Science.gov

Sample records for administrative regulations conditions

  1. 78 FR 29245 - U.S. General Services Administration Federal Property Management Regulations; Administrative Wage...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-05-20

    ... Administration Federal Property Management Regulations; Administrative Wage Garnishment AGENCY: Office of the... amending the U.S. General Services Administration Property Management Regulation (GSPMR) to remove... telephone number. The Administrative Wage Garnishment Code of Federal Regulations (CFR) Parts affected...

  2. Administrative Regulations: Department of Desegregation Implementation.

    ERIC Educational Resources Information Center

    Fleming, Margaret, Ed.

    Pursuant to the July 1979 Remedial Order of the Federal District Court, this document represents the Cleveland Board of Education Administrative Regulations for the desegregation of the Cleveland school system. Seventeen areas are covered by the regulations: transportation, student assignments, safety and security, community relations, student…

  3. 77 FR 40493 - Export Administration Regulations

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-07-10

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF COMMERCE Bureau of Industry and Security 15 CFR Parts 740, 742, 748, 750, 752, and 760 Export Administration Regulations CFR Correction In Title 15 of the Code of Federal Regulations, Parts 300 to 799, revised as...

  4. 7 CFR 52.1 - Administration of regulations.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... MARKETING ACT OF 1946 PROCESSED FRUITS AND VEGETABLES, PROCESSED PRODUCTS THEREOF, AND CERTAIN OTHER PROCESSED FOOD PRODUCTS 1 Regulations Governing Inspection and Certification § 52.1 Administration...

  5. 7 CFR 52.1 - Administration of regulations.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... MARKETING ACT OF 1946 PROCESSED FRUITS AND VEGETABLES, PROCESSED PRODUCTS THEREOF, AND CERTAIN OTHER PROCESSED FOOD PRODUCTS 1 Regulations Governing Inspection and Certification § 52.1 Administration...

  6. 7 CFR 52.1 - Administration of regulations.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... MARKETING ACT OF 1946 PROCESSED FRUITS AND VEGETABLES, PROCESSED PRODUCTS THEREOF, AND CERTAIN OTHER PROCESSED FOOD PRODUCTS 1 Regulations Governing Inspection and Certification § 52.1 Administration...

  7. 42 CFR 417.412 - Qualifying condition: Administration and management.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... AND HUMAN SERVICES (CONTINUED) MEDICARE PROGRAM HEALTH MAINTENANCE ORGANIZATIONS, COMPETITIVE MEDICAL... 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)...

  8. 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...

  9. Charge regulation: A generalized boundary condition?

    NASA Astrophysics Data System (ADS)

    Markovich, Tomer; Andelman, David; Podgornik, Rudi

    2016-01-01

    The three most commonly used boundary conditions for charged colloidal systems are constant charge (insulator), constant potential (conducting electrode) and charge regulation (ionizable groups at the surface). It is usually believed that the charge regulation is a generalized boundary condition that reduces in some specific limits to either constant-charge or constant-potential boundary conditions. By computing the disjoining pressure between two symmetric planes for these three boundary conditions, both numerically (for all inter-plate separations) and analytically (for small inter-plate separations), we show that this is not, in general, the case. In fact, the limit of charge regulation is a separate boundary condition, yielding a disjoining pressure with a different characteristic separation scaling. Our findings are supported by several examples demonstrating that the disjoining pressure at small separations for the charge regulation boundary condition depends on the details of the dissociation/association process.

  10. 42 CFR 493.1100 - Condition: Facility administration.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 42 Public Health 5 2011-10-01 2011-10-01 false Condition: Facility administration. 493.1100 Section 493.1100 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) STANDARDS AND CERTIFICATION LABORATORY REQUIREMENTS Facility Administration...

  11. 42 CFR 493.1100 - Condition: Facility administration.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 5 2010-10-01 2010-10-01 false Condition: Facility administration. 493.1100 Section 493.1100 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) STANDARDS AND CERTIFICATION LABORATORY REQUIREMENTS Facility Administration...

  12. 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…

  13. 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.

  14. 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.... (see 15 CFR 758.1(b) and 772.1, definition of the United States.) (b) Requirements to place...

  15. 15 CFR 30.16 - Export Administration Regulations.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 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.... (see 15 CFR 758.1(b) and 772.1, definition of the United States.) (b) Requirements to place...

  16. 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.... (see 15 CFR 758.1(b) and 772.1, definition of the United States.) (b) Requirements to place...

  17. 7 CFR 1150.272 - Responsibility for administration of regulations.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... MARKETING SERVICE (Marketing Agreements and Orders; Milk), DEPARTMENT OF AGRICULTURE DAIRY PROMOTION PROGRAM Procedure for Certification of Milk Producer Organizations § 1150.272 Responsibility for administration of regulations. The Dairy Division shall have the responsibility for administering the provisions of this subpart....

  18. 7 CFR 1150.272 - Responsibility for administration of regulations.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... MARKETING SERVICE (Marketing Agreements and Orders; Milk), DEPARTMENT OF AGRICULTURE DAIRY PROMOTION PROGRAM Procedure for Certification of Milk Producer Organizations § 1150.272 Responsibility for administration of regulations. The Dairy Division shall have the responsibility for administering the provisions of this subpart....

  19. 7 CFR 1150.272 - Responsibility for administration of regulations.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... MARKETING SERVICE (MARKETING AGREEMENTS AND ORDERS; MILK), DEPARTMENT OF AGRICULTURE DAIRY PROMOTION PROGRAM Procedure for Certification of Milk Producer Organizations § 1150.272 Responsibility for administration of regulations. The Dairy Division shall have the responsibility for administering the provisions of this subpart....

  20. Flavor preference conditioning by oral self-administration of ethanol.

    PubMed

    Cunningham, C L; Niehus, J S

    1997-12-01

    Oral self-administration and operant tasks have been used successfully to confirm ethanol's positive reinforcing effects in rats. However, in flavor conditioning tasks, ethanol is typically found to have aversive effects. The present studies explored this apparent paradox by examining the change in value of a flavor paired with orally self-administered ethanol in two different limited-access procedures. Rats were food-deprived and trained to drink (experiment 1) or to barpress for (experiment 2) 10% (v/v) ethanol during daily 30-min sessions using prandial initiation techniques. All rats were then exposed to a differential flavor conditioning procedure in which banana or almond extract was added to the drinking solution. One flavor (counterbalanced) was always mixed with ethanol (CS+), whereas the other flavor was mixed with water (CS-). By the end of conditioning, rats in both experiments drank more flavored ethanol than flavored water, confirming ethanol's efficacy as a reinforcer. Moreover, barpress rates for CS+ exceeded those for CS- in the operant task. Ethanol doses self-administered in final sessions averaged about 1 g/kg. The effect of the flavor-ethanol contingency was assessed in preference tests that offered a choice between the two flavor solutions without ethanol. In both experiments, subjects developed a preference for the flavor that had been paired with ethanol. Thus, the outcome of flavor conditioning was consistent with that of the oral self-administration tasks in providing evidence of ethanol's rewarding effects. These experiments confirm and extend previous studies showing that flavor aversion is not the inevitable result of flavor-ethanol association in rats. It seems likely that ethanol's nutrient and pharmacological effects both contributed to the development of conditioned flavor preference.

  1. 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...

  2. Differential facilitative effects of glucose administration on Stroop task conditions.

    PubMed

    Brandt, Karen R; Gibson, E Leigh; Rackie, James M

    2013-12-01

    Previous research has demonstrated that glucose administration improves memory performance. These glucose facilitation effects have been most reliably demonstrated in medial temporal lobe tasks with the greatest effects found for cognitively demanding tasks. The aim of the proposed research was to first explore whether such effects might be demonstrated in a frontal lobe task. A second aim was to investigate whether any beneficial effects of glucose may arise more prominently under tasks of increasing cognitive demand. To achieve these aims, the Stroop Task was administered to participants and effects of a drink of glucose (25 g) were compared with an aspartame-sweetened control drink on performance in young adults. Results demonstrated that glucose ingestion significantly reduced RTs in the congruent and incongruent conditions. No effect on error rates was observed. Of most importance was the finding that this glucose facilitative effect was significantly greatest in the most cognitively demanding task, that is, the incongruent condition. The present results support the contention that the glucose facilitation effect is most robust under conditions of enhanced task difficulty and demonstrate that such benefits extend to frontal lobe function.

  3. 77 FR 66466 - General Services Administration Regulation; Information Collection; Packing List Clause

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-11-05

    ... From the Federal Register Online via the Government Publishing Office GENERAL SERVICES ADMINISTRATION General Services Administration Regulation; Information Collection; Packing List Clause AGENCY... information collection documents from the General Services Administration, Regulatory Secretariat (MVCB),...

  4. 77 FR 5020 - General Services Administration Acquisition Regulation; Information Collection; GSA Form 527...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-02-01

    ... ADMINISTRATION General Services Administration Acquisition Regulation; Information Collection; GSA Form 527... and Financial Information'' on your attached document. Fax: (202) 501-4067. Mail: General Services... provided. SUPPLEMENTARY INFORMATION: A. Purpose The General Services Administration will be requesting...

  5. 13 CFR 101.407 - May the Administrator waive these regulations?

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 13 Business Credit and Assistance 1 2010-01-01 2010-01-01 false May the Administrator waive these regulations? 101.407 Section 101.407 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION ADMINISTRATION Intergovernmental Partnership § 101.407 May the Administrator waive these regulations?...

  6. Conditional gene vectors regulated in cis

    PubMed Central

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

    2008-01-01

    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. PMID:18566006

  7. 75 FR 59102 - Defense Federal Acquisition Regulation Supplement; Part 204, Administrative Matters

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-27

    ... guidance on mapping PII and supplementary PII numbers stored in the Electronic Document Access system to... Defense Acquisition Regulations System 48 CFR Part 204 Defense Federal Acquisition Regulation Supplement; Part 204, Administrative Matters AGENCY: Defense Acquisition Regulations System, Department of...

  8. 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

    ... condition standards as required by 24 CFR part 5, subpart G, the Regulatory Agreement and/or the Housing... 24 Housing and Urban Development 2 2010-04-01 2010-04-01 false Administrative process for scoring... and Urban Development Regulations Relating to Housing and Urban Development (Continued) OFFICE...

  9. 41 CFR 105-1.101 - General Services Administration Property Management Regulations.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ...-INTRODUCTION 1.1-Regulations System § 105-1.101 General Services Administration Property Management Regulations... 41 Public Contracts and Property Management 3 2010-07-01 2010-07-01 false General Services Administration Property Management Regulations. 105-1.101 Section 105-1.101 Public Contracts and...

  10. Scientific Self-Regulation: A Brief Primer for Research Administrators

    ERIC Educational Resources Information Center

    Atkinson, Timothy N.

    2005-01-01

    The National Academies of Science recently recommended a battery of guidelines for Academe to create an "environment" conducive to the responsible conduct of research. These guidelines affect the research administration field as a whole, as research administrators will be expected to assist in these changes. Research administrators,…

  11. 76 FR 81941 - General Services Administration Acquisition Regulation; Information Collection; Price Reductions...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-29

    ... From the Federal Register Online via the Government Publishing Office GENERAL SERVICES ADMINISTRATION General Services Administration Acquisition Regulation; Information Collection; Price Reductions.... FOR FURTHER INFORMATION CONTACT: Ms. Dana Munson, General Services Acquisition Policy Division,...

  12. 78 FR 27239 - General Services Administration Acquisition Regulation; Submission for OMB Review; Industrial...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-05-09

    ... ADMINISTRATION General Services Administration Acquisition Regulation; Submission for OMB Review; Industrial... the Office of Management and Budget (OMB) a request to review and approve a reinstatement of a previously approved information collection requirement regarding industrial funding fee and sales...

  13. [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.

  14. 50 CFR 260.1 - Administration of regulations.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... ADMINISTRATION, DEPARTMENT OF COMMERCE PROCESSED FISHERY PRODUCTS, PROCESSED PRODUCTS THEREOF, AND CERTAIN OTHER PROCESSED FOOD PRODUCTS INSPECTION AND CERTIFICATION Inspection and Certification of Establishments...

  15. Discretionary death: conditions, dilemmas, and normative regulation.

    PubMed

    Machado, Nora

    2005-11-01

    The author examines a major shift in the conceptualization and practices relating to death and dying in Western and other societies with advanced medicine. This shift is the result of socio-technical and cultural developments characterized by but not limited to the routine widespread application of life support technologies in the hospital together with notions of increased patient rights. It has resulted in a class of end-of-life situations, which the author defines as "discretionary death." The concept of discretionary death underscores the role of contextual and discretionary factors in end-of-life decision-making. The author identifies and discusses the necessary and complex process of norm formation that informs and regulates end-of-life medical practice and establishes societal consensus across society with respect to legitimizing "discretionary death."

  16. 42 CFR 486.324 - Condition: Administration and governing body.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... service area that have facilities for organ donation. (3) Systematic efforts, including professional... hospitals in establishing and implementing protocols for making routine inquiries about organ donations by... FURNISHED BY SUPPLIERS Requirements for Certification and Designation and Conditions for Coverage:...

  17. 42 CFR 486.324 - Condition: Administration and governing body.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... service area that have facilities for organ donation. (3) Systematic efforts, including professional... hospitals in establishing and implementing protocols for making routine inquiries about organ donations by... FURNISHED BY SUPPLIERS Requirements for Certification and Designation and Conditions for Coverage:...

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

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 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...

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

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 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...

  20. Allopregnanolone Elevations Following Pregnenolone Administration are Associated with Enhanced Activation of Emotion Regulation Neurocircuits

    PubMed Central

    Sripada, Rebecca K.; Marx, Christine E.; King, Anthony P.; Rampton, Jessica C.; Ho, Shaun; Liberzon, Israel

    2013-01-01

    Background The neurosteroid allopregnanolone is a potent allosteric modulator of the GABA(A) receptor with anxiolytic properties. Exogenous administration of allopregnanolone reduces anxiety, and allopregnanolone blockade impairs social and affective functioning. However, the neural mechanism whereby allopregnanolone improves mood and reduces anxiety is unknown. In particular, brain imaging has not been used to link neurosteroid effects to emotion regulation neurocircuitry. Methods To investigate the brain basis of allopregnanolone’s impact on emotion regulation, participants were administered 400mg of pregnenolone (N=16) or placebo (N=15) and underwent 3T fMRI while performing the Shifted-Attention Emotion Appraisal Task (SEAT), which probes emotional processing and regulation. Results Compared to placebo, allopregnanolone was associated with reduced activity in the amygdala and insula across all conditions. During the appraisal condition, allopregnanolone increased activity in the dorsal medial prefrontal cortex and enhanced connectivity between the amygdala and dorsal medial prefrontal cortex, an effect that was associated with reduced self-reported anxiety. Conclusions These results demonstrate that in response to emotional stimuli, allopregnanolone reduces activity in regions associated with generation of negative emotion. Furthermore, allopregnanolone may enhance activity in regions linked to regulatory processes. Aberrant activity in these regions has been linked to anxiety psychopathology. These results thus provide initial neuroimaging evidence that allopregnanolone may be a target for pharmacological intervention in the treatment of anxiety disorders, and suggest potential future directions for research into neurosteroid effects on emotion regulation neurocircuitry. PMID:23348009

  1. 77 FR 2726 - General Services Administration Acquisition Regulation; Information Collection; Contract...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-01-19

    ... ADMINISTRATION General Services Administration Acquisition Regulation; Information Collection; Contract Financing... 1142 was inadvertently deleted as part of the rewrite of GSAR regulations on Contract Financing. GSA... Information Collection 3090- 0080, Contract Financing Final Payment; (GSAR Part 532 and 552.232-72; GSA...

  2. 78 FR 6824 - Considerations Regarding Food and Drug Administration Review and Regulation of Drugs for the...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-01-31

    ... HUMAN SERVICES Food and Drug Administration Considerations Regarding Food and Drug Administration Review and Regulation of Drugs for the Treatment of Amyotrophic Lateral Sclerosis; Public Hearing AGENCY: Food and Drug Administration, HHS. ACTION: Notice of public hearing; request for comments. SUMMARY:...

  3. 75 FR 73984 - Amendments to General Regulations of the Food and Drug Administration

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-11-30

    ...'' (62 FR 62466, November 21, 1997). This guidance document may be accessed at http://www.fda.gov... 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....

  4. 7 CFR 52.1 - Administration of regulations.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... MARKETING ACT OF 1946 AND THE EGG PRODUCTS INSPECTION ACT PROCESSED FRUITS AND VEGETABLES, PROCESSED PRODUCTS THEREOF, AND CERTAIN OTHER PROCESSED FOOD PRODUCTS 1 Regulations Governing Inspection...

  5. 7 CFR 52.1 - Administration of regulations.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... MARKETING ACT OF 1946 AND THE EGG PRODUCTS INSPECTION ACT PROCESSED FRUITS AND VEGETABLES, PROCESSED PRODUCTS THEREOF, AND CERTAIN OTHER PROCESSED FOOD PRODUCTS 1 Regulations Governing Inspection...

  6. 42 CFR 485.56 - Condition of participation: Governing body and administration.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 5 2010-10-01 2010-10-01 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...

  7. 42 CFR 485.56 - Condition of participation: Governing body and administration.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 42 Public Health 5 2011-10-01 2011-10-01 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...

  8. 75 FR 33682 - Export Administration Regulations; Technical Amendments

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-15

    ... most recently by the Notice of August 13, 2009 (74 FR 41325 (August 14, 2009)), has continued the EAR....; E.O. 13222, 66 FR 44025, 3 CFR, 2001 Comp., p. 783; Notice of August 13, 2009, 74 FR 41325 (August... Bureau of Industry and Security 15 CFR Part 766 RIN 0694-AE93 Export Administration...

  9. 15 CFR 710.6 - Relationship between the Chemical Weapons Convention Regulations and the Export Administration...

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... are implemented in the Export Administration Regulations (EAR) (15 CFR parts 730 through 774) and the International Traffic in Arms Regulations (ITAR) (22 CFR parts 120 through 130). See in particular §§ 742.2 and..., Tobacco, Firearms and Explosives Regulations in 27 CFR part 447....

  10. 15 CFR 710.6 - Relationship between the Chemical Weapons Convention Regulations and the Export Administration...

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... are implemented in the Export Administration Regulations (EAR) (15 CFR parts 730 through 774) and the International Traffic in Arms Regulations (ITAR) (22 CFR parts 120 through 130). See in particular §§ 742.2 and..., Tobacco, Firearms and Explosives Regulations in 27 CFR part 447....

  11. 15 CFR 710.6 - Relationship between the Chemical Weapons Convention Regulations and the Export Administration...

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... are implemented in the Export Administration Regulations (EAR) (15 CFR parts 730 through 774) and the International Traffic in Arms Regulations (ITAR) (22 CFR parts 120 through 130). See in particular §§ 742.2 and..., Tobacco, Firearms and Explosives Regulations in 27 CFR part 447....

  12. 15 CFR 710.6 - Relationship between the Chemical Weapons Convention Regulations and the Export Administration...

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... are implemented in the Export Administration Regulations (EAR) (15 CFR parts 730 through 774) and the International Traffic in Arms Regulations (ITAR) (22 CFR parts 120 through 130). See in particular §§ 742.2 and..., Tobacco, Firearms and Explosives Regulations in 27 CFR part 447....

  13. 32 CFR 250.7 - Pertinent portions of Export Administration Regulations (EAR).

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... technical data under the authority of this part. Export Administration Regulations 15 CFR 379.3 General... accordance with the regulations of the Patent and Trademark Office 37 CFR part 5. See § 370.10(j).) ... Regulations (EAR). 250.7 Section 250.7 National Defense Department of Defense (Continued) OFFICE OF...

  14. 22 CFR 120.42 - Subject to the Export Administration Regulations (EAR).

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... found at 15 CFR parts 730 through 774. ... 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)....

  15. 32 CFR 250.7 - Pertinent portions of Export Administration Regulations (EAR).

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... technical data under the authority of this part. Export Administration Regulations 15 CFR 379.3 General... accordance with the regulations of the Patent and Trademark Office 37 CFR part 5. See § 370.10(j).) ... Regulations (EAR). 250.7 Section 250.7 National Defense Department of Defense (Continued) OFFICE OF...

  16. 32 CFR 250.7 - Pertinent portions of Export Administration Regulations (EAR).

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... technical data under the authority of this part. Export Administration Regulations 15 CFR 379.3 General... accordance with the regulations of the Patent and Trademark Office 37 CFR part 5. See § 370.10(j).) ... Regulations (EAR). 250.7 Section 250.7 National Defense Department of Defense (Continued) OFFICE OF...

  17. 32 CFR 250.7 - Pertinent portions of Export Administration Regulations (EAR).

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... technical data under the authority of this part. Export Administration Regulations 15 CFR 379.3 General... accordance with the regulations of the Patent and Trademark Office 37 CFR part 5. See § 370.10(j).) ... Regulations (EAR). 250.7 Section 250.7 National Defense Department of Defense (Continued) OFFICE OF...

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

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... are implemented in the Export Administration Regulations (EAR) (15 CFR parts 730 through 774) and the International Traffic in Arms Regulations (ITAR) (22 CFR parts 120 through 130). See in particular §§ 742.2 and..., Tobacco, Firearms and Explosives Regulations in 27 CFR part 447....

  19. 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...

  20. 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...

  1. 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...

  2. 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...

  3. 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...

  4. 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... HEALTH AND HUMAN SERVICES (CONTINUED) STANDARDS AND CERTIFICATION CONDITIONS OF PARTICIPATION... Condition of participation: Governing body and administration. The facility must have a governing body...

  5. The Mirror of Brass: The Compensation and Working Conditions of College and University Administrators.

    ERIC Educational Resources Information Center

    Ingraham, Mark H.; King, Francis P.

    This book describes the compensation which chief administrators in American colleges and universities receive, the conditions under which they work, their attitudes toward these conditions, and their suggestions for improving these conditions. The study sample is composed of presidents, academic vice presidents, deans of liberal arts colleges,…

  6. 75 FR 1788 - General Services Administration Acquisition Regulation; Submission for OMB Review; GSA Form 1364...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-01-13

    ... From the Federal Register Online via the Government Publishing Office GENERAL SERVICES ADMINISTRATION General Services Administration Acquisition Regulation; Submission for OMB Review; GSA Form 1364...: Under the provisions of the Paperwork Reduction Act of 1995 (44 U.S.C. Chapter 35), the General...

  7. 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

    ... Regulations (CFR) Parts 1-99, Parts 200-299, Parts 500-599, and Parts 600-799. Relevant sections of the FDA... 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...

  8. 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

    ... Regulations (CFR) Parts 1-99, Parts 200-299, Parts 500-599, and Parts 600-799. Relevant sections of the FDA... 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...

  9. 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... announcing a public workshop entitled ``FDA Clinical Trial Requirements, Regulations, Compliance, and Good... representatives. The program will focus on the relationships among the FDA and clinical trial staff,...

  10. 77 FR 15370 - General Services Administration Acquisition Regulation; Information Collection; Price Reductions...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-03-15

    ... date of the notice of request for comments regarding OMB Control No. 3090-0235, Price Reductions Clause, published in the Federal Register at 76 FR 81941, on December 29, 2011. DATES: Submit comments on or before... ADMINISTRATION General Services Administration Acquisition Regulation; Information Collection; Price...

  11. 77 FR 58380 - General Services Administration Acquisition Regulation; Submission for OMB Review; Price...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-09-20

    ... ADMINISTRATION General Services Administration Acquisition Regulation; Submission for OMB Review; Price... collection requirement regarding the GSAR Price Reductions Clause. A notice was published in the Federal Register at 76 FR 89141, on December 29, 2011. One respondent submitted comments. Public comments...

  12. 75 FR 3236 - Federal Acquisition Regulation; Submission for OMB Review; Cost Accounting Standards Administration

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-01-20

    ... requirement concerning cost accounting standards administration. A request for public comments was published in the Federal Register at 74 FR 58628, on November 13, 2009. No comments were received. Public... Regulation; Submission for OMB Review; Cost Accounting Standards Administration AGENCIES: Department...

  13. 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/

  14. 43 CFR 19.6 - Regulations respecting administration and uses of wilderness areas under jurisdiction of the...

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Regulations respecting administration and... § 19.6 Regulations respecting administration and uses of wilderness areas under jurisdiction of the Secretary. Regulations respecting administration and use of areas under the jurisdiction of the...

  15. 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…

  16. 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... Regulation Supplement (DFARS) to improve the effectiveness of DoD oversight of contractor business systems.... Background Contractor business systems and internal controls are the first line of defense against...

  17. 34 CFR 299.2 - What general administrative regulations apply to ESEA programs?

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... governments. Note: 34 CFR 222.13 indicates which EDGAR provisions apply to title VIII programs (Impact Aid... 34 Education 1 2011-07-01 2011-07-01 false What general administrative regulations apply to ESEA programs? 299.2 Section 299.2 Education Regulations of the Offices of the Department of Education OFFICE...

  18. 34 CFR 299.2 - What general administrative regulations apply to ESEA programs?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... governments. Note: 34 CFR 222.13 indicates which EDGAR provisions apply to title VIII programs (Impact Aid... 34 Education 1 2010-07-01 2010-07-01 false What general administrative regulations apply to ESEA programs? 299.2 Section 299.2 Education Regulations of the Offices of the Department of Education OFFICE...

  19. 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...

  20. 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...

  1. 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...

  2. 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...

  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. 32 CFR 644.314 - Rules and regulations of the General Services Administration (GSA).

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 32 National Defense 4 2010-07-01 2010-07-01 true Rules and regulations of the General Services Administration (GSA). 644.314 Section 644.314 National Defense Department of Defense (Continued) DEPARTMENT OF THE ARMY (CONTINUED) REAL PROPERTY REAL ESTATE HANDBOOK Disposal § 644.314 Rules and regulations...

  5. 32 CFR 644.314 - Rules and regulations of the General Services Administration (GSA).

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 32 National Defense 4 2011-07-01 2011-07-01 false Rules and regulations of the General Services Administration (GSA). 644.314 Section 644.314 National Defense Department of Defense (Continued) DEPARTMENT OF THE ARMY (CONTINUED) REAL PROPERTY REAL ESTATE HANDBOOK Disposal § 644.314 Rules and regulations...

  6. NRF2 Regulates PINK1 Expression under Oxidative Stress Conditions

    PubMed Central

    Murata, Hitoshi; Takamatsu, Hitoshi; Liu, Sulai; Kataoka, Ken; Huh, Nam-ho; Sakaguchi, Masakiyo

    2015-01-01

    Mutations of the PTEN-induced putative kinase 1 (PINK1) gene are a cause of autosomal recessive forms of Parkinson’s disease. Recent studies have revealed that PINK1 is an essential factor for controlling mitochondrial quality, and that it protects cells from oxidative stresses. Although there has been considerable progress in the elucidation of various aspects of PINK1 protein regulation such as activation, stability and degradation, the transcriptional regulation of PINK1 mRNA under stress conditions remains unclear. In this study, we found that nuclear factor (erythroid-derived 2)-like 2 (NRF2), an antioxidant transcription factor, regulates PINK1 expression under oxidative stress conditions. Damaged mitochondria arising from stress conditions induced NRF2-dependent transcription of the PINK1 gene through production of reactive oxygen species (ROS). Either an ROS scavenger or forced expression of KEAP1, a potent inhibitory partner to NRF2, restricted PINK1 expression induced by activated NRF2. Transcriptionally up-regulated PINK1 diminished oxidative stress-associated cell death. The results indicate that PINK1 expression is positively regulated by NRF2 and that the NRF2-PINK1 signaling axis is deeply involved in cell survival. PMID:26555609

  7. The Establishment and Administration of Operant Conditioning Programs in a State Hospital for the Retarded.

    ERIC Educational Resources Information Center

    Ball, Thomas S., Ed.

    Seven articles treat the establishment of operant conditioning programs for the mentally retarded at Pacific State Hospital in California. Emphasis is on the administrative rather than the demonstration of research aspects of operant conditioning programs. Following an introduction and overview, the medical director's point of view on operant…

  8. Phosphodiesterase 10A regulates alcohol and saccharin self-administration in rats.

    PubMed

    Logrip, Marian L; Vendruscolo, Leandro F; Schlosburg, Joel E; Koob, George F; Zorrilla, Eric P

    2014-06-01

    A history of stress produces increases in rodent relapse-like alcohol self-administration behavior and regional brain gene expression of phosphodiesterase 10A (PDE10A), a dual-specificity cyclic adenosine monophosphate/cyclic guanosine monophosphate-inhibiting enzyme. Here, we tested the hypothesis that administration of TP-10, a specific PDE10A inhibitor, would reduce alcohol self-administration in conditions predisposing to elevated self-administration. TP-10 administration dose-dependently (0.562, 1.0 mg/kg; subcutaneously) reduced relapse-like alcohol self-administration regardless of stress history enhancement of relapse-like behavior. TP-10 also reduced alcohol self-administration in genetically alcohol-preferring rats, as well as in alcohol-non-dependent and -dependent rats. Effective systemic TP-10 doses did not alter alcohol pharmacokinetics, significantly reduce motor activity or intrabout operant response speed, or promote a conditioned place aversion. TP-10 also reduced saccharin self-administration, suggesting a general role for PDE10A in the self-administration of reinforcing substances. PDE10A inhibition in the dorsolateral striatum, but not the nucleus accumbens, reduced alcohol self-administration. Taken together, the results implicate dorsolateral striatum PDE10A in facilitating alcohol intake and support further investigation of PDE10A systems in the pathophysiology and potential treatment of substance use disorders.

  9. 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.

  10. 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.

  11. 77 FR 25932 - Revisions to the Export Administration Regulations (EAR): Control of Energetic Materials and...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-05-02

    ... rule (76 FR 41958) (herein ``the July 15 proposed rule'') that set forth a framework for how articles... Administration Regulations (EAR). On November 7, 2011 (76 FR 68675) (herein ``the November 7 proposed rule...), as extended by the Notice of August 12, 2011, 76 FR 50661 (August 16, 2011), has continued the...

  12. 78 FR 45026 - Revisions to the Export Administration Regulations (EAR): Control of Military Electronic...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-07-25

    .... 78, No. 143 / Thursday, July 25, 2013 / Proposed Rules#0;#0; ] DEPARTMENT OF COMMERCE Bureau of..., reducing incentives for foreign manufacturers to design out and avoid U.S.-origin content and services, and... Administration Regulations: Initial Implementation of Export Control Reform'' (78 FR 22660, April 16,...

  13. 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

    ... Fiscal Service Bureau of the Fiscal Service 31 CFR Chapter II, Parts 202-391 RIN 1510-AB31 Regulatory Reorganization; Administrative Changes to Regulations Due to the Consolidation of the Financial Management Service and the Bureau of the Public Debt Into the Bureau of the Fiscal Service AGENCY: Bureau of...

  14. 75 FR 76692 - Defense Federal Acquisition Regulation Supplement; Business Systems-Definition and Administration...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-12-09

    ... (DFARS Case 2009-D038) in the Federal Register on January 15, 2010 (75 FR 2457). The public comment... rule, DoD published a second proposed rule with request for comments on December 3, 2010 (75 FR 75550... Federal Acquisition Regulation Supplement; Business Systems--Definition and Administration (DFARS...

  15. 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

    ... to be discussed are FDA regulations with respect to importing pharmaceutical products, medical... meeting. SUMMARY: The Food and Drug Administration (FDA) is announcing the following meeting..., Chicago, IL 60661; 312-596-4217; email: lisa.misevicz@fda.hhs.gov . Registration: Send...

  16. 44 CFR 4.13 - May the Administrator waive any provision of these regulations?

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 44 Emergency Management and Assistance 1 2011-10-01 2011-10-01 false May the Administrator waive any provision of these regulations? 4.13 Section 4.13 Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT AGENCY, DEPARTMENT OF HOMELAND SECURITY GENERAL INTERGOVERNMENTAL REVIEW OF...

  17. 44 CFR 4.13 - May the Administrator waive any provision of these regulations?

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 44 Emergency Management and Assistance 1 2014-10-01 2014-10-01 false May the Administrator waive any provision of these regulations? 4.13 Section 4.13 Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT AGENCY, DEPARTMENT OF HOMELAND SECURITY GENERAL INTERGOVERNMENTAL REVIEW OF...

  18. 32 CFR 250.7 - Pertinent portions of Export Administration Regulations (EAR).

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... technical data under the authority of this part. Export Administration Regulations 15 CFR 379.3 General... nominal cost, or obtained without costs, or are readily available at libraries open to the public. The...) Instruction in academic institutions and academic laboratories, excluding information that involves...

  19. 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

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HOUSING AND URBAN DEVELOPMENT RIN 2502-ZA05 Federal Housing Administration (FHA)--Temporary Exemption From Compliance With FHA's Regulation on Property Flipping AGENCY: Office of the Assistant Secretary for...

  20. 76 FR 81363 - Federal Housing Administration (FHA): Temporary Exemption From Compliance With FHA's Regulation...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-28

    ... transactions include, for example, sales by HUD of real estate-owned (REO) properties under HUD's regulations... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HOUSING AND URBAN DEVELOPMENT 24 CFR Part 203 RIN 2502-ZA05 Federal Housing Administration (FHA):...

  1. 76 FR 76072 - Revisions to the Export Administration Regulations (EAR): Control of Gas Turbine Engines and...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-06

    ... Administration Regulations (EAR): Control of Gas Turbine Engines and Related Items the President Determines No... publishes this proposed rule that describes how military gas turbine engines and related articles that the... USML Category XIX the military gas turbine engines and related articles that would remain on the...

  2. 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 §...

  3. 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 §...

  4. 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 §...

  5. 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 §...

  6. 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 §...

  7. 78 FR 13675 - Federal Acquisition Regulation; Submission for OMB Review; Cost Accounting Standards Administration

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-28

    ... was published in the Federal Register at 77 FR 69441, on November 19, 2012. Two respondents submitted... the Federal Register at 75 FR 3236, on January 20, 2010. Based on data from the Federal Procurement... Regulation; Submission for OMB Review; Cost Accounting Standards Administration AGENCY: Department of...

  8. [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.

  9. [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. PMID:25536762

  10. 7 CFR 301.50-4 - Conditions governing the interstate movement of regulated articles from quarantined areas.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... DOMESTIC QUARANTINE NOTICES Pine Shoot Beetle § 301.50-4 Conditions governing the interstate movement of... beetle; and (2) The point of origin of the regulated article is indicted on the waybill. (c) With a... permit, which the Administrator has found to be adequate to prevent the spread of the pine shoot...

  11. 7 CFR 301.50-4 - Conditions governing the interstate movement of regulated articles from quarantined areas.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... DOMESTIC QUARANTINE NOTICES Pine Shoot Beetle § 301.50-4 Conditions governing the interstate movement of... beetle; and (2) The point of origin of the regulated article is indicted on the waybill. (c) With a... permit, which the Administrator has found to be adequate to prevent the spread of the pine shoot...

  12. 7 CFR 301.50-4 - Conditions governing the interstate movement of regulated articles from quarantined areas.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... DOMESTIC QUARANTINE NOTICES Pine Shoot Beetle § 301.50-4 Conditions governing the interstate movement of... beetle; and (2) The point of origin of the regulated article is indicted on the waybill. (c) With a... permit, which the Administrator has found to be adequate to prevent the spread of the pine shoot...

  13. 7 CFR 301.50-4 - Conditions governing the interstate movement of regulated articles from quarantined areas.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... DOMESTIC QUARANTINE NOTICES Pine Shoot Beetle § 301.50-4 Conditions governing the interstate movement of... beetle; and (2) The point of origin of the regulated article is indicted on the waybill. (c) With a... permit, which the Administrator has found to be adequate to prevent the spread of the pine shoot...

  14. 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. PMID:27194113

  15. 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.

  16. Chronic social stress conditions differentially modify vulnerability to amphetamine self-administration.

    PubMed

    Lemaire, V; Deminière, J M; Mormède, P

    1994-06-27

    Using social instability and cohabitation with females as chronic stress, we observed that neuroendocrine systems were differentially activated according to the experimental design. We show here that amphetamine self-administration, a paradigm to study the reinforcing effects of psychostimulants, is also differentially affected by these conditions. Coexistence with females increases amphetamine self-administration and this effect is reduced when social instability is superimposed. On the other hand, locomotor response to amphetamine is not modified by either social factor, suggesting a specific involvement of a subset of dopaminergic neurons. PMID:7953651

  17. 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

  18. 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.

  19. Hypocretin/Orexin Regulation of Dopamine Signaling and Cocaine Self-Administration Is Mediated Predominantly by Hypocretin Receptor 1

    PubMed Central

    2015-01-01

    Extensive evidence suggests that the hypocretins/orexins influence cocaine reinforcement and dopamine signaling via actions at hypocretin receptor 1. By comparison, the involvement of hypocretin receptor 2 in reward and reinforcement processes has received relatively little attention. Thus, although there is some evidence that hypocretin receptor 2 regulates intake of some drugs of abuse, it is currently unclear to what extent hypocretin receptor 2 participates in the regulation of dopamine signaling or cocaine self-administration, particularly under high effort conditions. To address this, we examined the effects of hypocretin receptor 1, and/or hypocretin receptor 2 blockade on dopamine signaling and cocaine reinforcement. We used in vivo fast scan cyclic voltammetry to test the effects of hypocretin antagonists on dopamine signaling in the nucleus accumbens core and a progressive ratio schedule to examine the effects of these antagonists on cocaine self-administration. Results demonstrate that blockade of either hypocretin receptor 1 or both hypocretin receptor 1 and 2 significantly reduces the effects of cocaine on dopamine signaling and decreases the motivation to take cocaine. In contrast, blockade of hypocretin receptor 2 alone had no significant effects on dopamine signaling or self-administration. These findings suggest a differential involvement of the two hypocretin receptors, with hypocretin receptor 1 appearing to be more involved than hypocretin receptor 2 in the regulation of dopamine signaling and cocaine self-administration. When considered with the existing literature, these data support the hypothesis that hypocretins exert a permissive influence on dopamine signaling and motivated behavior via preferential actions on hypocretin receptor 1. PMID:25496218

  20. Hypocretin/Orexin regulation of dopamine signaling and cocaine self-administration is mediated predominantly by hypocretin receptor 1.

    PubMed

    Prince, Courtney D; Rau, Andrew R; Yorgason, Jordan T; España, Rodrigo A

    2015-01-21

    Extensive evidence suggests that the hypocretins/orexins influence cocaine reinforcement and dopamine signaling via actions at hypocretin receptor 1. By comparison, the involvement of hypocretin receptor 2 in reward and reinforcement processes has received relatively little attention. Thus, although there is some evidence that hypocretin receptor 2 regulates intake of some drugs of abuse, it is currently unclear to what extent hypocretin receptor 2 participates in the regulation of dopamine signaling or cocaine self-administration, particularly under high effort conditions. To address this, we examined the effects of hypocretin receptor 1, and/or hypocretin receptor 2 blockade on dopamine signaling and cocaine reinforcement. We used in vivo fast scan cyclic voltammetry to test the effects of hypocretin antagonists on dopamine signaling in the nucleus accumbens core and a progressive ratio schedule to examine the effects of these antagonists on cocaine self-administration. Results demonstrate that blockade of either hypocretin receptor 1 or both hypocretin receptor 1 and 2 significantly reduces the effects of cocaine on dopamine signaling and decreases the motivation to take cocaine. In contrast, blockade of hypocretin receptor 2 alone had no significant effects on dopamine signaling or self-administration. These findings suggest a differential involvement of the two hypocretin receptors, with hypocretin receptor 1 appearing to be more involved than hypocretin receptor 2 in the regulation of dopamine signaling and cocaine self-administration. When considered with the existing literature, these data support the hypothesis that hypocretins exert a permissive influence on dopamine signaling and motivated behavior via preferential actions on hypocretin receptor 1. PMID:25496218

  1. Influence of cue-conditioning on acquisition, maintenance and relapse of cocaine intravenous self-administration.

    PubMed

    Deroche-Gamonet, Véronique; Piat, Frédéric; Le Moal, Michel; Piazza, Pier Vincenzo

    2002-04-01

    Conditioning theories propose that, through a Pavlovian associative process, discrete stimuli acquire the ability to elicit neural states involved in the maintenance and relapse of a drug-taking behaviour. Experimental evidence indicates that drug-related cues play a role in relapse, however, their influence on the development and maintenance of drug self-administration has been poorly investigated. In this report, we analysed the effects of a drug-associated cue light on acquisition, maintenance and reinstatement of intravenous cocaine self-administration. The results show that a cocaine-associated cue light can act as an incentive in absence of the drug, but does not directly modify drug-reinforcing effects. Contingent and non-contingent presentations of a cocaine-associated cue light reinstated an extinguished self-administration behaviour. However, regardless of whether or not a cue light was associated with cocaine infusions, rats acquire cocaine intravenous self-administration reaching the same levels of intake. Furthermore, after self-administration has been acquired in presence of the cue light, the omission of the cue light or its non-contingent presentation did not modify rat behaviour. In conclusion, our work shows that cocaine-associated explicit cues do not directly interfere with the reinforcing effects of the drug.

  2. Regulation of free corticosterone and CBG capacity under different environmental conditions in altricial nestlings.

    PubMed

    Almasi, Bettina; Roulin, Alexandre; Jenni-Eiermann, Susanne; Breuner, Creagh W; Jenni, Lukas

    2009-01-01

    The concentration of circulating glucocorticoids is regulated in response to environmental and endogenous conditions. Total circulating corticosterone, the main glucocorticoid in birds, consists of a fraction which is bound to corticosterone-binding globulins (CBG) and a free fraction. There is increasing evidence that the environment modulates free corticosterone levels through varying the concentration of CBG, but experimental evidence is lacking. To test the hypothesis that the regulation of chronic stress in response to endogenous and environmental conditions involves variation in both corticosterone release and CBG capacity, we performed an experiment with barn owl (Tyto alba) nestlings in two different years with pronounced differences in environmental conditions and in nestlings experimentally fed ad libitum. In half of the individuals we implanted a corticosterone-releasing pellet to artificially increase corticosterone levels and in the other half we implanted a placebo pellet. We then repeatedly collected blood samples to measure the change in total and free corticosterone levels as well as CBG capacity. The increase in circulating total corticosterone after artificial corticosterone administration varied with environmental conditions and with the food regime of the nestlings. The highest total corticosterone levels were found in nestlings growing up in poor environmental conditions and the lowest in ad libitum fed nestlings. CBG was highest in the year with poor environmental conditions, so that, contrary to total corticosterone, free corticosterone levels were low under poor environmental conditions. When nestlings were fed ad libitum total corticosterone, CBG and free corticosterone did not increase when administering corticosterone. These results suggest that depending on the individual history an animal experienced during development the HPA-axis is regulated differently. PMID:19467233

  3. Heckler v. Chaney: judicial and administrative regulation of capital punishment by lethal injection.

    PubMed

    Stolls, M

    1985-01-01

    Capital punishment by lethal injection, which was expected to be the most safe and effective of available methods, can produce unusually cruel and inhuman death. In Heckler v. Chaney, inmates sentenced to death by lethal injection, as well as members of both the medical and legal communities, challenged the Food and Drug Administration's (FDA) refusal to regulate certain drugs used for capital punishment by lethal injection. By declining to review the FDA's nonenforcement decision, the Supreme Court also declined an opportunity to reevaluate its standard for determining cruel and unusual punishment, which upholds any method of execution that is no more unusually cruel than existing methods. This Comment examines the propriety of judicial and administrative regulation of capital punishment by lethal injection.

  4. 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.

  5. Regulation of legume nodulation by acidic growth conditions.

    PubMed

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

    2013-03-01

    Legumes represent some of the most important crop species worldwide. They are able to form novel root organs known as nodules, within which biological nitrogen fixation is facilitated through a symbiotic interaction with soil-dwelling bacteria called rhizobia. This provides legumes with a distinct advantage over other plant species, as nitrogen is a key factor for growth and development. Nodule formation is tightly regulated by the plant and can be inhibited by a number of external factors, such as soil pH. This is of significant agricultural and economic importance as much of global legume crops are grown on low pH soils. Despite this, the precise mechanism by which low pH conditions inhibits nodule development remains poorly characterized.

  6. 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...

  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, 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...

  9. A case for tobacco content regulation by the U.S. Food and Drug Administration

    PubMed Central

    du Toit, J.A.

    2010-01-01

    Although many people welcome the recent move by the United States to give its Food and Drug Administration (fda) the authority to regulate the content of tobacco, some worry that such regulation constitutes unwarranted interference with the freedom of competent adult tobacco consumers. The concern for protecting the autonomy of individuals is valuable indeed, but given the highly addictive nature of tobacco products (and especially the nicotine in tobacco products), the continued use of tobacco by smokers cannot —without straining credulity—be said to be autonomous. This fact, combined with a proper construal of the fda’s role and an appreciation of the substantial morbidity and mortality associated with tobacco use, makes a strong case for content regulation. PMID:20697516

  10. Preference for flavored wheat straw by lambs conditioned with intraruminal administrations of sodium propionate.

    PubMed

    Villalba, J J; Provenza, F D

    1996-10-01

    We hypothesized that volatile fatty acids are feedback signals that condition food preferences in ruminants, and we tested two predictions based on this hypothesis: 1) low doses of propionate condition preferences for low-quality foods (Exp. 1 and 2) preferences are not caused by osmotic load (Exp. 2). In Exp. 1, lambs were offered chopped wheat straw flavored with either oregano or onion on odd days, whereas on even days flavors were switched and lambs received capsules containing sodium propionate. During four 8-d conditioning periods, the amounts of propionate delivered ranged from .7 to 1.4% of the daily DE intake (Period 1) or were fixed at .7% (Period 2) and 1% of the daily DE intake (Periods 3 and 4). After each 8-d conditioning period, lambs were offered oregano- and onion-flavored straw. Conditioning was then suspended and lambs were offered onion- and oregano-flavored straw at weekly intervals for 1 mo (extinction). Lambs preferred the flavor paired with propionate during conditioning (P < .001) and extinction (P < .07). During Exp. 2, a different group of lambs was conditioned as in Exp. 1, but sodium chloride was delivered at osmotic loads equivalent to those when propionate supplied .7% and 1% of the daily DE intake. Lambs strongly avoided the flavor paired with sodium chloride (P < .001). Thus, lambs acquired preferences for straw conditioned with doses of propionate typically considered ineffective in the regulation of food intake, and osmolalities generated by propionate did not cause, but probably attenuated, food preferences.

  11. 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.

  12. The Effect of Growth Hormone Administration on the Regulation of Mitochondrial Apoptosis in-Vivo

    PubMed Central

    Keane, James; Tajouri, Lotti; Gray, Bon

    2015-01-01

    The purpose of this study was to determine whether recombinant human growth hormone (rhGH) would show any significant effects on the expression of apoptosis regulating proteins in peripheral blood mononuclear cells (PBMCs). Additionally, the potential for post-transcriptional regulation of gene expression by miRNA was assessed in two cellular compartments, the cytosol and the mitochondria. Ten male subjects were subcutaneously injected with either rhGH (1 mg) or saline (0.9%) for seven consecutive days in a double-blinded fashion. Blood sampling was undertaken prior to treatment administration and over a period of three weeks following treatment cessation. Bcl-2 and Bak gene and protein expression levels were measured in PBMCs, while attention was also directed to the expression of miR-181a and miR-125b, known translational inhibitors of Bcl-2 and Bak respectively. Results showed that rhGH significantly decreased Bak protein concentrations compared to placebo samples for up to 8 days post treatment. While cytosolic miRNA expression was not found to be significantly affected by rhGH, measurement of the expression of miR-125b in mitochondrial fractions showed a significant down-regulation eight days post-rhGH administration. These findings suggest that rhGH induces short-term anti-apoptotic effects which may be partially mediated through a novel pathway that alters the concentration of mitochondrially-associated miRNAs. PMID:26057745

  13. 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.

  14. 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

  15. Augmentation of the development of behavioral tolerance to cannabinoid administration through pavlovian conditioning.

    PubMed

    Hill, Matthew N; Gorzalka, Boris B; Choi, Joyce W

    2004-01-01

    This investigation examined the effects, in female rats, of a Pavlovian conditioning paradigm on the development of tolerance to hypolocomotion induced by the cannabinoid agonist HU-210. Rats were administered HU-210 and placebo in either an associative or a nonassociative fashion. The results indicated that rats in the associative paradigm developed tolerance significantly faster than those in the nonassociative group (p < 0.03). Subsequently, once tolerance had developed, the associative group of rats was administered HU-210 and placebo in the opposite environments. There were no differences found in locomotion between the CS+ and CS- environments following administration of HU-210. However, when the placebo was administered in the CS+ environment, there was a trend towards increased activity levels (p = 0.06), suggesting withdrawal-like behavior. These findings indicate that the underlying physiological mechanisms of tolerance development in the cannabinoid system are hastened by conditioning, but that these physiological alterations are not contingent upon the associative parameters used for drug administration.

  16. Effects of melatonin in a place preference conditioning depend on the time of administration.

    PubMed

    Papp, Mariusz; Litwa, Ewa; Łasoń-Tyburkiewicz, Magdalena; Gruca, Piotr

    2010-01-01

    A conditioned place preference paradigm was used to assess potential rewarding properties of melatonin. The conditioning with melatonin was carried out at two periods of the 12-h light/dark cycle: in the morning (08.30-10.00) and in the evening (18.30-20.00). Morning administration of melatonin (2.5, 5 and 10 mg/kg) did not support conditioned place preference. In contrast, evening conditioning with melatonin caused a clear shift towards the drug-paired side. This effect was dose-dependent; higher doses of 2.5, 5, 10 and 50 mg/kg induced conditioned preference while lower doses of 0.5 and 1 mg/kg were ineffective. The increase in the side preference induced by the two most effective doses of melatonin (10 and 50 mg/kg) were comparable to that induced by 1 mg/kg of amphetamine, and was significantly attenuated by the melatonin antagonist, S 22153 (20 mg/kg). In chronic experiment, melatonin (10 mg/kg) caused similar increase of the time spent on conditioned side both in animals administered vehicle for 7 days and in rats receiving 10 mg/kg of melatonin for the same period of time. Potent activity in the conditioned preference model suggests that melatonin may have rewarding properties, which moreover, is not tolerated following repeated pre-exposure to the drug. These findings may indicate potential abuse liability of melatonin, and therefore, its use by humans should require a careful monitoring for abuse and/or dependency.

  17. Regulation of rat MOR-1 gene expression after chronic intracerebroventricular administration of morphine

    PubMed Central

    ZHU, ZHI-PING; BADISA, RAMESH B.; PALM, DONALD E.; GOODMAN, CARL B.

    2012-01-01

    The μ-opioid receptor is the primary site for the action of morphine. In the present study, we investigated the regulation of the μ-opioid receptor mRNA levels in the locus ceruleus, ventral tegmental area, nucleus accumbens, and hypothalamus of the rat brain following intracerebroventricular administration of morphine for 7 days. The isolated mRNA from these regions was subjected to real-time quantitative RT-PCR to determine the regulation of μ-opioid receptor gene expression. It was observed that 7 days of treatment with morphine significantly down-regulated the μ-opioid receptor mRNA levels in the hypothalamus of the brain in comparison to the control group. However, the μ-opioid receptor levels in the locus ceruleus, ventral tegmental area, and nucleus accumbens regions remained the same as the control levels. Down-regulation of μ-opioid receptor mRNA levels in the hypothalamus region of the brain indicates the probable role of opioids to influence neuroendocrine function. The results further indicate that cellular adaptation for morphine tolerance is tissue-specific. These findings help us to understand the mechanism of morphine tolerance in various regions of the brain. PMID:22089925

  18. 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

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

    PubMed

    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

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

    PubMed

    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

  1. Oral Administration of Fermented Probiotics Improves the Condition of Feces in Adult Horses

    PubMed Central

    ISHIZAKA, Saori; MATSUDA, Akira; AMAGAI, Yosuke; OIDA, Kumiko; JANG, Hyosun; UEDA, Yuko; TAKAI, Masaki; TANAKA, Akane; MATSUDA, Hiroshi

    2014-01-01

    ABSTRACT The effects of probiotics on horses are still controversial. The present study was a randomized, double-blinded, placebo-controlled crossover study designed to evaluate the ability of probiotics to improve intestinal conditions in adult horses. Fermented probiotics were administered to 10 healthy adult geldings for 28 days. The clinical condition of the horses was monitored daily, and the blood and feces were biochemically analyzed every 14 days. In the probiotic-treated group, the concentration of carboxylic acids in the feces was increased at days 14 and 28. In contrast to the fecal pH in the control group, which increased at days 14 and 28, the fecal pH in the probiotic-treated group did not increase. Additionally, the relative amounts of enteropathogenic bacterial DNA were diminished in the probiotic-treated group. These results suggest that probiotic bacteria proliferated in the equine intestine. No instances of abnormal clinical conditions or abnormal values in blood tests were observed throughout the study. Oral administration of fermented probiotics may have the ability to improve the intestinal environment biochemically and microbiologically without the risk of adverse effects. PMID:25558179

  2. 45 CFR 63.8 - Supplemental regulations and grant conditions.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ....8 Section 63.8 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION GRANT... (formerly the Office of Economic Opportunity): 45 CFR 1060.2 (Income Poverty Guidelines.) 45 CFR 1060.3 (Limitation on Benefits to Those Voluntarily Poor.) 45 CFR 1067.1 (Suspension and Termination of...

  3. 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.

  4. The new E.U. Animal Transport Regulation: improved welfare and health or increased administration?

    PubMed

    Hartung, J

    2006-03-01

    There is public discussion of the new E.U. Animal Transport Regulation No 1/2005 of Dec. 2004 and its advantages and draw-backs. This Regulation is no longer a Directive, so that it is directly applicable in the Members States. Although the Regulation is recognised to have great potential to improve welfare and health of transported animals, it will also increase administrative work. Most improvements will come through better education and the increased responsibilities of animal attendants, drivers, keepers and transport organisers, and through the stricter control mechanisms (log book, training, instructions etc.) and the introduction of the GPS control systems to further enhance the transparency of animal movements. The formats of the transport certificates used in all Member States will be harmonised. Technical records will be kept on air temperature and water consumption. Contact offices in all member states for transport affairs will improve the exchange of data between the responsible authorities and harmonise control and surveillance practice. Specific regulations are now in place for horses (broken, unbroken, registered) and for the transport age of young animals (piglets, lambs, calves, foals). In spite of some substantial improvements there are still significant gaps in our knowledge of both normal and long transports, for example optimal journey times, food and water supply on long transports, environmental factors such as vibration, motion, light and ventilation requirements in different European geographical regions. The same is true for the epidemiological aspects of the prevention of disease transmission; for example, very little is known about the bacterial and particulate emissions of the animal transport vehicles which travel across Europe. A serious drawback of the regulation is the fact that it does not abolish the unloading of animals on long transports to rest for 24 h at staging points, so that the concomitant risks to health and welfare

  5. 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. PMID:26852857

  6. 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.

  7. 7 CFR 301.91-4 - Conditions governing the interstate movement of regulated articles from regulated areas in...

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... without stopping except under normal traffic conditions such as traffic lights or stop signs) any... of European larch canker; (ii) If the article originated outside of any regulated area; and (iii)...

  8. Opioid regulation of Pavlovian overshadowing in fear conditioning.

    PubMed

    Zelikowsky, Moriel; Fanselow, Michael S

    2010-08-01

    In Pavlovian overshadowing, a stimulus that predicts a biologically important event reduces conditioning to another, equally predictive stimulus. We tested the effects of an opioid antagonist and dopamine agonist on the ability of a salient white noise to overshadow a less salient light. Rats were conditioned to fear a light or a noise-light compound using a mild footshock. Compound-conditioned rats trained under the saline vehicle revealed significant overshadowing of the light by the noise. This overshadowing effect was significantly attenuated in rats trained under the opioid antagonist naltrexone, consistent with an opioid-mediated negative feedback model of conditioning. In line with predictions made by negative feedback-type models, we failed to obtain overshadowing with few trials, suggesting that the processes underlying conditioning during initial trials do not contribute to the opioid-dependent Pavlovian overshadowing obtained in our preparation. Lastly, we compared the involvement of dopamine-mediated and opioid-mediated processes in overshadowing by conditioning rats under the partial dopamine D1 receptor agonist SKF 38393 or the opioid antagonist naltrexone. Both naltrexone and SKF 38393 were found to attenuate overshadowing; however, the behavioral profiles produced by each pharmacological manipulation were distinct. Collectively, these studies demonstrate an important role for both opioid- and dopamine-mediated processes in multiple-trial overshadowing.

  9. CB1 Receptors Regulate Alcohol-Seeking Behavior and Alcohol Self-administration of Female Alcohol-Preferring (P) Rats

    PubMed Central

    Getachew, Bruk; Hauser, Sheketha R.; Dhaher, Ronnie; Bell, Richard L.; Oster, Scott M.; McBride, William J.; Rodd, Zachary A.

    2015-01-01

    Rationale The endogenous cannabinoid (CB) system mediates a number of behaviors associated with drug-seeking and drug self-administration. In this study the effects of CB1 receptor manipulations on operant ethanol (EtOH) responding during EtOH-seeking, EtOH- relapse as well as on-going EtOH self-administration were determined. Methods Alcohol-preferring (P) rats were trained in 2-lever operant chambers to self-administer 15% EtOH (v/v) and water on a concurrent fixed-ratio 5 – fixed-ratio 1 (FR5-FR1) schedule of reinforcement in daily 1-hr sessions. After 10 weeks, rats underwent 7 extinction sessions, followed by 2 weeks in their home cages without access to EtOH or operant chambers. Rats were then returned to the operant chambers for testing of EtOH-seeking behavior (no EtOH present) for 4 sessions. After a week in their home cages following the EtOH-seeking test, rats were returned to the operant chambers with access to EtOH and water (relapse). Rats were then maintained in the operant chambers for daily 1-hr sessions with access to 15% EtOH and water for several weeks. Results The CB1 receptor antagonist (SR141716A), at doses of 1 and 2 mg/kg, i.p. reduced EtOH-seeking and transiently reduced EtOH self-administration during relapse and maintenance. Conversely, treatment with the CB1 receptor agonist CP, 55-940, at doses of 1 and 10 μg/kg i.p., increased EtOH-seeking and EtOH self-administration during relapse. Conclusions The results of this study demonstrate that activation of CB1 receptors are involved in regulating EtOH-seeking as well as the reinforcing effects of EtOH under relapse and on-going self-administration conditions. PMID:21110997

  10. 21 CFR 10.90 - Food and Drug Administration regulations, recommendations, and agreements.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATIVE PRACTICES AND PROCEDURES General Administrative... Commissioner, e.g., model State and local ordinances, or personnel practices for reducing radiation...

  11. 21 CFR 10.90 - Food and Drug Administration regulations, recommendations, and agreements.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATIVE PRACTICES AND PROCEDURES General Administrative... Commissioner, e.g., model State and local ordinances, or personnel practices for reducing radiation...

  12. 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

    ... condition standards as required by 24 CFR part 5, subpart G, the Regulatory Agreement and/or the Housing... GENERAL INTRODUCTION TO FHA PROGRAMS Physical Condition of Multifamily Properties § 200.857 Administrative... documents for review. Once the technical review and database adjustment periods have expired, as provided...

  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

    ... condition standards as required by 24 CFR part 5, subpart G, the Regulatory Agreement and/or the Housing... GENERAL INTRODUCTION TO FHA PROGRAMS Physical Condition of Multifamily Properties § 200.857 Administrative... documents for review. Once the technical review and database adjustment periods have expired, as provided...

  14. Modeling insulin kinetics: responses to a single oral glucose administration or ambulatory-fed conditions.

    PubMed

    Lenbury, Y; Ruktamatakul, S; Amornsamarnkul, S

    2001-01-01

    This paper presents a nonlinear mathematical model of the glucose-insulin feedback system, which has been extended to incorporate the beta-cells' function on maintaining and regulating plasma insulin level in man. Initially, a gastrointestinal absorption term for glucose is utilized to effect the glucose absorption by the intestine and the subsequent release of glucose into the bloodstream, taking place at a given initial rate and falling off exponentially with time. An analysis of the model is carried out by the singular perturbation technique in order to derive boundary conditions on the system parameters which identify, in particular, the existence of limit cycles in our model system consistent with the oscillatory patterns often observed in clinical data. We then utilize a sinusoidal term to incorporate the temporal absorption of glucose in order to study the responses in the patients under ambulatory-fed conditions. A numerical investigation is carried out in this case to construct a bifurcation diagram to identify the ranges of parametric values for which chaotic behavior can be expected, leading to interesting biological interpretations. PMID:11226623

  15. 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.

  16. Design Principles of a Conditional Futile Cycle Exploited for Regulation

    PubMed Central

    Tolla, Dean A.; Kiley, Patricia J.; Lomnitz, Jason G.; Savageau, Michael A.

    2015-01-01

    In this report, we characterize the design principles of futile cycling in providing rapid adaptation by regulatory proteins that act as environmental sensors. In contrast to the energetically wasteful futile cycles that are avoided in metabolic pathways, here we describe a conditional futile cycle exploited for a regulatory benefit. The FNR (fumarate and nitrate reduction) cycle in Escherichia coli operates under two regimes – a strictly futile cycle in the presence of O2 and as a pathway under anoxic conditions. The computational results presented here use FNR as a model system and provide evidence that cycling of this transcription factor and its labile sensory cofactor between active and inactive states affords rapid signaling and adaptation. We modify a previously developed mechanistic model to examine a family of FNR models each with different cycling speeds but mathematically constrained to be otherwise equivalent, and we identify a trade-off between energy expenditure and response time that can be can be tuned by evolution to optimize cycling rate of the FNR system for a particular ecological context. Simulations mimicking experiments with proposed double mutant strains offer suggestions for experimentally testing our predictions and identifying potential fitness effects. Our approach provides a computational framework for analyzing other conditional futile cycles, which when placed in their larger biological context may be found to confer advantages to the organism. PMID:25851148

  17. Effects of exercise conditioning on thermoregulatory responses to repeated administration of chlorpyrifos.

    PubMed

    Rowsey, Pamela Johnson; Metzger, Bonnie L; Carlson, John; Gordon, Christopher J

    2003-05-01

    Little is known about the effects of physical activity (i.e., exercise training) on susceptibility to environmental toxicants. Chlorpyrifos (CHP), an organophosphate (OP) insecticide, affects thermoregulation, causing an acute period of hypothermia followed by a delayed fever. Since exercise conditioning alters the thermoregulatory responses of rodents, this study examined whether exercise training would alter the thermoregulatory response to repeated CHP administration in the female Sprague-Dawley rat. Core temperature (T(c)) and motor activity (MA) were monitored by radiotelemetry in rats housed at an ambient temperature (T(a)) of 22 degrees C. The rats either were provided with continuous access to running wheels (exercise group) or were housed in standard cages without wheels (sedentary group). The exercise group rats ran predominantly at night with an average of 7.6 km/24h. After 8 weeks the rats in both groups were gavaged daily with corn oil or 10mg/kg CHP (dissolved in corn oil) for 4 days. CHP induced an immediate hypothermic response followed by a delayed fever throughout the next day in the sedentary group rats after the first three doses of CHP. The exercise group rats showed no hypothermia after the first dose of CHP. However, they became hypothermic after the second and third doses of CHP. The exercise group rats developed a smaller daytime fever after each dose of CHP compared to the sedentary group rats. Overall, exercise training attenuated the hypothermic and febrile effects of repeated CHP. Thus, the data suggest that a sedentary lifestyle may increase the sensitivity to OP insecticides. Exercise training was also associated with a more rapid recovery of plasma cholinesterase activity. PMID:12706752

  18. Participation of signaling cascades in the regulation of erythropoiesis under conditions of cytostatic treatment.

    PubMed

    Dygai, A M; Zhdanov, V V; Miroshnichenko, L A; Udut, E V; Zyuz'kov, G N; Simanina, E V; Chaikovskii, A V; Stavrova, L A; Trofimova, E S; Burmina, Ya V

    2015-01-01

    We studied the role of signaling pathways in the regulation of erythropoiesis against the background of myelosuppression caused by administration of 5-fluorouracil. The important role of cyclic AMP in the maturation of erythroid progenitors after cytostatic treatment was demonstrated. The secretory activity of myelokaryocytes during the period of erythroid hemopoiesis recovery is mainly regulated via the p38 MAPK signaling pathway; non-erythropoietin factors are involved in the formation of erythropoietic activity of adherent cells of the microenvironment.

  19. Participation of signaling cascades in the regulation of erythropoiesis under conditions of cytostatic treatment.

    PubMed

    Dygai, A M; Zhdanov, V V; Miroshnichenko, L A; Udut, E V; Zyuz'kov, G N; Simanina, E V; Chaikovskii, A V; Stavrova, L A; Trofimova, E S; Burmina, Ya V

    2015-01-01

    We studied the role of signaling pathways in the regulation of erythropoiesis against the background of myelosuppression caused by administration of 5-fluorouracil. The important role of cyclic AMP in the maturation of erythroid progenitors after cytostatic treatment was demonstrated. The secretory activity of myelokaryocytes during the period of erythroid hemopoiesis recovery is mainly regulated via the p38 MAPK signaling pathway; non-erythropoietin factors are involved in the formation of erythropoietic activity of adherent cells of the microenvironment. PMID:25578863

  20. 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... Commissioner, e.g., model State and local ordinances, or personnel practices for reducing radiation exposure... be rescinded and has no force or effect whatever....

  1. 21 CFR 10.90 - Food and Drug Administration regulations, recommendations, and agreements.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATIVE PRACTICES AND PROCEDURES General Administrative... Commissioner, e.g., model State and local ordinances, or personnel practices for reducing radiation exposure... rescinded and has no force or effect whatever....

  2. 21 CFR 10.90 - Food and Drug Administration regulations, recommendations, and agreements.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATIVE PRACTICES AND PROCEDURES General Administrative... Commissioner, e.g., model State and local ordinances, or personnel practices for reducing radiation exposure... rescinded and has no force or effect whatever....

  3. 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.

  4. Serotonin-3 Receptors in the Posterior Ventral Tegmental Area Regulate Ethanol Self-Administration of Alcohol-Preferring (P) Rats

    PubMed Central

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

    2015-01-01

    Several studies indicated the involvement of serotonin-3 (5-HT3) receptors in regulating alcohol-drinking behavior. The objective of this study was to determine the involvement of 5-HT3 receptors within the ventral tegmental area (VTA) in regulating ethanol self-administration by alcohol-preferring (P) rats. Standard two-lever operant chambers were used to examine the effects of 7 consecutive bilateral micro-infusions of ICS205-930 (ICS), a 5-HT3 receptor antagonist, directly into the posterior VTA on the acquisition and maintenance of 15% (v/v) ethanol self-administration. P rats readily acquired ethanol self-administration by the 4th session. The three highest doses (0.125, 0.25 and 1.25 ug) of ICS prevented acquisition of ethanol self-administration. During the acquisition post-injection 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 3 highest doses (0.75, 1.0 and 1.25 ug) of ICS significantly increased responding on the ethanol lever; following the 7-day dosing regimen, responding on the ethanol lever returned to control levels. Micro-infusion of ICS into the posterior VTA did not alter the low responding on the water lever, and did not alter saccharin (0.0125% w/v) self-administration.. Micro-infusion of ICS into the anterior VTA did not alter ethanol self-administration. Overall, the results of this study suggest that 5-HT3 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-HT3 receptor antagonist may alter neuronal circuitry within the posterior VTA. PMID:20682192

  5. 77 FR 59790 - General Services Administration Acquisition Regulation (GSAR); Rewrite of Part 504...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-10-01

    ... October 9, 2008, GSA published in the Federal Register at 73 FR 59589 a proposed rule with a request for... (GSAR); Rewrite of Part 504; Administrative Matters AGENCY: Office of Acquisition Policy, General... Administrative Matters and Forms. This final rule is part of the General Services Administration...

  6. AF-MSCs fate can be regulated by culture conditions

    PubMed Central

    Zagoura, D S; Trohatou, O; Bitsika, V; Makridakis, M; Pappa, K I; Vlahou, A; Roubelakis, M G; Anagnou, N P

    2013-01-01

    Human mesenchymal stem cells (hMSCs) represent a population of multipotent adherent cells able to differentiate into many lineages. In our previous studies, we isolated and expanded fetal MSCs from second-trimester amniotic fluid (AF) and characterized them based on their phenotype, pluripotency and proteomic profile. In the present study, we investigated the plasticity of these cells based on their differentiation, dedifferentiation and transdifferentiation potential in vitro. To this end, adipocyte-like cells (AL cells) derived from AF-MSCs can regain, under certain culture conditions, a more primitive phenotype through the process of dedifferentiation. Dedifferentiated AL cells derived from AF-MSCs (DAF-MSCs), gradually lost the expression of adipogenic markers and obtained similar morphology and differentiation potential to AF-MSCs, together with regaining the pluripotency marker expression. Moreover, a comparative proteomic analysis of AF-MSCs, AL cells and DAF-MSCs revealed 31 differentially expressed proteins among the three cell populations. Proteins, such as vimentin, galectin-1 and prohibitin that have a significant role in stem cell regulatory mechanisms, were expressed in higher levels in AF-MSCs and DAF-MSCs compared with AL cells. We next investigated whether AL cells could transdifferentiate into hepatocyte-like cells (HL cells) directly or through a dedifferentiation step. AL cells were cultured in hepatogenic medium and 4 days later they obtained a phenotype similar to AF-MSCs, and were termed as transdifferentiated AF-MSCs (TRAF-MSCs). This finding, together with the increase in pluripotency marker expression, indicated the adaption of a more primitive phenotype before transdifferentiation. Additionally, we observed that AF-, DAF- and TRAF-MSCs displayed similar clonogenic potential, secretome and proteome profile. Considering the easy access to this fetal cell source, the plasticity of AF-MSCs and their potential to dedifferentiate and

  7. 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

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF COMMERCE Bureau of Industry and Security 15 CFR Part 738 RIN 0694-AE62 Amendments to the Export Administration Regulations (EAR) Based Upon the Accession of Albania and Croatia to Formal Membership in the North...

  8. Education Department General Administrative Regulations. 34 CFR Parts 74, 75, 76, 77, 79, 80, 81, 82, 85 and 86.

    ERIC Educational Resources Information Center

    Department of Education, Washington, DC.

    During calendar year 1994, the U.S. Department of Education published significant revisions to the Education Department General Administrative Regulations (EDGAR). These regulatory changes addressed the noncompeting continuation (NCC) application process for discretionary grants and cooperative agreements, the Department's implementation of the…

  9. 17 CFR 230.508 - Insignificant deviations from a term, condition or requirement of Regulation D.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ..., Dec. 30, 1958, unless otherwise noted. Cross Reference: For regulations of Small Business Administration under the Small Business Investment Act of 1958, see 13 CFR, Chapter I. ... Small Business Investment Companies Authority: Sections 230.601 to 230.610a issued under sec. 19,...

  10. 17 CFR 230.508 - Insignificant deviations from a term, condition or requirement of Regulation D.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ..., Dec. 30, 1958, unless otherwise noted. Cross Reference: For regulations of Small Business Administration under the Small Business Investment Act of 1958, see 13 CFR, Chapter I. ... Small Business Investment Companies Authority: Sections 230.601 to 230.610a issued under sec. 19,...

  11. 17 CFR 230.508 - Insignificant deviations from a term, condition or requirement of Regulation D.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ..., Dec. 30, 1958, unless otherwise noted. Cross Reference: For regulations of Small Business Administration under the Small Business Investment Act of 1958, see 13 CFR, Chapter I. ... Small Business Investment Companies Authority: Sections 230.601 to 230.610a issued under sec. 19,...

  12. 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

  13. 42 CFR 485.918 - Condition of participation: Organization, governance, administration of services, and partial...

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ...) STANDARDS AND CERTIFICATION CONDITIONS OF PARTICIPATION: SPECIALIZED PROVIDERS Conditions of Participation... been discharged from an inpatient mental health facility. (a) Standard: Governing body and... management of the CMHC, the services it furnishes, its fiscal operations, and continuous quality...

  14. Adequacy of Science Teaching Conditions as Perceived by Administrators and Teachers

    ERIC Educational Resources Information Center

    Reineke, Robert; Welch, Wayne

    1975-01-01

    Compares principals' and teachers' perception of teaching conditions with the more positive views being possessed by principals. Information related to relative adequacy of conditions described by five scales, Effectiveness, Curriculum, Load, Facilities and Support is presented. (EB)

  15. 42 CFR 418.100 - Condition of Participation: Organization and administration of services.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... goals, with patient needs and goals as priority. (b) Standard: Governing body and administrator. A governing body (or designated persons so functioning) assumes full legal authority and responsibility for... reporting to the governing body is responsible for the day-to-day operation of the hospice....

  16. 42 CFR 484.14 - Condition of participation: Organization, services, and administration.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ...) Standard: Services furnished. Part-time or intermittent skilled nursing services and at least one other... personnel, and the staff; employs qualified personnel and ensures adequate staff education and evaluations... administrator. (d) Standard: Supervising physician or registered nurse. The skilled nursing and...

  17. 42 CFR 484.14 - Condition of participation: Organization, services, and administration.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ...) Standard: Services furnished. Part-time or intermittent skilled nursing services and at least one other... personnel, and the staff; employs qualified personnel and ensures adequate staff education and evaluations... administrator. (d) Standard: Supervising physician or registered nurse. The skilled nursing and...

  18. 42 CFR 418.100 - Condition of Participation: Organization and administration of services.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... goals, with patient needs and goals as priority. (b) Standard: Governing body and administrator. A governing body (or designated persons so functioning) assumes full legal authority and responsibility for... reporting to the governing body is responsible for the day-to-day operation of the hospice....

  19. 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…

  20. 76 FR 17138 - Food and Drug Administration Clinical Trial Requirements, Regulations, Compliance, and Good...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-03-28

    ... HUMAN SERVICES Food and Drug Administration Food and Drug Administration Clinical Trial Requirements... public workshop on FDA's clinical trial requirements is designed to aid the clinical research... interaction with FDA representatives. The program will focus on the relationships among FDA and clinical...

  1. 77 FR 8886 - Food and Drug Administration Clinical Trial Requirements, Regulations, Compliance, and Good...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-02-15

    ... HUMAN SERVICES Food and Drug Administration Food and Drug Administration Clinical Trial Requirements... public workshop on FDA's clinical trial requirements is designed to aid the clinical research... interaction with FDA representatives. The program will focus on the relationships among FDA and clinical...

  2. 76 FR 78933 - Food and Drug Administration Clinical Trial Requirements, Regulations, Compliance, and Good...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-20

    ... HUMAN SERVICES Food and Drug Administration Food and Drug Administration Clinical Trial Requirements... workshop. The public workshop on FDA's clinical trial requirements is designed to aid the clinical research... interaction with FDA representatives. The program will focus on the relationships among FDA and clinical...

  3. 76 FR 51040 - Food and Drug Administration Clinical Trial Requirements, Regulations, Compliance, and Good...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-08-17

    ... HUMAN SERVICES Food and Drug Administration Food and Drug Administration Clinical Trial Requirements... workshop. The public workshop on FDA's clinical trial requirements is designed to aid the clinical research... interaction with FDA representatives. The program will focus on the relationships among FDA and clinical...

  4. 75 FR 51824 - Food and Drug Administration Clinical Trial Requirements, Regulations, Compliance, and Good...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-23

    ... HUMAN SERVICES Food and Drug Administration Food and Drug Administration Clinical Trial Requirements... workshop. The public workshop on FDA's clinical trial requirements is designed to aid the clinical research... interaction with FDA representatives. The program will focus on the relationships among FDA and clinical...

  5. 75 FR 1788 - General Services Administration Regulation; Submission for OMB Review; Packing List Clause

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-01-13

    ... comments was published in the Federal Register at 74 FR 52811, October 14, 2009. No comments were received... Administration, 1800 F Street, NW., Room 4041, Washington, DC 20405. Please cite OMB Control No. 3090-0246... General Services Administration, Regulatory Secretariat (MVPR), 1800 F Street, NW., Room 4041,...

  6. 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...

  7. 75 FR 48872 - General Services Administration Acquisition Regulation; Rewrite of GSAR Part 541, Acquisition of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-12

    ... must provide that the limit can only be increased by affirmative action of the Government. Comment: The... Administration (GSA). ACTION: Final rule. SUMMARY: The General Services Administration (GSA) is amending the... Federal Register at 71 FR 7910, an Advanced Notice of Proposed Rulemaking (ANPR) with a request...

  8. 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

    ... Regulations (CFR) Parts 1-99, Parts 200-299, Parts 500-599, and Parts 600-799. Relevant sections of the FDA... Directive 65/65/EEC of 26 January 1965 on the approximation of provisions laid down by law, regulation, or... Directive 75/319/EEC of 20 May 1975 on the approximation of provisions laid down by law, regulation...

  9. 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

    ... Regulations (CFR) Parts 1-99, Parts 200-299, Parts 500-599, and Parts 600-799. Relevant sections of the FDA... Directive 65/65/EEC of 26 January 1965 on the approximation of provisions laid down by law, regulation, or... Directive 75/319/EEC of 20 May 1975 on the approximation of provisions laid down by law, regulation...

  10. 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

  11. 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

  12. 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.

  13. μ Opioid Receptor Expression after Morphine Administration Is Regulated by miR-212/132 Cluster.

    PubMed

    Garcia-Concejo, Adrian; Jimenez-Gonzalez, Ada; Rodríguez, Raquel E

    2016-01-01

    Since their discovery, miRNAs have emerged as a promising therapeutical approach in the treatment of several diseases, as demonstrated by miR-212 and its relation to addiction. Here we prove that the miR-212/132 cluster can be regulated by morphine, through the activation of mu opioid receptor (Oprm1). The molecular pathways triggered after morphine administration also induce changes in the levels of expression of oprm1. In addition, miR-212/132 cluster is actively repressing the expression of mu opioid receptor by targeting a sequence in the 3' UTR of its mRNA. These findings suggest that this cluster is closely related to opioid signaling, and function as a post-transcriptional regulator, modulating morphine response in a dose dependent manner. The regulation of miR-212/132 cluster expression is mediated by MAP kinase pathway, CaMKII-CaMKIV and PKA, through the phosphorylation of CREB. Moreover, the regulation of both oprm1 and of the cluster promoter is mediated by MeCP2, acting as a transcriptional repressor on methylated DNA after prolonged morphine administration. This mechanism explains the molecular signaling triggered by morphine as well as the regulation of the expression of the mu opioid receptor mediated by morphine and the implication of miR-212/132 in these processes. PMID:27380026

  14. μ Opioid Receptor Expression after Morphine Administration Is Regulated by miR-212/132 Cluster

    PubMed Central

    Garcia-Concejo, Adrian; Jimenez-Gonzalez, Ada; Rodríguez, Raquel E.

    2016-01-01

    Since their discovery, miRNAs have emerged as a promising therapeutical approach in the treatment of several diseases, as demonstrated by miR-212 and its relation to addiction. Here we prove that the miR-212/132 cluster can be regulated by morphine, through the activation of mu opioid receptor (Oprm1). The molecular pathways triggered after morphine administration also induce changes in the levels of expression of oprm1. In addition, miR-212/132 cluster is actively repressing the expression of mu opioid receptor by targeting a sequence in the 3’ UTR of its mRNA. These findings suggest that this cluster is closely related to opioid signaling, and function as a post-transcriptional regulator, modulating morphine response in a dose dependent manner. The regulation of miR-212/132 cluster expression is mediated by MAP kinase pathway, CaMKII-CaMKIV and PKA, through the phosphorylation of CREB. Moreover, the regulation of both oprm1 and of the cluster promoter is mediated by MeCP2, acting as a transcriptional repressor on methylated DNA after prolonged morphine administration. This mechanism explains the molecular signaling triggered by morphine as well as the regulation of the expression of the mu opioid receptor mediated by morphine and the implication of miR-212/132 in these processes. PMID:27380026

  15. 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

  16. Regulation of lipid droplet-associated proteins following growth hormone administration and feed restriction in lactating Holstein cows.

    PubMed

    Faylon, M P; Koltes, D E; Spurlock, D M

    2014-05-01

    Lipid metabolism plays a crucial role in the adaptation of dairy cows to periods of energy insufficiency. The objective of the current study was to determine if lipolytic proteins are consistently regulated when energy mobilization is stimulated by different factors. We evaluated 2 models of altered energy balance in mid-lactation Holstein cows, including feed restriction (FR) and administration of bovine growth hormone (GH), by quantifying the abundance and (or) phosphorylation of hormone-sensitive lipase (HSL), perilipin (PLIN), and adipose triglyceride lipase (ATGL). For GH administration, adipose tissue and blood samples were collected 4d before and 3 and 7d after administration of GH (n=20 cows). Similarly, adipose and blood samples were obtained 6d before and 1 and 4d after initiation of FR (n=18 cows). Estimated net energy balance decreased and nonesterified fatty acid concentration increased in both experimental models. Decreased ATGL and PLIN protein abundance was observed with GH administration and FR. Additionally, the abundance of phosphorylated HSLSer565 decreased in both models. Decreased abundance of phosphorylated PLIN was observed with GH administration, but not FR. Decreased ATGL protein abundance appears to be a consistent response to energy insufficiency in lactating cows, as this response was also described with negative energy balance at the onset of lactation. In contrast, the abundance of PLIN protein and phosphorylation of HSL using antibodies targeting serine residue 565 of HSL (HSLSer565) were altered in the current research, but not at the onset of lactation. Our findings demonstrate that lipolysis is altered through the regulation of multiple proteins, and that this regulation differs according to physiological state in lactating cows. PMID:24630665

  17. 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....S.C. app. 5; 22 U.S.C. 7201 et seq.; 22 U.S.C. 7210; E.O. 13026, 61 FR 58767, 3 CFR, 1996 Comp.,...

  18. Conditioned place aversion to the "hangover" phase of acute ethanol administration in the rat.

    PubMed

    Morse, A C; Schulteis, G; Holloway, F A; Koob, G F

    2000-08-01

    The purpose of this study was to examine ethanol's delayed effects (termed hangover) using conditioned place testing. Four groups of rats received a single pairing of a distinctive environment (tactile and visual) 10 h after injection with ethanol (0, 2, 3, 4 g/kg, i.p. ) or saline in a counterbalanced design. Rats receiving 3 and 4 g/kg ethanol showed a conditioned place aversion to ethanol hangover. Conditioning 10 h after 0 or 2 g/kg ethanol did not produce a significant place preference or aversion. The results suggest that the hangover following an acute injection of high doses of ethanol (3-4 g/kg) produces a significant and dose-related conditioned place aversion in the rat.

  19. 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

    ... transactions include sales by HUD of real estate-owned (REO) properties under HUD's regulations in 24 CFR part... Register on May 21, 2010, at 75 FR 28633. The May 2010 notice waived HUD's regulations through December 31... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HOUSING...

  20. 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...

  1. 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.

  2. [Condition of microflora of the nasopharynx in immunization with live influenza vaccine for oral administration].

    PubMed

    Kolotilova, L V; Shablovskaia, E A; Urin, A I; Lomnitskaia, V B; Vygovskaia, T V

    1975-07-01

    The authors present data concerning the state of the microflora of the nasopharynx in the immunization of adults and schoolchildren with the living influenza vaccine for oral administration. During the vaccinal process there occurred qualitative changes in the microbial pattern of the nasopharynx and a reduction in the level of the salivary lysozyme. The most pronounced changes were seen after the first vaccination, when the seeding efficiency of the pathogenic staphylococcus the E. coli and the Pr. mirabilis increased considerably. At the same time the incidence of isolation of the pathogenic staphylococcus, neisseria, and hemolytic streptococcus was decreased. The mentioned changes in the microbial flora directly depended on the dynamics of the survival of the vaccine influenza virus.

  3. 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.

  4. 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

  5. Administration of activated glial condition medium in the nucleus accumbens extended extinction and intensified reinstatement of methamphetamine-induced conditioned place preference.

    PubMed

    Arezoomandan, Reza; Moradi, Marzieh; Attarzadeh-Yazdi, Ghassem; Tomaz, Carlos; Haghparast, Abbas

    2016-07-01

    Methamphetamine (METH) is a psychostimulant drug with significant abuse potential and neurotoxic effects. A high percentage of users relapse to use after detoxification and no effective medication has been developed for treatment of METH addiction. Developing evidences indicated the role of glial cells in drugs abused related phenomena. However, little is known about the role of these cells in the maintenance and reinstatement of METH-seeking behaviors. Therefore, the current study was conducted to clarify the role of glial cells in the maintenance and reinstatement of METH-induced conditioned place preference (CPP) in rats. Astrocyte condition medium (ACM) and neuroglia conditioned medium (NCM) are liquid mediums prepared from primary astrocyte and neuroglia cells. These mediums seem to contain many factors that release by glia cells. CPP was induced by systemic administration of METH (1mg/kg for 5days, s.c.). Following the establishment of CPP, the rats were given daily bilateral injections (0.5μl/side) of either vehicle, ACM or NCM into the nucleus accumbens (NAc) and then were tested for the maintenance and reinstatement. Intra-NAc administration of ACM treated with METH, could extend the extinction period and also, intensified the magnitude of METH reinstatement. Furthermore, intra-accumbal administration of NCM treated with METH notably delayed the extinction period by four days and significantly increased the magnitude of CPP score in the reinstatement phase compared to the post-test phase. Collectively, these findings suggested that activation of glial cells may be involved in the maintenance and reinstatement of METH-seeking behaviors. It provides new evidence that glia cells might be considered as a potential target for the treatment of METH addiction. PMID:27346277

  6. Adequacy of Teaching Conditions as Perceived by Administrators and Teachers. Research Paper No. 7.

    ERIC Educational Resources Information Center

    Reineke, Robert; Welch, Wayne

    This research study sought to examine the degree of heterophily which was indicated between principals and teachers regarding the perceived adequacy of school conditions. The sample comprised principals and teachers randomly selected from five regions. Three of the regions focused on science teachers while the other two involved mathematics…

  7. 78 FR 303 - General Services Administration Acquisition Regulation; Information Collection; Proposal To Lease...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-01-03

    ... and Budget (OMB) a request to review and approve an extension of a previously approved information... required by regulation, but necessary to (1) evaluate whether the physical attributes of offered...

  8. 77 FR 35310 - Revisions to the Export Administration Regulations (EAR): Control of Military Training Equipment...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-06-13

    ... Administration's ongoing Export Control Reform Initiative, BIS published a proposed rule (76 FR 41958) (herein... 7, 2011, BIS published a rule (76 FR 68675) proposing several changes to the framework initially..., ``specially designed'' for military applications, it was identified in the new ECCNs proposed in this...

  9. 77 FR 22191 - Revisions to the Export Administration Regulations (EAR): Export Control Classification Number...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-04-13

    ... Administrative practice and procedure, Exports, Inventions and patents, Research science and technology. 15 CFR... identified in an existing ECCN. As BIS explained in the proposed rule issued on July 15, 2011 (76 FR 41958... Initiative, the Bureau of Industry and Security (BIS) published a proposed rule (76 FR 41958) (herein...

  10. 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…

  11. 78 FR 57156 - General Services Administration Acquisition Regulation; Submission for OMB Review; Modifications...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-09-17

    ... Acquisition Policy Division, GSA, 202-357-9652 or email Dana.Munson@gsa.gov for clarification of content. For... Services Administration, Regulatory Secretariat Division (MVCB), 2250C, 1800 F Street NW., Washington, DC...-72 Modifications (Multiple Award Schedule), is being reinstated at GSAR 552.238-81,...

  12. 78 FR 43972 - Amendments to the Export Administration Regulations: Implementation of Limited Syria Waiver for...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-07-23

    ...). See 69 FR 26766 (May 14, 2004). In addition, BIS later made administrative changes to General Order No.... See 74 FR 77115 (Dec. 12, 2011). On June 12, 2013, the Secretary of State exercised authority..., 2001 (3 CFR, 2001 Comp., p. 783 (2002)), as amended by Executive Order 13637 of March 8, 2013, 78...

  13. 77 FR 69768 - General Services Administration Acquisition Regulation (GSAR); Rewrite of Part 504...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-11-21

    ... (GSA) published a document in the Federal Register on October 1, 2012 (77 FR 59790), revising... published in the Federal Register at 77 FR 59790 on October 1, 2012 contained a typographical error. This...); Rewrite of Part 504, Administrative Matters; Correction AGENCY: Office of Acquisition Policy,...

  14. 75 FR 73951 - Amendments to General Regulations of the Food and Drug Administration

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-11-30

    ... procedures for issuing a direct final rule? In the Federal Register of November 21, 1997 (62 FR 62466), FDA... document entitled ``Guidance for FDA and Industry: Direct Final Rule Procedures'' (62 FR 62466). This... HUMAN SERVICES Food and Drug Administration 21 CFR Parts 1, 14, and 17 RIN 0910-AG55 Amendments...

  15. 39 CFR 233.9 - Regulations governing remission or mitigation of administrative, civil, and criminal forfeitures.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... related crime would be any offense involving a violation of the Federal laws relating to drugs, or the... considering remission or mitigation of administrative forfeitures under the jurisdiction of the Postal... and, where required, took all reasonable steps under the circumstances to ensure that such...

  16. Insensitivity of well-conditioned mature sheep to central administration of a leptin receptor antagonist.

    PubMed

    Foskolos, A; Ehrhardt, R A; Hileman, S M; Gertler, A; Boisclair, Y R

    2015-11-01

    Ruminants remain productive during the energy insufficiency of late pregnancy or early lactation by evoking metabolic adaptations sparing available energy and nutrients (e.g. higher metabolic efficiency and induction of insulin resistance). A deficit in central leptin signaling triggers these adaptations in rodents but whether it does in ruminants remains unclear. To address this issue, five mature ewes were implanted with intracerebroventricular (ICV) cannula in the third ventricle. They were used in two experiments with an ovine leptin antagonist (OLA) when well-conditioned (average body condition score of 3.7 on a 5 point scale). The first experiment tested the ability of OLA to antagonize leptin under in vivo conditions. Ewes received continuous ICV infusion of artificial cerebrospinal fluid (aCSF), ovine leptin (4 µg/h) or the combination of ovine leptin (4 µg/h) and its mutant version OLA (40 µg/h) for 48 h. Dry matter intake (DMI) was measured every day and blood samples were collected on the last day of infusion. ICV infusion of leptin reduced DMI by 24% (P < 0.05), and this effect was completely abolished by OLA co-infusion. A second experiment tested whether a reduction in endogenous leptin signaling in the brain triggers metabolic adaptations. This involved continuous ICV infusions of aCSF or OLA alone (40 µg/h) for 4 consecutive days. The infusion of OLA did not alter voluntary DMI over the treatment period or on any individual day. OLA did not affect plasma variables indicative of insulin action (glucose, non-esterified fatty acids, insulin and the disposition of plasma glucose during an insulin tolerance test) or plasma cortisol, but tended to reduce plasma triiodothyronine and thyroxine (P < 0.07). Overall, these data show that a reduction of central leptin signaling has little impact on insulin action in well-conditioned mature sheep. They also raise the possibility that reduced central leptin signaling plays a role in controlling thyroid

  17. 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

  18. Region-specific up-regulation of oxytocin receptor binding in the brain of mice following chronic nicotine administration.

    PubMed

    Zanos, Panos; Georgiou, Polymnia; Metaxas, Athanasios; Kitchen, Ian; Winsky-Sommerer, Raphaelle; Bailey, Alexis

    2015-07-23

    Nicotine addiction is considered to be the main preventable cause of death worldwide. While growing evidence indicates that the neurohypophysial peptide oxytocin can modulate the addictive properties of several abused drugs, the regulation of the oxytocinergic system following nicotine administration has so far received little attention. Here, we examined the effects of long-term nicotine or saline administration on the central oxytocinergic system using [(125)I]OVTA autoradiographic binding in mouse brain. Male, 7-week old C57BL6J mice were treated with either nicotine (7.8 mg/kg daily; rate of 0.5 μl per hour) or saline for a period of 14-days via osmotic minipumps. Chronic nicotine administration induced a marked region-specific upregulation of the oxytocin receptor binding in the amygdala, a brain region involved in stress and emotional regulation. These results provide direct evidence for nicotine-induced neuroadaptations in the oxytocinergic system, which may be involved in the modulation of nicotine-seeking as well as emotional consequence of chronic drug use. PMID:26037668

  19. Education Department General Administrative Regulations. 34 CFR Parts 74, 75, 76, 77, 79, 80, 81, 82, 85, 86, 97, 98, and 99.

    ERIC Educational Resources Information Center

    Department of Education, Washington, DC.

    This publication by the U.S. Department of Education is an unofficial version of the Department's General Administrative Regulations. The volume incorporates final regulations that the Department published too late to appear in the official July 1, 1998, version of Title 34 of the Code of Federal Regulations issued by the Office of the Federal…

  20. Insensitivity of well-conditioned mature sheep to central administration of a leptin receptor antagonist.

    PubMed

    Foskolos, A; Ehrhardt, R A; Hileman, S M; Gertler, A; Boisclair, Y R

    2015-11-01

    Ruminants remain productive during the energy insufficiency of late pregnancy or early lactation by evoking metabolic adaptations sparing available energy and nutrients (e.g. higher metabolic efficiency and induction of insulin resistance). A deficit in central leptin signaling triggers these adaptations in rodents but whether it does in ruminants remains unclear. To address this issue, five mature ewes were implanted with intracerebroventricular (ICV) cannula in the third ventricle. They were used in two experiments with an ovine leptin antagonist (OLA) when well-conditioned (average body condition score of 3.7 on a 5 point scale). The first experiment tested the ability of OLA to antagonize leptin under in vivo conditions. Ewes received continuous ICV infusion of artificial cerebrospinal fluid (aCSF), ovine leptin (4 µg/h) or the combination of ovine leptin (4 µg/h) and its mutant version OLA (40 µg/h) for 48 h. Dry matter intake (DMI) was measured every day and blood samples were collected on the last day of infusion. ICV infusion of leptin reduced DMI by 24% (P < 0.05), and this effect was completely abolished by OLA co-infusion. A second experiment tested whether a reduction in endogenous leptin signaling in the brain triggers metabolic adaptations. This involved continuous ICV infusions of aCSF or OLA alone (40 µg/h) for 4 consecutive days. The infusion of OLA did not alter voluntary DMI over the treatment period or on any individual day. OLA did not affect plasma variables indicative of insulin action (glucose, non-esterified fatty acids, insulin and the disposition of plasma glucose during an insulin tolerance test) or plasma cortisol, but tended to reduce plasma triiodothyronine and thyroxine (P < 0.07). Overall, these data show that a reduction of central leptin signaling has little impact on insulin action in well-conditioned mature sheep. They also raise the possibility that reduced central leptin signaling plays a role in controlling thyroid

  1. US Food and Drug Administration regulations governing label claims for food products, including probiotics.

    PubMed

    Saldanha, Leila G

    2008-02-01

    The US Congress has granted the Food and Drug Administration the authority to permit manufacturers to use claims in food labels that fit into the following broad categories: health claims, structure/function claims, nutrient content claims, and dietary guidance messages. This article outlines the scope and evolution of these claims and how they are used in the marketing of probiotics. Probiotics are live microorganisms (in most cases, bacteria) that are similar to beneficial microorganisms found in the human gut.

  2. 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…

  3. 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

  4. Axonal trafficking of an antisense RNA transcribed from a pseudogene is regulated by classical conditioning

    PubMed Central

    Korneev, Sergei A.; Kemenes, Ildiko; Bettini, Natalia L.; Kemenes, George; Staras, Kevin; Benjamin, Paul R.; O'Shea, Michael

    2013-01-01

    Natural antisense transcripts (NATs) are endogenous RNA molecules that are complementary to known RNA transcripts. The functional significance of NATs is poorly understood, but their prevalence in the CNS suggests a role in brain function. Here we investigated a long NAT (antiNOS-2 RNA) associated with the regulation of nitric oxide (NO) production in the CNS of Lymnaea, an established model for molecular analysis of learning and memory. We show the antiNOS-2 RNA is axonally trafficked and demonstrate that this is regulated by classical conditioning. Critically, a single conditioning trial changes the amount of antiNOS-2 RNA transported along the axon. This occurs within the critical time window when neurotransmitter NO is required for memory formation. Our data suggest a role for the antiNOS-2 RNA in establishing memories through the regulation of NO signaling at the synapse. PMID:23293742

  5. 75 FR 22819 - Considerations Regarding Food and Drug Administration Review and Regulation of Articles for the...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-30

    ... and Regulation of Articles for the Treatment of Rare Diseases; Public Hearing AGENCY: Food and Drug... by which FDA considers articles for people with rare diseases, a recent public law (Agriculture..., marketing authorization for, and postmarket surveillance of, articles for rare diseases. The scope of...

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

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ..., minerals, food additives and dietary supplements, and bottled water. These items do not fall within the... Regulations (EAR). In this part, references to the EAR are references to 15 CFR chapter VII, subchapter C... applications to export and reexport items on the U.S. Munitions List. (See 22 CFR parts 120 through 130.)...

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

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ..., minerals, food additives and dietary supplements, and bottled water. These items do not fall within the... Regulations (EAR). In this part, references to the EAR are references to 15 CFR chapter VII, subchapter C... items on the U.S. Munitions List. (See 22 CFR parts 120 through 130.) Dual use. Items that have...

  8. 15 CFR 772.1 - Definitions of terms as used in the Export Administration Regulations (EAR).

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ..., minerals, food additives and dietary supplements, and bottled water. These items do not fall within the... Regulations (EAR). In this part, references to the EAR are references to 15 CFR chapter VII, subchapter C..., responsible for reviewing applications to export and reexport items on the U.S. Munitions List. (See 22...

  9. 15 CFR 772.1 - Definitions of terms as used in the Export Administration Regulations (EAR).

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ..., minerals, food additives and dietary supplements, and bottled water. These items do not fall within the... Regulations (EAR). In this part, references to the EAR are references to 15 CFR chapter VII, subchapter C... items on the U.S. Munitions List. (See 22 CFR parts 120 through 130.) Dual use. Items that have...

  10. 20 CFR 672.500 - What administrative regulations apply to the YouthBuild program?

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... requirements found in 20 CFR part 667, except those that apply only to the WIA Title I-B program and those that... grants requirements: Circular A-110 (codified at 2 CFR part 215), and Circular A-102 at 29 CFR parts 95 and 97, as applicable; (2) The Department's regulations at 29 CFR part 37, which implement...

  11. 20 CFR 672.500 - What administrative regulations apply to the YouthBuild program?

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... requirements found in 20 CFR part 667, except those that apply only to the WIA Title I-B program and those that... grants requirements: Circular A-110 (codified at 2 CFR part 215), and Circular A-102 at 29 CFR parts 95 and 97, as applicable; (2) The Department's regulations at 29 CFR part 37, which implement...

  12. 20 CFR 672.500 - What administrative regulations apply to the YouthBuild program?

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... requirements found in 20 CFR part 667, except those that apply only to the WIA Title I-B program and those that... grants requirements: Circular A-110 (codified at 2 CFR part 215), and Circular A-102 at 29 CFR parts 95 and 97, as applicable; (2) The Department's regulations at 29 CFR part 37, which implement...

  13. 75 FR 53864 - Updated Statements of Legal Authority for the Export Administration Regulations

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-02

    ..., Inventions and patents, Research, Science and technology. 15 CFR Parts 736, 738, 770, and 772 Exports. 15 CFR... Regarding Export Control Regulations (74 FR 50681, August 16, 2010), which is the most recent such annual... recordkeeping requirements, Science and technology. 0 Accordingly, parts 730, 732, 734, 736, 738, 740, 742,...

  14. 76 FR 58393 - Updated Statements of Legal Authority for the Export Administration Regulations

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-09-21

    ... procedure, Exports, Inventions and patents, Research, Science and technology. 15 CFR Parts 736, 738, 770... notice of August 12, 2011--Continuation of Emergency Regarding Export Control Regulations (76 FR 50661... procedure, Exports, Reporting and recordkeeping requirements, Science and technology. Accordingly, parts...

  15. 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)

  16. 77 FR 73289 - Hazardous Substances and Articles; Administration and Enforcement Regulations: Revisions to...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-12-10

    ... rulemaking to amend and to update regulations on the CPSC's animal testing methods under the FHSA. 77 FR... ) approved by the Commission. 77 FR 38751. The proposed codification at 16 CFR 1500.232 would make the ICCVAM... FR 38754). We received three comments on the proposed rule. Two of the comments were from...

  17. 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

    ... that appeared in the Federal Register of November 30, 2010 (75 FR 73951). The direct final rule amends... (75 FR 73951), FDA solicited comments concerning the direct final rule for a 75-day period ending... authority to regulate these products under the Family Smoking Prevention and Tobacco Control Act,...

  18. 78 FR 69543 - Amendments to General Regulations of the Food and Drug Administration; Technical Amendments

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-11-20

    ... Federal Register of November 30, 2010 (75 FR 73951), we amended certain regulations in part 1 (21 CFR part... products under the Tobacco Control Act (75 FR 73951 at 73952). However, the revisions inadvertently created... to section 302 of the Federal Food, Drug, and Cosmetic Act (FD&C Act) (21 U.S.C. 332); Revised Sec....

  19. 78 FR 61743 - Revisions to the Export Administration Regulations: Initial Implementation of Export Control...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-10-03

    ... October 3, 2013 Part VII Department of Commerce Bureau of Industry and Security 15 CFR Parts 730, 732, 734... / Rules and Regulations#0;#0; ] DEPARTMENT OF COMMERCE Bureau of Industry and Security 15 CFR Parts 730... Reform; Correction AGENCY: Bureau of Industry and Security, Commerce. ACTION: Final rule;...

  20. 77 FR 74631 - General Services Administration Acquisition Regulation: Modifications (Multiple Award Schedules...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-12-17

    ... (Multiple Award Schedules); Information Collection AGENCY: Office of Acquisition Policy, General Services... Modifications (Multiple Award Schedule). DATES: Submit comments on or before: February 15, 2013. FOR FURTHER... Acquisition Regulation (GSAR) to add clause 552.243-72; Modifications (Multiple Award Schedules). Under...

  1. 77 FR 56766 - Updated Statements of Legal Authority for the Export Administration Regulations

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-09-14

    ... 746 of the EAR with respect to Syria is based in part on Executive Order 13338, 69 FR 26751, 3 CFR... August 15, 2012--Continuation of Emergency Regarding Export Control Regulations, 77 FR 49699 (August 16... Actions of the Government of Syria, 77 FR 27559 (May 10, 2012), which is the most recent such...

  2. 76 FR 6149 - Federal Housing Administration (FHA): Temporary Exemption From Compliance With FHA's Regulation...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-02-03

    ... provided in the May 21, 2010 (75 FR 28632), that led to HUD's decision to issue the waiver. Section 203.37a... include, for example, sales by HUD of real estate-owned (REO) properties under HUD's regulations in 24 CFR... for Housing--Federal Housing Commissioner. Appendix Assessment of Exemption From Compliance With...

  3. 15 CFR 772.1 - Definitions of terms as used in the Export Administration Regulations (EAR).

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... Regulations (EAR). In this part, references to the EAR are references to 15 CFR chapter VII, subchapter C... magnetometers) together with software that permit reduction of rigid body rotation noise of the platform... items on the U.S. Munitions List. (See 22 CFR parts 120 through 130.) Dual use. Items that have...

  4. 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

  5. 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

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

    PubMed

    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

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

    PubMed

    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

  8. Short-term, high-dose administration of corticosterone by injection facilitates trace eyeblink conditioning in young male rats.

    PubMed

    Wentworth-Eidsaune, Christine L; Hennessy, Michael B; Claflin, Dragana I

    2016-02-01

    Glucocorticoids released as part of the physiological response to stress are known to affect cognitive function, presumably via effects on the hippocampus. Trace classical eyeblink conditioning is an associative learning task which depends on the hippocampus and has been used to examine the development of learning processes in young mammals. Previously, we demonstrated deficits in trace eyeblink conditioning associated with postnatal administration of the glucocorticoid corticosterone by creating a sustained elevation with methods such as subcutaneous timed-release pellets and osmotic mini-pumps which were active over several days. In the present study, we examined the effects of an oscillating pattern of corticosterone elevation on subsequent trace eyeblink conditioning. Twice daily corticosterone injections (high, low, or vehicle) were administered over a 3-day period, starting at postnatal day 15. Then, on postnatal day 28, animals underwent trace classical eyeblink conditioning to examine the possible influence of earlier corticosterone elevations on the development of learning and memory. Eyeblink conditioning was affected by corticosterone treatments, but only for males, and only very early in acquisition; Males receiving the high dose of corticosterone exhibited facilitation of learning relative to controls. These data demonstrate that oscillating corticosterone elevations produce opposite effects on this associative learning task than do sustained elevations.

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

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 48 Federal Acquisition Regulations System 2 2011-10-01 2011-10-01 false Change in Rates or Terms and Conditions of Service for Regulated Services. 52.241-7 Section 52.241-7 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION (CONTINUED) CLAUSES AND FORMS SOLICITATION PROVISIONS...

  10. 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

    ... 48 Federal Acquisition Regulations System 2 2010-10-01 2010-10-01 false Change in Rates or Terms and Conditions of Service for Regulated Services. 52.241-7 Section 52.241-7 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION (CONTINUED) CLAUSES AND FORMS SOLICITATION PROVISIONS...

  11. 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...

  12. 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.

  13. 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. PMID:25820086

  14. 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

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

    PubMed

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

    2013-01-18

    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.

  16. Regulation of skeletal muscle protein degradation and synthesis by oral administration of lysine in rats.

    PubMed

    Sato, Tomonori; Ito, Yoshiaki; Nagasawa, Takashi

    2013-01-01

    Several catabolic diseases and unloading induce muscle mass wasting, which causes severe pathological progression in various diseases and aging. Leucine is known to attenuate muscle loss via stimulation of protein synthesis and suppression of protein degradation in skeletal muscle. The aim of this study was to investigate the effects of lysine intake on protein degradation and synthesis in skeletal muscle. Fasted rats were administered 22.8-570 mg Lys/100 g body weight and the rates of myofibrillar protein degradation were assessed for 0-6 h after Lys administration. The rates of myofibrillar protein degradation evaluated by MeHis release from the isolated muscles were markedly suppressed after administration of 114 mg Lys/100 g body weight and of 570 mg Lys/100 g body weight. LC3-II, a marker of the autophagic-lysosomal pathway, tended to decrease (p=0.05, 0.08) after Lys intake (114 mg/100 g body weight). However, expression of ubiquitin ligase E3 atrogin-1 mRNA and levels of ubiquitinated proteins were not suppressed by Lys intake. Phosphorylation levels of mTOR, S6K1 and 4E-BP1 in the gastrocnemius muscle were not altered after Lys intake. These results suggest that Lys is able to suppress myofibrillar protein degradation at least partially through the autophagic-lysosomal pathway, not the ubiquitin-proteasomal pathway, whereas Lys might be unable to stimulate protein synthesis within this time frame. PMID:24418875

  17. Regulation of skeletal muscle protein degradation and synthesis by oral administration of lysine in rats.

    PubMed

    Sato, Tomonori; Ito, Yoshiaki; Nagasawa, Takashi

    2013-01-01

    Several catabolic diseases and unloading induce muscle mass wasting, which causes severe pathological progression in various diseases and aging. Leucine is known to attenuate muscle loss via stimulation of protein synthesis and suppression of protein degradation in skeletal muscle. The aim of this study was to investigate the effects of lysine intake on protein degradation and synthesis in skeletal muscle. Fasted rats were administered 22.8-570 mg Lys/100 g body weight and the rates of myofibrillar protein degradation were assessed for 0-6 h after Lys administration. The rates of myofibrillar protein degradation evaluated by MeHis release from the isolated muscles were markedly suppressed after administration of 114 mg Lys/100 g body weight and of 570 mg Lys/100 g body weight. LC3-II, a marker of the autophagic-lysosomal pathway, tended to decrease (p=0.05, 0.08) after Lys intake (114 mg/100 g body weight). However, expression of ubiquitin ligase E3 atrogin-1 mRNA and levels of ubiquitinated proteins were not suppressed by Lys intake. Phosphorylation levels of mTOR, S6K1 and 4E-BP1 in the gastrocnemius muscle were not altered after Lys intake. These results suggest that Lys is able to suppress myofibrillar protein degradation at least partially through the autophagic-lysosomal pathway, not the ubiquitin-proteasomal pathway, whereas Lys might be unable to stimulate protein synthesis within this time frame.

  18. 76 FR 77115 - Amendments to the Export Administration Regulations: Facilitating Enhanced Public Understanding...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-12

    ... that of August 12, 2011 (76 FR 50,661 (Aug. 16, 2011)), has continued the Regulations in effect under.... 13026, 61 FR 58767, 3 CFR, 1996 Comp., p. 228; E.O. 13222, 66 FR 44025, 3 CFR, 2001 Comp., p. 783; Notice of August 12, 2011 (76 FR 50661 (Aug. 16, 2011)). Sec. 732.1 0 2. Section 732.1 is amended by: 0...

  19. 7 CFR 301.86-4 - Conditions governing the interstate movement of regulated articles from quarantined areas.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... experimental or scientific purposes; or (ii) The regulated article originates outside the quarantined area and... traffic conditions such as traffic lights and stop signs); and (C) The regulated article is not...

  20. [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.

  1. Environmental conditions and transcriptional regulation in Escherichia coli: a physiological integrative approach.

    PubMed

    Martínez-Antonio, Agustino; Salgado, Heladia; Gama-Castro, Socorro; Gutiérrez-Ríos, Rosa María; Jiménez-Jacinto, Verónica; Collado-Vides, Julio

    2003-12-30

    Bacteria develop a number of devices for sensing, responding, and adapting to different environmental conditions. Understanding within a genomic perspective how the transcriptional machinery of bacteria is modulated, as a response for changing conditions, is a major challenge for biologists. Knowledge of which genes are turned on or turned off under specific conditions is essential for our understanding of cell behavior. In this study we describe how the information pertaining to gene expression and associated growth conditions (even with very little knowledge of the associated regulatory mechanisms) is gathered from the literature and incorporated into RegulonDB, a database on transcriptional regulation and operon organization in E. coli. The link between growth conditions, signal transduction, and transcriptional regulation is modeled in the database in a simple format that highlights biological relevant information. As far as we know, there is no other database that explicitly clarifies the effect of environmental conditions on gene transcription. We discuss how this knowledge constitutes a benchmark that will impact future research aimed at integration of regulatory responses in the cell; for instance, analysis of microarrays, predicting culture behavior in biotechnological processes, and comprehension of dynamics of regulatory networks. This integrated knowledge will contribute to the future goal of modeling the behavior of E. coli as an entire cell. The RegulonDB database can be accessed on the web at the URL: http://www.cifn.unam.mx/Computational_Biology/regulondb/. PMID:14708114

  2. 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

  3. Epigenetic modulation of Homer1a transcription regulation in amygdala and hippocampus with pavlovian fear conditioning.

    PubMed

    Mahan, Amy L; Mou, Liping; Shah, Nirali; Hu, Jia-Hua; Worley, Paul F; Ressler, Kerry J

    2012-03-28

    The consolidation of conditioned fear involves upregulation of genes necessary for long-term memory formation. An important question remains as to whether this results in part from epigenetic regulation and chromatin modulation. We examined whether Homer1a, which is required for memory formation, is necessary for Pavlovian cued fear conditioning, whether it is downstream of BDNF-TrkB activation, and whether this pathway utilizes histone modifications for activity-dependent transcriptional regulation. We initially found that Homer1a knock-out mice exhibited deficits in cued fear conditioning (5 tone-shock presentations with 70 dB, 6 kHz tones and 0.5 s, 0.6 mA footshocks). We then demonstrated that: (1) Homer1a mRNA increases after fear conditioning in vivo within both amygdala and hippocampus of wild-type mice; (2) it increases after BDNF application to primary hippocampal and amygdala cultures in vitro; and (3) these increases are dependent on transcription and MAPK signaling. Furthermore, using chromatin immunoprecipitation we found that both in vitro and in vivo manipulations result in decreases in Homer1 promoter H3K9 methylation in amygdala cells but increases in Homer1 promoter H3 acetylation in hippocampal cells. However, no changes were observed in H4 acetylation or H3K27 dimethylation. Inhibition of histone deacetylation by sodium butyrate enhanced contextual but not cued fear conditioning and enhanced Homer1 H3 acetylation in the hippocampus. These data provide evidence for dynamic epigenetic regulation of Homer1a following BDNF-induced plasticity and during a BDNF-dependent learning process. Furthermore, upregulation of this gene may be regulated through distinct epigenetic modifications in the hippocampus and amygdala.

  4. The regulators of yeast PHO system participate in the transcriptional regulation of G1 cyclin under alkaline stress conditions.

    PubMed

    Nishizawa, Masafumi

    2015-03-01

    The yeast Pho85 kinase oversees whether environmental conditions are favourable for cell growth and enables yeast cells to express only genes that are appropriate for the conditions. Alkaline stress perturbs transport of molecules across the plasma membrane that is vital for cell survival. Progression through the cell cycle is halted until the cells can adapt to the stress conditions. I found that Pho85 is required for CLN2 expression and that overproduction of the transcription factors Pho4, Rim101 and Crz1, all targets of Pho85, inhibited CLN2 expression. CLN2 expression in the absence of Pho85 could be recovered only when all the three transcription factors were deleted. Whi5, a functional homologue of the mammalian Rb protein, represses CLN2 expression and is inactivated when phosphorylated by either of the CDK-cyclin complexes, Cdc28-Cln3 or Pho85-Pcl9. Under alkaline conditions, the absence of Whi5 caused an increase in CLN2 expression but failed to do so when Pho85 was also absent, or when Pho4 was overproduced. The expression level of CLN2 in a Δpho85 Δpho4 Δrim101 Δcrz1 quadruple mutant was stimulated when the Whi5 activity was repressed by overproduction of Pho85-Pcl9. These results indicate that Whi5 is also under control of alkaline stress. The inhibitory function of Whi5 on CLN2 is dependent on Rpd3 HDAC, and the absence of Rpd3 could also suppress the inhibitory effect of Pho4 overproduction. Based on these findings, a model is presented in which Pho85 and Pho4 functions in CLN2 regulation under alkaline conditions.

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

    PubMed

    2001-07-01

    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.

  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. Identification of plasticity-associated genes regulated by Pavlovian fear conditioning in the lateral amygdala.

    PubMed

    Ploski, Jonathan E; Park, Kevin W; Ping, Junli; Monsey, Melissa S; Schafe, Glenn E

    2010-02-01

    Most recent studies aimed at defining the cellular and molecular mechanisms of Pavlovian fear conditioning have focused on protein kinase signaling pathways and the transcription factor cAMP-response element binding protein (CREB) that promote fear memory consolidation in the lateral nucleus of the amygdala (LA). Despite this progress, there still remains a paucity of information regarding the genes downstream of CREB that are required for long-term fear memory formation in the LA. We have adopted a strategy of using microarray technology to initially identify genes induced within the dentate gyrus following in vivo long-term potentiation (LTP) followed by analysis of whether these same genes are also regulated by fear conditioning within the LA. In the present study, we first identified 34 plasticity-associated genes that are induced within 30 min following LTP induction utilizing a combination of DNA microarray, qRT-PCR, and in situ hybridization. To determine whether these genes are also induced in the LA following Pavlovian fear conditioning, we next exposed rats to an auditory fear conditioning protocol or to control conditions that do not support fear learning followed by qRT-PCR on mRNA from microdissected LA samples. Finally, we asked whether identified genes induced by fear learning in the LA are downstream of the extracellular-regulated kinase/mitogen-activated protein kinase signaling cascade. Collectively, our findings reveal a comprehensive list of genes that represent the first wave of transcription following both LTP induction and fear conditioning that largely belong to a class of genes referred to as 'neuronal activity dependent genes' that are likely calcium, extracellular-regulated kinase/mitogen-activated protein kinase, and CREB-dependent.

  8. Regulation of kinesin-transport by microtubule age and polymerization conditions

    NASA Astrophysics Data System (ADS)

    Xu, Jing; Liang, Winnie; King, Stephen; Faysal, K.

    2015-03-01

    Microtubules are fundamental biopolymers in cells, formed via self-assembly (``polymerization'') of tubulin dimers. Microtubule polymerization conditions have been shown to alter the presence of defects in microtubule lattices, including point defects (missing tubulin dimers) and line defects (protofilament disruption). Potential impact of these lattice defects on molecular motor-based transport is not yet understood. Here we investigate the impact of microtubule polymerization conditions on multiple-kinesin transport, using single-molecule-type optical trapping experiments. We find that kinesin-based cargoes pause preferentially at specific locations along individual microtubules, and that the pause frequency and duration is strongly dependent on microtubule age and polymerization condition. Within each polymerization condition and for fresh microtubules, we also observe significant variations in multiple-kinesin travel distances, depending on which microtubules the motors travel along. Taken together, our study suggests an important role of microtubule lattice defect in regulating intracellular transport.

  9. 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.

  10. Regulated hypothermia in the hypothyroid rat induced by administration of propylthiouracil.

    PubMed

    Yang, Y; Gordon, C J

    1997-05-01

    Propylthiouracil (PTU), an antithyroidal drug that reduces serum L-thyroxine (T4) and 3,5,3'-triiodothyronine (T3), is presumed to lower core temperature (T0) by impairing metabolic thermogenesis. However, it is not understood why PTU-treated animals cannot use behavioral and other thermoeffectors to maintain normal Tc. Male rats were administered PTU in drinking water (0.05 mg/ml) while the following parameters were measured: 1) Tc and motor activity (MA) recorded by radiotelemetry for 24 h at ambient temperatures (Ta) of 10-30 degrees C; 2) selected Ta, MA, and Tc in a temperature gradient; and 3) Tc, MA, and grooming behavior during exposure to heat stress (TH = 34.5 degrees C) for 2 h. PTU reduced serum levels of T4, and T3 by 95 and 60%, respectively. Tc decreased after 3 days of PTU treatment; a 0.5 degree C decrease in Tc persisted throughout the PTU treatment. PTU rats exposed to Ta of 10-30 degrees C maintained a consistent hypothermic Tc during the light phase; however, a deficit in the stability of Tc at night was noted during exposure to 10 degrees C. In the temperature gradient, PTU rats selected warmer Ta, but their Tc was maintained at the same hypothermic levels as observed at fixed Ta values of 15-30 degrees C. Heat stress caused Tc of control rats to increase to 39 degrees C, whereas Tc of the PTU rats was maintained below 38 degrees C. The regulation of Tc at hypothermic levels over a wide range of Ta values and when rats were housed in a temperature gradient indicates that chronic PTU induces a state of regulated hypothermia. PMID:9176328

  11. Three Brassica rapa metallothionein genes are differentially regulated under various stress conditions.

    PubMed

    Ahn, Young Ock; Kim, Sun Ha; Lee, Jeongyeo; Kim, Hyeran; Lee, Haeng-Soon; Kwak, Sang-Soo

    2012-03-01

    The expression profiles of three Brassica rapa metallothionein genes (BrMT 1-3) were determined in 7-day-old seedlings exposed to various exogenous factors including plant hormones, heavy metals and abiotic stresses. BrMT1, BrMT2, and BrMT3 were representatives of MT gene type 1, type 2, and type 3, respectively, according to their cysteine alignment. BrMT2 showed a relatively higher basal expression level compared to BrMT1 and BrMT3 under normal conditions. The BrMT1 transcript was markedly increased by various factors including ethephon, polyethylene glycol and hydrogen peroxide, with no down-regulation evident. On the contrary, BrMT2 expression was down-regulated by abscisic acid, salicylic acid, and methyl jasmonate. Heavy metals did not increase BrMT2 expression. BrMT3 expression was only marginally and non-significantly up- and down-regulated by the stress conditions tested. Promoter regions of BrMT1 and BrMT2 display different cis-acting elements supporting the different responses of both genes against various stresses. The results demonstrate the differential regulation of BrMT1-3 by various plant exogenous factors, and indicate the utility of the BrMT1 promoter as a multiple stress inducible promoter.

  12. Post-training, but not post-reactivation, administration of amphetamine and anisomycin modulates Pavlovian conditioned approach.

    PubMed

    Blaiss, Cory A; Janak, Patricia H

    2007-05-01

    The psychostimulant, amphetamine (AMPH), and the protein synthesis inhibitor, anisomycin (ANI), have been shown to modulate the consolidation and reconsolidation of several types of learning. To determine whether Pavlovian conditioned approach (PCA) is modulated in a similar manner, we examined the effects of post-training and post-reactivation administration of both AMPH and ANI on memory for PCA. Male Long-Evans rats received PCA training sessions during which presentations of a CS+ were followed by sucrose delivery. AMPH (1 mg/kg, s.c.) injected immediately but not 6h after the first training session enhanced PCA behavior. ANI (150 mg/kg, s.c.) injected immediately but not 3h after the first training session impaired PCA behavior. This impairment was not due to the development of a conditioned taste aversion. To examine whether PCA can also be modulated by post-reactivation administration of AMPH and ANI, rats were given an injection of AMPH, ANI, or vehicle immediately after a memory reactivation session. Upon testing, the behavior of both the AMPH- and the ANI-treated rats was unaffected. This result remained consistent when the experiment was repeated with changes to various behavioral parameters (i.e., amount of training, length of memory reactivation). These findings indicate that AMPH and ANI act during the post-training but not the post-reactivation period to enhance and impair, respectively, the learning of PCA. This suggests that the consolidation of PCA can be modulated in a manner comparable to other types of learned associations, but once learned, the memory appears to be relatively robust and stable.

  13. Post-training, but not Post-reactivation, Administration of Amphetamine and Anisomycin Modulates Pavlovian Conditioned Approach

    PubMed Central

    Blaiss, Cory A.; Janak, Patricia H.

    2007-01-01

    The psychostimulant, amphetamine (AMPH), and the protein synthesis inhibitor, anisomycin (ANI), have been shown to modulate the consolidation and reconsolidation of several types of learning. To determine whether Pavlovian conditioned approach (PCA) is modulated in a similar manner, we examined the effects of post-training and post-reactivation administration of both AMPH and ANI on memory for PCA. Male Long-Evans rats received PCA training sessions during which presentations of a CS+ were followed by sucrose delivery. AMPH (1 mg/kg, s.c.) injected immediately but not 6 hrs after the first training session enhanced PCA behavior. ANI (150 mg/kg, s.c.) injected immediately but not 3 hrs after the first training session impaired PCA behavior. This impairment was not due to the development of a conditioned taste aversion. To examine whether PCA can also be modulated by post-reactivation administration of AMPH and ANI, rats were given an injection of AMPH, ANI, or vehicle immediately after a memory reactivation session. Upon testing, the behavior of both the AMPH- and the ANI-treated rats was unaffected. This result remained consistent when the experiment was repeated with changes to various behavioral parameters (i.e. amount of training, length of memory reactivation). These findings indicate that AMPH and ANI act during the post-training but not the post-reactivation period to enhance and impair, respectively, the learning of PCA. This suggests that the consolidation of PCA can be modulated in a manner comparable to other types of learned associations, but once learned, the memory appears to be relatively robust and stable. PMID:17258476

  14. Agenda-building influences on the news media's coverage of the U.S. Food and Drug Administration's push to regulate tobacco, 1993-2009.

    PubMed

    Foster, Caroline; Thrasher, Jim; Kim, Sei-Hill; Rose, India; Besley, John; Navarro, Ashley

    2012-01-01

    Citing agenda-building theory, this article examines the influence of three key factors on the news media's coverage of the process of placing tobacco and tobacco products under regulation of the U.S. Food and Drug Administration between 1993 and 2009. We analyzed data from a content analysis of 570 news articles from The New York Times and Washington Post and found that the media published significantly more FDA regulation articles during the Clinton administration than during the Bush administration. Our analysis links that imbalance of media coverage to the influence of the president of the United States (Clinton and Bush, during the duration of this study), journalistic routines and real world events. We compared the Clinton and Bush era news coverage on article prominence, article topics, and reasons to support/oppose FDA regulation and found significant differences, which we suggest led to the imbalance of news articles in the two administrations. PMID:23293806

  15. 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

    ... regulated article is moved through the quarantined area without stopping (except for refueling and for traffic conditions such as traffic lights and stop signs); and (C) The regulated article is not unpacked... authorized to stop the person or means of conveyance to determine whether a regulated article is present...

  16. [General functional state (tonus) of the brain and conditioned reflexes as the mechanisms of it's regulation].

    PubMed

    Khananashvili, M M

    2008-01-01

    The article is dedicated to P.S. Kupalov, due to his 120 Anniversary. P.S. Kupalov was the disciple of I.P. Pavlov and his nearest collaborator. Right after I.P. Pavlov, he was at the head of the Institute of Experimental Medicine in St-Petersburg, where he developed a number of new ideas, concerning conditioned reflexes. Thus, he discovered shortened conditioned reflexes--central mechanisms of regulation of general functional state of the brain, and he created, on the base of the studies of unlimited motor activity in animals using his own method of situational conditioned reflexes, the conception of situational conditioned reflexes. P.S. Kupalov found out a number of new explanations for development of experimental neuroses and determined their mechanisms, as well. He was the one among the first disciples of I.P. Pavlov, who indicated at the complex structural-functional organization of conditioned reflexes, and he played the great part for the creation of modern theory about the nature of behavior, based on conditioned reflexes. The most important theses of P.S. Kupalov's conception, which is of great cognitive significance at the moment, as well as some results of the studies by his disciples and followers, developing the ideas of P.S. Kupalov, are presented in the article. PMID:19178077

  17. 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. PMID:26037253

  18. 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.

  19. `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

    2016-10-01

    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.

  20. `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

    2016-10-01

    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. PMID:27180319

  1. Gonadal and pituitary responsiveness of stallions is not down-regulated by prolonged pulsatile administration of GnRH.

    PubMed

    Brinsko, S P; Squires, E L; Pickett, B W; Nett, T M

    1998-01-01

    The objective of this study was to determine if prolonged pulsatile administration of homologous gonadotropin-releasing hormone (GnRH) at therapeutic or 5x therapeutic doses would cause down-regulation of the stallion's hypothalamic-pituitary-testicular axis. Fifteen stallions were randomly assigned to three treatment groups (n=5/group) and received a 0.5 ml subcutaneous dose of saline (group 1), 50 microg GnRH (group 2), or 250 microg GnRH (group 3) every 2 hours for 75 days. Weekly evaluations of follicle stimulating hormone, luteinizing hormone, and testosterone and monthly evaluations of daily sperm output and spermatozoal motility failed to demonstrate any decreased pituitary or gonadal responsiveness within or among treatment groups (P > 0.1) as a result of treatment with GnRH. Results of this study demonstrate that the hypothalamic-pituitary-testicularaxis of the stallion, unlike that of other domestic species, is remarkably refractory to GnRH-induced down-regulation.

  2. 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

  3. Microcystin Production and Regulation under Nutrient Stress Conditions in Toxic Microcystis Strains

    PubMed Central

    Pimentel, Juliana S. M.

    2014-01-01

    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. PMID:25038094

  4. 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.

  5. Precise conditional immortalization of mouse cells using tetracycline-regulated SV40 large T-antigen.

    PubMed

    Anastassiadis, Konstantinos; Rostovskaya, Maria; Lubitz, Sandra; Weidlich, Stefanie; Stewart, A Francis

    2010-04-01

    Cellular immortalization provides a way for expansion and subsequent molecular characterization of rare cell types. Ideally, immortalization can be achieved by the reversible expression of immortalizing proteins. Here, we describe the use of conditional immortalization based on a modified tetracycline-regulated system for the expression of SV40 large T-antigen in embryonic stem (ES) cells and mice. The modified system relies on a codon improved reverse tetracycline transactivator (irtTA) fused to the ligand-binding domain (LBD) of the androgen receptor (irtTA-ABD) or of a mutated glucocorticoid receptor (irtTA-GBD*). Induction of T-antigen is conferred only after addition of two ligands, one to activate the LBD (mibolerone for irtTA-ABD or dexamethasone for irtTA-GBD*) and one to activate the tetracycline transactivator (doxycycline). In ES cells, changes in gene expression upon large T induction were limited and reversible upon deinduction. Similarly, expression of T-antigen was very tightly regulated in mice. We have isolated and expanded bone marrow mesenchymal stem cells that could be genetically manipulated and maintained their differentiation properties after several passages of expansion under conditions that induce the expression of large T-antigen. PMID:20146354

  6. [Under hypoxia condition contactin-1 regulates migration of MKN45 cells through RhoA pathway].

    PubMed

    Yang, G; Song, J G; Li, Y; Gong, S P

    2015-01-01

    Recent studies have suggested that contactin-1 has a key role in cancer cell proliferation and migration, however the detailed mechanism of this process is still unclear. Here, human gastric cancer cell line MKN45 was employed. It was found that under hypoxia conditions contactin-1 mRNA and protein levels were both up-regulated by HIF-1alpha expression. Furthermore, although hypoxia increased the migration rate of MKN45 cells, contactin-1 (CNTN1) shRNA reversed this process. Meanwhile, RhoA V14 and RhoA V14N19 mutation constructs were employed, and it was found that constitutively active form of RhoA reversed the cell migration suppression induced by contactin-1 knockdown, while dominant-negative form of RhoA blocked hypoxia induced hypermigration. Apart from this, contactin-1 displayed the ability to phosphorylate the RhoA activator p115 RhoGEF. Thus, under hypoxia conditions, elevated HIF-1alpha seems to up-regulate contactin-1 expression and by this activate RhoA and facilitate migration of cancer cells. PMID:25916117

  7. 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

  8. Flavonoid biosynthesis-related genes in grape skin are differentially regulated by temperature and light conditions.

    PubMed

    Azuma, Akifumi; Yakushiji, Hiroshi; Koshita, Yoshiko; Kobayashi, Shozo

    2012-10-01

    Temperature and light are important environmental factors that affect flavonoid biosynthesis in grape berry skin. However, the interrelationships between temperature and light effects on flavonoid biosynthesis have not been fully elucidated at the molecular level. Here, we investigated the effects of temperature and light conditions on the biosynthesis of flavonoids (anthocyanins and flavonols) and the expression levels of related genes in an in vitro environmental experiment using detached grape berries. Sufficient anthocyanin accumulation in the grape skin was observed under a low temperature (15 °C) plus light treatment, whereas high temperature (35 °C) or dark treatment severely suppressed anthocyanin accumulation. This indicates that the accumulation of anthocyanins is dependent on both low temperature and light. qRT-PCR analysis showed that the responses of three MYB-related genes (VlMYBA1-3, VlMYBA1-2, and VlMYBA2) to temperature and light differed greatly even though the products of all three genes had the ability to regulate anthocyanin biosynthesis pathway genes. Furthermore, the expression levels of other MYB-related genes and many flavonoid biosynthesis pathway genes were regulated independently by temperature and light. We also found that temperature and light conditions affected the anthocyanin composition in the skin through the regulation of flavonoid biosynthesis pathway genes. Our results suggest that low temperature and light have a synergistic effect on the expression of genes in the flavonoid biosynthesis pathway. These findings provide new information about the relationships between environmental factors and flavonoid accumulation in grape berry skin.

  9. [Simulation of administrative influence on a public health under conditions of changing the terminal values during the process of society transformation].

    PubMed

    Fed'ko, O A

    2010-01-01

    The article is devoted to the study of interrelation between terminal values and subjective health in the context of community development and modeling of possible directions of administrative influence on a public health taking into account such interrelation. The structural model of influence of terminal values on a subjective health is presented and the assessment of possible changes of health on the population level under condition of the introduction of the proper administrative interventions is given.

  10. Opioid receptors in the midbrain periaqueductal gray regulate extinction of pavlovian fear conditioning.

    PubMed

    McNally, Gavan P; Pigg, Michael; Weidemann, Gabrielle

    2004-08-01

    Four experiments studied the role of opioid receptors in the midbrain periaqueductal gray matter (PAG), an important structure eliciting conditioned fear responses, in the extinction of Pavlovian fear. Rats received pairings of an auditory conditioned stimulus (CS) with a foot shock unconditioned stimulus (US). The freezing conditioned response (CR) elicited by the CS was then extinguished via nonreinforced presentations of the CS. Microinjection of the opioid receptor antagonist naloxone into the ventrolateral PAG (vlPAG) before nonrein-forced CS presentations impaired development of extinction, but such microinjections at the end of extinction did not reinstate an already extinguished freezing CR. This role for opioid receptors in fear extinction was specific to the vlPAG because infusions of naloxone into the dorsal PAG did not impair fear extinction. Finally, the impairment of fear extinction produced by vlPAG infusions of naloxone was dose-dependent. These results show for the first time that the midbrain PAG contributes to fear extinction and specifically identify a role for vlPAG opioid receptors in the acquisition but not the expression of such extinction. Taken together with our previous findings, we suggest that, during fear conditioning, activation of vlPAG opioid receptors contributes to detection of the discrepancy between the actual and expected outcome of the conditioning trial. vlPAG opioid receptors regulate the learning that accrues to the CS and other stimuli present on a trial because they instantiate an associative error correction process influencing US information reaching the site of CS-US convergence in the amygdala. During nonreinforcement, this vlPAG opioid receptor contribution signals extinction.

  11. Regulation of feeding behavior and plasma testosterone in response to central neuropeptide Y administration in a songbird.

    PubMed

    Davies, Scott; Deviche, Pierre

    2015-08-01

    In mammalian and avian model species, neuropeptide Y (NPY) simultaneously promotes feeding behavior and suppresses the secretion of reproductive hormones, thereby modulating the resource allocation trade-off between investing in essential somatic processes or in the reproductive system. Investigations into this dual role of NPY in birds have focused on domesticated species and, to our knowledge, no study has examined this role in songbirds. We determined whether NPY treatment acutely regulates feeding behavior and activity of the reproductive system in a male songbird, the Abert's Towhee, Melozone aberti. Intracerebroventricular (ICV) administration of NPY promoted behaviors associated with feeding (decreased latency to initiate pecking in the food bowl, increased number of feeding bouts following treatment, and increased number of pecks into the food bowl during each feeding bout), and it stimulated hopping and drinking behavior. By contrast, we found no effect of NPY treatment on plasma testosterone secretion 60 min after treatment. These results suggest that in male Abert's Towhees NPY stimulates feeding behavior, but provide no evidence that this peptide concurrently influences testosterone secretion.

  12. 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.

  13. Development of a Multipurpose GATEWAY-Based Lentiviral Tetracycline-Regulated Conditional RNAi System (GLTR)

    PubMed Central

    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. PMID:24841113

  14. 7 CFR 301.53-4 - Conditions governing the interstate movement of regulated articles from quarantined areas.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... scientific purposes; or (2) The regulated article originates outside the quarantined area and is moved... stopping (except for refueling or for traffic conditions, such as traffic lights or stop signs), or...

  15. 7 CFR 301.85-3 - Conditions governing the interstate movement of regulated articles from quarantined States. 2

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... DOMESTIC QUARANTINE NOTICES Golden Nematode Quarantine and Regulations § 301.85-3 Conditions governing the... of the golden nematode and the person in possession thereof has been so notified; or (v) Through or... golden nematode exists; or (v) Through or reshipped from any regulated area if the articles...

  16. 7 CFR 301.50-4 - Conditions governing the interstate movement of regulated articles from quarantined areas.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... certificate or limited permit, if: (1)(i) The regulated article originates outside any quarantined area and is... conditions, such as traffic lights or stop signs) during October, November, or December, or when ambient air temperature is below 10 °C (50 °F); or (ii) The regulated article originates outside any quarantined area...

  17. Recombinase-based conditional and reversible gene regulation via XTR alleles

    PubMed Central

    Robles-Oteiza, Camila; Taylor, Sarah; Yates, Travis; Cicchini, Michelle; Lauderback, Brian; Cashman, Christopher R.; Burds, Aurora A.; Winslow, Monte M.; Jacks, Tyler; Feldser, David M.

    2015-01-01

    Synthetic biological tools that enable precise regulation of gene function within in vivo systems have enormous potential to discern gene function in diverse physiological settings. Here we report the development and characterization of a synthetic gene switch that, when targeted in the mouse germline, enables conditional inactivation, reports gene expression and allows inducible restoration of the targeted gene. Gene inactivation and reporter expression is achieved through Cre-mediated stable inversion of an integrated gene-trap reporter, whereas inducible gene restoration is afforded by Flp-dependent deletion of the inverted gene trap. We validate our approach by targeting the p53 and Rb genes and establishing cell line and in vivo cancer model systems, to study the impact of p53 or Rb inactivation and restoration. We term this allele system XTR, to denote each of the allelic states and the associated expression patterns of the targeted gene: eXpressed (XTR), Trapped (TR) and Restored (R). PMID:26537451

  18. Recombinase-based conditional and reversible gene regulation via XTR alleles.

    PubMed

    Robles-Oteiza, Camila; Taylor, Sarah; Yates, Travis; Cicchini, Michelle; Lauderback, Brian; Cashman, Christopher R; Burds, Aurora A; Winslow, Monte M; Jacks, Tyler; Feldser, David M

    2015-01-01

    Synthetic biological tools that enable precise regulation of gene function within in vivo systems have enormous potential to discern gene function in diverse physiological settings. Here we report the development and characterization of a synthetic gene switch that, when targeted in the mouse germline, enables conditional inactivation, reports gene expression and allows inducible restoration of the targeted gene. Gene inactivation and reporter expression is achieved through Cre-mediated stable inversion of an integrated gene-trap reporter, whereas inducible gene restoration is afforded by Flp-dependent deletion of the inverted gene trap. We validate our approach by targeting the p53 and Rb genes and establishing cell line and in vivo cancer model systems, to study the impact of p53 or Rb inactivation and restoration. We term this allele system XTR, to denote each of the allelic states and the associated expression patterns of the targeted gene: eXpressed (XTR), Trapped (TR) and Restored (R). PMID:26537451

  19. Down-regulation of EPHX2 gene transcription by Sp1 under high-glucose conditions.

    PubMed

    Oguro, Ami; Oida, Shoko; Imaoka, Susumu

    2015-09-15

    sEH (soluble epoxide hydrolase), which is encoded by the EPHX2 gene, regulates the actions of bioactive lipids, EETs (epoxyeicosatrienoic acids). Previously, we found that high-glucose-induced oxidative stress suppressed sEH levels in a hepatocarcinoma cell line (Hep3B) and sEH was decreased in streptozotocin-induced diabetic mice in vivo. In the present study, we investigated the regulatory mechanisms underlying EPHX2 transcriptional suppression under high-glucose conditions. The decrease in sEH was prevented by an Sp1 (specificity protein 1) inhibitor, mithramycin A, and overexpression or knockdown of Sp1 revealed that Sp1 suppressively regulated sEH expression, in contrast with the general role of Sp1 on transcriptional activation. In addition, we found that AP2α (activating protein 2α) promoted EPHX2 transcription. The nuclear transport of Sp1, but not that of AP2α, was increased under high glucose concomitantly with the decrease in sEH. Within the EPHX2 promoter -56/+32, five Sp1-binding sites were identified, and the mutation of each of these sites showed that the first one (SP1_1) was important in both suppression by Sp1 and activation by AP2α. Furthermore, overexpression of Sp1 diminished the binding of AP2α by DNA-affinity precipitation assay and ChIP, suggesting competition between Sp1 and AP2α on the EPHX2 promoter. These findings provide novel insights into the role of Sp1 in transcriptional suppression, which may be applicable to the transcriptional regulation of other genes.

  20. State Regulation of Medication Administration by Unlicensed Assistive Personnel in Residential Care and Adult Day Services Settings.

    PubMed

    Carder, Paula C; O'Keeffe, Janet

    2016-09-01

    Residential care settings and adult day services are two community-based care options used by older adults with chronic health conditions. Most states have regulatory provisions that allow unlicensed assistive personnel (UAP) to administer medications. The current national policy study examined state regulations to identify which states permit UAP to administer medications, as well as staffing and training requirements. Key findings include states lack clear and adequate provisions for nurse oversight of UAP who administer medications, although adult day service regulations provide a greater level of nurse oversight than residential care settings. Specifically, 32 states require residential care to hire a nurse, but only six include provisions regarding nurse availability (e.g., on-call, on-site, number of hours). In contrast, 10 of 20 states that require adult day service programs to hire a nurse provide availability provisions. Nurse oversight of UAP is an important means of assuring quality care and reducing errors; thus, state regulatory agencies might need to strengthen nurse oversight provisions. [Res Gerontol Nurs. 2016; 9(5):209-222.]. PMID:27054368

  1. Modelling hyporheic processes for regulated rivers under transient hydrological and hydrogeological conditions

    NASA Astrophysics Data System (ADS)

    Siergieiev, D.; Ehlert, L.; Reimann, T.; Lundberg, A.; Liedl, R.

    2014-08-01

    Understanding the effects of major hydrogeological controls on hyporheic exchange and bank storage is essential for river water management, groundwater abstraction, restoration and ecosystem sustainability. Analytical models cannot adequately represent complex settings with, for example, transient boundary conditions, varying geometry of surface water-groundwater interface, unsaturated and overland flow, etc. To understand the influence of parameters such as (1) sloping river banks, (2) varying hydraulic conductivity of the riverbed and (3) different river discharge wave scenarios on hyporheic exchange characteristics such as (a) bank storage, (b) return flows and (c) residence time, a 2-D hydrogeological conceptual model and, subsequently, an adequate numerical model were developed. The numerical model was calibrated against observations in the aquifer adjacent to the hydropower regulated Lule River, Northern Sweden, which has predominantly diurnal discharge fluctuations during summer and long-lasting discharge peaks during autumn and winter. Modelling results revealed that bank storage increased with river wave amplitude, wave duration and smaller slope of the river bank, while maximum exchange flux decreased with wave duration. When a homogeneous clogging layer covered the entire river-aquifer interface, hydraulic conductivity positively affected bank storage. The presence of a clogging layer with hydraulic conductivity < 0.001 m d-1 significantly reduced the exchange flows and virtually eliminated bank storage. The bank storage return/fill time ratio was positively related to wave amplitude and the hydraulic conductivity of the interface and negatively to wave duration and bank slope. Discharge oscillations with short duration and small amplitude decreased bank storage and, therefore, the hyporheic exchange, which has implications for solute fluxes, redox conditions and the spawning potential of riverbeds. Based on these results, river regulation strategies can

  2. Modelling hyporheic processes for regulated rivers under transient hydrological and hydrogeological conditions

    NASA Astrophysics Data System (ADS)

    Siergieiev, D.; Ehlert, L.; Reimann, T.; Lundberg, A.; Liedl, R.

    2015-01-01

    Understanding the effects of major hydrogeological controls on hyporheic exchange and bank storage is essential for river water management, groundwater abstraction, restoration and ecosystem sustainability. Analytical models cannot adequately represent complex settings with, for example, transient boundary conditions, varying geometry of surface water-groundwater interface, unsaturated and overland flow, etc. To understand the influence of parameters such as (1) sloping river banks, (2) varying hydraulic conductivity of the riverbed and (3) different river discharge wave scenarios on hyporheic exchange characteristics such as (a) bank storage, (b) return flows and (c) residence time, a 2-D hydrogeological conceptual model and, subsequently, an adequate numerical model were developed. The numerical model was calibrated against observations in the aquifer adjacent to the hydropower-regulated Lule River, northern Sweden, which has predominantly diurnal discharge fluctuations during summer and long-lasting discharge peaks during autumn and winter. Modelling results revealed that bank storage increased with river wave amplitude, wave duration and smaller slope of the river bank, while maximum exchange flux decreased with wave duration. When a homogeneous clogging layer covered the entire river-aquifer interface, hydraulic conductivity positively affected bank storage. The presence of a clogging layer with hydraulic conductivity < 0.001 m d-1 significantly reduced the exchange flows and virtually eliminated bank storage. The bank storage return/fill time ratio was positively related to wave amplitude and the hydraulic conductivity of the interface and negatively to wave duration and bank slope. Discharge oscillations with short duration and small amplitude decreased bank storage and, therefore, the hyporheic exchange, which has implications for solute fluxes, redox conditions and the potential of riverbeds as fish-spawning locations. Based on these results, river

  3. 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...

  4. 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...

  5. 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...

  6. 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...

  7. 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...

  8. 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

  9. Visual Input Regulates Circuit Configuration in Courtship Conditioning of Drosophila melanogaster

    PubMed Central

    Joiner, Mei-ling A.; Griffith, Leslie C.

    2000-01-01

    Courtship and courtship conditioning are behaviors that are regulated by multiple sensory inputs, including chemosensation and vision. Globally inhibiting CaMKII activity in Drosophila disrupts courtship plasticity while leaving visual and chemosensory perception intact. Light has been shown to modulate CaMKII-dependent memory formation in this paradigm and the circuitry for the nonvisual version of this behavior has been investigated. In this paradigm, volatile and tactile pheromones provide the primary driving force for courtship, and memory formation is dependent upon intact mushroom bodies and parts of the central complex. In the present study, we use the GAL4/UAS binary expression system to define areas of the brain that require CaMKII for modulation of courtship conditioning in the presence of visual, as well as chemosensory, information. Visual input suppressed the ability of mushroom body- and central complex-specific CaMKII inhibition to disrupt memory formation, indicating that the cellular circuitry underlying this behavior can be remodeled by changing the driving sensory modality. These findings suggest that the potential for plasticity in courtship behavior is distributed among multiple biochemically and anatomically distinct cellular circuits. PMID:10706600

  10. Interferon induction in marrow-derived macrophages: regulation by L cell conditioned medium.

    PubMed

    Fleit, H B; Rabinovitch, M

    1981-09-01

    Mouse bone marrow cells grown in medium enriched with L cell conditioned medium (LCM) as a source of colony stimulating factor (CSF) yield populations of adherent macrophages which are quite sensitive to induction of interferon (IFN) by viral and nonviral inducers. We examined the role of LCM in the sensitivity of marrow macrophage cultures to IFN induction. Removal of LCM from the cultures for as little as 3 hours markedly reduced the IFN titers induced by a double stranded ribopolynucleotide (poly I:C) or a lipopolysaccharide (LPS), while induction by Newcastle disease virus (NDV) was unaffected. Addition of anti-CSF serum to LCM medium also reduced IFN titers in response to polyI:C but had no effect on NDV induction. The inhibitory effect of anit-CSF indicates that the LCM requirement is at least partially related to the colony stimulating activity of the medium. We postulate that CSF regulates the initial interaction of macrophages with polyI:C or LPS rather than the synthesis and secretion of interferon by the phagocytes. Nearly complete restoration of IFN induction with polyI:C was obtained when LCM deprived cultures were reincubated with LCM medium previously conditioned by marrow cultures.

  11. 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,...

  12. 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,...

  13. 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,...

  14. 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,...

  15. 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,...

  16. 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.

  17. 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

  18. 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

  19. TRPM6 kinase activity regulates TRPM7 trafficking and inhibits cellular growth under hypomagnesic conditions.

    PubMed

    Brandao, Katherine; Deason-Towne, Francina; Zhao, Xiaoyun; Perraud, Anne-Laure; Schmitz, Carsten

    2014-12-01

    The channel kinases TRPM6 and TRPM7 are both members of the melastatin-related transient receptor potential (TRPM) subfamily of ion channels and the only known fusions of an ion channel pore with a kinase domain. TRPM6 and TRPM7 form functional, tetrameric channel complexes at the plasma membrane by heteromerization. TRPM6 was previously shown to cross-phosphorylate TRPM7 on threonine residues, but not vice versa. Genetic studies demonstrated that TRPM6 and TRPM7 fulfill non-redundant functions and that each channel contributes uniquely to the regulation of Mg(2+) homeostasis. Although there are indications that TRPM6 and TRPM7 can influence each other's cellular distribution and activity, little is known about the functional relationship between these two channel-kinases. In the present study, we examined how TRPM6 kinase activity influences TRPM7 serine phosphorylation, intracellular trafficking, and cell surface expression of TRPM7, as well as Mg(2+)-dependent cellular growth. We found TRPM7 serine phosphorylation via the TRPM6 kinase, but no TRPM6 serine phosphorylation via the TRPM7 kinase. Intracellular trafficking of TRPM7 was altered in HEK-293 epithelial kidney cells and DT40 B cells in the presence of TRPM6 with intact kinase activity, independently of the availability of extracellular Mg(2+), but TRPM6/7 surface labeling experiments indicate comparable levels of the TRPM6/7 channels at the plasma membrane. Furthermore, using a complementation approach in TRPM7-deficient DT40 B-cells, we demonstrated that wild-type TRPM6 inhibited cell growth under hypomagnesic cell culture conditions in cells co-expressing TRPM6 and TRPM7; however, co-expression of a TRPM6 kinase dead mutant had no effect-a similar phenotype was also observed in TRPM6/7 co-expressing HEK-293 cells. Our results provide first clues about how heteromer formation between TRPM6 and TRPM7 influences the biological activity of these ion channels. We show that TRPM6 regulates TRPM7 intracellular

  20. [Influence of chronic melipramine administration abolition on locomotion and defensive conditioned reflexes in passive and active avoidance in rats].

    PubMed

    Orlova, N V; Folomkina, A A; Koshtoiants, O Kh; Bazian, A S

    2005-01-01

    The chronic (21 days duration) administration of tricyclic antidepressant melipramine of Wistar rats strain (15 mg/kg daily, intraperitoneally) evoked weight loss of animals. The 7 days after melipramine abolition its sedative effect was observed in the "open field" test by decrease of locomotion and the number of boles. The 7 and 14 days after melipramine abolition the difference between control and melipramine treated animals in passive and active avoidance learning and memory not found. The experimental results comparison with the literature data show, that chronic melipramine administration of intact animals evokes a sedative state. This conclusion does not contradict to idea of punishment function of brain serotoninergic system. PMID:15828425

  1. 49 CFR 171.22 - Authorization and conditions for the use of international standards and regulations.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... Aviation Organization's Technical Instructions for the Safe Transport of Dangerous Goods by Air (ICAO Technical Instructions), the International Maritime Dangerous Goods Code (IMDG Code), Transport Canada's Transportation of Dangerous Goods Regulations (Transport Canada TDG Regulations), and the International...

  2. 49 CFR 171.22 - Authorization and conditions for the use of international standards and regulations.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... Aviation Organization's Technical Instructions for the Safe Transport of Dangerous Goods by Air (ICAO Technical Instructions), the International Maritime Dangerous Goods Code (IMDG Code), Transport Canada's Transportation of Dangerous Goods Regulations (Transport Canada TDG Regulations), and the International...

  3. 49 CFR 171.22 - Authorization and conditions for the use of international standards and regulations.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... Aviation Organization's Technical Instructions for the Safe Transport of Dangerous Goods by Air (ICAO Technical Instructions), the International Maritime Dangerous Goods Code (IMDG Code), Transport Canada's Transportation of Dangerous Goods Regulations (Transport Canada TDG Regulations), and the International...

  4. 49 CFR 171.22 - Authorization and conditions for the use of international standards and regulations.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... Aviation Organization's Technical Instructions for the Safe Transport of Dangerous Goods by Air (ICAO Technical Instructions), the International Maritime Dangerous Goods Code (IMDG Code), Transport Canada's Transportation of Dangerous Goods Regulations (Transport Canada TDG Regulations), and the International...

  5. A Role for p38 Mitogen-activated Protein Kinase-mediated Threonine 30-dependent Norepinephrine Transporter Regulation in Cocaine Sensitization and Conditioned Place Preference*

    PubMed Central

    Mannangatti, Padmanabhan; NarasimhaNaidu, Kamalakkannan; Damaj, Mohamad Imad; Ramamoorthy, Sammanda; Jayanthi, Lankupalle Damodara

    2015-01-01

    The noradrenergic and p38 mitogen-activated protein kinase (p38 MAPK) systems are implicated in cocaine-elicited behaviors. Previously, we demonstrated a role for p38 MAPK-mediated norepinephrine transporter (NET) Thr30 phosphorylation in cocaine-induced NET up-regulation (Mannangatti, P., Arapulisamy, O., Shippenberg, T. S., Ramamoorthy, S., and Jayanthi, L. D. (2011) J. Biol. Chem. 286, 20239–20250). The present study explored the functional interaction between p38 MAPK-mediated NET regulation and cocaine-induced behaviors. In vitro cocaine treatment of mouse prefrontal cortex synaptosomes resulted in enhanced NET function, surface expression, and phosphorylation. Pretreatment with PD169316, a p38 MAPK inhibitor, completely blocked cocaine-mediated NET up-regulation and phosphorylation. In mice, in vivo administration of p38 MAPK inhibitor SB203580 completely blocked cocaine-induced NET up-regulation and p38 MAPK activation in the prefrontal cortex and nucleus accumbens. When tested for cocaine-induced locomotor sensitization and conditioned place preference (CPP), mice receiving SB203580 on cocaine challenge day or on postconditioning test day exhibited significantly reduced cocaine sensitization and CPP. A transactivator of transcription (TAT) peptide strategy was utilized to test the involvement of the NET-Thr30 motif. In vitro treatment of synaptosomes with TAT-NET-Thr30 (wild-type peptide) completely blocked cocaine-mediated NET up-regulation and phosphorylation. In vivo administration of TAT-NET-Thr30 peptide but not TAT-NET-T30A (mutant peptide) completely blocked cocaine-mediated NET up-regulation and phosphorylation. In the cocaine CPP paradigm, mice receiving TAT-NET-Thr30 but not TAT-NET-T30A on postconditioning test day exhibited significantly reduced cocaine CPP. Following extinction, TAT-NET-Thr30 when given prior to cocaine challenge significantly reduced reinstatement of cocaine CPP. These results demonstrate that the direct inhibition of p38

  6. Regulation of Transaminase C Synthesis in Escherichia coli: Conditional Leucine Auxotrophy

    PubMed Central

    McGilvray, Derek; Umbarger, H. E.

    1974-01-01

    The regulation of synthesis of the valine-alanine-α-aminobutyrate transaminase (transaminase C) was studied in Escherichia coli mutants lacking the branched-chain amino acid transaminase (transaminase B). An investigation was made of two strains, CU2 and CU2002, each carrying the same transaminase B lesion but exhibiting different growth responses on a medium supplemented with branched-chain amino acids. Both had the absolute isoleucine requirement characteristic of ilvE auxotrophs, but growth of strain CU2 was stimulated by valine, whereas that of strain CU2002 was markedly inhibited by valine. Strain CU2002 behaved like a conditional leucine auxotroph in that the inhibition by valine was reversed by leucine. Results of enzymatic studies showed that synthesis of transaminase C was repressed by valine in strain CU2002 but not in strain CU2. Inhibition by valine in strain CU2002 appears to be the combined effect of repression on transaminase C synthesis and valine-dependent feedback inhibition of α-acetohydroxy acid synthase activity, causing α-ketoisovalerate (and hence leucine) limitation. The ilvE markers of strains CU2 and CU2002 were each transferred by transduction to a wild-type genetical background. All ilvE recombinants from both crosses resembled strain CU2002 and were inhibited by valine in the presence of isoleucine. Thus, strain CU2 carries an additional lesion that allows it to grow on a medium containing isoleucine plus valine. It is concluded that conditional leucine auxotrophy is characteristic of mutants carrying an ilvE lesion alone. PMID:4616947

  7. Myosin II regulates actin rearrangement-related structural synaptic plasticity during conditioned taste aversion memory extinction.

    PubMed

    Bi, Ai-Ling; Wang, Yue; Zhang, Shuang; Li, Bo-Qin; Sun, Zong-Peng; Bi, Hong-Sheng; Chen, Zhe-Yu

    2015-03-01

    Similar to memory formation, memory extinction is also a new learning process that requires synaptic plasticity. Actin rearrangement is fundamental for synaptic plasticity, however, whether actin rearrangement in the infralimbic cortex (IL) plays a role in memory extinction, as well as the mechanisms underlying it, remains unclear. Here, using a conditioned taste aversion (CTA) paradigm, we demonstrated increased synaptic density and actin rearrangement in the IL during the extinction of CTA. Targeted infusion of an actin rearrangement inhibitor, cytochalasin D, into the IL impaired memory extinction and de novo synapse formation. Notably, we also found increased myosin II phosphorylation in the IL during the extinction of CTA. Microinfusion of a specific inhibitor of the myosin II ATPase, blebbistatin (Blebb), into the IL impaired memory extinction as well as the related actin rearrangement and changes in synaptic density. Moreover, the extinction deficit and the reduction of synaptic density induced by Blebb could be rescued by the actin polymerization stabilizer jasplakinolide (Jasp), suggesting that myosin II acts via actin filament polymerization to stabilize synaptic plasticity during the extinction of CTA. Taken together, we conclude that myosin II may regulate the plasticity of actin-related synaptic structure during memory extinction. Our studies provide a molecular mechanism for understanding the plasticity of actin rearrangement-associated synaptic structure during memory extinction.

  8. Non-coding RNAs in marine Synechococcus and their regulation under environmentally relevant stress conditions

    PubMed Central

    Gierga, Gregor; Voss, Björn; Hess, Wolfgang R

    2012-01-01

    Regulatory small RNAs (sRNAs) have crucial roles in the adaptive responses of bacteria to changes in the environment. Thus far, potential regulatory RNAs have been studied mainly in marine picocyanobacteria in genetically intractable Prochlorococcus, rendering their molecular analysis difficult. Synechococcus sp. WH7803 is a model cyanobacterium, representative of the picocyanobacteria from the mesotrophic areas of the ocean. Similar to the closely related Prochlorococcus it possesses a relatively streamlined genome and a small number of genes, but is genetically tractable. Here, a comparative genome analysis was performed for this and four additional marine Synechococcus to identify the suite of possible sRNAs and other RNA elements. Based on the prediction and on complementary microarray profiling, we have identified several known as well as 32 novel sRNAs. Some sRNAs overlap adjacent coding regions, for instance for the central photosynthetic gene psbA. Several of these novel sRNAs responded specifically to environmentally relevant stress conditions. Among them are six sRNAs changing their accumulation level under cold stress, six responding to high light and two to iron limitation. Target predictions suggested genes encoding components of the light-harvesting apparatus as targets of sRNAs originating from genomic islands and that one of the iron-regulated sRNAs might be a functional homolog of RyhB. These data suggest that marine Synechococcus mount adaptive responses to these different stresses involving regulatory sRNAs. PMID:22258101

  9. 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.

  10. 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.

  11. 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.

  12. 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

  13. 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…

  14. The NMDA antagonist MK-801 disrupts reconsolidation of a cocaine-associated memory for conditioned place preference but not for self-administration in rats

    PubMed Central

    Brown, Travis E.; Lee, Brian R.; Sorg, Barbara A.

    2008-01-01

    Recent research suggests that drug-related memories are reactivated after exposure to environmental cues and may undergo reconsolidation, a process that can strengthen memories. Conversely, reconsolidation may be disrupted by certain pharmacological agents such that the drug-associated memory is weakened. Several studies have demonstrated disruption of memory reconsolidation using a drug-induced conditioned place preference (CPP) task, but no studies have explored whether cocaine-associated memories can be similarly disrupted in cocaine self-administering animals after a cocaine priming injection, which powerfully reinstates drug-seeking behavior. Here we used cocaine-induced CPP and cocaine self-administration to investigate whether the N-methyl-D-aspartate receptor antagonist (+)-5methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine maleate (MK-801) given just prior to reactivation sessions would suppress subsequent cocaine-primed reinstatement (disruption of reconsolidation). Systemic injection of MK-801 (0.05 or 0.20 mg/kg administered intraperitoneally) in rats just prior to reactivation of the cocaine-associated memory in the CPP context attenuated subsequent cocaine-primed reinstatement, while no disruption occurred in rats that did not receive reactivation in the CPP context. However, in rats trained to self-administer cocaine, systemic administration of MK-801 just prior to either of two different types of reactivation sessions had no effect on subsequent cocaine-primed reinstatement of lever-pressing behavior. Thus, systemic administration of MK-801 disrupted the reconsolidation of a cocaine-associated memory for CPP but not for self-administration. These findings suggest that cocaine-CPP and self-administration do not use similar neurochemical processes to disrupt reconsolidation or that cocaine-associated memories in self-administering rats do not undergo reconsolidation, as assessed by lever-pressing behavior under cocaine reinstatement

  15. 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 SERVICES (CONTINUED) MEDICARE PROGRAM...

  16. 7 CFR 301.92-4 - Conditions governing the interstate movement of regulated, restricted, and associated articles...

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ...) ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE DOMESTIC QUARANTINE NOTICES... all other applicable Federal domestic plant quarantines and regulations must also be met. (1) With a... for refueling, rest stops, emergency repairs, and for traffic conditions, such as traffic lights...

  17. 7 CFR 301.92-4 - Conditions governing the interstate movement of regulated, restricted, and associated articles...

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ...) ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE DOMESTIC QUARANTINE NOTICES... all other applicable Federal domestic plant quarantines and regulations must also be met. (1) With a... for refueling, rest stops, emergency repairs, and for traffic conditions, such as traffic lights...

  18. 7 CFR 301.92-4 - Conditions governing the interstate movement of regulated, restricted, and associated articles...

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ...) ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE DOMESTIC QUARANTINE NOTICES... all other applicable Federal domestic plant quarantines and regulations must also be met. (1) With a... for refueling, rest stops, emergency repairs, and for traffic conditions, such as traffic lights...

  19. 7 CFR 301.92-4 - Conditions governing the interstate movement of regulated, restricted, and associated articles...

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ...) ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE DOMESTIC QUARANTINE NOTICES... all other applicable Federal domestic plant quarantines and regulations must also be met. (1) With a... for refueling, rest stops, emergency repairs, and for traffic conditions, such as traffic lights...

  20. 7 CFR 301.92-4 - Conditions governing the interstate movement of regulated, restricted, and associated articles...

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ...) ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE DOMESTIC QUARANTINE NOTICES... all other applicable Federal domestic plant quarantines and regulations must also be met. (1) With a... for refueling, rest stops, emergency repairs, and for traffic conditions, such as traffic lights...

  1. 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...

  2. 7 CFR 301.48-4 - Conditions governing the interstate movement of regulated articles from quarantined States.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 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...

  3. 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."

  4. 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.

  5. 36 CFR 251.14 - Conditions, rules and regulations to govern exercise of timber rights reserved in conveyance to...

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 36 Parks, Forests, and Public Property 2 2012-07-01 2012-07-01 false Conditions, rules and regulations to govern exercise of timber rights reserved in conveyance to the United States. 251.14 Section 251.14 Parks, Forests, and Public Property FOREST SERVICE, DEPARTMENT OF AGRICULTURE LAND...

  6. 36 CFR 251.15 - Conditions, rules and regulations to govern exercise of mineral rights reserved in conveyances to...

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 251.15 Parks, Forests, and Public Property FOREST SERVICE, DEPARTMENT OF AGRICULTURE LAND USES Miscellaneous Land Uses Natural Resources Control § 251.15 Conditions, rules and regulations to govern exercise... shall be cause for revocation of all rights to use, occupy, or disturb the surface of the lands...

  7. 36 CFR 251.14 - Conditions, rules and regulations to govern exercise of timber rights reserved in conveyance to...

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 251.14 Parks, Forests, and Public Property FOREST SERVICE, DEPARTMENT OF AGRICULTURE LAND USES Miscellaneous Land Uses Natural Resources Control § 251.14 Conditions, rules and regulations to govern exercise... paragraphs (b) and (c) of this section, in conveyance of lands to the United States under authorized...

  8. 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

    ... 251.15 Parks, Forests, and Public Property FOREST SERVICE, DEPARTMENT OF AGRICULTURE LAND USES Miscellaneous Land Uses Natural Resources Control § 251.15 Conditions, rules and regulations to govern exercise... permit shall be cause for termination of all rights to use, occupy, or disturb the surface of the...

  9. 36 CFR 251.15 - Conditions, rules and regulations to govern exercise of mineral rights reserved in conveyances to...

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 251.15 Parks, Forests, and Public Property FOREST SERVICE, DEPARTMENT OF AGRICULTURE LAND USES Miscellaneous Land Uses Natural Resources Control § 251.15 Conditions, rules and regulations to govern exercise... shall be cause for revocation of all rights to use, occupy, or disturb the surface of the lands...

  10. 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

    ... 251.15 Parks, Forests, and Public Property FOREST SERVICE, DEPARTMENT OF AGRICULTURE LAND USES Miscellaneous Land Uses Natural Resources Control § 251.15 Conditions, rules and regulations to govern exercise... permit shall be cause for termination of all rights to use, occupy, or disturb the surface of the...

  11. 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

    ... 251.14 Parks, Forests, and Public Property FOREST SERVICE, DEPARTMENT OF AGRICULTURE LAND USES Miscellaneous Land Uses Natural Resources Control § 251.14 Conditions, rules and regulations to govern exercise... paragraphs (b) and (c) of this section, in conveyance of lands to the United States under authorized...

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

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 251.14 Parks, Forests, and Public Property FOREST SERVICE, DEPARTMENT OF AGRICULTURE LAND USES Miscellaneous Land Uses Natural Resources Control § 251.14 Conditions, rules and regulations to govern exercise... paragraphs (b) and (c) of this section, in conveyance of lands to the United States under authorized...

  13. 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

    ... 251.15 Parks, Forests, and Public Property FOREST SERVICE, DEPARTMENT OF AGRICULTURE LAND USES Miscellaneous Land Uses Natural Resources Control § 251.15 Conditions, rules and regulations to govern exercise... permit shall be cause for termination of all rights to use, occupy, or disturb the surface of the...

  14. 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...

  15. 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...

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

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 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. 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." PMID:27085591

  18. 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...

  19. 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...

  20. 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...

  1. 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...

  2. 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...

  3. Autophagy regulates the apoptosis of bone marrow-derived mesenchymal stem cells under hypoxic condition via AMP-activated protein kinase/mammalian target of rapamycin pathway.

    PubMed

    Zhang, Zheng; Yang, Ming; Wang, Yabin; Wang, Le; Jin, Zhitao; Ding, Liping; Zhang, Lijuan; Zhang, Lina; Jiang, Wei; Gao, Guojie; Yang, Junke; Lu, Bingwei; Cao, Feng; Hu, Taohong

    2016-06-01

    Bone marrow-derived mesenchymal stem cells (BM-MSCs) have been demonstrated as an ideal autologous stem cells source for cell-based therapy for myocardial infarction (MI). However, poor viability of donor stem cells after transplantation limits their therapeutic efficiency, whereas the underlying mechanism is still poorly understood. Autophagy, a highly conserved process of cellular degradation, is required for maintaining homeostasis and normal function. Here, we investigated the potential role of autophagy on apoptosis in BM-MSCs induced by hypoxic injury. BM-MSCs, isolated from male C57BL/6 mice, were subjected to hypoxia and serum deprivation (H/SD) injury for 6, 12, and 24 h, respectively. The autophagy state was regulated by 3-methyladenine (3MA) and rapamycin administration. Furthermore, compound C was administrated to inhibit AMPK. The apoptosis induced by H/SD was determined by TUNEL assays. Meanwhile, autophagy was measured by GFP-LC3 plasmids transfection and transmission electron microscope. Moreover, protein expressions were evaluated by Western blot assay. In the present study, we found that hypoxic stress increased autophagy and apoptosis in BM-MSCs time dependently. Meanwhile, hypoxia increased the activity of AMPK/mTOR signal pathway. Moreover, increased apoptosis in BM-MSCs under hypoxia was abolished by 3-MA, whereas was aggravated by rapamycin. Furthermore, the increased autophagy and apoptosis in BM-MSCs induced by hypoxia were abolished by AMPK inhibitor compound C. These data provide evidence that hypoxia induced AMPK/mTOR signal pathway activation which regulated the apoptosis and autophagy in BM-MSCs. Furthermore, the apoptosis of BM-MSCs under hypoxic condition was regulated by autophagy via AMPK/mTOR pathway. PMID:27005844

  4. Staphylococcus epidermidis SrrAB Regulates Bacterial Growth and Biofilm Formation Differently under Oxic and Microaerobic Conditions

    PubMed Central

    Wu, Youcong; Wu, Yang; Zhu, Tao; Han, Haiyan; Liu, Huayong; Xu, Tao; Francois, Patrice; Fischer, Adrien; Bai, Li; Götz, Friedrich

    2014-01-01

    SrrAB expression in Staphylococcus epidermidis strain 1457 (SE1457) was upregulated during a shift from oxic to microaerobic conditions. An srrA deletion (ΔsrrA) mutant was constructed for studying the regulatory function of SrrAB. The deletion resulted in retarded growth and abolished biofilm formation both in vitro and in vivo and under both oxic and microaerobic conditions. Associated with the reduced biofilm formation, the ΔsrrA mutant produced much less polysaccharide intercellular adhesion (PIA) and showed decreased initial adherence capacity. Microarray analysis showed that the srrA mutation affected transcription of 230 genes under microaerobic conditions, and 51 genes under oxic conditions. Quantitative real-time PCR confirmed this observation and showed downregulation of genes involved in maintaining the electron transport chain by supporting cytochrome and quinol-oxidase assembly (e.g., qoxB and ctaA) and in anaerobic metabolism (e.g., pflBA and nrdD). In the ΔsrrA mutant, the expression of the biofilm formation-related gene icaR was upregulated under oxic conditions and downregulated under microaerobic conditions, whereas icaA was downregulated under both conditions. An electrophoretic mobility shift assay further revealed that phosphorylated SrrA bound to the promoter regions of icaR, icaA, qoxB, and pflBA, as well as its own promoter region. These findings demonstrate that in S. epidermidis SrrAB is an autoregulator and regulates biofilm formation in an ica-dependent manner. Under oxic conditions, SrrAB modulates electron transport chain activity by positively regulating qoxBACD transcription. Under microaerobic conditions, it regulates fermentation processes and DNA synthesis by modulating the expression of both the pfl operon and nrdDG. PMID:25404696

  5. Staphylococcus epidermidis SrrAB regulates bacterial growth and biofilm formation differently under oxic and microaerobic conditions.

    PubMed

    Wu, Youcong; Wu, Yang; Zhu, Tao; Han, Haiyan; Liu, Huayong; Xu, Tao; Francois, Patrice; Fischer, Adrien; Bai, Li; Götz, Friedrich; Qu, Di

    2015-02-01

    SrrAB expression in Staphylococcus epidermidis strain 1457 (SE1457) was upregulated during a shift from oxic to microaerobic conditions. An srrA deletion (ΔsrrA) mutant was constructed for studying the regulatory function of SrrAB. The deletion resulted in retarded growth and abolished biofilm formation both in vitro and in vivo and under both oxic and microaerobic conditions. Associated with the reduced biofilm formation, the ΔsrrA mutant produced much less polysaccharide intercellular adhesion (PIA) and showed decreased initial adherence capacity. Microarray analysis showed that the srrA mutation affected transcription of 230 genes under microaerobic conditions, and 51 genes under oxic conditions. Quantitative real-time PCR confirmed this observation and showed downregulation of genes involved in maintaining the electron transport chain by supporting cytochrome and quinol-oxidase assembly (e.g., qoxB and ctaA) and in anaerobic metabolism (e.g., pflBA and nrdD). In the ΔsrrA mutant, the expression of the biofilm formation-related gene icaR was upregulated under oxic conditions and downregulated under microaerobic conditions, whereas icaA was downregulated under both conditions. An electrophoretic mobility shift assay further revealed that phosphorylated SrrA bound to the promoter regions of icaR, icaA, qoxB, and pflBA, as well as its own promoter region. These findings demonstrate that in S. epidermidis SrrAB is an autoregulator and regulates biofilm formation in an ica-dependent manner. Under oxic conditions, SrrAB modulates electron transport chain activity by positively regulating qoxBACD transcription. Under microaerobic conditions, it regulates fermentation processes and DNA synthesis by modulating the expression of both the pfl operon and nrdDG.

  6. 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

  7. 41 CFR 102-35.5 - What is the scope of the General Services Administration's regulations on the disposal of...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... of the Federal Property Management Regulations (FPMR)(41 CFR parts 101-42 and 101-45). With two..., the Northern Mariana Islands, the Federated States of Micronesia, the Marshall Islands, and Palau....

  8. The relation between dopamine oxidation currents in the nucleus accumbens and conditioned increases in motor activity in rats following repeated administration of d-amphetamine or cocaine.

    PubMed

    Di Ciano, P; Blaha, C D; Phillips, A G

    1998-03-01

    Chronoamperometric recording techniques were used to monitor extracellular dopamine efflux in the nucleus accumbens associated with unconditioned and conditioned increases in motor activity in rats, following the intravenous administration of either d-amphetamine (0.63 mg/kg) or cocaine (3 mg/kg), or the presentation of a conditioned stimulus paired repeatedly with one of these psychostimulants. Each drug was administered daily for 7 days, either in the home cage or an environment in which a compound stimulus (light offset, odour) was presented. Rats in control groups received saline instead of drug in the distinctive test environment. On day 7 of training, significant increases in unconditioned motor activity were observed in the 30 min session following infusions of either d-amphetamine or cocaine. Associated dopamine oxidation currents in the nucleus accumbens increased immediately following administration of either drug and remained significantly elevated above baseline during the entire 30 min recording period. On the test day, presentation of the conditioned stimulus with vehicle infusions, in the distinct environment, was accompanied by an increase in dopamine oxidation currents and a conditioned increase in motor activity, only in the groups in which these stimuli had been paired with d-amphetamine or cocaine. Neither the magnitude or duration of the conditioned motor activity matched the corresponding change in extracellular dopamine efflux in the nucleus accumbens. Accordingly, it is argued that the increase in dopamine concentration serves as a neurochemical correlate of the unconditioned and conditioned stimuli. The change in motor activity constitutes the unconditioned and conditioned responses that are subserved by the neural systems activated by the initial rise in extracellular dopamine. PMID:9753179

  9. 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

    ... condition standards as required by 24 CFR part 5, subpart G, the Regulatory Agreement and/or the Housing... the Internet or by hard copy via certified mail. (d) Technical review of physical inspection results... other appropriate means. (g) Owner's responsibility to notify residents of inspection; and...

  10. 48 CFR 1852.217-70 - Property administration and reporting.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 48 Federal Acquisition Regulations System 6 2010-10-01 2010-10-01 true Property administration and reporting. 1852.217-70 Section 1852.217-70 Federal Acquisition Regulations System NATIONAL AERONAUTICS AND.... All excess items, however, costing $500 or more and in condition Code 7 or better (GSA Condition...

  11. Regulation of Expression of abcA and Its Response to Environmental Conditions

    PubMed Central

    Villet, Regis A.; Truong-Bolduc, Que Chi; Wang, Yin; Estabrooks, Zoe; Medeiros, Heidi

    2014-01-01

    The ATP-dependent transporter gene abcA in Staphylococcus aureus confers resistance to hydrophobic β-lactams. In strain ISP794, abcA is regulated by the transcriptional regulators MgrA and NorG and shares a 420-nucleotide intercistronic region with the divergently transcribed pbp4 gene, which encodes the transpeptidase Pbp4. Exposure of exponentially growing cells to iron-limited media, oxidative stress, and acidic pH (5.5) for 0.5 to 2 h had no effect on abcA expression. In contrast, nutrient limitation produced a significant increase in abcA transcripts. We identified three additional regulators (SarA, SarZ, and Rot) that bind to the overlapping promoter region of abcA and pbp4 in strain MW2 and investigated their role in the regulation of abcA expression. Expression of abcA is decreased by 10.0-fold in vivo in a subcutaneous abscess model. In vitro, abcA expression depends on rot and sarZ regulators. Moenomycin A exposure of strain MW2 produced an increase in abcA transcripts. Relative to MW2, the MIC of moenomycin was decreased 8-fold for MW2ΔabcA and increased 10-fold for the MW2 abcA overexpresser, suggesting that moenomycin is a substrate of AbcA. PMID:24509312

  12. 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.

  13. Gene Regulation by H-NS as a Function of Growth Conditions Depends on Chromosomal Position in Escherichia coli

    PubMed Central

    Brambilla, Elisa; Sclavi, Bianca

    2015-01-01

    Cellular adaptation to changing environmental conditions requires the coordinated regulation of expression of large sets of genes by global regulatory factors such as nucleoid associated proteins. Although in eukaryotic cells genomic position is known to play an important role in regulation of gene expression, it remains to be established whether in bacterial cells there is an influence of chromosomal position on the efficiency of these global regulators. Here we show for the first time that genome position can affect transcription activity of a promoter regulated by the histone-like nucleoid-structuring protein (H-NS), a global regulator of bacterial transcription and genome organization. We have used as a local reporter of H-NS activity the level of expression of a fluorescent reporter protein under control of an H-NS−regulated promoter (Phns) at different sites along the genome. Our results show that the activity of the Phns promoter depends on whether it is placed within the AT-rich regions of the genome that are known to be bound preferentially by H-NS. This modulation of gene expression moreover depends on the growth phase and the growth rate of the cells, reflecting the changes taking place in the relative abundance of different nucleoid proteins and the inherent heterogeneous organization of the nucleoid. Genomic position can thus play a significant role in the adaptation of the cells to environmental changes, providing a fitness advantage that can explain the selection of a gene’s position during evolution. PMID:25701587

  14. Adjustment of carbon fluxes to light conditions regulates the daily turnover of starch in plants: a computational model.

    PubMed

    Pokhilko, Alexandra; Flis, Anna; Sulpice, Ronan; Stitt, Mark; Ebenhöh, Oliver

    2014-03-01

    In the light, photosynthesis provides carbon for metabolism and growth. In the dark, plant growth depends on carbon reserves that were accumulated during previous light periods. Many plants accumulate part of their newly-fixed carbon as starch in their leaves in the day and remobilise it to support metabolism and growth at night. The daily rhythms of starch accumulation and degradation are dynamically adjusted to the changing light conditions such that starch is almost but not totally exhausted at dawn. This requires the allocation of a larger proportion of the newly fixed carbon to starch under low carbon conditions, and the use of information about the carbon status at the end of the light period and the length of the night to pace the rate of starch degradation. This regulation occurs in a circadian clock-dependent manner, through unknown mechanisms. We use mathematical modelling to explore possible diurnal mechanisms regulating the starch level. Our model combines the main reactions of carbon fixation, starch and sucrose synthesis, starch degradation and consumption of carbon by sink tissues. To describe the dynamic adjustment of starch to daily conditions, we introduce diurnal regulators of carbon fluxes, which modulate the activities of the key steps of starch metabolism. The sensing of the diurnal conditions is mediated in our model by the timer α and the "dark sensor"β, which integrate daily information about the light conditions and time of the day through the circadian clock. Our data identify the β subunit of SnRK1 kinase as a good candidate for the role of the dark-accumulated component β of our model. The developed novel approach for understanding starch kinetics through diurnal metabolic and circadian sensors allowed us to explain starch time-courses in plants and predict the kinetics of the proposed diurnal regulators under various genetic and environmental perturbations.

  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, 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...

  18. 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...

  19. 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...

  20. 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,...

  1. 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...

  2. Differences in extinction of cue-maintained conditioned responses associated with self-administration: alcohol versus a non-alcoholic reinforcer

    PubMed Central

    Holtyn, August F.; Kaminski, Barbara J.; Wand, Gary S.; Weerts, Elise M.

    2014-01-01

    Background Stimuli paired with alcohol may evoke conditioned responses that influence consumption and relapse. Understanding extinction of conditioned responses for both alcohol and non-alcoholic reinforcers, and their relation to subsequent consumption, may be useful in identifying methods to maintain abstinence. Methods Nine baboons self-administered alcohol (n=4) or a non-alcoholic reinforcer (orange-flavored Tang®, n=5) under a three-component chained schedule of reinforcement (CSR). Each component was associated with distinct stimuli and response requirements, which modeled periods of anticipation (Component 1), seeking (Component 2), and consumption (Component 3). No behavioral contingencies were in effect during Component 1. Responses in Component 2, required to gain access to Component 3, provided indices of seeking behavior. Alcohol or Tang was available only in Component 3. Initial conditions parametrically manipulated the concentration of alcohol (2–6% w/v) or Tang (25–100%) that was available for self-administration. The breaking point (BP) of alcohol- and Tang-seeking responses at each of the concentrations was determined by adding a progressive ratio schedule to Component 2. Extinction of responding under stimulus conditions identical to those during baseline, but with no access to alcohol or Tang, was examined using across- and within-session extinction procedures. Results The BP for 2% w/v alcohol was lower than that for 4% and 6%, which were closely similar. For Tang, BPs increased as the concentration increased. When concentrations of alcohol and Tang were adjusted to produce comparable BPs, self-administration of Tang was higher when compared to alcohol; however, alcohol-related cues maintained higher BPs than Tang-related cues when only water was available for self-administration. Alcohol seeking and self-administration responses were more resistant to extinction than those for Tang. Conclusions Stimuli paired with alcohol or non

  3. Delayed Administration of Bone Marrow Mesenchymal Stem Cell Conditioned Medium Significantly Improves Outcome After Retinal Ischemia in Rats

    PubMed Central

    Dreixler, John C.; Poston, Jacqueline N.; Balyasnikova, Irina; Shaikh, Afzhal R.; Tupper, Kelsey Y.; Conway, Sineadh; Boddapati, Venkat; Marcet, Marcus M.; Lesniak, Maciej S.; Roth, Steven

    2014-01-01

    Purpose. Delayed treatment after ischemia is often unsatisfactory. We hypothesized that injection of bone marrow stem cell (BMSC) conditioned medium after ischemia could rescue ischemic retina, and in this study we characterized the functional and histological outcomes and mechanisms of this neuroprotection. Methods. Retinal ischemia was produced in adult Wistar rats by increasing intraocular pressure for 55 minutes. Conditioned medium (CM) from rat BMSCs or unconditioned medium (uCM) was injected into the vitreous 24 hours after the end of ischemia. Recovery was assessed 7 days after ischemia using electroretinography, at which time we euthanized the animals and then prepared 4-μm-thick paraffin-embedded retinal sections. TUNEL and Western blot were used to identify apoptotic cells and apoptosis-related gene expression 24 hours after injections; that is, 48 hours after ischemia. Protein content in CM versus uCM was studied using tandem mass spectrometry, and bioinformatics methods were used to model protein interactions. Results. Intravitreal injection of CM 24 hours after ischemia significantly improved retinal function and attenuated cell loss in the retinal ganglion cell layer. CM attenuated postischemic apoptosis and apoptosis-related gene expression. By spectral counting, 19 proteins that met stringent identification criteria were increased in the CM compared to uCM; the majority were extracellular matrix proteins that mapped into an interactional network together with other proteins involved in cell growth and adhesion. Conclusions. By restoring retinal function, attenuating apoptosis, and preventing retinal cell loss after ischemia, CM is a robust means of delayed postischemic intervention. We identified some potential candidate proteins for this effect. PMID:24699381

  4. Intravenous or intranasal administration of gliadin is able to down-regulate the specific immune response in mice.

    PubMed

    Rossi, M; Maurano, F; Caputo, N; Auricchio, S; Sette, A; Capparelli, R; Troncone, R

    1999-08-01

    The mucosal lesion in coeliac disease (CD) represents an immunologically mediated injury triggered by gliadin and is restricted by a particular assortment of major histocompatibility complex (MHC) class II genes. Therefore, immunomodulatory strategies to tolerize gliadin-specific, class II-restricted T-cell responses could represent an alternative to current treatments of CD, which are based on a gluten-free diet. In this study, BALB/c mice derived from a gluten-free diet colony were tolerized by either intranasal (i.n.) or intravenous (i.v.) administration of single or multiple doses of gliadin. While a single dose failed to induce tolerance, a significant decrease in gliadin-specific T-cell proliferation was detected (P < 0.001) after multiple i.n. or i.v. administrations. No significant difference in antibody titre was detected for antigen-specific immunoglobulin G (IgG) or the IgG1 subclass, but a lower IgG2a-specific titre was observed. Both interferon-gamma (IFN-gamma) and interleukin (IL)-2 expression, measured by enzyme-linked immunosorbent assay (ELISA) and reverse transcription-polymerase chain reaction (RT-PCR), were reduced on antigen administration, both i.v. and i.n. Neither regimen showed a regulatory effect on IL-4 production. As T helper 1 (Th1) cytokines seem to be important in the pathogenesis of CD, our data therefore highlight the potential of i.n. and i.v. routes for the design of useful immunomodulatory strategies for CD.

  5. Up-regulation of 5-HT2B receptor density and receptor-mediated glycogenolysis in mouse astrocytes by long-term fluoxetine administration.

    PubMed

    Kong, Ebenezer K C; Peng, Liang; Chen, Ye; Yu, Albert C H; Hertz, Leif

    2002-02-01

    The effects were studied of short-term (1 week) versus long-term (2-3 weeks) fluoxetine treatment of primary cultures of mouse astrocytes, differentiated by treatment with dibutyryl cyclic AMP. From previous experiments it is known that acute treatment with fluoxetine stimulates glycogenolysis and increases free cytosolic Ca2+ concentration ([Ca2+]i]) in these cultures, whereas short-term (one week) treatment with 10 microM down-regulates the effects on glycogen and [Ca2+]i, when fluoxetine administration is renewed (or when serotonin is administered). Moreover, antagonist studies have shown that these responses are evoked by activation of a 5-HT2, receptor that is different from the 5-HT2A receptor and therefore at that time tentatively were interpreted as being exerted on 5-HT2C receptors. In the present study the cultures were found by RT-PCR to express mRNA for 5-HT2A and 5-HT2B receptors, but not for the 5-HT2C receptor, identifying the 5-HT2 receptor activated by fluoxetine as the 5-HT2B receptor, the most recently cloned 5-Ht2 receptor and a 5-HT receptor known to be more abundant in human, than in rodent, brain. Both short-term and long-term treatment with fluoxetine increased the specific binding of [3H]mesulergine, a ligand for alL three 5-HT2 receptors. Long-term treatment with fluoxetine caused an agonist-induced up-regulation of the glycogenolytic response to renewed administration of fluoxetine, whereas short-term treatment abolished the fluoxetine-induced hydrolysis of glycogen. Thus, during a treatment period similar to that required for fluoxetine's clinical response to occur, 5-HT2B-mediated effects are initially down-regulated and subsequently up-regulated. PMID:11930908

  6. 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.

  7. Transsynaptic EphB/Ephrin-B signaling regulates growth of presynaptic boutons required for classical conditioning.

    PubMed

    Li, Wei; Zheng, Zhaoqing; Keifer, Joyce

    2011-06-01

    Learning-related presynaptic remodeling has been documented in only a few systems, and its molecular mechanisms are largely unknown. Here we describe a role for the bidirectional EphB/ephrin-B signaling system in structural plasticity of presynaptic nerve terminals using an in vitro model of classical conditioning. Conditioning or BDNF application induced significant growth of auditory nerve presynaptic boutons that convey the conditioned stimulus to abducens motor neurons. Interestingly, bouton enlargement occurred only for those synapses apposed to motor neuron dendrites rather than to somata. Phosphorylation of ephrin-B1, but not EphB2, was induced by both conditioning and BDNF application and was inhibited by postsynaptic injections of ephrin-B antibody. Finally, suppression of postsynaptic ephrin-B function inhibited presynaptic bouton enlargement that was rescued by activation of EphB2 by ephrin-B1-Fc. These data provide evidence for ephrin-B-induced EphB2 forward signaling in presynaptic structural plasticity during classical conditioning. They also reveal a functional interaction between BDNF/TrkB and the Eph/ephrin signaling systems in the coordination of presynaptic and postsynaptic modifications during conditioning.

  8. Enhanced interaction of Vibrio cholerae virulence regulators TcpP and ToxR under oxygen-limiting conditions.

    PubMed

    Fan, Fenxia; Liu, Zhi; Jabeen, Nusrat; Birdwell, L Dillon; Zhu, Jun; Kan, Biao

    2014-04-01

    Vibrio cholerae is the causative agent of the diarrheal disease cholera. The ability of V. cholerae to colonize and cause disease requires the intricately regulated expression of a number of virulence factors during infection. One of the signals sensed by V. cholerae is the presence of oxygen-limiting conditions in the gut. It has been shown that the virulence activator AphB plays a key role in sensing low oxygen concentrations and inducing the transcription of another key virulence activator, TcpP. In this study, we used a bacterial two-hybrid system to further examine the effect of oxygen on different virulence regulators. We found that anoxic conditions enhanced the interaction between TcpP and ToxR, identified as the first positive regulator of V. cholerae virulence genes. We further demonstrated that the TcpP-ToxR interaction was dependent on the primary periplasmic protein disulfide formation enzyme DsbA and cysteine residues in the periplasmic domains of both ToxR and TcpP. Furthermore, we showed that in V. cholerae, an interaction between TcpP and ToxR is important for virulence gene induction. Under anaerobic growth conditions, we detected ToxR-TcpP heterodimers, which were abolished in the presence of the reducing agent dithiothreitol. Our results suggest that V. cholerae may sense intestinal anoxic signals by multiple components to activate virulence.

  9. Developmental change in the neurophysiological correlates of self-regulation in high- and low-emotion conditions

    PubMed Central

    Lamm, Connie; Lewis, Marc D.

    2010-01-01

    One of the most important tasks of childhood is learning to self-regulate in the presence of negative emotions. Until recently, almost no research has examined the neurophysiological correlates of emotional self-regulation as it develops over childhood and adolescence. We were interested in plotting a fine-grained developmental profile of the neural underpinnings of self-regulation, in the context of negative emotion, for 7- to 14-year-old children. We predicted that children would recruit less cortical activation with age in the service of self-regulation, reflecting increased neural efficiency with development. We also predicted that children would recruit more cortical activation with increased negative emotion, possibly reflecting greater demand on cortical resources. We administered a go/nogo task with an emotion induction block and we measured the amplitude of the N2, an event-related potential associated with inhibitory control, as it varied with block and with age. Furthermore, we estimated activation for a ventral prefrontal region of interest (ROI; suggestive of orbital frontal, ventromedial prefrontal, or rostral anterior cingulate activation) and a dorsomedial prefrontal ROI (suggestive of dorsal anterior cingulate activation) frequently modeled as cortical generators underlying the N2. Results revealed a marginal decrease in mediofrontal scalp activation, but a more pronounced decrease in activation of the ventromedial prefrontal ROI, with age. There were no age-related changes in dorsomedial prefrontal ROI activation. Lastly, as predicted, we found increased ventral prefrontal ROI activation during the negative emotion induction, possibly reflecting greater recruitment of frontocortical resources underlying emotion regulation, but developmental change in this activation was no different than for the other conditions. Thus, both self-regulation in general and emotion regulation in particular recruited less cortical activation with age, suggesting more

  10. Developmental change in the neurophysiological correlates of self-regulation in high- and low-emotion conditions.

    PubMed

    Lamm, Connie; Lewis, Marc D

    2010-01-01

    One of the most important tasks of childhood is learning to self-regulate in the presence of negative emotions. Until recently, almost no research has examined the neurophysiological correlates of emotional self-regulation as it develops over childhood and adolescence. We were interested in plotting a fine-grained developmental profile of the neural underpinnings of self-regulation, in the context of negative emotion, for 7- to 14-year-old children. We predicted that children would recruit less cortical activation with age in the service of self-regulation, reflecting increased neural efficiency with development. We also predicted that children would recruit more cortical activation with increased negative emotion, possibly reflecting greater demand on cortical resources. We administered a Go No-Go task with an emotion induction block and we measured the amplitude of the N2, an event related potential associated with inhibitory control, as it varied with block and with age. Furthermore, we estimated activation for a ventral prefrontal region of interest (ROI; suggestive of orbital frontal, ventromedial prefrontal, or rostral anterior cingulate activation) and a dorsomedial prefrontal ROI (suggestive of dorsal anterior cingulate activation) frequently modeled as cortical generators underlying the N2. Results revealed a marginal decrease in mediofrontal scalp activation, but a more pronounced decrease in activation of the ventromedial prefrontal ROI, with age. There were no age-related changes in dorsomedial prefrontal ROI activation. Lastly, as predicted, we found increased ventral prefrontal ROI activation during the negative emotion induction, possibly reflecting greater recruitment of frontocortical resources underlying emotion regulation, but developmental change in this activation was no different than for the other conditions. Thus, both self-regulation in general and emotion regulation in particular recruited less cortical activation with age, suggesting more

  11. 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

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

    PubMed

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

    2013-12-01

    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 (0.06mg/kg) under an FR 3 schedule during daily 23h sessions. Rats were then exposed to saline extinction and reacquisition of NSA, followed by weekly reductions in the unit dose (0.03 to 0.00025mg/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 (r(2) 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 males

  13. Regulations for the administration and enforcement of the Radiation Control for Health and Safety Act of 1968

    SciTech Connect

    Not Available

    1988-04-01

    The purpose of the Act is to protect the public from unnecessary exposure to radiation from electronic products, including ionizing, nonionizing, electromagnetic, or particulate radiation, or any sonic, infrasonic, or ultrasonic wave. The regulations in the publication cover general provisions, statements of policy and interpretation, radiation protection recommendations, recordkeeping and reporting requirements for manufacturers, dealers, and distributors; notification requirements for defects or failure to comply; repurchase, repairs, or replacement of electronic products; importation of products; and performance standards for television receivers, cathode ray tubes, diagnostic x-ray equipment, radiographic equipment, fluoroscopic equipment, computer aided tomography equipment, microwave ovens, laser products, sunlamps, ultraviolet lamps, mercury lamps, and ultrasonic therapy products.

  14. The Natural Antimicrobial Enzyme Lysozyme is Up-Regulated in Gastrointestinal Inflammatory Conditions.

    PubMed

    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

  15. Requirement of ArcA for redox regulation in Escherichia coli under microaerobic but not anaerobic or aerobic conditions.

    PubMed

    Alexeeva, Svetlana; Hellingwerf, Klaas J; Teixeira de Mattos, M Joost

    2003-01-01

    In Escherichia coli, the two-component regulatory ArcAB system functions as a major control system for the regulation of expression of genes encoding enzymes involved in both aerobic and anaerobic catabolic pathways. Previously, we have described the physiological response of wild-type E. coli to changes in oxygen availability through the complete range from anaerobiosis to full aerobiosis (S. Alexeeva, B. de Kort, G. Sawers, K. J. Hellingwerf, and M. J. Teixeira de Mattos, J. Bacteriol. 182:4934-4940, 2000, and S. Alexeeva, K. J. Hellingwerf, and M. J. Teixeira de Mattos, J. Bacteriol. 184:1402-1406, 2002). Here, we address the question of the contribution of the ArcAB-dependent transcriptional regulation to this response. Wild-type E. coli and a mutant lacking the ArcA regulator were grown in glucose-limited chemostat cultures at controlled levels of oxygen availability ranging from full aerobiosis to complete anaerobiosis. A flux analysis of the distribution of catabolic fluxes over parallel pathways was carried out, and the intracellular redox state (as reflected by the NADH/NAD ratio) was monitored for all steady states. Deletion of ArcA neither significantly altered the in vivo activity of the pyruvate dehydrogenase complex and pyruvate formate lyase nor significantly affected catabolism under fully aerobic and fully anaerobic conditions. In contrast, profound effects of the absence of ArcA were seen under conditions of oxygen-restricted growth: increased respiration, an altered electron flux distribution over the cytochrome o- and d-terminal oxidases, and a significant change in the intracellular redox state were observed. Thus, the ArcA regulator was found to exert major control on flux distribution, and it is concluded that the ArcAB system should be considered a microaerobic redox regulator.

  16. 18 CFR 415.50 - General conditions.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 18 Conservation of Power and Water Resources 2 2010-04-01 2010-04-01 false General conditions. 415.50 Section 415.50 Conservation of Power and Water Resources DELAWARE RIVER BASIN COMMISSION ADMINISTRATIVE MANUAL BASIN REGULATIONS-FLOOD PLAIN REGULATIONS Enforcement § 415.50 General conditions. On...

  17. 18 CFR 415.50 - General conditions.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 18 Conservation of Power and Water Resources 2 2011-04-01 2011-04-01 false General conditions. 415.50 Section 415.50 Conservation of Power and Water Resources DELAWARE RIVER BASIN COMMISSION ADMINISTRATIVE MANUAL BASIN REGULATIONS-FLOOD PLAIN REGULATIONS Enforcement § 415.50 General conditions. On...

  18. 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…

  19. 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)…

  20. Network activity in neurons of the motor and prefrontal areas of the cortex in trained cats in conditions of systemic administration of m-cholinoreceptor blockers.

    PubMed

    Khokhlova, V N; Merzhanova, G Kh; Dolbakyan, E E

    2002-01-01

    Experiments on five cats already trained to an operant conditioned food-procuring reflex to light were used to study the network activity of cells in the frontal and motor areas of the cortex accompanying disruption of conditioned reflex behavior in conditions of systemic administration of m-cholinoreceptor blockers. The activity of cortical neurons and their network properties were assessed using auto- and cross-correlation histograms. Doses of central m-cholinoreceptor blockers (the non-selective blocker scopolamine and the relatively selective m1-cholinoreceptor blocker trihexyphenidyl) disrupted performance of the operant motor reflex but had no effect on the appearance of contextual behavior and responses to switching on of the conditioned signal (standing up, elevating the paw). This was accompanied by 1) changes in the patterns of neuron activity in the moor and frontal areas of the cortex, with increases in train, rhythmic, and rhythmic train activity in cortical cells; 2) appearance of synchronicity in the operation of cortical neurons; 3) decreases in the numbers of direct interneuronal connections in the motor and frontal areas of the cortex and in the numbers of connections between these structures.

  1. 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

  2. [The regulation of human cardiac activity during the cyclical change of barometric pressure under sealed-cabin conditions].

    PubMed

    Novikov, V S; Myznikov, I L; Bortnovskiĭ, V N

    1992-01-01

    A cyclic change of barometric pressure from 790 to 720 mm Hg once a day to twice within 3 days under sealed conditions results in a functional rearrangement of the mechanisms to control cardiac activity which cause the predominance of vagotonic responses determined by a decrease of the body reserves and its asthenization. At the beginning of staying under pressurized conditions (2nd week) it appears as an occurrence of meteorotropic responses (in 13% of subjects tested) and at the end of living in pressurized conditions (9th week) as a significant decline with a change ("removal") in: pressure, index of strain, vegetative index of rhythm, index of regulation processes, index of vegetative equilibrium and as an increase in the number of individuals responding to a cyclic change of barometric pressure up to 44% which is indicative of a moderate relationship between manifestation rate of these sensations and an effect duration of a given factor.

  3. Physico-chemical Stability of MabThera Drug-product Solution for Subcutaneous Injection under in-use Conditions with Different Administration Materials.

    PubMed

    Mueller, Claudia; Dietel, Elke; Heynen, Severin R; Nalenz, Heiko; Goldbach, Pierre; Mahler, Hanns-Christian; Schmidt, Johannes; Grauschopf, Ulla; Schoenhamnmer, Karin

    2015-01-01

    MabThera is an essential component of the standard-of-care regimens in the treatment of non-Hodgkin lymphoma and Chronic Lymphatic Leukemia. MabThera for subcutaneous injection is a novel line extension that has been approved by the European Medicines Agency for the treatment of patients with follicular lymphoma and diffuse large B-cell lymphoma. This study aimed to evaluate in-use stability data of MabThera subcutaneous drug-product solution in single-use syringes for subcutaneous administration according to the European Medicines Agency guideline. The drug-product solution was exposed to material contact surfaces of five different administration setups commonly used in subcutaneous drug delivery. MabThera subcutaneous was transferred under aseptic conditions into polypropylene and polycarbonate syringes and stored for 1, 2, and 4 weeks at 2°C to 8°C followed by 24 hours at 30°C. After storage, subcutaneous administration was simulated and MabThera subcutaneous drug-product solution quality attributes were evaluated by using compendial physico-chemical tests, as well as suitable and validated molecule- and formulation-specific analytical methods. MabThera subcutaneous vials were treated and analyzed in parallel. The physico-chemical results of MabThera subcutaneous in the different setups were comparable to the control for all timepoints. No change in drug-product quality after storage and simulated administration was found compared to the control. However, since single-dose products do not contain preservatives, microbial contamination and growth needs to be avoided and product sterility needs to be ensured. The results showed that MabThera subcutaneous remains compatible and stable, from a physico-chemical perspective, for up to 4 weeks at 2°C to 8°C followed by 24 hours at 30°C with the contact materials tested in this study. In order to avoid and minimize microbial growth, MabThera subcutaneous should be used immediately after removal from the original

  4. Physico-chemical Stability of MabThera Drug-product Solution for Subcutaneous Injection under in-use Conditions with Different Administration Materials.

    PubMed

    Mueller, Claudia; Dietel, Elke; Heynen, Severin R; Nalenz, Heiko; Goldbach, Pierre; Mahler, Hanns-Christian; Schmidt, Johannes; Grauschopf, Ulla; Schoenhamnmer, Karin

    2015-01-01

    MabThera is an essential component of the standard-of-care regimens in the treatment of non-Hodgkin lymphoma and Chronic Lymphatic Leukemia. MabThera for subcutaneous injection is a novel line extension that has been approved by the European Medicines Agency for the treatment of patients with follicular lymphoma and diffuse large B-cell lymphoma. This study aimed to evaluate in-use stability data of MabThera subcutaneous drug-product solution in single-use syringes for subcutaneous administration according to the European Medicines Agency guideline. The drug-product solution was exposed to material contact surfaces of five different administration setups commonly used in subcutaneous drug delivery. MabThera subcutaneous was transferred under aseptic conditions into polypropylene and polycarbonate syringes and stored for 1, 2, and 4 weeks at 2°C to 8°C followed by 24 hours at 30°C. After storage, subcutaneous administration was simulated and MabThera subcutaneous drug-product solution quality attributes were evaluated by using compendial physico-chemical tests, as well as suitable and validated molecule- and formulation-specific analytical methods. MabThera subcutaneous vials were treated and analyzed in parallel. The physico-chemical results of MabThera subcutaneous in the different setups were comparable to the control for all timepoints. No change in drug-product quality after storage and simulated administration was found compared to the control. However, since single-dose products do not contain preservatives, microbial contamination and growth needs to be avoided and product sterility needs to be ensured. The results showed that MabThera subcutaneous remains compatible and stable, from a physico-chemical perspective, for up to 4 weeks at 2°C to 8°C followed by 24 hours at 30°C with the contact materials tested in this study. In order to avoid and minimize microbial growth, MabThera subcutaneous should be used immediately after removal from the original

  5. Different MK-801 administration schedules induce mild to severe learning impairments in an operant conditioning task: role of buspirone and risperidone in ameliorating these cognitive deficits.

    PubMed

    Rapanelli, Maximiliano; Frick, Luciana Romina; Bernardez-Vidal, Micaela; Zanutto, Bonifacio Silvano

    2013-11-15

    Blockade of N-methyl-d-aspartate receptor (NMDA) by the noncompetitive NMDA receptor (NMDAR) antagonist MK-801 produces behavioral abnormalities and alterations in prefrontal cortex (PFC) functioning. Due to the critical role of the PFC in operant conditioning task learning, we evaluated the effects of acute, repeated postnatal injections of MK-801 (0.1mg/kg) on learning performance. We injected Long-Evans rats i.p. with MK-801 (0.1mg/kg) using three different administration schedules: injection 40 min before beginning the task (during) (n=12); injection twice daily for six consecutive days prior to beginning the experimental procedures (prior) (n=12); or twice daily subcutaneous injections from postnatal day 7 to 11 (postnatal) (n=12). Next, we orally administered risperidone (serotonin receptor 2A and dopamine receptor 2 antagonist, 1mg/kg) or buspirone (serotonin receptor 1A partial agonist, 10mg/kg) to animals treated with the MK-801 schedule described above. The postnatal and prior administration schedules produced severe learning deficits, whereas injection of MK-801 just before training sessions had only mild effects on acquisition of an operant conditioning. Risperidone was able to reverse the detrimental effect of MK-801 in the animals that were treated with MK-801 during and prior training sessions. In contrast, buspirone was only effective at mitigating the cognitive deficits induced by MK-801 when administered during the training procedures. The data demonstrates that NMDA antagonism disrupts basic mechanisms of learning in a simple PFC-mediated operant conditioning task, and that buspirone and risperidone failed to attenuate the learning deficits when NMDA neurotransmission was blocked in the early stages of the postnatal period.

  6. 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. PMID:24948065

  7. 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. PMID:27610089

  8. 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.

  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. 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.

  11. 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.

  12. Multiple cytochrome P-450 genes are concomitantly regulated by vitamin A under steady-state conditions and by retinoic acid during hepatic first-pass metabolism.

    PubMed

    Ross, A Catharine; Cifelli, Christopher J; Zolfaghari, Reza; Li, Nan-Qian

    2011-01-01

    Vitamin A (retinol) is an essential precursor for the production of retinoic acid (RA), which in turn is a major regulator of gene expression, affecting cell differentiation throughout the body. Understanding how vitamin A nutritional status, as well as therapeutic retinoid treatment, regulates the expression of retinoid homeostatic genes is important for improvement of dietary recommendations and therapeutic strategies using retinoids. This study investigated genes central to processes of retinoid uptake and storage, release to plasma, and oxidation in the liver of rats under steady-state conditions after different exposures to dietary vitamin A (deficient, marginal, adequate, and supplemented) and acutely after administration of a therapeutic dose of all-trans-RA. Over a very wide range of dietary vitamin A, lecithin:retinol acyltransferase (LRAT) as well as multiple cytochrome P-450s (CYP26A1, CYP26B1, and CYP2C22) differed by diet and were highly correlated with one another and with vitamin A status assessed by liver retinol concentration (all correlations, P < 0.05). After acute treatment with RA, the same genes were rapidly and concomitantly induced, preceding retinoic acid receptor (RAR)β, a classical direct target of RA. CYP26A1 mRNA exhibited the greatest dynamic range (change of log 2(6) in 3 h). Moreover, CYP26A1 increased more rapidly in the liver of RA-primed rats than naive rats, evidenced by increased CYP26A1 gene expression and increased conversion of [(3)H]RA to polar metabolites. By in situ hybridization, CYP26A1 mRNA was strongly regulated within hepatocytes, closely resembling retinol-binding protein (RBP)4 in location. Overall, whether RA is produced endogenously from retinol or administered exogenously, changes in retinoid homeostatic gene expression simultaneously favor both retinol esterification and RA oxidation, with CYP26A1 exhibiting the greatest dynamic change.

  13. 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.

  14. Self-Regulation of Solar Coronal Heating Process via the Collisionless Reconnection Condition

    SciTech Connect

    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. 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. PMID:18233563

  16. Adaptive Response of Group B Streptococcus to High Glucose Conditions: New Insights on the CovRS Regulation Network

    PubMed Central

    Di Palo, Benedetta; Rippa, Valentina; Santi, Isabella; Brettoni, Cecilia; Muzzi, Alessandro; Metruccio, Matteo Maria Emiliano; Grifantini, Renata; Telford, John L.; Paccani, Silvia Rossi; Soriani, Marco

    2013-01-01

    Although the contribution of carbohydrate catabolism to bacterial colonization and infection is well recognized, the transcriptional changes during these processes are still unknown. In this study, we have performed comparative global gene expression analysis of GBS in sugar-free versus high glucose milieu. The analysis revealed a differential expression of genes involved in metabolism, transport and host-pathogen interaction. Many of them appeared to be among the genes previously reported to be controlled by the CovRS two-component system. Indeed, the transcription profile of a ΔcovRS strain grown in high-glucose conditions was profoundly affected. In particular, of the total genes described to be regulated by glucose, ∼27% were under CovRS control with a functional role in protein synthesis, transport, energy metabolism and regulation. Among the CovRS dependent genes, we found bibA, a recently characterized adhesin involved in bacterial serum resistance and here reported to be down-regulated by glucose. ChIP analysis revealed that in the presence of glucose, CovR binds bibA promoter in vivo, suggesting that CovR may act as a negative regulator or a repressor. We also demonstrated that, as for other target promoters, chemical phosphorylation of CovR in aspartic acid increases its affinity for the bibA promoter region. The data reported in this study contribute to the understanding of the molecular mechanisms modulating the adaptation of GBS to glucose. PMID:23585887

  17. Employee Retirement Income Security Act of 1974; rules and regulations for administration and enforcement; claims procedure--Department of Labor. Notice of proposed rulemaking.

    PubMed

    1998-09-01

    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.

  18. N-feedback regulation is synchronized with nodule carbon alteration in Medicago truncatula under excessive nitrate or low phosphorus conditions.

    PubMed

    Sulieman, Saad; Schulze, Joachim; Tran, Lam-Son Phan

    2014-03-15

    The aim of the present study was to test the hypothesis that the higher nodule amino acid content induced under certain treatments may play a role in the N-feedback regulation of nitrogenase (EC 1.18.6.1) activity by restricting the carbon supply to the functioning nodules. Growing Medicago truncatula plants under sub-optimal phosphorus conditions or upon exposure to large supply of nitrate caused significant asparagine accumulation in nodules of the treated plants. In addition, there was a remarkable decline in the nodule succinate content under phosphorus deprivation while malate was tended to increase. Interestingly, the relative share of succinate in the symbiotic tissues was totally inhibited, i.e. reached zero, by excessive nitrate application. These results provide evidence that succinate might be greatly affected by asparagine content of the nodule fraction, thereby restricting cellular carbon supply to the functioning bacteroids which leads to down-regulation of nodule metabolism and nitrogenase activity.

  19. 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

    2014-08-01

    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.

  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. Forest soil respiration rate and delta13C is regulated by recent above ground weather conditions.

    PubMed

    Ekblad, Alf; Boström, Björn; Holm, Anders; Comstedt, Daniel

    2005-03-01

    Soil respiration, a key component of the global carbon cycle, is a major source of uncertainty when estimating terrestrial carbon budgets at ecosystem and higher levels. Rates of soil and root respiration are assumed to be dependent on soil temperature and soil moisture yet these factors often barely explain half the seasonal variation in soil respiration. We here found that soil moisture (range 16.5-27.6% of dry weight) and soil temperature (range 8-17.5 degrees C) together explained 55% of the variance (cross-validated explained variance; Q2) in soil respiration rate (range 1.0-3.4 micromol C m(-2) s(-1)) in a Norway spruce (Picea abies) forest. We hypothesised that this was due to that the two components of soil respiration, root respiration and decomposition, are governed by different factors. We therefore applied PLS (partial least squares regression) multivariate modelling in which we, together with below ground temperature and soil moisture, used the recent above ground air temperature and air humidity (vapour pressure deficit, VPD) conditions as x-variables. We found that air temperature and VPD data collected 1-4 days before respiration measurements explained 86% of the seasonal variation in the rate of soil respiration. The addition of soil moisture and soil temperature to the PLS-models increased the Q2 to 93%. delta13C analysis of soil respiration supported the hypotheses that there was a fast flux of photosynthates to root respiration and a dependence on recent above ground weather conditions. Taken together, our results suggest that shoot activities the preceding 1-6 days influence, to a large degree, the rate of root and soil respiration. We propose this above ground influence on soil respiration to be proportionally largest in the middle of the growing season and in situations when there is large day-to-day shifts in the above ground weather conditions. During such conditions soil temperature may not exert the major control on root respiration. PMID

  2. Conditions that regulate the growth of moulds inoculated into bottled mineral water.

    PubMed

    Criado, Maria Victoria; Fernández Pinto, Virginia E; Badessari, Alicia; Cabral, Daniel

    2005-04-01

    The influence of different storage conditions (temperature, illumination, brand of mineral water and storage time) on growth of mould spores was studied. Alternaria alternata, Penicillium citrinum and Cladosporium cladosporioides spores were inoculated in bottles of mineral and mineralised water, packaged in polyethylene terephtalate (PET). The bottles were incubated under different storage conditions. The strains had been isolated from bottled mineral water in a previous study. Storage time was the parameter that had the most important influence in mould growth. The spores grew into visible colonies after 5 month of incubation in bottles just filled, and in a month in bottles that had been stored for 5 month. This could be due to the migration of compounds from PET packaging material into mineral water. This compounds could be used as nutrients (organic matter) for mould growth. The plasticizer additive di-n-butyl phthalate (DBP) concentration in recently bottled mineral water and in 5-month stored bottles was measured. An increase of 20% of DBP concentration was observed. A. alternata and P. citrinum strains were toxicological characterised. Both strains produced mycotoxins in vitro, and P. citrinum produced citrinin in mineral water, posing a potential health risk for consumers.

  3. The hidden function of photosynthesis: a sensing system for environmental conditions that regulates plant acclimation responses.

    PubMed

    Pfannschmidt, Thomas; Yang, Chunhong

    2012-06-01

    Plants convert light energy from the sun into chemical energy by photosynthesis. Since they are sessile, they have to deal with a wide range of conditions in their immediate environment. Many abiotic and biotic parameters exhibit considerable fluctuations which can have detrimental effects especially on the efficiency of photosynthetic light harvesting. During evolution, plants, therefore, evolved a number of acclimation processes which help them to adapt photosynthesis to such environmental changes. This includes protective mechanisms such as excess energy dissipation and processes supporting energy redistribution, e.g. state transitions or photosystem stoichiometry adjustment. Intriguingly, all these responses are triggered by photosynthesis itself via the interplay of its light reaction and the Calvin-Benson cycle with the residing environmental condition. Thus, besides its primary function in harnessing and converting light energy, photosynthesis acts as a sensing system for environmental changes that controls molecular acclimation responses which adapt the photosynthetic function to the environmental change. Important signalling parameters directly or indirectly affected by the environment are the pH gradient across the thylakoid membrane and the redox states of components of the photosynthetic electron transport chain and/or electron end acceptors coupled to it. Recent advances demonstrate that these signals control post-translational modifications of the photosynthetic protein complexes and also affect plastid and nuclear gene expression machineries as well as metabolic pathways providing a regulatory framework for an integrated response of the plant to the environment at all cellular levels.

  4. Conditions that regulate the growth of moulds inoculated into bottled mineral water.

    PubMed

    Criado, Maria Victoria; Fernández Pinto, Virginia E; Badessari, Alicia; Cabral, Daniel

    2005-04-01

    The influence of different storage conditions (temperature, illumination, brand of mineral water and storage time) on growth of mould spores was studied. Alternaria alternata, Penicillium citrinum and Cladosporium cladosporioides spores were inoculated in bottles of mineral and mineralised water, packaged in polyethylene terephtalate (PET). The bottles were incubated under different storage conditions. The strains had been isolated from bottled mineral water in a previous study. Storage time was the parameter that had the most important influence in mould growth. The spores grew into visible colonies after 5 month of incubation in bottles just filled, and in a month in bottles that had been stored for 5 month. This could be due to the migration of compounds from PET packaging material into mineral water. This compounds could be used as nutrients (organic matter) for mould growth. The plasticizer additive di-n-butyl phthalate (DBP) concentration in recently bottled mineral water and in 5-month stored bottles was measured. An increase of 20% of DBP concentration was observed. A. alternata and P. citrinum strains were toxicological characterised. Both strains produced mycotoxins in vitro, and P. citrinum produced citrinin in mineral water, posing a potential health risk for consumers. PMID:15808368

  5. The calcium-sensing receptor as a regulator of cellular fate in normal and pathological conditions.

    PubMed

    Diez-Fraile, A; Lammens, T; Benoit, Y; D'Herde, K G M A

    2013-02-01

    The calcium-sensing receptor (CaSR) belongs to the evolutionarily conserved family of plasma membrane G protein-coupled receptors (GPCRs). Early studies identified an essential role for the CaSR in systemic calcium homeostasis through its ability to sense small changes in circulating calcium concentration and to couple this information to intracellular signaling pathways that influence parathyroid hormone secretion. However, the presence of CaSR protein in tissues is not directly involved in regulating mineral ion homeostasis points to a role for the CaSR in other cellular functions including the control of cellular proliferation, differentiation and apoptosis. This position at the crossroads of cellular fate designates the CaSR as an interesting study subject is likely to be involved in a variety of previously unconsidered human pathologies, including cancer, atherosclerosis and Alzheimer's disease. Here, we will review the recent discoveries regarding the relevance of CaSR signaling in development and disease. Furthermore, we will discuss the rational for developing and using CaSR-based therapeutics. PMID:23228129

  6. The MYB96 Transcription Factor Regulates Cuticular Wax Biosynthesis under Drought Conditions in Arabidopsis[W

    PubMed Central

    Seo, Pil Joon; Lee, Saet Buyl; Suh, Mi Chung; Park, Mi-Jeong; Go, Young Sam; Park, Chung-Mo

    2011-01-01

    Drought stress activates several defense responses in plants, such as stomatal closure, maintenance of root water uptake, and synthesis of osmoprotectants. Accumulating evidence suggests that deposition of cuticular waxes is also associated with plant responses to cellular dehydration. Yet, how cuticular wax biosynthesis is regulated in response to drought is unknown. We have recently reported that an Arabidopsis thaliana abscisic acid (ABA)–responsive R2R3-type MYB transcription factor, MYB96, promotes drought resistance. Here, we show that transcriptional activation of cuticular wax biosynthesis by MYB96 contributes to drought resistance. Microarray assays showed that a group of wax biosynthetic genes is upregulated in the activation-tagged myb96-1D mutant but downregulated in the MYB96-deficient myb96-1 mutant. Cuticular wax accumulation was altered accordingly in the mutants. In addition, activation of cuticular wax biosynthesis by drought and ABA requires MYB96. By contrast, biosynthesis of cutin monomers was only marginally affected in the mutants. Notably, the MYB96 protein acts as a transcriptional activator of genes encoding very-long-chain fatty acid–condensing enzymes involved in cuticular wax biosynthesis by directly binding to conserved sequence motifs present in the gene promoters. These results demonstrate that ABA-mediated MYB96 activation of cuticular wax biosynthesis serves as a drought resistance mechanism. PMID:21398568

  7. Lesions of cholinergic pedunculopontine tegmental nucleus neurons fail to affect cocaine or heroin self-administration or conditioned place preference in rats.

    PubMed

    Steidl, Stephan; Wang, Huiling; Wise, Roy A

    2014-01-01

    Cholinergic input to the ventral tegmental area (VTA) is known to contribute to reward. Although it is known that the pedunculopontine tegmental nucleus (PPTg) provides an important source of excitatory input to the dopamine system, the specific role of PPTg cholinergic input to the VTA in cocaine reward has not been previously determined. We used a diphtheria toxin conjugated to urotensin-II (Dtx::UII), the endogenous ligand for urotensin-II receptors expressed by PPTg cholinergic but not glutamatergic or GABAergic cells, to lesion cholinergic PPTg neurons. Dtx::UII toxin infusion resulted in the loss of 95.78 (±0.65)% of PPTg cholinergic cells but did not significantly alter either cocaine or heroin self-administration or the development of cocaine or heroin conditioned place preferences. Thus, cholinergic cells originating in PPTg do not appear to be critical for the rewarding effects of cocaine or of heroin.

  8. Multiple abiotic stimuli are integrated in the regulation of rice gene expression under field conditions.

    PubMed

    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. PMID:26609814

  9. 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...

  10. Down-regulation of the autophagy gene, ATG7, protects bone marrow-derived mesenchymal stem cells from stressful conditions

    PubMed Central

    Molaei, Sedigheh; Amiri, Fatemeh; Harati, Mozhgan Dehghan; Bahadori, Marzie; Jaleh, Fatemeh; Jalili, Mohammad Ali; Mohammadi Roushandeh, Amaneh

    2015-01-01

    Background Mesenchymal stem cells (MSCs) are valuable for cell-based therapy. However, their application is limited owing to their low survival rate when exposed to stressful conditions. Autophagy, the process by which cells recycle the cytoplasm and dispose of defective organelles, is activated by stress stimuli to adapt, tolerate adverse conditions, or trigger the apoptotic machinery. This study aimed to determine whether regulation of autophagy would affect the survival of MSCs under stress conditions. Methods Autophagy was induced in bone marrow-derived MSCs (BM-MSCs) by rapamycin, and was inhibited via shRNA-mediated knockdown of the autophagy specific gene, ATG7. ATG7 expression in BM-MSCs was evaluated by reverse transcription polymerase chain reaction (RT-PCR), western blot, and quantitative PCR (qPCR). Cells were then exposed to harsh microenvironments, and a water-soluble tetrazolium salt (WST)-1 assay was performed to determine the cytotoxic effects of the stressful conditions on cells. Results Of 4 specific ATG7-inhibitor clones analyzed, only shRNA clone 3 decreased ATG7 expression. Under normal conditions, the induction of autophagy slightly increased the viability of MSCs while autophagy inhibition decreased their viability. However, under stressful conditions such as hypoxia, serum deprivation, and oxidative stress, the induction of autophagy resulted in cell death, while its inhibition potentiated MSCs to withstand the stress conditions. The viability of autophagy-suppressed MSCs was significantly higher than that of relevant controls (P<0.05, P<0.01 and P<0.001). Conclusion Autophagy modulation in MSCs can be proposed as a new strategy to improve their survival rate in stressful microenvironments. PMID:26157777

  11. 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.

  12. 7 CFR 760.900 - Administration.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... SPECIAL PROGRAMS INDEMNITY PAYMENT PROGRAMS 2005-2007 Livestock Indemnity Program § 760.900 Administration. (a) The regulations in this subpart specify the terms and conditions applicable to the 2005-2007 Livestock Indemnity Program (2005-2007 LIP), which will be administered under the general supervision...

  13. 7 CFR 760.900 - Administration.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... SPECIAL PROGRAMS INDEMNITY PAYMENT PROGRAMS 2005-2007 Livestock Indemnity Program § 760.900 Administration. (a) The regulations in this subpart specify the terms and conditions applicable to the 2005-2007 Livestock Indemnity Program (2005-2007 LIP), which will be administered under the general supervision...

  14. Beneficial effect of spironolactone administration on ethynylestradiol-induced cholestasis in the rat: involvement of up-regulation of multidrug resistance-associated protein 2.

    PubMed

    Ruiz, María L; Villanueva, Silvina S M; Luquita, Marcelo G; Ikushiro, Shin-ichi; Mottino, Aldo D; Catania, Viviana A

    2007-11-01

    The effect of spironolactone (SL) administration on 17alpha-ethynylestradiol (EE)-induced cholestasis was studied, with emphasis on expression and activity of Mrps. Adult male Wistar rats were divided into the following groups: EE (5 mg/kg daily for 5 days, s.c.), SL (200 micromol/kg daily for 3 days, i.p.), EE+SL (same doses, SL administered the last 3 days of EE treatment), and controls. SL prevented the decrease in bile salt-independent fraction of bile flow induced by EE, in association with normalization of biliary excretion of glutathione. Western blot studies indicate that EE decreased the expression of multidrug resistance-associated protein 2 (Mrp2) by 41% and increased that of Mrp3 by 200%, whereas SL only affected Mrp2 expression (+60%) with respect to controls. The EE+SL group showed increased levels of Mrp2 and Mrp3 to the same extent as that registered for the individual treatments. Real-time polymerase chain reaction studies indicated that up-regulation of Mrp2 and Mrp3 by SL and EE, respectively, was at the transcriptional level. To estimate Mrp2 and Mrp3 activities, apical and basolateral excretion of acetaminophen glucuronide (APAP-glu), a common substrate for both transporters, was measured in the recirculating isolated perfused liver model. Biliary/perfusate excretion ratio was decreased in EE (-88%) and increased in SL (+36%) with respect to controls. Coadministration of rats with SL partially prevented (-53%) impairment induced by EE in this ratio. In conclusion, SL administration to EE-induced cholestatic rats counteracted the decrease in bile flow and biliary excretion of glutathione and APAP-glu, a model Mrp substrate, findings associated with up-regulation of Mrp2 expression. PMID:17686906

  15. 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

    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 per 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 per kg) or intravenously self-administered (0.03 mg per kg per infusion) nicotine injections. The highest LY235959 dose (5 mg per 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 alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid 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 microM) increased NMDA receptor-mediated excitatory postsynaptic currents in rat CeA slices, similar to its previously described effects in the VTA. Finally, infusion of LY235959 (0.1-10 ng per 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.

  16. Single session of cocaine intravenous self-administration shapes goal-oriented behaviours and up-regulates Arc mRNA levels in rat medial prefrontal cortex.

    PubMed

    Fumagalli, Fabio; Franchi, Carlotta; Caffino, Lucia; Racagni, Giorgio; Riva, Marco A; Cervo, Luigi

    2009-04-01

    To separate the direct pharmacological effects of cocaine from those associated with active drug self-administration we employed a yoked control-operant paradigm and investigated the expression of well established markers of the rapid action of cocaine, i.e. the inducible early genes Arc and Zif268 and trophic factors, i.e. brain-derived neurotrophic factor (BDNF) and basic fibroblast growth factor (FGF-2), in rats after a single intravenous (i.v.) cocaine self-administration session. Animals self-administering cocaine (SA, 0.25 mg/0.1 ml saline per infusion, 2-h session) did more active lever-presses than yoked-cocaine (YC) and yoked-vehicle (YV) animals. This goal-oriented behaviour was accompanied by a selective increase in Arc mRNA levels in the medial prefrontal cortex (mPFC). There were no changes in the expression of the other genes in this brain region. mRNA levels of Arc and Zif268 in striatum and Zif268 in the nucleus accumbens markedly increased both in SA and YC animals; but there was no change in the expression of FGF-2 and BDNF. No changes were observed in hippocampus, hypothalamus, frontal cortex, and midbrain in SA and YC animals compared to YV animals in any of the genes. These findings demonstrate that a single session of cocaine i.v. self-administration is sufficient to shape rat behaviour towards goal-directed behaviours and selectively up-regulate Arc expression in mPFC (of SA animals), providing the first evidence that the mPFC's function is already profoundly influenced by the first voluntary cocaine exposure.

  17. 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

  18. 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

  19. Seasonal regulation of reproduction: altered role of melatonin under naturalistic conditions in hamsters.

    PubMed

    Butler, Matthew P; Turner, Kevin W; Park, Jin Ho; Schoomer, Elanor E; Zucker, Irving; Gorman, Michael R

    2010-09-22

    The seasonal reproductive cycle of photoperiodic rodents is conceptualized as a series of discrete melatonin-dependent neuroendocrine transitions. Least understood is the springtime restoration of responsiveness to winter-like melatonin signals (breaking of refractoriness) that enables animals to once again respond appropriately to winter photoperiods the following year. This has been posited to require many weeks of long days based on studies employing static photoperiods instead of the annual pattern of continually changing photoperiods under which these mechanisms evolved. Maintaining Siberian hamsters under simulated natural photoperiods, we demonstrate that winter refractoriness is broken within six weeks after the spring equinox. We then test whether a history of natural photoperiod exposure can eliminate the requirement for long-day melatonin signalling. Hamsters pinealectomized at the spring equinox and challenged 10 weeks later with winter melatonin infusions exhibited gonadal regression, indicating that refractoriness was broken. A photostimulatory effect on body weight is first observed in the last four weeks of winter. Thus, the seasonal transition to the summer photosensitive phenotype is triggered prior to the equinox without exposure to long days and is thereafter melatonin-independent. Distinctions between photoperiodic and circannual seasonal organization erode with the incorporation in the laboratory of ecologically relevant day length conditions. PMID:20444712

  20. 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

  1. 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.

  2. PSGL-1 regulates the migration and proliferation of CD8(+) T cells under homeostatic conditions.

    PubMed

    Veerman, Krystle M; Carlow, Douglas A; Shanina, Iryna; Priatel, John J; Horwitz, Marc S; Ziltener, Hermann J

    2012-02-15

    P-selectin glycoprotein ligand-1 (PSGL-1), a heavily glycosylated sialomucin expressed on most leukocytes, has dual function as a selectin ligand for leukocyte rolling on vascular selectins expressed in inflammation and as a facilitator of resting T cell homing into lymphoid organs. In this article, we document disturbances in T cell homeostasis present in PSGL-1(null) mice. Naive CD4(+) and CD8(+) T cell frequencies were profoundly reduced in blood, whereas T cell numbers in lymph nodes and spleen were at or near normal levels. Although PSGL-1(null) T cells were less efficient at entering lymph nodes, they also remained in lymph nodes longer than PSGL-1(+/+) T cells, suggesting that PSGL-1 supports T cell egress. In addition, PSGL-1(null) CD8(+) T cell proliferation was observed under steady-state conditions and PSGL-1(null) CD8(+) T cells were found to be hyperresponsive to homeostatic cytokines IL-2, IL-4, and IL-15. Despite these disturbances in T cell homeostasis, PSGL-1(null) mice exhibited a normal acute response (day 8) to lymphocytic choriomeningitis virus infection but generated an increased frequency of memory T cells (day 40). Our observations demonstrate a novel pleiotropic influence of PSGL-1 deficiency on several aspects of T cell homeostasis that would not have been anticipated based on the mild phenotype of PSGL-1(null) mice. These potentially offsetting effects presumably account for the near-normal cellularity seen in lymph nodes of PSGL-1(null) mice.

  3. 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

  4. Regulation of HIF-1α signaling and chemoresistance in acute lymphocytic leukemia under hypoxic conditions of the bone marrow microenvironment.

    PubMed

    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

    2012-08-01

    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.

  5. 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. PMID:26897459

  6. Regulation of oxidative phosphorylation in different muscles and various experimental conditions.

    PubMed Central

    Korzeniewski, Bernard

    2003-01-01

    It has been shown previously that direct stimulation of oxidative-phosphorylation complexes in parallel with the stimulation of ATP usage is able to explain the stability of intermediate metabolite (ATP/ADP, phosphocreatine/creatine, NADH/NAD+, protonmotive force) concentrations accompanied by a large increase in oxygen consumption and ATP turnover during transition from rest to intensive exercise in skeletal muscle. It has been also postulated that intensification of parallel activation in the ATP supply-demand system is one of the mechanisms of training-induced adaptation of oxidative phosphorylation in skeletal muscle. In the present paper, it is demonstrated, using the computer model of oxidative phosphorylation in intact skeletal muscle developed previously, that the direct activation of oxidative phosphorylation during muscle contraction can account for the following kinetic properties of oxidative phosphorylation in skeletal muscle encountered in different experimental studies: (i) increase in the respiration rate per mg of mitochondrial protein at a given ADP concentration as a result of muscle training and decrease in this parameter in hypothyroidism; (ii) asymmetry (different half-transition time, t(1/2)) in phosphocreatine concentration time course between on-transient (rest-->work transition) and off-transient (recovery after exercise); (iii) overshoot in phosphocreatine concentration during recovery after exercise; (iv) variability in the kinetic properties of oxidative phosphorylation in different kinds of muscle under different experimental conditions. No other postulated mechanism is able to explain all these phenomena at the same time and therefore the present paper strongly supports the idea of the parallel activation of ATP usage and different oxidative-phosphorylation complexes during muscle contraction. PMID:12901719

  7. Quorum-regulated biofilms enhance the development of conditionally viable, environmental Vibrio cholerae.

    PubMed

    Kamruzzaman, M; Udden, S M Nashir; Cameron, D Ewen; Calderwood, Stephen B; Nair, G Balakrish; Mekalanos, John J; Faruque, Shah M

    2010-01-26

    The factors that enhance the waterborne spread of bacterial epidemics and sustain the pathogens in nature are unclear. The epidemic diarrheal disease cholera caused by Vibrio cholerae spreads through water contaminated with the pathogen. However, the bacteria exist in water mostly as clumps of cells, which resist cultivation by standard techniques but revive into fully virulent form in the intestinal milieu. These conditionally viable environmental cells (CVEC), alternatively called viable but nonculturable cells, presumably play a crucial role in cholera epidemiology. However, the precise mechanism causing the transition of V. cholerae to the CVEC form and this form's significance in the biology of the pathogen are unknown. Here we show that this process involves biofilm formation that is dependent on quorum sensing, a regulatory response that is controlled by cell density. V. cholerae strains carrying mutations in genes required for quorum sensing and biofilm formation displayed altered CVEC formation in environmental water following intestinal infections. Analysis of naturally occurring V. cholerae CVEC showed that organisms that adopt this quiescent physiological state typically exist as clumps of cells that comprise a single clone closely related to isolates causing the most recent local cholera epidemic. These results support a model of cholera transmission in which in vivo-formed biofilms convert to CVEC upon the introduction of cholera stools into environmental water. Our data further suggest that a temporary loss of quorum sensing due to dilution of extracellular autoinducers confers a selective advantage to communities of V. cholerae by blocking quorum-mediated regulatory responses that would break down biofilms and thus interfere with CVEC formation.

  8. EFFECTS OF ADMINISTRATION ROUTE, DIETARY CONDITION, AND BLOOD GLUCOSE LEVEL ON KINETICS AND UPTAKE OF 18F-FDG IN MICE

    PubMed Central

    Wong, Koon-Pong; Sha, Wei; Zhang, Xiaoli; Huang, Sung-Cheng

    2011-01-01

    The effects of dietary condition and blood glucose level on the kinetics and uptake of 18F-FDG in mice were systematically investigated using intraperitoneal and tail-vein injection. Methods Dynamic PET was performed for 60 min on 23 isoflurane-anesthetized male C57BL/6 mice after intravenous (n = 11) or intraperitoneal (n = 12) injection of 18F-FDG. Five and 6 mice in the intravenous and intraperitoneal groups, respectively, were kept fasting overnight (18 ± 2 h), and the others were fed ad libitum. Serial blood samples were collected from the femoral artery to measure 18F-FDG and glucose concentrations. Image data were reconstructed using filtered backprojection with CT-based attenuation correction. The standardized uptake value (SUV) was estimated from the 45- to 60-min image. The metabolic rate of glucose (MRGlu) and 18F-FDG uptake constant (Ki) were derived by Patlak graphical analysis. Results In the brain, SUV and Ki were significantly higher in fasting mice with intraperitoneal injection, but MRGlu did not differ significantly under different dietary states and administration routes. Cerebral Ki was inversely related to elevated blood glucose levels, irrespective of administration route or dietary state. In myocardium, SUV, Ki, and MRGlu were significantly lower in fasting than in nonfasting mice for both routes of injection. Myocardial SUV and Ki were strongly dependent on the dietary state, and Ki did not correlate with the blood glucose level. Similar results were obtained for skeletal muscle, although the differences were not as pronounced. Conclusions Intraperitoneal injection is a valid alternative route, providing pharmacokinetic data equivalent to data from tail-vein injection for small-animal 18F-FDG PET. Cerebral Ki varies inversely with blood glucose level, but the measured cerebral MRGlu does not correlate with blood glucose level or dietary condition. Conversely, the Ki values of the myocardium and skeletal muscle are strongly dependent on

  9. 7 CFR 62.100 - Administrator.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... Definitions Administration § 62.100 Administrator. The LS Program Deputy Administrator is charged with the administration of official assessments conducted according to the regulations in this part and approved...

  10. 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. PMID:26781878

  11. 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

  12. 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...

  13. 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...

  14. 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...

  15. 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...

  16. 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...

  17. Role of ACTH in the Interactive/Paracrine Regulation of Adrenal Steroid Secretion in Physiological and Pathophysiological Conditions.

    PubMed

    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

  18. 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.

  19. 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.

  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. Calcium regulates the cell-to-cell water flow pathway in maize roots during variable water conditions.

    PubMed

    Wu, Yan; Liu, Xiaofang; Wang, Weifeng; Zhang, Suiqi; Xu, Bingcheng

    2012-09-01

    Soil water shortages can decrease root hydraulic conductivity and affect Ca uptake and movement through the plant. In this study, the effects of extra Ca(2+) applied in nutrient solution on the hydraulic properties of the whole roots (Lp(r)) and cortical cells (Lp(cell)) of maize (Zea mays L.) subjected to variable water conditions were investigated. Under well-watered conditions, extra Ca(2+) significantly increased the root Ca content, total root length, and lateral root number; however, it reduced the root cortical cell volume, Lp(r), and Lp(cell). Hg(2+) inhibition experiments suggested that extra Ca(2+) could reduce the contribution of the cell-to-cell water flow pathway. Osmotic stress (10% PEG6000) significantly decreased the cortical cell volume, Lp(r), and Lp(cell) in the control plants, but smaller decreases were observed in the extra Ca(2+) plants. The Hg(2+) treatment reduced the Lp(r) larger in the extra Ca(2+) plants (74.6%) than in the control plants (53.2%), suggesting a higher contribution of the cell-to-cell pathway. The larger Hg(2+) inhibition of the Lp(cell) in the extra Ca(2+) roots (67.2%) when compared to the controls (56.4%) indicated that extra Ca(2+) can mitigate the inhibition of aquaporin expression and/or activity levels via osmotic stress. After 2 d of rehydration, the extra Ca(2+) helped the Lp(r) and Lp(cell) to recover almost completely, but these properties only partially recovered in the control plants. In conclusion, extra Ca(2+) may adjust the contribution of cell-to-cell pathway by regulating the expression and/or activity levels of AQPs according to water availability; this regulation may weaken negative effects and optimize water use. PMID:22841977

  3. 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. PMID:19470091

  4. 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.

  5. 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.

  6. A Systematic Review Exploring the Social Cognitive Theory of Self-Regulation as a Framework for Chronic Health Condition Interventions

    PubMed Central

    Tougas, Michelle E.; Hayden, Jill A.; McGrath, Patrick J.; Huguet, Anna; Rozario, Sharlene

    2015-01-01

    Background Theory is often recommended as a framework for guiding hypothesized mechanisms of treatment effect. However, there is limited guidance about how to use theory in intervention development. Methods We conducted a systematic review to provide an exemplar review evaluating the extent to which use of theory is identified and incorporated within existing interventions. We searched electronic databases PubMed, PsycINFO, CENTRAL, and EMBASE from inception to May 2014. We searched clinicaltrials.gov for registered protocols, reference lists of relevant systematic reviews and included studies, and conducted a citation search in Web of Science. We included peer-reviewed publications of interventions that referenced the social cognitive theory of self-regulation as a framework for interventions to manage chronic health conditions. Two reviewers independently assessed articles for eligibility. We contacted all authors of included studies for information detailing intervention content. We describe how often theory mechanisms were addressed by interventions, and report intervention characteristics used to address theory. Results Of 202 articles that reported using the social cognitive theory of self-regulation, 52% failed to incorporate self-monitoring, a main theory component, and were therefore excluded. We included 35 interventions that adequately used the theory framework. Intervention characteristics were often poorly reported in peer-reviewed publications, 21 of 35 interventions incorporated characteristics that addressed each of the main theory components. Each intervention addressed, on average, six of eight self-monitoring mechanisms, two of five self-judgement mechanisms, and one of three self-evaluation mechanisms. The self-monitoring mechanisms ‘Feedback’ and ‘Consistency’ were addressed by all interventions, whereas the self-evaluation mechanisms ‘Self-incentives’ and ‘External rewards’ were addressed by six and four interventions

  7. 5 CFR 370.106 - Terms and conditions.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 5 Administrative Personnel 1 2013-01-01 2013-01-01 false Terms and conditions. 370.106 Section 370.106 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT CIVIL SERVICE REGULATIONS INFORMATION TECHNOLOGY EXCHANGE PROGRAM § 370.106 Terms and conditions. (a) A Federal employee detailed under this...

  8. 5 CFR 370.106 - Terms and conditions.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 5 Administrative Personnel 1 2012-01-01 2012-01-01 false Terms and conditions. 370.106 Section 370.106 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT CIVIL SERVICE REGULATIONS INFORMATION TECHNOLOGY EXCHANGE PROGRAM § 370.106 Terms and conditions. (a) A Federal employee detailed under this...

  9. 5 CFR 370.106 - Terms and conditions.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 5 Administrative Personnel 1 2014-01-01 2014-01-01 false Terms and conditions. 370.106 Section 370.106 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT CIVIL SERVICE REGULATIONS INFORMATION TECHNOLOGY EXCHANGE PROGRAM § 370.106 Terms and conditions. (a) A Federal employee detailed under this...

  10. Regulation of glutamine synthetase isoforms in two differentially drought-tolerant rice (Oryza sativa L.) cultivars under water deficit conditions.

    PubMed

    Singh, Kamal Krishna; Ghosh, Shilpi

    2013-02-01

    KEY MESSAGE : The regulation of GS isoforms by WD was organ specific. Two GS isoforms i.e. OsGS1;1 and OsGS2 were differentially regulated in IR-64 (drought-sensitive) and Khitish (drought-tolerant) cultivars of rice. Water deficit (WD) has adverse effect on rice (Oryza sativa L.) and acclimation requires essential reactions of primary metabolism to continue. Rice plants utilize ammonium as major nitrogen source, which is assimilated into glutamine by the reaction of Glutamine synthetase (GS, EC 6.3.1.2). Rice plants possess one gene (OsGS2) for chloroplastic GS2 and three genes (OsGS1;1, OsGS1;2 and OsGS1;3) for cytosolic GS1. Here, we report the effect of WD on regulation of GS isoforms in drought-sensitive (cv. IR-64) and drought-tolerant (cv. Khitish) rice cultivars. Under WD, total GS activity in root and leaf decreased significantly in IR-64 seedlings in comparison to Khitish seedlings. The reduced GS activity in IR-64 leaf was mainly due to decrease in GS2 activity, which correlated with decrease in corresponding transcript and polypeptide contents. GS1 transcript and polypeptide accumulated in leaf during WD, however, GS1 activity was maintained at a constant level. Total GS activity in stem of both the varieties was insensitive to WD. Among GS1 genes, OsGS1;1 expression was differently regulated by WD in the two rice varieties. Its transcript accumulated more abundantly in IR-64 leaf than in Khitish leaf. Following WD, OsGS1;1 mRNA level in stem and root tissues declined in IR-64 and enhanced in Khitish. A steady OsGS1;2 expression patterns were noted in leaf, stem and root of both the cultivars. Results suggest that OsGS2 and OsGS1;1 expression may contribute to drought tolerance of Khitish cultivar under WD conditions.

  11. Intracerebroventricular administration of ouabain, a Na/K-ATPase inhibitor, activates tyrosine hydroxylase through extracellular signal-regulated kinase in rat striatum.

    PubMed

    Yu, Hyun Sook; Kim, Se Hyun; Park, Hong Geun; Kim, Yong Sik; Ahn, Yong Min

    2011-11-01

    Alteration in dopamine neurotransmission has been reported to be involved in the mania of bipolar disorder. Tyrosine hydroxylase (TH) is the rate-limiting enzyme that is crucial for dopamine biosynthesis, and its activity is tightly regulated by phosphorylation at multiple N-terminal serine residues. Previously, we have reported that intracerebroventricular (ICV) injection of ouabain, a selective Na/K-ATPase inhibitor, induces hyperactivity in rats that mimics manic symptoms related to the activation of extracellular signal-regulated protein kinase1/2 (ERK1/2), which plays crucial roles in the modulation of TH phosphorylation. In this study, we investigated the effects of ICV injection of ouabain on TH phosphorylation in rat striatum and the involvement of ERK1/2 in ouabain-induced TH activation. ICV ouabain induced an acute dose-dependent increase in locomotor activity and in TH phosphorylation in rat striatum. TH phosphorylation at Ser19 was significantly increased with 100, 500, and 1000μM ouabain, and phosphorylation at Ser31 and Ser40 was significantly increased with 500 and 1000μM. We also found that ICV pretreatment with U0126, a specific MEK1/2 inhibitor, attenuated the 1000μM ouabain-induced increase in TH phosphorylation at Ser19, Ser31, and Ser40, as well as the hyperactivity of rats. Moreover, the increased phosphorylation of TH (Ser19, Ser31, and Ser40) was maintained until 8h after single administration ouabain was accompanied by increased phosphorylation of ERK1/2 (Thr202/Tyr204) and p90RSK (Thr359/Ser363). These findings imply that TH activation of the ERK1/2 signal pathway could play an important role in ouabain-induced hyperactivity of rats, a mania model. PMID:21871514

  12. 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.

  13. 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.

  14. 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. PMID:27470016

  15. 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.

  16. Regulation of type 1 inositol 1,4,5-triphosphate receptor by dopamine receptors in cocaine-induced place conditioning.

    PubMed

    Kurokawa, Kazuhiro; Mizuno, Koji; Shibasaki, Masahiro; Ohkuma, Seitaro

    2012-02-01

    Recent study shows that type 1 inositol-1,4,5-triphosohate receptors (IP(3) Rs) may be involved in amphetamine-induced conditioned preference, but little is known about its role in psychological dependence on cocaine. This study investigated the role and regulation of IP(3) R-1 in mice with cocaine-induced place preference. The cocaine-induced place preference was dose-dependently inhibited by intracerebroventricular pretreatment with IP(3) R antagonists, 2-aminophenoxyethane-borate (2-APB), and xestospongin C. The levels of IP(3) R-1 in the frontal cortex and nucleus accumbens of cocaine-conditioned mice significantly increased, which was completely abolished by SCH23390 and sulpiride, selective dopamine D1 and D2 receptor antagonists, respectively. These findings suggest that IP(3) R-1-mediated intracellular signaling pathway may play an important role in the development of cocaine-induced place preference and that the expression of IP(3) R-1 is controlled by both dopamine D1 and D2 receptors in the frontal cortex and nucleus accumbens of mice with cocaine-induced place preference.

  17. 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.

  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. 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. PMID:27281343

  20. 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.

  1. Focal adhesion kinase regulates the activity of the osmosensitive transcription factor TonEBP/NFAT5 under hypertonic conditions

    PubMed Central

    Neuhofer, Wolfgang; Küper, Christoph; Lichtnekert, Julia; Holzapfel, Konstantin; Rupanagudi, Khader V.; Fraek, Maria-Luisa; Bartels, Helmut; Beck, Franz-Xaver

    2014-01-01

    TonEBP/NFAT5 is a major regulator of the urinary concentrating process and is essential for the osmoadaptation of renal medullary cells. Focal adhesion kinase (FAK) is a mechanosensitive non-receptor protein tyrosine kinase expressed abundantly in the renal medulla. Since osmotic stress causes cell shrinkage, the present study investigated the contribution of FAK on TonEBP/NFAT5 activation. Osmotic stress induced time-dependent activation of FAK as evidenced by phosphorylation at Tyr-397, and furosemide reduces FAK Tyr-397 phosphorylation in the rat renal medulla. Both pharmacological inhibition of FAK and siRNA-mediated knockdown of FAK drastically reduced TonEBP/NFAT5 transcriptional activity and target gene expression in HEK293 cells. This effect was not mediated by impaired nuclear translocation or by reduced transactivating activity of TonEBP/NFAT5. However, TonEBP/NFAT5 abundance under hypertonic conditions was diminished by 50% by FAK inhibition or siRNA knockdown of FAK. FAK inhibition only marginally reduced transcription of the TonEBP/NFAT5 gene. Rather, TonEBP/NFAT5 mRNA stability was diminished significantly by FAK inhibition, which correlated with reduced reporter activity of the TonEBP/NFAT5 mRNA 3′ untranslated region (3′-UTR). In conclusion, FAK is a major regulator of TonEBP/NFAT5 activity by increasing its abundance via stabilization of the mRNA. This in turn, depends on the presence of the TonEBP/NFAT5 3′-UTR. PMID:24772088

  2. Health Care Financing Administration--Medicare and Medicaid; provider agreements: redesignation and rewrite of Medicare regulations; effective dates; effect of change in ownership. Final rule with comment period.

    PubMed

    1980-04-01

    These regulations revise and redesignate the policies pertaining to provider agreements under the Medicare program to simplify them and to make them easier to read. We have made substantive changes only in the provisions relating to the effective date of the agreement and the effect of a change in ownership. These substantive changes were issued as proposed rulemaking on February 5, 1979, and will also apply to the Medicaid program. The substantive changes make provider agreements effective on the date of the onsite health and safety survey if all Federal requirements are met. If all requirements are not met, the effective date is the date the requirements are met or the date the provider submits an acceptable plan of correction or waiver request. The revised regulations also provide that existing provider agreements be assigned to new owners, subject to the terms and conditions under which they were originally issued. The intent of the substantive changes is to achieve maximum uniformity of policy for the two programs and to provide continuity of coverage for beneficiaries and recipients when there is change of ownership. PMID:10297749

  3. 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.

  4. 7 CFR 301.85-3 - Conditions governing the interstate movement of regulated articles from quarantined States. 2

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... samples for processing, testing, or analysis may be moved interstate from any quarantined State under the... specifically authorized by the Deputy Administrator in emergency situations, soil samples for processing... required to be attached to such soil samples except in those situations where the Deputy Administrator...

  5. 7 CFR 301.85-3 - Conditions governing the interstate movement of regulated articles from quarantined States. 2

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... samples for processing, testing, or analysis may be moved interstate from any quarantined State under the... specifically authorized by the Deputy Administrator in emergency situations, soil samples for processing... required to be attached to such soil samples except in those situations where the Deputy Administrator...

  6. 7 CFR 301.85-3 - Conditions governing the interstate movement of regulated articles from quarantined States. 2

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... samples for processing, testing, or analysis may be moved interstate from any quarantined State under the... specifically authorized by the Deputy Administrator in emergency situations, soil samples for processing... required to be attached to such soil samples except in those situations where the Deputy Administrator...

  7. 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.

  8. Negative growth regulation in a glioblastoma tumor cell line that conditionally expresses human wild-type p53

    SciTech Connect

    Mercer, W.E.; Shields, M.T.; Amin, M.; Sauve, G.J. ); Appella, E.; Romano, J.W.; Ullrich, S.J. )

    1990-08-01

    To investigate the effect that human wild-type p53 (wt-p53) expression has on cell proliferation the authors constructed a recombinant plasmid, pM47, in which wt-p53 cDNA is under transcriptional control of the hormone-inducible mouse mammary tumor virus promoter linked to the dominant biochemical selection marker gene Eco gpt. The pM47 plasmid was introduced into T98G cells derived from a human glioblastomas multiforme tumor, and a stable clonal cell line, GM47.23, was derived that conditionally expressed wt-p53 following exposure to dexamethasone. The authors show that induction of wt-p53 expression in exponentially growing cells inhibits cell cycle progression and that the inhibitory effect is reversible upon removal of the inducer or infection with simian virus 40. Moreover, when growth-arrested cells are stimulated to proliferate, induction of wt-p53 expression inhibits G{sub 0}/G{sub 1} progression into S phase and the cells accumulate with a DNA content equivalent to cells arrested in the G{sub 0}/G{sub 1} phase of the cell cycle. Taken together, these studies suggest that wt-p53 may play a negative role in growth regulation.

  9. 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

  10. 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

  11. 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.

  12. 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...

  13. 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...

  14. 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...

  15. 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...

  16. 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...

  17. 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. PMID:27225459

  18. 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....

  19. Leptins and leptin receptor expression in the goldfish (Carassius auratus). Regulation by food intake and fasting/overfeeding conditions.

    PubMed

    Tinoco, Ana Belén; Nisembaum, Laura Gabriela; Isorna, Esther; Delgado, María Jesús; de Pedro, Nuria

    2012-04-01

    Leptin is a hormone involved in feeding and body weight regulation in vertebrates, but the relationship between energy status and leptin has not been clearly established in fish. The aim of this study was to investigate in a teleost, the goldfish (Carassius auratus), the tissue expression pattern of two leptins (gLep-aI and gLep-aII) and leptin receptor (gLepR); and the effect of feeding on expression of these genes. Leptin system expression in goldfish was firstly analyzed in fish under overfeeding (2 weeks) or fasting (1 week), and secondly, at different postfeeding times (0, 3, 6, 9 and 12h). Goldfish has two Lep-a paralog genes, gLep-aI was widely expressed in central and peripheral tissues, whereas gLep-aII was preferentially expressed in brain. This different distribution pattern of leptins suggests that they can play different physiological roles in goldfish. The gLepR mRNA was ubiquitous expressed, with the highest expression in the telencephalon and hypothalamus. No significant differences in the leptin system expression were found among control, overfed and fasting groups, suggesting an apparent lack of correlation between nutritional status and leptin system in goldfish. Hepatic expression of gLep-aI significantly increased 9h after feeding time, while hypothalamic leptin system expression did not change after feeding. In summary, leptin in goldfish could signal short-term changes in food intake, as postprandial satiety, but seems to be independent of fasting/overfeeding conditions in this teleost. The widespread distribution of leptins and leptin receptor in goldfish strongly supports that this hormone may have pleitropic actions in fish.

  20. 18 CFR 415.40 - Administrative agency.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 18 Conservation of Power and Water Resources 2 2011-04-01 2011-04-01 false Administrative agency. 415.40 Section 415.40 Conservation of Power and Water Resources DELAWARE RIVER BASIN COMMISSION ADMINISTRATIVE MANUAL BASIN REGULATIONS-FLOOD PLAIN REGULATIONS Administration § 415.40 Administrative agency....