the woman's fitness. Leave shall not affect a woman's grade, salary, incremental date, conditions of service, seniority, or eligibility for advancement or promotion.

  14. Permafrost conditions in peatlands regulate magnitude, timing, and chemical composition of catchment dissolved organic carbon export.

    PubMed

    Olefeldt, David; Roulet, Nigel T

    2014-10-01

    Permafrost thaw in peatlands has the potential to alter catchment export of dissolved organic carbon (DOC) and thus influence downstream aquatic C cycling. Subarctic peatlands are often mosaics of different peatland types, where permafrost conditions regulate the hydrological setting of each type. We show that hydrological setting is key to observed differences in magnitude, timing, and chemical composition of DOC export between permafrost and nonpermafrost peatland types, and that these differences influence the export of DOC of larger catchments even when peatlands are minor catchment components. In many aspects, DOC export from a studied peatland permafrost plateau was similar to that of a forested upland catchment. Similarities included low annual export (2-3 g C m(-2) ) dominated by the snow melt period (~70%), and how substantial DOC export following storms required wet antecedent conditions. Conversely, nonpermafrost fens had higher DOC export (7 g C m(-2) ), resulting from sustained hydrological connectivity during summer. Chemical composition of catchment DOC export arose from the mixing of highly aromatic DOC from organic soils from permafrost plateau soil water and upland forest surface horizons with nonaromatic DOC from mineral soil groundwater, but was further modulated by fens. Increasing aromaticity from fen inflow to outlet was substantial and depended on both water residence time and water temperature. The role of fens as catchment biogeochemical hotspots was further emphasized by their capacity for sulfate retention. As a result of fen characteristics, a 4% fen cover in a mixed catchment was responsible for 34% higher DOC export, 50% higher DOC concentrations and ~10% higher DOC aromaticity at the catchment outlet during summer compared to a nonpeatland upland catchment. Expansion of fens due to thaw thus has potential to influence landscape C cycling by increasing fen capacity to act as biogeochemical hotspots, amplifying aquatic C cycling, and

  15. Once is too much: Conditioned aversion develops immediately and predicts future cocaine self-administration behavior in rats

    PubMed Central

    Colechio, Elizabeth M.; Imperio, Caesar G.; Grigson, Patricia S.

    2014-01-01

    Rats emit aversive taste reactivity (TR) behavior (i.e., gapes) following intraoral delivery of a cocaine-paired taste cue and greater conditioned aversive TR at the end of training predicts greater drug-seeking and taking. Here, we examined the development of this conditioned aversive TR behavior on a trial by trial basis in an effort to determine when the change in behavior occurs and whether early changes in this behavior can be used to predict later drug-taking. The results show that conditioned aversive TR to a cocaine-paired cue occurs very early in training (i.e., following as few as 1 – 2 taste-drug pairings) and, importantly, that it can be used to predict later drug-seeking and drug-taking in rats. PMID:24773440

  16. Once is too much: conditioned aversion develops immediately and predicts future cocaine self-administration behavior in rats.

    PubMed

    Colechio, Elizabeth M; Imperio, Caesar G; Grigson, Patricia S

    2014-04-01

    Rats emit aversive taste reactivity (TR) behavior (i.e., gapes) following intraoral delivery of a cocaine-paired taste cue and greater conditioned aversive TR at the end of training predicts greater drug-seeking and taking. Here, we examined the development of this conditioned aversive TR behavior on a trial-by-trial basis in an effort to determine when the change in behavior occurs and whether early changes in this behavior can be used to predict later drug taking. The results show that conditioned aversive TR to a cocaine-paired cue occurs very early in training (i.e., following as few as 1-2 taste-drug pairings) and, importantly, that it can be used to predict later drug seeking and drug taking in rats.

  17. 49 CFR 171.22 - Authorization and conditions for the use of international standards and regulations.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... MATERIALS REGULATIONS GENERAL INFORMATION, REGULATIONS, AND DEFINITIONS Authorization and Requirements for... subchapter and the regulations of a foreign entity, is permitted under this subchapter. (4) Each person who... reporting requirements in §§ 171.15 and 171.16 of this part for incidents occurring within the...

  18. Regulation of glycerol metabolism in Enterobacter aerogenes NBRC12010 under electrochemical conditions.

    PubMed

    Hatayama, Kouta; Yagishita, Tatsuo

    2009-06-01

    Enterobacter aerogenes NBRC12010 was able to ferment glycerol to ethanol and hydrogen gas. Fermentation of glycerol ceased in the stationary phase of growth, and it was activated by electrochemical reactions using thionine as an electron transfer mediator from bacterial cells to an electrode. Using resting cells of E. aerogenes NBRC12010 in only citrate buffer solution, the cells did not consume glycerol at all, but they could metabolize glucose. These results suggest that the regulation of glycerol metabolism occurred at enzymatic steps before glycolysis. In E. aerogenes NBRC12010, glycerol was metabolized via glycerol dehydrogenase (GDH) and then dehydroxyacetone kinase. The GDH-catalyzed reaction mainly depended on the ratio of NAD(+)/NADH. At a NAD(+)/NADH ratio of nearly 1 or less, it was substantially suppressed and glycerol metabolism stopped. When the ratio was higher than 1, GDH was activated and glycerol was metabolized. Thus, the reaction of glycerol metabolism depended on the balance of cellular NAD(+)/NADH. Exogenous NADH was oxidized to NAD(+) by electrochemical reactions with thionine. We proposed the activation mechanism of glycerol metabolism under electrochemical conditions.

  19. Use of conditioned media is critical for studies of regulation in response to rapid heat shock.

    PubMed

    Mahat, Dig B; Lis, John T

    2017-01-01

    Heat shock response (HSR) maintains and restores protein homeostasis when cells are exposed to proteotoxic heat stress. Heat shock (HS) triggers a rapid and robust change in genome-wide transcription, protein synthesis, and chaperone activity; and therefore, the HSR has been widely used as a model system in these studies. The conventional method of performing instantaneous HS in the laboratory uses heated fresh media to induce HSR when added to cells. However, addition of fresh media to cells may evoke additional cellular responses and signaling pathways. Here, we compared the change in global transcription profile when HS is performed with either heated fresh media or heated conditioned media. We found that the use of heated fresh media induces transcription of hundreds of genes that HS alone does not induce, and masks or partially masks HS-mediated downregulation of thousands of genes. The fresh-media-dependent upregulated genes encode ribosomal subunit proteins involved in translation and RNA processing factors. More importantly, fresh media also induce transcription of several heat shock protein genes (Hsps) in a heat shock factor 1 (HSF1)-independent manner. Thus, we conclude that a conventional method of HS with heated fresh media causes changes in transcription regulation that confound the actual change caused solely by elevated temperature of cells.

  20. Two time scale output feedback regulation for ill-conditioned systems

    NASA Technical Reports Server (NTRS)

    Calise, A. J.; Moerder, D. D.

    1986-01-01

    Issues pertaining to the well-posedness of a two time scale approach to the output feedback regulator design problem are examined. An approximate quadratic performance index which reflects a two time scale decomposition of the system dynamics is developed. It is shown that, under mild assumptions, minimization of this cost leads to feedback gains providing a second-order approximation of optimal full system performance. A simplified approach to two time scale feedback design is also developed, in which gains are separately calculated to stabilize the slow and fast subsystem models. By exploiting the notion of combined control and observation spillover suppression, conditions are derived assuring that these gains will stabilize the full-order system. A sequential numerical algorithm is described which obtains output feedback gains minimizing a broad class of performance indices, including the standard LQ case. It is shown that the algorithm converges to a local minimum under nonrestrictive assumptions. This procedure is adapted to and demonstrated for the two time scale design formulations.

  1. 75 FR 1020 - Amendments to the Export Administration Regulations (EAR) Based Upon the Accession of Albania and...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-01-08

    ... Regulations (EAR) Based Upon the Accession of Albania and Croatia to Formal Membership in the North Atlantic... * * * * * * * Albania \\2 3\\ X X ...... X ....... X X X X ...... ...... ...... ...... ...... * * * * * * * Croatia \\3\\...

  2. The effects of the co-administration of the α₁-adrenoreceptor antagonist prazosin on the anxiolytic effect of citalopram in conditioned fear stress in the rat.

    PubMed

    Takamura, Naoki; Masuda, Takahiro; Inoue, Takeshi; Nakagawa, Shin; Koyama, Tsukasa

    2012-10-01

    Several studies have shown that the α₁-adrenoreceptor is involved in controlling extracellular serotonin levels. The administration of the α₁-adrenoreceptor antagonist prazosin was shown to decrease extracellular serotonin levels in the hippocampus, the prefrontal cortex and the raphe nucleus, while the administration of the α₁-adrenoreceptor agonist cirazoline was shown to increase serotonin levels. Furthermore, the elevation of serotonin levels induced by the selective serotonin reuptake inhibitor (SSRI) citalopram was attenuated by prazosin. Thus, α₁-adrenoreceptor antagonists may affect SSRI-induced increases in extracellular serotonin levels and their antidepressive and anxiolytic effects. However, little is known about the influence of α₁-adrenoreceptor antagonists on the behavioral pharmacological effects of SSRIs. The conditioned fear stress-induced freezing behavior is an animal model of anxiety and can detect the anxiolytic effect of SSRIs. To clarify whether an α₁-adrenoreceptor antagonist affects the anxiolytic action of SSRIs, we examined the effects of the co-administration of the α₁-adrenoreceptor antagonist prazosin and the SSRI citalopram using the contextual conditioned fear stress model. Low-dose prazosin (0.03 mg/kg) significantly attenuated the citalopram (3 mg/kg)-induced decrease in conditioned freezing. Moreover, high-dose (0.5 mg/kg), but not low-dose (0.03 mg/kg), prazosin significantly attenuated citalopram (10 mg/kg)-induced decreases in conditioned freezing. These drugs did not affect the spontaneous motor activity of the rats. Therefore, these results suggest that blocking the α₁-adrenoreceptor decreases the anxiolytic effect of citalopram.

  3. Characterization of an inhaled toluene drug discrimination in mice: effect of exposure conditions and route of administration.

    PubMed

    Shelton, Keith L; Slavova-Hernandez, Galina

    2009-06-01

    The drug discrimination procedure in animals has been extensively utilized to model the abuse related, subjective effects of drugs in humans, but it has seldom been used to examine abused volatile inhalants like toluene. The present study sought to characterize the temporal aspects of toluene's discriminative stimulus as well assess toluene blood concentrations under identical exposure conditions. B6SJLF1/J mice were trained to discriminate 10 min of exposure to 6000 ppm inhaled toluene vapor from air. Toluene vapor concentration dependently substituted for the training exposure condition with longer exposures to equivalent concentrations producing greater substitution than shorter exposures. Toluene's discriminative stimulus effects dissipated completely by 60 min after the cessation of exposure. Injected liquid toluene dose-dependently substituted for toluene vapor as well as augmenting the discriminative stimulus effects of inhaled toluene. Toluene blood concentrations measured under several exposure conditions which produced full substitution were all nearly identical suggesting that the concentration of toluene in the animal tissues at the time of testing determined discriminative performance. These results indicate that the discriminative stimulus effects of inhaled toluene vapor are likely mediated by CNS effects rather than by its pronounced peripheral stimulus effects.

  4. Rewarding effects of electrical stimulation of the insular cortex: decayed effectiveness after repeated tests and subsequent increase in vertical behavioral activity and conditioned place aversion after naloxone administration.

    PubMed

    García, Raquel; Zafra, Maria A; Puerto, Amadeo

    2015-02-01

    The insular cortex has been associated with various aversive and rewarding sensory, regulatory, and learning processes. The objective of this study was to examine the characteristics of the reinforcement induced by electrical stimulation of this brain area in rats. Results obtained confirm that electrical stimulation of the insular cortex may induce conditioned place and flavor preferences but the learning acquired is not transferred in a reversal test. Unexpectedly, they also demonstrate that this rewarding effect diminishes after repeated tests. In follow-up experiments, locomotor activity tests revealed an increased number of rearings (a sensitization index) in stimulated animals. Furthermore, in these same animals, administration of low doses of naloxone, an opiate antagonist, developed place aversion toward the maze compartment for which the animals had previously shown preference. These results are interpreted in relation to the effects induced by the repeated administration of natural and artificial rewarding stimuli.

  5. Effects of high-dose methadone maintenance on cocaine place conditioning, cocaine self-administration, and mu-opioid receptor mRNA expression in the rat brain.

    PubMed

    Leri, Francesco; Zhou, Yan; Goddard, Benjamin; Cummins, Erin; Kreek, Mary Jeanne

    2006-07-01

    Methadone maintenance at appropriate doses can effectively reduce cocaine abuse in heroin-dependent individuals. In the present studies, we investigated the effect of high-dose methadone maintenance cocaine conditioned place preference (CPP) and cocaine intravenous self-administration. Rats implanted with methadone-filled osmotic mini-pumps (20 and 55 mg/kg/day, SC) and conditioned with cocaine (1, 5, and 20 mg/kg, i.p.) did not express cocaine CPP. Similarly, rats implanted with methadone pumps (55 mg/kg/day) after cocaine conditioning (20 mg/kg) displayed neither spontaneous nor cocaine-precipitated (20 mg/kg, i.p.) CPP. In contrast, methadone maintenance (30 and 55 mg/kg/day, SC) did not alter the intravenous self-administration (continuous schedule of reinforcement) of various doses of cocaine (0.1, 0.5, and 2.0 mg/kg/inf). To explore neuropharmacological interactions between methadone maintenance and cocaine conditioning, we quantitatively measured mRNA levels of mu-opioid receptor (MOR) and proopiomelanocortin genes 10 days after methadone maintenance. MOR mRNA levels in both the nucleus accumbens core and frontal cortex were significantly elevated in rats exposed to cocaine during CPP conditioning. However, upregulation of MOR mRNA levels in the nucleus accumbens core were reduced by methadone maintenance in a dose-dependent manner. In conclusion, our results suggest that high-dose methadone maintenance does not alter the direct reinforcing effect of cocaine, but blocks spontaneous and cocaine-precipitated cocaine-seeking, possibly by preventing MOR alterations in the nucleus accumbens core induced by cocaine conditioning.

  6. Hydrogen profiles of dobutamine hydrochloride and fentanyl citrate solutions according to intravenous administration systems, temperature, and luminosity conditions.

    PubMed

    Barros, Daniele Porto; Fonseca, Fernando Luiz Affonso; Pedreira, Mavilde da Luz Gonçalves; Peterlini, Maria Angélica Sorgini

    2014-01-01

    Factors such as temperature, light exposure, drug concentration, ionic strength, time of infusion, and duration of drug association can influence the effectiveness of pharmacological solutions, which can compromise the solutions' quality, resulting in unstable solutions and drug incompatibility. The aim of this study was to determine the pH of solutions of dobutamine hydrochloride, fentanyl citrate, and their combination in 5% dextrose in water (D5W) under various light exposures and temperature conditions over time. The analysis was performed by measuring the pH of the substances in both pharmacological (commercial) preparations and in D5W under dark fluorescent light in the presence or absence of sunlight exposures, intravenous apparatus packaging (clear and amber burettes), and temperature (22°C and 37°C). Samples were collected immediately after preparation and after 0.5, 1, 2, 3, 4, and 24 hours of exposure to the various conditions; data were analyzed using mean standard deviations. Of the 260 pH values obtained, 50 (19.2%) were from commercial preparations and 210 (80.8%) from solutions exposed to various experimental conditions. Significant pH differences were found among the vials of the commercial preparation drugs. The largest pH value difference (0.88) was observed for fentanyl citrate, in which a pH increase of 0.88 (4.23 ± 0.62) was observed. The combination of drugs in D5W resulted in more acidic values than those of fentanyl citrate and of D5W and fentanyl citrate in D5W, but they were closer to what was observed for the solution of dobutamine hydrochloride in D5W. This solution was more acidic than fentanyl citrate diluted in D5W. The lower acidity of fentanyl citrate had a minor influence on the final pH of the combined drug solution in D5W. Under most conditions, the drug solutions kept at 22°C had pH values that were more acidic and less variable. Temperature was a major factor controlling the chemical behavior of the solutions analyzed

  7. Complementary regulation of four Eucalyptus CBF genes under various cold conditions

    PubMed Central

    Navarro, M.; Marque, G.; Ayax, C.; Keller, G.; Borges, J. P.; Marque, C.; Teulières, C.

    2009-01-01

    CBF transcription factors play central roles in the control of freezing tolerance in plants. The isolation of two additional CBF genes, EguCBF1c and EguCBF1d, from E. gunnii, one of the cold-hardiest Eucalyptus species, is described. While the EguCBF1D protein sequence is very similar to the previously characterized EguCBF1A and EguCBF1B sequences, EguCBF1C is more distinctive, in particular in the AP2-DBD (AP2-DNA binding domain). The expression analysis of the four genes by RT-qPCR reveals that none of them is specific to one stress but they are all preferentially induced by cold, except for the EguCBF1c gene which is more responsive to salt. The calculation of the transcript copy number enables the quantification of constitutive CBF gene expression. This basal level, significant for the four genes, greatly influences the final EguCBF1 transcript level in the cold. A cold shock at 4 °C, as well as a progressive freezing which mimics a natural frost episode, trigger a fast and strong response of the EguCBF1 genes, while growth at acclimating temperatures results in a lower but more durable induction. The differential expression of the four EguCBF1 genes under these cold regimes suggests that there is a complementary regulation. The high accumulation of the CBF transcript, observed in response to the different types of cold conditions, might be a key for the winter survival of this evergreen broad-leaved tree. PMID:19457981

  8. Persistent Na+ current modifies burst discharge by regulating conditional backpropagation of dendritic spikes.

    PubMed

    Doiron, Brent; Noonan, Liza; Lemon, Neal; Turner, Ray W

    2003-01-01

    The estimation and detection of stimuli by sensory neurons is affected by factors that govern a transition from tonic to burst mode and the frequency characteristics of burst output. Pyramidal cells in the electrosensory lobe of weakly electric fish generate spike bursts for the purpose of stimulus detection. Spike bursts are generated during repetitive discharge when a frequency-dependent broadening of dendritic spikes increases current flow from dendrite to soma to potentiate a somatic depolarizing afterpotential (DAP). The DAP eventually triggers a somatic spike doublet with an interspike interval that falls inside the dendritic refractory period, blocking spike backpropagiation and the DAP. Repetition of this process gives rise to a rhythmic dendritic spike failure, termed conditional backpropagation, that converts cell output from tonic to burst discharge. Through in vitro recordings and compartmental modeling we show that burst frequency is regulated by the rate of DAP potentiation during a burst, which determines the time required to discharge the spike doublet that blocks backpropagation. DAP potentiation is magnified through a positive feedback process when an increase in dendritic spike duration activates persistent sodium current (I(NaP)). I(NaP) further promotes a slow depolarization that induces a shift from tonic to burst discharge over time. The results are consistent with a dynamical systems analysis that shows that the threshold separating tonic and burst discharge can be represented as a saddle-node bifurcation. The interaction between dendritic K(+) current and I(NaP) provides a physiological explanation for a variable time scale of bursting dynamics characteristic of such a bifurcation.

  9. The individual mandate as healthcare regulation: what the Obama Administration should have said in NFIB v. Sebelius.

    PubMed

    Moncrieff, Abigail R

    2013-01-01

    There was an argument that the Obama Administration's lawyers could have made--but didn't--in defending Obamacare's individual mandate against constitutional attack. That argument would have highlighted the role of comprehensive health insurance in steering individuals' healthcare savings and consumption decisions. Because consumer-directed healthcare, which reaches its apex when individuals self-insure, suffers from several known market failures and because comprehensive health insurance policies play an unusually aggressive regulatory role in attempting to correct those failures, the individual mandate could be seen as an attempt to eliminate inefficiencies in the healthcare market that arise from individual decisions to self-insure. This argument would done a better job than the Obama Administration's of aligning the individual mandate with existing Commerce Clause and Necessary and Proper Clause precedent, and it would have done a better job of addressing the conservative Justices' primary concerns with upholding the mandate. This Article lays out this forgone defense of the individual mandate.

  10. Central Fos expression and conditioned flavor avoidance in rats following intragastric administration of bitter taste receptor ligands.

    PubMed

    Hao, Shuzhen; Dulake, Michelle; Espero, Elvis; Sternini, Catia; Raybould, Helen E; Rinaman, Linda

    2009-03-01

    G protein-coupled receptors that signal bitter taste (T2Rs) are expressed in the mucosal lining of the oral cavity and gastrointestinal (GI) tract. In mice, intragastric infusion of T2R ligands activates Fos expression within the caudal viscerosensory portion of the nucleus of the solitary tract (NTS) through a vagal pathway (Hao S, Sternini C, Raybould HE. Am J Physiol Regul Integr Comp Physiol 294: R33-R38, 2008). The present study was performed in rats to further characterize the distribution and chemical phenotypes of brain stem and forebrain neurons activated to express Fos after intragastric gavage of T2R ligands, and to determine a potential behavioral correlate of this central neural activation. Compared with relatively low brain stem and forebrain Fos expression in control rats gavaged intragastrically with water, rats gavaged intragastrically with T2R ligands displayed significantly increased activation of neurons within the caudal medial (visceral) NTS and caudal ventrolateral medulla, including noradrenergic neurons, and within the lateral parabrachial nucleus, central nucleus of the amygdala, and paraventricular nucleus of the hypothalamus. A behavioral correlate of this Fos activation was evidenced when rats avoided consuming flavors that previously were paired with intragastric gavage of T2R ligands. While unconditioned aversive responses to bitter tastants in the oral cavity are often sufficient to inhibit further consumption, a second line of defense may be provided postingestively by ligand-induced signaling at GI T2Rs that signal the brain via vagal sensory inputs to the caudal medulla.

  11. Ethanol conditioned place preference and alterations in ΔFosB following adolescent nicotine administration differ in rats exhibiting high or low behavioral reactivity to a novel environment.

    PubMed

    Philpot, Rex M; Engberg, Melanie E; Wecker, Lynn

    2014-04-01

    This study determined the effects of adolescent nicotine administration on adult alcohol preference in rats exhibiting high or low behavioral reactivity to a novel environment, and ascertained whether nicotine altered ΔFosB in the ventral striatum (vStr) and prefrontal cortex (PFC) immediately after drug administration or after rats matured to adulthood. Animals were characterized as exhibiting high (HLA) or low (LLA) locomotor activity in the novel open field on postnatal day (PND) 31 and received injections of saline (0.9%) or nicotine (0.56 mg free base/kg) from PND 35 to 42. Ethanol-induced conditioned place preference (CPP) was assessed on PND 68 following 8 days conditioning in a biased paradigm; ΔFosB was measured on PND 43 or PND 68. Following adolescent nicotine exposure, HLA animals demonstrated a CPP when conditioned with ethanol; LLA animals were unaffected. Further, adolescent nicotine exposure for 8 days increased levels of ΔFosB in limbic regions in both HLA and LLA rats, but this increase persisted into adulthood only in LLA animals. Results indicate that adolescent nicotine exposure facilitates the establishment of an ethanol CPP in HLA rats, and that sustained elevations in ΔFosB are not necessary or sufficient for the establishment of an ethanol CPP in adulthood. These studies underscore the importance of assessing behavioral phenotype when determining the behavioral and cellular effects of adolescent nicotine exposure.

  12. Methylphenidate self-administration and conditioned place preference in an animal model of attention-deficit hyperactivity disorder: the spontaneously hypertensive rat.

    PubMed

    dela Peńa, Ike C; Ahn, Hyung Seok; Choi, Ji Young; Shin, Chan Young; Ryu, Jong Hoon; Cheong, Jae Hoon

    2011-02-01

    The abuse potential of methylphenidate, the most commonly used drug for attention-deficit hyperactivity disorder (ADHD), has been shown in many studies. However, it is not yet known whether methylphenidate has reinforcing or rewarding effects in any animal model of ADHD. In this study, we investigated whether methylphenidate facilitates self-administration and induces conditioned place preference in the spontaneously hypertensive rat (SHR), the most validated animal model of ADHD. We also explored whether the behavioral responses of SHR differ from those of Wistar rats, the strain representing the 'normal' heterogeneous population. ADHD is highly prevalent among adolescents, such that behavioral assays should be conducted in adolescent SHR. In line with this, we carried out conditioned place preference tests in adolescent SHR and Wistar rats and observed strain and age-related differences in behavioral responses to the motivational effects of methylphenidate. Self-administration tests confirmed the reinforcing effect of methylphenidate in SHR, and showed that, in FR2 and FR3 schedules, SHR responded more to methylphenidate infusions than the Wistar rats. In conditioned place preference tests, both strains responded similarly to the rewarding effects of methylphenidate. However, it was found that adolescence also alters the euphorigenic effects of methylphenidate, most especially in SHR. The implications of these findings are discussed.

  13. [Autonomic regulation at emotional stress under hypoxic conditions in the elderly with physiological and accelerated aging: effect of hypoxic training].

    PubMed

    Os'mak, E D; Asanov, É O

    2014-01-01

    The effect of hypoxic training on autonomic regulation in psycho-emotional stress conditions in hypoxic conditions in older people with physiological (25 people) and accelerated (28 people) aging respiratory system. It is shown that hypoxic training leads to an increase in vagal activity indicators (HF) and reduced simpatovagal index (LF/HF), have a normalizing effect on the autonomic balance during stress loads in older people with different types of aging respiratory system.

  14. ERK/MAPK Regulates Hippocampal Histone Phosphorylation Following Contextual Fear Conditioning

    ERIC Educational Resources Information Center

    Levenson, Jonathan M.; Sweatt, J. David; Chwang, Wilson B.; O'Riordan, Kenneth J.

    2006-01-01

    Long-term memory formation is regulated by many distinct molecular mechanisms that control gene expression. An emerging model for effecting a stable, coordinated pattern of gene transcription involves epigenetic tagging through modifications of histones or DNA. In this study, we investigated the regulation of histone phosphorylation in the…

  15. 7 CFR 301.52-2 - Authorization for Deputy Administrator to list regulated areas and suppressive or generally...

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ..., DEPARTMENT OF AGRICULTURE DOMESTIC QUARANTINE NOTICES Pink Bollworm Quarantine and Regulations § 301.52-2... States, territories, or districts, or portions thereof, in which pink bollworm has been found or in which there is reason to believe that pink bollworm is present, or which it is deemed necessary to...

  16. 7 CFR 301.52-2 - Authorization for Deputy Administrator to list regulated areas and suppressive or generally...

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ..., DEPARTMENT OF AGRICULTURE DOMESTIC QUARANTINE NOTICES Pink Bollworm Quarantine and Regulations § 301.52-2... States, territories, or districts, or portions thereof, in which pink bollworm has been found or in which there is reason to believe that pink bollworm is present, or which it is deemed necessary to...

  17. 7 CFR 301.52-2 - Authorization for Deputy Administrator to list regulated areas and suppressive or generally...

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ..., DEPARTMENT OF AGRICULTURE DOMESTIC QUARANTINE NOTICES Pink Bollworm Quarantine and Regulations § 301.52-2... States, territories, or districts, or portions thereof, in which pink bollworm has been found or in which there is reason to believe that pink bollworm is present, or which it is deemed necessary to...

  18. 7 CFR 301.52-2 - Authorization for Deputy Administrator to list regulated areas and suppressive or generally...

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ..., DEPARTMENT OF AGRICULTURE DOMESTIC QUARANTINE NOTICES Pink Bollworm Quarantine and Regulations § 301.52-2... States, territories, or districts, or portions thereof, in which pink bollworm has been found or in which there is reason to believe that pink bollworm is present, or which it is deemed necessary to...

  19. 7 CFR 301.52-2 - Authorization for Deputy Administrator to list regulated areas and suppressive or generally...

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ..., DEPARTMENT OF AGRICULTURE DOMESTIC QUARANTINE NOTICES Pink Bollworm Quarantine and Regulations § 301.52-2... States, territories, or districts, or portions thereof, in which pink bollworm has been found or in which there is reason to believe that pink bollworm is present, or which it is deemed necessary to...

  20. 77 FR 5387 - Amendment to the Export Administration Regulations: Addition of a Reference to a Provision of the...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-02-03

    ... Regulations: Addition of a Reference to a Provision of the Iran Sanctions Act of 1996 (ISA) and Statement of... Iran Sanctions Act of 1996 (ISA), which states BIS's licensing policy for export and reexport... Amendment The Iran Sanctions Act of 1996 (50 U.S.C. 1701 note) (ISA) requires the President to...

  1. The basic leucine zipper stress response regulator Yap5 senses high-iron conditions by coordination of [2Fe-2S] clusters.

    PubMed

    Rietzschel, Nicole; Pierik, Antonio J; Bill, Eckhard; Lill, Roland; Mühlenhoff, Ulrich

    2015-01-01

    Iron is an essential, yet at elevated concentrations toxic trace element. To date, the mechanisms of iron sensing by eukaryotic iron-responsive transcription factors are poorly understood. The Saccharomyces cerevisiae transcription factor Yap5, a member of the Yap family of bZIP stress response regulators, administrates the adaptive response to high-iron conditions. Despite the central role of the iron-sensing process for cell viability, the molecule perceived by Yap5 and the underlying regulatory mechanisms are unknown. Here, we show that Yap5 senses high-iron conditions by two Fe/S clusters bound to its activator domain (Yap5-AD). The more stable iron-regulatory Fe/S cluster at the N-terminal cysteine-rich domain (n-CRD) of Yap5 is detected in vivo and in vitro. The second cluster coordinated by the C-terminal CRD can only be shown after chemical reconstitution, since it is bound in a labile fashion. Both clusters are of the [2Fe-2S] type as characterized by UV/visible (UV/Vis), circular dichroism, electron paramagnetic resonance (EPR), and Mössbauer spectroscopy. Fe/S cluster binding to Yap5-AD induces a conformational change that may activate transcription. The cluster-binding motif of the n-CRD domain is highly conserved in HapX-like transcription factors of pathogenic fungi and thus may represent a general sensor module common to many eukaryotic stress response regulators.

  2. The Basic Leucine Zipper Stress Response Regulator Yap5 Senses High-Iron Conditions by Coordination of [2Fe-2S] Clusters

    PubMed Central

    Rietzschel, Nicole; Pierik, Antonio J.; Bill, Eckhard; Mühlenhoff, Ulrich

    2014-01-01

    Iron is an essential, yet at elevated concentrations toxic trace element. To date, the mechanisms of iron sensing by eukaryotic iron-responsive transcription factors are poorly understood. The Saccharomyces cerevisiae transcription factor Yap5, a member of the Yap family of bZIP stress response regulators, administrates the adaptive response to high-iron conditions. Despite the central role of the iron-sensing process for cell viability, the molecule perceived by Yap5 and the underlying regulatory mechanisms are unknown. Here, we show that Yap5 senses high-iron conditions by two Fe/S clusters bound to its activator domain (Yap5-AD). The more stable iron-regulatory Fe/S cluster at the N-terminal cysteine-rich domain (n-CRD) of Yap5 is detected in vivo and in vitro. The second cluster coordinated by the C-terminal CRD can only be shown after chemical reconstitution, since it is bound in a labile fashion. Both clusters are of the [2Fe-2S] type as characterized by UV/visible (UV/Vis), circular dichroism, electron paramagnetic resonance (EPR), and Mössbauer spectroscopy. Fe/S cluster binding to Yap5-AD induces a conformational change that may activate transcription. The cluster-binding motif of the n-CRD domain is highly conserved in HapX-like transcription factors of pathogenic fungi and thus may represent a general sensor module common to many eukaryotic stress response regulators. PMID:25368382

  3. 42 CFR 418.116 - Condition of participation: Compliance with Federal, State, and local laws and regulations...

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 42 Public Health 3 2014-10-01 2014-10-01 false Condition of participation: Compliance with Federal, State, and local laws and regulations related to the health and safety of patients. 418.116 Section 418.116 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN...

  4. 42 CFR 418.116 - Condition of participation: Compliance with Federal, State, and local laws and regulations...

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 42 Public Health 3 2011-10-01 2011-10-01 false Condition of participation: Compliance with Federal, State, and local laws and regulations related to the health and safety of patients. 418.116 Section 418.116 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN...

  5. 7 CFR 301.52-3 - Conditions governing the interstate movement of regulated articles from quarantined States. 2

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... DOMESTIC QUARANTINE NOTICES Pink Bollworm Quarantine and Regulations § 301.52-3 Conditions governing the... present a hazard of the spread of the pink bollworm and the person in possession thereof has been so... articles has been notified by an inspector that a hazard of spread of the pink bollworm exists; or...

  6. 7 CFR 301.52-3 - Conditions governing the interstate movement of regulated articles from quarantined States. 2

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... DOMESTIC QUARANTINE NOTICES Pink Bollworm Quarantine and Regulations § 301.52-3 Conditions governing the... present a hazard of the spread of the pink bollworm and the person in possession thereof has been so... articles has been notified by an inspector that a hazard of spread of the pink bollworm exists; or...

  7. 7 CFR 301.52-3 - Conditions governing the interstate movement of regulated articles from quarantined States. 2

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... DOMESTIC QUARANTINE NOTICES Pink Bollworm Quarantine and Regulations § 301.52-3 Conditions governing the... present a hazard of the spread of the pink bollworm and the person in possession thereof has been so... articles has been notified by an inspector that a hazard of spread of the pink bollworm exists; or...

  8. 7 CFR 301.52-3 - Conditions governing the interstate movement of regulated articles from quarantined States. 2

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... DOMESTIC QUARANTINE NOTICES Pink Bollworm Quarantine and Regulations § 301.52-3 Conditions governing the... present a hazard of the spread of the pink bollworm and the person in possession thereof has been so... articles has been notified by an inspector that a hazard of spread of the pink bollworm exists; or...

  9. 7 CFR 301.52-3 - Conditions governing the interstate movement of regulated articles from quarantined States. 2

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... DOMESTIC QUARANTINE NOTICES Pink Bollworm Quarantine and Regulations § 301.52-3 Conditions governing the... present a hazard of the spread of the pink bollworm and the person in possession thereof has been so... articles has been notified by an inspector that a hazard of spread of the pink bollworm exists; or...

  10. 7 CFR 301.48-4 - Conditions governing the interstate movement of regulated articles from quarantined States.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... DOMESTIC QUARANTINE NOTICES Japanese Beetle Quarantine and Regulations § 301.48-4 Conditions governing the... threat to spread the Japanese beetle because adult beetle populations are not present; or (b) The... be free of and safeguarded against Japanese beetle; or (c) The aircraft is loaded during the hours...

  11. 7 CFR 301.48-4 - Conditions governing the interstate movement of regulated articles from quarantined States.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... DOMESTIC QUARANTINE NOTICES Japanese Beetle Quarantine and Regulations § 301.48-4 Conditions governing the... threat to spread the Japanese beetle because adult beetle populations are not present; or (b) The... be free of and safeguarded against Japanese beetle; or (c) The aircraft is loaded during the hours...

  12. 42 CFR 418.116 - Condition of participation: Compliance with Federal, State, and local laws and regulations...

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 42 Public Health 3 2012-10-01 2012-10-01 false Condition of participation: Compliance with Federal, State, and local laws and regulations related to the health and safety of patients. 418.116 Section 418.116 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN...

  13. Statistical description of wetland hydrological connectivity to the River Murray in South Australia under both natural and regulated conditions

    NASA Astrophysics Data System (ADS)

    Robinson, Sean J.; Souter, Nicholas J.; Bean, Nigel G.; Ross, Joshua V.; Thompson, Richard M.; Bjornsson, Kjartan T.

    2015-12-01

    The effect of river regulation on the connectivity of the South Australian River Murray to its floodplain wetlands was examined using unregulated 'natural' and 'regulated' river flow data simulated between the years 1895 to 2009. A sample of 185 wetlands was used to calculate a range of connectivity statistics under both simulation scenarios. These statistics summarised the timing and duration of both connection and disconnection, as well as inundated area. Wetlands ranged from being permanently inundated, connected multiple times per year due to both small fluctuations in river level and the annual flood pulse, to flooded with diminishing frequency depending on the size of the annual flood pulse and their position on the floodplain. Under the natural scenario a wide range of wetland connectivity profiles were recorded whereas under the regulated scenario wetlands tended to be either permanently inundated or infrequently flooded. Under natural conditions wetlands that required higher flow before connecting were less frequently connected and for shorter periods. Under regulated conditions a larger proportion of wetland area was permanently connected than under natural conditions, however the annual flood pulse connected a larger area of wetlands under natural conditions. The information derived from this analysis can be used to design wetland management plans for individual wetlands within a river-wide management regime restoring lost hydrological variability.

  14. Analysis 320 coal mine accidents using structural equation modeling with unsafe conditions of the rules and regulations as exogenous variables.

    PubMed

    Zhang, Yingyu; Shao, Wei; Zhang, Mengjia; Li, Hejun; Yin, Shijiu; Xu, Yingjun

    2016-07-01

    Mining has been historically considered as a naturally high-risk industry worldwide. Deaths caused by coal mine accidents are more than the sum of all other accidents in China. Statistics of 320 coal mine accidents in Shandong province show that all accidents contain indicators of "unsafe conditions of the rules and regulations" with a frequency of 1590, accounting for 74.3% of the total frequency of 2140. "Unsafe behaviors of the operator" is another important contributory factor, which mainly includes "operator error" and "venturing into dangerous places." A systems analysis approach was applied by using structural equation modeling (SEM) to examine the interactions between the contributory factors of coal mine accidents. The analysis of results leads to three conclusions. (i) "Unsafe conditions of the rules and regulations," affect the "unsafe behaviors of the operator," "unsafe conditions of the equipment," and "unsafe conditions of the environment." (ii) The three influencing factors of coal mine accidents (with the frequency of effect relation in descending order) are "lack of safety education and training," "rules and regulations of safety production responsibility," and "rules and regulations of supervision and inspection." (iii) The three influenced factors (with the frequency in descending order) of coal mine accidents are "venturing into dangerous places," "poor workplace environment," and "operator error."

  15. 36 CFR 251.14 - Conditions, rules and regulations to govern exercise of timber rights reserved in conveyance to...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... Miscellaneous Land Uses Natural Resources Control § 251.14 Conditions, rules and regulations to govern exercise... disposal shall comply with known air and water quality criteria and standards and include necessary... and maintain buildings, facilities, and other improvements, including roads needed to log the...

  16. 7 CFR 301.48-4 - Conditions governing the interstate movement of regulated articles from quarantined States.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... DOMESTIC QUARANTINE NOTICES Japanese Beetle Quarantine and Regulations § 301.48-4 Conditions governing the... threat to spread the Japanese beetle because adult beetle populations are not present; or (b) The... be free of and safeguarded against Japanese beetle; or (c) The aircraft is loaded during the hours...

  17. High endogenous estradiol is associated with enhanced cognitive emotion regulation of physiological conditioned fear responses in women.

    PubMed

    Graham, Bronwyn M; Ash, Catherine; Den, Miriam L

    2017-02-28

    The sex hormone estradiol has a modifying role in the underlying neurobiology of cognitive emotion regulation, although whether estradiol is associated with outcomes of techniques like cognitive restructuring is unknown. In the present study 34 women with regular menstrual cycles participated in a one-day differential fear conditioning procedure. Women then received cognitive restructuring training, involving the reappraisal of their initial thoughts about the conditioning procedure to reduce their emotional responses, before repeating the conditioning procedure. Endogenous estradiol levels (ascertained by a blood sample) were not associated with subjective or physiological indices of conditioned fear during the first conditioning session. Following cognitive restructuring, however, women with high estradiol exhibited significantly reduced physiological arousal in the presence of the conditioned stimulus, relative to women with low estradiol. No group differences were observed in subjective fear ratings obtained after the second conditioning procedure, although those obtained during the second habitation phase (taking place immediately following cognitive restructuring) were lower amongst high estradiol women. Progesterone was not associated with any outcomes measures. Together, these results suggest that the outcomes of cognitive emotion regulation may be enhanced during periods of naturally high estradiol.

  18. Regulation of Akt-mTOR, ubiquitin-proteasome and autophagy-lysosome pathways in response to formoterol administration in rat skeletal muscle.

    PubMed

    Joassard, Olivier Roger; Amirouche, Adel; Gallot, Yann Simon; Desgeorges, Marine Maud; Castells, Josiane; Durieux, Anne-Cécile; Berthon, Phanélie; Freyssenet, Damien Gilles

    2013-11-01

    Administration of β2-agonists triggers skeletal muscle anabolism and hypertrophy. We investigated the time course of the molecular events responsible for rat skeletal muscle hypertrophy in response to 1, 3 and 10 days of formoterol administration (i.p. 2000μg/kg/day). A marked hypertrophy of rat tibialis anterior muscle culminated at day 10. Phosphorylation of Akt, ribosomal protein S6, 4E-BP1 and ERK1/2 was increased at day 3, but returned to control level at day 10. This could lead to a transient increase in protein translation and could explain previous studies that reported increase in protein synthesis following β2-agonist administration. Formoterol administration was also associated with a significant reduction in MAFbx/atrogin-1 mRNA level (day 3), suggesting that formoterol can also affect protein degradation of MAFbx/atrogin1 targeted substrates, including MyoD and eukaryotic initiation factor-3f (eIF3-f). Surprisingly, mRNA level of autophagy-related genes, light chain 3 beta (LC3b) and gamma-aminobutyric acid receptor-associated protein-like 1 (Gabarapl1), as well as lysosomal hydrolases, cathepsin B and cathepsin L, was significantly and transiently increased after 1 and/or 3 days, suggesting that autophagosome formation would be increased in response to formoterol administration. However, this has to be relativized since the mRNA level of Unc-51-like kinase1 (Ulk1), BCL2/adenovirus E1B interacting protein3 (Bnip3), and transcription factor EB (TFEB), as well as the protein content of Ulk1, Atg13, Atg5-Atg12 complex and p62/Sqstm1 remained unchanged or was even decreased in response to formoterol administration. These results demonstrate that the effects of formoterol are mediated, in part, through the activation of Akt-mTOR pathway and that other signaling pathways become more important in the regulation of skeletal muscle mass with chronic administration of β2-agonists.

  19. Constitutive and conditional mutant mouse models for understanding dopaminergic regulation of orofacial movements: emerging insights and challenges.

    PubMed

    Tomiyama, Katsunori; Drago, John; Waddington, John L; Koshikawa, Noriaki

    2012-01-01

    Among numerous mechanisms implicated in the regulation of orofacial movements, dopamine-containing neurons have received the most extensive study. Here we review the effects of a) constitutive knockout of D(1-5) dopamine receptors and b) conditional mutations with progressive ablation of D(1) receptor-expressing cells, on the topography of spontaneous and D(1)-like agonist-induced orofacial movements. In constitutive knockouts, D(1) and D(2) exert primary roles in regulating horizontal and vertical jaw movements, respectively, in opposite directions; in contrast, both D(1) and D(2) receptors regulate tongue protrusions and incisor chattering, in the same direction. D(3) and D(5) receptors play more subtle roles in regulating orofacial movements, while D(4) receptors do not play any material role. Progressive loss of forebrain D(1) receptor-expressing cells in CamKIIa/Cre D(1)Tox mutants is associated primarily with decreases in head and vibrissae movements, while progressive loss of striatal D(1) receptor-expressing cells in DARPP-32/Cre D(1)Tox mutants is associated primarily with reductions in jaw movements and tongue protrusions but increases in head and vibrissae movements. Further application of constitutive and particularly conditional mutants may clarify further not only dopaminergic regulation of orofacial movements but also the pathophysiology of orofacial dysfunction in Huntington's disease and Parkinson's disease.

  20. Differentiation and proliferation of periosteal osteoblast progenitors are differentially regulated by estrogens and intermittent parathyroid hormone administration.

    PubMed

    Ogita, Mami; Rached, Marie Therese; Dworakowski, Elzbieta; Bilezikian, John P; Kousteni, Stavroula

    2008-11-01

    The periosteum is now widely recognized as a homeostatic and therapeutic target for actions of sex steroids and intermittent PTH administration. The mechanisms by which estrogens suppress but PTH promotes periosteal expansion are not known. In this report, we show that intermittent PTH(1-34) promotes differentiation of periosteal osteoblast precursors as evidenced by the stimulation of the expression or activity of alkaline phosphatase as well as of targets of the bone morphogenetic protein 2 (BMP-2) and Wnt pathways. In contrast, 17beta-estradiol (E2) had no effect by itself. However, it attenuated PTH- or BMP-2-induced differentiation of primary periosteal osteoblast progenitors. Administration of intermittent PTH to ovariectomized mice induced rapid phosphorylation of the BMP-2 target Smad1/5/8 in the periosteum. A replacement dose of E2 had no effect by itself but suppressed PTH-induced phosphorylation of Smad1/5/8. In contrast to its effects to stimulate periosteal osteoblast differentiation, PTH promoted and subsequently suppressed proliferation of periosteal osteoblast progenitors in vitro and in vivo. E2 promoted proliferation and attenuated the antiproliferative effect of PTH. Both hormones protected periosteal osteoblasts from apoptosis induced by various proapoptotic agents. These observations suggest that the different effects of PTH and estrogens on the periosteum result from opposing actions on the recruitment of early periosteal osteoblast progenitors. Intermittent PTH promotes osteoblast differentiation from periosteum-derived mesenchymal progenitors through ERK-, BMP-, and Wnt-dependent signaling pathways. Estrogens promote proliferation of early osteoblast progenitors but inhibit their differentiation by osteogenic agents such as PTH or BMP-2.

  1. Sex differences in nicotine self-administration in rats during progressive unit dose reduction: Implications for nicotine regulation policy

    PubMed Central

    Grebenstein, Patricia; Burroughs, Danielle; Zhang, Yan; LeSage, Mark G.

    2013-01-01

    Reducing the nicotine content in tobacco products is being considered by the FDA as a policy to reduce the addictiveness of tobacco products. Understanding individual differences in response to nicotine reduction will be critical to developing safe and effective policy. Animal and human research demonstrating sex differences in the reinforcing effects of nicotine suggests that males and females may respond differently to nicotine-reduction policies. However, no studies have directly examined sex differences in the effects of nicotine unit-dose reduction on nicotine self-administration (NSA) in animals. The purpose of the present study was to examine this issue in a rodent self-administration model. Male and female rats were trained to self-administer nicotine (0.06 mg/kg) under an FR 3 schedule during daily 23 h sessions. Rats were then exposed to saline extinction and reacquisition of NSA, followed by weekly reductions in the unit dose (0.03 to 0.00025 mg/kg) until extinction levels of responding were achieved. Males and females were compared with respect to baseline levels of intake, resistance to extinction, degree of compensatory increases in responding during dose reduction, and the threshold reinforcing unit dose of nicotine. Exponential demand-curve analysis was also conducted to compare the sensitivity of males and females to increases in the unit price (FR/unit dose) of nicotine (i.e., elasticity of demand or reinforcing efficacy). Females exhibited significantly higher baseline intake and less compensation than males. However, there were no sex differences in the reinforcement threshold or elasticity of demand. Dose–response relationships were very well described by the exponential demand function (r2 values > 0.96 for individual subjects). These findings suggest that females may exhibit less compensatory smoking in response to nicotine reduction policies, even though their nicotine reinforcement threshold and elasticity of demand may not differ from

  2. Administrators: Nursing Home Administrator

    ERIC Educational Resources Information Center

    Kahl, Anne

    1976-01-01

    Responsibilities, skills needed, training needed, earnings, employment outlook, and sources of additional information are outlined for the administrator who holds the top management job in a nursing home. (JT)

  3. Regulation of Pleiotrophin, Midkine, Receptor Protein Tyrosine Phosphatase β/ζ, and Their Intracellular Signaling Cascades in the Nucleus Accumbens During Opiate Administration

    PubMed Central

    Laorden, María Luisa; Milanés, María Victoria

    2016-01-01

    Background: Most classes of addictive substances alter the function and structural plasticity of the brain reward circuitry. Midkine (MK) and pleiotrophin (PTN) are growth/differentiation cytokines which, similarly to neurotrophins, play an important role in repair, neurite outgrowth, and cell differentiation. PTN or MK signaling through receptor protein tyrosine phosphatase β/ζ (RPTPβ/ζ), leads to the activation of extracellular signal-regulated kinases and thymoma viral proto-oncogene. This activation induces morphological changes and modulates addictive behaviors. Besides, there is increasing evidence that during the development of drug addiction, astrocytes contribute to the synaptic plasticity by synthesizing and releasing substances such as cytokines. Methods: In the present work we studied the effect of acute morphine administration, chronic morphine administration, and morphine withdrawal on PTN, MK, and RPTPβ/ζ expression and on their signaling pathways in the nucleus accumbens. Results: Present results indicated that PTN, MK, and RPTPβ/ζ levels increased after acute morphine injection, returned to basal levels during chronic opioid treatment, and were up-regulated again during morphine withdrawal. We also observed an activation of astrocytes after acute morphine injection and during opiate dependence and withdrawal. In addition, immunofluorescence analysis revealed that PTN, but not MK, was overexpressed in astrocytes and that dopaminoceptive neurons expressed RPTPβ/ζ. Conclusions: All these observations suggest that the neurotrophic and behavioral adaptations that occur during opiate addiction could be, at least partly, mediated by cytokines. PMID:26164717

  4. Growth Regulator Herbicides Prevent Invasive Annual grass Seed Production Under Field Conditions

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Growth regulator herbicides, such as 2,4-D, dicamba, picloram, and aminopyralid, are commonly used to control broadleaf weeds in grasslands, non-croplands and cereal crops (e.g. wheat, barley). If applied to cereals at late growth stages, while the grasses are developing reproductive parts, the her...

  5. 49 CFR 171.22 - Authorization and conditions for the use of international standards and regulations.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... and the transportation in commerce of hazardous materials in accordance with the International Civil... international transport standards and regulations authorized in paragraph (a) of this section (e.g., paragraph 1... transported in the United States in full compliance (i.e., packaged, marked, labeled, classed,...

  6. microRNAs and the regulation of neuronal plasticity under stress conditions.

    PubMed

    Schouten, M; Aschrafi, A; Bielefeld, P; Doxakis, E; Fitzsimons, C P

    2013-06-25

    In the brain, the connection between sensory information triggered by the presence of a stressor and the organism's reaction involves limbic areas such as the hippocampus, amygdala and prefrontal cortex. Consequently, these brain regions are the most sensitive to stress-induced changes in neuronal plasticity. However, the specific effects of stress on neuronal plasticity in these regions largely differ. Despite these regional differences, in many cases the steps leading to brain adaptation to stress involve highly coordinated changes in gene expression affecting cell metabolism, neuronal plasticity and synaptic transmission. In adult life the effects of stress on neuronal plasticity are largely reversible but stress in early life induces persistent changes in neuronal plasticity that increases vulnerability to develop psychopathologies and aging-related cognitive decline, suggesting the involvement of epigenetic mechanisms. A growing body of evidence demonstrates that microRNAs (miRs) are key players in epigenetic regulation. In this forefront review we present a critical look on the literature demonstrating the regulation of neuronal plasticity by miRs and the molecular mechanisms of target specificity in neurons. We propose that further progress in the identification of miR's function beyond single target identification would require a combination of developmental expression studies, bioinformatics and a deeper understanding of large networks of targets involved in epigenetic regulation. This will help to extend our understanding of the role miRs play in the regulation of stress-induced neuronal plasticity.

  7. The effect of active and passive intravenous cocaine administration on the extracellular signal-regulated kinase (ERK) activity in the rat brain.

    PubMed

    Miszkiel, Joanna; Detka, Jan; Cholewa, Joanna; Frankowska, Małgorzata; Nowak, Ewa; Budziszewska, Bogusława; Przegaliński, Edmund; Filip, Małgorzata

    2014-08-01

    According to a current hypothesis of learning processes, recent papers pointed out to an important role of the extracellular signal-regulated kinase (ERK), in drug addiction. We employed the Western blotting techniques to examine the ERK activity immediately after cocaine iv self-administration and in different drug-free withdrawal periods in rats. To distinguish motivational vs. pharmacological effects of the psychostimulant intake, a "yoked" procedure was used. Animals were decapitated after 14 daily cocaine self-administration sessions or on the 1st, 3rd or 10th extinction days. At each time point the activity of the ERK was assessed in several brain structures, including the prefrontal cortex, hippocampus, dorsal striatum and nucleus accumbens. Passive, repeated iv cocaine administration resulted in a 45% increase in ERK phosphorylation in the hippocampus while cocaine self-administration did not change brain ERK activity. On the 1st day of extinction, the activity of the ERK in the prefrontal cortex was decreased in rats with a history of cocaine chronic intake: by 66% for "active" cocaine group and by 35% for "yoked" cocaine group. On the 3rd day the reduction in the ERK activity (25-34%) was observed in the hippocampus for both cocaine-treated groups, and also in the nucleus accumbens for "yoked" cocaine group (40%). On the 10th day of extinction there was no significant alteration in ERK activity in any group of rats. Our findings suggest that cortical ERK is involved in cocaine seeking behavior in rats. They also indicate the time and regional adaptations in this enzyme activity after cocaine withdrawal.

  8. Muscarinic receptor plasticity in the brain of senescent rats: down-regulation after repeated administration of diisopropyl fluorophosphate

    SciTech Connect

    Pintor, A.; Fortuna, S.; Volpe, M.T.; Michalek, H.

    1988-01-01

    Potential age-related differences in the response of Fischer 344 rats to subchronic treatment with diisopropylfluorophosphate (DFP) were evaluated in terms of brain cholinesterase (ChE) inhibition and muscarinic receptor sites. Male 3- and 24-month old rats were sc injected with sublethal doses of DFP for 2 weeks and killed 48 hrs after the last treatment. In the cerebral cortex, hippocampus and striatum of control rats a significant age-related reduction of ChE and of maximum number of /sup 3/H-QNB binding sites (Bmax) was observed. The administration of DFP to senescent rats resulted in more pronounced and longer lasting syndrome of cholinergic stimulation, with marked body weight loss and 60% mortality. The percentage inhibition of brain ChE induced by DFP did not differ between young and senescent rats. As expected, in young rats DFP caused a significant decrease of Bmax, which in the cerebral cortex reached about 40%. In the surviving senescent rats, the percentage decrease of Bmax due to DFP with respect to age-matched controls was very similar to that of young animals, especially in the cerebral cortex. Thus there is great variability in the response of aged rats to DFP treatment, from total failure of adaptive mechanisms resulting in death to considerable muscarinic receptor plasticity.

  9. Extended access to methamphetamine self-administration up-regulates dopamine transporter levels 72 hours after withdrawal in rats.

    PubMed

    D'Arcy, Christina; Luevano, Joe E; Miranda-Arango, Manuel; Pipkin, Joseph A; Jackson, Jonathan A; Castañeda, Eddie; Gosselink, Kristin L; O'Dell, Laura E

    2016-01-01

    Previous studies have demonstrated that there are persistent changes in dopamine systems following withdrawal from methamphetamine (METH). This study examined changes in striatal dopamine transporter (DAT), tyrosine hydroxylase (TH) and dopamine receptor 2 (D2) 72 h after withdrawal from METH intravenous self- administration (IVSA). Rats were given limited (1h) or extended (6h) access to METH IVSA (0.05 mg/kg/0.1 ml infusion) for 22 days. Controls did not receive METH IVSA. The rats given extended access to IVSA displayed higher METH intake during the first hour of drug access compared to rats given limited access. Extended access to METH also produced a concomitant increase in striatal DAT levels relative to drug-naïve controls. There were no changes in TH or D2 levels across groups. Previous studies have reported a decrease in striatal DAT levels during protracted periods (>7 days) of withdrawal from METH IVSA. This study extends previous work by showing an increase in striatal DAT protein expression during an earlier time point of withdrawal from this drug. These results are an important step toward understanding the dynamic changes in dopamine systems that occur during different time points of withdrawal from METH IVSA.

  10. Effects of intraperitoneal administration of the GABA B receptor agonist baclofen on food intake in rats measured under different feeding conditions.

    PubMed

    Ebenezer, Ivor S; Patel, Sunit M

    2011-02-25

    The effects of intraperitoneal (i.p.) administration of the GABA(B) receptor agonist baclofen were assessed in rats under different feeding conditions. In Experiment 1, it was observed that baclofen (1-4 mg/kg) significantly (at least, P<0.05) increased cumulative food intake in non-deprived rats during the 120 min measurement period during the early light phase of the light-dark cycle. By contrast, during the early dark phase of the light-dark cycle in non-deprived rats, the 1mg/kg doses of baclofen significantly increased cumulative feeding at 30, 60 and 120 min (at least P<0.05), the 2mg/kg dose significantly increased feeding at 30 and 60 min (at least P<0.05) and the 4 mg/kg dose had no effects on feeding. In Experiment 2, baclofen (1-4 mg/kg) was found to produce no significant effects on food intake in rats that were food-deprived for 22 h. In Experiment 3, the effects of baclofen were investigated on food intake in 16 h food-deprived rats that had received an oral preload for 2h prior to drug administration. Baclofen (1-4 mg/kg) significantly increased cumulative food consumption (at least, P<0.05) only during the first 30 min after administration in these animals. The results of this study indicate that the effects of baclofen on food intake may be related to the state of hunger or satiety of the animals and the time during the light-dark cycle when the drug is administered.

  11. Conditional knockdown of target gene expression by tetracycline regulated transcription of double strand RNA.

    PubMed

    Hou, Xubin; Omi, Minoru; Harada, Hidekiyo; Ishii, Shunsuke; Takahashi, Yoshiko; Nakamura, Harukazu

    2011-01-01

    In vivo electroporation has served as an effective tool for the study of developmental biology. Here we report tetracycline inducible gene knockdown by electroporation. Our system consists of genome integration of a cassette encoding long double strand RNA (dsRNA) of a gene of interest by electroporation, transcription of which is assured by RNA polymerase II, and induction of transcription of dsRNA by tetracyclin. Long dsRNA decapped by ribozyme in the cassette and without poly A tail is processed into siRNA within nuclei. We could successfully induce knockdown of En2 and Coactosin by Dox administration.

  12. Employee Retirement Income Security Act of 1974; rules and regulations for administration and enforcement; claims procedure--Department of Labor. Notice of proposed rulemaking.

    PubMed

    1998-09-09

    This document contains a proposed regulation revising the minimum requirements for benefit claims procedures of employee benefit plans covered by Title I of the Employee Retirement Income Security Act of 1974 (ERISA or the Act). This proposed regulation would establish new standards for the processing of group health disability, pension, and other employee benefit plan claims filed by participants and beneficiaries. In the case of group health plans, as well as certain plans providing disability benefits, the new standards are intended to ensure more timely benefit determinations, improved access to information on which a benefit determination is made, and greater assurance that participants and beneficiaries will be afforded a full and fair review of denied claims. If adopted as final, the proposed regulation would affect participants and beneficiaries of employee benefit plans, plan, fiduciaries, and others who assist in the provision of plan benefits, such as third-party benefits administrators and health service providers or health maintenance organizations that provide benefits to participants and beneficiaries of employee benefit plans.

  13. 7 CFR 201.3 - Administrator.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing Practices), DEPARTMENT OF AGRICULTURE (CONTINUED) FEDERAL SEED ACT FEDERAL SEED ACT REGULATIONS Administration § 201.3 Administrator. The Administrator of the Agricultural Marketing Service...

  14. IRF5 is a novel regulator of CXCL13 expression in breast cancer that regulates CXCR5(+) B- and T-cell trafficking to tumor-conditioned media.

    PubMed

    Pimenta, Erica Maria; De, Saurav; Weiss, Ryan; Feng, Di; Hall, Kelly; Kilic, Sarah; Bhanot, Gyan; Ganesan, Shridar; Ran, Sophia; Barnes, Betsy J

    2015-01-01

    Clinical studies using prognostic and predictive signatures have shown that an immune signal emanating from whole tumors reflects the level of immune cell infiltration--a high immune signal linked to improved outcome. Factors regulating immune cell trafficking to the tumor, however, are not known. Previous work has shown that expression of interferon regulatory factor 5 (IRF5), a critical immune regulator, is lost in ~80% of invasive ductal carcinomas examined. We postulated that IRF5-positive and -negative breast tumors would differentially regulate immune cell trafficking to the tumor. Using a focused tumor inflammatory array, differences in cytokine and chemokine expression were examined between IRF5-positive and -negative MDA-MB-231 cells grown in three-dimensional culture. A number of cytokines/chemokines were found to be dysregulated between cultures. CXCL13 was identified as a direct target of IRF5 resulting in the enhanced recruitment of B and T cells to IRF5-positive tumor-conditioned media. The ability of IRF5 to regulate mediators of cell migration was confirmed by enzyme-linked immunosorbent assay, chromatin immunoprecipitation assay, small interfering RNA knockdown and immunofluorescence staining of human breast tumor tissues. Analysis of primary immune cell subsets revealed that IRF5 specifically recruits CXCR5(+) B and T cells to the tumor; CXCR5 is the receptor for CXCL13. Analysis of primary breast tumor tissues revealed a significant correlation between IRF5 and CXCL13 expression providing clinical relevance to the study. Together, these data support that IRF5 directly regulates a network of genes that shapes a tumor immune response and may, in combination with CXCL13, serve as a novel prognostic marker for antitumor immunity.

  15. Temperature conditions and heat supply of apartments in an apartment house with individual regulators

    NASA Astrophysics Data System (ADS)

    Danilevskii, L. N.

    2011-03-01

    This paper presents the results of mathematical modeling of the values of the temperature and the heat source power in apartments of an apartment house with individual regulators. It has been shown that for the existing structures of buildings the heat transfer between apartments with individual thermoregulation strongly influences the values of the heat source power established in apartments in the process of regulation. Without changing the total heating load of the building, this process leads to considerable deviations of readings of the thermal energy meters in apartments from the thermal energy actually consumed for their heating. This fact throws doubt upon the expediency of installing individual calorimeters in an apartment house with thermoregulation in each apartment.

  16. Light-dark condition regulates sirtuin mRNA levels in the retina.

    PubMed

    Ban, Norimitsu; Ozawa, Yoko; Inaba, Takaaki; Miyake, Seiji; Watanabe, Mitsuhiro; Shinmura, Ken; Tsubota, Kazuo

    2013-11-01

    Sirtuins (Sirt1-7) are nicotinamide adenine dinucleotide (NAD)-dependent protein deacetylases/ADP-ribosyltransferases that modulate many metabolic responses affecting aging. Sirtuins expressed in tissues and organs involved in systemic metabolism have been extensively studied. However, the characteristics of sirtuins in the retina, where local energy expenditure changes dynamically in response to light stimuli, are largely unknown. Here we analyzed sirtuin mRNA levels by real-time PCR, and found that all seven sirtuins are highly expressed in the retina compared with other tissues, such as liver. We then analyzed the sirtuin mRNA profiles in the retina over time, under a 12-h light/12-h dark cycle (LD condition) and in constant darkness (DD condition). All seven sirtuins showed significant daily variation under the LD condition, with all except Sirt6 being increased in the dark phase. The expression patterns were different under the DD condition, suggesting that sirtuin mRNA levels except Sirt6 are affected by light-dark condition. These findings were not obtained in the brain and liver. In addition, the mRNA expression patterns of Nicotinamide phosphoribosyltransferase (Nampt), peroxisome proliferator-activated receptor gamma coactivator (PGC1α), and transcription factor A, mitochondrial (Tfam) in the retina, were similar to those of the sirtuins except Sirt6. Our observations provide new insights into the metabolic mechanisms of the retina and the sirtuins' regulatory systems.

  17. Intrahippocampal administration of D2 but not D1 dopamine receptor antagonist suppresses the expression of conditioned place preference induced by morphine in the ventral tegmental area.

    PubMed

    Haghparast, Abbas; Esmaeili, Mohammad-Hossein; Taslimi, Zahra; Kermani, Mojtaba; Yazdi-Ravandi, Saeid; Alizadeh, Amir-Mohammad

    2013-04-29

    The ventral tegmental area (VTA) as a major source of dopamine neurons projecting to cortical and limbic regions has a crucial role in reward and addiction. The current study assessed the role of D1 and D2 receptors within the dorsal hippocampus (CA1) in the expression of conditioned place preference (CPP) by intra-VTA morphine in the rats. In the present study, 160 adult male albino Wistar rats weighing 220-290g were bilaterally implanted by two cannulae into the CA1 and VTA. The CPP paradigm was done and animal displacement, conditioning score and locomotor activity were recorded. For blocking the dopamine D1/D2 receptors in the dorsal hippocampus, SCH23390 (0.02, 0.05, 0.2 and 0.5μg per side) or sulpiride (0.25, 0.75, 1.5 and 3μg per side) were microinjected into the CA1, just 5min before the CPP test on the post-conditioning day. All animals received intra-VTA morphine (1μg per side) during 3-days conditioning phase. Our results showed that sulpiride (1.5 and 3μg) but not SCH23390 in the dorsal hippocampus significantly decreased the expression of CPP induced by intra-VTA morphine (p<0.001). Intra-CA1 administration of these antagonists alone, in all doses, could not induce CPP. We suggest that D2 receptors in the CA1 region of hippocampus have a key role in the expression of CPP induced by morphine at the level of the VTA and there is a relationship between dopaminergic D2 receptors and opioidergic systems in these areas in reward circuit.

  18. Influence of sedentary versus physically active conditions on regulation of plasma renin activity and vasopressin.

    PubMed

    Mueller, Patrick J

    2008-09-01

    Physical inactivity is an independent risk factor for cardiovascular disease. Sedentary animals compared to physically active controls exhibit enhanced sympathoexcitatory responses, including arterial baroreflex-mediated sympathoexcitation. Hypotension-induced sympathoexcitation is also associated with the release of vasoactive hormones. We hypothesized that sedentary conditions may enhance release of the vasoactive hormones AVP and ANG II. To test this hypothesis, the humoral response to hypotension was examined in conscious rats after 9-12 wk of sedentary conditions or "normally active" conditions. Normally active conditions were produced by allowing rats access to running wheels in their home cages. Running distance peaked after 4 wk (4.5 +/- 0.7 km/day), and the total distance run after 9 wk was 174 +/- 23 km (n = 25). Similar levels of hypotension were induced in conscious sedentary or physically active animals with the arterial vasodilator, diazoxide (25 mg/kg iv). Control experiments used a saline injection of equivalent volume. Plasma samples were collected and assayed for plasma AVP concentration and plasma renin activity (PRA). Sedentary conditions significantly enhanced resting and hypotension-induced PRA relative to normal physical activity. In contrast, resting and hypotension-induced AVP levels were not statistically different between groups. These data suggest that baroreflex-mediated activation of the renin-angiotensin system, but not AVP secretion, is enhanced by sedentary conditions. We speculate that augmented activation of the renin-angiotensin system may be related to enhanced sympathetic outflow observed in sedentary animals and may contribute to increased risk of cardiovascular disease in the sedentary population.

  19. The Natural Antimicrobial Enzyme Lysozyme is Up-Regulated in Gastrointestinal Inflammatory Conditions

    PubMed Central

    Rubio, Carlos A.

    2014-01-01

    The cells that line the mucosa of the human gastrointestinal tract (GI, that is, oral cavity, oesophagus, stomach, small intestine, large intestine, and rectum) are constantly challenged by adverse micro-environmental factors, such as different pH, enzymes, and bacterial flora. With exception of the oral cavity, these microenvironments also contain remnant cocktails of secreted enzymes and bacteria from upper organs along the tract. The density of the GI bacteria varies, from 103/mL near the gastric outlet, to 1010/mL at the ileocecal valve, to 1011 to 1012/mL in the colon. The total microbial population (ca. 1014) exceeds the total number of cells in the tract. It is, therefore, remarkable that despite the prima facie inauspicious mixture of harmful secretions and bacteria, the normal GI mucosa retains a healthy state of cell renewal. To counteract the hostile microenvironment, the GI epithelia react by speeding cell exfoliation (the GI mucosa has a turnover time of two to three days), by increasing peristalsis, by eliminating bacteria through secretion of plasma cell-immunoglobulins and by increasing production of natural antibacterial compounds, such as defensin-5 and lysozyme. Only recently, lysozyme was found up-regulated in Barrett’s oesophagitis, chronic gastritis, gluten-induced atrophic duodenitis (coeliac disease), collagenous colitis, lymphocytic colitis, and Crohn’s colitis. This up-regulation is a response directed to the special types of bacteria recently detected in these diseases. The aim of lysozyme up-regulation is to protect individual mucosal segments to chronic inflammation. The molecular mechanisms connected to the crosstalk between the intraluminal bacterial flora and the production of lysozyme released by the GI mucosae, are discussed. Bacterial resistance continues to exhaust our supply of commercial antibiotics. The potential use of lysozyme to treat infectious diseases is receiving much attention. PMID:25437608

  20. Impaired Behavior Regulation under Conditions of Concurrent Variable Schedules of Reinforcement in Children with ADHD

    ERIC Educational Resources Information Center

    Taylor, David; Lincoln, Alan J.; Foster, Sharon L.

    2010-01-01

    Objective: To bridge theory of response inhibition and learning in children with ADHD. Method: Thirty ADHD and 30 non-ADHD children (ages 9-12) were compared under concurrent variable interval (VI-15 sec., VI-30 sec. and VI- 45 sec.) reinforcement schedules that required the child to switch between the three schedules under conditions of…

  1. Host physiological condition regulates parasitic plant performance: Arceuthobium vaginatum subsp. cryptopodum on Pinus ponderosa.

    PubMed

    Bickford, Christopher P; Kolb, Thomas E; Geils, Brian W

    2005-12-01

    Much research has focused on effects of plant parasites on host-plant physiology and growth, but little is known about effects of host physiological condition on parasite growth. Using the parasitic dwarf mistletoe Arceuthobium vaginatum subsp. cryptopodum (Viscaceae) and its host Pinus ponderosa, we investigated whether changes in host physiological condition influenced mistletoe shoot development in northern Arizona forests. We conducted two studies in two consecutive years and used forest thinning (i.e., competitive release) to manipulate host physiological condition. We removed dwarf mistletoe shoots in April, before the onset of the growing season, and measured the amount of regrowth in the first season after forest thinning (Study I: n=38 trees; Study II: n=35 trees). Thinning increased tree uptake of water and carbon in both studies, but had no effect on leaf N concentration or delta13C. Mistletoe shoot growth was greater on trees with high uptake of water and carbon in thinned stands than trees with low uptake in unthinned stands. These findings show that increased resource uptake by host trees increases resources to these heterotrophic dwarf mistletoes, and links mistletoe performance to changes in host physiological condition.

  2. Hedonic and Nucleus Accumbens Neural Responses to a Natural Reward Are Regulated by Aversive Conditioning

    ERIC Educational Resources Information Center

    Roitman, Mitchell F.; Wheeler, Robert A.; Tiesinga, Paul H. E.; Roitman, Jamie D.; Carelli, Regina M.

    2010-01-01

    The nucleus accumbens (NAc) plays a role in hedonic reactivity to taste stimuli. Learning can alter the hedonic valence of a given stimulus, and it remains unclear how the NAc encodes this shift. The present study examined whether the population response of NAc neurons to a taste stimulus is plastic using a conditioned taste aversion (CTA)…

  3. LORETA Neurofeedback in the Precuneus: Operant Conditioning in Basic Mechanisms of Self-Regulation.

    PubMed

    Cannon, Rex L; Baldwin, Debora R; Diloreto, Dominic J; Phillips, Sherman T; Shaw, Tiffany L; Levy, Jacob J

    2014-10-01

    Low-resolution brain electomagnetic tomography (LORETA) neurofeedback provides a mechanism to influence the electrical activity of the brain in intracranial space. The aim of this study was to determine the effects of LORETA neurofeedback (LNFB) in the precuneus as a mechanism for improving self-regulation in controls and a heterogeneous diagnostic group (DX). Thirteen participants completed between 10 and 20 sessions of LNFB training in a 3-voxel cluster in the left precuneus. The participants included 5 nonclinical university students, and 8 adults with heterogeneous psychiatric diagnoses. We assessed the effects of LNFB with neurophysiological measures as well as pre- and post-Personality Assessment Inventory (PAI) subscales and selected subtests from the Delis-Kaplan Executive Function System (DKEFS). There was a significant total relative power increase at the precuneus for baseline contrasts for the control group. The DX group did not reach significant levels. All participants showed improvements in executive functions and tended to report significantly less psychopathology. The basic neural mechanisms of self-regulation are poorly understood. The data obtained in this study demonstrate that LNFB in a heterogeneous population enhances executive functions while concordantly decreasing endorsement of psychological symptoms. The alpha frequency in the brain may represent integrative functioning relative to operant efficiency and self-regulatory mechanisms.

  4. Silicon: a duo synergy for regulating crop growth and hormonal signaling under abiotic stress conditions.

    PubMed

    Kim, Yoon-Ha; Khan, Abdul Latif; Lee, In-Jung

    2016-12-01

    Abiotic stresses, such as salinity, heavy metals and drought, are some of the most devastating factors hindering sustainable crop production today. Plants use their own defensive strategies to cope with the adverse effects of these stresses, via the regulation of the expression of essential phytohormones, such as gibberellins (GA), salicylic acid (SA), jasmonates (JA), abscisic acid (ABA) and ethylene (ET). However, the efficacy of the endogenous defensive arsenals of plants often falls short if the stress persists over an extended period. Various strategies are developed to improve stress tolerance in plants. For example, silicon (Si) is widely considered to possess significant potential as a substance which ameliorate the negative effects of abiotic stresses, and improves plant growth and biomass accumulation. This review aims to explain how Si application influences the signaling of the endogenous hormones GA, SA, ABA, JA and ET during salinity, wounding, drought and metal stresses in crop plants. Phytohormonal cross talk plays an important role in the regulation of induced defences against stress. However, detailed molecular and proteomic research into these interactions is needed in order to identify the underlying mechanisms of stress tolerance that is imparted by Si application and uptake.

  5. Punctual Transcriptional Regulation by the Rice Circadian Clock under Fluctuating Field Conditions[OPEN

    PubMed Central

    Matsuzaki, Jun; Kawahara, Yoshihiro; Izawa, Takeshi

    2015-01-01

    Plant circadian clocks that oscillate autonomously with a roughly 24-h period are entrained by fluctuating light and temperature and globally regulate downstream genes in the field. However, it remains unknown how punctual internal time produced by the circadian clock in the field is and how it is affected by environmental fluctuations due to weather or daylength. Using hundreds of samples of field-grown rice (Oryza sativa) leaves, we developed a statistical model for the expression of circadian clock-related genes integrating diurnally entrained circadian clock with phase setting by light, both responses to light and temperature gated by the circadian clock. We show that expression of individual genes was strongly affected by temperature. However, internal time estimated from expression of multiple genes, which may reflect transcriptional regulation of downstream genes, is punctual to 22 min and not affected by weather, daylength, or plant developmental age in the field. We also revealed perturbed progression of internal time under controlled environment or in a mutant of the circadian clock gene GIGANTEA. Thus, we demonstrated that the circadian clock is a regulatory network of multiple genes that retains accurate physical time of day by integrating the perturbations on individual genes under fluctuating environments in the field. PMID:25757473

  6. NMDA receptors regulate nicotine-enhanced brain reward function and intravenous nicotine self-administration: Role of the ventral tegmental area and central nucleus of the amygdala

    PubMed Central

    Kenny, Paul J.; Chartoff, Elena; Roberto, Marisa; Carlezon, William A.; Markou, Athina

    2009-01-01

    Nicotine is considered an important component of tobacco responsible for the smoking habit in humans. Nicotine increases glutamate-mediated transmission throughout brain reward circuitries. This action of nicotine could potentially contribute to its intrinsic rewarding and reward-enhancing properties, which motivate consumption of the drug. Here we show that the competitive N-methyl-D-aspartate (NMDA) receptor antagonist LY235959 (0.5–2.5 mg/kg) abolished nicotine-enhanced brain reward function, reflected in blockade of the lowering of intracranial self-stimulation (ICSS) thresholds usually observed after experimenter-administered (0.25 mg/kg) or intravenously self-administered (0.03 mg/kg/infusion) nicotine injections. The highest LY235959 dose (5 mg/kg) tested reversed the hedonic valence of nicotine from positive to negative, reflected in nicotine-induced elevations of ICSS thresholds. LY235959 doses that reversed nicotine-induced lowering of ICSS thresholds also markedly decreased nicotine self-administration without altering responding for food reinforcement, whereas the α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor antagonist NBQX had no effects on nicotine intake. In addition, nicotine self-administration upregulated NMDA receptor subunit expression in the central nucleus of the amygdala (CeA) and ventral tegmental area (VTA), suggesting important interactions between nicotine and the NMDA receptor. Furthermore, nicotine (1 μM) increased NMDA receptor-mediated excitatory postsynaptic currents (EPSCs) in rat CeA slices, similar to its previously described effects in the VTA. Finally, infusion of LY235959 (0.1–10 ng/side) into the CeA or VTA decreased nicotine self-administration. Taken together, these data suggest that NMDA receptors, including those in the CeA and VTA, gate the magnitude and valence of the effects of nicotine on brain reward systems, thereby regulating motivation to consume the drug. PMID:18418357

  7. Valsartan independent of AT₁ receptor inhibits tissue factor, TLR-2 and -4 expression by regulation of Egr-1 through activation of AMPK in diabetic conditions.

    PubMed

    Ha, Yu Mi; Park, Eun Jung; Kang, Young Jin; Park, Sang Won; Kim, Hye Jung; Chang, Ki Churl

    2014-10-01

    Patients suffering from diabetes mellitus (DM) are at a severe risk of atherothrombosis. Early growth response (Egr)-1 is well characterized as a central mediator in vascular pathophysiology. We tested whether valsartan independent of Ang II type 1 receptor (AT1R) can reduce tissue factor (TF) and toll-like receptor (TLR)-2 and -4 by regulating Egr-1 in THP-1 cells and aorta in streptozotocin-induced diabetic mice. High glucose (HG, 15 mM) increased expressions of Egr-1, TF, TLR-2 and -4 which were significantly reduced by valsartan. HG increased Egr-1 expression by activation of PKC and ERK1/2 in THP-1 cells. Valsartan increased AMPK phosphorylation in a concentration and time-dependent manner via activation of LKB1. Valsartan inhibited Egr-1 without activation of PKC or ERK1/2. The reduced expression of Egr-1 by valsartan was reversed by either silencing Egr-1, or compound C, or DN-AMPK-transfected cells. Valsartan inhibited binding of NF-κB and Egr-1 to TF promoter in HG condition. Furthermore, valsartan reduced inflammatory cytokine (TNF-α, IL-6 and IL-1β) production and NF-κB activity in HG-activated THP-1 cells. Interestingly, these effects of valsartan were not affected by either silencing AT1R in THP-1 cells or CHO cells, which were devoid of AT1R. Importantly, administration of valsartan (20 mg/kg, i.p) for 8 weeks significantly reduced plasma TF activity, expression of Egr-1, TLR-2, -4 and TF in thoracic aorta and improved glucose tolerance of streptozotocin-induced diabetic mice. Taken together, we concluded that valsartan may reduce atherothrombosis in diabetic conditions through AMPK/Egr-1 regulation.

  8. Music Regulators in Two String Quartets: A Comparison of Communicative Behaviors between Low- and High-Stress Performance Conditions.

    PubMed

    Biasutti, Michele; Concina, Eleonora; Wasley, David; Williamon, Aaron

    2016-01-01

    In ensemble performances, group members use particular bodily behaviors as a sort of "language" to supplement the lack of verbal communication. This article focuses on music regulators, which are defined as signs to other group members for coordinating performance. The following two music regulators are considered: body gestures for articulating attacks (a set of movements externally directed that are used to signal entrances in performance) and eye contact. These regulators are recurring observable behaviors that play an important role in non-verbal communication among ensemble members. To understand how they are used by chamber musicians, video recordings of two string quartet performances (Quartet A performing Bartók and Quartet B performing Haydn) were analyzed under two conditions: a low stress performance (LSP), undertaken in a rehearsal setting, and a high stress performance (HSP) during a public recital. The results provide evidence for more emphasis in gestures for articulating attacks (i.e., the perceived strength of a performed attack-type body gesture) during HSP than LSP. Conversely, no significant differences were found for the frequency of eye contact between HSP and LSP. Moreover, there was variability in eye contact during HSP and LSP, showing that these behaviors are less standardized and may change according to idiosyncratic performance conditions. Educational implications are discussed for improving interpersonal communication skills during ensemble performance.

  9. Music Regulators in Two String Quartets: A Comparison of Communicative Behaviors between Low- and High-Stress Performance Conditions

    PubMed Central

    Biasutti, Michele; Concina, Eleonora; Wasley, David; Williamon, Aaron

    2016-01-01

    In ensemble performances, group members use particular bodily behaviors as a sort of “language” to supplement the lack of verbal communication. This article focuses on music regulators, which are defined as signs to other group members for coordinating performance. The following two music regulators are considered: body gestures for articulating attacks (a set of movements externally directed that are used to signal entrances in performance) and eye contact. These regulators are recurring observable behaviors that play an important role in non-verbal communication among ensemble members. To understand how they are used by chamber musicians, video recordings of two string quartet performances (Quartet A performing Bartók and Quartet B performing Haydn) were analyzed under two conditions: a low stress performance (LSP), undertaken in a rehearsal setting, and a high stress performance (HSP) during a public recital. The results provide evidence for more emphasis in gestures for articulating attacks (i.e., the perceived strength of a performed attack-type body gesture) during HSP than LSP. Conversely, no significant differences were found for the frequency of eye contact between HSP and LSP. Moreover, there was variability in eye contact during HSP and LSP, showing that these behaviors are less standardized and may change according to idiosyncratic performance conditions. Educational implications are discussed for improving interpersonal communication skills during ensemble performance. PMID:27610089

  10. Retinal proteins associated with redox regulation and protein folding play central roles in response to high glucose conditions.

    PubMed

    Wang, Ssu-Han; Lee, Wen-Chi; Chou, Hsiu-Chuan

    2015-03-01

    Diabetic retinopathy typically causes poor vision and blindness. A previous study revealed that a high blood glucose concentration induces glycoxidation and weakens the retinal capillaries. Nevertheless, the molecular mechanisms underlying the effects of high blood glucose induced diabetic retinopathy remain to be elucidated. In the present study, we cultured the retinal pigmented epithelial cell line ARPE-19 in mannitol-balanced 5.5, 25, and 100 mM glucose media and investigated protein level alterations. Proteomic analysis revealed significant changes in 137 protein features, of which 124 demonstrated changes in a glucose concentration dependent manner. Several proteins functionally associated with redox regulation, protein folding, or the cytoskeleton are affected by increased glucose concentrations. Additional analyses also revealed that cellular oxidative stress, including endoplasmic reticulum stress, was significantly increased after treatment with high glucose concentrations. However, the mitochondrial membrane potential and cell survival remained unchanged during treatment with high glucose concentrations. To summarize, in this study, we used a comprehensive retinal pigmented epithelial cell based proteomic approach for identifying changes in protein expression associated retinal markers induced by high glucose concentrations. Our results revealed that a high glucose condition can induce cellular oxidative stress and modulate the levels of proteins with functions in redox regulation, protein folding, and cytoskeleton regulation; however, cell viability and mitochondrial integrity are not significantly disturbed under these high glucose conditions.

  11. Regulation of UVR8 photoreceptor dimer/monomer photo-equilibrium in Arabidopsis plants grown under photoperiodic conditions.

    PubMed

    Findlay, Kirsten M W; Jenkins, Gareth I

    2016-08-01

    The UV RESISTANCE LOCUS 8 (UVR8) photoreceptor specifically mediates photomorphogenic responses to UV-B. Photoreception induces dissociation of dimeric UVR8 into monomers to initiate responses. However, the regulation of dimer/monomer status in plants growing under photoperiodic conditions has not been examined. Here we show that UVR8 establishes a dimer/monomer photo-equilibrium in plants growing in diurnal photoperiods in both controlled environments and natural daylight. The photo-equilibrium is determined by the relative rates of photoreception and dark-reversion to the dimer. Experiments with mutants in REPRESSOR OF UV-B PHOTOMORPHOGENESIS 1 (RUP1) and RUP2 show that these proteins are crucial in regulating the photo-equilibrium because they promote reversion to the dimer. In plants growing in daylight, the UVR8 photo-equilibrium is most strongly correlated with low ambient fluence rates of UV-B (up to 1.5 μmol m(-2) s(-1) ), rather than higher fluence rates or the amount of photosynthetically active radiation. In addition, the rate of reversion of monomer to dimer is reduced at lower temperatures, promoting an increase in the relative level of monomer at approximately 8-10 °C. Thus, UVR8 does not behave like a simple UV-B switch under photoperiodic growth conditions but establishes a dimer/monomer photo-equilibrium that is regulated by UV-B and also influenced by temperature.

  12. The isoenzyme of glutaminyl cyclase is an important regulator of monocyte infiltration under inflammatory conditions.

    PubMed

    Cynis, Holger; Hoffmann, Torsten; Friedrich, Daniel; Kehlen, Astrid; Gans, Kathrin; Kleinschmidt, Martin; Rahfeld, Jens-Ulrich; Wolf, Raik; Wermann, Michael; Stephan, Anett; Haegele, Monique; Sedlmeier, Reinhard; Graubner, Sigrid; Jagla, Wolfgang; Müller, Anke; Eichentopf, Rico; Heiser, Ulrich; Seifert, Franziska; Quax, Paul H A; de Vries, Margreet R; Hesse, Isabel; Trautwein, Daniela; Wollert, Ulrich; Berg, Sabine; Freyse, Ernst-Joachim; Schilling, Stephan; Demuth, Hans-Ulrich

    2011-09-01

    Acute and chronic inflammatory disorders are characterized by detrimental cytokine and chemokine expression. Frequently, the chemotactic activity of cytokines depends on a modified N-terminus of the polypeptide. Among those, the N-terminus of monocyte chemoattractant protein 1 (CCL2 and MCP-1) is modified to a pyroglutamate (pE-) residue protecting against degradation in vivo. Here, we show that the N-terminal pE-formation depends on glutaminyl cyclase activity. The pE-residue increases stability against N-terminal degradation by aminopeptidases and improves receptor activation and signal transduction in vitro. Genetic ablation of the glutaminyl cyclase iso-enzymes QC (QPCT) or isoQC (QPCTL) revealed a major role of isoQC for pE(1) -CCL2 formation and monocyte infiltration. Consistently, administration of QC-inhibitors in inflammatory models, such as thioglycollate-induced peritonitis reduced monocyte infiltration. The pharmacologic efficacy of QC/isoQC-inhibition was assessed in accelerated atherosclerosis in ApoE3*Leiden mice, showing attenuated atherosclerotic pathology following chronic oral treatment. Current strategies targeting CCL2 are mainly based on antibodies or spiegelmers. The application of small, orally available inhibitors of glutaminyl cyclases represents an alternative therapeutic strategy to treat CCL2-driven disorders such as atherosclerosis/restenosis and fibrosis.

  13. The isoenzyme of glutaminyl cyclase is an important regulator of monocyte infiltration under inflammatory conditions

    PubMed Central

    Cynis, Holger; Hoffmann, Torsten; Friedrich, Daniel; Kehlen, Astrid; Gans, Kathrin; Kleinschmidt, Martin; Rahfeld, Jens-Ulrich; Wolf, Raik; Wermann, Michael; Stephan, Anett; Haegele, Monique; Sedlmeier, Reinhard; Graubner, Sigrid; Jagla, Wolfgang; Müller, Anke; Eichentopf, Rico; Heiser, Ulrich; Seifert, Franziska; Quax, Paul H A; de Vries, Margreet R; Hesse, Isabel; Trautwein, Daniela; Wollert, Ulrich; Berg, Sabine; Freyse, Ernst-Joachim; Schilling, Stephan; Demuth, Hans-Ulrich

    2011-01-01

    Acute and chronic inflammatory disorders are characterized by detrimental cytokine and chemokine expression. Frequently, the chemotactic activity of cytokines depends on a modified N-terminus of the polypeptide. Among those, the N-terminus of monocyte chemoattractant protein 1 (CCL2 and MCP-1) is modified to a pyroglutamate (pE-) residue protecting against degradation in vivo. Here, we show that the N-terminal pE-formation depends on glutaminyl cyclase activity. The pE-residue increases stability against N-terminal degradation by aminopeptidases and improves receptor activation and signal transduction in vitro. Genetic ablation of the glutaminyl cyclase iso-enzymes QC (QPCT) or isoQC (QPCTL) revealed a major role of isoQC for pE1-CCL2 formation and monocyte infiltration. Consistently, administration of QC-inhibitors in inflammatory models, such as thioglycollate-induced peritonitis reduced monocyte infiltration. The pharmacologic efficacy of QC/isoQC-inhibition was assessed in accelerated atherosclerosis in ApoE3*Leiden mice, showing attenuated atherosclerotic pathology following chronic oral treatment. Current strategies targeting CCL2 are mainly based on antibodies or spiegelmers. The application of small, orally available inhibitors of glutaminyl cyclases represents an alternative therapeutic strategy to treat CCL2-driven disorders such as atherosclerosis/restenosis and fibrosis. PMID:21774078

  14. Self-regulation of solar coronal heating process via the collisionless reconnection condition.

    PubMed

    Uzdensky, Dmitri A

    2007-12-31

    I propose a new paradigm for solar coronal heating viewed as a self-regulating process keeping the plasma marginally collisionless. The mechanism is based on the coupling between two effects. First, coronal density controls the plasma collisionality and hence the transition between the slow collisional Sweet-Parker and the fast collisionless reconnection regimes. In turn, coronal energy release leads to chromospheric evaporation, increasing the density and thus inhibiting subsequent reconnection of the newly reconnected loops. As a result, statistically, the density fluctuates around some critical level, comparable to that observed in the corona. In the long run, coronal heating can be represented by repeating cycles of fast reconnection events (nanoflares), evaporation episodes, and long periods of slow magnetic stress buildup and radiative cooling of the coronal plasma.

  15. Socioeconomic variation in the burden of chronic conditions and health care provision – analyzing administrative individual level data from the Basque Country, Spain

    PubMed Central

    2013-01-01

    Background Chronic diseases are posing an increasing challenge to society, with the associated burden falling disproportionally on more deprived individuals and geographical areas. Although the existence of a socioeconomic health gradient is one of the main concerns of health policy across the world, health information systems commonly do not have reliable data to detect and monitor health inequalities and inequities. The objectives of this study were to measure the level of socioeconomic-related inequality in prevalence of chronic diseases and to investigate the extent and direction of inequities in health care provision. Methods A dataset linking clinical and administrative information of the entire population living in the Basque Country, Spain (over 2 million individuals) was used to measure the prevalence of 52 chronic conditions and to quantify individual health care costs. We used a concentration-index approach to measure the extent and direction of inequality with respect to the deprivation of the area of residence of each individual. Results Most chronic diseases were found to be disproportionally concentrated among individuals living in more deprived areas, but the extent of the imbalance varies by type of disease and sex. Most of the variation in health care utilization was explained by morbidity burden. However, even after accounting for differences in morbidity, pro-poor horizontal inequity was present in specialized outpatient care, emergency department, prescription, and primary health care costs and this fact was more apparent in females than males; inpatient costs exhibited an equitable distribution in both sexes. Conclusions Analyses of comprehensive administrative clinical information at the individual level allow the socioeconomic gradient in chronic diseases and health care provision to be measured to a level of detail not possible using other sources. This frequently updated source of information can be exploited to monitor trends and evaluate

  16. Degranulation, density, and distribution of mast cells in the rat thalamus: a light and electron microscopic study in basal conditions and after intracerebroventricular administration of nerve growth factor.

    PubMed

    Florenzano, F; Bentivoglio, M

    2000-09-04

    In the adult rat brain mast cells reside selectively in the thalamus. We investigated thalamic mast cells stained by acidic toluidine blue or pinacyanol, and with histamine immunocytochemistry, focusing on their state of activity revealed by degranulation. Mast cells exhibited perivascular prevalence and high quantitative variability, between cases and in different sections, with no asymmetry or topographical selectivity in thalamic nuclei. Pinacyanol, alone or with erythrosine, stained mast cells with higher sensitivity than toluidine blue. However, toluidine blue was highly predictive of pinacyanol staining and provided the best resolution of mast cell cytoplasmic features. Histamine immunocytochemistry labeled 61% of pinacyanol-stained mast cells. Intensely toluidine blue-stained granulated cells, as well as cells exhibiting different degrees of degranulation that paralleled lighter staining, were observed. The response of thalamic mast cells to intracerebroventricular administration of nerve growth factor (NGF) and control cytochrome-c injections was evaluated after 2, 24, and 72 hours. No obvious changes in mast cell number or distribution were found after treatment, but massive degranulation was frequently observed after NGF administration. Significant decrease of staining intensity of mast cells, supporting enhanced degranulation, was documented in NGF-treated animals by quantitative image analysis. Ultrastructural features of mast cell degranulation, with granule coalescence and matrix dissolution, were detected in untreated and NGF-treated cases. The findings point out that mast cells are active in the thalamus in basal conditions and that NGF has the potential to elicit long-lasting degranulation of thalamic mast cells in vivo, exerting a direct effect and/or priming these cells to react to endogenous stimuli.

  17. MIZ1-regulated hydrotropism functions in the growth and survival of Arabidopsis thaliana under natural conditions

    PubMed Central

    Iwata, Satoru; Miyazawa, Yutaka; Fujii, Nobuharu; Takahashi, Hideyuki

    2013-01-01

    Background and Aims Root hydrotropism is a response to water-potential gradients that makes roots bend towards areas of higher water potential. The gene MIZU-KUSSEI1 (MIZ1) that is essential for hydrotropism in Arabidopsis roots has previously been identified. However, the role of root hydrotropism in plant growth and survival under natural conditions has not yet been proven. This study assessed how hydrotropic response contributes to drought avoidance in nature. Methods An experimental system was established for the study of Arabidopsis hydrotropism in soil. Characteristics of hydrotropism were analysed by comparing the responses of the miz1 mutant, transgenic plants overexpressing MIZ1 (MIZ1OE) and wild-type plants. Key Results Wild-type plants developed root systems in regions with higher water potential, whereas the roots of miz1 mutant plants did not show a similar response. This pattern of root distribution induced by hydrotropism was more pronounced in MIZ1OE plants than in wild-type plants. In addition, shoot biomass and the number of plants that survived under drought conditions were much greater in MIZ1OE plants. Conclusions These results show that hydrotropism plays an important role in root system development in soil and contributes to drought avoidance, which results in a greater yield and plant survival under water-limited conditions. The results also show that MIZ1 overexpression can be used for improving plant productivity in arid areas. PMID:23658369

  18. Early developmental gene regulation in Strongylocentrotus purpuratus embryos in response to elevated CO₂ seawater conditions.

    PubMed

    Hammond, LaTisha M; Hofmann, Gretchen E

    2012-07-15

    Ocean acidification, or the increased uptake of CO(2) by the ocean due to elevated atmospheric CO(2) concentrations, may variably impact marine early life history stages, as they may be especially susceptible to changes in ocean chemistry. Investigating the regulatory mechanisms of early development in an environmental context, or ecological development, will contribute to increased understanding of potential organismal responses to such rapid, large-scale environmental changes. We examined transcript-level responses to elevated seawater CO(2) during gastrulation and the initiation of spiculogenesis, two crucial developmental processes in the purple sea urchin, Strongylocentrotus purpuratus. Embryos were reared at the current, accepted oceanic CO(2) concentration of 380 microatmospheres (μatm), and at the elevated levels of 1000 and 1350 μatm, simulating predictions for oceans and upwelling regions, respectively. The seven genes of interest comprised a subset of pathways in the primary mesenchyme cell gene regulatory network (PMC GRN) shown to be necessary for the regulation and execution of gastrulation and spiculogenesis. Of the seven genes, qPCR analysis indicated that elevated CO(2) concentrations only had a significant but subtle effect on two genes, one important for early embryo patterning, Wnt8, and the other an integral component in spiculogenesis and biomineralization, SM30b. Protein levels of another spicule matrix component, SM50, demonstrated significant variable responses to elevated CO(2). These data link the regulation of crucial early developmental processes with the environment that these embryos would be developing within, situating the study of organismal responses to ocean acidification in a developmental context.

  19. Protein profiling of rat ventral prostate following chronic finasteride administration: identification and localization of a novel putative androgen-regulated protein.

    PubMed

    Cayatte, Corinne; Pons, Catherine; Guigonis, Jean-Marie; Pizzol, Jérôme; Elies, Laetitia; Kennel, Philippe; Rouquié, David; Bars, Rémi; Rossi, Bernard; Samson, Michel

    2006-11-01

    To better understand the effects of antiandrogens on the prostate, we investigated the changes in the proteome of rat ventral prostate (VP) following treatment with a well characterized 5alpha-reductase inhibitor, finasteride. Sprague-Dawley rats were treated daily by gavage with finasteride at 0, 1, 5, 25, and 125 mg/kg/day. Changes in plasma hormone levels as well as the weight and histology of sex accessory tissues were determined after 28 days of treatment and showed a dose-related decrease of VP weights together with a marked atrophy of the tissue visible at the macroscopic and microscopic levels. In addition, significant reductions in seminal vesicle and epididymis weights were noted. VP proteins were analyzed by two-dimensional gel electrophoresis: 37 proteins, mainly involved in protein synthesis, processing, and cellular trafficking and in metabolism, detoxification, and oxidative stress, were identified as modulated by finasteride. The prominent feature of this study is the demonstration of finasteride dose-dependent up-regulation of a protein similar to l-amino-acid oxidase 1 (Lao1). An up-regulation of this protein was also observed with the antiandrogen flutamide. Lao1 expression occurred as early as 48 h after antiandrogen administration and persisted throughout the treatment duration. Immunohistochemistry showed that this protein was only detectable in epithelial cells and secretory vesicles. Altogether these data point to a potential use of Lao1 to reveal antiandrogen-induced prostate injury.

  20. Involvement of MicroRNAs in the Regulation of Muscle Wasting during Catabolic Conditions*

    PubMed Central

    Soares, Ricardo José; Cagnin, Stefano; Chemello, Francesco; Silvestrin, Matteo; Musaro, Antonio; De Pitta, Cristiano; Lanfranchi, Gerolamo; Sandri, Marco

    2014-01-01

    Loss of muscle proteins and the consequent weakness has important clinical consequences in diseases such as cancer, diabetes, chronic heart failure, and in aging. In fact, excessive proteolysis causes cachexia, accelerates disease progression, and worsens life expectancy. Muscle atrophy involves a common pattern of transcriptional changes in a small subset of genes named atrophy-related genes or atrogenes. Whether microRNAs play a role in the atrophy program and muscle loss is debated. To understand the involvement of miRNAs in atrophy we performed miRNA expression profiling of mouse muscles under wasting conditions such as fasting, denervation, diabetes, and cancer cachexia. We found that the miRNA signature is peculiar of each catabolic condition. We then focused on denervation and we revealed that changes in transcripts and microRNAs expression did not occur simultaneously but were shifted. Indeed, whereas transcriptional control of the atrophy-related genes peaks at 3 days, changes of miRNA expression maximized at 7 days after denervation. Among the different miRNAs, microRNA-206 and -21 were the most induced in denervated muscles. We characterized their pattern of expression and defined their role in muscle homeostasis. Indeed, in vivo gain and loss of function experiments revealed that miRNA-206 and miRNA-21 were sufficient and required for atrophy program. In silico and in vivo approaches identified transcription factor YY1 and the translational initiator factor eIF4E3 as downstream targets of these miRNAs. Thus miRNAs are important for fine-tuning the atrophy program and their modulation can be a novel potential therapeutic approach to counteract muscle loss and weakness in catabolic conditions. PMID:24891504

  1. Involvement of microRNAs in the regulation of muscle wasting during catabolic conditions.

    PubMed

    Soares, Ricardo José; Cagnin, Stefano; Chemello, Francesco; Silvestrin, Matteo; Musaro, Antonio; De Pitta, Cristiano; Lanfranchi, Gerolamo; Sandri, Marco

    2014-08-08

    Loss of muscle proteins and the consequent weakness has important clinical consequences in diseases such as cancer, diabetes, chronic heart failure, and in aging. In fact, excessive proteolysis causes cachexia, accelerates disease progression, and worsens life expectancy. Muscle atrophy involves a common pattern of transcriptional changes in a small subset of genes named atrophy-related genes or atrogenes. Whether microRNAs play a role in the atrophy program and muscle loss is debated. To understand the involvement of miRNAs in atrophy we performed miRNA expression profiling of mouse muscles under wasting conditions such as fasting, denervation, diabetes, and cancer cachexia. We found that the miRNA signature is peculiar of each catabolic condition. We then focused on denervation and we revealed that changes in transcripts and microRNAs expression did not occur simultaneously but were shifted. Indeed, whereas transcriptional control of the atrophy-related genes peaks at 3 days, changes of miRNA expression maximized at 7 days after denervation. Among the different miRNAs, microRNA-206 and -21 were the most induced in denervated muscles. We characterized their pattern of expression and defined their role in muscle homeostasis. Indeed, in vivo gain and loss of function experiments revealed that miRNA-206 and miRNA-21 were sufficient and required for atrophy program. In silico and in vivo approaches identified transcription factor YY1 and the translational initiator factor eIF4E3 as downstream targets of these miRNAs. Thus miRNAs are important for fine-tuning the atrophy program and their modulation can be a novel potential therapeutic approach to counteract muscle loss and weakness in catabolic conditions.

  2. Gabapentinoid Insensitivity after Repeated Administration is Associated with Down-Regulation of the α(2)δ-1 Subunit in Rats with Central Post-Stroke Pain Hypersensitivity.

    PubMed

    Yang, Yan; Yang, Fei; Yang, Fan; Li, Chun-Li; Wang, Yan; Li, Zhen; Lu, Yun-Fei; Yu, Yao-Qing; Fu, Han; He, Ting; Sun, Wei; Wang, Rui-Rui; Chen, Jun

    2016-02-01

    The α2δ-1 subunit of the voltage-gated Ca(2+) channel (VGCC) is a molecular target of gabapentin (GBP), which has been used as a first-line drug for the relief of neuropathic pain. GBP exerts its anti-nociceptive effects by disrupting trafficking of the α2δ-1 subunit to the presynaptic membrane, resulting in decreased neurotransmitter release. We previously showed that GBP has an anti-allodynic effect in the first two weeks; but this is followed by insensitivity in the later stage after repeated administration in a rat model of central post-stroke pain (CPSP) hypersensitivity induced by intra-thalamic hemorrhage. To explore the mechanisms underlying GBP insensitivity, the cellular localization and time-course of expression of the α2δ-1 subunit in both the thalamus and spinal dorsal horn were studied in the same model. We found that the α2δ-1 subunit was mostly localized in neurons, but not astrocytes and microglia. The level of α2δ-1 protein increased in the first two weeks after injury but then decreased in the third week, when GBP insensitivity occurred. Furthermore, the α2δ-1 down-regulation was likely caused by later neuronal loss in the injured thalamus through a mechanism other than apoptosis. In summary, the present results suggest that the GBP receptor α2δ-1 is mainly expressed in thalamic neurons in which it is up-regulated in the early stage of CPSP but this is followed by dramatic down-regulation, which is likely associated with GBP insensitivity after long-term use.

  3. On Necessary and Sufficient Conditions for Regulation of Linear Systems Over Rings,

    DTIC Science & Technology

    1980-10-09

    book (e.g., Bourbaki [1972, Chapt. 2]). Let (m&Ii, be the set of maximal ideals of k[z, zI] such that (2.11) rank [zl - F, G]g< n. After these...Khargonekar [1980], where a . theory of observers and coefficient assignment by causal dynamic state feedback was developed. Although the split condition is...this research was done when the author was at the Center for Mathematical System Theory , University of Florida, Gainesville. Florida 32611, and was

  4. 48 CFR 552.270-17 - Delivery and Condition.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 48 Federal Acquisition Regulations System 4 2011-10-01 2011-10-01 false Delivery and Condition. 552.270-17 Section 552.270-17 Federal Acquisition Regulations System GENERAL SERVICES ADMINISTRATION... Delivery and Condition. As prescribed in 570.703, insert the following clause: Delivery and Condition...

  5. 48 CFR 552.270-17 - Delivery and Condition.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 48 Federal Acquisition Regulations System 4 2010-10-01 2010-10-01 false Delivery and Condition. 552.270-17 Section 552.270-17 Federal Acquisition Regulations System GENERAL SERVICES ADMINISTRATION... Delivery and Condition. As prescribed in 570.603, insert the following clause: Delivery and Condition...

  6. [Immune-regulating effect of phenibut under lipopolysaccharide-induced immune stress conditions].

    PubMed

    Samotrueva, M A; Tiurenkov, I N; Teplyĭ, D L; Kuleshevskaia, N R; Khlebtsova, E V

    2010-05-01

    The immunoregulating effect of phenibut has been demonstrated on the model of immune stress caused by the injection of lipopolysaccharide from Pseudomonas aeruginosa. The degree of expression of the specific (in a delayed-type hypersensitivity reaction and passive hemagglutination) and nonspecific (phagocytic activity of neutrophils) links of immunomodulation was studied. The formation of lipopolysaccharide (LPS) induced immune stress is characterized by the increase of the indicated parameters of immunity. It is found that phenibut (under intraabdominal injection of 25 mg/kg within 5 days) removes the manifestations of hyperreactivity of the cellular link of immunity, and also restores the amount of phagocytic cells, which is evidence of the immunomodulating properties of the drug under conditions of hyperimmunization.

  7. Administrative Law Judges

    EPA Pesticide Factsheets

    The Administrative Law Judges conduct hearings and render decisions in proceedings between the EPA and persons, businesses, government entities, and other organizations which are or are alleged to be regulated under environmental laws.

  8. Regulated expression of an isopentenyltransferase gene (IPT) in peanut significantly improves drought tolerance and increases yield under field conditions.

    PubMed

    Qin, Hua; Gu, Qiang; Zhang, Junling; Sun, Li; Kuppu, Sundaram; Zhang, Yizheng; Burow, Mark; Payton, Paxton; Blumwald, Eduardo; Zhang, Hong

    2011-11-01

    Isopentenyltransferase (IPT) is a critical enzyme in the cytokinin biosynthetic pathway. The expression of IPT under the control of a maturation- and stress-induced promoter was shown to delay stress-induced plant senescence that resulted in an enhanced drought tolerance in both monocot and dicot plants. This report extends the earlier findings in tobacco and rice to peanut (Arachis hypogaea L.), an important oil crop and protein source. Regulated expression of IPT in peanut significantly improved drought tolerance in both laboratory and field conditions. Transgenic peanut plants maintained higher photosynthetic rates, higher stomatal conductance and higher transpiration than wild-type control plants under reduced irrigation conditions. More importantly, transgenic peanut plants produced significantly higher yields than wild-type control plants in the field, indicating a great potential for the development of crops with improved performance and yield in water-limited areas of the world.

  9. 5 CFR 315.710 - Professional and administrative career employees serving under Schedule B appointments.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 5 Administrative Personnel 1 2012-01-01 2012-01-01 false Professional and administrative career... PERSONNEL MANAGEMENT CIVIL SERVICE REGULATIONS CAREER AND CAREER-CONDITIONAL EMPLOYMENT Conversion to Career or Career-Conditional Employment From Other Types of Employment § 315.710 Professional...

  10. 5 CFR 315.710 - Professional and administrative career employees serving under Schedule B appointments.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 5 Administrative Personnel 1 2013-01-01 2013-01-01 false Professional and administrative career... PERSONNEL MANAGEMENT CIVIL SERVICE REGULATIONS CAREER AND CAREER-CONDITIONAL EMPLOYMENT Conversion to Career or Career-Conditional Employment From Other Types of Employment § 315.710 Professional...

  11. 5 CFR 315.710 - Professional and administrative career employees serving under Schedule B appointments.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 5 Administrative Personnel 1 2014-01-01 2014-01-01 false Professional and administrative career... PERSONNEL MANAGEMENT CIVIL SERVICE REGULATIONS CAREER AND CAREER-CONDITIONAL EMPLOYMENT Conversion to Career or Career-Conditional Employment From Other Types of Employment § 315.710 Professional...

  12. 5 CFR 315.710 - Professional and administrative career employees serving under Schedule B appointments.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 5 Administrative Personnel 1 2011-01-01 2011-01-01 false Professional and administrative career... PERSONNEL MANAGEMENT CIVIL SERVICE REGULATIONS CAREER AND CAREER-CONDITIONAL EMPLOYMENT Conversion to Career or Career-Conditional Employment From Other Types of Employment § 315.710 Professional...

  13. 5 CFR 315.710 - Professional and administrative career employees serving under Schedule B appointments.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 5 Administrative Personnel 1 2010-01-01 2010-01-01 false Professional and administrative career... PERSONNEL MANAGEMENT CIVIL SERVICE REGULATIONS CAREER AND CAREER-CONDITIONAL EMPLOYMENT Conversion to Career or Career-Conditional Employment From Other Types of Employment § 315.710 Professional...

  14. Hormonal regulation of reproductive growth under normal and heat-stress conditions in legume and other model crop species.

    PubMed

    Ozga, Jocelyn A; Kaur, Harleen; Savada, Raghavendra P; Reinecke, Dennis M

    2016-12-23

    Legume crops are grown throughout the world and provide an excellent food source of digestible protein and starch, as well as dietary fibre, vitamins, minerals, and flavonoids. Fruit and seeds from legumes are also an important source of vegetables for a well-balanced diet. A trend in elevated temperature as a result of climate change increases the risk of a heat stress-induced reduction in legume crop yield. High temperatures during the crop reproductive development phase are particularly detrimental to fruit/seed production because the growth and development of the reproductive tissues are sensitive to small changes in temperature. Hormones are signalling molecules that play important roles in a plant's ability to integrate different environmental inputs and modify their developmental processes to optimize growth, survival, and reproduction. This review focuses on the hormonal regulation of reproductive development and heat stress-induced alteration of this regulation during (i) pollination, (ii) early fruit set, and (iii) seed development that affects fruit/seed yield in legume and other model crops. Further understanding of hormone-regulated reproductive growth under non-stress and heat-stress conditions can aid in trait selection and the development of gene modification strategies and cultural practices to improve heat tolerance in legume crops contributing to improved food security.

  15. Sympathetic, parasympathetic and enteric regulation of the gastrointestinal vasculature in rainbow trout (Oncorhynchus mykiss) under normal and postprandial conditions.

    PubMed

    Seth, Henrik; Axelsson, Michael

    2010-09-15

    The control of the gastrointestinal hyperemia that occurs after feeding in most animals is of fundamental importance for the subsequent absorption, metabolism and redistribution of nutrients. Yet, in fish, it has received little attention and the nature of it is far from clear. We sought to investigate the importance of extrinsic and intrinsic innervation of the gastrointestinal tract in the regulation of gastrointestinal blood flow in rainbow trout (Oncorhynchus mykiss). The contribution of the extrinsic innervation, i.e. by the sympathetic and the parasympathetic nervous system, was examined by comparing the response to the injection of a predigested nutrient diet into the proximal intestine of untreated fish with the response in fish in which the splanchnic and vagal innervation of the gut had been removed. We also injected the predigested nutrient diet into anaesthetized fish treated with tetrodotoxin that would block the intrinsic innervation of the gut (i.e. enteric nervous system). Our results confirm the notion that the sympathetic portion of the extrinsic innervation maintains the basal vascular tone, but neither the splanchnic nor the vagal innervation is fundamental to the postprandial hyperemia. However, the tetrodotoxin treatment completely abolished the postprandial hyperemia, indicating the importance of the enteric nervous system. In conclusion, it seems as though the enteric nervous system is essential to the regulation of the postprandial hyperemia, and that the extrinsic innervation is involved mainly in the regulation of gastrointestinal blood flow under normal conditions and in response to central coordination with other organs.

  16. Daily regulation of body temperature rhythm in the camel (Camelus dromedarius) exposed to experimental desert conditions.

    PubMed

    Bouâouda, Hanan; Achâaban, Mohamed R; Ouassat, Mohammed; Oukassou, Mohammed; Piro, Mohamed; Challet, Etienne; El Allali, Khalid; Pévet, Paul

    2014-09-01

    In the present work, we have studied daily rhythmicity of body temperature (Tb) in Arabian camels challenged with daily heat, combined or not with dehydration. We confirm that Arabian camels use heterothermy to reduce heat gain coupled with evaporative heat loss during the day. Here, we also demonstrate that this mechanism is more complex than previously reported, because it is characterized by a daily alternation (probably of circadian origin) of two periods of poikilothermy and homeothermy. We also show that dehydration induced a decrease in food intake plays a role in this process. Together, these findings highlight that adaptive heterothermy in the Arabian camel varies across the diurnal light-dark cycle and is modulated by timing of daily heat and degrees of water restriction and associated reduction of food intake. The changed phase relationship between the light-dark cycle and the Tb rhythm observed during the dehydration process points to a possible mechanism of internal desynchronization during the process of adaptation to desert environment. During these experimental conditions mimicking the desert environment, it will be possible in the future to determine if induced high-amplitude ambient temperature (Ta) rhythms are able to compete with the zeitgeber effect of the light-dark cycle.

  17. Multiple abiotic stimuli are integrated in the regulation of rice gene expression under field conditions

    PubMed Central

    Plessis, Anne; Hafemeister, Christoph; Wilkins, Olivia; Gonzaga, Zennia Jean; Meyer, Rachel Sarah; Pires, Inês; Müller, Christian; Septiningsih, Endang M; Bonneau, Richard; Purugganan, Michael

    2015-01-01

    Plants rely on transcriptional dynamics to respond to multiple climatic fluctuations and contexts in nature. We analyzed the genome-wide gene expression patterns of rice (Oryza sativa) growing in rainfed and irrigated fields during two distinct tropical seasons and determined simple linear models that relate transcriptomic variation to climatic fluctuations. These models combine multiple environmental parameters to account for patterns of expression in the field of co-expressed gene clusters. We examined the similarities of our environmental models between tropical and temperate field conditions, using previously published data. We found that field type and macroclimate had broad impacts on transcriptional responses to environmental fluctuations, especially for genes involved in photosynthesis and development. Nevertheless, variation in solar radiation and temperature at the timescale of hours had reproducible effects across environmental contexts. These results provide a basis for broad-based predictive modeling of plant gene expression in the field. DOI: http://dx.doi.org/10.7554/eLife.08411.001 PMID:26609814

  18. Fimasartan Ameliorates Nonalcoholic Fatty Liver Disease through PPARδ Regulation in Hyperlipidemic and Hypertensive Conditions

    PubMed Central

    Jang, Yoo-Na; Han, Yoon-Mi; Kim, Hyun-Min; Jeong, Jong-Min

    2017-01-01

    To investigate the effects of fimasartan on nonalcoholic fatty liver disease in hyperlipidemic and hypertensive conditions, the levels of biomarkers related to fatty acid metabolism were determined in HepG2 and differentiated 3T3-L1 cells treated by high fatty acid and liver and visceral fat tissue samples of spontaneously hypertensive rats (SHRs) given high-fat diet. In HepG2 cells and liver tissues, fimasartan was shown to increase the protein levels of peroxisome proliferator-activated receptor delta (PPARδ), phosphorylated 5′ adenosine monophosphate-activated protein kinase (p-AMPK), phosphorylated acetyl-CoA carboxylase (p-ACC), malonyl-CoA decarboxylase (MCD), medium chain acyl-CoA dehydrogenase (MCAD), and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), and it led to a decrease in the protein levels of 11 beta-hydroxysteroid dehydrogenase 1 (11β-HSDH1), fatty acid synthase (FAS), and tumor necrosis factor-alpha (TNF-α). Fimasartan decreased lipid contents in HepG2 and differentiated 3T3-L1 cells and liver tissues. In addition, fimasartan increased the adiponectin level in visceral fat tissues. The antiadipogenic effects of fimasartan were offset by PPARδ antagonist (GSK0660). Consequently, fimasartan ameliorates nonalcoholic fatty liver disease mainly through the activation of oxidative metabolism represented by PPARδ-AMPK-PGC-1α pathway. PMID:28386270

  19. Three-dimensional spherical spatial boundary conditions differentially regulate osteogenic differentiation of mesenchymal stromal cells

    PubMed Central

    Lo, Yin-Ping; Liu, Yi-Shiuan; Rimando, Marilyn G.; Ho, Jennifer Hui-Chun; Lin, Keng-hui; Lee, Oscar K.

    2016-01-01

    The spatial boundary condition (SBC) arising from the surrounding microenvironment imposes specific geometry and spatial constraints that affect organogenesis and tissue homeostasis. Mesenchymal stromal cells (MSCs) sensitively respond to alterations of mechanical cues generated from the SBC. However, mechanical cues provided by a three-dimensional (3D) environment are deprived in a reductionist 2D culture system. This study investigates how SBC affects osteogenic differentiation of MSCs using 3D scaffolds with monodispersed pores and homogenous spherical geometries. MSCs cultured under SBCs with diameters of 100 and 150 μm possessed the greatest capability of osteogenic differentiation. This phenomenon was strongly correlated with MSC morphology, organization of actin cytoskeleton, and distribution of focal adhesion involving α2 and α5 integrins. Further silencing either α2 or α5 integrin significantly reduced the above mentioned mechanosensitivity, indicating that the α2 and α5 integrins as mechano-sensitive molecules mediate MSCs’ ability to provide enhanced osteogenic differentiation in response to different spherical SBCs. Taken together, the findings provide new insights regarding how MSCs respond to mechanical cues from the surrounding microenvironment in a spherical SBC, and such biophysical stimuli should be taken into consideration in tissue engineering and regenerative medicine in conjunction with biochemical cues. PMID:26884253

  20. Photodynamic Graphene Quantum Dot: Reduction Condition Regulated Photoactivity and Size Dependent Efficacy.

    PubMed

    Du, Dou; Wang, Kun; Wen, Ya; Li, Yan; Li, Yong Y

    2016-02-10

    Prequenching and selective activation of photosensitizer (PS) are highly desired in photodynamic therapy (PDT) to avoid off-target effect due to nonspecific activation and poor targeting selectivity of PS. In this study, nanographene materials as a unique π-conjugated planar system for electronic transfer were employed as the robust platform for temporarily quenching of PS. Photosensitizer chlorin e6 (Ce6) was integrated onto planar structure of graphene quantum dot (GQD) or graphene oxide (GO) via a reduction cleavable disulfide linker. The formed hybrid nanosystem displayed considerable fluorescence quenching and slight phototoxicity, even under the condition of light irradiation, while the photoactivity of PS could be selectively recovered in the presence of the reducing agent. Compared with graphene oxide system with larger size (around 200 nm), GQD nanosystem exhibited significantly improved tumor accumulation via enhanced permeation and retention effect (EPR effect). The in vivo study demonstrated extremely effective suppression of tumor growth for the group treated with the GQD nanosystem with cleavable linker, revealing the promising application of the presented novel strategy.

  1. Expression profiles of sugarcane under drought conditions: Variation in gene regulation.

    PubMed

    Andrade, Júlio César Farias de; Terto, Jackeline; Silva, José Vieira; Almeida, Cícero

    2015-12-01

    Drought is a major factor in decreased sugarcane productivity because of the resulting morphophysiological effects that it causes. Gene expression studies that have examined the influence of water stress in sugarcane have yielded divergent results, indicating the absence of a fixed pattern of changes in gene expression. In this work, we investigated the expression profiles of 12 genes in the leaves of a drought-tolerant genotype (RB72910) of sugarcane and compared the results with those of other studies. The genotype was subjected to 80-100% water availability (control condition) and 0-20% water availability (simulated drought). To analyze the physiological status, the SPAD index, Fv/Fm ratio, net photosynthesis (A), stomatal conductance (gs) and stomatal transpiration (E) were measured. Total RNA was extracted from leaves and the expression of SAMDC, ZmPIP2-1 protein, ZmTIP4-2 protein, WIP protein, LTP protein, histone H3, DNAj, ferredoxin I, β-tubulin, photosystem I, gene 1 and gene 2 was analyzed by quantitative real-time PCR (RT-PCR). Important differences in the expression profiles of these genes were observed when compared with other genotypes, suggesting that complex defense mechanisms are activated in response to water stress. However, there was no recognizable pattern for the changes in expression of the different proteins associated with tolerance to drought stress.

  2. Expression profiles of sugarcane under drought conditions: Variation in gene regulation

    PubMed Central

    de Andrade, Júlio César Farias; Terto, Jackeline; Silva, José Vieira; Almeida, Cícero

    2015-01-01

    Abstract Drought is a major factor in decreased sugarcane productivity because of the resulting morphophysiological effects that it causes. Gene expression studies that have examined the influence of water stress in sugarcane have yielded divergent results, indicating the absence of a fixed pattern of changes in gene expression. In this work, we investigated the expression profiles of 12 genes in the leaves of a drought-tolerant genotype (RB72910) of sugarcane and compared the results with those of other studies. The genotype was subjected to 80–100% water availability (control condition) and 0–20% water availability (simulated drought). To analyze the physiological status, the SPAD index, Fv/Fm ratio, net photosynthesis (A), stomatal conductance (g s) and stomatal transpiration (E) were measured. Total RNA was extracted from leaves and the expression of SAMDC, ZmPIP2-1 protein, ZmTIP4-2 protein, WIP protein, LTP protein, histone H3, DNAj, ferredoxin I, β-tubulin, photosystem I, gene 1 and gene 2 was analyzed by quantitative real-time PCR (RT-PCR). Important differences in the expression profiles of these genes were observed when compared with other genotypes, suggesting that complex defense mechanisms are activated in response to water stress. However, there was no recognizable pattern for the changes in expression of the different proteins associated with tolerance to drought stress. PMID:26537606

  3. Daily regulation of body temperature rhythm in the camel (Camelus dromedarius) exposed to experimental desert conditions

    PubMed Central

    Bouâouda, Hanan; Achâaban, Mohamed R.; Ouassat, Mohammed; Oukassou, Mohammed; Piro, Mohamed; Challet, Etienne; El Allali, Khalid; Pévet, Paul

    2014-01-01

    Abstract In the present work, we have studied daily rhythmicity of body temperature (Tb) in Arabian camels challenged with daily heat, combined or not with dehydration. We confirm that Arabian camels use heterothermy to reduce heat gain coupled with evaporative heat loss during the day. Here, we also demonstrate that this mechanism is more complex than previously reported, because it is characterized by a daily alternation (probably of circadian origin) of two periods of poikilothermy and homeothermy. We also show that dehydration induced a decrease in food intake plays a role in this process. Together, these findings highlight that adaptive heterothermy in the Arabian camel varies across the diurnal light–dark cycle and is modulated by timing of daily heat and degrees of water restriction and associated reduction of food intake. The changed phase relationship between the light–dark cycle and the Tb rhythm observed during the dehydration process points to a possible mechanism of internal desynchronization during the process of adaptation to desert environment. During these experimental conditions mimicking the desert environment, it will be possible in the future to determine if induced high‐amplitude ambient temperature (Ta) rhythms are able to compete with the zeitgeber effect of the light–dark cycle. PMID:25263204

  4. Sex differences in contextual fear conditioning are associated with differential ventral hippocampal extracellular signal-regulated kinase activation.

    PubMed

    Gresack, J E; Schafe, G E; Orr, P T; Frick, K M

    2009-03-17

    Although sex differences have been reported in hippocampal-dependent learning and memory, including contextual fear memories, the underlying molecular mechanisms contributing to such differences are not well understood. The present study examined the extent to which sex differences in contextual fear conditioning are related to differential activation of the extracellular signal-regulated kinase/mitogen-activated protein kinase (ERK/MAPK), a protein kinase critically involved in memory formation. We first show that male rats exhibit more long-term retention of contextual fear conditioning than female rats. During a tone test, females spent more time freezing than males, although both sexes exhibited robust retention of auditory fear learning. Using Western blot analysis, we then show that phosphorylated ERK levels in ventral, but not dorsal, hippocampus are higher in males than females, relative to same-sex controls, 60 minutes after fear conditioning. Post-conditioning increases in ERK activation were observed in the amygdala in both males and females, suggesting a selective effect of sex on hippocampal ERK activation. Together, these findings suggest that differential activation of the ERK signal transduction pathway in male and female rats, particularly in the ventral hippocampus, is associated with sex differences in contextual fear.

  5. Regulation of HIF-1α signaling and chemoresistance in acute lymphocytic leukemia under hypoxic conditions of the bone marrow microenvironment

    PubMed Central

    Frolova, Olga; Samudio, Ismael; Benito, Juliana Maria; Jacamo, Rodrigo; Kornblau, Steven M.; Markovic, Ana; Schober, Wendy; Lu, Hongbo; Qiu, Yi Hua; Buglio, Daniela; McQueen, Teresa; Pierce, Sherry; Shpall, Elizabeth; Konoplev, Sergej; Thomas, Deborah; Kantarjian, Hagop; Lock, Richard; Andreeff, Michael; Konopleva, Marina

    2012-01-01

    Overcoming resistance to chemotherapy is the main therapeutic challenge in the treatment of acute lymphocytic leukemia (ALL). Interactions between leukemia cells and the microenvironment promote leukemia cell survival and confer resistance to chemotherapy. Hypoxia is an integral component of bone marrow (BM) microenvironment. Hypoxia-inducible factor-1α (HIF-1), a key regulator of the cellular response to hypoxia, regulates cell growth and metabolic adaptation to hypoxia. HIF-1α expression, analyzed by Reverse Phase Protein Arrays in 92 specimens from newly diagnosed patients with pre-B-ALL, had a negative prognostic impact on survival (p = 0.0025). Inhibition of HIF-1α expression by locked mRNA antagonist (LNA) promoted chemosensitivity under hypoxic conditions, while pharmacological or genetic stabilization of HIF-1α under normoxia inhibited cell growth and reduced apoptosis induction by chemotherapeutic agents. Co-culture of pre-B ALL or REH cells with BM-derived mesenchymal stem cells (MSC) under hypoxia resulted in further induction of HIF-1α protein and acquisition of the glycolytic phenotype, in part via stroma-induced AKT/mTOR signaling. mTOR blockade with everolimus reduced HIF-1α expression, diminished glucose uptake and glycolytic rate and partially restored the chemosensitivity of ALL cells under hypoxia/stroma co-cultures. Hence, mTOR inhibition or blockade of HIF-1α-mediated signaling may play an important role in chemosensitization of ALL cells under hypoxic conditions of the BM microenvironment. PMID:22785211

  6. A novel conditional mouse model for Nkx2-5 reveals transcriptional regulation of cardiac ion channels.

    PubMed

    Furtado, Milena B; Wilmanns, Julia C; Chandran, Anjana; Tonta, Mary; Biben, Christine; Eichenlaub, Michael; Coleman, Harold A; Berger, Silke; Bouveret, Romaric; Singh, Reena; Harvey, Richard P; Ramialison, Mirana; Pearson, James T; Parkington, Helena C; Rosenthal, Nadia A; Costa, Mauro W

    2016-01-01

    Nkx2-5 is one of the master regulators of cardiac development, homeostasis and disease. This transcription factor has been previously associated with a suite of cardiac congenital malformations and impairment of electrical activity. When disease causative mutations in transcription factors are considered, NKX2-5 gene dysfunction is the most common abnormality found in patients. Here we describe a novel mouse model and subsequent implications of Nkx2-5 loss for aspects of myocardial electrical activity. In this work we have engineered a new Nkx2-5 conditional knockout mouse in which flox sites flank the entire Nkx2-5 locus, and validated this line for the study of heart development, differentiation and disease using a full deletion strategy. While our homozygous knockout mice show typical embryonic malformations previously described for the lack of the Nkx2-5 gene, hearts of heterozygous adult mice show moderate morphological and functional abnormalities that are sufficient to sustain blood supply demands under homeostatic conditions. This study further reveals intriguing aspects of Nkx2-5 function in the control of cardiac electrical activity. Using a combination of mouse genetics, biochemistry, molecular and cell biology, we demonstrate that Nkx2-5 regulates the gene encoding Kcnh2 channel and others, shedding light on potential mechanisms generating electrical abnormalities observed in patients bearing NKX2-5 dysfunction and opening opportunities to the study of novel therapeutic targets for anti-arrhythmogenic therapies.

  7. FoxO3a regulates hematopoietic homeostasis through a negative feedback pathway in conditions of stress or aging

    PubMed Central

    Miyamoto, Kana; Kato, Reiko; Yoshimura, Akihiko; Motoyama, Noboru

    2008-01-01

    Stress or aging of tissue-specific stem cells is considered central to the decline of tissue homeostasis in the elderly, although little is known of molecular mechanisms underlying hematopoietic stem cell (HSC) aging and stress resistance. Here, we report that mice lacking the transcription factor forkhead box O3a (FoxO3a) develop neutrophilia associated with inhibition of the up-regulation of negative regulator of cell proliferation, Sprouty-related Ena/VASP homology 1 domain-containing proteins 2 (Spred2) and AKT and ERK activation, in HSCs during hematopoietic recovery following myelosuppressive stress conditions. Compared with aged wild-type mice, more severe neutrophilia was also observed in aged Foxo3a-deficient mice. AKT and ERK activation and inhibition of Spred2 were detected in HSCs from aged FoxO3a-deficient mice. Spred2-deficient mice also developed neutrophilia during hematopoietic recovery following myelosuppressive stress, indicating that FoxO3a plays a pivotal role in maintenance, integrity, and stress resistance of HSCs through negative feedback pathways for proliferation. This will provide new insight into the hematopoietic homeostasis in conditions of aging and stress. PMID:18799725

  8. Role of endogenous cortistatin in the regulation of ghrelin system expression at pancreatic level under normal and obese conditions.

    PubMed

    Chanclón, Belén; Luque, Raúl M; Córdoba-Chacón, José; Gahete, Manuel D; Pozo-Salas, Ana I; Castaño, Justo P; Gracia-Navarro, Francisco; Martínez-Fuentes, Antonio J

    2013-01-01

    Ghrelin-system components [native ghrelin, In1-ghrelin, Ghrelin-O-acyltransferase enzyme (GOAT) and receptors (GHS-Rs)] are expressed in a wide variety of tissues, including the pancreas, where they exert different biological actions including regulation of neuroendocrine secretions, food intake and pancreatic function. The expression of ghrelin system is regulated by metabolic conditions (fasting/obesity) and is associated with the progression of obesity and insulin resistance. Cortistatin (CORT), a neuropeptide able to activate GHS-R, has emerged as an additional link in gut-brain interplay. Indeed, we recently reported that male CORT deficient mice (cort-/-) are insulin-resistant and present a clear dysregulation in the stomach ghrelin-system. The present work was focused at analyzing the expression pattern of ghrelin-system components at pancreas level in cort-/- mice and their control littermates (cort +/+) under low- or high-fat diet. Our data reveal that all the ghrelin-system components are expressed at the mouse pancreatic level, where, interestingly, In1-ghrelin was expressed at higher levels than native-ghrelin. Thus, GOAT mRNA levels were significantly lower in cort-/- mice compared with controls while native ghrelin, In1-ghrelin and GHS-R transcript levels remained unaltered under normal metabolic conditions. Moreover, under obese condition, a significant increase in pancreatic expression of native-ghrelin, In1-ghrelin and GHS-R was observed in obese cort+/+ but not in cort-/- mice. Interestingly, insulin expression and release was elevated in obese cort+/+, while these changes were not observed in obese cort-/- mice. Altogether, our results indicate that the ghrelin-system expression is clearly regulated in the pancreas of cort+/+ and cort -/- under normal and/or obesity conditions suggesting that this system may play relevant roles in the endocrine pancreas. Most importantly, our data demonstrate, for the first time, that endogenous CORT is essential

  9. Redox crisis underlies conditional light-dark lethality in cyanobacterial mutants that lack the circadian regulator, RpaA.

    PubMed

    Diamond, Spencer; Rubin, Benjamin E; Shultzaberger, Ryan K; Chen, You; Barber, Chase D; Golden, Susan S

    2017-01-24

    Cyanobacteria evolved a robust circadian clock, which has a profound influence on fitness and metabolism under daily light-dark (LD) cycles. In the model cyanobacterium Synechococcus elongatus PCC 7942, a functional clock is not required for diurnal growth, but mutants defective for the response regulator that mediates transcriptional rhythms in the wild-type, regulator of phycobilisome association A (RpaA), cannot be cultured under LD conditions. We found that rpaA-null mutants are inviable after several hours in the dark and compared the metabolomes of wild-type and rpaA-null strains to identify the source of lethality. Here, we show that the wild-type metabolome is very stable throughout the night, and this stability is lost in the absence of RpaA. Additionally, an rpaA mutant accumulates excessive reactive oxygen species (ROS) during the day and is unable to clear it during the night. The rpaA-null metabolome indicates that these cells are reductant-starved in the dark, likely because enzymes of the primary nighttime NADPH-producing pathway are direct targets of RpaA. Because NADPH is required for processes that detoxify ROS, conditional LD lethality likely results from inability of the mutant to activate reductant-requiring pathways that detoxify ROS when photosynthesis is not active. We identified second-site mutations and growth conditions that suppress LD lethality in the mutant background that support these conclusions. These results provide a mechanistic explanation as to why rpaA-null mutants die in the dark, further connect the clock to metabolism under diurnal growth, and indicate that RpaA likely has important unidentified functions during the day.

  10. Zonation related function and ubiquitination regulation in human hepatocellular carcinoma cells in dynamic vs. static culture conditions

    PubMed Central

    2012-01-01

    Background Understanding hepatic zonation is important both for liver physiology and pathology. There is currently no effective systemic chemotherapy for human hepatocellular carcinoma (HCC) and its pathogenesis is of special interest. Genomic and proteomic data of HCC cells in different culture models, coupled to pathway-based analysis, can help identify HCC-related gene and pathway dysfunctions. Results We identified zonation-related expression profiles contributing to selective phenotypes of HCC, by integrating relevant experimental observations through gene set enrichment analysis (GSEA). Analysis was based on gene and protein expression data measured on a human HCC cell line (HepG2/C3A) in two culture conditions: dynamic microfluidic biochips and static Petri dishes. Metabolic activity (HCC-related cytochromes P450) and genetic information processing were dominant in the dynamic cultures, in contrast to kinase signaling and cancer-specific profiles in static cultures. That, together with analysis of the published literature, leads us to propose that biochips culture conditions induce a periportal-like hepatocyte phenotype while standard plates cultures are more representative of a perivenous-like phenotype. Both proteomic data and GSEA results further reveal distinct ubiquitin-mediated protein regulation in the two culture conditions. Conclusions Pathways analysis, using gene and protein expression data from two cell culture models, confirmed specific human HCC phenotypes with regard to CYPs and kinases, and revealed a zonation-related pattern of expression. Ubiquitin-mediated regulation mechanism gives plausible explanations of our findings. Altogether, our results suggest that strategies aimed at inhibiting activated kinases and signaling pathways may lead to enhanced metabolism-mediated drug resistance of treated tumors. If that were the case, mitigating inhibition or targeting inactive forms of kinases would be an alternative. PMID:22296956

  11. Embracing 21st Century Information Sharing: Defining a New Paradigm for the Food and Drug Administration's Regulation of Biopharmaceutical Company Communications with Healthcare Professionals.

    PubMed

    Spears, James M; Francer, Jeffrey K; Turner, Natale A

    2015-01-01

    The Food and Drug Administration (FDA) plays a unique role in protecting the public health and minimizing the risk of the distribution of unsafe or ineffective medicines in the United States. Perhaps equally as important for public health, however, is the need for healthcare professionals to be well informed about the benefits and risks of the medicines they prescribe. In this way, information sharing is critical to healthcare delivery. FDA's current interpretation of laws and regulations governing healthcare communications prohibits biopharmaceutical companies from sharing certain accurate, data-driven information about FDA-approved uses and medically accepted alternative uses of FDA-approved drugs with healthcare professionals. Often, these uses are the standard of care for good medical practice and are, accordingly, reimbursed under the federal healthcare programs. FDA has failed to describe adequately how manufacturers can share truthful and non-misleading information about such uses with healthcare professionals and formulary decision makers. This failure could impede medical innovation, negatively impact patient care, and increase healthcare costs. To improve public health, FDA should reform its current approach and provide manufacturers with a clear safe harbor on how to share data and information on both approved uses and medically accepted alternative uses of FDA-approved drugs with healthcare professionals. This Article describes key principles for a new regulatory paradigm.

  12. Differential regulation of catalytic and non-catalytic trkB messenger RNAs in the rat hippocampus following seizures induced by systemic administration of kainate.

    PubMed

    Dugich-Djordjevic, M M; Ohsawa, F; Okazaki, T; Mori, N; Day, J R; Beck, K D; Hefti, F

    1995-06-01

    Ribonuclease protection analysis and quantitative in situ hybridization histochemistry were used to investigate the coordination and regional expression of catalytic and non-catalytic trkB messenger RNAs in the adult rat hippocampus following systemic kainate-induced seizures. Changes in trkB expression were compared with the messenger RNA expression of its neurotrophic ligands, brain-derived neurotrophic factor and neurotrophin-3. TrkB messenger RNA expression was increased in the dentate granule cells at 1-4 h following the onset of seizures, and returned to control levels 16-24 h thereafter. In addition, seizures also induced expression of trkB messenger RNA in putative non-neuronal cells at four to seven days in the molecular layer of the dentate gyrus and the stratum lacunosum moleculare of the CA1 region. Hybridization with probes specific for the non-catalytic trkB receptor and the catalytic trkB receptor revealed that the increases at four and seven days in the molecular layers of the hippocampus reflected an up-regulation of only the non-catalytic form of the receptor. Furthermore, the neuronal increases observed 1-4 h were due to an up-regulation of both trkB TK- and trkB TK+ messenger RNAs. It was established that systemic administration of kainate increased brain-derived neurotrophic factor messenger RNA levels in the pyramidal and granule cell regions of the hippocampus 1-4 h following the onset of behaviorally manifested seizure activity. Early changes in neuronal expression of trkB TK- and trkB TK+ messenger RNA paralleled changes in brain-derived neurotrophic factor messenger RNA in the dentate granule cell and CA1 pyramidal cell layers, but not in the CA3 subregion. These data suggest that concomitant regulation of brain-derived neurotrophic factor and its cognate receptor may play a role in the selective vulnerability of hippocampal subregions to kainate-induced neuropathology. Furthermore, these data suggest a dual function for trkB receptor

  13. 7 CFR 301.86-4 - Conditions governing the interstate movement of regulated articles from quarantined areas.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... experimental or scientific purposes; or (ii) The regulated article originates outside the quarantined area and... regulated articles from quarantined areas. 301.86-4 Section 301.86-4 Agriculture Regulations of the... regulated articles from quarantined areas. (a) Any regulated article may be moved interstate from...

  14. 7 CFR 301.51-4 - Conditions governing the interstate movement of regulated articles from quarantined areas.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... experimental or scientific purposes; or (ii) The regulated article originates outside the quarantined area and... regulated articles from quarantined areas. 301.51-4 Section 301.51-4 Agriculture Regulations of the... of regulated articles from quarantined areas. (a) Any regulated article may be moved interstate...

  15. Cloning of mid-G1 serum response genes and identification of a subset regulated by conditional myc expression.

    PubMed Central

    Tavtigian, S V; Zabludoff, S D; Wold, B J

    1994-01-01

    The emergence of cells from a quiescent G0 arrested state into the cell cycle is a multistep process that begins with the immediate early response to mitogens and extends into a specialized G1 phase. Many immediate early serum response genes including c-fos, c-myc, and c-jun are transcriptional regulators. To understand their roles in regulating cell cycle entry and progression, the identities of their regulatory targets must be determined. In this work we have cloned cDNA copies of messenger RNAs that are either up- or down-regulated at a mid-G1 point in the serum response (midserum-response [mid-SR]). The mid-SR panel is expected to include both direct and indirect targets of immediate early regulators. This expectation was confirmed by the identification of several transcriptional targets of conditional c-myc activity. In terms of cellular function, the mid-SR class is also expected to include execution genes needed for progression through G1 and into S-phase. DNA sequence data showed that the mid-SR panel included several genes already known to be involved in cell cycle progression or growth transformation, suggesting that previously unknown cDNAs in the same group are good candidates for other G1 execution functions. In functional assays of G0-->S-phase progression, c-myc expression can bypass the requirement for serum mitogens and drive a large fraction of G0 arrested cells through G1 into S-phase. However, beyond this general similarity, little is known about the relation of a serum-driven progression to a myc-driven progression. Using the mid-SR collection as molecular reporters, we found that the myc driven G1 differs qualitatively from the serum driven case. Instead of simply activating a subset of serum response genes, as might be expected, myc regulated some genes inversely relative to serum stimulation. This suggests that a myc driven progression from G0 may have novel properties with implications for its action in oncogenesis. Images PMID:8049528

  16. An HP1 isoform-specific feedback mechanism regulates Suv39h1 activity under stress conditions.

    PubMed

    Raurell-Vila, Helena; Bosch-Presegue, Laia; Gonzalez, Jessica; Kane-Goldsmith, Noriko; Casal, Carmen; Brown, Jeremy P; Marazuela-Duque, Anna; Singh, Prim B; Serrano, Lourdes; Vaquero, Alejandro

    2017-02-01

    The presence of H3K9me3 and heterochromatin protein 1 (HP1) are hallmarks of heterochromatin conserved in eukaryotes. The spreading and maintenance of H3K9me3 is effected by the functional interplay between the H3K9me3-specific histone methyltransferase Suv39h1 and HP1. This interplay is complex in mammals because the three HP1 isoforms, HP1α, β, and γ, are thought to play a redundant role in Suv39h1-dependent deposition of H3K9me3 in pericentric heterochromatin (PCH). Here, we demonstrate that despite this redundancy, HP1α and, to a lesser extent, HP1γ have a closer functional link to Suv39h1, compared to HP1β. HP1α and γ preferentially interact in vivo with Suv39h1, regulate its dynamics in heterochromatin, and increase Suv39h1 protein stability through an inhibition of MDM2-dependent Suv39h1-K87 polyubiquitination. The reverse is also observed, where Suv39h1 increases HP1α stability compared HP1β and γ. The interplay between Suv39h1 and HP1 isoforms appears to be relevant under genotoxic stress. Specifically, loss of HP1α and γ isoforms inhibits the upregulation of Suv39h1 and H3K9me3 that is observed under stress conditions. Reciprocally, Suv39h1 deficiency abrogates stress-dependent upregulation of HP1α and γ, and enhances HP1β levels. Our work defines a specific role for HP1 isoforms in regulating Suv39h1 function under stress via a feedback mechanism that likely regulates heterochromatin formation.

  17. New Methodology for Evaluating Optimal Pricing for Primary Regulation of Deregulated Power Systems under Steady State Condition

    NASA Astrophysics Data System (ADS)

    Satyaramesh, P. V.; RadhaKrishna, C.

    2013-06-01

    A generalized pricing structure for procurement of power under frequency ancillary service is developed in this paper. It is a frequency linked-price model and suitable for deregulation market environment. This model takes into consideration: governor characteristics and frequency characteristics of generator as additional parameters in load flow method. The main objective of the new approach proposed in this paper is to establish bidding price structure for frequency regulation services in competitive ancillary electrical markets under steady state condition. Lot of literatures are available for calculating the frequency deviations with respect to load changes by using dynamic simulation methods. But in this paper, the model computes the frequency deviations for additional requirements of power under steady state with considering power system network topology. An attempt is also made in this paper to develop optimal bidding price structure for the frequency-regulated systems. It gives a signal to traders or bidders that the power demand can be assessed more accurately much closer to real time and helps participants bid more accurate quantities on day-ahead market. The recent trends of frequency linked-price model existing in Indian power systems issues required for attention are also dealt in this paper. Test calculations have been performed on 30-bus system. The paper also explains adoptability of 33 this model to practical Indian power system. The results presented are analyzed and useful conclusions are drawn.

  18. Regulation of heat shock protein message in Jurkat cells cultured under serum-starved and gravity-altered conditions

    NASA Technical Reports Server (NTRS)

    Lewis, M. L.; Hughes-Fulford, M.

    2000-01-01

    Although our understanding of effects of space flight on human physiology has advanced significantly over the past four decades, the potential contribution of stress at the cellular and gene regulation level is not characterized. The objective of this ground-based study was to evaluate stress gene regulation in cells exposed to altered gravity and environmentally suboptimal conditions. We designed primers to detect message for both the constitutive and inducible forms of the heat shock protein, HSP-70. Applying the reverse transcriptase-polymerase chain reaction (RT-PCR), we probed for HSP-70 message in human acute T-cell leukemia cells, Jurkat, subjected to three types of environmental stressors: (1) altered gravity achieved by centrifugation (hypergravity) and randomization of the gravity vector in rotating bioreactors, (2) serum starvation by culture in medium containing 0.05% serum, and (3) temperature elevation (42 degrees C). Temperature elevation, as the positive control, significantly increased HSP-70 message, while centrifugation and culture in rotating bioreactors did not upregulate heat shock gene expression. We found a fourfold increase in heat shock message in serum-starved cells. Message for the housekeeping genes, actin and cyclophilin, were constant and comparable to unstressed controls for all treatments. We conclude that gravitational perturbations incurred by centrifugal forces, exceeding those characteristic of a Space Shuttle launch (3g), and culture in rotating bioreactors do not upregulate HSP-70 gene expression. In addition, we found RT-PCR useful for evaluating stress in cultured cells. Copyright 2000 Wiley-Liss, Inc.

  19. CSF HCO3- regulation in isosmotic conditions: the role of brain PCO2 and plasma HCO3-.

    PubMed

    Nattie, E E; Romer, L

    1978-05-01

    We have studied in anesthetized cats the response of CSF HCO3- to (1) an increase in CSF PCO2, plasma HCO3- controlled at the normal value; (2) an increase in plasma HCO3-, CSF PCO2 controlled at the normal value; and (3) an increase in both CSF PCO2 and plasma HCO3-. Plasma HCO3- was controlled via HCO3-/Cl- exchange without altering plasma Na concentration or osmolarity using the technique of peritoneal dialysis. The results suggest that CSF HCO3- regulation in these conditions is dependent on (1) a PCO2-dependent process in which HCO3- ions are formed in brain cells or choroid plexus and (2) an ionic movement of HCO3- from plasma to CSF dependent on an increase in plasma HCO3-. The first process is largely completed by 3 hours; the second takes 6 hours or more. An analysis of plasma and CSF HCO3-, Cl- and unmeasured anions (UA), (Na+ + K+ -CL- -HCO3-), suggests that CSF HCO3- regulation may be complex involving ionic exchanges of three or more anions between brain extracellular fluid, plasma and brain cells.

  20. Role of ACTH in the Interactive/Paracrine Regulation of Adrenal Steroid Secretion in Physiological and Pathophysiological Conditions

    PubMed Central

    Lefebvre, Hervé; Thomas, Michaël; Duparc, Céline; Bertherat, Jérôme; Louiset, Estelle

    2016-01-01

    In the normal human adrenal gland, steroid secretion is regulated by a complex network of autocrine/paracrine interactions involving bioactive signals released by endothelial cells, nerve terminals, chromaffin cells, immunocompetent cells, and adrenocortical cells themselves. ACTH can be locally produced by medullary chromaffin cells and is, therefore, a major mediator of the corticomedullary functional interplay. Plasma ACTH also triggers the release of angiogenic and vasoactive agents from adrenocortical cells and adrenal mast cells and, thus, indirectly regulates steroid production through modulation of the adrenal blood flow. Adrenocortical neoplasms associated with steroid hypersecretion exhibit molecular and cellular defects that tend to reinforce the influence of paracrine regulatory loops on corticosteroidogenesis. Especially, ACTH has been found to be abnormally synthesized in bilateral macronodular adrenal hyperplasia responsible for hypercortisolism. In these tissues, ACTH is detected in a subpopulation of adrenocortical cells that express gonadal markers. This observation suggests that ectopic production of ACTH may result from impaired embryogenesis leading to abnormal maturation of the adrenogonadal primordium. Globally, the current literature indicates that ACTH is a major player in the autocrine/paracrine processes occurring in the adrenal gland in both physiological and pathological conditions. PMID:27489549

  1. Regulation of cambial activity in relation to environmental conditions: understanding the role of temperature in wood formation of trees.

    PubMed

    Begum, Shahanara; Nakaba, Satoshi; Yamagishi, Yusuke; Oribe, Yuichiro; Funada, Ryo

    2013-01-01

    The timing of cambial reactivation plays an important role in determination of the amount and quality of wood and the environmental adaptivity of trees. Environmental factors, such as temperature, influence the growth and development of trees. Temperatures from late winter to early spring affect the physiological processes that are involved in the initiation of cambial cell division and xylem differentiation in trees. Cumulative elevated temperatures from late winter to early spring result in earlier initiation of cambial reactivation and xylem differentiation in tree stems and an extended growth period. However, earlier cambial reactivation increases the risk for frost damage because the cold tolerance of cambium decreases after cambial reactivation. The present review focuses on temperature regulation on the timing of cambial reactivation and xylem differentiation in trees, and also highlights recent advances in our understanding of seasonal changes in the cold stability of microtubules in trees. The review also summarizes the present understanding of the relationships between the timing of cambial reactivation, the start of xylem differentiation and changes in levels of storage materials in trees, as well as an attempt to identify the source of energy for cell division and differentiation. A better understanding of the mechanisms that regulate wood formation in trees and the influence of environmental conditions on such mechanisms should help in efforts to improve and enhance the exploitation of wood for commercial applications and to prepare for climatic change.

  2. Distinct Redox Regulation in Sub-Cellular Compartments in Response to Various Stress Conditions in Saccharomyces cerevisiae

    PubMed Central

    Ayer, Anita; Sanwald, Julia; Pillay, Bethany A.; Meyer, Andreas J.; Perrone, Gabriel G.; Dawes, Ian W.

    2013-01-01

    Responses to many growth and stress conditions are assumed to act via changes to the cellular redox status. However, direct measurement of pH-adjusted redox state during growth and stress has never been carried out. Organellar redox state (EGSH) was measured using the fluorescent probes roGFP2 and pHluorin in Saccharomyces cerevisiae. In particular, we investigated changes in organellar redox state in response to various growth and stress conditions to better understand the relationship between redox-, oxidative- and environmental stress response systems. EGSH values of the cytosol, mitochondrial matrix and peroxisome were determined in exponential and stationary phase in various media. These values (−340 to −350 mV) were more reducing than previously reported. Interestingly, sub-cellular redox state remained unchanged when cells were challenged with stresses previously reported to affect redox homeostasis. Only hydrogen peroxide and heat stress significantly altered organellar redox state. Hydrogen peroxide stress altered the redox state of the glutathione disulfide/glutathione couple (GSSG, 2H+/2GSH) and pH. Recovery from moderate hydrogen peroxide stress was most rapid in the cytosol, followed by the mitochondrial matrix, with the peroxisome the least able to recover. Conversely, the bulk of the redox shift observed during heat stress resulted from alterations in pH and not the GSSG, 2H+/2GSH couple. This study presents the first direct measurement of pH-adjusted redox state in sub-cellular compartments during growth and stress conditions. Redox state is distinctly regulated in organelles and data presented challenge the notion that perturbation of redox state is central in the response to many stress conditions. PMID:23762325

  3. Distinct redox regulation in sub-cellular compartments in response to various stress conditions in Saccharomyces cerevisiae.

    PubMed

    Ayer, Anita; Sanwald, Julia; Pillay, Bethany A; Meyer, Andreas J; Perrone, Gabriel G; Dawes, Ian W

    2013-01-01

    Responses to many growth and stress conditions are assumed to act via changes to the cellular redox status. However, direct measurement of pH-adjusted redox state during growth and stress has never been carried out. Organellar redox state (E GSH) was measured using the fluorescent probes roGFP2 and pHluorin in Saccharomyces cerevisiae. In particular, we investigated changes in organellar redox state in response to various growth and stress conditions to better understand the relationship between redox-, oxidative- and environmental stress response systems. E GSH values of the cytosol, mitochondrial matrix and peroxisome were determined in exponential and stationary phase in various media. These values (-340 to -350 mV) were more reducing than previously reported. Interestingly, sub-cellular redox state remained unchanged when cells were challenged with stresses previously reported to affect redox homeostasis. Only hydrogen peroxide and heat stress significantly altered organellar redox state. Hydrogen peroxide stress altered the redox state of the glutathione disulfide/glutathione couple (GSSG, 2H(+)/2GSH) and pH. Recovery from moderate hydrogen peroxide stress was most rapid in the cytosol, followed by the mitochondrial matrix, with the peroxisome the least able to recover. Conversely, the bulk of the redox shift observed during heat stress resulted from alterations in pH and not the GSSG, 2H(+)/2GSH couple. This study presents the first direct measurement of pH-adjusted redox state in sub-cellular compartments during growth and stress conditions. Redox state is distinctly regulated in organelles and data presented challenge the notion that perturbation of redox state is central in the response to many stress conditions.

  4. Regulation of MDA-MB-231 cell proliferation by GSK-3β involves epigenetic modifications under high glucose conditions

    SciTech Connect

    Gupta, Chanchal; Kaur, Jasmine; Tikoo, Kulbhushan

    2014-05-15

    Hyperglycemia is a critical risk factor for development and progression of breast cancer. We have recently reported that high glucose induces phosphorylation of histone H3 at Ser 10 as well as de-phosphorylation of GSK-3β at Ser 9 in MDA-MB-231 cells. Here, we elucidate the mechanism underlying hyperglycemia-induced proliferation in MDA-MB-231 breast cancer cells. We provide evidence that hyperglycemia led to increased DNA methylation and DNMT1 expression in MDA-MB-231 cells. High glucose condition led to significant increase in the expression of PCNA, cyclin D1 and decrease in the expression of PTPN 12, p21 and PTEN. It also induced hypermethylation of DNA at the promoter region of PTPN 12, whereas hypomethylation at Vimentin and Snail. Silencing of GSK-3β by siRNA prevented histone H3 phosphorylation and reduced DNMT1 expression. We show that chromatin obtained after immunoprecipitation with phospho-histone H3 was hypermethylated under high glucose condition, which indicates a cross-talk between DNA methylation and histone H3 phosphorylation. ChIP-qPCR analysis revealed up-regulation of DNMT1 and metastatic genes viz. Vimentin, Snail and MMP-7 by phospho-histone H3, which were down-regulated upon GSK-3β silencing. To the best of our knowledge, this is the first report which shows that interplay between GSK-3β activation, histone H3 phosphorylation and DNA methylation directs proliferation of breast cancer cells. - Highlights: • High glucose induces phosphorylation of histone H3 and dephosphorylation of GSK-3β. • Moreover, hyperglycemia also leads to increased DNA methylation in MDA-MB-231 cells. • Inhibition of GSK-3β prevented histone H3 phosphorylation and reduced DNMT1 levels. • Interplay exists between GSK-3β, histone H3 phosphorylation and DNA methylation.

  5. Ectomycorrhizal fungi enhance nitrogen and phosphorus nutrition of Nothofagus dombeyi under drought conditions by regulating assimilative enzyme activities.

    PubMed

    Alvarez, Maricel; Huygens, Dries; Olivares, Erick; Saavedra, Isabel; Alberdi, Miren; Valenzuela, Eduardo

    2009-08-01

    Drought stress conditions (DC) reduce plant growth and nutrition, restraining the sustainable reestablishment of Nothofagus dombeyi in temperate south Chilean forest ecosystems. Ectomycorrhizal symbioses have been documented to enhance plant nitrogen (N) and phosphorus (P) uptake under drought, but the regulation of involved assimilative enzymes remains unclear. We studied 1-year-old N. dombeyi (Mirb.) Oerst. plants in association with the ectomycorrhizal fungi Pisolithus tinctorius (Pers.) Coker & Couch. and Descolea antartica Sing. In greenhouse experiments, shoot and root dry weights, mycorrhizal colonization, foliar N and P concentrations, and root enzyme activities [glutamate synthase (glutamine oxoglutarate aminotransferase (GOGAT), EC 1.4.1.13-14), glutamine synthetase (GS, EC 6.3.1.2), glutamate dehydrogenase (GDH, EC 1.4.1.2-4), nitrate reductase (NR, EC 1.6.6.1), and acid phosphomonoesterase (PME, EC 3.1.3.1-2)] were determined as a function of soil-water content. Inoculation of N. dombeyi with P. tinctorius and D. antartica significantly stimulated plant growth and increased plant foliar N and P concentrations, especially under DC. Ectomycorrhizal inoculation increased the activity of all studied enzymes relative to non-mycorrhizal plants under drought. We speculate that GDH is a key enzyme involved in the enhancement of ectomycorrhizal carbon (C) availability by fuelling the tricarboxylic acid (TCA) cycle under conditions of drought-induced carbon deficit. All studied assimilative enzymes of the ectomycorrhizal associations, involved in C, N, and P transfers, are closely interlinked and interdependent. The up-regulation of assimilative enzyme activities by ectomycorrhizal fungal root colonizers acts as a functional mechanism to increase seedling endurance to drought. We insist upon incorporating ectomycorrhizal inoculation in existing Chilean afforestation programs.

  6. Regulation of pH in the mammalian central nervous system under normal and pathological conditions: facts and hypotheses.

    PubMed

    Obara, Marta; Szeliga, Monika; Albrecht, Jan

    2008-05-01

    The maintenance of pH homeostasis in the CNS is of key importance for proper execution and regulation of neurotransmission, and deviations from this homeostasis are a crucial factor in the mechanism underlying a spectrum of pathological conditions. The first few sections of the review are devoted to the brain operating under normal conditions. The article commences with an overview of how extrinsic factors modelling the brain at work: neurotransmitters, depolarising stimuli (potassium and voltage changes) and cyclic nucleotides as major signal transducing vehicles affect pH in the CNS. Further, consequences of pH alterations on the major aspects of CNS function and metabolism are outlined. Next, the major cellular events involved in the transport, sequestration, metabolic production and buffering of protons that are common to all the mammalian cells, including the CNS cells. Since CNS function reflects tight interaction between astrocytes and neurons, the pH regulatory events pertinent to either cell type are discussed: overwhelming evidence implicates astrocytes as a key player in pH homeostasis in the brain. The different classes of membrane proteins involved in proton shuttling are listed and their mechanisms of action are given. These include: the Na+/H+ exchanger, different classes of bicarbonate transporters acting in a sodium-dependent- or -independent mode, monocarboxylic acid transporters and the vacuolar-type proton ATPase. A separate section is devoted to carbonic anhydrase, which is represented by multiple isoenzymes capable of pH buffering both in the cell interior and in the extracellular space. Next, impairment of pH regulation and compensatory responses occurring in brain affected by different pathologies: hypoxia/ischemia, epilepsy, hyperammonemic encephalopathies, cerebral tumours and HIV will be described. The review is limited to facts and plausible hypotheses pertaining to phenomena directly involved in pH regulation: changes in pH that

  7. Regulation of Mnemiopsis leidyi dynamics by potential changes in temperature and zooplankton conditions in the Black Sea.

    NASA Astrophysics Data System (ADS)

    Salihoglu, B.; Fach, B.; Oguz, T.

    2009-04-01

    Providing a comprehensive understanding of the effects that cause formations of ctenophore blooms in the Black Sea is the main objective of this study. In order to analyse ctenophore dynamics in the Black Sea a zero-dimensional population based model of the ctenophore Mnemiopsis leidyi is developed. The stage resolving ctenophore model combines the modified form of stage resolving approach of Fennel, 2001 with the growth dynamics model of Kremer, 1976; Kremer and Reeve, 1989 under 4 stages of model-ctenophore. These stages include the different growth characteristics of egg, juvenile, transitional and adult stages. The dietary patterns of the different stages follows the observations obtained from the literature. The model is able to represent consistent development patterns, while reflecting the physiological complexity of a population of Mnemiopsis leidyi. Model results suggest that different nutritional requirement of each stage may serve as the bottlenecks for population growth and only when growth conditions are favorable for both larval and lobate stages, the high overall population growth rates may occur. Model is also used to analyse the influence of climatic changes on Mnemiopsis leidyi reproduction and outburst. This study presents and discussed how potential changes in temperature and zooplankton conditions in the Black Sea may regulate Mnemiopsis leidyi dynamics.

  8. Ecological and evolutionary conditions for fruit abortion to regulate pollinating seed-eaters and increase plant production

    USGS Publications Warehouse

    Holland, J. Nathaniel; DeAngelis, Donald L.

    2002-01-01

    Coevolved mutualisms, such as those between senita cacti, yuccas, and their respective obligate pollinators, benefit both species involved in the interaction. However, in these pollination mutualisms the pollinator's larvae impose a cost on plants through consumption of developing seeds and fruit. The effects of pollinators on benefits and costs are expected to vary with the abundance of pollinators, because large population sizes result in more eggs and larval seed-eaters. Here, we develop the hypothesis that fruit abortion, which is common in yucca, senita, and plants in general, could in some cases have the function of limiting pollinator abundance and, thereby, increasing fruit production. Using a general steady-state model of fruit production and pollinator dynamics, we demonstrate that plants involved in pollinating seed-eater mutualisms can increase their fecundity by randomly aborting fruit. We show that the ecological conditions under which fruit abortion can improve plants fecundity are not unusual. They are best met when the plant is long-lived, the population dynamics of the pollinator are much faster than those of the plant, the loss of one fruit via abortion kills a larva that would have the expectation of destroying more than one fruit through its future egg laying as an adult moth, and the effects of fruit abortion on pollinator abundance are spatially localized. We then use the approach of adaptive dynamics to find conditions under which a fruit abortion strategy based on regulating the pollinator population could feasibly evolve in this type of plant–pollinator interaction.

  9. Ubiquitin Ligase, MuRF-1 regulates myosin heavy chain type IIa transcripts during muscle atrophy under microgravity conditions

    NASA Astrophysics Data System (ADS)

    Kagawa, Sachiko

    Skeletal muscles are vulnerable to marked atrophy under microgravity conditions. We previously reported that gastrocnemius muscle atrophy by spaceflight was specifically sensitive to the ubiquitin-proteasome proteolytic pathway. We also screened more over 26,000 skeletal muscle genes in rats exposed to real weightlessness and found that the expression of Ubiquitin Ligase, Muscle specific Ring Finger-1 (MuRF-1) upregulated under microgravity. In the present study, we examined the role of MuRF-1 in microgravity-induced muscle atrophy. The amounts of MuRF-1 transcripts significantly increased in skeletal muscle after denervation, an in vivo model of microgravity-induced unloading. MuRF-1 deficient (MuRF-1-/-) mice significantly inhibited reduction of muscle weight for muscle atrophy, compared with wild type mice. Interestingly, MuRF-1-/- mice significantly inhibited upregulation of myosin heavy chain (MyHC) type IIa transcrips, while wild type mice significantly increased expression of MyHC type IIa transcripts in denervated skeletal muscle. Our present results suggest that MuRF-1 may play an important role in regulation of MyHC type IIa during muscle atrophy under microgravity conditions.

  10. Hydrological conditions regulate dissolved organic matter quality in an intermittent headwater stream. From drought to storm analysis.

    PubMed

    Guarch-Ribot, Alba; Butturini, Andrea

    2016-11-15

    Storms and droughts are an essential driver for the dissolved organic matter (DOM) concentration in headwater streams. However, the relationship between DOM quality and discharge (Q) has not been addressed in depth and the impact of other hydro-climatic or biogeochemical drivers has not been explored. In this study DOM quality variability was explored at seasonal and storm event scales during an intensive 2.5-year-long sampling in a Mediterranean stream characterized by a severe summer drought. DOM quality was described in terms of absorbance and fluorescence properties. Most of the DOM properties were strongly related to discharge revealing the input of allochthonous, degraded, aromatic, humic and increased-molecular-size DOM under high flow conditions. However, these relationships disappeared or reversed during drying and rewetting periods. Each DOM response at the storm event scale (DOM-Q hysteresis) was outlined with two descriptors that summarised its trend (dilution/flushing/chemostasis) and shape (linear/nonlinear response). Multiple linear regression and commonality analysis showed that, in addition to the magnitude of storm episodes, antecedent hydrological conditions, namely pre-event basal flow and the magnitude of the previous storm event, played a significant role in regulating the trends and shapes of DOM-Q hysteresis.

  11. Ecological and evolutionary conditions for fruit abortion to regulate pollinating seed-eaters and increase plant reproduction.

    PubMed

    Holland, J Nathaniel; DeAngelis, Donald L

    2002-05-01

    Coevolved mutualisms, such as those between senita cacti, yuccas, and their respective obligate pollinators, benefit both species involved in the interaction. However, in these pollination mutualisms the pollinator's larvae impose a cost on plants through consumption of developing seeds and fruit. The effects of pollinators on benefits and costs are expected to vary with the abundance of pollinators, because large population sizes result in more eggs and larval seed-eaters. Here, we develop the hypothesis that fruit abortion, which is common in yucca, senita, and plants in general, could in some cases have the function of limiting pollinator abundance and, thereby, increasing fruit production. Using a general steady-state model of fruit production and pollinator dynamics, we demonstrate that plants involved in pollinating seed-eater mutualisms can increase their fecundity by randomly aborting fruit. We show that the ecological conditions under which fruit abortion can improve plants fecundity are not unusual. They are best met when the plant is long-lived, the population dynamics of the pollinator are much faster than those of the plant, the loss of one fruit via abortion kills a larva that would have the expectation of destroying more than one fruit through its future egg laying as an adult moth, and the effects of fruit abortion on pollinator abundance are spatially localized. We then use the approach of adaptive dynamics to find conditions under which a fruit abortion strategy based on regulating the pollinator population could feasibly evolve in this type of plant-pollinator interaction.

  12. Hydrolysis and photolysis of diacylhydrazines-type insect growth regulator JS-118 in aqueous solutions under abiotic conditions.

    PubMed

    Hu, J-Y; Liu, C; Zhang, Y-C; Zheng, Z-X

    2009-05-01

    JS-118 is a diacylhydrazines-type insect growth regulator which is now used extensively in China. The hydrolysis and photolysis of the pesticide JS-118 in aqueous solutions have been assessed under natural and controlled conditions in this project. Hydrolysis experimental results show that JS-118 is quite stable in aqueous solutions in dark, with no significant variations be observed in degradation under various conditions. Abiotic hydrolysis is relatively unimportant compared to photolysis. The rate of photodecomposition of JS-118 in aqueous solutions follows first-order kinetics both in UV radiation and natural sunlight. The degradation rates are faster under UV light than sunlight, with the half-lives (t (1/2) = ln2/k) of 6.00-10.85 min and 6.63-10.16 day, respectively. Under UV light, two major photoproducts are detected, and tentatively identified according to HPLC-MS spectral information as N-t-butyl-N-(3,5-dimethylbenzoyl) and 3,7-dimethyl-benzoatedihydrofuran. The corresponding photolysis pathways of JS-118 are also proposed. The results obtained indicate that direct photoreaction is an important dissipation pathway of JS-118 in natural water systems.

  13. 49 CFR 385.711 - Administrative review.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... Transportation Other Regulations Relating to Transportation (Continued) FEDERAL MOTOR CARRIER SAFETY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION FEDERAL MOTOR CARRIER SAFETY REGULATIONS SAFETY FITNESS PROCEDURES... America-domiciled motor carrier may request FMCSA to conduct an administrative review if it believes...

  14. 48 CFR 3028.106 - Administration.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 48 Federal Acquisition Regulations System 7 2010-10-01 2010-10-01 false Administration. 3028.106 Section 3028.106 Federal Acquisition Regulations System DEPARTMENT OF HOMELAND SECURITY, HOMELAND SECURITY... 3028.106 Administration....

  15. Repeated administration of desipramine and a GABAB receptor antagonist, CGP 36742, discretely up-regulates GABAB receptor binding sites in rat frontal cortex.

    PubMed Central

    Pratt, G. D.; Bowery, N. G.

    1993-01-01

    1. GABAB receptor binding site densities within laminar regions of the rat frontal cortex were examined autoradiographically following repeated administration (21 days) of the antidepressants desipramine, paroxetine and amitriptyline in addition to the GABAB receptor antagonists, CGP 35348 and CGP 36742. beta 1-Adrenoceptor autoradiography was studied in parallel with that for GABAB receptor sites. 2. The effects of these compounds were examined concomitantly on the GABAB receptor-mediated inhibition of forskolin- and enhancement of noradrenaline-stimulated cyclic AMP production. 3. GABAB receptor binding was increased by both desipramine (20 mg kg-1, p.o. and 10 mg kg-1, i.p.) and CGP 36742 (100 mg kg-1, i.p.) in the outer laminar region of the frontal cortex by around 50% above control levels. Conversely, no significant changes were mediated by paroxetine, amitriptyline, CGP 35348 or the GABAB receptor agonist, baclofen. 4. With the exception of paroxetine, all compounds down-regulated the total beta-adrenoceptor population throughout frontal cortical laminae which was attributable to the beta 1-adrenoceptor subtype. In contrast, the reduction in beta-adrenoceptors mediated by CGP 35348 and CGP 36742 did not occur as a consequence of reduced beta 1-adrenoceptor numbers. 5. Protracted treatment with CGP 35348, failed to influence forskolin-stimulated cyclic AMP production; however, a significant increase in the accumulation of cyclic AMP produced in response to forskolin was seen after treatment with CGP 36742. 6. Such discretely localized changes in GABAB receptor densities induced by desipramine and CGP 36742 may provide an explanation for the discrepancies reported in membrane binding studies and possibly implicate a role for GABAB receptor antagonists in antidepressant therapy. Images Figure 1 Figure 3 PMID:8242244

  16. Impaired recovery of brain muscarinic receptor sites following an adaptive down-regulation induced by repeated administration of diisopropyl fluorophosphate in aged rats

    SciTech Connect

    Pintor, A.; Fortuna, S.; De Angelis, S.; Michalek, H. )

    1990-01-01

    Potential age-related differences in the recovery rate of brain cholinesterase activity (ChE) and muscarinic acetylcholine receptor binding sites (mAChRs) following reduction induced by repeated treatment with diisopropyl fluorophosphate (DFP) were evaluated in Sprague-Dawley rats. Male 3- and 24-month old rats were s.c. injected with DFP on alternate days for 2 weeks and killed 48 hr and 7, 14, 21, 28 and 35 days after the last treatment. In the hippocampus and striatum, but not in the cerebral cortex, of control rats there as a significant age-related decline of ChE activity and maximal density of 3H-QNB binding sites (Bmax). The repeated administration of DFP during the first week caused a syndrome of cholinergic stimulation both in aged and young rats. The syndrome was more pronounced, in terms of intensity and duration in aged than in young animals resulting in 40 and 12% mortality, respectively; during the second week the syndrome attenuated in the two age-groups. The percentage inhibition of brain ChE at the end of DFP treatment did not differ between young and surviving aged rats. The down-regulation of mACRs was present in the three brain regions of both young and age rats (from 20 to 40%). Factorial analysis of variance showed significant differences for age, recovery rate, and significant interaction between age and recovery rate, both for ChE and mAChRs in young rats the three brain areas.

  17. Regulation of the Axillary Osmidrosis-Associated ABCC11 Protein Stability by N-Linked Glycosylation: Effect of Glucose Condition.

    PubMed

    Toyoda, Yu; Takada, Tappei; Miyata, Hiroshi; Ishikawa, Toshihisa; Suzuki, Hiroshi

    2016-01-01

    ATP-binding cassette C11 (ABCC11) is a plasma membrane protein involved in the transport of a variety of lipophilic anions. ABCC11 wild-type is responsible for the high-secretion phenotypes in human apocrine glands, such as that of wet-type ear wax, and the risk of axillary osmidrosis. We have previously reported that mature ABCC11 is a glycoprotein containing two N-linked glycans at Asn838 and Asn844. However, little is known about the role of N-linked glycosylation in the regulation of ABCC11 protein. In the current study, we investigated the effects of N-linked glycosylation on the protein level and localization of ABCC11 using polarized Madin-Darby canine kidney II cells. When the N-linked glycosylation in ABCC11-expressing cells was chemically inhibited by tunicamycin treatment, the maturation of ABCC11 was suppressed and its protein level was significantly decreased. Immunoblotting analyses demonstrated that the protein level of the N-linked glycosylation-deficient mutant (N838Q and N844Q: Q838/844) was about half of the ABCC11 wild-type level. Further biochemical studies with the Q838/844 mutant showed that this glycosylation-deficient ABCC11 was degraded faster than wild-type probably due to the enhancement of the MG132-sensitive protein degradation pathway. Moreover, the incubation of ABCC11 wild-type-expressing cells in a low-glucose condition decreased mature, glycosylated ABCC11, compared with the high-glucose condition. On the other hand, the protein level of the Q838/844 mutant was not affected by glucose condition. These results suggest that N-linked glycosylation is important for the protein stability of ABCC11, and physiological alteration in glucose may affect the ABCC11 protein level and ABCC11-related phenotypes in humans, such as axillary osmidrosis.

  18. Regulation of the Axillary Osmidrosis-Associated ABCC11 Protein Stability by N-Linked Glycosylation: Effect of Glucose Condition

    PubMed Central

    Toyoda, Yu; Takada, Tappei; Miyata, Hiroshi; Ishikawa, Toshihisa; Suzuki, Hiroshi

    2016-01-01

    ATP-binding cassette C11 (ABCC11) is a plasma membrane protein involved in the transport of a variety of lipophilic anions. ABCC11 wild-type is responsible for the high-secretion phenotypes in human apocrine glands, such as that of wet-type ear wax, and the risk of axillary osmidrosis. We have previously reported that mature ABCC11 is a glycoprotein containing two N-linked glycans at Asn838 and Asn844. However, little is known about the role of N-linked glycosylation in the regulation of ABCC11 protein. In the current study, we investigated the effects of N-linked glycosylation on the protein level and localization of ABCC11 using polarized Madin-Darby canine kidney II cells. When the N-linked glycosylation in ABCC11-expressing cells was chemically inhibited by tunicamycin treatment, the maturation of ABCC11 was suppressed and its protein level was significantly decreased. Immunoblotting analyses demonstrated that the protein level of the N-linked glycosylation-deficient mutant (N838Q and N844Q: Q838/844) was about half of the ABCC11 wild-type level. Further biochemical studies with the Q838/844 mutant showed that this glycosylation-deficient ABCC11 was degraded faster than wild-type probably due to the enhancement of the MG132-sensitive protein degradation pathway. Moreover, the incubation of ABCC11 wild-type-expressing cells in a low-glucose condition decreased mature, glycosylated ABCC11, compared with the high-glucose condition. On the other hand, the protein level of the Q838/844 mutant was not affected by glucose condition. These results suggest that N-linked glycosylation is important for the protein stability of ABCC11, and physiological alteration in glucose may affect the ABCC11 protein level and ABCC11-related phenotypes in humans, such as axillary osmidrosis. PMID:27281343

  19. Administrative Synergy

    ERIC Educational Resources Information Center

    Hewitt, Kimberly Kappler; Weckstein, Daniel K.

    2012-01-01

    One of the biggest obstacles to overcome in creating and sustaining an administrative professional learning community (PLC) is time. Administrators are constantly deluged by the tyranny of the urgent. It is a Herculean task to carve out time for PLCs, but it is imperative to do so. In this article, the authors describe how an administrative PLC…

  20. Plant Signals Disrupt (regulate?) Arbuscular Mycorrhizal Fungal Growth Under Enhanced Ozone and CO2 Growing Conditions for Populus tremuloides

    NASA Astrophysics Data System (ADS)

    Miller, R. M.; Podila, G. K.

    2008-12-01

    evaluating microarray data of more than 2300 genes that are regulated (out of 25,000) in aspen mycorrhizal roots, the eCO2 responsive and eO3 tolerant aspen ecotype 271 demonstrated upregulation for antioxidant genes under eCO2+eO3 conditions. We found decreased expression of both neutral and acid invertase genes indicating that the availability of carbohydrate to the fungus is reduced. We also found an increase in plant amino acid transporters under eO3 and eCO2+eO3 that partitions more nitrogen to the plant from mycorrhizal roots and triggers the fungus into an N-starvation and lipid storage mode. This observation is supported by down-regulation of genes involved in nitrogen utilization in Glomus and the enrichment of hyphal 15N content, as well as an increase in the AMF marker storage lipid (neutral fatty acid 16:1w5c)in the root. The up-regulation of pathways involved in the formation of triglycerides that can be taken up by the fungus may be a critical step for changes in Glomus lipid metabolism. Also, in support of the above findings, is the rather high expression of genes involved in iron sequestration by aspen clone 271 when exposed to both eO3 and eCO2+eO3 fumigation. Iron is needed for both fatty acid (FA) desaturases and fatty acid synthase. Under eCO2+eO3, we found down-regulation of FA desaturases in Glomus, suggesting reduced levels of iron could be a potential signal for the fungus to go into storage mode and reduced growth of extraradical hyphae into the soil.

  1. 48 CFR 702.170-2 - Administrator.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Administrator. 702.170-2 Section 702.170-2 Federal Acquisition Regulations System AGENCY FOR INTERNATIONAL DEVELOPMENT GENERAL DEFINITIONS OF WORDS AND TERMS Definitions 702.170-2 Administrator. Administrator means the Administrator...

  2. mRNAs involved in copper homeostasis are regulated by the nonsense-mediated mRNA decay pathway depending on environmental conditions.

    PubMed

    Peccarelli, Megan; Scott, Taylor D; Steele, Megan; Kebaara, Bessie W

    2016-01-01

    The nonsense-mediated mRNA decay pathway (NMD) is an mRNA degradation pathway that degrades mRNAs that prematurely terminate translation. These mRNAs include mRNAs with premature termination codons as well as many natural mRNAs. In Saccharomyces cerevisiae a number of features have been shown to target natural mRNAs to NMD. However, the extent to which natural mRNAs from the same functional group are regulated by NMD and how environmental conditions influence this regulation is not known. Here, we examined mRNAs involved in copper homeostasis and are predicted to be sensitive to NMD. We found that the majority of these mRNAs have long 3'-UTRs that could target them for degradation by NMD. Analysis of one of these mRNAs, COX19, found that the long 3'-UTR contributes to regulation of this mRNA by NMD. Furthermore, we examined an additional mRNA, MAC1 under low copper conditions. We found that low copper growth conditions affect NMD sensitivity of the MAC1 mRNA demonstrating that sensitivity to NMD can be altered by environmental conditions. MAC1 is a copper sensitive transcription factor that regulates genes involved with high affinity copper transport. Our results expand our understanding of how NMD regulates mRNAs from the same functional group and how the environment influences this regulation.

  3. 5 CFR 315.202 - Conversion from career-conditional to career tenure.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 5 Administrative Personnel 1 2013-01-01 2013-01-01 false Conversion from career-conditional to career tenure. 315.202 Section 315.202 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT CIVIL SERVICE REGULATIONS CAREER AND CAREER-CONDITIONAL EMPLOYMENT The Career-Conditional Employment...

  4. 5 CFR 315.202 - Conversion from career-conditional to career tenure.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 5 Administrative Personnel 1 2012-01-01 2012-01-01 false Conversion from career-conditional to career tenure. 315.202 Section 315.202 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT CIVIL SERVICE REGULATIONS CAREER AND CAREER-CONDITIONAL EMPLOYMENT The Career-Conditional Employment...

  5. 5 CFR 315.202 - Conversion from career-conditional to career tenure.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 5 Administrative Personnel 1 2014-01-01 2014-01-01 false Conversion from career-conditional to career tenure. 315.202 Section 315.202 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT CIVIL SERVICE REGULATIONS CAREER AND CAREER-CONDITIONAL EMPLOYMENT The Career-Conditional Employment...

  6. 5 CFR 315.202 - Conversion from career-conditional to career tenure.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 5 Administrative Personnel 1 2011-01-01 2011-01-01 false Conversion from career-conditional to career tenure. 315.202 Section 315.202 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT CIVIL SERVICE REGULATIONS CAREER AND CAREER-CONDITIONAL EMPLOYMENT The Career-Conditional Employment...

  7. 5 CFR 315.202 - Conversion from career-conditional to career tenure.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 5 Administrative Personnel 1 2010-01-01 2010-01-01 false Conversion from career-conditional to career tenure. 315.202 Section 315.202 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT CIVIL SERVICE REGULATIONS CAREER AND CAREER-CONDITIONAL EMPLOYMENT The Career-Conditional Employment...

  8. VERS Handbook for Administrators on Career-Vocational Education Services for Disadvantaged Students and Students with Handicapping Conditions. Fourth Revision. Impact Programs.

    ERIC Educational Resources Information Center

    Apolloni, Tony, Ed.

    This handbook was produced by the California Vocational Education Resource System (VERS) to assist administrators in planning, implementing, and monitoring career-vocational education services for students with special needs (disabled, disadvantaged, or limited English proficient) in regular vocational education classrooms. The guide is organized…

  9. Regulation of presynaptic Ca2+, synaptic plasticity and contextual fear conditioning by a N-terminal β-amyloid fragment.

    PubMed

    Lawrence, James L M; Tong, Mei; Alfulaij, Naghum; Sherrin, Tessi; Contarino, Mark; White, Michael M; Bellinger, Frederick P; Todorovic, Cedomir; Nichols, Robert A

    2014-10-22

    Soluble β-amyloid has been shown to regulate presynaptic Ca(2+) and synaptic plasticity. In particular, picomolar β-amyloid was found to have an agonist-like action on presynaptic nicotinic receptors and to augment long-term potentiation (LTP) in a manner dependent upon nicotinic receptors. Here, we report that a functional N-terminal domain exists within β-amyloid for its agonist-like activity. This sequence corresponds to a N-terminal fragment generated by the combined action of α- and β-secretases, and resident carboxypeptidase. The N-terminal β-amyloid fragment is present in the brains and CSF of healthy adults as well as in Alzheimer's patients. Unlike full-length β-amyloid, the N-terminal β-amyloid fragment is monomeric and nontoxic. In Ca(2+) imaging studies using a model reconstituted rodent neuroblastoma cell line and isolated mouse nerve terminals, the N-terminal β-amyloid fragment proved to be highly potent and more effective than full-length β-amyloid in its agonist-like action on nicotinic receptors. In addition, the N-terminal β-amyloid fragment augmented theta burst-induced post-tetanic potentiation and LTP in mouse hippocampal slices. The N-terminal fragment also rescued LTP inhibited by elevated levels of full-length β-amyloid. Contextual fear conditioning was also strongly augmented following bilateral injection of N-terminal β-amyloid fragment into the dorsal hippocampi of intact mice. The fragment-induced augmentation of fear conditioning was attenuated by coadministration of nicotinic antagonist. The activity of the N-terminal β-amyloid fragment appears to reside largely in a sequence surrounding a putative metal binding site, YEVHHQ. These findings suggest that the N-terminal β-amyloid fragment may serve as a potent and effective endogenous neuromodulator.

  10. Metabolic Regulation and Coordination of the Metabolism in Bacteria in Response to a Variety of Growth Conditions.

    PubMed

    Shimizu, Kazuyuki

    2016-01-01

    Living organisms have sophisticated but well-organized regulation system. It is important to understand the metabolic regulation mechanisms in relation to growth environment for the efficient design of cell factories for biofuels and biochemicals production. Here, an overview is given for carbon catabolite regulation, nitrogen regulation, ion, sulfur, and phosphate regulations, stringent response under nutrient starvation as well as oxidative stress regulation, redox state regulation, acid-shock, heat- and cold-shock regulations, solvent stress regulation, osmoregulation, and biofilm formation, and quorum sensing focusing on Escherichia coli metabolism and others. The coordinated regulation mechanisms are of particular interest in getting insight into the principle which governs the cell metabolism. The metabolism is controlled by both enzyme-level regulation and transcriptional regulation via transcription factors such as cAMP-Crp, Cra, Csr, Fis, P(II)(GlnB), NtrBC, CysB, PhoR/B, SoxR/S, Fur, MarR, ArcA/B, Fnr, NarX/L, RpoS, and (p)ppGpp for stringent response, where the timescales for enzyme-level and gene-level regulations are different. Moreover, multiple regulations are coordinated by the intracellular metabolites, where fructose 1,6-bisphosphate (FBP), phosphoenolpyruvate (PEP), and acetyl-CoA (AcCoA) play important roles for enzyme-level regulation as well as transcriptional control, while α-ketoacids such as α-ketoglutaric acid (αKG), pyruvate (PYR), and oxaloacetate (OAA) play important roles for the coordinated regulation between carbon source uptake rate and other nutrient uptake rate such as nitrogen or sulfur uptake rate by modulation of cAMP via Cya.

  11. [Italian Decree D.lgs 231/2001--"Regulations regarding administrative responsibilities of corporate bodies of Companies and Associations including those not legally recognized"--an organizational model for the healthcare area].

    PubMed

    Roberti, Giovanni; Fiore, Rosalia; Franco, Claudia; Pimpinella, Giovanni; Piscioneri, Patrizia

    2010-01-01

    Healthcare organizations must implement organizational and management models of regulation and control systems for effectively preventing possible administrative torts by personnel. We define an organizational management and control model for healthcare organizations, based on the legal dispositions of Decree n.231/2001. The model identifies critical points in the administrative and healthcare services delivery processes that are at high-risk of violations to the code. Its primary aim is to prevent torts by the personnel and safeguard the organization at the same time.

  12. 7 CFR 3411.9 - Other conditions.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 15 2010-01-01 2010-01-01 false Other conditions. 3411.9 Section 3411.9 Agriculture Regulations of the Department of Agriculture (Continued) COOPERATIVE STATE RESEARCH, EDUCATION, AND EXTENSION....9 Other conditions. The Administrator may, with respect to any grant or to any class of...

  13. 78 FR 4026 - Definition of Troubled Condition

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-01-18

    ... ADMINISTRATION 12 CFR Parts 700, 701, 741, 747, and 750 RIN 3133-AD97 Definition of Troubled Condition AGENCY... a final rule amending the definition of ``troubled condition'' as that term is used to trigger the... officials, and as that term appears elsewhere in NCUA's regulations. Generally, the current...

  14. 77 FR 45285 - Definition of Troubled Condition

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-07-31

    ... ADMINISTRATION 12 CFR Parts 700, 701, 741 and 750 RIN 3133-AD97 Definition of Troubled Condition AGENCY: National... proposes to amend the definition of ``troubled condition'' as that term appears in Sec. 701.14 and elsewhere in NCUA's regulations. Generally, under the current definition, only a state supervisory...

  15. Ncl Synchronously Regulates Na+, K+, and Cl− in Soybean and Greatly Increases the Grain Yield in Saline Field Conditions

    PubMed Central

    Do, Tuyen Duc; Chen, Huatao; Hien, Vu Thi Thu; Hamwieh, Aladdin; Yamada, Tetsuya; Sato, Tadashi; Yan, Yongliang; Cong, Hua; Shono, Mariko; Suenaga, Kazuhiro; Xu, Donghe

    2016-01-01

    Salt stress inhibits soybean growth and reduces gain yield. Genetic improvement of salt tolerance is essential for sustainable soybean production in saline areas. In this study, we isolated a gene (Ncl) that could synchronously regulate the transport and accumulation of Na+, K+, and Cl− from a Brazilian soybean cultivar FT-Abyara using map-based cloning strategy. Higher expression of the salt tolerance gene Ncl in the root resulted in lower accumulations of Na+, K+, and Cl− in the shoot under salt stress. Transfer of Ncl with the Agrobacterium-mediated transformation method into a soybean cultivar Kariyutaka significantly enhanced its salt tolerance. Introgression of the tolerance allele into soybean cultivar Jackson, using DNA marker-assisted selection (MAS), produced an improved salt tolerance line. Ncl could increase soybean grain yield by 3.6–5.5 times in saline field conditions. Using Ncl in soybean breeding through gene transfer or MAS would contribute to sustainable soybean production in saline-prone areas. PMID:26744076

  16. Pathways Regulating Spheroid Formation of Human Follicular Thyroid Cancer Cells under Simulated Microgravity Conditions: A Genetic Approach

    PubMed Central

    Riwaldt, Stefan; Bauer, Johann; Wehland, Markus; Slumstrup, Lasse; Kopp, Sascha; Warnke, Elisabeth; Dittrich, Anita; Magnusson, Nils E.; Pietsch, Jessica; Corydon, Thomas J.; Infanger, Manfred; Grimm, Daniela

    2016-01-01

    Microgravity induces three-dimensional (3D) growth in numerous cell types. Despite substantial efforts to clarify the underlying mechanisms for spheroid formation, the precise molecular pathways are still not known. The principal aim of this paper is to compare static 1g-control cells with spheroid forming (MCS) and spheroid non-forming (AD) thyroid cancer cells cultured in the same flask under simulated microgravity conditions. We investigated the morphology and gene expression patterns in human follicular thyroid cancer cells (UCLA RO82-W-1 cell line) after a 24 h-exposure on the Random Positioning Machine (RPM) and focused on 3D growth signaling processes. After 24 h, spheroid formation was observed in RPM-cultures together with alterations in the F-actin cytoskeleton. qPCR indicated more changes in gene expression in MCS than in AD cells. Of the 24 genes analyzed VEGFA, VEGFD, MSN, and MMP3 were upregulated in MCS compared to 1g-controls, whereas ACTB, ACTA2, KRT8, TUBB, EZR, RDX, PRKCA, CAV1, MMP9, PAI1, CTGF, MCP1 were downregulated. A pathway analysis revealed that the upregulated genes code for proteins, which promote 3D growth (angiogenesis) and prevent excessive accumulation of extracellular proteins, while genes coding for structural proteins are downregulated. Pathways regulating the strength/rigidity of cytoskeletal proteins, the amount of extracellular proteins, and 3D growth may be involved in MCS formation. PMID:27070589

  17. 5 CFR 831.101 - Administration.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 5 Administrative Personnel 2 2010-01-01 2010-01-01 false Administration. 831.101 Section 831.101 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT (CONTINUED) CIVIL SERVICE REGULATIONS (CONTINUED) RETIREMENT Administration and General Provisions § 831.101 Administration. (a) OPM has charge of...

  18. 7 CFR 56.3 - Administration.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 3 2011-01-01 2011-01-01 false Administration. 56.3 Section 56.3 Agriculture... EGGS Grading of Shell Eggs General § 56.3 Administration. The Administrator shall perform, for and... administration of the provisions of the Act and the regulations in this part. The Administrator is authorized...

  19. 7 CFR 56.3 - Administration.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 3 2010-01-01 2010-01-01 false Administration. 56.3 Section 56.3 Agriculture... EGGS Grading of Shell Eggs General § 56.3 Administration. The Administrator shall perform, for and... administration of the provisions of the Act and the regulations in this part. The Administrator is authorized...

  20. 5 CFR 179.307 - Administrative offset.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 5 Administrative Personnel 1 2014-01-01 2014-01-01 false Administrative offset. 179.307 Section 179.307 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT CIVIL SERVICE REGULATIONS CLAIMS COLLECTION STANDARDS Administrative Offset § 179.307 Administrative offset. (a) If the debtor does...

  1. PprM is necessary for up-regulation of katE1, encoding the major catalase of Deinococcus radiodurans, under unstressed culture conditions.

    PubMed

    Jeong, Sun-Wook; Seo, Ho Seong; Kim, Min-Kyu; Choi, Jong-Il; Lim, Heon-Man; Lim, Sangyong

    2016-06-01

    Deinococcus radiodurans is a poly-extremophilic organism, capable of tolerating a wide variety of different stresses, such as gamma/ultraviolet radiation, desiccation, and oxidative stress. PprM, a cold shock protein homolog, is involved in the radiation resistance of D. radiodurans, but its role in the oxidative stress response has not been investigated. In this study, we investigated the effect of pprM mutation on catalase gene expression. pprM disruption decreased the mRNA and protein levels of KatE1, which is the major catalase in D. radiodurans, under normal culture conditions. A pprM mutant strain (pprM MT) exhibited decreased catalase activity, and its resistance to hydrogen peroxide (H2O2) decreased accordingly compared with that of the wild-type strain. We confirmed that RecG helicase negatively regulates katE1 under normal culture conditions. Among katE1 transcriptional regulators, the positive regulator drRRA was not altered in pprM (-), while the negative regulators perR, dtxR, and recG were activated more than 2.5-fold in pprM MT. These findings suggest that PprM is necessary for KatE1 production under normal culture conditions by down-regulation of katE1 negative regulators.

  2. Administrative Ecology

    ERIC Educational Resources Information Center

    McGarity, Augustus C., III; Maulding, Wanda

    2007-01-01

    This article discusses how all four facets of administrative ecology help dispel the claims about the "impossibility" of the superintendency. These are personal ecology, professional ecology, organizational ecology, and community ecology. Using today's superintendency as an administrative platform, current literature describes a preponderance of…

  3. Homology-Based Modeling of Universal Stress Protein from Listeria innocua Up-Regulated under Acid Stress Conditions

    PubMed Central

    Tremonte, Patrizio; Succi, Mariantonietta; Coppola, Raffaele; Sorrentino, Elena; Tipaldi, Luca; Picariello, Gianluca; Pannella, Gianfranco; Fraternali, Franca

    2016-01-01

    An Universal Stress Protein (USP) expressed under acid stress condition by Listeria innocua ATCC 33090 was investigated. The USP was up-regulated not only in the stationary phase but also during the exponential growth phase. The three dimensional (3D) structure of USP was predicted using a combined proteomic and bioinformatics approach. Phylogenetic analysis showed that the USP from Listeria detected in our study was distant from the USPs of other bacteria (such as Pseudomonas spp., Escherichia coli, Salmonella spp.) and clustered in a separate and heterogeneous class including several USPs from Listeria spp. and Lactobacillus spp. An important information on the studied USP was obtained from the 3D-structure established through the homology modeling procedure. In detail, the Model_USP-691 suggested that the investigated USP had a homo-tetrameric quaternary structure. Each monomer presented an architecture analogous to the Rossmann-like α/β-fold with five parallel β-strands, and four α-helices. The analysis of monomer-monomer interfaces and quality of the structure alignments confirmed the model reliability. In fact, the structurally and sequentially conserved hydrophobic residues of the β-strand 5 (in particular the residues V146 and V148) were involved in the inter-chains contact. Moreover, the highly conserved residues I139 and H141 in the region α4 were involved in the dimer association and functioned as hot spots into monomer–monomer interface assembly. The hypothetical assembly of dimers was also supported by the large interface area and by the negative value of solvation free energy gain upon interface interaction. Finally, the structurally conserved ATP-binding motif G-2X-G-9X-G(S/T-N) suggested for a putative role of ATP in stabilizing the tetrameric assembly of the USP. Therefore, the results obtained from a multiple approach, consisting in the application of kinetic, proteomic, phylogenetic and modeling analyses, suggest that Listeria USP could

  4. 7 CFR 352.3 - Enforcement and administration.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 5 2010-01-01 2010-01-01 false Enforcement and administration. 352.3 Section 352.3 Agriculture Regulations of the Department of Agriculture (Continued) ANIMAL AND PLANT HEALTH INSPECTION... Programs shall find that existing conditions of danger of plant pest escape or dissemination involved...

  5. 7 CFR 352.3 - Enforcement and administration.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 5 2011-01-01 2011-01-01 false Enforcement and administration. 352.3 Section 352.3 Agriculture Regulations of the Department of Agriculture (Continued) ANIMAL AND PLANT HEALTH INSPECTION... Protection and Quarantine Programs shall find that existing conditions of danger of plant pest escape...

  6. 7 CFR 301.76-7 - Additional conditions for issuance of certificates and limited permits for regulated articles...

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... limited permits for regulated articles moved interstate from areas quarantined for citrus greening. 301.76... permits for regulated articles moved interstate from areas quarantined for citrus greening. (a) Additional... moved interstate in that container. (4) A copy of the certificate is attached to the consignee's copy...

  7. 7 CFR 301.76-7 - Additional conditions for issuance of certificates and limited permits for regulated articles...

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... limited permits for regulated articles moved interstate from areas quarantined for citrus greening. 301.76... permits for regulated articles moved interstate from areas quarantined for citrus greening. (a) Additional... moved interstate in that container. (4) A copy of the certificate is attached to the consignee's copy...

  8. 7 CFR 301.76-7 - Additional conditions for issuance of certificates and limited permits for regulated articles...

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... limited permits for regulated articles moved interstate from areas quarantined for citrus greening. 301.76... permits for regulated articles moved interstate from areas quarantined for citrus greening. (a) Additional... limited permit attached to the consignee's copy of the waybill. (5) The nursery stock is moved...

  9. 7 CFR 301.76-6 - Additional conditions for issuance of certificates and limited permits for regulated articles...

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... limited permits for regulated articles moved interstate from areas quarantined for Asian citrus psyllid... certificates and limited permits for regulated articles moved interstate from areas quarantined for Asian... be moved interstate is clearly labeled with the certificate. (4) A copy of the certificate will...

  10. 7 CFR 301.76-7 - Additional conditions for issuance of certificates and limited permits for regulated articles...

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... limited permits for regulated articles moved interstate from areas quarantined for citrus greening. 301.76... permits for regulated articles moved interstate from areas quarantined for citrus greening. (a) Additional... moved interstate in that container. (4) A copy of the certificate is attached to the consignee's copy...

  11. 7 CFR 301.76-6 - Additional conditions for issuance of certificates and limited permits for regulated articles...

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... limited permits for regulated articles moved interstate from areas quarantined for Asian citrus psyllid... certificates and limited permits for regulated articles moved interstate from areas quarantined for Asian... be moved interstate is clearly labeled with the certificate. (4) A copy of the certificate will...

  12. 7 CFR 301.76-6 - Additional conditions for issuance of certificates and limited permits for regulated articles...

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... limited permits for regulated articles moved interstate from areas quarantined for Asian citrus psyllid... certificates and limited permits for regulated articles moved interstate from areas quarantined for Asian... been sealed with an agricultural seal placed by an inspector. (3) The container that will be...

  13. 7 CFR 301.76-6 - Additional conditions for issuance of certificates and limited permits for regulated articles...

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... limited permits for regulated articles moved interstate from areas quarantined only for Asian citrus... issuance of certificates and limited permits for regulated articles moved interstate from areas quarantined... be moved interstate is clearly labeled with the certificate. (4) A copy of the certificate will...

  14. A genome-wide siRNA screen reveals multiple mTORC1 independent signaling pathways regulating autophagy under normal nutritional conditions

    PubMed Central

    Lipinski, Marta M.; Hoffman, Greg; Ng, Aylwin; Zhou, Wen; Py, Bénédicte F.; Hsu, Emily; Liu, Xuxin; Eisenberg, Jason; Liu, Jun; Blenis, John; Xavier, Ramnik J.; Yuan, Junying

    2010-01-01

    Summary Autophagy is a cellular catabolic mechanism that plays an essential function in protecting multicellular eukaryotes from neurodegeneration, cancer and other diseases. However, we still know very little about mechanisms regulating autophagy under normal homeostatic conditions when nutrients are not limiting. In a genome-wide human siRNA screen, we demonstrate that under normal nutrient conditions up regulation of autophagy requires the type III PI3 kinase, but not inhibition of mTORC1, the essential negative regulator of starvation-induced autophagy. We show that a group of growth factors and cytokines inhibit the type III PI3 kinase through multiple pathways, including the MAPK-ERK1/2, Stat3, Akt/Foxo3 and CXCR4/GPCR, which are all known to positively regulate cell growth and proliferation. Our study suggests that the type III PI3 kinase integrates diverse signals to regulate cellular levels of autophagy, and that autophagy and cell proliferation may represent two alternative cell fates that are regulated in a mutually exclusive manner. PMID:20627085

  15. Inhibition of mitogen-activated protein kinase-extracellular signal-regulated kinase disrupts latent inhibition of cued fear conditioning in C57BL/6 mice.

    PubMed

    Lewis, Michael C; Davis, Jennifer A; Gould, Thomas J

    2004-12-01

    The mitogen-activated protein kinase (MAPK)-extracellular signal-regulated kinase (ERK) cascade has been implicated in a variety of associative conditioning tasks. However, the role of the MAPK-ERK cascades in modulating conditioning is less clear. The authors examined the effect of the potent and selective MAPK-ERK inhibitor SL327 on latent inhibition of cued fear conditioning. The results demonstrate that 50 mg/kg and 100 mg/kg SL327 disrupt latent inhibition of cued fear conditioning. These data provide evidence for an essential role of the MAPK-ERK cascade in tasks that modulate the strength of associative conditioning. The results are discussed in relation to the molecular mechanisms that support latent inhibition of cued fear conditioning.

  16. The Effect on the Flow Conditions of Chinese Sturgeons’ Spawning Sites in the Process of Peak Regulation between the Three Gorges Dam and Gezhou Dam

    NASA Astrophysics Data System (ADS)

    Hui, Guo; Minghai, Huang; Feng, Jin

    Chinese sturgeon (Acipenser sinensis Gray) is a kind of key protected fish in ChangJiang river. Recently the Three Gorges dam has run, the peak regulation process between the two dams has serious effect on the formed spawning sites. Based on the previous research results of suitable flow conditions about the spawning sites, this article builds a 2-D shallow water numerical model, calculates the flow conditions of the spawning sites in the process of peak regulation. The results show that the water depth and velocity are various and affect the spawning sites in one 24-hours process of peak regulation, as a whole, when the discharge is below 9000 m3/s and 7500 m3/s respectively, the two spawning sites will be affected seriously.

  17. PIF1 promotes phytochrome-regulated growth under photoperiodic conditions in Arabidopsis together with PIF3, PIF4, and PIF5

    PubMed Central

    Soy, Judit; Leivar, Pablo; Monte, Elena

    2014-01-01

    Seedlings growing under diurnal conditions display maximal growth at the end of the night in short-day (SD) photoperiods. Current evidence indicates that this behaviour involves the action of PHYTOCHROME-INTERACTING FACTOR 3 (PIF3) together with PIF4 and PIF5, through direct regulation of growth-related genes at dawn coinciding with a PIF3 accumulation peak generated by phytochrome-imposed oscillations in protein abundance. Here, to assess how alterations in PIF3 levels impact seedling growth, the night-specific accumulation of PIF3 was modulated by releasing SD-grown seedlings into continuous light, or by exposing them to a phytochrome-inactivating end-of-day far-red pulse (EOD-FRp). The data show a strong direct correlation between PIF3 accumulation, PIF3-regulated induction of growth-related genes, and hypocotyl elongation, and suggest that growth promotion in SD conditions involves factors other than PIF3, PIF4, and PIF5. Using a pif1 mutant, evidence is provided that PIF1 also contributes to inducing hypocotyl elongation during the dark period under diurnal conditions. PIF1 displayed constitutive transcript levels in SD conditions, suggesting that phytochrome-imposed oscillations in PIF1 protein abundance determine its accumulation and action during the night, similar to PIF3 and in contrast to PIF4 and PIF5, which oscillate diurnally due to a combination of circadian clock-regulated transcription and light control of protein accumulation. Furthermore, using single and higher order pif mutants, the relative contribution of each member of the PIF quartet to the regulation of morphogenesis and the expression of selected growth marker genes under SD conditions, or under SD conditions supplemented with an EOD-FRp, is defined. Collectively, the data indicate that PIF1, PIF3, PIF4, and PIF5 act together to promote and optimize growth under photoperiodic conditions. PMID:24420574

  18. Streamflow statistics for unregulated and regulated conditions for selected locations on the Yellowstone, Tongue, and Powder Rivers, Montana, 1928-2002

    USGS Publications Warehouse

    Chase, Katherine J.

    2013-01-01

    Major floods in 1996 and 1997 on the Yellowstone River in Montana intensified public debate over the effects of human activities on the Yellowstone River. In 1999, the Yellowstone River Conservation District Council was formed to address conservation issues on the river. The Yellowstone River Conservation District Council partnered with the U.S. Army Corps of Engineers to conduct a cumulative-effects study on the main stem of the Yellowstone River. The cumulative-effects study is intended to provide a basis for future management decisions in the watershed. Streamflow statistics, such as flow-frequency and flow-duration data calculated for unregulated and regulated streamflow conditions, are a necessary component of the cumulative effects study. The U.S. Geological Survey, in cooperation with the Yellowstone River Conservation District Council and the U.S. Army Corps of Engineers, calculated streamflow statistics for unregulated and regulated conditions for the Yellowstone, Tongue, and Powder Rivers for the 1928–2002 study period. Unregulated streamflow represents flow conditions that might have occurred during the 1928–2002 study period if there had been no water-resources development in the Yellowstone River Basin. Regulated streamflow represents estimates of flow conditions during the 1928–2002 study period if the level of water-resources development existing in 2002 was in place during the entire study period. Peak-flow frequency estimates for regulated and unregulated streamflow were developed using methods described in Bulletin 17B. High-flow frequency and low-flow frequency data were developed for regulated and unregulated streamflows from the annual series of highest and lowest (respectively) mean flows for specified n-day consecutive periods within the calendar year. Flow-duration data, and monthly and annual streamflow characteristics, also were calculated for the unregulated and regulated streamflows.

  19. 5 CFR 831.1804 - Conditions for requesting an offset.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 5 Administrative Personnel 2 2010-01-01 2010-01-01 false Conditions for requesting an offset. 831.1804 Section 831.1804 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT (CONTINUED) CIVIL SERVICE REGULATIONS (CONTINUED) RETIREMENT Agency Requests to OPM for Recovery of a Debt from the Civil...

  20. 5 CFR 359.902 - Conditions of removal.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 5 Administrative Personnel 1 2010-01-01 2010-01-01 false Conditions of removal. 359.902 Section 359.902 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT CIVIL SERVICE REGULATIONS REMOVAL FROM THE SENIOR EXECUTIVE SERVICE; GUARANTEED PLACEMENT IN OTHER PERSONNEL SYSTEMS Removal of Noncareer...